Theme: Neurostomatological syndromes: sympathalgia, neurotrophic diseases (Kvinke’s oedema, Meyja disease, Rossolimo–Rosental syndrome), glossodinia, Shegren syndrome

Acute disorders of cerebral blood circulation

Demyelination diseases: multiple sclerosis, lateral amyotrophic sclerosis

 

Acute disorders of cerebral blood circulation

 

1. Epidemiology of cerebrovascular diseases.

Among all the neurological diseases of adult life the cerebrovascular ones clearly rank first in frequency and importance. At least 50 % of the neurological disorders are of this type. The prevalence of strokes all over the world is about 1.5 – 7.4 per 1000 of the general population. In Ukraine it is 3.27 per 1000 of the general population. Cerebral stroke is the commonest vascular disease of the brain. Every year there are about 6 mln cases of stroke: among them – 1 mln in Western Europe, about 500 000 in the United States, 300 000 – in Russia, 200 000 – in Japan and 130 000 – in Ukraine.

Stroke after heart diseases and cancer is the third commonest cause of death according to the World Health Organization data.

During the last 15 years there has been a marked enlargement in the prevalence of stroke in Ukraine in about 3.4 times and in incidence in 3 times approximately.

 

 

ANATOMY OF THE BLOOD SUPPLY OF THE BRAIN

The brain is supplied by two paired arteries, the inter­nal carotid arteries anteriorly and the vertebral arter­ies posteriorly. The vertebral arteries unite to form the basilar artery. These two arterial systems form the cir­cle of Willis at the base of the brain, a unique anasto­motic system that gives rise to all of the vessels sup­plying the cerebral hemispheres (Fig. 8-1).

 

Internal Carotid Artery

The internal carotid artery rises in the neck as one of two branches of the common carotid artery. It ascends in the neck and enters the carotid canal in the petrous temporal bone where it ascends, loops for­ward and medially, and ascends again to enter the cranial cavity. The artery enters the cavernous sinus and passes forward, closely related to sella and hy­pophysis medially, and the third, fourth, sixth, and ophthalmic and maxillary divisions of the fifth cranial nerves laterally. The terminal portion of the internal carotid artery ascends and pierces the dura medial to the anterior clinoid process, where the artery is closely related to the optic nerve. The cavernous and terminal portions of the internal carotid artery are fre­quently referred to as the carotid siphon.

The branches of the internal carotid artery in­clude:

1.  Petrous portion                                         

A. Caroticotympanic artery—supplies the ante­rior and part of the medial wall of the middle ear.

2.  Cavernous portion

A.  Cavernous arteries—small vessels supplying the hypophysis and the wall of the cavernous sinus.

B.  Hypophyseal arteries — supply the hypophysis.

C.  Semilunar   artery—supplies   the   trigeminal (gasserian: semilunar) ganglion.

D.  Anterior meningeal arteries—supply the dura of the anterior cranial fossa.

3.  Supraclinoid portion

A.  Ophthalmic artery

B.  Anterior choroidal artery

C.  Posterior communicating artery

4.  Terminal portion

A.  Anterior cerebral artery

B.  Middle cerebral artery

 

Ophthalmic Artery

The ophthalmic artery rises from the supraclinoid portion of the internal carotid artery, pierces the dura, and accompanies the optic nerve through the optic foramen and into the orbit. The artery passes medi­ally, superior to the optic nerve, to the roof of the or­bit, where it divides into the supratrochlear and dorsal nasal arteries. Branches of the ophthalmic artery anastomose with branches of the external carotid sys­tem. This anastomosis may supply blood to intracra­nial structures by reversal of flow following insuffi­ciency or occlusion of the internal carotid artery.

The branches of the ophthalmic artery include:

1. Central retinal artery—arises from the oph­thalmic artery and enters the optic nerve close to the eye. The artery emerges from the center of the optic disc in the optic cup and divides into several branches supplying the optic disc and retina.

2.  Ciliary arteries—several in number, which sup­ply the sclera, choroid, lens and conjunctiva of the eye.

3.  Lacrimal  artery—arises  from the  ophthalmic artery near the optic foramen and runs laterally along the upper border of the lateral rectus mus­cle to supply the lacrimal gland.

4.  Supraorbital artery—arises from the ophthalmic artery and passes above the eye to accompany the \ supraorbital nerve. The artery supplies the skin muscle, and other structures over the foreheads and anastomoses with branches of the superficial! Temporal artery.                                               

5.  Ethmoidal arteries—supply  the ethmoidal si­nuses, the nasal cavity, and the dura of the ante­rior fossa.

6.  Dorsal nasal artery—distributed to the outer surface of the nose and anastomoses with the angu­lar artery.

7.  Frontal artery—supplies the medial aspect of the forehead.

8.  Superior and inferior palpebral arteries—encir­cle the eyelids near the facial margins.

9.  Muscular   branches—supply   the   extraocular muscles.

10. Anterior choroidal artery—arises from the ter­minal portion of the internal carotid artery and passes posteriorly along the optic tract to reach the lateral geniculate body. The artery then enters the choroidal fissure and supplies the choroid plexus in the inferior horn of the lateral ventricle. In its course, the artery supplies the optic tract, the cerebral peduncle, the lateral portion of the lateral geniculate body, the posterior two-thirds of the posterior limb of the internal capsule, the retrolenticular and infralentricular portions of the internal capsule, the optic radiation, the hip­pocampus, the choroid plexus, the tail of the cau­date nucleus, and the amygdala.

 

Posterior Communicating Artery

The posterior communicating artery arises from the terminal portion of the internal carotid artery and passes posteriorly, immediately above the oculomotor nerve, to anastomose with the posterior cerebral artery. Branches of the posterior communicating artery supply the thalamus, subthalamus, internal capsule, mamillary bodies, optic chiasm, and optic tract.

 

Anterior Cerebral Artery

The anterior cerebral artery arises from the terminal portion of the internal carotid artery and passes anteromedially above the optic nerve to come into con­tact with the opposite anterior cerebral artery. The two arteries are connected by a short anterior commu­nicating artery, then pass around the genu and body of the corpus callosum to anastomose with branches of the posterior cerebral artery at the level of the pari­etooccipital fissure.

The branches of the anterior cerebral artery in­clude:

1.  Anterior communicating artery—supplies the op­tic chiasm and hypothalamus.

2.  Perforating branches—penetrate the anterior per­forating substance and lamina terminalis to supply the rostrum of the corpus callosum and the septum pellucidum.

3.  Recurrent branch (medial striate artery, recurrent artery of Heubner)—is distributed to the head of the caudate nucleus and the anterior limb of the internal capsule.

4.  Cortical branches

A.  Orbital branches—supply the orbital and me­dial surfaces of the frontal lobe.

B.  Frontopolar   branch—supplies   the   anterior portion of the medial aspect of the superior frontal gyrus and extends about 1 inch onto the superior lateral surface.

C.  Pericallosal  branch—supplies   the  cingulate gyrus and corpus callosum.

D.  Callosal marginal branch—supplies the cingu­late gyrus, the medial aspect of the superior frontal gyrus, and the paracentral lobule.

 

Middle Cerebral Artery

The middle cerebral artery should be regarded as the intracranial extension of the internal carotid artery. Emboli entering the internal carotid artery invariably enter the middle cerebral artery. The middle cerebral artery runs laterally in the lateral fissure between frontal and temporal lobes (Fig. 8-2) to reach the sur­face of the insula, where it divides into several branches.

1.    Lenticulostriate   arteries   —   perforating branches that arise close to the origin of the middle cerebral artery and penetrate the substance of the brain to supply the head of the caudate nucleus, putamen, globus pallidus, and internal capsule.

2.    Cortical branches—radiate outward from the middle cerebral artery as it lies on the insula. Cor­tical branches that can be recognized by arteriography are  the   orbitofrontal,   frontal,   pre-Rolandic,   post-Rolandic, anterior parietal, posterior parietal, an angu­lar branch following the line of the lateral fissure, and the anterior, middle, and posterior temporal branches extending over the surface of the temporal lobe.

Vertebral Artery   –

The vertebral artery arises from the first portion of the subclavian artery in the neck. The anatomical course can be considered in four parts.

First part—ascends posteromedial^ and enters the foramen of the transverse process of the sixth cer­vical vertebra.

Second part—ascends through the foramina of the transverse processes of the upper sixth cervical vertebra.

Third part—curls backward in a groove behind the superior articular process of the atlas and passes through the foramen magnum.

Fourth part—pierces the dura to lie on the ven­tral surface of the medulla, where it ascends to the lower border of the pons to unite with the vertebral artery from the opposite side, forming the basilar artery.

The branches of the vertebral artery include:

1.    Spinal branches accompany the nerve roots into the spinal canal. Only one or two of these branches anastomoses with the anterior spinal artery.

2.    Muscular branches — supply the deep mus­cles of the neck.

3.    Meningeal branches—arise from the verte­bral arteries at the level of foramen magnum and sup­ply the dura of the posterior fossa and the falx cere­bri.

4.    Anterior spinal artery—arises from the vertebral artery near its termination and descends over the surface of the medulla to unite with the artery from the opposite site and form one anterior spinal artery. This artery lies on the ventral surface of the spinal cord and terminates as a fine vessel in the cauda equina. The anterior spinal artery supplies the medial and inferior portions of the medulla, including the medullary pyramids, and all of the spinal cord, except the posterior columns and posterior horns of the gray matter.

5. Posterior inferior cerebellar artery—arises from the fourth portion of the vertebral artery and passes around the medulla, onto the inferior surface of the cerebellum, where it divides into two branches. The posterior inferior cerebellar artery supplies the lateral portion of the medulla and the inferior cerebel­lar peduncle. The medial branch supplies the inferior vermis, the medial aspect of the cerebellar hemi­sphere, and the choroid plexus of the fourth ventricle. The lateral branch supplies the inferior surface of the cerebellar hemisphere. There is a well-developed anastomosis with the anterior inferior cerebellar and superior cerebellar arteries.

 

Basilar Artery

The basilar artery (Fig. 8-3) takes origin at the in­ferior border of the pons from the junction of the two vertebral arteries and ascends in the median groove of the pons to terminate at the upper border of the pons by dividing into the two posterior cerebral arteries.

The branches of the basilar artery include:

1.  Pontine branches—supply the pons.

2.  Internal auditory artery—accompanies the sev­enth and eighth cranial nerves into the internal au­ditory meatus and supplies the inner ear.

3.  Anterior inferior cerebellar artery—arises just above the lower border of the pons and passes around the pons onto the inferior surfaces of the cerebellar hemisphere and anastomosis with the posterior inferior cerebellar artery.

4.  Superior cerebellar artery—arises just below the termination of the basilar artery and passes around the pons, separated from the posterior cerebral artery by the oculomotor nerve. The superior cere­bellar artery supplies the superior and middle cerebellar peduncles, the pineal gland, the choroid plexus of the third ventricle, and the superior sur­face of the cerebellum.

 

Posterior Cerebral Artery

The posterior cerebral artery arises at the termination of the basilar artery, where it is separated from the superior cerebellar artery by the oculomotor nerve. The posterior communicating artery, a branch of the internal carotid artery, joins the posterior cerebral artery, which winds around the cerebral peduncle onto the tentorial surface of the occipital lobe.

The branches of the posterior cerebral artery in­clude:

1.  Posteromedial arteries—enter the posterior perfo­rated substances to supply the medial surface of the thalamus and the wall of the third ventricle.

2.  Posterior choroidal artery—runs beneath the splenium of the corpus callosum to supply the choroid plexus of the third ventricle.

3.  Posterolateral arteries—supply the lateral thala­mus and the midbrain.

4.  Anterior temporal branches—supply the uncus and the fusiform gyrus of the temporal lobe.

5.  Posterior temporal branches—supply the inferior temporal gyrus.

6.  Calcarine branches—supply the medial surface of the occipital lobe with a short extension onto the superior lateral surface of the hemisphere and the occipital pole. The posterior cerebral artery anas­tomoses with the anterior cerebral artery at the level of the parietooccipital fissure on the medial surface of the hemisphere.

 

 

 

Arterial Circle of Willis

This unique anastomosis, which lies at the base of the brain, is derived from the internal carotid and verte­bral arterial systems (see Fig. 8-1). The anterior por­tion of the circle is formed by the two anterior cere­bral arteries derived from the internal carotid arteries and connected by the anterior communicating artery. The posterior portion of the circle consists of the two posterior cerebral arteries, which are the terminal branches of the basilar artery. The posterior cerebral

arteries are connected to the internal carotid artery on each side by the posterior communicating arteries. The circle of Willis encloses the optic chiasm, the infundibulum, the tuber cinereum, and the mamillary bodies.

 

ANATOMY OF THE VENOUS DRAINAGE OF THE BRAIN

The cerebrovenous system can be divided into two subdivisions, the superficial external venous drainage and the deep internal venous drainage. Both systems eventually drain into the venous sinuses.

The upper lateral surface of the cerebral hemi­sphere is drained by the superficial cerebral veins, which enter the superior longitudinal sinus. The su­perficial middle cerebral vein also drains the lateral surface of the cerebral hemispheres and passes for­ward in the lateral fissure to enter the cavernous si­nus. The superficial middle cerebral vein communi­cates with the superior longitudinal sinus through the superior anastomotic vein of Trolard and with the transverse sinus through the inferior anastomotic vein of Labbe. The inferior cerebral veins drain the orbital surface of the frontal lobe, the lateral aspect of the temporal lobe, and the lateral aspect of the occipital lobe to empty into the cavernous sinus and transverse sinuses. The veins over the insula unite to form the deep middle cerebral vein, which passes anteriorly deep to the lateral fissure and joins the basal vein of Rosenthal. This latter structure arises in the anterior perforating substance by the union of the anterior cerebral vein and the veins of the corpus callosum. The basal vein is joined by the deep middle cerebral vein as it passes posteriorly in close relationship to ^l the uncus and hippocampus. The basal vein then 1 winds around the midbrain to unite with the basal vein from the opposite side, at the origin of the great cerebral vein.

The deep internal group of cerebral veins drain the central structures of the cerebral hemisphere and are closely related to the ventricular system.

The terminal (thalamostriate) vein arises from the inferior horn of the lateral ventricle and follows the tail of the caudate nucleus into the body of the lat­eral ventricle, lying between the caudate nucleus and the thalamus. The terminal vein runs forward to the intraventricular foramen and is joined by the anterior caudate vein, the septal vein, which drains the septum pellucidum, and the choroidal vein, which drains the choroid plexus of the lateral ventricle to form the in­ternal cerebral vein. This structure turns at its origin, forming the venous angle, and then passes along the roof of the third ventricle and through the velum interpositum to join with the opposite internal cerebral vein. The great vein of Galen is formed by the union of the internal cerebral veins and the junction of the basal veins of Rosenthal. After a short course, the great cerebral vein is joined by the inferior sagittal si­nus to form the straight sinus.

The intracranial venous sinuses are thin-walled endothelial-lined structures lying within the dura. The superior longitudinal sinus takes origin at the fora­men cecum anteriorly and passes in the superior sur­face of the falx cerebri to the internal occipital protu­berance, then turns to the right to form the right transverse sinus. The superior longitudinal sinus re­ceives the superior cerebral veins. The walls of the si­nus contain granulations that are responsible for the absorption of cerebrospinal fluid (CSF) into the ve­nous system. The inferior longitudinal sinus arises in the free margin of the falx cerebri by the union of a number of small veins and runs posteriorly to termi­nate in the straight sinus at the junction of the falx cerebri and the tentorium cerebelli. The straight sinus is formed by the union of the great vein of Galen and the inferior longitudinal sinus and passes posteriorly in the junction of the falx cerebri and tentorium cere­belli. The straight sinus terminates at the internal oc­cipital protuberance by becoming the left transverse sinus. The transverse sinuses arise at the internal oc­cipital protuberance and run along the edge of the tentorium cerebelli to end at the base of the petrous temporal bone, where they become the sigmoid si­nuses. The transverse sinuses receives most of the ve­nous drainage from the cerebellum. The sigmoid si­nuses are a direct continuation of the transverse sinuses, beginning at the base of the petrous temporal bone and terminating at the jugular foramen as the in­ternal jugular vein.

The cavernous sinus arises anteriorly from the superior ophthalmic vein at the superior orbital fis­sure and passes posteriorly, close to the sella turcica and terminates by dividing into the superior and infe­rior petrosal sinuses. The cavernous sinuses commu­nicate with each other through the intercavernous si­nuses, which lie anteriorly and posteriorly to the sella turcica. The lateral walls of the cavernous sinuses contain the third, fourth, and sixth nerves and the ophthalmic and maxillary divisions of the trigeminal nerve. The intracavernous portion of the internal carotid artery is contained within the cavernous sinus. The superior petrosal sinus arises from the cavernous sinus at the apex of the petrous temporal bone and passes along the edge of the tentorium cerebelli to terminate in the transverse sinus. The inferior petrosal sinus also rises at the apex of the petrous temporal bone and enters a groove lying in the junction of the petrous temporal and occipital bones to terminate in the jugular bulb of the internal jugular vein.

 

2. The main reasons and risk – factors of cerebral blood – circulation disturbances.

    There are a lot of reasons and risk – factors of cerebral blood – circulation disturbances. But the commonest are 3 of them:

1.      Atherosclerosis of cerebral vessels and general atherosclerosis. In 75 % of all cases it is the main reason of all acute cerebral blood – circulation disturbances.

2.      Hypertension – the frequency of hypertension in case of stroke is about 72 %.

3.      Combination of atherosclerosis and hypertension.

      Besides these main reasons there are some others which can cause cerebral blood – circulation disturbances.

4.      Symptomatic arterial hypertension (for example caused by kidney diseases)

5.      Heart diseases such as inborn and acquired cardiac abnormalities, arrhythmias, IHD, atherosclerosis, cardiosclerosis, angina pectoris, myocardial infarction.

6.      Infectious and infectious – allergic vasculitis (at rheumatism, connective tissue diseases, lues)

7.      Arterial hypotension.

8.      Vasomotor dystonia.

9.      Blood diseases (polycythemia, leucosis, haemophilia)

10. Kidney diseases.

11. Endocrine diseases (diseases of thyroid gland, pancreas, suprarenal glands)

12. Diabetes mellitus.

13. Toxic lesion of vessels at endogenous and exogenous intoxication ( at acute and chronic kidney or liver failure, alcoholic intoxication )

14. Traumatic lesion of vessels (at haemorrhage – subdural, epidural, ventricular, parenchymatous).

15. Artery and vein compression (especially in cervical part of spinal cord – for example at osteochondrosis)

16. Inborn and acquired Willis circle abnormalities – occlusion, stenosis of MAH and neck, aneurism, constriction of vessels.

17. Brain tumours.

 

For these reasons’ realization they should be combined with risk – factors, such as

·        Age (the elder person is, the highest risk of cerebrovascular disease is)

·        Sex (at the age of up to 55 – 60 years fatality from cerebrovascular disease is higher in men, after 55 – 60 years – it is higher in women)

·        Heredity (in particular to heart and cerebrovascular diseases)

·        Alcohol abuse

·        Cigarette smoking

·        Hyperlipidemia and hyperglycaemia

·        Arterial hypertension

·        Hypodynamia

·        Meteorological dependence ( especially people with labile autonomic nervous system )

·        Personal type (picnotic type), stress, high carbohydrate diet.

Combination of three and more factors increases risk of development of acute neurological deficit.

 

Classification of cerebrovascular diseases

According to World Health Organization classification all cerebrovascular diseases are divided into 3 groups:

A.     Premonitary and initial symptoms of brain blood supply insufficiency

B.     Acute cerebral blood circulation disturbances

1.      Dynamic cerebral blood circulation disturbances

2.      Acute hypertonic encephalopathy

3.      Haemorrhage – subdural, epidural

4.      Intracerebral hemorrhage

5.      Brain infarction (nonembolic)

6.      Brain infarction (embolic)

C.    Dyscirculative encephalopathy or chronic cerebral blood circulation insufficiency or slowly progressive insufficiency of cerebral blood circulation.

 

Dynamic cerebral blood circulation disturbances (DCBCD)

DCBCD – are acute brain dyscirculation events which usually are developed against the main diseases. They are associated with temporary general and focal brain symptoms. They have tendency to involution during 24 hours.

    To DCBCD belong

1.      Transient ischemic attacks ( TIA ) – they take about 1/3 of all DCBCD

2.      Hypertonic crisis  – it takes about 2/3 of all DCBCD

     This disease is very common and takes about 1/3 of all cases of cerebrovascular diseases.

 

Etiology

TIA is usually associated with:

·        Atherosclerosis

·        Stenosis of MAH

·        Heart diseases (abnormalities, myocardial infarction)

·        Sometimes vasculitis, systemic vascular diseases

In 30 – 40 % of patients with TIA stroke is developed in 5 years. In 20 % of them stroke is developed in 1 month, in 50 % – it is developed in a year. The possibility of stroke development is higher at repeated TIA and depends on age of the patient (it is getting higher in 1.5 times with every 10 years).

 

Pathogenesis

 

 

The main pathogenic mechanisms are:

A.     Thromboembolic

B.     Hemodynamic

They are very closely associated with each other.

A.     The commonest of them are thromboembolic. That means microembolism of cerebral vessels.

Microembols are divided into arteriogenic and cardiogenic.

Arteriogenic microembols are small units that originate from clots and are the result of destroyed atherosclerotic plaques.

Thrombocytic embols are crumbling. That is the main reason of rapid involution of neurological deficit.

Cardiogenic microembols can cause TIA in patients with arrhythmias, heart abnormalities, after myocardial infarction, in patients with rheumatic endocarditis.

 

B.     Haemodynamic  mechanisms

1.       Atherosclerotic stenosis of cerebral vessels or MAH, especially in association with hypotension, arrhythmias and myocardial infarction.

 

 

2.       Thrombosis of neck magistral artery.

 

Thrombosis of Medial cerebral artery

 

     

 

3.       In the subclavian steal syndrome the patient has a narrowed subclavian artery and the arm “steals” blood from the basilar artery via the vertebral artery. There may be a cervical bruit and a difference in blood pressure between the arms. At times of arm exercise the patient may experience vertebrobasilar insufficiency.

4.       Spasm of cerebral vessels and as a result perivascular oedema and hypoxia of brain tissue.

5.       Inborn stenosis , abnormalities of MAH

6.       Compression of vertebral artery by osteophytes at cervical osteochondrosis.

7.        Vessels insufficiency (contradiction between real and demandable blood supply). This can occur at heart failure, hypotension, internal bleeding.

 

Clinical picture of TIA

      TIA is usually characterized by focal neurological symptoms. The last usually dominate over general brain symptoms. Thus TIA is regional DCBCD. They are usually acute and develop suddenly.

There are 2 main groups of TIA’s symptoms:

a.      focal

b.     general brain symptoms

General, if they present, usually manifest as headache, dizziness, short loss of consciousness. Focal symptoms depend on the vessel territory.

 

TIAs in carotid distribution (They take 30 % of all TIAs)

 

 

 

 

Carotid distribution – is a territory of internal carotid arteries and their branches – ophthalmic artery, anterior cerebral artery, and middle cerebral artery. Via anterior cerebral artery carotid distribution supplies anterior part of frontal lobe, internal surface of hemisphere to sulcus parietooccipitalis , via middle cerebral artery – the cortex of frontal, parietal, temporal lobe, internal capsula and nucleus.

 

 

1.      The most common symptoms are subjective sensory disorders, such as numbness, tingling in face and extremities; and objective sensory disorders such as hyperesthesia of superficial sensation in face and extremities, sometimes deep sensation in fingers and toes.

2.      Very often motor disorders together with sensory ones are observed. They are central paresis of extremity or fingers with hyperreflexia, pathologic signs of Babinski, Rossolimo. Hemiparesis or hemiplegia is observed only in severe cases.

3.      Sometimes distorting language (transient aphasia) is observed.

4.      When TIA occurs in the internal carotid artery territory ophthalmic – piramidal syndrome is developed. It usually manifests as blindness or reduction of vision on the same side and hemiparesis on the opposite side. It is known as Lasko – Radowich syndrome.

5.      Focal Jackson motor or sensory epileptic attacks are observed in patients with MAH pathology.

 

TIAs in vertebrobasilar distribution (They take about 70 % of all TIAs)

     

             

 

 

This territory provides blood supply of brainstem, cerebellum, occipital lobe cortex, mediobasal structures of temporal lobes.

1.      Vestibular syndrome. It manifests as systemic dizziness, occipital headache, nystagmus, equilibrium disorders.

2.      Brainstem – cerebellum syndrome. It manifests as equilibrium, coordination and synergy of action disorders.

3.      Paresis of oculomotor muscles with convergence disorders, diplopia, cross – eye.

4.      Bulbar syndrome with swallowing, voice and speech disorders.

5.      Alternation syndromes are quite rare.

6.      Vision disorders of cortex character such as photopsias, hemianopsia, quadric hemianopsia and optic phenomena.

7.      Atonic – adynamic syndrome. It is observed at acute ischemia of reticular formation and lower olives in medulla oblongata in case of “drop – attacks “ – the attacks of sudden loss of muscle tone that cause patient’s falling down without loss of consciousness .These attacks manifest at cervical spinal cord disorders in case of sudden turning out or head retroversion.  Sometimes symptom of Sistine chapel can occur when loss of muscle tone is associated with loss of consciousness.

8.      At ischemia of mediobasal structures of temporal lobe one can Korsakov syndrome observe – the attacks of temporary memory disorders on current events associated with confabulator component and disorientation.

9.      Paroxysmal hypersomnic and katalepsic syndromes with autonomic – vascular crisis are observed at ischemia of hypothalamic structures.

10. Syndrome of temporal epilepsy.

11. In the subclavian steal syndrome the patient has a narrowed subclavian artery and the arm “steals” blood from the basilar artery via the vertebral artery. There may be a cervical bruit and a difference in blood pressure between the arms. At times of arm exercise the patient may experience vertebrobasilar insufficiency.

 

      Except carotid and vertebrobasilar cerebral ischemic crisis there are associated dynamic cerebral blood circulation disturbances such as:

·        Coronary – cerebral crisis

·        Aorto – cerebral crisis

·        Liver- cerebral crisis

·        Cholecysto – cerebral crisis

 

TIA with neurological symptoms that clinically disappear within 24 hours but leave changes  at CT such as low density zones  are regarded as “ minor ischemic strokes “.

      It is important to mention that the duration of TIAs is from several minutes up to 24 hours. But usually it is 10 – 15 minutes.

     One of TIA‘s characteristic features is relapse, when attacks are observed 3 – 5 times per year. There is one more peculiarity, which is necessary to remember – the attacks in vertebrobasilar territory are more common and are frequently repeated in spite of TIA in carotid territory.

But TIA in carotid territory prognosis is much more serious. Usually in one or two years after first attack stroke is developed.

     Another peculiarity is that if TIA is observed several times per 24 hours it means there is pathology of MA. Transient in word TIA concerns only neurological clinical picture, but has nothing to do with hemodynamic cerebral disturbances, as they are observed during the next 3 weeks.

 

Hypertensive cerebral crisis

It takes about 13 – 15 % of all acute disturbances of cerebral blood circulation.

Pathogenesis In course of a set of experiments it was found out that the spasm of veins during increasing of blood pressure displays a reaction of cerebral blood circulation regulation. The spasm of veins protects our brain from excessive perfusion. In case of rapid and severe increasing of blood pressure the system of self-regulation cannot compensate it. That is the main reason of disturbance of self-regulation system of blood circulation and brain hyperemia. It also promotes brain oedema, blood circulation deficiency and ischemia of brain tissues.

 

Clinical features of hypertensive crisis:

• General

• Regional

• Mixed

Hypertensive crisis is a manifestation of hypertension or symptomatic arterial hypertension exacerbation. It manifests as general cerebral and focal symptoms.

Except high blood pressure severe headache, heavy head, psychomotor agitation, obscured consciousness , heart beating, shortness of breath, heart pain, nausea, vomiting, sometimes epileptic attacks are observed in case of hypertensive cerebral crisis . It is also usually accompanied by autonomic disturbances, such as sweating, feeling of cold in extremities, change of face colour, heart and breathe rate.

According to the system of hemodynamics  there are three types of crisises

·        Hyperkinetic

·        Hypokinetic

·        Eukinetic

 

1.      Hyperkinetic type usually is accompanied by increasing of heart outflow with increased heart index more than 4.5 l per min in m² and normal general peripheral resistance.

2.      Hypokinetic type is accompanied by decreasing of heart outflow with decreased heart index to 2.8 l per min in m² and high general peripheral resistance.

3.      Eukinetic type is accompanied by normal heart outflow and slightly increased general peripheral resistance.

 

The main clinical features of hyperkinetic crisis are:

1.      There is a rapid development of crisis without portents.

2.      Mainly systolic blood pressure is increased (More than 180-200 mm)

3.      General cerebral symptoms are well – expressed. That means psychomotor agitation, severe headache with nausea and vomiting.

4.      There are well – expressed autonomic disorders, such as shortness of breath, red or pale skin, and polyuria.

5.      The duration of crisis is up to several hours.

 

The main clinical features of hypokinetic crisis are:

1.      There is gradual development against long lasting hypertension background.

2.      Mainly diastolic blood pressure is increased.

3.      There is well – expressed EKG – changes: slow intra – ventricular conductivity, decreasing of ST – segment.

 In this case the risk of ischemic stroke is too high.

The main clinical features of eukinetic crisis are:

1.      A rapid development.

2.      Both systolic and diastolic blood pressures are increased.

3.      The symptoms of acute left – ventricular insufficiency and lung oedema can be observed.

 

According to the duration hypertensive crisises are divided into:

1.      Mild, which last up to 1 hour

2.      Mediate (they last several hours)

3.      Severe (they last from 5 –6 hours up to 24 hours)

 

The frequency:

·      Mild hypertensive crisis are:

Frequent – means they are observed more than 4 times per month;

Moderate frequent – means they are observed 3 – 4 times per month;

Rare – means they are observed 1 – 2 times per month;

 

·      Mediate and severe hypertensive crisis are:

Frequent – means they are observed more than 5 times per year;

Moderate frequent – means they are observed 3 – 5 times per year;

Rare – means they are observed 1 – 2 times per year.

 

Diagnostics of dynamic blood circulation disturbances

      When the symptoms of blood circulation disturbances last from several minutes up to hour there are no problems with diagnosis of dynamic blood circulation disturbances, such as transient ischemic attack or hypertensive crisis. In case of rapid development of general cerebral and focal symptomatic and duration up to several hours usually the diagnosis of dynamic blood circulation disturbances is put afterwards, as nobody knows the results (sometimes stroke is developed in such a way).

      Very often transient ischemic attack or hypertensive crisis is the first sign of heart – vascular system disorders. That’s why it is very important to reveal the main disease. That’s why we need additional methods of patient’s examination.

 

Additional methods of patients’ with DCBCD medical examination

1.      Ultrasonic doplerography – finds out the absence or presence of stenosis and occlusions of magistral arteries of head and neck.

 

 

 

 

2.      Rheoencephalography – finds out asymmetry of blood circulation, the state of vessel tonus and elasticity of vessels.

3.      EEG – finds out diffuse and local changes of brain bioelectric potentials.

4.      X –ray examination of cervical part of spinal cord – finds out osteochondrosis, spinal abnormalities.

 

 

5.      EKG – finds out the state of coronal vessels, rhythm disorders, and coronary insufficiency.

6.      Otoneurological examination is recommended in case of expressed vestibular syndrome in order to exclude labyrinth pathology.

7.      Ophthalmic examination – finds out sclerotic or hypertensive changes on eye fundus.

 

 

8.      Blood analysis.

9.      Coagulation test – finds out increased aggregation of thrombocytes, erythrocytes, and hematocrit.

10. Biochemical blood analysis – finds out proteinemia, increased cholesterin, b– lipoprotein, pre-b– lipoprotein.

 

Differential diagnosis

Dynamic blood circulation disturbances are usually differentiated with:

1.      Migraine crisis

2.      Partial epileptic attacks

3.      Vestibular crisis

4.      Multiple sclerosis

5.      Brain tumor

6.      Hypoglycemia

7.      Faint

 

Treatment of dynamic blood circulation disturbances

      Hospitalization is necessary for the patients with:

a.      Severe cerebral – vascular crisis that can result in stroke

b.      Repeated attacks with well – expressed focal symptoms

c.      Severe hypertensive crisis with high blood pressure

d.      Coronary – cerebral attack, suspected myocardial infarction or angina pectoris.

 

The main principals of DBCD treatment

1.      To normalize blood pressure

2.      To improve brain hemodynamic

3.      To improve microcirculation and rheologic properties of blood, to prevent aggregation of blood cells

4.      To decrease vessels’ penetrance

5.      To prevent brain oedema, to decrease intracranial hypertension

6.      To improve heart activity

7.      To improve brain metabolism

8.      To overcome autonomic syndrome

 

Treatment of hypertensive crisis

1.      At all kinds of crisis  hypotensive medications are used:

·        Clofelin 1ml 0.01 % i/v in 20 ml of physiologic solution

·        Dibasol 0.5% 2 – 4 ml i/m or i/v

·        Euphyllini 2.4% 10.0  i/v in physiologic solution

·        Antagonists of Calcium  (finoptini 0.5% 2 ml i/v in 10 ml of physiologic solution)

·        Cardioselective b-adrenoblockers (athenolol  25 – 50 mg per day)

·        Nifidipine 10- 20 mg

·        Inhibitors of ACE – Enalapril 5 – 10 mg

·        In case of too high blood pressure with left ventricule insufficiency and lung edema ganglioblockers are used – benzohexonium 2.5 % 0.5 – 1 ml i/m or s/c in glucose solution by drops.

 

2.      In case of hypertensive hypokinetic crisis we usually begin with:

• Dibasol 0.5% 4 – 6 ml

• b-adrenoblockers – Anaprilini 0.1% 5 ml i/v 

But the last are contraindicated at bradycardia, disoders of atrioventricular conduction.

 

3.      In case of hypokinetic crisis we start with peripheral vasodilatators:

• Apresin – 2% 1 ml i/v by drops;

• Diazoxid 1.5% 20 ml 3 – 4 times per day.

 

4. At eukinetic crisis we usually use clofelini, antagonists of calcium, spasmolytics.

 

5. At all kinds of hypertensive crisis with psychoemotional and autonomic reaction we prescribe I/v by drops:

• Aminazini 2.5% 1 ml in 200 ml of physiologic solution

• Sibazoni 0.5% 2 ml

• Pipolfeni 2.5% 2 ml

 

1.      In order to prevent brain edema we use euphillini 2.4 % solution 10 ml with 2 ml lazix 

2.      To decrease brain hypoxia we use Na oxybutiras 20% 10 ml i/v in glucose solution.

 

Treatment of TIA

1. Blood pressure normalization

a.       At heart failure and systolic blood pressure less than 120 mm glycosides are used:

·        Corglyconi 0.06 % 1.0 + strophantini 0.05 % 1.0 in 20 ml of 40 % glucose  i/v

·        Cordiamini 1 ml s/c

·        Sulfocamfocaini 10 % 2ml i/m

·        Cofeini 10 % 1ml s/c

·        Mesatoni 1- 0.05 % 1 ml s/c or i/m at low BP

·        Prednisoloni 60 – 120 mg i/v by drops with 200 ml 5 % glucose

b.       At hypertension hypotensive therapy and spasmolytics are used in usual doses.

 

4.      To improve brain hemodynamic vasoactive medications are used:

·        Euphilini 2.4 % 10 ml

·        Cavintoni 10 – 20 mg i/v with 20 ml 0.9 % NaCl

·        Sermioni 4 –8 mg i/v by drops

·        Ksantinoli nicotinas 15 % 2 ml i/m

 

3. To improve microcirculation and rheologic properties of blood, to prevent    aggregation of blood cells. (It is especially important in case of well expressed focal neurological symptoms in order to prevent stroke).

·        Direct anticoagulants:

– Heparini 5 –10 000 U. s/c 3 –4 times per day during 3 –5 days, than 2 500 U. 4 times per day during 3 – 4 days;

– Fraxiparini 0.3 x 2

·        Indirect anticoagulants:

–       Pelentani 0.1 – 0.3

–       Fenilini 0.015 – 0.03

–       Syncumar 0.004 2-3 times per day during 2-3 weeks

 

4. Antiagregants:

·        Aspirini 70 –80 mg once a day

·        Ticlidi 0.25 2 times per day during 2- 3 months

·        Trentali 2% 5 ml i/v by drops (it is contraindicated at myocardial infarction, do not use it with heparin or on an empty stomach)

·        Agapurini 1 pill 3 times per day

·        Reopoliglucini 200 –400 ml i/v by drops

·        Solcoserili 10 –20 ml i/v by drops during 5 –7 days

·        Ksantinoli nicotinas 15 % 1 –2 ml i/m

·        Curantili 0.025 3 times per day (it is contraindicated at low BP, heart failure)

·        Plavix 75 mg per day

·        Parmidini 0.5 3 times per day

 

1.      To prevent brain edema, to decrease intracranial hypertension:

·        Furasemidi 40 –80 mg per day

·        Lasix 1% 2ml i/v or i/m

·        Manitoli 10 –20 % 200 ml i/v

·        Dexoni 4-6 mg i/v or i/m

·        Albumini 5 % 100 ml

·        Vit E 5% 2 ml i/m, Aevit 1 ml i/m, Unitioli 5 ml

 

6. To improve brain metabolism:

·        Nootropil 20 % 5- 10 ml

·        Instenoni 2 ml i/m or i/v by drops

·        Solcoserili 10 –20 ml i/v by drops

·        Actovegini 2 ml i/m or i/v (it is contraindicated at cardiovascular failure, oliguria, lung edema)

·        Cerebrolisini 15 % 1.0 ml i/m

 

7. Antioxydants:

·        Vit E 1 ml i /m

·        Tiatriasolini 1 ml i /m

·        Emoxipini 2.0 i/m

 

8. Symptomatic treatment:

·        At vomiting and hiccup – cerukal, aminasini, galoperidol, validol

·        At headache – tramadol, analgini

·        At agitation – sedatives and anxyolytics

 

Surgical treatment – is used at stenosis of general or internal carotid artery (when stenosis is more than 70 % according to ultrasonographic data). Thrombinectomy is used.

Prevention means in term diagnosis and treatment of main disease (first of all atherosclerosis, hypertension, and heart diseases).

 

Working efficiency The persons with DCBCD are regarded temporary disabled. In case of frequent and repeated DCBCD it is necessary to employ patient in order to exclude mental and physical strain or direct him to MSEC to fix up the group of disability.

 

Students’ practical Study Program.

 

Step I.  Aim: To make the clinical diagnosis. For this purpose it is necessary:

1.      To determine types of acute disorders of the cerebral circulation.

2.      To determine Carotid or Vertebrobasilar vessels distribution.

3.      To find the reasons to cause disorders of cerebral circulation.

4.      To formulate the diagnosis, for example:

a)     TIA in Left Carotid Distribution from cerebral atherosclerosis and hypertensive disease, stenosis of the left vertebral vessel

b)                                                                                                                                   DE III st (intracerebral subarachnoid hemorrhage – aneurysm of cerebral vessel’s, 1995 y)

TIA may occur in carotid or vertebrobasilar territory. The differential points between these two types of TIAs are:

1. TIAs in carotid distribution

–         transient blindness in the eye on the same side as a narrowed internal carotid artery (amaurosis fugax). Patient may report a “shade coming down” over his eye.

–         Transient aphasia.

–         Motor and sensory symptoms in a single extremity (upper or lower), or a clumsy “bear’s paw” hand.

2. TIAs in vertebrobasilar distribution

–         slurred speech, dizziness, ataxia, syncope, numbness around lips or face, double vision,

–         hemiparesis and hemisensory loss do not parallel each other in the individual limb as in carotid disease.

Differential diagnosis. Migraine may be accompanied by transient neurologic deficits (visual disturbances, motor or sensory symptoms) and can usually be identified by the headache that follows the neurologic deficit, the gastrointestinal symptoms, and by the fact that it appears in patients younger than those with cerebrovascular disease. Nevertheless, older people do experience migraines phenomena, and there may not always be prominent headache symptoms.

Keep in mind that focal seizures may produce transient neurologic symptoms (numbness, leg or arm weakness) which may persist for hours. Obtain an EEG if seizures are suspected.

Some systemic factors are known to be associated with TIAs. Well-recognized ones are anemia, polycythemia, thrombocytosis, and hypoglycemia.

Step II. Aim: Administer emergency treatment. For this purpose it is necessary to choose:

1. emergency therapy of TIAs.

2. differentiated emergency therapy of hypertensive crisis.

3. rehabilitation and prophylactic programs for cerebrovascular patients.

 

Strokes

 

Definition

     In broadest sense, the World Health Organization has defined stroke as “rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other then that of vascular origin”.

 

Epidemiology

     According to World Health Organization data about 150 to 740 people per 100 000 population suffer from stroke all over the world. In the United States of America there are about 400 000 patients with stroke every year. In Europe there are about 1 mln people with stroke every year. In Ukraine according to 1997 data 130 890 patients had stroke and 54 000 of them died. During the last 30 years the frequency of stroke has increased significantly all over the world.

 

Classification of stroke     Stroke is classified by the pathology of the underlying focal

brain injury into either infarction or hemorrhage. Infarction is much more common than hemorrhage. The proportion between them is 4:1 (80 % to 20%).

 

Hemorrhagic stroke means hemorrhage.

 

 

According to the localization of hemorrhage it is divided into such groups:

1.      Intracerebral (when the hemorrhage is into the substance or parenchyma of the brain)

2.      Membrane

a)     subarachnoid (when the bleeding originates in the subarachnoid spaces surrounding the brain)

b)     epidural and subdural (traumatic)

3.      Combined

a)     subarachnoid – parenchymatous

b)     parenchymatous– subarachnoid

c)      parenchymatous–ventricular

d)     ventricular

     

Etiology

The most common causes of hemorrhage are:

1.      Hypertension

2.      Symptomatic arterial hypertension (at kidney diseases, systemic  vessel processes)

3.      Inborn arterial and arterial – venous malformations

4.      Blood diseases (leucosis, polycythemia)

5.      Cerebral atherosclerosis

6.      Intoxications, such as uremia, sepsis

 

Pathogenesis

       Hemorrhage results from rupture of the vessel anywhere within the cranial cavity or diapedesis in case of increased penetrance of vessel’s wall. Rupture of the vessel is much more common and takes about 80 % of all stroke cases while diapedesis occurs only in 20 % of cases.

       Hypertension has been implicated as the main cause of hemorrhage. Hypertension is the cause of a weakening in the walls of arterioles and the formation of micro aneurysms. Among elderly nonhypertensive patients with recurrent hemorrhages, amyloidal angiopathy has been implicated as an important cause. Others causes include arterial-venous malformations, aneurysms, bleeding disorders or anticoagulation, trauma, tumors, cavernous angiomas and drug abuse.

 

 

Pathomorphology 

    In case of hemorrhagic stroke we distinguish hematoma – like hemorrhage and transudation – like hemorrhage.

     According to the localization there are:

1.      Lateral hemorrhage (they are located laterally compared with the internal capsule. They take about 40 % of all hemorrhages).

 

 

2.      Medial hemorrhage (they are located medially compared with the internal scapula and take about 10 % of all hemorrhages).

 

 

3.      Combined hemorrhages (they take the whole region of basal nuclei: subcortical nuclei, thalamus, and internal capsule. They take about 16 % of all hemorrhages).

 

 

4.      Cerebellar hemorrhages (6 – 10 %)

5.      Brain stem hemorrhages (5 %).

 

 

       Primary ventricular hemorrhages are very rare. In case of large hemorrhage brain edema is developed. The last is associated with dislocation of brain stem which is the main cause of patients’ death.

 

 

 

     The main cause of death is rupture into the ventricular system and brain stem hemorrhage with lesion of main vital centers.

 

Clinical picture There are three main periods of stroke:

1.      Acute (up to 3 – 4 months)

2.      Renewal (up to 1 year)

3.      Residual

 

Acute period is divided into such stages:

1.      Precursors

2.      Apoplectic stroke

3.      Focal signs

 

      Usually hemorrhage has rapid development in day time during physical or emotional stress. The patients are usually young. And they have risk – factors in anamnesis. Precursors are very rare.

      Two main groups of symptoms are typical for hemorrhage – general cerebral and focal. Typically general cerebral symptoms prevail over focal ones in case of hemorrhage.

      General cerebral symptoms mean severe headache, vomiting, consciousness disorders.

       While examining patients with consciousness disorders we should pay attention to the possibility of contact with patient, his ability to follow commands, to say what has happened with him, to orient in the space and time and so on.

         Sometimes sopor occurs at the beginning of hemorrhage, which can develop in coma in a few hours.

    

Coma is characterized by deep consciousness disorder, disturbance of breathing and heart activity. The patient doesn’t respond to stimuli.

        At atonic coma all reflexes are lost, blood pressure is decreased and there is breathing disturbance.

       In case of coma development response to stimuli is absent, eyes are closed, mouth is opened, face is red, lips are cyanotic, neck vessels are pulsing, there is breathing disturbance, skin is cold, pulse is strained and slow, blood pressure is increased, temperature increases in 24 hours. Patient is lying on his back. All muscles are relaxed. Pupils are changed (there can be anizokoria, cross – eyes, sometimes gaze paresis can be observed).Mouth angle is a little bit lower. On the opposite side hemiplegia is often observed: the arm is falling down like bine, there is hypotonia of muscles, reflexes are low, and Babinski sign is often observed too.

        Sometimes meningeal signs, vomiting and dysphagia are observed too. Retention of urine or involuntary urination can also occur. In case of cortex irritation epileptic attacks can be developed. Large hemisphere hemorrhage is often complicated by secondary brain stem syndrome. It manifests as progressive breathing disorders, disturbance of heart activity, consciousness, eye movements, changes of muscle tonus (hormetonia), autonomic disorders (sweating, tachycardia, hyperthermia).

 

Brain stem hemorrhage is associated with tetraparesis, alternating syndromes, eye movement disorders, nystagmus, gorge disorders, cerebellar syndromes.

     

 Pons hemorrhage manifests as ptosis, gaze paresis, increased muscular tone                   (hormetonia).

     

 Cerebellar hemorrhage usually starts with dizziness, severe headache in occipital lobe, vomiting. Eye movement disorders, ptosis, Gervig – Mazhandi syndrome, Parino syndrome are observed. It is also associated with cerebellar symptoms, such as nystagmus, dysartria, hypotonia, and ataxia. Paresis of extremities is not common.

       The most common complication of intracerebral hemorrhage is rupture into the ventricle system. This is usually associated with worsening of patient’s state, hyperthermia, breathing disorders, and hormetonia. Hormetonia manifests as changes of muscle tone in extremities, when hypotonia is changed into hypertonia in a few seconds or minutes.

     

 At right hemisphere hemorrhage involuntary movements ionparalysed extremities are observed and they are called parakinesis.

 

    

  

On the side of lesion there is anizokoria, Bechterev phenomena, painful trigeminal and occipital points, automatic movements, gaze paralysis, Kerning sign.

 

            

 

        On the opposite side – positive Bare’s sign, mouth angle is located lower thaormally.

 

   

 

foot is turned outside,                                                                                     pathological signs,

 

 

;                                                                               

 hypotonia, hyporeflexia

 

 

 

The run of the disease

      The patients with brain hemorrhage are in very severe state. 70 % to 95 % of them died. About 40 % – 45 % of them die during the first day, the rest of them – live 3 or 5 days.

      The main cause of death is compression of brain stem as a result of brain edema and rupture into ventricular system associated with disorders of vital centers.

       In case of good prognosis the patients usually recover from coma, then reflexes appear, general cerebral symptoms regress, the patients start to gorge, then they start to move, sensation and speech renew also.

 

Diagnostics

     In case of rapid development of all symptoms with loss of consciousness, high blood pressure and presence of focal symptoms there is no problem with putting diagnosis. But when the hemorrhage starts gradually without loss of consciousness, then it is much more difficult to put a diagnosis. In this case instrumental and laboratory examination has a great meaning.

    In blood usually leucocytosis, related lymphopenia, hyperglycemia (up to 8 – 10 mmole/l) is observed.

     In liquor which is flowing out under high pressure during lumbar puncture a great number of erythrocytes are found.

 

 

1.      normal, 2. subarachnoid haemorrhage, 3. intracerebral haematoma, 4. serous meningitis

2.     

 

 

    On eye fundus – retinal hemorrhages, hypertonic angioretinopathy and Salus symptoms are observed.

 

        

 

    At echoencephaloscopy there is dislocation of middle structures on 6 –7 sm to the healthy side.

 

 

    By means of angiography we can find out aneurysm, dislocation of blood vessels, to find out zone “without vessels “.

 

             

 

EEG

 

   

 

CT and MRI find out hyperdensive focuses.

 

Mixed parenchimatous-ventricular haemorrhage                                                               Epidural haematoma

 

            

 

Subdural haematoma

 

 

Differential diagnosis

1.      Infarction of brain (thrombembolic)

2.      Epistatus

3.      Uremic coma

4.      Diabetic coma

5.      Traumatic hemorrhage

6.      Brain tumor with inside hemorrhage.

 

Subarachnoid hemorrhage (SH)

 

Etiology The most common cause of SH is aneurysm rupture. The other causes include hypertension, atherosclerosis, blood diseases, rheumatism, brain tumors, and uremia and so on. The rupture risk – factors are physical or emotional stress, changes of blood pressure, alcohol usage.

   

 According to Samoiylov (1990) there are 8 kind of etiologic factors of subarachnoid hemorrhage:

1.      Aneurysmatic (50 – 62 %) – aneurysm rupture.

2.      Hypertensive (at hypertension)

3.      Atherosclerotic (15 %)

4.      Traumatic (5 – 6 %)

5.      Infectious – toxic (8.5 %)

6.      Blastomatose (at tumors)

7.      Pathohemic (at blood diseases)

8.      Cryptogenic (4 – 4.8 %)

 

 

 

Table 9-2

Signs and symptoms of aneurysms according to site of origin

 

Clinical features

      The development of the disease is rapid, without precursors. Although some of patients have symptoms of aneurysm: headache in frontal lobe, paresis of CN (Oculomotor N is often damaged).

     The first signs of SH are severe headache or feeling of hot liquid flowing in the brain. At the beginning this pain is local (in the region of occipital lobe) than it becomes more diffuse. Later pains ieck, back appear, sometimes they irradiate in legs. Simultaneously with headache vomiting and nausea occur. Besides these symptoms there are often general cerebral symptoms, such as short loss of consciousness, psychomotor excitement, seizures.

     In a few hours or the next day meningeal syndrome occur. It manifests as rigidity of occipital muscles, symptoms of Kernig, Brudzinski, and general hyperesthesia. Significant focal neurologic symptoms are not common. Only in case of basal hemorrhage CNs suffers (that is the reason of ptosis, cross – eye, dyplopia, paresis of mimic muscles).

That’s why lesion of CNs is typical for basal aneurysm rupture.

In acute stage of hemorrhage a lot of patients have focal symptoms: paresis of extremities, sensory and speech disorders. Usually it can be explained by associated brain hemorrhage, arterial spasm and as a result local ischemia. Spasm is usually developed on the 3rd – 4 th day and lasts till 3rd – 4 th week.

On the second or third day almost all patients with SH have increased temperature to 37.5 – 38°. Leucocytosis is also observed. In liquor fresh blood is found out.

    In severe cases significant disorders of heart – vascular system and breathing are observed.

 

The main complications of SH are:

1.    Arterial   vasospasm   occurs   in   approxi­mately 30 percent of cases of SAH and has a peak in­cidence 6 to 8 days postbleed. However, it can occur from 4 to 12 days after aneurysm rupture. Once va­sospasm develops, it can persist for several days to several weeks.

Patients with a large volume of blood in the basal cisterns carry the highest risk of spasm.¹⁸ Blood in the sylvian fissure indicates intermediate risk.¹⁹ About 12 percent of patients with extensive va­sospasm will develop permanent neurological deficits or die.

The pathogenesis of vasospasm is obscure. It probably related to the presence of oxyhemoglobin in the subarachnoid blood clot, leading to the release of cytokines that stimulate release of endothelia, an agent known to cause vasospasm. Increased concen­trations of endothelia have been demonstrated in plasma and cerebrospinal fluid (CSF) after SAH.

An alternative hypothesis proposes that the presence of blood in the subarachnoid space leads to inflammation and the release of platelet activating factor from inflammatory cells, platelets, and vascular endothelium, resulting in contraction of the muscle in cerebral arterial walls and vasospasm.

2.    Rebleeding following ruptured aneurysm is maximum in the first 24 h with a cumulative risk of about 20 percent in the next 14 days. Rebleeding re­sults in death in about 60 percent of affected cases.

3.    Intracerebral hematoma can produce a con­tralateral homonymous hemianopia and hemiparesis.

4.    A subdural hematoma may result from rup­ture of an aneurysm into the subdural space.

5.    Acute hydrocephalus is the result of occlu­sion of the subarachnoid space by breakdown prod­ucts of red blood cell disintegration and the ensuing inflammatory   response.   Hydrocephalus   occurs   in more than 50 percent of cases of SAH within 30 days of the hemorrhage but can occur quickly within a pe­riod of several hours following SAH. Ventricular peri­toneal shunting may be required in those who show delayed neurological deterioration and persistent ven­tricular enlargement.

 

6.    Cardiac arrhythmias and in some cases car­diac injury with pulmonary edema presumably the result of cerebral or brainstem injury are recognized complications of SAH.

7.    Inappropriate secretion of antidiuretic hor­mone may occur in severe SAH or as a postoperative complication. Some patients develop hyponatremia due to inhibition of renal tubular sodium absorption rather than inappropriate secretion of antidiuretic hor­mone.

8.    Pulmonary and urinary tract infections, de­hydration, electrolyte disturbances, and the develop­ment of decubiti are not unusual in comatosed patients.

9.    Epilepsy develops in 9 percent of patients who survive SAH, occurring within 4 weeks after the hemorrhage in the majority of cases.

 

Diagnostic Procedures

1.      Computed tomography (CT) scanning is the procedure of choice in the diagnosis of SAH and will confirm the diagnosis in 85 percent of cases, if this study is performed within 48 h of bleeding.

A CT

scan will reveal blood in the basal cisterns in most patients with SAH (Fig. 9-3), and the extent of an in­tracerebral hematoma, cerebral infarction, cerebral edema, and acute hydrocephalus are readily demon­strated.  Intraventricular and intracerebral bleeding and hydrocephalus have adverse effects on survival. Localized thick or diffuse collections of subarachnoid blood in the basal cisterns are associated with a high risk of vasospasm and a poorer prognosis.²⁸ Aneurysms are occasionally seen in an enhanced CT scan.

 

Subarachnoid haemorrhage in posterior cranial fosse.                               Subarachnoid haemorrhage in anterior cranial fosse.

    

 

 

 

 

2.    Magnetic resonance imaging (MRI) scan­ning has no advantage in the diagnosis in the early stages of SAH. However, MRI may detect the site of blood clot when it is no longer detectable by CT and is useful in detecting the probable source of hemor­rhage in cases with multiple aneurysms. Magnetic resonance angiography should always be performed in cases of SAH when cerebral angiography fails to demonstrate an aneurysm and is regarded as the supe­rior technique when compared to digital subtraction angiography in some centers.

3. Lumbar puncture reveals a bloody CSF un­der increased pressure. The supernatant fluid is xan­thochromic within 6 h of SAH. There is a polymor­phonuclear pleocytosis within 24 h, and later, appearance of mononuclear cells. Red blood cells usually disappear from the CSF by 5 days; their per­sistence indicates that further hemorrhage has oc­curred. Xanthochromia usually lasts for about 28 days. An estimate of the date of onset of SAH can be made by measuring the presence of oxyhemoglobin and bilirubin in the xanthochromic fluid by CSF spectrophotometry. Oxyhemoglobin appears at the onset of SAH and gradually disappears. Bilirubin ap­pears after 2 or 3 days and increases in amount as oxyhemoglobin decreases. Recurrent hemorrhage is associated with a late rise in the presence of oxyhe­moglobin. Lumbar puncture continues to have an im­portant role in the diagnosis of SAH.

4.    Skull x-rays occasionally show the pres­ence of calcification in the wall of an aneurysm. Ero­sion of the lateral wall of the sella or anterior clinoid processes may occur. Pineal shift occurs in the pres­ence of a large hematoma. An ophthalmic aneurysm can cause enlargement of the optic foramen.

5.    Fourvessel  arteriography with multiple views to demonstrate the origin of each of the major intracranial arteries should be performed as early as possible in all cases of SAH (Fig. 9-5). The objective of this study is the demonstration of the origin of the aneurysm to define the neck of the aneurysm, and to detect the presence of multiple aneurysms (Fig. 9-6), or demonstrate the presence or absence of vasospasm. The complication rate of arteriography performed by an experienced neuroradiologist, using modern tech­niques, is less than 1 percent. Rebleeding from a rup­tured aneurysm during arteriography is rare, occur­ring in less than 3 percent of cases. The risk of  rebleeding is significantly higher during the first 6 h after the initial event.³² Consequently, it is prudent to delay arteriography for at least 6 h after the initial hemorrhage.

6.    CT angiography. High-quality CT angiog­raphy provides adequate depiction of aneurysms in 90 percent of cases allowing surgery to be performed on the basis of CT angiography alone.

 

       

 

7.    Transcranial Doppler ultrasound monitor­ing is a useful procedure in the detection of va­sospasm leading to delayed ischemic neurological deficits complicating SAH.

 

 

 

Prognosis Usually is not good. As during the 2nd – 4th weeks recurrent hemorrhage can occur which can cause patient’s death.

Thus we usually put the diagnosis of SH in case of:

1.      Stroke – like development with general cerebral and meningeal symptoms and absence of significant focal neurologic deficit.

2.      The presence of blood in liquor (bleeding liquor during first day and yellow liquor on 3rd – 5th day)

3.      Retinal hemorrhages are on eye fundus

 

Differential diagnosis:

1.      Meningitis

2.      Acute food toxic infection

3.      Infectious diseases

     Lumbar puncture, CT, MRI, US helps to put diagnosis; angiography helps to find localization and sizes of aneurysm.

 

Brain infarction

Classification

      Brain infarction is divided into:

1.      atherothrombotic,

2.      cardioembolic,

3.      hemodynamic,

4.      hemorheologic

5.      Lacunar infarction.

 

Atherothrombotic and cardioembolic occurs in case of plugging of extracranial or intracranial vessel by atherosclerotic plague, thrombus or embolus from the heart.

Hemodynamic – one occurs at angiospasm in case of atherosclerosis, vascular insufficiency, central hemodynamics disorders. Rheologic – occurs in case of disturbance of rheologic blood properties.

 

Etiology

The most common causes of brain infarction are:

·        Atherosclerotic lesion of MAH

·        Combination of atherosclerosis with hypertension

·        Chronic ischemic heart disease with rhythm disorders

·        Combination of atherosclerosis with diabetes

·        Rheumatism, heart abnormalities (inborn and acquired)

·        Vasculitis

 

Pathogenesis

Atherothrombotic brain infarction occurs at thrombosis in case of atherosclerotic lesions, disturbance of rheologic blood properties, central hemodynamic disorders.

 

Cardioembolic brain infarction occurs at embolus plugged cerebral vessel.

The sources of embolus are:

a)     parts of aortal or arterial thrombus

b)     Parts of thrombus in case of heart abnormalities, such as mitral stenosis, aortal abnormality, rheumatic or bacterial endocarditis, myocardial infarctions, cardiosclerosis, cardiomyopathy.

3.   Embolism can occur at thrombophlebitis, lung abscess, malignant tumors, and sepsis.

4. Fat embolism occurs at bone fractures, after surgery associated with trauma of subcutaneous tissue.

5. Gas embolism occurs at surgery on lungs, at pneumothorax. 

      Usually it is difficult to distinguish thrombosis and embolism. That’s why we use the term “thromboembolism“.

 

Hemorheologic brain infarction

      Usually occurs at disturbance of self – regulation of brain blood circulation, in case of MAH abnormalities and long lasting angiospasm.

 

The lacunar syndrome

This condition is associated with small areas of in­farction deep in the cerebral white matter of the cere­bral hemispheres or in the pons, resulting from:

1.  Small vessel disease with lipohyalinosis and fibri­noid degeneration

2.  Decreased perfusion of penetrating arteries from proximal narrowing of larger vessels

3.  Branch artery atheromatous occlusion

4.  Embolism

However, the widespread use of MRI and CT scan­ning has shown that the lacunar state is not uncom­mon in asymptomatic individuals. Consequently, the diagnosis of lacunar syndrome should be approached with caution.

The lacunar stroke may be defined as a unilat­eral motor or sensory deficit without visual field deficit or disturbance of consciousness or language. The CT scan may show a small, sharply marginated hypodense lesion in the subcortical area, with the di­ameter smaller than 20 mm. Multiple lacunes are strongly related to hypertension and diabetes mellitus. Lacunar infarction is an acute onset of focal neurological deficits lasting more than 24 h. There are six recognized lacunar syndromes:

1.  Pure motor, hemiplegia or hemiparesis

2.  Dysarthria, clumsy hand syndrome

3.  Ataxic hemiparesis

4.  Sensorimotor stroke

5.  Pure sensory stroke

6.  Unilateral dystonia and involuntary movements such as choreoathetosis following lacunar infarc­tion of the putamen or globus pallidus  or hemiballismus owing to subthalamic infarction

Risk factors include hypertension, diabetes mellitus, heart disease, heavy alcohol consumption, cigarette smoking, and lack of physical exercise. La­cunar infarcts are the most common finding in cere­bral infarction in young adults.

 

Diagnostic Procedures All patients should re­ceive full evaluation for diseases of the blood vessels, atheroselerosis, arteriosclerosis heart disease abnormal­ities of blood constituents, and reduced cerebral perfu­sion. These investigations have been outlined under di­agnostic procedures for TIAs. Future developments of MRI with diffusion and perfusion studies, PET, and SPECT will define the location and extent of damage to cerebral tissue, and may permit earlier identification of blood vessel involvement in the lacunar state.

 

Treatment Control of risk factors (smoking, hy­pertension, diabetes mellitus) and treatment with an­tiplatelet agents or anticoagulants are of limited value, suggesting that the process of lacunar infarc­tion has advanced to a point where treatment of risk factors is ineffective.

 

Pathophysiology

     As a result of brain infarction in case of blood circulation less than 10 ml per 100 g of brain tissue in 1 min zone of focal necrosis is formed.

 

     During the first 6 hours this zone is surrounded by region with borderline blood circulation (18 – 20 ml per 100 g in 1 min). This region is called penumbra.

The neurons within this region are preserved structurally but their function suffers. During first 3 – 6 hours we can renew their function, that’s why this period is known as “therapeutic window “.

      After 6 hours zone of brain infarction is formed completely. Pathobiochemical and pathophysiological changes are observed in penumbra region. One of the main reasons of neurons death is accumulation of glutamat, which causes brain edema and disturbance of synaptic transference. The number of intracellular enzymes is increased. That causes activation of thrombocytes, microcirculation disorders, and ischemia. As a result ruination of neurons occurs.

 

Clinical features:

Acute period of brain infarction is divided into three stages:

1. Precursors

2. Apoplectic stroke

3. Focal signs

 

To precursors belong transient ischemic attacks in the same region where brain infarction is developed. Brain infarction usually is developed in elderly people at any time. Gradually during several hours focal neurologic symptoms are developed. Sometimes the beginning of brain infarction (BI) is rapid, especially in case of embolic stroke. But one of the most important differential features of BI is the prevalence of focal symptoms over the general cerebral ones.

General cerebral symptoms manifest as headache, vomiting, consciousness disorders. These symptoms are usually observed at thrombembolic stroke and are increased according to the brain edema.

   Focal symptoms depend on localization of the infarction, damaged vessel and state of collateral blood circulation. The most common brain infarctions are in the region of middle cerebral artery.

       Middle cerebral  artery  blood – supplies basal nuclei, internal capsule, a part of temporal lobe, middle and lower parts or pre – and post central gyruses, opercular region, a part of parietal lobe, gyrus angularis, posterior parts of upper and middle frontal gyruses.

 

 

If the artery’s main trunk is occluded hemiplegia, hemianesthesia, gaze paresis, speech disorders (such as motor, sensory, total aphasia) occur when the lesion is in left hemisphere and apractice – agnostic syndrome occur when the lesion is right hemisphere.

If the artery’s cortical branches are occluded motor and sensory disorders in upper extremity, hemianopsia, sensomotor aphasia, apraxia, alexia, acalculia occur when the lesion is in left hemisphere and anozognosia, and autotopognosia occur when the lesion is right hemisphere.

If the artery’s posterior branches are occluded hemianesthesia, bathianesthesia, astereognosis, afferent paresis of extremities, hemianopsia, sensory aphasia, agraphia, alexia, acalculia and apraxia occur.

Anterior cerebral artery blood – supplies the cortex of frontal lobe (superior frontal    gyrus), superior part of anterior central gyrus, superior part of posterior central gyrus, corpus callosum, a part of superior parietal lobulus, orbital part of frontal lobe, lobulus paracentralis.

Infarction in the area of the anterior cerebral artery causes spastic hemiparesis with the prevalence in proximal part of upper extremity and distal part of lower extremity. This kind of BI is associated with the symptoms of oral automatism, psychiatric disorders, dysphagia, dysphonia, astasia, abasia, motor aphasia, retention of urine.

If the internal carotid artery is occluded before ophthalmic artery alternating optic – hemiplegic syndrome takes place. That means blindness or visual disorders on the side of lesion and hemiparesis on the opposite side. There is absence of internal carotid artery pulsation oeck.

If the internal carotid artery is occluded intracranial hemiplegia, hemianesthesia, well expressed general cerebral symptoms as a result of brain edema, compression or dislocation of brain stem are observed.

      When the infarction is in the region of vertebral – basilar vessels occipital lobes and brain stem suffers.

       Infarction in cortical branches region manifest as visual disturbances: homonymic hemianopsia with preserved macular vision or upper qudrantive hemianopsia, sometimes visual agnosia and metamorphopsia can occur. If the lesion is in the left hemisphere alexia, sensory and semantic aphasia can be observed.

If the process is distributed on mediobasal part of temporal lobe, memory disorders, such as Korsak syndrome usually take place.

Posterior cerebral artery blood supplies occipital lobe, posterior part of lower and middle temporal gyruses, basal and mediobasal part of temporal lobe, deep thalamocollicular branches blood supply thalamus, hypothalamus, posterior – lower parts of cortex of parietal lobe.

 

Infarction in the region of the posterior cerebral artery causes hemianopsia, visual agnosia, hemianesthesia, hyperpathia, desorientation in space and time, disorders of space –optical gnosis.

Infarction in the region of deep branches of posterior cerebral artery that blood supplies thalamus, posterior part of occipital lobe, corpus callosum, radiate crown, causes thalamic syndrome of Dejerin – Russi. Than last manifests as hemianesthesia, hyperpathia, dysesthesia, thalamic pains, hemianopsia, pseudoathetosis, hemiataxia, and dynamic hemiparesis on the opposite side.

Infarctions in the region of vertebral artery Vertebral artery blood supplies brain stem; oblongata brain, cerebellum, cortex of occipital lobe, part of cervical part of the spinal cord. It can be damaged extra – or intra cranially.

In case of extracranial lesion systemic dizziness, hearing, visual, eye movements, vestibular, equilibrium disorders and paresis with sensory disturbances in extremities are observed. Some patients have “drop- attacks “.

In case of intracranial lesion alternating syndromes of oblongata brain occur.

      Infarctions in the region of basilar artery cause the lesion of pons, cerebellum, hypothalamus, cortex of occipital lobe. In case of acute occlusion loss of consciousness, eye movements disorders, pseudobulbar syndrome, tetraplegia, muscle tone disturbance, sometimes even cerebellar symptoms and cortical blindness occur. Most of these patients die because of the vital functions disorders.

When the lesion is in pons syndromes of Miyar – Hyubler, Fowil, Brisso – Siquar and alternating hemianesthesia occur.

Infarction in the region of mesencephalon causes Parino syndrome, which manifests as gaze paresis upwards.

Infarction in the region of brain peduncles causes Weber or Benedict alternating syndrome. Sometimes Clode and Fua – Nikolesku syndrome can be observed.

Clinical features Atherothrombotic stroke

      Occur at older age

      Developed during some ours and days

      TIA present in anamnesis

      Developed at night or in the morning time

      Stenosis and occlusion of MAH at ultrasound examination

      Decreased of Internal Carotid artery pulsation on the neck

 

Clinical features Cardioembolic stroke

      Precursors absent

      Acute onset at emotional and physician activity

      General cerebral signs are very intensive:

Loss of consciousness,

Seizures and psychomotor agitation

Severe headache

      Embolism of vessels of retina, extremities, other inner organs

      Embolism of different arteries of the brain

      Embolism of cortical branches of the brain arteries

      Maximal neurological deficit at debut of stroke

      More often Median cerebral artery are lesion

 

 

Lacune

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Diagnostics of Brain Infarction The main peculiarities are:

·        Before stroke period in the previous history (TIA in anamnesis)

·        The beginning of the stroke is gradual

·        Data of somatic and neurological status

·        Additional methods of diagnostics

       Usually the patients with BI have rheologic disturbances.

Liquor is pellucid, without significant changes. There is focus of pathologic activity on EEG. USG finds out occlusion, stenosis of carotic and vertebral arteries.

Angiography

CT reveals hypodensive focus on the second day. MRI helps to find out small focuses and those, located in the brain stem.

 

 

          

 

              

 

Differential diagnosis

3.      Traumatic hemorrhage, trauma of brain

4.      Myocardial infarction

5.      Epilepsy

6.      Uremic coma

7.      Hyperglycemic coma

8.      Hypoglycemic coma

9.      Brain tumor with inside hemorrhage

 

While differentiation we should pay attention on anamnesis, run of the disease, symptoms, blood pressure, MAH state, eye fundus state, EKG, laboratory data, LP data.

Alcoholic coma is characterized by alcohol odour, psychomotor agitation, red eyes and face, seizures, normal blood pressure, low reflexes, enlargement of liver.

Uremic coma is characterized by ammonium odour, oliguria, edema, and ascites.

Diabetic coma is characterized by acetone odour, Kusmaul breathing, dry skin, hypotonia, hyporeflexia, hyperglycemia, glucosuria, acetone and sugar in urine.

      Hypoglycemic coma is characterized by wet skin, normal breathing, seizures, and low sugar level in blood.

Epileptic coma is characterized by seizures, there is episyndrome in anamnesis. EEG helps to put a diagnosis.

Running of the disease There are three main kinds of stroke running:

1.      Favourable, when all damaged functions are renewed.

2.      Remittent when the patient state is worsening because of associated pneumonia or other complications.

3.      Progressive, which usually causes death of the patient.

       The most severe are hemorrhages. Mortality in this case is from 60 to 90 %. Especially increases mortality in case of hemorrhage in ventricles, brain stem and cerebellum.

Favourable prognosis is in case of limited hemorrhages, small in size, without brain edema and secondary brain stem syndrome development.

Mortality at brain infarction is in 20 – 27 % of all cases.

 

Strokes treatment

There are nondifferential and differential kinds of stroke treatment.

Nondifferential treatment includes:

1.      Prevention and treatment of pulmonary insufficiency

2.      Liquidation of heart – vascular disorders

3.      Brain edema treatment

4.      Normalization of water – electrolytes balance and acid – alkali balance

5.      Osmose correction

6.      Improving of brain metabolism

7.      Liquidation of hyperthermia and other autonomic disorders

 

1.      Prevention and treatment of pulmonary insufficiency

a)     the patient is lying on the bed with his head elevated

b)     cleaning of patient’s oral cavity

c)      tracheostomia (at inspiratory muscles paralysis)

d)     at lung edema patient is given oxygen; narcosis, Bobrov’s apparatus, 2 ml 1 % lazix, 2 ml 1% dimedroli, 2 ml 0.1 % atropini I / m  are used.

e)     Antibiotics are used in order to prevent pneumonia

2.      Liquidation of heart – vascular disorders

a)     At increased blood pressure we use:

·        Clofelini 1 – 3 ml 0.01 % solution i/m, i/v.

·        Dibasoli 3 – 4 ml 1 % solution i/v

·        Droperidoli 1 ml 0.25 % solution i/v

·        Rasedili 1 – 2 ml 0.1 % i/v, I / m,

·        In case of hyperkynetic type of blood circulation we use b– adrenoblockers (anaprilini, obzidani, inderal )

·         In case of hypokynetic type of blood circulation we use peripheral vasodilatators (Natrii nytroprussidi , appresini) in combination with euphyllini

b)     At low blood pressure we prescribe

·        Dexamethazoni 4 – 8 mg i/v by drops in physiological solution

·        Prednizoloni 60 – 120 mg i/v by drops in physiological solution

·        In order to improve heart activity we use strofantini, corgliconi, cordiamini

3. Brain edema treatment

Diuretics, corticosteroids, albumini, ganglioblockers, 20 % mannit, manitoli, glycerini, lazix, diakarbi are used.

4. Normalization of water – electrolytes balance and acid – alkali balance

      We should estimate patient’s necessity in water according to his secretion, the level of Na in blood, hematocritis. An average water necessity is 35 ml per kg, in patients with loss of consciousness it is 50 ml per kg. We should correct patient’s hyper- or hyponatriemia,   hyper- or hypokaliemia.  4 % solution of natrium bicarbonates i/v, trisaminum is used at metabolic acidosis. KCl i/v is used at metabolic alkalosis.

5.  Osmose correction

    Normally blood osmose is within 280 – 295, urine osmose is 600 – 900 mosm per liter.

   At stroke usually we have hyperosmose, which manifests as increased hematocritis, hyperagrigation.

 

6. Improving of brain metabolism

 Vit E, piracetami, aminaloni, cerebrolysini natrii oxybutiras are used.

7. Liquidation of hyperthermia and other autonomic disorders.

At hyperthermia we use

·        reopirini 5ml

·        analgini 50 % 2.0

·        aspizoli 0.5 g

 At autonomic disorders we introduce

·        sibazoni 0.5 % 1 ml

·        haloperidoli 0.5 % 1 ml

·        dimedroli 1 % 2 ml

·        natrii oxybutiras  20 % 10 ml

 

Differential treatment of haemorrhage:

The main directions of treatment are:

1.      To lower increased blood pressure

2.      To liquidate brain edema and lower intracranial pressure

3.      To increase coagulative properties of blood and decrease penetrance of vessels’ wall

4.      To prevent and treat cerebral vessels spasm

5.      To normalize vital and autonomic functions and prevent complications

6.      To treat hypoxia and brain metabolism disorders

1.        To lower increased blood pressure

Clofelini, b-aqdrenoblockers (anaprilini, obzidani, inderali), Calcium antagonists (nifidipini, adalat) IACE (capoten, enalapril, renarapril) are used.

At too high blood pressure ganglioblockers are used:

–          Pentamini 5% 1.0

–          Benzohexonium 2.5 % 1 ml

–          Arfonad 5 ml 5 % i/v in physiologic solution

 

2.        To liquidate brain edema and lower intracranial pressure

The same measures as in nondifferential treatment are used.

3.        To increase coagulative properties of blood and decrease penetrance of vessels’ wall

a)     CaCl2 10 – 20 ml 10 % i/v

      Vicasoli 1 – 2 ml 1 % i/v

         ascorbinic acid 2 – 5 ml 5 – 10 % solution I/m

b)     Antifibrinolytics:

   EAKA 100 ml 5 % solution 1–2 times per day I/v by drops during 5 – 7 days. Then we use it orally – 3 g every 3 –4 hours up to 3 weeks.

c)      At decompensated fibrinolysis we use

Trasiloli 20 – 30 000 U i/v by drops in 250 ml of physiologic solution

Hordox 5 000 U i/v by drops every other day

d)     to normalize microcirculation we use:

dicinoni 2 ml 12.5 % solution 2 – 3 times per day during 10 days, then 2 tablets (0.5 g) every day.

Ascorutini, rutamini (1 ml i/m 1 – 2 times per day)

4.        To prevent and treat cerebral vessels spasm:

Antagonists of Calcium are used:

Nimotop is introduced I / v 15 mg per kg per day during 5 – 6 hours. On the 5^th – 7 th day it is used orally 60 mg every 4 hours during 7 – 10 days.

5. To normalize vital and autonomic functions and prevent complications

6. To treat hypoxia and brain metabolism disorders.

The same measures as iondifferential treatment are used.

7. Symptomatic treatment.

At severe headache

·        baralhini 5 mli/ v

·        combination of analgini ( 4 ml 50 % solution ) with 1 ml 1 % dimedroli and novocaini 5 ml 0.5 % solution

·        promedoli are used.

At vomiting

·        haloperidoli 1 – 2 ml 0.5 % solution

·         droperidoli 1 ml 0.25 % solution  are used

At seizures

·        sibazoni 2 – 4 ml 0.5 % solution,

·        natrii oxybutiras 10 ml 20 % solution i/v are used

Surgical treatment is used at lateral or lobar hemorrhages less the 100 ml.

At subarachnoid hemorrhages surgical treatment is recommended during first 48 hours or on the second week.

In renewal period we prescribe

·        cerebrolizini 5 ml 2 – 3 times per day

·        piracetami 10 ml 20 % solution

·        instenoni 2 ml

·        actovegini 2 ml twice a day

 

Differential treatment of brain infarction

The main directions are:

1.      To renew blood circulation in zone of ischemia.

2.      To correct rheologic and coagulative properties of blood, to improve microcirculation.

3.      To prevent disorders of cerebral metabolism.

4.      To decrease brain edema.

5.      To treat brain hypoxia.

 

1.   To renew blood circulation in zone of ischemia

a)     . Actilaza 100 mg I/v by drops every 2 – 3 hours.

b)     Inhibitors of glutamat excretion (difenin, nimotop, MgSO4) are used. Nimotop is used 15 mg in 1500 ml of physiologic solution i/v by drops, or in tablets 30 – 60 mg 4 times per day.

In order to improve perfusion we use cavinton 20 mg I/v by drops.

At hyperperfussion we use:

·        euphyllini 10 ml 2.4 % solution,

·        penthoxiphyllini,

·        diuretics (manitol 15 % 100 – 200 ml) 

·        albumini 100 ml I/v

 

2.   To correct rheologic and coagulative properties of blood, to improve microcirculation

a) anticoagulative therapy is used only at progressive stroke:

·        heparini 5 000 U 4 times per day during 5 – 7 days, the 2 500 U during next 3 –4 days.

·        Fraxiparini is considered to be even more effective.

b)  Antiagregants are used also:

·        penthoxiphyllini 5 – 10 ml 2 % solution I /v by drops during 10 days, then 200 mg 3 –4 times per day up to 1 month.

·        Sermioni 4 mg I / v by drops during 10 days, then 1 tablet 3 times per day up to 1 month.

·        Ticlid 250 mg twice a day.

·        Aspirini 250 mg once a day.

·        Dipiridamoli 1 – 2 ml i/v by drops during 10 days, then 25 mg 2 –3 times per day.

c)      Hemodilution is reached by introduction of reopoliglucini 400 ml I / v by drops during 5 – 7 days.

3.      To decrease brain edema.

·        Glycerini 1 g per 1 kg is used I/v

·        Dexamethazoni 16 – 32 mg per day

4.      To treat brain hypoxia.

·        Vit E 1 ml i/m.

·        Piracetam 10 – 20 ml i/v by drops.

In case of stenosis, occlusion of MAH surgical treatment can be used.

Prognosis During the first two days the state of patients with brain infarction is very severe. In a few days it is going better. Recurrent stroke can occur during the first year, sometimes during the first 2 or 3 years.

Prevention means in time treatment of heart – vascular diseases, hypertension and rhythm disorders.

 

HYPERTENSIVE ENCEPHALOPATHY

Hypertensive encephalopathy is a syndrome charac­terized by marked elevation of blood pressure and ev­idence of increased intracranial pressure.

 

Etiology and Pathology Most patients with hy­pertensive encephalopathy have a long history of es­sential hypertension. In other cases, the elevation of blood pressure is secondary to another disease process such as acute glomerulonephritis, chronic nephritis, pheochromocytoma, Cushing disease, or acute toxemia of pregnancy.

There is diffuse cerebral edema and cerebral vasospasm. Microscopic examination reveals pe­techial hemorrhages and fibrinoid necrosis of the ar­teries.

The patient complains of severe headache with nausea and vomiting. Visual disturbances, including blurring of vision and scotomata, are frequent. Con­fusion, with progression to stupor, convulsions, and coma are seen in untreated cases. Examination of the fundi reveals papilledema and hypertensive retinal changes. Focal neurological signs are not characteris­tic but may be seen as a postictal phenomenon or when intracranial hemorrhage occurs.

 

Diagnostic Procedures The MRI and CT scans reveal diffuse cerebral edema.

 

Treatment Hypertensive encephalopathy is a med­ical emergency and the blood pressure should be re­duced as rapidly and safely as possible.

 

Prognosis Untreated hypertensive encephalopa­thy is fatal. Follow-up care and appropriate long-term medication allow patients to survive for many years.

 

Students’ practical Study Program.

Step I.  Aim: To make the topical diagnosis. For this purpose it is necessary:

1. To determine types of stroke.

Intracranial hemorrhage is usually deep, most commonly affecting putamen, thalamus, pons or cerebellum. Intracranial hemorrhage also occurs during waking hours, usually in a known hypertensive patient. The full deficit is seldom present at onset but develops gradually over minutes to hours. There is no warning, and headache is usually but not invariably present.

In subarachnoid hemorrhage, the neurologic deficit, if any, depends on where the bleeding occurs. Subarachnoid hemorrhage occurs abruptly with severe headache as the cardinal feature, often coming on during physical exertion.

2. To determine Carotid or Vertebrobasilar vessels distribution.

3. To find the reasons to cause disorders of cerebral circulation.

4. To find the periods of stroke.

5. To formulate the diagnosis, for example:

a)      Ischemic thrombotic stroke in Left Carotid Distribution from cerebral atherosclerosis and

   Hypertensive disease, acute period.

b)      Intracerebral subarachnoid hemorrhage, acute period, aneurysm of cerebral vessels.

Step II. Aim: Administer emergency treatment. For this purpose it is necessary to choose:

1. Undifferentiated emergency therapy of strokes.

2. Differentiated emergency therapy.

3. Rehabilitation and prophylactic programs for stroke patients.

 

 

Multiple sclerosis is a demyelinating disease of the central nervous system (CNS) caused by an autoim­mune reaction that is the result of a complex interac­tion of genetic and environmental factors.

 

Epidemiology

Multiple sclerosis is more common in women, with a female:male ratio of 2.1:1. The disease is rare in children and has a peak incidence at 30 to 33 years of age, with a decline in the late forties. The upper limit of age at onset has usually been accepted as 59 years, but late onset of multiple sclerosis after the age of 60 years is reported. However, these cases probably rep­resent late occurrence of overt symptoms in individu­als who have had the disease in a subclinical or un­recognized fashion for many years.

The natural history of multiple sclerosis has been studied extensively and it is clearly a disease of temperate zones, with an increase in the prevalence gradient south to north in the northern hemisphere, and north to south in the southern hemisphere. Three zones of high, medium, and low prevalence rates can be recognized. High-frequency prevalence rates of more than 30 per 100,000 population occur in areas lying between latitudes 45° and 65° north or south. This includes northern Europe, southern Canada, the northern United States, New Zealand, and southern Australia. These areas of high frequency are bounded by areas of medium frequency with preva­lence rates of 5 to 25 per 100,000 and include south­ern Europe, the southern United States, and most of Australia. Tropical areas of Asia, Africa, and South America have low prevalence rates of less than 5 per 100,000. Anomalies do occur, however, with levels as high as 170 per 100,000 reported in Switzerland, 53 per 100,000 in southern Spain, 59 per 100,000 in Sardinia, and 32 to 58 per 100,000 in Italy and Sicily.

These figures cannot be attributed to climate alone, however, because there are well-documented ethnic differences. Multiple sclerosis predominantly affects people of northern European extraction. In the United States, African-American men are less likely to develop multiple sclerosis when compared to white men in the same geographic area. Studies in Japan, Korea, and Hong Kong indicate a very low prevalence in populations in these countries. Simi­larly, persons of Asian extraction who have lived for several generations in the United States have a low prevalence rate for multiple sclerosis.

Such findings suggest a genetic factor in multi­ple sclerosis, and family studies have demonstrated that the risk of multiple sclerosis is increased for rela­tives of patients with the disease. Studies in Vancou­ver, British Columbia indicate a family rate for multi­ple sclerosis approaching 20 percent, with a lifetime age-correlated risk for the sibling of a patient of more than 25 times the lifetime risk in the general popula­tion. Twin studies indicate a concordance of 26 per­cent for monozygotic pairs compared to 2.4 percent in like-sex dizygotic twins—a figure similar to that for nontwin siblings of multiple sclerosis patients. This supports the view that differences in monozy­gotic and dizygotic twins have a genetic basis.

At the present time, evidence suggests that mul­tiple sclerosis is influenced by several genes, the ma­jor histocompatibility (MHC) complex class 2, HLA-DRII allele having the strongest association with the disease iorthern European populations. However, the association of different class 1 and class 2 alleles has been reported in other populations. Consequently, the current impression is that multiple sclerosis is probably polygenic, the result of complex genetic factors involving the interaction of genes and coding within and outside of the MHC complex. However, epidemiologic studies in Israel and the Faroe Is­lands point to involvement of environmental factors in multiple sclerosis. The ongoing study of the dis­ease in the inhabitants of the Faroe Islands—now ex­periencing a fourth epidemic of multiple sclerosis — suggests that multiple sclerosis is the result of an unidentified infection transmitted person to person and requiring a prolonged exposure of at least 2 years. Susceptibility is limited to ages 11 years to 45 years at the start of exposure and a further 6 years to onset in those who develop clinical signs of multi­ple sclerosis. However, these figures are the results of a study in one isolated community, and although they express findings in that community, they should not be extrapolated to multiple sclerosis on a global scale, because multiple sclerosis has been clearly demonstrated in children as young as 5 years.

At the present time, it is considered probable that both genetic and environmental factors are in­volved in multiple sclerosis, with infection as the major environmental agent, in that both viral and bacterial infections can initiate or precipitate attacks of multiple sclerosis. Evidence for a direct involve­ment of a viral agent such as human T-cell lymphotropic virus (HTLV)-l, herpes simplex virus (HSV)-l, HSV-6, scrapie, parainfluenza virus 1, measles virus, coronavirus, simian virus, chimpanzee cytomegalovirus, and LM7 retrovirus in multiple sclerosis is less compelling. The role of environ­mental factors other than infection has been studied, including the relationship of trauma and multiple sclerosis, indicating that patients are at no greater risk to experience an exacerbation of multiple sclerosis af­ter trauma than at other times, nor is it likely that trauma is ever a causal factor in initiating the disease process. The role of emotional stress in multiple sclerosis is more controversial because stress is diffi­cult to define and quantitate.

 

Etiology, Pathology, and Pathogenesis

The etiology is unknown. The pathological changes in multiple sclerosis show variation, depending on the age of focal demyelination (the plaque). In the acute state, there is active demyelination with accumulation of sudanophilic myelin breakdown products. The area is edematous and there is marked perivascular cuffing around veins and venules by lymphocytes and macrophages. Plaques are frequently located in the periventricular distribution, particularly in the cere­bral hemispheres, but plaques can occur at any site in the white matter and often penetrate into the gray matter of the cortex and deeper gray matter structures in the cerebrum and cerebellum. Because multiple sclerosis is a disease of the CNS, plaque formation is not uncommon in the brainstem, cerebellum, spinal cord, and the optic nerves, which are structurally part of the CNS, in which the oligodendrocytes are anti-genically similar to the oligodendrocytes in the spinal cord.

All multiple sclerosis lesions show a variable degree of axonal loss, ranging from 10 to 20 percent in milder forms of the disease, to 80 percent in se­vere, acute multiple sclerosis.

Epidemiologic studies support the concept that multiple sclerosis results from an aberrant immune reactivity occurring in a genetically susceptible host who has acquired a specific, or one or more nonspe­cific, neurotropic infections at a critical age. Ge­netic susceptibility is thought to be associated with genes within or close to the HLA-DR DQ subregion, located in the short arm of chromosome 6. This primary infection results in a self-sustaining, organ-specific autoimmune disorder that remains latent until activated by a subsequent infection years after the primary event. An alternative explanation suggests that the mechanism is one of persistent systemic viral infection, which contributes to the changes in the CNS periodically, or to a persistent CNS viral infec­tion that is targeted by T cells unpredictably, resulting in an inflammatory response producing myelin dam­age (bystander response). The common factor in any one of these theoretical situations is the activation of an autoimmune event within the CNS, directed against myelin antigen-specific T cells, but no spe­cific antigen has as yet been identified. Antibodies to myelin basic protein appear to be the most frequent finding in multiple sclerosis, but reactivity to other myelin antigens is a possibility. Candidates include proteolipid protein, the most abundant myelin protein in humans, myelin oligodendrocyte glycoprotein, myelin-associated protein, minor myelin proteins, or heat shock proteins.

The autoimmune reaction probably begins with a systemic infection that is associated with liberation of γ-interferon, resulting in activation of CD4 T lym­phocytes. The lymphocytes attach to adhesion mole­cules on the surface endothelium of postcapillary venules, roll along the surface of the endothelium, producing endothelial cell activation, followed by passage of the CD4 T lymphocytes into the CNS—in effect, disrupting the blood-brain barrier. Once within the CNS, the T-lymphocyte receptors respond to antigen presented by MHC class 2 molecules on macrophages and astrocytes, but oligodendrocytes are usually preserved at this stage. The antigen T-cell receptor interaction is followed by stimulation of helper T cells, T-cell proliferation, and B-cell and macrophage activation, with release of cytokines such as •γ-interferon, tissue necrosis factor, interleukin-12, and proteases. The cytokines induce a local inflam­matory reaction with further disruption of the blood-brain barrier, followed by a major influx of CD4 lymphocytes and monocytes into the lesion. Myelin damage results from the combined effect of cytotoxic cytokines, particularly tissue necrosis factor and cytotoxic cells.

Oligodendrocytes appear to survive and prolif­erate in the presence of acute demyelination and in­teract with hypertrophied astrocytes, an association that may represent a short-term protective mecha­nism. Consequently, active demyelination and remyelination can occur in acute lesions. Oligodendro­cyte depletion in chronic multiple sclerosis lesions may be a slow, insidious process, spanning a pro­tracted period during which there is gradual cell dropout.

 

Classification of Multiple Sclerosis

Although multiple sclerosis can affect any site in the CNS, it is possible to recognize eight types of the dis­ease (Table 7-1):

1.    Relapsing-remitting multiple sclerosis. This is the classical form of multiple sclerosis that often be­gins in the late teens or twenties with a severe attack followed by complete or incomplete recovery. Approx­imately 70 percent of patients with multiple sclerosis experience a relapsing-remitting course initially.³⁸ Fur­ther attacks occur at unpredictable intervals, each fol­lowed by increasing disability. The relapsing-remitting pattern tends to change into the secondary progressive form of the disease in the late thirties.

2.    Primary progressive multiple sclerosis. The disease runs a steady deteriorating course that may be interrupted by periods of quiescence without improvement. The rate of progression is variable; at its most severe, this form of multiple sclerosis can termi­nate in death within a few years. In contrast, the more chronic form of progressive multiple sclerosis is simi­lar to the benign form of the disease.

 

Table 7-1

Eight Types of Multiple Sclerosis

1.  Relapsing-remitting

2.  Primary progressive

3.  Secondary progressive

4.  Relapsing progressive

5.  Benign

6.  Spinal form

7.  Neuromyelitis optica (Devic disease)

8.  Marburg variant

 

3.    Secondary progressive multiple sclerosis. The relapsing-remitting form of the disease fre­quently develops into secondary progressive multiple sclerosis after a variable period of time but usually in the late thirties.

4.    Relapsing progressive multiple sclerosis. Occasional cases are encountered where patients with a progressive form of multiple sclerosis have super­imposed relapses with no significant recovery.

5.    Benign multiple sclerosis. About 20 per­cent of cases have the benign form of multiple sclero­sis. This may be defined as multiple sclerosis in which the patient is able to function at the level of full employment or provide care of home and family independently 10 years after the appearance of the first symptoms. It is extremely unlikely that these pa­tients will ever be incapacitated by the disease and they should continue to live a full life span with only occasional minor symptoms.

The existence of a benign form of multiple sclerosis increases the importance of recording the date of the first symptoms in patients who appear to have few residual abnormal signs several years after the onset of the disease. These patients may be in­formed that they have a benign form of multiple scle­rosis 10 years following their first recorded symptom and that the benign course will continue in the years ahead.

6.    Spinal form of multiple sclerosis.  This form of multiple sclerosis presents with symptoms and signs of predominantly spinal cord involvement from the beginning and maintains this pattern. There may be a clear-cut pattern of relapse and remission initially, followed by the secondary progressive form of the disease after several years, or the presentation may be one of steady deterioration from the onset.

7.    Neuromyelitis  optica (Devic syndrome). Most cases of this syndrome are believed to be exam­ples of multiple sclerosis presenting with acute trans­verse myelitis followed by optic neuritis. Many pa­tients follow a relapsing-remitting course indistin­guishable from multiple sclerosis.

8.    Marburg variant. This rare and malignant form of multiple sclerosis is associated with a fulmi­nating course of progressive impairment of con­sciousness, severe visual loss, dysarthria, dysphagia, respiratory insufficiency, and rapid deterioration. It is indistinguishable from acute disseminated encepha­lomyelitis. The Marburg variant may result from the autoimmune process of multiple sclerosis occurring in  an  individual  with  developmentally  immature myelin basic protein.

 

Clinical Features

The diagnosis of multiple sclerosis is based on the clinical demonstration of multiple levels of involve­ment of the CNS. Symptoms may be grouped under several headings.

 

Sensory Symptoms

Sensory symptoms are the most common symptoms experienced by patients with multiple sclerosis. These symptoms are often forgotten or ignored by both patient and physician. Even prolonged sensory symptoms fail to evoke con­cern, in contrast to the almost immediate response that occurs with weakness or paralysis. Consequently, many patients date the onset of multiple sclerosis from the first appearance of weakness, visual loss, or other symptoms of dramatic onset rather than forgot­ten or poorly recorded sensory symptoms.

Sensory symptoms include impairment of sen­sation (hypesthesia), tingling (paresthesias), and uncomfortable sensations (dysesthesias) often referred to as “burning,” which may be present for days, weeks, or months without objective abnormalities. All patients with suspected multiple sclerosis should be carefully questioned about the occurrence of pre­vious sensory symptoms.

 

Motor Symptoms

Paralysis or paresis of upper or lower limbs is the most common presenting symptom in patients with multiple sclerosis. Paraparesis is a common early complaint when the patient gives a history of increasing weakness and stiffness of the lower extremities, associated with progressive impair­ment of gait. Examination shows signs of upper mo­tor neuron involvement with spasticity, increased ten­don reflexes, and extensor plantar responses. These findings may be quite subtle in the early states of the disease.

 

Visual Symptoms

Optic neuritis presents with sudden visual loss and pain on eye movement and a unilateral headache. The condition may be followed by a rapid progression to total loss of vision in the af­fected eye (Fig. 7-1) When vision is preserved, there is monocular blurring; a central, paracentral, or centrocecal scotoma; and impairment of color vision. In optic neuritis, there may be edema of the optic discs, but the appearance can be normal in retrobulbar neu­ritis, when the inflammatory response is localized and located proximally in the optic nerve. Temporal pal­lor is a later development because of demyelination of the maculopapular bundle. However, subclinical involvement of the optic nerve can occur and may be present without symptoms, when the patient first pre­sents with signs of multiple sclerosis or may be iden­tified when the patient presents with the first symp­toms of optic neuritis, indicating prior subclinical involvement of the optic nerve.

Recovery from optic neuritis is unpredictable. Many patients experience no further problems for several years and then develop symptoms of brain or spinal cord involvement, indicating multiple sclero­sis. However, not all optic neuritis is multiple sclero­sis, and only 50 percent of adolescents and young adults who present with the sudden onset of optic neuritis   subsequently   develop   multiple   sclerosis.

 

 

Those with a large time interval between the optic neuritis and the development of additional symptoms have a better prognosis. The clinician should always inquire about the possibility of preceding symptoms in any patient who presents with optic neuritis be­cause the presence of symptoms some years before the more dramatic visual symptoms might indicate a more benign prognosis.

Diplopia is indicative of third or sixth nerve in­volvement in the brainstem. The fourth nerve is rarely involved in isolation. Intemuclear ophthalmoplegia is pathognomonic of multiple sclerosis and rarely has another etiology. Unilateral or bilateral Marcus Gunn pupil is often present in optic or retrobulbar neuritis.

 

Bladder Involvement

The early symptoms of bladder dysfunction consist of occasional urgency of micturition followed by mild nocturia occurring once a night. The events gradually increase ium­ber, disturbing the sleep of the patient and the bed partner. There is a concomitant increase in urinary frequency and urgency during the day, ultimately resulting in incontinence. Impaired bladder control is usually the result of spinal cord involvement in multiple sclerosis and decreasing bladder control usually parallels increasing paraparesis. However, this is not an inevitable relationship and some pa­tients retain adequate bladder function even when paraplegic.

The anatomical center for bladder control lies in the tegmentum of the pons. The center is under the influence of a higher level of control located in the medial aspect of the frontal lobes. Thus, the frontal lobes can signal the pontine bladder control center to inhibit bladder function or to initiate bladder empty­ing at will or when convenient. The pontine center then inhibits or permits bladder contraction through connections that traverse the spinal cord and exit through the parasympathetic outflow in the S2-S4 sacral nerves supplying the bladder.

A number of abnormal responses are associated with interruption of bulbar or spinal cord connections in multiple sclerosis.

1. Detrusor hyperreflexia. The interruption of the afferent impulses from the detrusor muscle of the bladder to the pontine micturition center by spinal cord disease results in an uninhibited reflex at the sacral cord level. The detrusor muscle is no longer inhibited as bladder volume increases and detrusor contraction is initiated in response to smaller volumes of urine, resulting in increasing frequency.

2.  Detrusor sphincter dyssynergia. The normal pat­tern of voiding is disturbed. The normal relaxation of the external sphincter is impaired and detrusor contraction is poorly coordinated and accompa­nied by contraction rather than relaxation of the external sphincter. The result is poor flow of urine and incomplete emptying of the bladder.

3.  Detrusor hypocontractility is a failure to empty the bladder secondary to insufficient detrusor pressure or a fading contraction on voiding.

 

Cerebellar Symptoms

Tremor, dysarthria, trun­cal ataxia, and limb ataxia are frequent symptoms of multiple sclerosis. Occasionally, cerebellar dysfunc­tion is the dominant feature in multiple sclerosis, when a patient presents with adequate vision and muscle strength shows serious disability from the cu­mulative effects of the several forms of cerebellar ataxia.

 

Brainstem Symptoms

Many patients with mul­tiple sclerosis develop signs of brainstem involve­ment. Involvement of the oculomotor and sixth cra­nial nerves as they traverse the substance of the brainstem results in diplopia. Intemuclear ophthalmo­plegia due to involvement of the interaxial fibers con­necting the third, fourth, and sixth nerve nuclei is not uncommon. Sensory loss over the face indicates in­volvement of the afferent fibers entering the pons from the trigeminal nucleus. Facial weakness may be due to involvement of the seventh nerve in the pons. Episodic dysarthria and dysphagia indicate involve­ment of the vagus nerve in the medulla, and dysarthria may be due to involvement of the vagus nerve, the glossopharyngeal nerve, and the hypoglos­sal nerve as they course through the medulla. Involve­ment of the corticospinal tracts in the brainstem can produce a progressive spastic quadriparesis; involve­ment of the cerebellar connections results in limb and truncal ataxia.

 

Spinal Cord Symptoms

Most patients with es­tablished multiple sclerosis have signs of spinal cord involvement. These signs include some degree of spastic paraparesis with increased tone in both lower limbs, bilateral ankle clonus, increased tendon re­flexes, and bilateral extensor plantar responses. It is not unusual to see a progression of paraparesis with increasing disability. This does not necessarily indi­cate progression of the disease but may be due to pro­gressive gliosis of plaques in the spinal cord. This scarring produces increasing traction on and destruc­tion of axons descending from higher centers in the CNS and results in increasing spasticity and para­paresis.

 

Abnormal Bowel Function

Constipation may be a major problem in advanced multiple sclerosis. Bowel incontinence can be a devastating experience to a patient with multiple sclerosis, particularly if the loss of control occurs in a social situation or in a crowded area such as a shopping center. Many pa­tients react to the incident with reluctance to leave home and are extremely apprehensive if they do so.

 

Memory Deficits and Dementia

Impaired cog­nitive processing is not unusual in multiple sclerosis when patients often display a verbal working memory deficit owing to a central processing problem. This has a significant impact on reading or other tasks that require the maintenance of verbal information over a short period of time. Dementia occurs in approxi­mately 50 percent of cases, with less cognitive im­pairment in patients with relapsing-remitting disease than in those with the progressive form. The disease can, however, remain predominantly spinobulbar in form, with little involvement of the white matter in the cerebral hemispheres and preservation of intel­lect. Patients with demyelination in the periventricu­lar white matter of the brain often show an explosive emotional response with inappropriate laughter or oc­casional crying during conversation. This condition results from the interruption of an inhibitory dopaminergic pathway connecting the thalamus and the frontal lobe. Despite the laughter, which has been incorrectly termed euphoria, many patients are de­pressed and are embarrassed by the inability to con­trol this often incongruous response.

 

Depression

Depression, or bipolar affective dis­order, is clearly associated with multiple sclerosis and may precede the onset of symptoms of multiple scle­rosis in some cases. Character or personality changes with impulsiveness or less inhibition in so­cial interactions may present problems or embar­rassment to family members.

 

Sexual Dysfunction

Sexual dysfunction is not uncommon in both men and women with multiple sclerosis. Men experience difficulty in achieving an erection because of diminished penile sensation or difficulty maintaining an erection. Others report fail­ure of orgasm. Sexual dysfunction in women with multiple sclerosis includes lower limb spasticity, lack of vaginal lubrication, and diminished vaginal sensa­tion, any of which can interfere with sexual function­ing.

 

Seizures

Epilepsy occurs in 1 to 5 percent of pa­tients with multiple sclerosis, a higher frequency than in the normal population. Seizures are associated with lesions in the cortical or subcortical area and the onset is usually associated with the presence of new lesions in the cortical gray matter or in subcortical re­gions. When seizures are associated with clinical re­lapse, the seizures rarely recur. Seizures not related to clinical relapse tend to recur occasionally but control is usually straightforward. Patients with multiple sclerosis, seizures, and progressive cognitive decline have a poor prognosis and are susceptible to status epilepticus.

 

Tonic Spasms

Tonic spasms are paroxysmal, uni­lateral stereotypical spasms of short duration precipi­tated by movement or hyperventilation, lasting 30 to 90 s and involving part or the whole of one side of the body. The attacks may be heralded by brief clonic movements. During an attack, the affected limb or limbs are usually extended, but the hands, fingers, feet, and toes may be drawn into a pseudodystonic posture. There may be a spread to the face on the same side with head turning. Speech may be affected by the distortion of the face. The patient is fully alert and usually experiences minimal pain or discomfort. The affected limbs may have a slight degree of weak­ness after an attack. The condition is believed to be the result of acute demyelination involving the corti­cospinal tracts in the brainstem or spinal cord.

 

Lhermitte’s Sign

Flexion of the head may result in an electric-like shock passing down the spine and into the limbs. This phenomenon, known as Lhermitte’s sign, while not pathognomonic, is highly sug­gestive of multiple sclerosis and may also precede the development of other symptoms by months or years in some cases.

 

Spasticity

The majority of patients with multiple sclerosis will show some evidence of spasticity, which may vary from a slight increase in tone to se­vere spastic paraplegia in flexion with limbs held in a permanent flexed posture at the knees and hips. In the mildest of cases, spasticity may present with no more than a slight increase in tendon reflexes and extensor plantar responses. In the most severe cases, spasticity may dominate the clinical picture and be responsible for severe disability.

 

Psychiatric Symptoms

Psychosis can occur in both chronic, progressive and relapsing-remitting forms of multiple sclerosis when it heralds increasing activity of the disease process. Paranoia or halluci­nations are unusual and are occasionally prominent symptoms when there is extensive involvement of both frontal and temporal lobes.

 

Fatigue

The majority of patients experience fa­tigue. The onset may be sudden and debilitating, with inability to continue even the simplest of tasks. Fatigue tends to be provoked by a high atmospheric temperature and many patients relate difficulties in functioning in the summer. Some are extremely sensi­tive to heat and report profound weakness after a hot bath or shower. A febrile illness has the same effect, with the appearance of symptoms suggesting a re­lapse of the disease. However, there is rapid return to the prefebrile state once the fever subsides.

 

Pain

Multiple sclerosis is not a painless disease and pain is occasionally a prominent feature. As many as 80 percent of patients experience painful muscle spasms, intermittent or constant limb pain, or spinal pain. Primary pain is usually dysesthetic, oc­curring most commonly in the lower limbs. However, truncal and upper limb dysesthesias can occur. The dysesthesias may be augmented by tic-like pains, tonic seizures are occasionally painful, and in some cases, Lhermitte’s sign is experienced as pain rather than paresthesias. Chronic pain can occur as a dyses­thesia in the extremities, in girdle-like fashion around the waist or abdomen, as low back pain or pain in the shoulders due to disuse with capsular adhesions.

Trigeminal neuralgia or atypical facial pain can occur at any stage of the disease. The occurrence of trigeminal neuralgia in a young person should always arouse the suspicion of multiple sclerosis.

Debilitated patients who use a wheelchair often develop joint pains from abnormal posture or from propelling the wheelchair manually. Spasticity and muscle cramps can cause severe pain.

 

Headache

 Migraine headaches are not unusual in multiple sclerosis. Retro-orbital pain presenting as a dull ache, and increasing on eye movement, occurs in optic and retrobulbar neuritis.

 

Respiratory Impairment

The incidence of respi­ratory failure in multiple sclerosis is low and usu­ally occurs in the presence of extensive spinal cord or brainstem involvement. Clinical indications of im­pending respiratory failure include orthopnea, para­doxical movements of the chest wall and abdominal muscles during respiration, and use of accessory muscles of respiration. Patients with suspected im­pairment of pulmonary function should be monitored carefully with a number of pulmonary function tests, including force vital capacity (FVC), maximal voluntary ventilation (MVV), and maximal expiratory pres­sure (MEP), coupled with the index score for pul­monary function, which provides a clinical tool for the rapid assessment of significant respiratory dys­function in multiple sclerosis.

 

Pregnancy

Multiple sclerosis does not reduce fer­tility. An apparent reduction in fertility may be sec­ondary to physical disability and to counseling against pregnancy by physicians. Other factors in­clude a decision by women with multiple sclerosis to forego marriage, to have fewer children, or to un­dergo sterilization. Multiple sclerosis does not affect the course of pregnancy and there is no difference in the duration of labor or frequency of difficult deliv­ery, premature labor or stillbirth.

Relapse rates of multiple sclerosis during preg­nancy are significantly reduced, particularly in the third trimester, but there is a significant increase in relapse rates during the first 3 months postpartum. Consequently, these facts should be discussed with a woman seeking advice prior to pregnancy and to her partner, explaining the present knowledge concerning pregnancy and multiple sclerosis. It is important that the partner realize that he will have to assume more responsibility for child care and reduce the burden of responsibility on the mother.

There is an apparent beneficial effect of preg­nancy in autoimmune diseases such as rheumatoid arthritis, suggesting that the beneficial effects of preg­nancy could be the result of immunomodulation or immunosuppression. However, the explanation for the alteration in the immune system remains illusive.

 

Diagnostic Procedures

1.    The diagnosis of multiple sclerosis is es­tablished by careful interpretation of clinical signs and symptoms. These indicate multiple levels of CNS involvement. The diagnosis may be strengthened by interpretation of other findings discussed below, but diagnosis remains a matter of clinical judgment.

2.    All patients should be fully investigated for the presence of infection. This includes aerobic and anaerobic blood cultures, urinalysis, culture and sen­sitivity, and chest x-ray to rule out pneumonia. Many patients have infections that are latent or occult. This dramatically affects response to treatment unless in­fection is eradicated. Patients with decubitus ulcers, which are chronic and deep, should receive bone scans to rule out the presence of osteomyelitis.

3.    Magnetic resonance imaging (MRI). An MRI scan of the brain is abnormal in 95 percent of definite cases of multiple sclerosis, but abnormal MRI findings alone are not sufficient to confirm a di­agnosis of multiple sclerosis without compatible clinical abnormalities.⁶⁰ MRI scans are abnormal in only 70 percent of patients with probable multiple sclero­sis and 30 to 50 percent of patients with possible multiple sclerosis, and some patients with multiple sclerosis may have normal MRI findings.

When patients have a diagnosis of probable multiple sclerosis, a positive MRI scan will raise the category to definite in about 50 percent of cases. The results of positive MRI scanning in those categorized as possibly having multiple sclerosis are less impres­sive, with only 5 percent changing category from pos­sible to definite. Nevertheless, progression to definite multiple sclerosis is more likely in those with dissem­inated MRI lesions at presentation and less likely in those without disseminated lesions. Other character­istic features are immediate proximity to the ventri­cles, lesions greater than 6 mm in diameter, and the presence of infratentorial lesions. Lesions present as multiple areas of increased signal intensity on proton density or T2-weighted image and as hypointense im­ages using Tl-weighted images. These lesions are situated predominantly in a periventricular distribu­tion around the lateral ventricles and in the white matter of the brainstem, cerebellum, and spinal cord (Figs. 7-2, 7-3). Lesions in the corpus callosum, which may show atrophy on sagittal images, are more specific for multiple sclerosis. However, the diagnosis of multiple sclerosis requires a history of two attacks with clinical evidence of two separate lesions. An MRI abnormality caow substitute for one of these lesions when it is clearly not related to the other clini­cally defined lesion. However, an individual who has had a single attack with a single lesion on MRI scan cannot be said to have definite multiple sclerosis and may have a monophasic acute disseminated en­cephalomyelitis. A repeat MRI scan taken 6 weeks later and demonstrating new lesions would justify a diagnosis of probable multiple sclerosis and lead to additional studies, including evoked potentials and examination for IgG and oligoclonal bands in the cerebrospinal fluid beyond 3 months.

Frequent interval MRI scans have shown that newly encountered lesions found on T2-weighted images have a transient enhancement following ad­ministration of gadolinium. In about two-thirds of the cases, these enhancing lesions will continue to show faded enhancement for 4 to 6 weeks with less than 2 percent showing enhancement beyond 3 months. Enhanced lesions tend to appear in clusters over time and lesions seen in T2-weighted MRI scans can regress in size but are unlikely to disappear. Serial studies have shown that the MRI attack rate greatly exceeds the clinical attack rate. There is a much lower rate of new lesions defined by MRI in primary pro­gressive multiple sclerosis than in secondary progres­sive multiple sclerosis and in the relapsing-remitting form of the disease.

Serial studies have also shown a considerable amount of clinically silent disease activity in relapsing-remitting and secondary progressive multiple sclero­sis, but there is a lack of correlation between MRI and clinical disability. Nevertheless, MRI as a measure of multiple sclerosis activity is now widely accepted as a surrogate marker of disease in treatment trials of evolv­ing therapies.

• To put veridical MS we have to reveal in patient at least 2 focuses of lesion and 2 exacerbations, or 2 exacerbations of 1 clinical focus and 1 paraclinical supposed focus.

• According to the accepted criteria there should be at least 3 focuses in MRI (2 of them should be located paraventricularly, 1 – subtentorialy (that means in brain stem or cerebellum). The diameter of focuses should be at least 6 mm, or there should be 4 focuses, 1 of them periventricularly.

•  

         

 

4. Examination of the cerebrospinal fluid (CSF). Acute exacerbations of multiple sclerosis may be accompanied by a lymphocytic or polymorphonu­clear pleocytosis in the CSF. This is short-lived and does not usually exceed 200 cells per cubic millime­ter. The CSF protein is elevated, particularly in early cases and during acute exacerbations. The level rarely exceeds 100 mg/dL. Gamma globulin elevation is seen in many cases and exceeds 13 percent of the to­tal protein content. About 70 percent of patients have evidence of abnormal intrathecal IgG synthesis, as demonstrated by the IgG index.

 

IgG CSF/IgG serum albumin CSF/albumin serum

 

An index greater than 0.7 indicates synthesis of IgG within the CNS. The presence of IgG oligoclonal bands is a more sensitive measure of local IgG pro­duction.  However,  this  finding is  nonspecific  and oligoclonal bands in the CSF have been seen in pa­tients suffering from cerebral infarction, brain tu­mors, paraneoplastic syndromes, diabetes mellitus, borreliosis, neurosyphilis, human immunodeficiency virus (HIV) infection, various connective tissue dis­eases, and hypothyroidism. Consequently, testing must include both serum and CSF. Detection in CSF alone or primarily in the CSF is an indication of local IgG synthesis, which is usually associated with multi­ple sclerosis. Oligoclonal bands (Table 7-2) are de­tected in 90 percent of the patients with clinically definite multiple sclerosis. This figure drops to 50 percent in optic neuritis and isolated brainstem and spinal cord disease. Elevation of myelin basic protein is present in approximately 80 percent of cases of acute multiple sclerosis or multiple sclerosis in exac­erbation. Antibodies to myelin, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG), and prote-olipid protein (PLP) are present in cells in the CSF but are not specific for multiple sclerosis.

5. Visual evoked potentials are positive in about 80 percent of patients with multiple sclerosis. Many of these patients have not had any visual symp­toms. Similarly, auditory evoked potentials are posi­tive in about 70 percent of patients with multiple scle­rosis and a number of these cases do not show clinical signs of brainstem involvement. Somatosen­sory evoked potentials are positive in about 60 per­cent of cases of multiple sclerosis. The presence of abnormal evoked potentials provide additional objec­tive evidence of a heterogenous involvement of the CNS.

Table 7-2

Oligoclonal Bands

Not specific for multiple sclerosis. Can occur in any disease with demyelination. Multiple sclerosis Neurosyphilis Viral encephalitis Bacterial meningitis Cerebral lupus erythematosus Lyme disease Neurosarcoidosis

6.    Neuropsychological testing is useful, par­ticularly in the early stages of apparent intellectual and cognitive failure, when it is necessary to distin­guish between early dementia and depression.

7.    Urological evaluation. Patients with estab­lished symptoms of urgency and frequency of mic­turition sufficient to cause inconvenience should have a limited urological evaluation with measurement of postvoid residual urine and a cystometrogram.

8.    Ophthalmology   evaluation.   An   opinion from an ophthalmologist should be obtained in the event of visual problems. Baseline evaluations of vi­sual acuity, visual fields, color vision and the pres­ence of scotomata are determined accurately and can be used for a comparison should visual deterioration continue.

 

Differential Diagnosis

Multiple sclerosis can mimic almost any chronic dis­ease affecting the CNS. The diagnosis is usually not difficult in well established cases, with evidence of multiple areas of involvement in the CNS, but early cases often present a problem in diagnosis. Various conditions (Table 7-3) can be confused with multiple sclerosis.

1.    The leukodystrophies. The adult forms of metachromatic  leukodystrophy,  Fabry  disease,  X-linked adrenaleukodystrophy,  globoid leukodystro­phy, and leukodystrophy with diffuse Rosenthal fiber formation can present with progressive deterioration and evidence of multiple areas of involvement in the CNS. There is a peripheral neuropathy with slowing of nerve  conduction  velocities  in  metachromatic leukodystrophy, which is not present in multiple scle­rosis. The demonstration of metachromatic material, low levels of arylsulfatase, and very long-chain fatty acids will establish the diagnosis. The diagnosis of leukodystrophy with diffuse Rosenthal fiber forma­tion can be made only by brain biopsy.

2.    Spinocerebellar degenerations. Autosomal dominant   spinocerebellar   degenerations,   sporadic late-onset olivopontocerebellar atrophies (multisys­tem disease), and Friedrich’s ataxia are occasionally misdiagnosed as multiple sclerosis. Diagnostic proce­dures in late-onset ataxias include MRI scanning of the brain and spinal cord and nerve conduction stud­ies. Metabolic evaluation consists of peripheral blood smears for acanthocytosis; determination of plasma amino acids, vitamin E, lactate and pyruvate levels; lipid and lipoprotein determination; and urinary or­ganic acid to identify abetalipoproteinemia, hypobetalipoproteinemia, vitamin E dysmetabolism, mito­chondrial cytopathies, and organic acidemias.

 

Table 7-3

MRI-Detected Abnormalities in White Matter Resembling Changes in Multiple Sclerosis

Acute disseminated encephalomyelitis

Adult-onset leukodystrophies

Multisystem disease

Spinocerebellar degeneration

Closed head injury

HIV encephalitis

HTLV-1 myelitis

Progressive multifocal leukoencephalopathy

Neurobrucellosis

Chronic granulomas

Beh§et disease

Sjogren syndrome

Brain tumors

Lymphoma

Cerebrovascular disease

Migraine ischemia

Cerebral vasculitis

B₁₂ deficiency

Moyamoya

Aging

Drug-induced encephalopathy

Cerebral lupus erythematosus

Neurosarcoidosis

Effects of radiation therapy

3.    Syphilis.   Both   meningeal   and   vascular syphilis may mimic multiple sclerosis. The diagnosis is established by abnormalities in the CSF and a posi­tive serologic test for syphilis.

4.    Wilson disease (hepatolenticular degenera­tion) usually presents with symptoms and signs of he­patic   involvement   and   neurological   dysfunction. However, a number of patients have minimal hepatic involvement with a broad range of neurological signs, including dysarthria, involuntary movements, and deteriorating coordination, followed by progressive de­mentia and behavioral abnormalities. A misdiagnosis of multiple sclerosis, particularly in those with marked cerebellar ataxia or psychiatric disorder, is not uncommon. Diagnosis is established by a positive slit lamp examination for Kayser-Fleischer rings, cataracts, and determination of serum, copper and ceruloplasmin, and of 24-hour urinary excretion of copper.

5.    The   antiphospholipid   syndrome,   which usually presents with deep venous thrombosis or stroke, can mimic multiple sclerosis when repeated minor strokes produce focal deficits and optic neuritis in a young adult.⁷⁴ Moreover, some patients will show the presence of areas of increased signal inten­sity in the periventricular area on a T2-weighted MRI. The diagnosis of the antiphospholipid syn­drome is established by a positive anticardiolipin and lupus anticoagulant in the serum.

6.    Lyme disease is of major concern in the eastern United States and appears to be spreading south and west. The disease is the cause of intermit­tent neurological symptoms. In the mildest form, it causes  Bell’s  palsy,  but  there  is  a  chronic  en­cephalomyelitis with intermittent signs of CNS in­volvement.

There may be a history of tick bite followed by a migratory rash and arthralgias. Lyme titers or Lyme polymerase chain reaction in the blood or spinal fluid will be positive in these patients.

7.    Behcet disease. The presence of cranial neuropathies, cerebellar ataxia, hemiparesis, quadri-paresis, pseudobulbar palsy, and peripheral neuropa­thy in an individual with oral ulcers, genital ulcers, and uveitis suggests Behcet disease. An MRI may re­veal findings resembling those seen in multiple scle­rosis.

8.    HTLV-1 infection. This retrovirus produces a myelopathy and spastic paraparesis and is an occa­sional cause of more widespread white matter dis­ease. Under these circumstances, it may be difficult to distinguish HTLV-1 infection from multiple sclerosis and appropriate antibody detection in both blood and CSF is necessary.

9.    Subacute combined degeneration of the spinal cord may resemble multiple sclerosis, particu­larly if there is an associated dementia and optic atro­phy. Serum B₁₂ levels are low in this condition. Al­though most cases of serum B₁₂ deficiency are acquired, inherited defects have been described in in­fants and children. Late-onset adult cases mimicking multiple sclerosis have occurred, suggesting that pa­tients diagnosed with multiple sclerosis should be screened for B₁₂ deficiency. Similarly, folate dysme-tabolism in the rare hereditary adult presentation may resemble multiple sclerosis.

10.    Brain tumor. The presence of a fixed sin­gle neurologic deficit in a young adult should always suggest the possibility of a brain tumor rather than multiple sclerosis. The diagnosis is established by MRI or computed tomography (CT) scanning.

11.    The arteritides. Both polyarteritis nodosa and systemic lupus erythematosus can produce multiple lesions in the CNS. However, other organs are often in­volved and there is evidence of peripheral neuropathy with an elevated sedimentation rate, abnormal nerve conduction velocities, and a positive nerve biopsy. Ab­normal antibodies in lupus erythematosus should reveal the presence of this condition, but abnormal antibodies are not always present in isolated cerebral lupus erythe­matosus. Similarly, isolated cranial arteritis can mimic multiple sclerosis and is often accompanied by a nor­mal sedimentation rate and a lack of any abnormal serum antibody levels. Diagnosis of this condition is es­tablished by angiography, which reveals beading and ir­regularity in the lumen of the intracranial arteries.

12.    Transverse myelitis. Multiple sclerosis is a relatively rare cause of transverse myelitis. Unless there is definite evidence of multiple areas of involve­ment of the CNS, other conditions causing transverse myelitis should be considered.

13.    Mitochondrial disorders. The association of optic atrophy, ataxia, spasticity, and hyperreflexia, usually associated with multiple sclerosis, can occur in Leber’s optic atrophy, now believed to be the result of mitochondrial DNA mutations. An electrocardio­gram and molecular diagnostic tests are suggested in suspected cases of Leber disease.

Other mitochondrial metabolic disorders can mimic multiple sclerosis, including MELAS syn­drome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), chronic milder forms of the MEERF syndrome (myoclonus epilepsy and ragged red fibers), and the adult form of Leigh syn­drome.

14.    Sjogren syndrome. There is a marked sim­ilarity in the clinical presentation of multiple sclerosis and Sjogren syndrome with CNS involvement. Both conditions may have optic neuritis, spinal cord in­volvement,    psychiatric    manifestations,    abnormal evoked potentials, similar CSF profiles, and indistin­guishable abnormalities on MRI and CT scans. Fea­tures that may distinguish Sjogren syndrome include the sicca complex, xerophthalmia, xerostomia, or re­current salivary gland enlargement, peripheral neu­ropathy, vasculitis in skin or muscle, elevated sedi­mentation    rate,    abnormal    antinuclear    antibody, positive rheumatoid factor, anti-RO(SSA)  or anti-LA(SSB) antibodies and decreased complement.

15.    Hereditary spastic paraparesis with pro­gressive lower limb weakness and spasticity, hyper­reflexia, and urinary incontinence can mimic multiple sclerosis, particularly when there is an associated op­tic atrophy. A positive family history suggesting an autosomal dominant trait and the slow progression of the disease should lead to the exclusion of multiple sclerosis.

 

Treatment

1.    Infection. Because there is strong evidence that the first attack or exacerbation of multiple sclero­sis may be caused by viral or bacterial infection, all infections should be treated promptly.

2.    Bed rest. Patients with acute multiple scle­rosis or an acute exacerbation of multiple sclerosis benefit from complete bed rest. Patients who are re­moved from the necessity of self-care and added wor­ries of the home environment improve with rest. However, the period of rest should not be protracted and no more than a few days in the great majority of patients. Once the patient shows improvement, the in­stitution of a graded program of physical therapy be­comes paramount.

3.    Corticosteroids.   Evidence   suggests   that high doses of intravenous corticosteroids (glucocorti­coids) may arrest the progress of multiple sclerosis.

Corticosteroids have several beneficial effects, in­cluding inhibition of secretion by antigen-presenting cells and T cells of the cytokines, tumor necrosis fac­tor a, and interleukin-6. An additional effect may be inhibition of secretion of 7-interferon and inter-leukin-12 by T cells.

About 85 percent of patients with relapsing-remitting multiple sclerosis shows objective signs of neurological improvement during treatment with in­travenous corticosteroids. Fifty percent of patients with progressive multiple sclerosis are improved by intravenous corticosteroids, although for many, the response is limited to a reduction in spasticity. This figure may improve if attention is paid to prevention of infection in the posttreatment period.

The short-term use of intravenous cortico­steroids is attended by few side effects. Some patients experience insomnia during treatment, a few show signs of euphoria; gastric upset with epigastric pain responds to ranitidine 150 mg ql2h. Hypomania or depression are unusual events. The daily dose and du­ration of therapy have not been determined, but an in­travenous dose of 1000 mg methylprednisolone over 3 h daily for 7 days, followed by alternate-day oral methylprednisolone, beginning with 96 mg (16 mg tablets X 6) at breakfast, and reducing by 8 mg q.o.d., will allow the hypothalamic-pituitary-adrenal axis to recover by the end of therapy. In the majority, this regimen will result in at least 6 months’ remission and several months or even years in many cases. The treatment can be repeated if relapse occurs.

As indicated under Diagnostic Procedures, all patients will have received full investigation for in­fection, including blood cultures, urinalysis, culture and sensitivity, and chest x-ray to rule out pneumonia before receiving corticosteroid therapy. Infections should be treated before and during treatment with corticosteroids. One of the major causes of failure or poor response to corticosteroids is the presence of a concomitant, untreated infection.

4. Immunosuppressive therapy. Long-term treatment with immunosuppressants may reduce the frequency of relapses in patients with multiple sclero­sis. Azathioprine is probably the safest drug in this category and has reduced relapse to 70 percent in 3 years, compared to 80 percent in the placebo group.

Azathioprine has few adverse effects and has not been shown to carry an increased risk of inducing neoplasia, unlike the more powerful immunosup­pressive therapies used to prevent transplant rejection.

Methotrexate, a drug used widely in the treat­ment of chronic autoimmune diseases such as rheumatoid arthritis and psoriasis, will reduce pro­gression of disability in chronic progressive multiple sclerosis. Low-dose therapy using 7.5 mg per week orally is effective, and adverse effects are few, but regular monitoring with complete blood counts and liver function tests is advised. Currently, low-dose oral methotrexate appears to be the best therapy for slowing deterioration in chronic progressive multiple sclerosis.

Cladribine, a specific antilymphocytic agent that is incorporated into DNA and induces lympho­cyte apoptosis, is reported to produce improvement in patients with chronic progressive multiple sclerosis. The drug, which is administered intravenously, has been reported to induce lymphopenia and severe but reversible aplastic anemia; the safety of cladribine has yet to be determined.

Results of studies of cyclosporine in multiple sclerosis have been equivocal. The drug may be bene­ficial in patients with frequently recurring or nearly continuous disease activity but unacceptable toxic­ity and marginal benefit have limited the use of cyclosporine in multiple sclerosis.

5.    Total lymphoid irradiation, originally intro­duced for the treatment of Hodgkin disease, has theo­retical benefits in multiple sclerosis, in that treatment produces a significant reduction in CD4 and CD8 lymphocytes. Potential risks of therapy, such as ma­lignancy, have limited the use of this modality, and the results of some studies have been equivocal.

6.    Plasmapheresis  has   marginal  benefit in multiple sclerosis and has not been accepted as an established therapy for this disease.

7.    Interferon β. Interferon β-lb (Betaseron) is reportedly effective in reducing clinical attacks of multiple sclerosis by approximately 30 percent over 24 months, when compared to placebo. Treatment reduces frequency of major attacks by 50 percent and produces immediate and significant reduction in contrast-enhanced MRI lesions and fewer new le­sions in patients receiving interferon B. The dose is 8 million units subcutaneously every other day.

Interferon β-la (Avonex) is also an available al­ternative therapeutic agent. It also lowers multiple sclerosis attack frequency by 30 percent and de­creases disease activity, measured by gadolinium-enhanced MRI. The dose is 6 million units intra­muscularly, once weekly.

Adverse effects of interferons include fever, chills, headache, and myalgia. These “flu-like” symp­toms begin 4 to 6 h after injection and last for a few hours. The response tends to resolve after a few weeks of therapy but can persist for several months in a minority of cases. Acetaminophen or ibuprofen, given 1 h before injection, reduces the flu-like re­sponse. The dose of acetominophen or ibuprofen can be repeated, should the flu-like symptoms still occur. The persistence of adverse effects requires reduction of the dose by 50 percent, that is, 4 million units of Betaseron and gradually increasing the dose to 8 mil­lion units over a period of 4 weeks. Prednisone 20 mg given 2 h before the injection of interferon 3 is also effective in reducing adverse effects.

Other adverse effects include redness at injec­tion sites, which occurs in many patients receiving Betaseron. The local reaction lasts for many weeks before resolution. Necrosis at the injection site is rare, but persistence of painful skin reactions requires the cessation of treatment.

Interferon β has been associated with depres­sion, which usually responds to a serotonin uptake in­hibitor such as fluoxetine. Inquiry should be made re­garding thoughts of suicide, which, if present, are an indication to stop treatment with interferon p.

The development of virus-neutralizing antibod­ies has been reported in 35 percent of multiple sclero­sis patients receiving interferon β-lb. The appearance of antibodies has minimal effect on clinical response and does not appear to be a reason for discontinuing therapy. The action of interferon β in multiple sclero­sis appears to be multifactorial, including sequestra­tion of T lymphocytes into lymphoid tissue and im­paired migration of T lymphocytes through the blood-brain barrier by inhibition of adhesion molecules on endothelial cells; decreased release of cy­tokines, including ^-interferon, from T lymphocytes; decreased tissue necrosis factor production by macrophages; and paradoxically, increased inter-leukin-6 production.

8.    Copolymer 1. The development of copoly­mer 1 was based on the premise that myelin basic protein is encephalitogenic and can cause experimen­tal allergic encephalomyelitis   (EAE) in animals. However, although some regions of the protein are encephalitogenic, other regions will suppress the de­velopment of EAE. This led to the synthesis and test­ing of several copolymers of amino acids, based on the amino acid composition of myelin basic protein. One such copolymer, designated copolymer 1, sup­pressed EAE in guinea pigs and other animals. The mechanism of suppression is not certain, but copoly­mer 1 seems to inhibit human T-cell lines specific for myelin basic protein. Consequently, the application of copolymer 1 to multiple sclerosis was a natural de­velopment   in   therapy.   A   double-blind   placebo-controlled trial of copolymer 1 in patients with re-lapsing-remitting multiple sclerosis over a 24-month period indicated a statistically significant reduction in the   copolymer   treated   group,   compared   to   the placebo group. The dose is 30 mg copolymer 1 daily by subcutaneous injection.  Side effects are mild, consisting of a local reaction at the site of injec­tion and rare transient palpitations, flushing, sweat­ing, or a feeling of chest tightness and anxiety.

9.    Immunoglobulin therapy. Treatment with intravenous immunoglobulin has received some atten­tion in recent years and there is some indication that IVIG may be safe and effective in reducing the fre­quency of exacerbations in relapsing-remitting multi­ple sclerosis.

10.    Physical therapy. All patients with multi­ple sclerosis should be evaluated by a physiatrist and should be placed in a graded program of physical therapy. This program should be under constant re­view so it can be modified, depending on the results of corticosteroid and other therapies, as well as the benefit of the physical therapy itself.

11.     Spasticity. Increased muscle tone, exag­gerated tendon reflexes, clonus, and spontaneous muscle spasms are often present in patients with ad­vanced multiple sclerosis. An acute increase in spas­ticity can occur during an exacerbation of multiple sclerosis, or spasticity may present as an insidious de­terioration over a period of months, when the deterio­ration is ofteot apparent to patient or therapist. Baclofen (Lioresal) is effective in reducing spasticity and can be given in doses up to 120 mg daily. The tendency is to underdose. The medication should be given in an initial dose of 20 mg ql2h orally, with gradual increments over several weeks to an ef­fective level. High doses, although reducing spastic­ity, may increase weakness in some cases. Diazepam (Valium) or clonazepam (Klonopin) are potent spas­molytic agents. The tendency to drowsiness can be mitigated by beginning with a low dose and only in­creasing when the patient is comfortable, that is, not drowsy.

Dantrolene sodium (Dantrium) is effective in reducing spasticity but has limited applications be­cause it almost invariably causes weakness. However, it can be useful for treatment of spasticity in nonam­bulatory patients with severe prolonged muscle con­tractions, who will not be adversely affected by the decrease in voluntary muscle power associated with the use of this drug. Adverse effects include damage to the liver, drowsiness, and light-headedness. An ini­tial dose of 25 mg/day may be increased by 25 mg in­crements every week, to a maximum dose of 100 mg/day.

Tizanidine is an effective antispastic agent with an antispasticity effect comparable to ba­clofen. Tizanidine dosage should be titrated begin­ning with 2 mg at night and gradually increasing by 2 mg every 4 days in divided doses, until therapeutic goals have been achieved without adverse effects. The larger dose should be given at bedtime to mini­mize adverse effects. The average daily dose is 18 to 24 mg, and the total daily dose should not exceed 36 mg. Adverse effects include dry mouth, drowsi­ness, hypotension, light-headedness, abnormal liver function tests, and the rare occurrence of hallucina­tions. These adverse effects tend to decrease in inten­sity as the duration of therapy increases.

Sudden muscle spasms (charley horses), whether nocturnal or diurnal, often respond to clonazepam, which is particularly useful for nocturnal spasms, in that clonazepam not only reduces spasm but also in­duces sleep without contributing to fatigue the next day.

When patients fail to respond to oral medica­tion, intrathecal baclofen delivered through a pro­grammed pump placed in the abdominal wall, with an intrathecal catheter in the spinal canal, produces re­markable reduction of spasticity and spasms in pa­tients with severe spastic paraparesis. Potentially am­bulatory patients have returned to walking in some cases.

Botulinum toxin is effective in reducing spas­ticity when injected into selected muscles but has had limited application to date.

12.    Visual difficulties. Patients should be en­couraged to report visual deterioration at the onset of the problem.  Because optic neuritis can develop rapidly,   further   deterioration   should   be   treated promptly, with intravenous or oral corticosteroids in a high dose. In many cases, this produces rapid im­provement in symptoms or stabilizes the condition, with subsequent slower but steady improvement in visual acuity.

13.    Weakness. It is very difficult to strengthen a muscle  weakened by central  denervation.  The potassium channel blocking agents 4-aminopyridine and 3-4-diaminopyridine may improve action poten­tial provocation in demyelinated axons and improve neurological function. Body cooling, using cooling vests or repeated cold showers in the summer months, are effective in those who are heat sensitive.

14.    Fatigue may strike without warning. Fam­ilies should be informed about the fatigue factor and the unpredictable development of this symptom. This prevents resentment when the patient is suddenly un­able to attend a long-planned social function and when there is a need for extra rest periods during the day. The intense fatigue associated with a febrile ill­ness will respond once the body core temperature re­turns to normal. Every patient with recent onset of fa­tigue should be evaluated for depression, medication effect, or intercurrent illness.

A number of drugs may help eliminate fatigue, including amantadine 100 mg twice a day, pemoline (Cylert) 37.5 mg morning and noon, methylphenidate (Ritalin)   10   mg   morning   and   noon,   fluoxetine (Prozac) 20 mg every morning, or selegiline 5 mg ql2h orally.

15.    Pain is a common feature of multiple scle­rosis. The treatment consists of physical therapy, when appropriate, and medication. Mild chronic pain may respond to acetaminophen or propoxyphene and acetaminophen   (Darvocet-N).    Nonsteroidal   anti­inflammatory drugs should be used with caution to avoid gastric ulceration. Ibuprofen 600 mg, given with meals, is an effective analgesic. Tramadol (Ul-tram) 50 mg with misoprostol (Cytotec) 100 μg, to limit the risk of gastric ulceration, will control mod­erately severe pain. Gabapentin beginning 300 mg 12h and increasing, as tolerated, to as high as 2700 mg in divided doses, or amitriptyline 10 mg q.h.s., in­creasing slowly by 10-mg increments to 80 to 100 mg daily, are both useful in pain control. Trigeminal neu­ralgia usually responds to carbamazepine but the re­sponse is less predictable in atypical facial pain. A painful Lhermitte’s sign often shows response to car­bamazepine or clonazepam as do tic-like extremity pains.   If opioids  are  prescribed,   the  medication should be prescribed by one practitioner. The risk of addiction with oral opioids is low. but dependency can occur. Neurolytic nerve blocks are required occa­sionally, including epidural blocks for chronic sciatic pain.

16.    Ankle edema. Swelling of the ankles in patients with limited walking or in those who are nonambulatory and confined to a wheelchair is a gravity effect with fluid accumulating in the depen­dent tissues of the feet and ankles. Consequently, the use of diuretics is of little value. The patient should lie supine for several hours a day, with the ankles ele­vated above the level of the heart. This can be accom­plished by having the patient lie supine with the feet elevated on a firm cushion or over the armrest of a sofa, thus permitting gravity-driven drainage over the lower limbs. The use of leotards or elastic stockings may also be helpful.

17.    Restricted mobility. Many patients with limited mobility resist the use of a wheelchair and re­quire a great deal of persuasion to use an electric cart. The idea that this will lead to further weakening is frequently expressed and is, of course, not true. The severe paraparetic with good upper limb function should be encouraged to use an electric cart. The in­creased mobility and broadening of the patient’s so­cial contacts is truly remarkable, once this is ac­cepted, and the electric cart is an essential therapeutic tool in many cases.

18.    Decubitus ulcers. Skin care is one of the paramount needs in the wheelchair-bound paraplegic patient or in those who are bedridden. With few ex­ceptions, skin breakdown and the development of de­cubitus ulcers is the result of neglect by caregivers. Treatment requires removal of pressure in the af­fected area and bacterial culture, followed by the use of appropriate antibiotics when the ulcer is infected. When the ulcer fails to heal or when the patient ap­pears to be deteriorating, the suspicion of an underly­ing osteomyelitis indicates the need for a radioactive bone scan to confirm this diagnosis. A protracted course of intravenous antibiotics is indicated in such cases. Deep (third degree) decubitus ulcers usually require debridement and plastic surgery with surgical reconstruction.

19.    Urinary tract infection. Cystitis is com­mon in female patients with multiple sclerosis and has an increased frequency in male patients using self-catheterization. Although pyelonephritis is un­common, it can occur in severely debilitated patients and is a potent factor in chronic illness, with ane­mia, weight loss, and fatigue. Urinary tract infec­tions require urinary culture and sensitivity testing, with the use of appropriate antibiotic therapy. Atten­tion to the symptoms of infection and immediate treatment facilitates the use of a Foley catheter or suprapubic catheter and increases the safety of self-catheterization.

20.    Management of bladder dysfunction.

A. Detrusor hyperreflexia. The early symptoms of bladder dysfunction are usu­ally caused by detrusor hyperreflexia, with urgency, frequency, and occasional nocturia. Most patients can be managed with an anticholinergic such as oxybutynin chloride 5 mg ql2h and increasing to 5 mg q8h if necessary. Tolterodine (Detrol) 2 mg ql2h is equally effective and has fewer adverse effects. Imipramine PM 75 to 100 mg q.h.s. is a useful alternative, particularly when nocturia is a problem. Pro-Banthine 15 mg with meals and at bedtime is an effective alternative. Hyoscyamine time release 0.375 mg at night is also effective in reducing noc­turia.

B.    Sphincter    detrusor    dyssynergia with poor flow, interrupted stream, and increased postvoid residual responds to prazosin 0.5 mg/day, increasing by 0.5-mg increments to an effective dose, if there are no hypotensive effects. Doxa­zosin mesylate tablets 1 mg q.h.s., in­creasing by increments to effect, are also helpful.

C.    Incomplete emptying with a post-micturition residual volume greater than 150 mL  requires intermittent self-catheterization. This technique has revo­lutionized the management of bladder dysfunction in multiple sclerosis but re­quires instruction and is a clean rather than sterile procedure. Repeated bladder infections are not unusual during the first few months of self-catheterization but are reduced as the bladder begins to tolerate the presence of bacteria and clean tech­nique improves. Anticholinergic drugs can be continued in patients performing intermittent self-catheterization.

D.    Surgical procedures. Severe or total incontinence requires the use of an in­dwelling catheter or suprapubic catheter. There seems to be little difference in the development of infection in these two tech­niques, but some patients find a suprapubic catheter with continuous drainage into a catheter bag more convenient than the transurethral   catheter,   and   the   choice should be offered, when appropriate.

Augmentation cystoplasty to in­crease the storage volume in a severely contracted hyperreflexic bladder is of oc­casional benefit for patients who can per­form self-catheterization.

21.    Intention tremor is a common sign in multiple sclerosis and many patients develop resting tremor enhanced by action in the later stages of the disease. These are difficult symptoms to control. De­vices to dampen tremor, such as weights applied to the wrists, are of limited benefit. Medication is unpre­dictable. Propranolol (Inderal) beginning 20 mg tid and increasing to as high as 240 mg/day when the long-acting preparation can be used, may be effective in some cases. Other drugs of occasional benefit in­clude clonazepam, primidone, and hydroxyzine. Car­bonic anhydrase inhibitors such as acetazolamide and Neptazane may help in some cases, and isoniazid in high doses has been reported to decrease tremor, but adverse effects are not uncommon. In many cases, a combination of drugs is the most effective approach to this problem.

22.    Unsteadiness (ataxia). No medications are available to modify ataxia. The physician must per­suade the patient who is at risk from falling to take reasonable precautions to reduce the effects of ataxia. Light-weight wheeled vehicles with hand brakes are useful, rather than the standard walker, which is slow and cumbersome. Severe ataxia is an indication for the use of an electric cart, even though the patient has little or no weakness, and this should be encouraged at an early stage, because improvement in ataxia is unusual.

23.    Contractures. Paraplegia and flexion with knee and hip contractures are common manifestations of neglect and should not happen in a well planned treatment program. Contractures can be prevented by physical therapy, appropriate splinting, and the use of antispasticity agents such as baclofen or tizanidine. If contractures are established, early surgical interven­tion is necessary to release joints and restore normal limb posture. The baclofen pump has major benefit when contractures are the result of severe flexor spasticity.

24.    Diplopia is often temporary during an ex­acerbation of multiple sclerosis and should be treated by patching one eye. The patch should be alternated over each eye daily. When diplopia is an established symptom, the use of prisms in eyeglasses may help. Surgical correction by an ophthalmologist is needed occasionally.

25.    Impairment of bowel control. Bowel in­continence can be a devastating event in patients with multiple sclerosis, sufficient in some cases to convert an outgoing, gregarious patient into a recluse. The problem can be solved by development of the innate but dormant gastrocolic reflex. The patient is in­structed to attempt bowel movements immediately af­ter breakfast each day. The reflex may not function for several weeks, but eventually, it will return and bowel evacuation becomes an automatic function in the morning. The patient is then free of worry about incontinence for the rest of the day.

Constipation is a common complaint. A stool softener such as docosate sodium 100 mg b.i.d. or bulk agents such as Metamucil may suffice in mild cases. When constipation is established, the patient should take 30 mL Milk of Magnesia, plus 2 senna tablets (Senokot) at night, if there has beeo bowel movement for 2 days. This should result in a bowel movement after breakfast the next morning. An alter­native method is to use lactulose syrup 1 to 2 table­spoons daily. In refractory cases, bisacodyl supposi­tory (Dulcolax) 10 mg can be used in the morning. Failure of bowel movement after these measures re­quires the periodic use of an enema.

Fecal impaction is a problem in bedridden or immobile patients. Manual removal of fecal material followed by enemas may be necessary. The venerable but extremely effective milk and molasses enema is recommended as a last resort.

26.    Sexual dysfunction. Sexual dysfunction is not uncommon in both men and women with multiple sclerosis, occurring in almost 80 percent of men with advanced multiple sclerosis and in approximately 50 percent of women with similar disability.

In men, failure to achieve erection rarely re­sponds to oral therapy with yohimbine or hormonal replacement, with parenteral testosterone which, in reality, should only be used for hypogonadal disor­ders. Penile prostheses are cumbersome and subject to infection. Intercavernous injection of alprostadil (prostaglandin E) or propiverine combined with phentolamine increases arterial inflow into the penis, while decreasing venous outflow. Both methods are effective, with restoration of ability to achieve satis­factory intercourse in the majority of cases. Adverse effects include mild pain and dizziness. The dose of alprostadil or propiverine should be titrated to achieve a satisfactory but not prolonged erection. Ad­verse effects are infrequent and include prolonged erection, priapism, hematoma, hypotension, and fibrosis.

Another method using transurethral supposito­ries of alprostadil is an equally successful alternative therapy, with fewer adverse effects. It is probable that sildenafil citrate tablets will supersede most methods for improving erectile function in males. The use of this drug is effective in most cases of erec­tile dysfunction with few serious adverse effects, the most common of which are headache in 16% of pa­tients, flushing in 10%, and dyspepsia in 7%.

Female sexual problems include loss of vaginal sensation or lubrication. The latter can be treated with vaginal lubricant. Loss of vaginal sensation requires empathy and understanding by a concerned partner who is prepared to assist in the development of satis­factory sexual foreplay.

Loss of vaginal sensation can be treated in some cases with a vibrator, which enhances sensation in the vaginal area.

27.    Cognitive dysfunction. About 40 percent of patients have cognitive difficulties, which are usually mild. The main deficits relate to retention and recall, short-term memory, attention, and de­layed processing of information. When these difficul­ties interfere with the ability to function, neuropsy­chological testing should be performed to measure the extent of deterioration and to exclude depression, which is a major cause of impaired memory in multi­ple sclerosis. A small percentage of patients do show significant disability with cognitive impairment, suf­ficient to interfere with daily activities. These situa­tions can be treated with a cognitive rehabilitation program, allowing the patient to circumvent or mini­mize these difficulties. Dementia, if sufficient to pro­duce declining ability to function independently, is rare” and often associated with atrophy of the cor­pus callosum.

28.    Respiratory impairment treatment should be directed to the control of infection followed by in­travenous corticosteroid therapy. The dictum—if in doubt, don’t wait, intubate and place the patient on a ventilator—is applicable in these cases.

29.    Bulbar dysfunction. Dysarthria is not un­usual in multiple sclerosis but is rarely of sufficient magnitude to interfere with communication. Should this happen, the services of a speech pathologist are indicated.

Dysphagia is, however, common and often un­detected in patients with multiple sclerosis. This in­volves a disturbance of both the oral and pharyngeal phase of swallowing, and evaluation by a speech ther­apist, including radiological investigations with a bar­ium swallow and visual fluoroscopy, is indicated. The speech pathologist can then suggest changes in diet and the use of various maneuvers to facilitate swal­lowing. In advanced cases, when dysphagia is a ma­jor problem, the patient should be fed through a per­cutaneous gastrostomy tube.

30.    Community services. Patients with severe multiple sclerosis who are unable to continue their employment, or who become increasingly dependent on others, face the prospect of growing problems at home and in the community. Most are not equipped to cope with the stress of chronic illness and should receive social service assessment and advice when­ever possible. This results in a smoother transition from hospital to home and better adjustment to home conditions, with improved support for the patient and the family. To this end, identification and referral to community resources available to multiple sclerosis patients should be implemented in all cases with more than a minor degree of disability.

31.    Simple prophylactic measures.

A.    Combat infection. In many cases, a relapse occurs after an infection. It is prudent, therefore, to treat all infections in multiple sclerosis patients seriously and to resort to the early use of antibiotics. This will not have any effect on viral in­fections but antibiotic therapy will reduce the risk of secondary bacterial infections such as sinusitis, bronchitis and pneumo­nia.

B.    Avoid fatigue. Some patients note relapse following periods of unexpected exercise. Ambulatory patients with multi­ple sclerosis should avoid sudden unex­pected athletic activities or prolonged ex­ertion. Those who wish to exercise should develop an incremental program of activ­ity and stop whenever they experience fatigue.

C.    Emotional stress. As a group, mul­tiple sclerosis patients experience more emotional stress than those who are well There are  increased  rates  of divorce more financial problems, and fewer op­portunities for gainful employment. Sub­standard care for the chronically disablec and limitations on mobility because of ; lack of transportation or lack of propei building access adds to the emotional dis tress   of   multiple   sclerosis   sufferers Whether such stress leads to exacerbatioi is debatable, but every effort should b< made to reduce emotional distress by ap propriate treatment or referral to commu nity agencies.

Patients with depression will oftei benefit from the use of appropriate antide pressants such as fluoxetine (Prozac), ser traline (Zoloft), or paroxetine (Paxil) which can be combined with psychothet apy in appropriate cases.

D.    Avoid excessive, prolonged expo sure to sunlight. Patients with multipl sclerosis experience considerable weak ness with the reappearance of previou symptoms if exposed to a hot environ ment, in particular, after prolonged expo sure to sunlight. The patient should b warned about this possibility and reas sured that the  symptoms  will resolv once   the   body   core   temperature   de creases.

 

Prognosis                                        ^;

The prognosis in multiple sclerosis has im proved in the last two decades. The mean surviva is now 20 to 25 years. This can be attributed to bette treatment and control of infection in debilitated pa tients. The physician should be frank with the patient and relatives in discussing the prognosis. Multiple sclerosis resembles a chronic infectious disease in presentation and prognosis. Consequently, multiple sclerosis may be benign, relapsing and remitting, pri­mary or secondary progressive, severely disabling, or fatal. In general, patients who present with mild symptoms and who have several mild relapses tend to remain in the mild category and do not become se­verely disabled. Approximately 20 percent of patients remain fully active and fully employed 10 years after the diagnosis of multiple sclerosis and should be in­formed that they have a benign form of the disease and will not be disabled by multiple sclerosis. How­ever, these patients must also be informed that mild exacerbations of multiple sclerosis will continue at unpredictable times well past the fiftieth year. More than 50 percent of patients continue to work full-time, whereas 33 percent are paraparetic, para­plegic, or quadriplegic, and 25 percent require inter­mittent or constant catheterization for bladder dysfunction.

The prognosis of multiple sclerosis can be im­proved by avoiding any precipitating factors. The pa­tients should be advised to identify and treat infec­tions promptly, to avoid unusual physical or emotional stress, and to avoid prolonged exposure to sunlight. All infections should be treated with the early use of antibiotics. Patients with chronic multiple sclerosis who are bedridden or confined to a wheel­chair often experience slow deterioration, which is not appreciated by patients or by relatives. The prog­nosis can be improved in these cases by regular reevaluation at 6-month intervals, followed by prompt attention to obvious areas of deterioration. Patients with urinary tract problems should be reevaluated fre­quently. Loss of function in the limbs calls for prompt reinstitution of physical therapy and treatment with intravenous corticosteroids. Paraparesis should not render a patient bedridden. Prescription of the correct type of wheelchair and instruction in the proper trans­fer from bed to chair permit broader contact with friends and relatives, improve morale, and improve the long-term outlook for the patient. Pregnancy is associated with clinical stability in most cases, but the postpartum period carries a risk of exacerbation of multiple sclerosis by two or three times the ex­pected relapse rate. Patients should be told that there is some increased risk of multiple sclerosis in the off­spring if one parent has the disease, but the actual risk is small.

 

 

Acute Disseminated Encephalomyelitis

This condition is an acute demyelinating disease be­lieved to be an autoimmune response to a systemic viral infection. The illness may begin within a week or as long as 4 weeks after an acute viral infection such as measles, varicella, or rubella, and rarely fol­lowing mumps or influenza (postinfectious en­cephalomyelitis). In many cases, the infectious com­ponent is unrecorded or may present as a mild upper respiratory tract infection. Acute disseminated en­cephalomyelitis used to be a recognized complication of vaccination against rabies or smallpox (postvacci­nal encephalomyelitis), but this condition has largely been eliminated by the use of modern rabies vaccines and by the eradication of smallpox worldwide. Occa­sional cases may be seen following injection of tetanus antiserum or earlier forms of rabies vaccine, which are still in use in Third World countries.

 

Pathology

The brain and spinal cord show the presence of perivascular cuffing with lymphocytes and plasma cells and scattered areas of perivascular demyelination. The primary lesion is believed to be a vasculopathy and discrete areas of hemorrhage are seen in some cases. The condition has a similar pathological appearance to experimental allergic en­cephalomyelitis. In some fulminating cases, the brain is swollen and shows the presence of numerous pe­techial hemorrhages or hematoma formation. Micro­scopic changes consist of necrosis of blood vessel walls and the passage of fibrinous exudate into the perivascular spaces. There are marked white matter edema and infiltration of abnormal areas with inflam­matory cells. The affected blood vessels may be sur­rounded by areas of necrosis and demyelination or ball or ring-like hemorrhages (acute hemorrhagic en­cephalomyelitis).

 

Clinical Features

 The decrease in the incidence of acute disseminated encephalomyelitis has been at­tributed to increased vaccination and immunization against infectious diseases. The onset is usually abrupt, occurring within a week of clinical evidence of infection, but the first symptoms have been re­ported before any signs of infection, and as long as 2 or 3 months after infection. The early symptoms

consist of headache, fever, anorexia, and lethargy. The subsequent course shows considerable variation. The illness may resemble a mild encephalitis with complete recovery, or there may be rapid progression to stupor and coma. Psychiatric symptoms consisting of personality changes, hallucinations, or acute para­noia are not uncommon. Seizures, sensory or motor disturbances, or dysfunction of bladder or bowel may occur.

 

Differential Diagnosis

The disseminated in­volvement of the CNS in acute disseminated en­cephalomyelitis produces a clinical picture that mim­ics acute multiple sclerosis. The development of symptoms following documented infections, how­ever, suggests the diagnosis of acute disseminated en­cephalomyelitis.

 

Diagnostic Procedures                                                                                                                             

1.    On lumbar puncture, the CSF is clear, with normal, slightly elevated pressure. There is a lympho­cytic pleocytosis and red blood cells are present in some cases. The protein and gamma globulin con­tents are elevated. The glucose content is normal.

2.    The EEG is abnormal in severe cerebral in­volvement, with diffuse slowing in the theta and delta range.

3.    The MRI scan shows the presence of nu­merous areas of increased signal intensity in the white matter of the brainstem and spinal cord, and in the gray matter of basal ganglia, thalamus, and tem­poral lobe cortex.

 

Treatment

1.    Plasmapheresis alone or combined with high-dose corticosteroids and cyclophosphamide may produce a successful recovery in some cases.

2.    The fulminating acute hemorrhagic form of the disease is associated with rapid increase in ICP and requires ICP monitoring, intravenous mannitol and high-dose barbiturate therapy.

 

Students’ practical Study Program.

Step I.  Aim: To put clinical diagnosis. For this purpose it is necessary:

1.      To determine clinical form of multiply sclerosis, acute disseminated encephalomyelitis, amyotrophic lateral sclerosis, acute myelitis by mean of scheme of differential diagnosis.

2.      To define basic clinical syndromes of locomotors, sensitive, coordinative dysfunction, cranial innervation.

3.      Carry out differential diagnosis between multiplex sclerosis and acute disseminated encephalomyelitis.

4.      To formulate clinical diagnosis, for example:

a)     Multiply sclerosis, cerebral-spinal form with presence of lower spastic paralysis, degree III, progradientive course

b)     Acute disseminated encephalomyelitis (encephalomyelopolyradiculoneuritis) with presence of mixed tetraparesis and disturbed sensation of radicular and polyneuritic type.

Step II. Aim: To prescribe therapy. For this it is necessary to pay attention to pathogenetic mechanism of demyelination diseases of nervous system, clinical forms, course of disease, presence of remission, acute periods, est.

For the treatment of multiply sclerosis prescribe:

–          general-clamping drags (ATPh, Cocarboxylase);

–          vitamins group B (B₁, B₆, B₁₂), ascorbinic acid (Vit C), nicotinic acid (PP);

–          hormones (prednisolone, metipred, dexamethazone, polcortolone) in onset of disease;

–          desensibilisation drugs (dimedrol, pipolphene, diazoline, claritin, hormones);

–          immunostimulators (T-activine, Thymaline, Sinacten-depo, Echinacea);

–          pyrogenic drugs (pyrogenal);

–          immunodepressors (hormones, asathyoprine);

–          myorelaxation drugs (Midocalm, Mellictine, Bactrophene);

–          biostimulators (aloe, vitreous body);

–          plasmapheresis.

In causes of ADEM also it is necessary to prescribe course of antibiotics therapy (series of penicillin, cephasolin), enzymes (desoxyribonucleinase, ribonucleinase) and antivirus remedies such as Reapherone, Acyclovir, Zovirax, hormones, desensibilisation medicines. Independently prescribes medicines for therapy of amyotrophic lateral sclerosis.

Step III. Aim: To fulfill preventive-examinative measures.

On reason from clinical diagnosis and effect of therapy to define prognosis about life, work, recovering, to take preventive measures, to fulfill medical labor examination and military medical examination.