Theme:

Theme: Meningitis: purulent (meningococcal and secondary) and serous (enteroviral: Coxsakie viruses, EKHO viruses, lymphocytic choriomeningitis, tuberculosis). Brain abscess.

Encephalitis: epidemic, spring-summer, polyseason, herpetic, rheumatic, parainfection, subacute sclerosing panencephalitis, rabies.

Cerebral arachnoiditis.

Poliomyelitis. Acute myelitis. Amyotrophic lateral sclerosis.

 

 

Meningitis

 

Meningitis is an acute infectious disease with involvement of the arachnoid and pia of the brain and spinal cord by pathogenic microorganisms. The most common organisms that cause meningitis are bacteria, viruses, sometimes fungus, micoplasma and rickettsia.

Classification

1.    According to the inflammatory process in the meninges and cerebrospinal fluid (CSF) changes all meningitis are divided into serous and suppurative, purulent. At serous meningitis there is increased number of lymphocytes in CSF, while at suppurative and purulent meningitis neutrophiles dominate.

2.    According to the pathogenesis there are primary and secondary meningitis. Primary meningitis are developed without previous general infection or infectious disease of any organ. Secondary ones are developed in case of general or focal infectious disease, that means that they are complications of different infectious diseases. For example tuberculous, syphilitic meningitis are considered to be secondary meningitis.

3.    According to the localization of pathologic process there are general, basal, convexital meningitis.

4.    According to the rate of development there are fulminant, acute, subacute, chronic meningitis.

5.    According to the severity there are mild, moderate and severe meningitis.

6.    According to the etiology there are bacterial, viral, fungal meningitis.

 

Pathogenesis

There are three ways of meninges infection:

1.    In case of open head or spinal trauma, fractures of scull basis associated with liquorrhea.

2.    Direct extension (sinusitis, mastoiditis, middle ear infection)

3.    Hematogenic way of infection (the source of infection is localized in intestine, stomach, nose).

      Organisms multiply rapidly in cerebrospinal fluid with inflammation of meninges. Neutrophiles react with release chemicals. Bacterial toxins and inflammatory response cause brain edema. Increased metabolic demand and reduced blood flow result as inadequate tissue perfusion. That causes raised intracranial pressure and systemic effects of infection.  

 

Pathomorphology

 The main changes at suppurative and purulent meningitis are:

a)    Infection and inflammatory response are generally confined to the subarachnoid space and the arachnoid and pia.

b)    Brain and meninges edema.

c)    Blood repletion of cortical veins

d)    Internal hydrocephalus

e)    Perivascular infiltration of cortical cells

      At serous meningitis meninges and brain edema, dilatation of liquor spaces is usually observed.

      At tuberculous meningitis basal exudation occurs. As a result of commissural process hydrocephalus and subarachnoid space obstruction can occur.

 

Clinical features

In spite of the etiology there are three common syndromes for all meningitis:

1.    General – infectious

2.    Meningeal

3.    CSF changes

 

1.  General – infectious syndrome means headache, shiver, inflammatory changes of blood, rash, tachycardia, tachypnoe with rhythm disorders.

 

2.  Meningeal   syndrome manifests as neck stiffness, Kernig sign, Brudzinski signs (upper, middle and lower ones), Lessage symptom (in children), Bechterev’s cheek bone phenomena. Increased intracranial pressure causes bulging of an unclosed anterior fontanelle in children.

 

Kernig sign

 

 

Upon meningeal symptoms general cerebral signs are developed. They are headache (as a result of increased intracranial pressure), vomiting, nausea, general hyperesthesia, changes of consciousness, psychomotor agitation, and seizures.

 

 

1.    CSF changes manifest as cellular – protein dissociation, colour changes, cerebrospinal fluid is cloudy (purulent), the sugar content is decreased; clot formation on standing is observed at tuberculous meningitis.

 

The results of CSF examination have an important meaning for differential diagnosis and prescription of etiotropic treatment. In order to put a diagnosis we should make bacteriologic and serologic examinations. Usually we use immunologic express – methods of investigation. They are:

·         Countercurrent immunoelectrophoresis (CIE)

·         Latex agglutination

These methods are used in order to reveal specific antigens (protein components of organisms). It is necessary to find out sensation of organisms to antibiotics in order to prescribe a proper therapy.

 

Epidemic cerebrospinal meningitis

 

Etiology

      It is usually caused by Meningococcus Weichselbaum. The source of infection is ill person or carrier. Meningococcal infection can manifests as suppurative meningitis, asymptomatic bacterio – carriage, nasopharyngitis, arthritis, meningococcemia.

 The entrance is mucose membrane of pharynx and nose. Meningococcal infection can be transmitted by air drops or contact. In most instances the spread of meningococcus is haematogenous. Usually this disease is observed in winter and spring. Meningococcus is instable at high temperature, humidity and day light.

 

Pathogenesis

      Meningococcus in upper respiratory ways usually causes primary nasopharygitis .The last in typical cases is rapidly cured. In those persons who are less resistant to infections meningococcus is getting into the blood and then it is spread in the human body. In severe cases meningococcemia develops, which is usually associated with typical hemorrhagic rash. Endotoxin can even cause endotoxic shock.

 

Clinical features and diagnosis  

       Incubation period of meningococcal infection lasts from 2 to 10 days (usually about 3 – 7 days).The onset of meningococcal meningitis is acute (about several hours). The temperature is elevated at 39 – 40°.

The main peculiarities of clinical picture are:

1.    General cerebral syndrome is well – expressed and increases rapidly. Meningeal syndrome increases during 2 – 3 days.

2.    Focal neurologic symptoms manifest as lesion of III-rd and IV- th CN’s – diplopia, ptosis, cross – eye, anizokoria.

3.    Herpes labialis is often observed on the 2 – nd or 5 –th day. Sometimes hemorrhagic rash occurs, that is the sign of meningococcemia.

4.    Sometimes brain tissue is involved. Then there is clinical picture of meningoencephalitis.  That means occurrence of hyperkinesis, ataxia, nystagmus, paralysis, seizures, sometimes epistatus.

5.    At severe meningoencephalitis inflammation of ventricles occurs. The last manifests as hormetonia, edema of optic nerves’ disk, disturbances of breathing and cardiac activity.

6.    Cerebrospinal fluid is cloudy (purulent), the cell count in the fluid is usually between hundreds and thousands/mm³. The protein content is increased to 10 – 15 g/l. The sugar content is decreased. Meningococcus can be found out in CSF.

      According to the clinical picture there are three main forms of meningitis. They are mild, moderate and severe one. Fulminant hypertoxic form is very rare.

 

Complications of meningoccocal meningitis Severe forms can be associated with pneumonia, myocarditis, pericarditis. The most dangerous complications are acute brain edema and bacterial endotoxic shock.

The course of meningococcal meningitis   There are fulminant, acute, abortive and recidivous course of the disease. The most common are the first and the second forms.

Diagnosis It is usually based on clinical features (acute onset, general infectious, general cerebral symptoms and meningeal syndrome, hemorrhagic rash), CSF examination and revealing of meningococcus.

 

Differential diagnosis We should differentiate this disease with:

·         other forms of meningitis

·         meningism at general infections (that means the absence of CSF changes in case of meningeal syndrome)

·         subarachnoid hemorrhage (usually general – infectious syndrome is absent, there is no blood in CSF).

 

Prognosis The disease lasts from 2 to 6 weeks. In case of adequate and in time treatment it is usually cured.

       Only functional changes of CNS such as asthenic syndrome, mild disorders of mental development may be observed after meningococcal meningitis. Focal symptoms such as paresis of extremities, CN’s, hydrocephalus, seizures, decreased vision, hearing loss, and arachnoiditis are very rare.

 

Secondary purulent meningitis

Etiology, pathogenesis

      Secondary purulent meningitis are observed in case of pyogenic source in the body. The disease is developed after direct extension from pyogenic source (for example pyogenic middle ear infection) or by means of metastasis from faraway pyogenic focuses (abscess, ulcerous endocarditis).

    Usually secondary purulent meningitis is caused by different coccus (pneumococcus, staphylococcus), Hemophilus influenzae.

 

Clinical features

      The onset of the disease is accompanied by chills and fever to 40º. Then meningeal syndrome, seizures, consciousness disorders, focal neurologic symptoms, autonomic disorders occur. Sometimes the clinical picture is very similar to sepsis.

      In CSF the cell count is very high. The protein content is significantly increased. Bacteria   (staphylo –, streptococcus) are usually found.

 

Treatment

      The measures of treatment of primary suppurative and secondary purulent meningitis are the same. But the secondary purulent meningitis needs liquidation of the source of infection. If necessary we can use surgical methods of treatment.

 

Treatment of suppurative, purulent meningitis

     The patient should be hospitalized in horizontal position and isolated before the revealing of the type of meningitis.

We use:

1.     Etiotropic treatment

2.     Pathogenic treatment

3.     Symptomatic treatment

 

1.     Etiotropic treatment

        Antibiotics

     Just after the putting diagnosis we should prescribe antibiotics. It’s a pity but sometimes it is difficult to reveal the organism that causes the disease. And we loose time. That’s why very often we start with antibiotic that has wide spectrum of action – Penicillinum.

    We use it in dose 300 000 U per kg (that means about 24 – 32 mlns of U per day 6 – 8 times i/m). At severe cases the dose is increased to 48 mlns. When the treatment is started later or the patient is in coma the dose is 60 mlns of U per day. And the first 4 – 12 mlns are used i/v.  Simultaneously we prescribe 3 mlns of U of Nystatinum. The treatment lasts from 7 to 10 days. The main sign which indicates us it’s time to put off the medication is CSF sanitation (that means cell counting less than 100/mcl, lymphocytes not less than 75 %)

·         For purulent meningitis treatment we can prescribe half- synthetic Penicillinum

·         (ampicillinum) in dose 300 – 400 mg per kg per day   i/v  or i/m.

·         Cephalosporines are also used for the treatment. For example such as Cephazolinum, Cephalomycinum, Ceftriakson, Cefotaxim. They are used 1 g 4 times per day I/m or I/v.

·         Aminoglycozides, such as Gentamycini, Kanamycini, Amikacini are also prescribed. Amikacinum is used 0.5 g 3 times per day. Gentamycinum is used 80 mg 2 – 3 times per day.

·         The most effective are combinations of different antibiotics. For example

1.    Penicillinum and Aminoglycozides ( Gentamycinum, Kanamycinum )

2.    Ampicillinum and Aminoglycozides

3.    Penicillinum and Cephalosporines of the second or third generation

4.    Aminoglycozides and Cephalosporines

5.    Tienamycinum

 

        Sulphanilamide

      Sulfamonomethoxine, Sulfapyridazinum, Sulfadimethoxinum are used 2 g twice a day during the first day, then 2 g once a day.

        The treatment of secondary purulent meningitis includes treatment of the source of infection (inflammation process in lungs, middle ear, and nose). Sometimes we use surgical methods of treatment in order to liquidate the source of infection.

 

2.     Pathogenetic treatment  includes:

·         Treatment of intoxication

·         Correction of heart – vascular and breathing disturbances

·         Liquidation of brain edema

·         Correction of water – electrolytes balance.

 

That’s why we use:

·         Treatment against intoxication

·         Dehydration

·         Hormones

·         Antihistamines

·         Nootrops

 

       To liquidate hypovolemia we prescribe Rheopolyglucinum 400 ml per day, 100 ml 5 % Albuminum, Plasma, Haemodesum.

       An average quantity of liquids is about 2 – 2.5 l per day. After introduction of 1 – 1.5 l we prescribe 2 – 4 ml of Lasix.

       We also use polarized compound (500 ml 5 % Glucose, 150 ml 1 % KCl, 10 U of Insulinum, 10,0 Pananginum, ATP, Cocarboxylase) and diuretics. In order to overcome metabolic acidosis we use Na hydrocarbonas 100 ml 4 %.

       Hormones are necessary in case of infectious – toxic shock treatment. We use Dexamethazonum 8 mg twice a day or Hydrocortisone 15 mg per kg. Glycosides   are also used in this case.

       Heparinum is prescribed in dose 5 000 U 4 times per day.

       Diuretics such as Manitol, Lasix, Glycocorticoids are used too.

       Antihistamine medications (CaCl2, Ca gluconas, Suprastinum, Dimedrolum, Tavegil) are used too.

       Nootrops such as Pyracetam, Nootropil, Actovegin, Instenon, and Cerebrolisyn are used.

 

3.  Symptomatic treatment

At acute kidney insufficiency we use hemodialysis.

At acute suprarenal glands insufficiency we introduce physical solution, Rheopolyglucinum plus 125 – 500 mg Hydrocortisone, 30 – 60 mg Prednisolone, 8 – 16 mg Dexamethasone, 500 – 1000 mg Ascorbin acid, Cordiamini, Strophanthinum.

At brain hypoxia we use nootropils and neuroleptics (Na oxybutiras, Relanium 0.5 % 2 ml, Sibazonum 2 – 4 ml).

At severe pain we use analgesics (Analginum, Baralginum, Tramadolum).

 

Prognosis About 20 – 25 % of all patients with suppurative, purulent meningitis die. In case of different complications and late diagnosis 60 – 80 % of all patients die. Death is much more common at secondary purulent meningitis and at pneumococal infection.

 

Serous meningitis

According to the etiology there are:

·         Bacterial serous meningitis (tuberculous, syphilitic meningitis)

·         Viral meningitis (acute lymphocytic choriomeningitis, parotid meningitis, influenza- meningitis, enteroviral, herpes – adenoviral – meningitis)

·         Fungal meningitis

 

 

Tuberculous meningitis

      Tuberculous meningitis is always secondary to tuberculosis elsewhere in the body. The primary focus of infection is usually in the lungs but may be in the lymph glands, bones, nasal sinuses or any organ of the body. This disease is observed in both – children and adults.

 

Pathomorphology 

     The process is usually most intense at the base of the brain, ependyma, III –rd and IV – th ventricules, choroids plexus. The inflammatory process may extend for a short distance into the cerebral substance. Proliferative changes are frequently seen in the inflamed vessels of the meninges, producing a panarteritis. All these changes lead to the CSF dynamics disturbances and hydrocephalus. The most typical feature of tuberculous meningitis are minute tubercles on the base of the brain.

 

Clinical features and diagnosis

1.    Tuberculous meningitis develops very slowly.

2.    There are three periods of the disease :

a) prodromal stage (with loss of appetite, general weakness, headache, irritability, increased temperature and sometimes vomiting)  lasts for  2 – 3 weeks.

b) meningeal stage

c) paralytic stage

3.    Meningeal syndrome is not well – expressed.

4.    Temperature is increased up to 38º sometimes 39º.

5.    Focal neurologic signs – paresis and paralysis of Oculomotor n. (III), Abducens n. (IV), Facial n. (VII), Optic n. (II). Sometimes Vestibulocochlear n. (VIII)   is involved.

6.    Encephalitic syndrome manifests as paresis, paralysis, aphasia, hyperkinesis, cerebellar disturbances.

7.    Subacute course of the disease. Sometimes acute course is observed in children. Chronic course may be in those persons who had used antituberculosis treatment previously.

 

Diagnosis

The CSF findings are quite characteristic. These include: 

·         Increased pressure

·         Slightly cloudy

·         Increased protein content to 1 – 5 g per l

·         Moderate pleocytosis of 100 – 300 cells/mm³, 70 – 80 % of them are lymphocytes

·         Decreased sugar content with values in the range of 0.15 to 0.3 g/l

·         Formation of a clot on standing during 12 – 24 hours, where bacilli of tuberculosis are usually found out.

In blood sometimes leucocytosis and increased SR (sedimentation rate) is observed.

 

Differential diagnosis Spinal form of tuberculous meningitis should be differentiated with spinal tumor or myelopathy.

 

Treatment

Etiotropic treatment includes:

·         Isoniazid 15 mg/kg 3 times per day

·         Rifampicinum 600 mg once a day

·         Pyrazinamide 30 mg/kg (1.5 – 2.5 g per day) twice a day

     They are used during three months. Then we use only Isoniazid and Rifampicinum during 7 months.

     The most recent medications are combinative ones such as Rifogal, Rifater (Rifampicinum 120 mg, Isoniazid 50 mg, Pyrazinamide 300 mg).

Streptomycinum is used in dose 1 g once a day.

Ethambutol – 25 mg/kg per day

Usually we use all these medications about three months, as all of them have side effects such as ototoxicity, lesion of optic nerve, diarrhea, thrombocytopenia, hepatitis.

       Pathogenetic and symptomatic treatment is the same as at suppurative and purulent meningitis.

 

Prognosis Mortality is about 10 %. Residual symptomatics includes epiattacks, eye movement disorders, hemiparesis, hearing loss, neuroendocrine disturbances.

       During the first year of the disease the patients are considered to be disabled, during the next 2 or 3 years they have limited abilities.

 

Serous viral meningitis

Acute lymphocytic choriomeningitis

    The cause of the disease is Armstrong virus. Viral reservoir is domestic mice. Human being is infected by means of food infected by mice. The main way of disease transmittance is hematogenic.

 

Clinical features

1.    Incubation period lasts for 1 – 2 weeks

2.    The onset is with headache, running nose, sore throat

3.    Moderate meningeal syndrome against high temperature – 39º – 40 º

4.    On 7- th or 10- th day general – infectious and meningeal signs disappear

5.    CSF is pellucid, pleocytosis is 300 – 500 cells, most of them are lymphocytes. The content of protein and sugar is the same.

6.    There are some atypical forms of meningitis, such as

·         Flu – like

·         Encephalomyelitic

·         Poliradiculoneuritic

·         Visceral

7.    Alopecia and orhitis can occur at the 7 th week of the disease.

 

Diagnosis According to the virusologic and serologic examination we put the diagnosis. For these we use blood and CSF during the beginning of the disease.

 

Treatment

Etiotropic treatment

1.    Interferonum 500 000 U. It is prescribed in dose 1 amp. once a day during 7 days or Reaferonum  1 mln U i/m

2.    Virolex – 250 mg 3 – 4 times per day or Aciclovir 200 mg 3 times per day, or Virasolom 2 caps. 3 – 4 times per day during 7 days.

3.    Stimulators of interferonum production – Prodigiosan – 1 ml 0.005 % i/m once every three days.

4.    Acidi ascorbinici , vit. B1, B6.

5.    Antibiotics in order to prevent pneumonia.

 

Pathogenetic treatment for all types of meningitis

1.    Desintoxication

2.    Dehydratation

3.    Desensibilization

4.    Hormones

5.    Nootrops

 

Prevention To liquidate mice in the houses.

 

Enteroviral meningitis

      The causes of the disease are Coxacci and ECHO (enteric citopatogenetic Human organs) virus.

 

Clinical features

1.    The disease is much more common in summer and autumn

2.    Epidemic focuses are very typical

3.    It is highly contagious disease

4.    Incubation period lasts for 10 days approximately

5.    The onset is acute with high temperature, well – expressed general cerebral syndrome (loss of consciousness, psychomotor agitation, seizures)

6.    Abdominal pain, diarrhea

7.    Enlargement of liver and spleen

8.    Myalgia

9.    Herpes –angina

10. Rash

11. Lymphatic nodules enlargement

12. CSF – pleocytosis 100 – 500 cell/mm³, most of the cells are lymphocytes

13. In 2 – 3 days the temperature is decreased, meningeal syndrome disappear

 

Diagnosis

1.    Virusologic examination of smears

2.    RN

3.    RCC

 

Treatment

Pathogenetic and symptomatic treatment is the same as at all the others meningitis.            

·      γ-globulin is used in dose 6 ml i/m once a day up to 5 days

·      RNA is prescribed in dose 30 mg 6 times per day up to the normalization of temperature

·      Antibiotics and sulphanilamides are prescribed in case of complications (otitis, pneumonia, tonsillitis)

·      At myalgia we use Indometacinum, Metindolum, Ibuprofenum, Ortofenum.

 

Parotid meningitis

      Usually this disease is observed in children, especially boys. The signs of meningitis appear on the 3-rd or 5 th day after parotitis. During that period virus can get into the other organs, such as pancreas and testis and as a result they can cause pancreatitis and orchitis. The virus is transmitted by air drops. Incubation period lasts for 3 weeks.

Clinical features and diagnosis

    The onset of the disease is acute. There are well expressed general infectious, meningeal and general cerebral syndromes. In children general weakness, sleepiness, sometimes agitation, hallucinations, consciousness disorders, general seizures are expressed.

 

There are different forms of parotid meningitis:

• Serous meningitis

• Meningism without meningitis

• Clinically asymptomatic meningitis

 

The CSF findings are quite characteristics. These include:

·         Increased pressure

·         Slightly cloudy

·         Increased protein content to 0.6 – 1 g per l

·         Moderate pleocytosis

·         Sugar content without changes

      Clinical picture mainly depends on increased intracranial pressure and not cytosis. All symptoms of the disease tends to disappear in 7 – 10 days. CSF returns to normal content a little bit longer.

 

Complications Orchitis, pancreatitis.

 Treatment the same measures are used as at others forms of meningitis.

 

 

Tuberculous Meningitis

Definition

Tuberculous meningitis is an infection of the meninges caused by the acid-fast bacillus My­cobacterium tuberculosis.

 

Etiology and Pathology

The bacilli usually en­ter the body by inhalation. Transmission through the skin or by ingestion are rare causes of infection. Once introduced, the organisms undergo multiplication and hematogenous dissemination and it is during this stage that the meninges are most likely to become in­volved. Cell-mediated immunity with migration of macrophages at the site of infection leads to the de­velopment of tubercles. When the immune response fails, the subarachnoid space is infected by rupture of meningeal tubercles followed by release of bacilli and the development of meningitis. Rupture of an in­tracerebral tuberculoma or direct extension from the adjacent focus (e.g., from the spinal or nasal sinuses) into the subarachonoid space is rare.

The presence of bacilli in the subarachnoid space is followed by an intense granulomatous in­flammation of the leptomeninges and subjacent cor­tex. A thick, heavy fibrous and necrotic exudate is produced, which tends to collect at the base of the brain.

The arteries at the base of the brain are in­volved, and there is inflammation of the adventitia and media, with narrowing and thrombosis of the lu­men. Cranial nerves II and III, and occasionally VII and VIII, are subject to compression by the heavy ex­udate.

 

Clinical Features

Although the incidence of tu­berculous meningitis had decreased in the United States and Western Europe through the 1980s, there has been a disturbing increase in the number of cases worldwide in recent years. This can be attributed to the emergence of drug-resistant bacilli, inadequate disease control programs, and the advent of HIV in­fection, all of which contribute to the current situa­tion.

The disease occurs in all ages, but the incidence is higher in infants, young children, and the aged. It is more common among the undernourished and in those areas of the world characterized by poor hy­giene and overcrowding.

There is a history of contact with an infected individual or a history of previous active tuberculosis in 30 to 50 percent of patients. In the early stages of the disease, the patient experiences anorexia, inter­mittent headache, lethargy, aching muscles, and low-grade fever. Irritability and poor feeding may be the only evidence of the illness in infants. Some 2 weeks after the initial febrile illness, the patient begins to complain of persistent headache and a stiff neck. This is associated with other signs of meningeal irritation, increased ICP, and focal neurological deficits, includ­ing cranial nerve palsies or hemiparesis. Infants may have a tense, bulging fontanelle. There is a slow pro­gression over a period of weeks to months, with in­creasing drowsiness, evidence of progressive neuro­logical dysfunction, and terminal coma and eventual death. In some cases, the infection is confined to the spinal cord and presents as a radiculomyelopathy. The course of the illness depends on the extent of the meningeal involvement, the immune response of the host, the virulence of the organism, and the stage at which treatment is administered.

Complications

1.    Arteritis may be followed by thrombosis of a major artery, resulting in cerebral infarction.

2.    Hydrocephalus. The granulomatous exu­date or an arachnoiditis may block the aqueduct of Sylvius, the foramina of Luschka and Magendie, or the subarachnoid space, impeding the flow of CSF and causing hydrocephalus.

3.    Seizures may occur at any time during the illness and are most common in children less than 2 years of age.

4.    Focal motor deficits and impaired cognitive and intellectual functioning can develop during the course of the illness and persist.

5.    Hypopituitarism as a sequel to tuberculous meningitis is not infrequent in childhood.

 

Differential Diagnosis

The differential diagnosis of tuberculous meningitis includes viral encephalitis, partially treated pyogenic meningitis, fungal infec­tions, and other inflammatory disorders that produce progressive neurological dysfunction. The presence of active tuberculosis elsewhere, and the results of CSF examination, are usually sufficient to establish the diagnosis.

 

Diagnostic Procedures

1. Lumbar puncture. Examination of the CSF is the only definitive procedure in the diagnosis of tu­berculous meningitis. The CSF is under increased pressure, is clear or slightly cloudy, and contains

a predominance of mononuclear cells (usually >400/mm³), increased protein (100 to 400 mg/dL), and a decreased glucose content. However, normal glucose levels can occur. It is usually difficult to iden­tify the bacilli in the CSF; examination of the ‘fibrin clot after centrifugation and careful staining by the Ziehl-Neelsen method is necessary. Bacterial culture or guinea pig inoculation requires 4 to 6 weeks’ incu­bation before a positive result might be expected. Consequently, treatment of tuberculous meningitis is often begun on an empiric basis as soon as the diag­nosis is suspected. However, the polymerase chain re­action is a sensitive technique for detection of mi-crobacterial and tuberculosis genome in the CSF,⁷¹ giving positive results within a few hours. The inhi­bition ELISA for M. tuberculosis antigen-5 is also a highly selective and reliable method for detecting in­fected patients within 48 to 72 h. The finding of in­creasing levels of adenosine deaminase activity in the CSF is highly suggestive of tuberculous meningitis.

2.    Protein levels greater than 1000 mg/dL in the CSF and a decreasing opening pressure on serial lumbar punctures   suggests   a   spinal   block.   The Queckenstedt test usually reveals lack of communica­tion through the spinal subarachnoid space. An MRI scan will confirm the presence of arachnoiditis. More than 50 percent of patients will have an elevated sedi­mentation rate and a positive tuberculin skin test.

3.     A chest x-ray should be obtained to detect pulmonary involvement.

4.    A CT scan may reveal enhancement of the basal cisterns. Tuberculomas appear as intense nodu­lar or ring-enhanced masses. The target sign, a cen­tral area of calcification and peripheral ring enhance­ment, is highly suggestive of tuberculoma. Serial CT scans are useful in identifying incipient complica­tions such as hydrocephalus, areas of calcification, encephalomalacia, tuberculous osteitis of the skull, and tuberculous otomastoiditis.

5.    The MRI scans are more sensitive than CT scans in detecting basal meningitis cerebral infarction owing to arteritis hydrocephalus and parenchymal tu­berculomas often in combination in AIDS patients. Tl-weighted gadolinium enhanced images are re­quired to demonstrate basal leptomeningeal involve­ment.

6. Arteriography may show the presence of arteritis of the circle of Willis or its major branches involved in the basal meningitis process. Affected vessels show irregular areas of narrowing and occlu­sion.

 

Treatment

1.    Tuberculous meningitis should be treated with a combination of antituberculous drugs. The drugs listed in Table 16-11 are suggested for the ini­tial treatment of tuberculous meningitis lasting 2 months, followed by an alteration in the regimen to complete the course over a 12-month period. The ad­dition of corticosteroids appears to increase survival rates and reduce neurological complications in tuber­culous meningitis. Drug-resistant cases require the substitution of more toxic drugs such as ethambutol, cycloserine, streptomycin, kanamycm ciprohexacm, or ethionamide, all of which require careful observa­tion for development of adverse effects. Pyndoxine must be administered in the dosage of 50 mg daily to avoid the development of isoniazid (INH)-induced neuropathy, encephalopathy, or seizures.

2.    Spinal arachnoiditis and arteritis may show improvement when treated with corticosteroids.

3.    Seizures should be adequately controlled with anticonvulsants. The dosage of phenytoin (Di­lantin) may require careful adjustment with frequent monitoring of free plasma phenytoin levels in patients taking INH because this drug inhibits the metabolism of phenytoin.

4.    Basal meningitis or a selectively placed tu­berculoma can impede or block the flow of CSF out of the   ventricular   system.   Consequently,   hydro­cephalus associated with deteriorating neurological symptoms should be treated by a ventriculoperitoneal shunting procedure to relieve elevated intraventricular pressure.

5.    Paradoxical progression of tuberculosis with the development of tuberculomas during treat­ment of tuberculous meningitis has been reported. The new lesions progress for some time then regress if the initial antituberculous drug regimen is not changed.

 

Prognosis

The mortality of tuberculous meningi­tis is still between 10 and 20 percent. The prognosis is poor in infants, the elderly, when treatment is de­layed, and in patients with poor nutrition or debilita­tion from HIV infection or other chronic diseases. The outcome is clearly associated with the stage of the disease at diagnosis and the introduction of early treatment. Those who are conscious and without neu­rological deficits have a good prognosis; those in coma at the beginning of treatment have a 20 percent mortality and only 20 percent make a complete re­covery.

 

Table 16-11

Suggested treatment of tuberculous meningitis

 

 

Tuberculoma

A tuberculoma is a granulomatous mass resulting from enlargement of a caseous tubercle. Tuberculoma formation is a rare indication of tuberculous infection in the United States and is more common in Canada, Great Britain, Asia, and Africa. Tuberculomas vary in size and are usually supratentorial and multiple. Most are located in the parietal lobe and may be attached to the dura and predominantly extracerebral or located deep within the brain parenchyma. Signs and symp­toms depend on the primary location of the mass, but most cases present with headache, vomiting, and seizures. The diagnosis is usually considered if there is evidence of systemic tuberculosis. A CT or MRI scan will identify a space-occupying mass. A con­trast-enhanced CT scan shows an enhancing mass with hypodense central necrosis and hypodense sur­rounding edema. A Tl gadolinium-enhanced MRI scan shows a strong rim enhancement, whereas a T2 gadolinium-enhanced scan shows hyperintense vaso­genic edema, hypointense granuloma ring, and a hy­perintense central necrosis.

Tuberculomas are treated with antituberculous drugs (see Table 16-11) and are often excised as a mass lesion before diagnosis. Hydrocephalus requires ventriculoperitoneal shunting. Paradoxical enlarge­ment during antituberculous therapy is encountered occasionally and can be fatal. Adjunctive therapy with steroids may be beneficial and improve the out­come.

 

Tuberculosis of the Spine

Single or multiple vertebral involvement by tubercu­losis is frequently followed by spinal cord compres­sion due to the development of a cold abscess in the epidural space (Pott disease).

The condition presents with pain in the back followed by signs of spinal cord involvement, includ­ing spastic paraparesis, urinary frequency and incon­tinence, and loss of sensation below the level of the cord compression. The site of compression can be lo­calized by MRI scanning.

Treatment consists of antituberculous therapy and surgical decompression using an anterior spinal decompression and fusion.

Tuberculosis or tuberculoma of the meninges or spinal cord without evidence of Pott disease is rare. Most cases present as extradural or arachnoid granu­lomas and intermedullary tuberculomas are extremely rare. The latter present as spinal cord tumors with progressive paraparesis, loss of bladder control, and back pain. A sensory level may be present with im­pairment of touch, pinprick, and a temperature below the level of the lesion, and there are increased tendon reflexes in the lower extremities and bilateral extensor plantar responses. Tuberculomas tend to be localized to the thoracic cord. The diagnosis is suggested by the presence of systemic tuberculosis, usually pulmonary disease. Biopsy may be necessary when the diagnosis is in doubt.

 

Treatment

Medical treatment of tuberculosis as outlined in Table 16-11 is indicated. Progressive neu­rological deficits may require surgical removal of the tuberculoma.

 

Brain abscess

 

Encapsulated or free pus in a substance of the brain tissue following an acute purulent infection is known as brain abscess. Abscesses may vary in size from a microscopic collection of inflammatory cells to an area of purulent necrosis involving the major part of one hemisphere. Abscess of the brain has been known for over two hundred years but the surgical treatment started with Macewen in 1880.

Etiology. Brain abscesses arise either as direct extension from infec­tions:

–          within the cranial cavity (mastoid, nasal sinuses, osteomyelitis of the skull),

–          from infections secondary to fracture of the skull,

–          as metastases from infection elsewhere in the body.

 Brain abscess occurs in about 2% of patients with congenital heart disease. It is generally believed that metastatic brain abscesses are usually multiple.

The infecting organism may be any of the common pyogenic bac­teria, but Staphylococcus aureus, Streptococcus viridans, hemolytic streptococcus, Enterobacteriaceae and anaerobes such as Bacteroides are most commonly found. Pneumococci, meningococci and Hemophilus influenzae are rarely recovered from brain abscesses. Not infrequently the abscess will be sterile by the time operation is performed. Brain abscess is an infrequent complication of infection with the Entamoeba histolytica.

Pathology The pathological changes in brain abscess are similar regardless of whether the infection extends to the brain directly from an epidural or subdural infection, by a retrograde thrombosis of veins or by metastasis through the arterial system.

In the first stage there is a suppurative necrosis of brain tissue (purulent encephalitis). When immunological forces control the spread of the infection the macroglia and fibroblasts proliferate in an attempt to surround the infected and necrotic tissue. The success of the body in limiting the spread of infection and the density of the capsule are the main factors in the final outcome. Edema of the adjacent portion of the cerebrum or of the entire hemisphere is a common finding.

 

Incidence. Brain abscesses are relatively rare and constitute less than 2% of the patients who are referred to a neurosurgeon for intracranial surgery. Brain abscess may occur it any age but it is more common in the first to third decades of life. The high incidence of mastoid and nasal sinus disease at this period. Males are slightly more frequently affected than are females.

 

Clinical features. The symptoms of brain abscess are essentially the same as those of any expanding lesion in the brain.

Symptoms of infection are lacking unless the focus which gave rise to the abscess is still active. Chills and fever at the onset of the invasion of the nervous system are said to be present in some cases but are distinctly rare except in cases where there is an embolic lesion in the brain secondary to acute endocarditis.

Since edema of neighboring brain tissue is common, increased intracranial pressure develops rapidly. Thus headache, nausea and vomiting are early symptoms. Convulsions, focal or generalized, are common.

The body temperature is normal or subnormal except when it is elevated as the result of other complications or activity of the septic focus which was the source of the abscess.

The pulse and respiratory rates are normal unless the intracranial pressure is greatly increased.

The optic discs are choked in over 50% of the cases, depending to some extent upon the site of the abscess. Inequality in the degree of the choking in the two eyes has no lateralizing value.

Signs of injury to the third or sixth cranial nerve as a result of increased intracranial pressure are occasionally seen. Focal signs include: Hemiparesis or hemiplegia when the abscess is in the cerebral hemispheres; torpidity and mental confusion are especially prominent with abscesses in the frontal lobe; hemianopia and aphasic disturbances, when the temporal or parieto-occipital lobes are involved; ataxia, intention tremor, nystagmus and other symptoms of cerebellar and vestibular dysfunction when the abscess is in the cerebellum. Not infrequently, however, the signs of an abscess in the cerebrum or cerebellum are limited to those resulting from increased intracranial pressure.

Abscesses in the brain stem are distinctly rare, and the diagnosis is usually established at necropsy. Fever, headache, cranial nerve palsies, hemiparesis, dysphagia and vomiting were the common symptoms.

 

Laboratory Data. Examination of the blood and urine is normal unless there is activity in the septic focus or unless complications are present.

The changes in the cerebrospinal fluid are related to the size, location and stage of development of the abscess and to the presence or absence of acute meningitis. When the latter is present, the cerebrospinal fluid findings are those commonly seen in acute purulent meningitis. They are essentially those of an expanding intracranial lesion (increased pressure) plus those which accompany an aseptic meningeal reaction. The pressure is elevated in almost all cases. In our series it was over 200 mm in 70% and greater than 300 mm in 60%. The fluids are usually clear and colorless but they may be cloudy or turbid in the early stages and a fine clot may form in fluids with a high cell count.

The cell count is directly related to the stage of encapsulation of the abscess and its nearness to the meningeal or ventricular surfaces. The cell count varies from normal to a thousand or more cells per cu mm. In early unencapsulated abscesses near the ventriculo-subarachnoid space the cell count is great, with a high percentage of polymorphonuclear leukocytes. The cell count is normal or only slightly increased when the abscess is firmly encapsulated.

The protein content is moderately increased in about 75% of the cases. The sugar content of the fluid is normal. A decrease in sugar content below 40 mg indicates that the meninges have been invaded by bacteria.

The electroencephalographic changes are similar to those which are found in cases with other space-occupying lesions.

Radionuclide scan is usually positive, but false negative results have been reported.

Roentgenograms of the skull may show separation of sutures in infants or children and an increase in the convolution markings. Widening of the sella turcica, thinning of the clinoid processes and displacement of the pineal gland may occur in adults.

Computerized tomography (CT) scan with contrast enhancement permits accurate determination of capsule formation and precise localization of the abscess.

 

 

Diagnosis. The diagnosis of a brain abscess can be made without difficulty when convulsions, focal neurological signs or increased intracranial pressure develop in a patient with an acute or chronic infection in the middle ear, mastoid, nasal sinuses, heart or lungs or with congenital heart disease. In the absence any obvious focus of infection, the diagnosis may be very difficult and may require com­puterized tomography or cerebral angiography.

 

Differential diagnosis. The common differenjtial diagnoses which must be considered are brain tumor, extradural or subdural abscess, sinus thrombosis, encephalitis and meningitis.

Most of these condi­tions can usually be differentiated by the history of the development of symptoms and the results of roentgenography of the skull, electroen­cephalogram and CT brain scan.

The diagnosis of meningitis is readily established by examination of the cerebrospinal fluid. The differential between brain tumor and abscess cannot be made before operation in many instances. The presence of an active focus of infection in the mastoid or nasal sinuses and a pleocytosis in the cerebrospinal fluid are strong evidence for the diagnosis of an abscess. Subdural, or rarely, epidural infections in the frontal regions may give signs and symptoms exactly the same as those of an abscess in the frontal lobe and in many the differential diagnosis cannot be made. Exploratory operation is indicated in both conditions.

Thrombosis of the lateral sinus often follows middle ear or mastoid infection and may be accompanied by convulsions and signs of increased intracranial pressure, making the differentiation between this condition and abscess of the temporal lobe or cerebellum difficult. The presence of focal neurological signs, hemiplegia, hemianopia or aphasia, are in favor of the diagnosis of an abscess. Similarly, chronic increased intracranial pressure may follow thrombosis or ligation of the lateral sinus. This condition is often described under the terms otitic hydrocephalus or hypertensive meningeal hydrops. The increased intracranial pressure with choked discs which occurs in these cases is due to interference with the drainage of blood from the brain.

Prognosis. The outcome of untreated brain abscess is, with rare exceptions, fatal. The mortality in surgically treated cases varies depending upon various factors:

–          Location and degree and encapsula­tion of the abscess,

–          site of the original infection,

–          presence of complica­tions

–          whether there are single or multiple abscesses.

 

Treatment. The treatment of brain abscess is surgical evacuation of the pus. The operation is usually delayed until the abscess is firmly encapsulated.

The surgical treatment of brain abscess varies from complete extirpa­tion to repeated drainage through a trephine opening. The ideal treatment is complete removal of the abscess within its capsule.

 Any method of surgical treatment should be combined with the administration of antibiotics in full therapeutic doses both pre- and postoperatively.

 

 

Encephalitis

 

   Encephalitis – means inflammation of the brain tissue. In pathogenesis of encephalitis besides infectious one there are three more factors. They are:

• Infectious – allergic

• Toxic (in this case it is known as encephalopathy)

• Allergic

 

Classification

Encephalitis are divided into

• Primary

• Secondary

 

Primary encephalitis

I.              Viral

1.     Seasonal (acaridan, gnat)

2.     Without seasonal characteristics

a.    Enteroviral

b.    Herpetic

c.    Flu – associated

d.    HIV – associated

3.     Caused by unknown virus  – epidemic

II.            Microbial  ( at neuro – lues , rheumatism )

 

Secondary encephalitis

1.     Parainfectious  ( at measles, small pox, rubella, scarlet fever, poliomyelitis )

2.     Postvaccinal  ( after antirabies, antipoliomyelitic, antidiphtheric vaccine)

 

According to the spreading of the pathological process encephalitis are divided into:

1.    Leukoencephalitis  – when white substance of the brain is mainly involved

2.    Polioencephalitis – when gray substance of the brain is mainly involved

3.    Panencephalitis – when there is diffuse lesion of the neurons of main pathways of brain and spinal cord

    The most common are parainfectious and postinfectious encephalitis. They take about 50 % of all encephalitis. 

     Among the primary encephalitis the most common are viral encephalitis (such as enteroviral, flu – associated, herpetic ones)

 

The common syndromes for all encephalitis are:

1.    General – infectious

2.    General – cerebral

3.    Focal

 

Epidemic encephalitis

Etiology. Etiological agent is unknown. It is supposed that this disease is caused by virus.

Pathogenesis. Virus penetrates through the mucous membrane of the nose, pharynx into the subarachnoid space of the brain and causes inflammation. This disease is much more common in winter and spring.

The source of infection is ill persons or healthy carriers

The incubation period lasts from 1 to 14 days. Infection is transmitted by air drop way.

It is much more often observed in 20 – 30 years old persons.

 

 

Pathology

    Vascular – inflammatory changes are mainly localized in central ganglions of hemispheres and brainstem. Usually the lesions are observed in midbrain, red nuclei, black substance, thalamus, hypothalamus and reticular formation.

    In acute stage exudation and proliferation takes place.

    In chronic stage degenerative changes of the neurons are observed.

 

 

 

Clinical features

There are two stages of the disease:

• Acute

• Chronic

 

There are three main symptoms in acute stage:

1.    Fever

2.    Eye movements disorders

3.    Sleep disorders

All of these symptoms are present at typical form of epidemic encephalitis.

1.    Fever. It manifests as increased temperature to 38 – 39º against general cerebral symptoms, such as headache, nausea, vomiting, muscle pain. Sometimes there are complains on upper respiratory ways disorders. This period lasts for about 2 weeks.

2.    Sleep disorders. This syndrome usually manifests as pathologic sleepiness. Sometimes pathologic insomnia can occur. In some cases the patient sleeps in day – time and cannot fall asleep at night.

3.    Eye movement disorders.  These symptoms usually occur in case of nuclei of Oculomotor nerve lesion. It manifests as diplopia, anizokoria, gaze paresis, converse symptom of Argil – Robertson, ptosis, cross eye, midriasis, nystagmus, ophthalmoplegia. 

 

 

Besides these three main syndromes of acute period sometimes we can observe the others. They are:

1.    Vestibular disorders

2.    Lesion of VII, XII, V CN’s

3.    Hyperkinesis

4.    Hypothalamic disturbances: disturbances of sweating, salivation, fatty skin, loss of flesh.

 Against general cerebral symptoms consciousness disorders appear such as – sopor, psychomotor agitation, fear, hallucinations.

In blood analysis there are leucocytosis (lymphocytic), increased SR.

     In CSF there is slight lymphocytic pleocytosis to 20 – 40 cells in 1 mm³, slightly increased sugar and protein content.

Besides typical form of acute stage sometimes atypical forms are observed. They are:

1.    Abortive – when all the symptoms of acute stage are not well expressed.

2.    Oculocephalgic – when eye movements disorders and severe headache dominate over the other symptoms.

3.    Vestibular – when vestibular syndrome dominates ( there are dizziness, vomiting, ataxia )

4.    Hyperkinetic – against the symptoms of acute stage hyperkinesis occur. Sometimes in this case sleep disorders, amyostatic symptoms and thalamic pains are observed.

5.    Flu – associated – It looks like flu – infection. General infectious symptoms prevail.

6.    Rare forms –

·         Epidemic hiccup

·         Peripheral form

·         Pseudoneurastenic

 

Course of the disease Acute stage lasts from 4 days to 1– 4 months. It is characterized by remission and exacerbations. Usually it is cured. In 35 – 50 % of all patients the results of acute stage is a chronic one. 

 

Chronic stage 

   It manifests as Parkinson syndrome in 90 % of patients or Hyperkinetic syndrome in 10 %.

There are three main groups of symptoms at Parkinson syndrome:

1.     Akinesia or hypokinesia

2.     Plastic hypertonia

3.     Static tremor

    Chronic stage lasts for several years. Usually it is not cured. Differential diagnosis should be made with Parkinson disease, vascular, posttraumatic, neuroleptic, toxic Parkinson disease.

Parkinson disease – is hereditary degenerative disease which usually occurs at the age of 45 – 60 years. Tremor prevails over hypokinesia. It is a family disease. The symptoms of acute stage are absent.

Vascular Parkinsonism – occurs at the age of 60 and later. There are well expressed symptoms of cerebral atherosclerosis – memory disorders, the symptoms of dyscirculative encephalopathy (vestibulo – cerebellar, cephalgic, pyramidal syndromes). There are vascular sclerotic changes on eye ground.

Neuroleptic Parkinsonism – occurs at long lasting usage of Galloperiolum, Tizercinum. At first autonomic disorders appear, then Parkinson syndrome occurs. It is also associated with hyperkinesis of oral muscles. There is dissociation of typical symptoms, for example akinesia with tremor without plastic hypertonus.

Traumatic Parkinsonism – is the result of cranial trauma.

Toxic Parkinsonism – is usually developed at Mn, CO intoxication. It is usually associated with polyneuropathy, psychiatric disorders, seizures, choreoatetosis.

 

 

 

 

 

Treatment

Acute stage

Etiotropic treatment

6.    Interferonum 500 000 U. It is prescribed in dose 1 amp. once a day during 7 days or Reaferonum  1 mln U i/m

7.    Virolex – 250 mg 3 – 4 times per day or Aciclovir 200 mg 3 times per day, or Virasolom 2 caps. 3 – 4 times per day during 7 days.

8.    Stimulators of interferonum production – Prodigiosan – 1 ml 0.005 % i/m once every three days.

9.    Acidi ascorbinici , vit. B1, B6.

10. Antibiotics in order to prevent pneumonia.

 

Pathogenetic treatment for all types of encephalitis (see treatment of meningitis)

6.    Desintoxication

7.    Dehydratation

8.    Desensibilization

9.    Hormones

10. Nootrops

 

Symptomatic treatment

Chronic stage

1.    Synthetic holinolytics:  Cyclodolum (0.01, 0.005), Romparkin, Parkopan (0.001, 0.002)

Stimulators of dophamine secretion

2.    Amantadine medications increase sensation of dophamine receptors to dophamine, excite dophamine receptors. Midantan (0.1 3 times per day), Amantadinum.

3.    Inhibitors of MAO (Jumex) – 5 mg 1 – 2 times per day.

4.    Stimulators of dophamine receptors – Bromcriptine, Akineton, Norakin (0.001 – 0.002).

5.    Medications that decrease converse catch of dophamine. Amitriptilinum, Amipraminum, Melipraminum.

6.    Substitutional therapy. Sinemet 3 – 6 tablets per day. Nacom – 3 – 6 tablets per day.

7.    In order to decrease tremor we use b – adrenoblockers: Anaprilinum 10 mg 3 times per day, Amitriptilinum 25 mg 3 times per day.

8.    In order to decrease muscle tonus Midocalm, Baclofen are used.

9.    Nootrops

10.  Physiotherapeutic methods.

 

Spring – summer encephalitis

 

Etiology and pathogenesis

    Etiological agent is a neurotropic virus of spring – summer encephalitis. It is resistant to the low temperature and it is unstable at temperature higher than 70 º. Reservoir of virus is Acaridan. Simultaneously they are transmitters of the infection. The disease is much more common in spring and summer because of the biological peculiarities of Acaridan. This disease is widely spread in Siberian, in Ukraine – in Carpathian and Volyn region, also in Western European countries.

     The person is usually infected by means of two ways. They are:

·         bite of Acaridan

·         while using of row milk, cheese ( made of wild goats )

Then with blood the virus penetrates into the central nervous system. In the third day after the bite the virus can be found in blood of the person. The incubation period lasts from 8 to 20 days.

 

 

 

 

Pathology

   There are hyperemia, brain edema, inflammatory changes, focuses of necrosis, vasculitis mainly in the oblongate brain and spinal cord. In chronic stage there are fibrous changes in meninges, arachnoid cysts in the anterior horns of the spinal cord and in the oblongate brain.

 

Clinical features

     At first headache and general weakness appears. The temperature is increased to 39–40º. There are such syndromes:

a)    general – infectious  (there is leucocytosis, increased SR in blood). The temperature curve has 2 hills. The space between them is equal to several days. The second hill means that the virus is already in the central nervous system. 

b)    General – cerebral  (headache, vomiting, seizures, disorders of consciousness)

c)    Meningeal – hallucinations

d)    CSF disorders – (cytosis up to 100 cells, protein content up to 2 g/l).

      Sometimes there are diarrhea and abdominal pain.

 

Clinical forms

1.    Polioencephalomyelitic ( typical form )

2.    Poliomyelitic

3.    Meningeal

4.    Encephalitic

5.    Meningoencephalitic

6.    Not well expressed

7.    Polyradiculoneuritic

 

 

1.    Polioencephalomyelitic (typical form)

On the third – fourth day of the disease there are:

a)    Flaccid paresis or paralysis in the shoulders, neck muscles (as a result of lesion in the anterior horns of the cervical segments). There is symptom of the “hanging head“.

b)    Bulbar syndrome with paresis of the muscles of pharynx, larynx, breathing disorders.

2.     Poliomyelitic

This form is associated with flaccid paralysis and paresis of extremities.

3.     Meningeal

This form manifest as acute serous meningitis. There is pleocytosis in CSF to 300 cells.

4.     Encephalitic

There are bulbar, pontine, midbrain, subcortical, capsular and hemispheres syndromes.

5.     Meningoencephalitic

There are symptoms of two previous described forms.

6.     Not well expressed

General infectious syndrome dominates over the others.

7.     Polyradiculoneuritic

This form is characterized by the symptoms of polyradiculoneuritis (flaccid paralysis, polineuritic type of sensory disorders, pain)

 

Chronic stage

This stage is characterized by such symptoms as:

1.    Kozhevnikov epilepsy – it is associated with myoclonus in certain group of muscles and periodic epileptic attacks.

2.    Poliomyelitic form – means progress of the acute stage

3.    ALS syndrome

4.    Syringomyelitic syndrome

5.    Syndrome of multiply encephalomyelitis

 

 

The course of the disease In the acute stage the symptoms are usually developed during the first 10 days. Then it slightly decreases. Renewal of functions lasts from 2 to 3 years. There is high mortality at meningoencephalitic and poliomyelitic forms associated with bulbar syndrome.

 

Diagnosis

1.    Epidemic anamnesis (endemic zone, the bite of Acaridan)

2.    The presence of virus in blood and CSF with its identification

3.    Serologic reactions

After the disease the patients usually have strong immunity.

 

Differential diagnosis

·         Serous meningitis

·         Acute poliomyelitis

·          Typhus

 

      The treatment of the acute stage There are specific and non -specific methods of treatment.

Specific treatment

1.    10 % Gamma globulin (made of serum of those people who live in endemic regions or were vaccinated against the etiologic agent of this disease)

2.    10 % Gamma globulin (made of serum of hyperimmunizated hoarses). It is used in dose 3 – 6 ml during 2 –3 days.

3.    The serum of those people who had this disease in dose 8 – 10 ml endolumbal or 50 ml i/m once a day during 2 – 3 days.

4.    Blood transfusion from those people who had this disease.

 

Non – specific treatment

1.    RNA – dose 25 mg 6 times per day during 5 – 6 days.

2.    Antibiotics in order to prevent pneumonia

3.    Hormones (16 – 24 mg per day)

4.    Diuretics (Diacarb, Sorbit, Manitol)

5.    Vitamins B1, B6, C

6.    Hemodes, Rheopoliglucin, Rheogluman, 5 % Glucosa

7.    Symptomatic treatment (glycosides, artificial ventilation, tracheostomy)

Renewal period:

1.    Vitamins B1, B6, B12

2.    Proserinum, Halantaminum

3.    Biostimulators (Aloe)

4.    ATP, Cocarboxilasa

5.    Anabolics

6.    Nootrops

7.    Physiotherapy

8.    Sanatorium treatment

Prevention:

1.    Active immunization with cultural vaccine three times with revaccination after 4–12 months.

2.    Passive immunization with hoarse hyperimmune serum in dose 10 – 20 ml i/m.

Primary poliseasonal encephalitis

To this group belong those encephalitis which are caused by Coxacci viruses (A9 B3 B6) and ECHO (2, 11, 24), that means enteroviral, herpetic, flu – associated.

 

Enteroviral encephalitis

Pathology

     There is well – expressed perivascular edema (especially in cortex, basal nuclei), focal destructive changes of white substance and inflammatory changes of vascular walls.

 

Clinical features

    Encephalitic signs are developed on the second – fifth days against expressed general – infectious and general – cerebral symptoms. There are such syndromes as:

·         Brainstem

·         Hemispheres

·         Cerebellar

 

1.    Hemispheres syndrome manifests as seizures against increased temperature, paresis, paralysis. Sometimes it is associated with aphatic disorders and hyperkinesis.

2.    Brainstem syndrome. It is characterized by CN’s disorders, such as diplopia, ptosis, cross eye (III CN), dizziness, nausea, vomiting , decreasing of hearing (VIII CN), dysarthria, dysphonia, dysphagia (caudal group of CN’s).

3.    Cerebellar syndrome manifests as static and dynamic ataxia against general infectious and general cerebral syndromes.

 

Diagnosis The diagnosis of this type of encephalitis is put according to the presence of focal symptoms on the second – fifth day after upper respiratory ways disorders or sub febrile temperature and general weakness. There is increased content of lymphocytes and increased pressure in CSF.

 

The course of the disease Usually the course of the disease is favourable with full regress of neurologic symptoms. Sometimes slight disorders of CN’s, paresis or aphasic disorders remain after the disease.

 

Treatment

1.    Antibiotics

2.    DNA – daza – 25 mg every 4 hours during 10 – 12 days.

3.    Hormones ( Dexamethazonum 8 – 16 mg)

4.    Desensibilizative ( Suprastinum, Pipolphenum, Tavegil )

5.    Hemodes, Rheopoliglucinum, Rheoglumanum in order to desintoxicate

6.    Symptomatic treatment

Herpetic encephalitis

Herpes simplex virus can damage different organs and systems of organs (skin, mucous membrane, liver, nervous system).

It is widely spread. Almost 70 – 90 % of all grown ups have antibodies to it. It can persist in patient’s body for a long time. At unfavorable conditions in those persons who have low immune response it can be activated.

It penetrates into the central nervous system with blood flow.

 

Pathology There is brain edema, focuses of necrosis and hemorrhages with neurons death. The lesion of mediobasal parts of temporal lobes and lower orbital parts of frontal lobes is very typical for the herpetic encephalitis. This can be explained by the fact that the virus penetrates through the bulbus ophthalmicus or trigeminal ganglion.

 

Clinical features The clinical picture is the same as at any other encephalitis (increased temperature, general cerebral symptoms).

 

Peculiarities

1.    General epileptic attacks

2.    Focal symptoms of temporal and frontal lobe

·         Smell and taste hallucinations

·         Anosmia

·         Memory disorders

·         Psychiatric disorders

·         Hemiparesis

·         Hyperkinesis

 

The course of the disease   The disease has severe course and rapid progress. Mortality is too high (50 – 70 % in case of absence of treatment). As a result of acute brain edema coma is developed with cutting – in syndrome which usually leads to patient’s death.

 

Diagnosis

1.    There is increased pressure, lymphocytic pleocytosis (from 100 to 500 cells in mm³), slightly increased protein content, sometimes erythrocytes in the CSF

2.    There are periodic high amplitude quick waves in temporal lobes on EEG

3.    There are hypodensive zones as a result of inflammatory changes as well as edema, small hemorrhages in frontal and temporal lobes on CT and MRI

4.    Positive serologic reactions

5.    Immunofluorescentive method

 

Treatment    Herpetic encephalitis has effective specific treatment.

1.    Acyclovir (Zovirax, Virolex) is used in dose 200 mg 5 times per day orally or i/v in dose 10 – 30 mg per kg 3 times per day. We usually use it during 10 – 14 days. This medication has small toxicity and is excreted by kidneys. Its side effects are nausea, headache, dermatitis, phlebitis. It is usually prescribed when we do not know exactly etiologic agent

2.    DNA – daza 25 mg i/m every 4 hours

3.    Interferonum 500 000 U i/m once a day

4.    Mannit, Manitol, Lasix

5.    Rheopoliglucinum, Rheoglumanum, Hemodes

6.    Immunomodulators (Immunoglobulin, T – activin, Timalinum)

7.    Symptomatic treatment

 

Prognosis    It depends on patients age, state of consciousness disorders. Mortality now is about 25 %. Half of those who survived have residual symptoms such as Korsakov syndrome, demention, epileptic attacks, and speech disorders.

 

Flu – associated encephalitis

It is caused by A1, A2, A3, B viruses and is usually the result of flu. The virus has toxic influence on the brain vessels receptors.

 

Pathogenesis The virus has neurotoxicity and causes circulation disturbances in the brain. It also stimulates immunologic reactions.

 

Pathology There are thrombovasculitis, small hemorrhages and perivascular changes in the brain tissue.

 

Clinical features

Common flu is characterized by general infectious and general cerebral symptoms – headache, painful eye movements, muscle pain, sleepiness. Usually in case of favourable course all these symptoms tend to disappear. Sometimes it is complicated with flu associated encephalitis, especially in those persons who have chronic diseases, brain diseases, chronic intoxication or brain trauma.

The disease starts rapidly with increased temperature, general cerebral, meningeal and focal symptoms after the flu.

The main syndromes are:

1.    Cortical syndrome – psychotic disorders, seizures

2.    Brain stem disorders  – lesion of III, IV, VIII, V – VII CN”s, hemiparesis

3.    Hypothalamic

4.    Cerebellar

 

1.    First of all general weakness, depression, irritation, emotional instability appear.

2.    Psychotic disorders manifest as hallucinations, paranoids, delirium

3.    Seizures are usually tonic – clonic with involuntary urination and tongue biting.

4.    Brainstem syndrome manifests as vestibular syndrome, lesion of III, IV, VI CN’s with eye movements disorders, ptosis, diplopia, cross – eye. Sometimes VII and XII CN’s and pyramidal path ways are involved ( in this case we can observe paresis of mimic muscles, tongue deviation, asymmetric stretch reflexes, pathologic reflexes of Babinski and others. In most severe cases spastic paralysis and paresis are developed.)

5.    Hypothalamic syndrome means changes of pulse, heart rate, skin colour.

6.    Cerebellar syndrome means ataxia, coordination disorders.

7.    Subcortical syndrome usually manifests as hyperkinesis against low muscle tone.

 

    In case of toxic form of flu associated encephalitis hemorrhagic flu associated meningoencephalitis can be developed. It is characterized by brain vessels tonus disturbances, small hemorrhages. Usually this disease is much more common among the young persons at the age of 16–40. The disease starts rapidly with general cerebral symptoms such as headache, sleepiness, loss of consciousness, vomiting, psychomotor agitation and well expressed meningeal syndrome.

   This disease should be differentiated with subarachnoid hemorrhage. Besides general cerebral syndrome there are focal one or two side cerebral symptoms (speech disorders, lesions of CN’s, bulbar syndrome, frontal release signs). There are changes on eye ground, lymphocytic pleocytosis, increased protein content and blood traces in CSF.

    Hemorrhagic encephalitis has severe course and usually leads to patients’ death. If the person survives some of the neurologic symptoms remain. When headache, dizziness and nausea remain for a long time and are increased at slight physical exercises then it is considered to be the sign of commissural arachnoiditis.

     At flu associated encephalitis there is leucocytosis or leucopenia in blood and lymphocytic pleocytosis in CSF.

The course of the disease in most cases is favourable. The disease lasts for a month and is usually cured.

Treatment

1.    Desintoxication

2.    Diuretics

3.    Gamma globulinum 6 mg per day i/m, Rimantadinum 0.1 3 times per day

4.    Dexamethazonum, Prednisolonum

5.    Antibiotics in order to prevent pneumonia

 

Encephalitis at general infections

Etiology and pathogenesis

    This type of encephalitis is very common at early childhood. Allergic process takes a special place in its pathogenesis. This encephalitis is usually associated with various infections in children, such as measles, scarlet fever, rubella, small pox.

Measles encephalitis and encephalomyelitis

Measles encephalitis is the most typical form of parainfectious encephalomyelitis. The frequency of this disease is 1:1000.

Pathology

There is fibrous edema of vessels’ walls and perivascular focuses of demyelination.

 

Clinical features

    The disease develops rapidly on the third – fifth day after the rash when the temperature is usually normal. Then suddenly it is going worse, the temperature increases  to 39 – 40º, the child becomes sleepy, has consciousness disorders, psychomotor agitation, seizures, sometimes meningeal syndrome is associated. In some cases focal signs can be observed such as paresis, paralysis, hyperkinesis, coordination disorders, lesion of II, III, VII CN’s.

When the spinal cord is involved in the process there is also paralysis of lower extremities, sensory disorders according to the conductive type, disturbance of function of pelvic organs.

There is mild lymphocytic pleocytosis to 200 cells per 1 mm³, increased content of protein in the CSF.

The course of the disease is severe. Mortality is 10 – 25 %. There are residuals such as seizures, hyperkinesis, and mental retardation.

 

Small pox encephalitis

The prevalence of this disease is 1 per 10 000. It has infectious – allergic character.

 

Pathology

    There is inflammation of brain tissue and focuses of demyelination. In severe cases there are purulent – hemorrhagic focuses.

 

Clinical features

The disease is usually developed on the third – seventh day after the rash. In 50 % of children there is benign cerebellar ataxia. In the rest ones there are pyramidal and extrapyramidal symptoms against general infectious, general cerebral and meningeal syndromes. There is lymphocytic pleocytosis to 100 – 200 cells, increased protein content in the CSF.

The course of the disease is favourable. Mortality is 10 %.

Residual symptoms – paresis, hyperkinesis, seizures.

Treatment

1.    Desensibilizative medications

2.    Hormones

3.    Against edema medications

4.    Dezintoxication

5.    Nootrops

6.    Symptomatic treatment

7.    Vitamins B1, B6, C

 

Postvaccinal encephalitis

This group of encephalitis are developed after the vaccination.

 

Pathogenesis This group of encephalitis belong to the allergic leucoencephalitis

 

Pathology There are small hemorrhages, brain edema, focuses of demyelinization in the brain and spinal cord.

 

Clinical features

    Usually this disease develops in vaccinated children, especially at late vaccination and revaccination. The disease develops on the 7 th – 12 th day after the vaccination and starts with increased temperature to 39 – 40 º, severe headache, vomiting, consciousness disorders, seizures. Sometimes meningeal signs appear. In some cases paresis, paralysis and coordination disorders are observed.

   There is mild lymphocytic pleocytosis in the CSF.

 

The course of the disease Usually it is favourable. Although in some cases paresis and paralysis remain for a long time. The main peculiarity of the course of the disease after antirabies vaccination is the clinical picture of acute encephalomyelopoliradiculoneuritis with well expressed bulbar syndrome, disturbance of breathing and heart – vascular activity, which can cause death of the patient.

 

Treatment

1.    Desensibilizative medications

2.    Hormones

3.    Diuretics

4.    Anti seizures medications

5.     Antipyretics

 

Acute toxic encephalopathy

    This encephalopathy develops after the viral infection and is usually associated with lipid degeneration of some internal organs, especially liver. It is much more common in children than in adults.

Etiology It is unknown till nowadays. It is considered that the disease is the result of viral effects and intoxication. The risk of the disease increases in case of Aspirin usage.

Pathology Brain edema without inflammation, liver enlargement.

Clinical features

After the viral infection when there is normal temperature, there are no respiratory or gastro – intestinal disorders suddenly it is going worse, the temperature increases again, sleepiness and consciousness disorders appear. This is known as first stage of Rayer syndrome.

The second stage – delirium and epileptic – attacks.

The third stage – superficial coma develops without any focal signs.

The 4^th and 5^th stage – deep coma develops, sometimes cutting in syndrome can occur and it can cause the death of the patient.

The disease can be stopped at any stage or can progress. The typical features are liver enlargement with its’ function disorders and pancreas disturbances.

 There are no changes in CSF. There is leucocytosis in blood.

Treatment

1.    Symptomatic

2.    Dehydratation (Manitol)

3.    ALV ( artificial lung ventilation)

4.    Correction of liver functions (Glucosa, Vicasolum, hepatoprotectors).

 

 

Viral Encephalitis

Definition Viral encephalitis is an acute febrile ill­ness with evidence of damage to the parenchymal tis­sues of the CNS, producing alterations of conscious­ness, focal neurological signs, and seizures.

 

Etiology and Pathology

The etiology cannot be identified in almost two-thirds of the cases of viral en­cephalitis but the advent of polymerase chain reaction testing is expanding identification of viral agents or other agents in this disease. The arthropod-borne viruses (arboviruses, Table 16-16) compose the largest category of identified agents in viral encephalitis. Herpes viruses and enteroviruses are also frequently reported. The pathogenicity of each virus varies be­cause some disturb neuronal function temporarily; others are capable of producing widespread neuronal death.

Acute viral encephalitis is characterized by in­flammation of and damage to neurons in the gray matter of the CNS. Neuronal inclusion bodies are seen in some encephalitides such as rabies and herpes simplex encephalitis. There is prominent perivascular cuffing by lymphocytes and plasma cells, and the lep-tomeninges are inflamed. Certain viruses have a predilection for particular areas of the CNS. Herpes simplex produces an intense inflammatory response in the temporal lobes; rabies virus has a predilection for the limbic system, whereas poliovirus infection is mainly confined to the motor neurons, particularly those in the spinal cord and brainstem.

 

Table 16-16

Arthropod-borne encephalitis

 

Clinical Features

Table 16-16 outlines the epi­demiological characteristics of the arthropod-borne encephalitides. These conditions, which constitute the  most frequent forms of encephalitides, are transmit­ted by a bloodsucking vector. The insect, usually a mosquito or tick, acquires the virus from an animal that is unaffected by a chronic viremia. The signs and symptoms of viral encephalitis show some variation, depending on the etiological agent. In most cases, there is an acute febrile course with signs of meningeal irritation, headache, nausea, photophobia, vomiting, alteration of consciousness, focal neurolog­ical deficits, and seizures. The mortality varies from high in Eastern equine encephalitis to low in Venezuelan equine encephalitis. Residual abnormali­ties include seizures. Changes in personality, ex­trapyramidal signs, dementia, and motor sensory im­pairment may complicate most viral encephalitides. A young age at presentation, presence of semicoma or coma, abnormal oculocephalic responses, and labora­tory demonstration of virus infection within the CNS are associated with a poor outcome.

 

Differential Diagnosis   See Table 16-16.

 

Diagnostic Procedures

1.    The CSF is clear and the pressure may or may not be elevated There is an early increase in polymorphonuclear cells in some cases, followed by lymphocytic pleocytosis. The glucose content is nor­mal and the protein content normal or mildly ele­vated.

2.    An MRI or CT scan should be obtained to rule out a space-occupying lesion in an acutely ill in­dividual (Fig. 16-11).

3.    An EEG may reveal focal or widespread slowing and may indicate the possible type of viral infection by EEG pattern, such as bitemporal slowing with 2- to 3-Hz spike and sharp wave complexes in the temporal leads in herpus simplex encephalitis.

4.    The CSF should be examined for virus DNA by polymerase chain reaction. This is a rapid, sensitive, and accurate procedure.

5.    The virus is occasionally cultured from the CSF, stool, urine, nasopharynx, or blood.

6.    Another method in establishing a diagnosis of viral encephalitis is the demonstration of a rise in antibody titers to a particular virus in acute and con­valescence sera. Titers are quantitated by hemagglutination-inhibition, complement fixation, or neutraliz­ing methods. This, however, is a delayed and often retrospective method of diagnosis.

 

Treatment

1. In the absence of viral identification, the patient should be assumed to be suffering from her­pes simplex encephalitis and treated with acyclovir or ganciclovir.

2.    The airway must be kept clear, and the semicomatose  or comatose patient  suctioned fre­quently. Every effort should be made to avoid pneu­monia.

3.    Adequate   fluid   and   electrolyte   balance should be maintained at all times.

4.    Seizures should be controlled with initial intravenous phenytoin or phosphenytoin followed by an intravenous diazepem drip.

5.    Increased ICP should be treated with intra­venous mannitol to keep the serum osmotic pressure between 300 and 320 mosmol.

 

 

Herpes Simplex 1 Encephalitis

 

Definition

Herpes simplex virus type 1 (HSV-1) encephalitis is an acute, frequently fatal, necrotizing encephalitis with a predilection for the temporal and orbital frontal areas of the brain.

 

Etiology and Pathology

Herpes simplex type 1 virus is a large, enveloped DNA virus that may possi­bly spread to the brain from the trigeminal ganglion or other sites where the virus may exist in a latent stage.

The virus exhibits tropism toward neurons in the temporal lobes of the brain and there may be ar­eas of necrosis and hemorrhage, diffuse mononuclear infiltration, neuronal cell loss, and eosinophilic in­tranuclear inclusions in surviving neurons. There is usually marked cerebral edema, which may affect one temporal lobe or one hemisphere, producing an asymmetrical swelling of the brain (Fig. 16-12).

 

Clinical Features

The virus is the major cause of herpes labialis (cold sores) and many people have serologic evidence of prior exposure to HSV-1 by the second decade of life.

Herpes simplex encephalitis affects children and adults with no sex preference, and the infection is not enhanced by a compromised immune system. The disease begins with flu-like symptoms, including fever, headache, and malaise, followed by the rapid development of meningeal irritation and disorienta­tion. There may be a prominent psychosis with hallu­cinations, disorientation, and disturbance of memory, followed by the appearance of focal neurological signs such as aphasia or hemiparesis. The patient is often unable to give a good medical history and rapid deterioration with stupor progressing to coma is not unusual.

An acute necrotizing myelitis with spinal cord necrosis and absence of cerebral involvement has been described. This condition can occur in immuno­compromised or nonimmunocompromised individu­als and carries a high mortality rate.

 

Diagnostic Procedures

1.    The CSF is under increased pressure, with a monocytic pleocytosis in the presence and the pres­ence of red blood cells in some cases. There is an ele­vated protein (60 to 150 mg/dL), and a normal glu­cose content. The antibody titers to HSV-1 may be elevated.

2.    Serology.  There  is  a  rise  in  anti-HSV complement-fixing antibody titers, but this test is

unreliable as a rapid diagnostic test and lacks sensi­tivity. The polymerase chain reaction test is usually positive by the third day, providing a reliable method for determining an etiological diagnosis of HSE, and is highly effective and essential for accurate di­agnosis.

3.    The EEG often shows periodic high-volt­age, 2- to 3-Hz spike and sharp wave complexes in the temporal leads.

4.    The MRI or CT scan shows the presence of swelling and edema, often more marked in one lobe or one hemisphere (Fig. 16-13).

5.    SPECT scans may depict increased perfu­sion   in   the   characteristically   involved   temporal lobes.

6.    Brain biopsy was the definitive procedure to establish the diagnosis of herpes simplex en­cephalitis. However, the polymerase chain reaction is so reliable that the need for brain biopsy is question­able.

 

Differential Diagnosis

The differential diagnosis includes brain abscess, bacterial or fungal meningitis, toxoplasmosis, other viral encephalitides, septic embolization, postinfectious encephalomyelitis, acute necrotizing hemorrhagic encephalitis, and toxic en­cephalopathies.

 

Treatment

1.    Acyclovir is the antiviral agent of choice for herpes simplex encephalitis. The drug should be administered as early as possible before the onset of coma. Survivors treated after the onset of coma in­variably show permanent neurological deficits. Con­sequently, acyclovir should be administered in all suspected cases without waiting for laboratory confir­mation of the diagnosis. An intravenous dose of 10 mg/kg infused over 1 h q8h for 10 days is recom­mended. Nephrotoxicity due to precipitation of acy­clovir crystals in renal tubules can be avoided by ade­quate hydration to maintain a good urinary output. Toxicity with tremors, hallucinations, agitation, or lethargy is rare. The development of resistance to acyclovir has not been a problem to date in the treat­ment of immunocompetent individuals.  However, acyclovir-resistant HSV strains have emerged in im­munocompromised patients. Intravenous foscarnet is the current treatment of choice in such cases.

2.  Increased ICP should be treated with an in­travenous infusion of mannitol and furosemide. Seizures require aggressive therapy. Surgical de­compression may be necessary to avoid herniation in cases with rapidly increasing ICP.

 

Prognosis

The mortality rate is 30 percent in pa­tients receiving early treatment with acyclovir. Coma is associated with 70 percent mortality and severe neurological deficits in the majority of survivors.

 

Herpes Simplex 2 Encephalitis

Infections of the CNS with herpes simplex virus 2 (HSV-2) accounts for 4-6 percent of cases of herpes simplex encephalitis. However, infection by HSV-2 usually presents as an aseptic meningitis occurring in individuals with primary genital HSV-2 infection. Symptoms consist of headache, stiff neck, photopho­bia, malaise, and fever. The CSF findings consist of a lymphocytic pleocytosis up to 1000 cells per cubic millimeter and normal glucose content. The disease is usually mild and self-limiting, but neurological deficits, including persistent headache, impaired con­centration, impaired hearing, and paraparesis, indi­cate occasional encephalitis. An ascending necrotiz­ing myelitis has been reported. Recurrent infections can occur.

 

                  

 

 

Diagnostic Procedures   As for HSV-1.

 

Treatment Intravenous acyclovir is indicated in any patient with signs of parenchymal involvement of the CNS.

 

Herpes Zoster (Varicella) Encephalitis

Encephalitis is a rare complication of varicella infec­tion and occurs about 7 to 10 days after the appear­ance of the rash. The encephalitis is usually mild with symptoms of headache, nausea, ataxia, dysarthria, and occasionally seizures. Complete recovery occurs in most cases, but an occasionally life-threatening, more diffuse encephalitis, with cranial nerve palsies, hemiplegia, aphasia, and coma, can occur. Encephali­tis has occasionally been reported after shingles. This complication is said to be rare but is probably more common than reported in the past. Many elderly pa­tients report malaise and fatigue and lack of energy after shingles. Careful neurological examination often reveals cerebellar ataxia in such cases, suggesting that a mild rhombencephalitis may have complicated the infection. These patients gradually recover after a period of 6 months or more.

 

Treatment   As for Rabies

 

Definition Rabies is an acute, almost invariably fa­tal infectious illness caused by a neurotropic virus of the rhabdovirus family.

 

Etiology and Pathology

The rabies virus is a bullet-shaped, enveloped RNA-containing virus that usually gains access to the body by a bite from a ra­bid animal. The virus then replicates locally in mus­cle cells, penetrates nerve endings, and travels in ret­rograde fashion up the nerve axons to the CNS. The virus then replicates once more, spreads throughout the CNS with a higher concentration in the limbic system of the brain and eventually travels out nerve trunks to all parts of the body. The virus is thought to act directly on specific membrane receptors.

The brain and spinal cord show perivascular and perineural mononuclear infiltration, and the leptomeninges are mildly inflamed. The disease is char­acterized by the presence of intracellular intracyto-plasmic eosinophilic inclusion bodies (Negri bodies).

 

Clinical Features

Human rabies has been identi­fied in all continents except Australia and Antarctica, but approximately 60 countries are reported to be ra­bies free, owing to geographical isolation, animal control programs, or quarantine regulations. More than 99 percent of cases occur in developing coun­tries, such as China and India, where rates have been reported as high as 3/100,000, although the rate is probably closer to 1/1,000,000 in developing coun­tries at this time. The disease is more common in children aged 5 to 14 years and in adults older than 50 years. Bats, skunks, raccoons, and dogs are implicated in human rabies cases in the United States; the mongoose and jackal in Africa; the fox in Europe and Canada; the wolf in western Asia; and the vampire bat in Central and South America. Occasion­ally rabies can be transmitted by other means than an animal bite, including inhalation of airborne virus in caves contaminated by bat secretions, or by inhala­tion in laboratories where the air is contaminated by virus. There are also reports of transmission from a rabid donor to a corneal transplant recipient.

The key to the early diagnosis of rabies is the history of exposure to a rabid or potentially rabid ani­mal. There is an incubation period of 20 to 90 days in the great majority of cases, although longer incuba­tion periods have been reported. This is followed by complaints of pain and paresthesias at the bite site, accompanied by fever, chills, headache, and myalgia in about 50 percent of cases. The majority of patients develop “furious” rabies characterized by a prodro­mal period of disorientation, bizarre behavior, hallu­cinations, insomnia, and hyperactivity, followed by cyclic arousal with agitation, associated with pharyn­geal and inspiratory muscle spasms on attempted swallowing. Eventually an intense terror develops at the mere thought of water, giving rise to the synonym “hydrophobia” for rabies. Autonomic disturbances are common and the patient may develop hypersaliva-tion, hypotension, hyperpyrexia, and tachycardia. There may be signs of meningeal irritation and cra­nial and peripheral nerve palsies. Periods of hyper­sensitivity can be precipitated by tactile, auditory, or visual stimuli. Hyperventilation, fasciculations, and seizures precede the development of stupor and even­tual coma. The patient eventually loses consciousness and dies from respiratory arrest or circulatory failure. Some patients may develop a clinical form of rabies termed “dumb” or “paralytic” rabies. This form of rabies is characterized by an acute ascending symmetrical or asymmetrical paralysis resembling the Guillain-Barre syndrome and occurs in about 15 percent of cases leading to respiratory and bulbar paralysis.

 

Complications

The major complications of rabies include cerebral edema, seizures, SIADH, pneumonia, atelectasis, cardiac arrhythmias, conges­tive heart failure, cardiac arrest, hypotension, gas­trointestinal bleeding, anemia, paralytic ileus, renal failure, and paralsysis of the urinary bladder.

 

Diagnostic Procedures

1.  Immunofluorescent rabies  antibody  staining  of skin biopsies is the most reliable diagnostic proce­dure.

2.  Rapid fluorescent focus inhibition test (RFFIT) measures rabies-neutralizing antibodies from in vitro cell cultures and is positive within 48 h.

3.  The CSF is usually under increased pressure with a lymphocytic pleocytosis. CSF antibody levels may not be positive until the seventh day of ill­ness.

4.  Serum neutralizing antibodies may be detected by the sixth day of illness.

5.  Rabies is rarely seen in the United States and is ofteot diagnosed until after death.¹⁶⁸ Early di­agnosis could be established by detection of rabies RNA by PCR.

 

Differential Diagnosis

1.  Tetanus may be distinguished from furious rabies by the presence of rigidity between muscle spasms and a short incubation period between the bite or wound and onset of symptoms in tetanus. The CSF is normal, and there is lack of hydrophobia in the tetanus patient.

2.  Postvaccinal encephalomyelitis is now rare and typically occurs some 2 weeks after the first dose of a vaccine.

 

Treatment

1.  All animal bites should be thoroughly treated. The wound should be vigorously flushed and scrubbed with a 20% soap solution. Tetanus prophylaxis and measures to control bacterial infection may be necessary.

2.  Human diploid cell rabies vaccine (HDCV) or ra­bies vaccine adsorbed (RVA) are currently the treatment of choice.

a. Pre-exposure dosage. Individuals such as vet­erinarians who are at high risk of exposure to rabies should receive three 1-mL intramuscular injections of HDCV or RVA, the second dose 1 week after the first, and the third 2 or 3 weeks after the second. Serum antibody levels should be determined 2 to 3 weeks after the last dose of vaccine to be sure of a satisfactory response. A booster dose of 1 mL intramuscularly every 2 years is recommended when there is a continu­ing risk of exposure to rabies.

b. Postexposure treatment. The decision whether or not to treat a patient requires consideration of several factors. The algorithm (Fig. 16-14) is a guide to the correct decision in human rabies postexposure prophylaxis.

When treatment is initiated, human rabies immune globulin (HRIG) should be adminis­tered in a dose of 20 μg/kg with half the dose infiltrated at the site of the wound and the rest given intramuscularly. At the same time, a 1-mL dose of HDCV or RVA should be given in­tramuscularly and repeated on days 3, 7, 14, and 28 after the first dose. A previously immu­nized person who demonstrated rabies antibod­ies, who was exposed to rabies, should receive two doses of 1 mL HDCV or RVA, one imme­diately and one 3 days later. Human rabies im­mune globulin is not indicated for such patients.

3.  Those involved in patient care should be vacci­nated and wear face masks, gloves, and gowns when in contact with the patient.

4. Patients with rabies should be treated in an inten­sive care unit. Patients are acutely ill and require careful monitoring of cardiovascular and pul­monary function, electrolytes, and parenteral flu­ids. The intense distress caused by hydrophobia can be reduced by adequate doses of a phen-othiazine combined with a benzodiazepine.

 

Prognosis There are occasional reports of pa­tients who have survived rabies. Unfortunately, the vast majority die of the disease.

 

HIV Infection and the Nervous System

Infection by HIV can involve the nervous system early in the course of the disease and at multiple levels from the brain to the peripheral nerve and muscle. Infection may be regarded as primary when the pathological changes are the direct result of HIV alone, or secondary in the case of opportunistic in­fections. In addition, there are undoubtedly active combinations of primary HIV infection and oppor­tunistic infections or pathological changes that are es­sentially the toxic effects of anti-HIV therapeutic agents.

The spectrum of HIV infection has gradually widened in the last decade. The early manifestations were the result of immunosuppression, with the de­velopment of meningitis and toxoplasmosis in the CNS. However, antibiotic control and prophylactic therapy have improved survival and permitted the development of additional complications such as CNS lymphoma and progressive multifocal en­cephalopathy or several disorders involving the spinal cord, peripheral nerve, and muscle.

 

HIV Dementia (AIDS Dementia Complex)

Definition This progressive dementia occurs in AIDS, owing to a direct primary HIV infection of neurons or an indirect neurotoxicity induced by the presence of the virus in the brain.

 

Etiology and Pathology Although there is ample evidence indicating the presence of HIV in brain in HIV dementia, there is no indication of direct neural infection. In addition, quantitative studies using the polymerase chain reaction show no signifi­cant differences in amounts of HIV DNA between brains of demented and nondemented HIV-infected patients. The virus may be transported into the brain by infected peripheral monocytes (Trojan horse theory) and it is believed that something associated with HIV-infected macrophages within the CNS leads to neurological damage. Alternatively, the virus may be transported into the CNS by infected T cells, which penetrate the blood-brain barrier. The virus then infects microglial cells, which may act as a reservoir for persistent infection. The production of gpl20, a surface protein of HIV, may lead to the opening of calcium channels, including NMDA-mediated channels in the neuronal membrane, an influx of calcium, and neuronal death. An alternative hy­pothesis suggests that the presence of HIV in glial cells results in the production of cytokines including tumor necrosis factor alpha, and interleukin-6, and metabolites of the arachidonic acid cascade, resulting in neuronal damage.

The brain shows diffuse atrophic changes, with dilatation of the ventricles and widening of the corti­cal sulci. There are multiple foci of inflammation, with microglia, macrophages, and multinucleated giant cells.

Clinical Features Dementia is usually a late development in HIV disease when the CD4 lympho­cyte count is less than 200 cells per cubic millimeter. The onset is insidious, and the progression usually slow. The earliest signs can only be established by serial neuropsychologic testing which will reveal early cognitive dysfunction and indicate the need for early treatment with protease inhibitors in triple-drug combinations preventing neuronal cell death. The primary complaint is difficulty with memory, attention, retrieval of information, and planning. This is followed by slowing of higher cognitive func­tions, including judgment, insight, calculation, and abstraction. Motor signs consist of progressive spasticity and ataxia, with impairment of gait. Later signs include behavioral changes, apathy, frank psychosis and in rare cases, severe generalized chorea. There is progression to paraparesis, in­continence, and seizures, with an inevitable pro­gression to death. Disorders such as toxoplasmosis lymphoma and progressive multifocal leukoencephalopathy can present with similar features and should be excluded.

 

Diagnostic Procedures

1.  Serological tests for HIV infection are positive.

2.  The CSF is abnormal, with a mild pleocytosis, ele­vated protein, increased IgG, intrathecal synthesis of anti-HIV IgG, and oligoclonal bands. The CSF markers include P₂-microglobulin neopterin and quinolinate in HIV infection. Cultures should be obtained to exclude opportunistic infection.

3.  An MRI shows cerebral atrophy, ventricular di­latation, and diffuse or multifocal increased signal intensity in the periventricular white matter (Fig. 16-15).

4.  Serial PET or SPECT scans will reveal early changes    in    brain    function    in    HIV-positive patients.

Treatment High doses of zidovudine, 1000 to 2000 mg/day, will produce improvement in some cases. Dideoxyinosine 400 mg/day has been recom­mended in those who fail to respond to or cannot tol­erate zidovudine. Combinations of idinavir, lamivudine, and zidovudine have resulted in remarkable improvement in the treatment of HIV infections. However, optimal treatment of HIV infection has yet to be established.

Peripheral Neuropathy in HIV Infection   Symmetrical peripheral neuropathy associated with HIV in­fection can present as two distinct pathologic entities. A distal symmetrical axonal neuropathy is a typical dying back phenomenon associated with macrophage infiltration of the peripheral nerves. Direct viral in­fection of the nerve is unlikely, and it is possible that cytokines such as tumor necrosis factor alpha and other cytokines may interact with nerve growth factors, pro­ducing axonal neuropathic changes. Associated condi­tions such as diabetes mellitus, alcoholism, or vitamin B₁₂ deficiency, and the use of antiretroviral nucleo­sides, may accentuate the neuropathy. Treatment should be directed toward control or diminution of ad­junctive factors, withdrawal of putative medications, and the use of amitriptyline, mexiletine, or gabapentin for pain control.

The inflammatory demyelinating polyneuropaty (IDP) of AIDS is similar to the Guillain-Barre syndrome. Acute IDP tends to occur early in the disease in patients with negative serum tests, test results for HIV, or at the time of serocon­version. However, cytomegalovirus infection is the likely agent when IDP occurs late in the disease and the CD4 count is low. Some patients respond to immunomodulating therapy with corticosteroids, plasmapheresis or intravenous immunoglobulin. Others should be treated with ganciclovir or foscarnet

therapy, if the PCR-for cytomegalovirus (CMV) is positive. Chronic IDP has also been described and is a slowly progressive disease. Most cases are the re­sult of CMV infection. Less common causes in­clude lymphoma, tuberculosis, and syphilis. Many patients improve when treated with ganciclovir or foscarnet.

Multifocal mononeuropathies are also a feature of HIV infection and can present as a series of asym­metrical polymononeuropathies and acute lum­bosacral polyradiculomyelopathy or, rarely, as an asymmetrical multifocal sensorimotor neuropathy. Most cases appear to be related to CMV infection. There may be a good response to ganciclovir or fos­carnet therapy.

 

Primary CNS Lymphoma There has been a marked increase in CNS lymphoma since the begin­ning of the AIDS epidemic.¹⁹⁰ The increase cannot, however, be entirely attributed to AIDS because the incidence of CNS lymphoma has increased in the non-AIDS population.

The presence of Epstein-Barr virus in AIDS-related lymphoma has been reported in almost 100 percent of cases. Since Epstein-Barr virus DNA can be detected in the CSF it may be of diagnostic value. Thallium 201 brain single photon emission computed tomography  is useful in differentiating cerebral lymphoma from toxoplasma encephalitis in AIDS patients.

 

Treatment Radiation therapy often produces re­markable but temporary improvement and prolonged survival for a median of 4 to 6 months. A combina­tion of radiation therapy and chemotherapy may in­crease survival time.

 

Vacuolar Myelopathy

Vacuolar myelopathy is often detected at autopsy in AIDS patients and tends to be associated with severe immunosuppression and advanced disease.

Etiology and Pathology Pathological changes consist of vacuolization of myelin sheaths with accu­mulation of macrophages and microglia; axons are preserved. There is no evidence for direct HIV in­volvement, and the myelin damage may be attributed to the presence of toxic cytokines such as tumor necrosis factor or vitamin B ₂ deficiency.

Other causes of myelopathy in AIDS include lymphoma, herpes zoster myelitis, CMV infection, and toxoplasmosis.

Clinical Features The condition presents as a slowly progressive spastic ataxic paraparesis with im­paired sphincter control and lower extremity sensory symptoms. Examination shows lower limb spasticity, weakness, ataxia, hyperreflexia, extensor plantar re­sponses, and a mild sensory impairment.

Treatment Symptomatic treatment includes measures to decrease spasticity, such as oral baclofen or the use of a baclofen pump, management of sphincter impairment, and physical therapy. There is no reported benefit from antiviral agents. The mean survival after the diagnosis of AIDS is approximately 12 months.

 

Myopathy Muscle involvement may be detected at any stage of HIV infection.

Etiology and Pathology Myopathy is be­lieved to be the result of an autoimmune responserather than a direct infection by the HIV virus Affected muscles show inflammation and myofiber degeneration resembling polymyositis. However, nemaline rod bodies, cytoplasm bodies, and mi­tochondrial abnormalities have been described. These findings have suggested that in some cases, the myopathy in AIDS may be the result of zidovudine therapy. Consequently muscle disorders in HIV in­fection may be

a)    HIV associated myopathies

b)    Zidovudine myopathy

c)    Opportunistic infections and tumoral infil­tration of muscle.

Clinical Features The symptoms are those of a myopathy with proximal muscle weakness, diffi­culty rising from a chair, and difficulty climbing stairs. Respiratory muscle dysfunction with dyspnea is a late feature. Weight loss is a prominent symp­tom and myalgia occurs in about 50 percent of cases.

Treatment

1.    Zidovudine should be withdrawn temporar­ily because of the putative association between my­opathy and zidovudine therapy. This may result in improvement in some cases, which implies that zi­dovudine therapy is implicated in the myopathic process, in which case the drug should be withheld permanently. However, the drug can be reintroduced in the face of progressive muscle weakness.

2.    Prednisone 60 mg daily improves strength in most patients and can be continued as an alternate-day therapy to minimize adverse effects.

 

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a multifocal demyelinating disease that has been reported as a nonmetastatic complication of neopla­sia. It also occurs in immunosuppression therapy in immunocompromised patients with leukemia, lym­phoma, tuberculosis, sarcoidosis (following renal transplantation), or AIDS. PML, once an extremely rare disease, has become much more frequent owing to the AIDS pandemic. The disease is the result of  infection with JC virus, a human papillomavirus which infects and destroysoligodendrocytes. The pathological changes consist of multiple areas of white matter demyelination, extending through the gray-white matter junction into the cortical gray mat­ter. There are perivascular inflammatory infiltrates and large “balloon” oligodendral glial cells, with nu­clear inclusions containing virions.

Clinical features include progressive dementia, visual loss, spastic quadriparesis, and ataxia. Death usually occurs less than a year after the onset of symptoms; HIV-associated progressive multifocal leukoencephalopathy has a median survival time of 2 to 4 months. About 10 percent of patients have a more benign course, with remission and prolonged survival.

 

Diagnostic Procedures

1.  The EEG shows progressive slowing of activity over both hemispheres.

2.  The MRI scan reveals extensive white matter lesions bilaterally on T2-weighted imaging (Fig. 16-16).

3.  The diagnosis is established by detection of JC virus DNA in the CSF by polymerase chain reac­tion or by brain biopsy.

 

Treatment Intravenous cytarabine (ARA-C) im­proves survival.

 

Neurological Opportunistic Infections in AIDS

There are three common opportunistic infections in patients with HIV infection.

a)  Toxoplasmosis

b)  Cytomegalovirus

c)  Cryptococcosis

 

Cytomegalovirus Infections

The majority of cases of CMV infection of the central or peripheral nervous system in adults occur in im­munocompromised individuals. This group includes patients receiving immunosuppressant therapy for or­gan transplantation or malignancy and patients with AIDS.

 

Etiology and Pathology  

The CMV is a DNA virus of the herpesvirus group, which produces swelling of infected cells that contain large intranu­clear inclusions. In infected adults, the brain shows diffuse or focal encephalitis with microglial nodules in the parenchyma and areas of demyelination in the central white matter of the cerebrum, brainstem, and spinal cord. Cytomegalovirus ventriculoencephalitis with hydrocephalus, vasculitis, and radiculomyelitis is a unique entity in patients with advanced HIV infection.

 

Clinical Features Encephalitis caused by CMV is a common complication of organ transplantation and AIDS and occasionally occurs in CMV infectious mononucleosis. The infection is probably the result of reactivation of a latent CMV infection because most adults possess antibodies to CMV. However, the ubiq­uitous nature of the virus is such that infection is eas­ily transferred person to person or by blood transfu­sion.

Infection by CMV in AIDS usually occurs when the CD4 lymphocyte count falls below 50 cells per cubic milliliter and is often accompanied by in­fection of other organs, particularly the lungs and adrenal glands.

Symptoms of encephalitis consist of the abrupt onset of headache, fever, and somnolence followed by focal neurological deficits and seizures. Cy­tomegalovirus polyradiculopathy is often present and can be the initial manifestation of AIDS in some races. The presence of retinal vasculopathy in AIDS is indicative of CMV infection.

 

Diagnostic Procedures

1.  On lumbar puncture, the CSF shows a mild pleo-cytosis, increased total protein, and IgG.

2.  The MRI scan reveals hydrocephalus and in­creased   signal   intensity   in   periventricular   or meningeal structures.

3.  Cytomegalovirus DNA can be demonstrated in the CSF using the polymerase chain reaction.

4.  Electrolyte abnormalities occur in patients with adrenal insufficiency.

5.  Confirmation of polyradiculopathy can be ob­tained by electromyography (EMG).

6.  Liver function tests are abnormal.

 

Treatment The use of the antiviral agents ganci­clovir or foscarnet, alone or in combination, increases survival time for several weeks.

 

Prognosis Survival is only a matter of weeks in most cases, particularly in those with AIDS.

Infants with CMV encephalitis acquired by transplacental passage from a recently infected mother or at birth develop severe brain damage in many cases. Survivors exhibit signs of multiple neu­rological abnormalities. Infants with mild or silent in­fection have some degree of sensorineural hearing loss.

 

Epstein-Barr Encephalitis

Epstein-Barr virus (EBV) is a DNA virus in the her­pes virus group. Infection by EBV results in infec­tious mononucleosis and is occasionally responsible for Bell’s palsy, Guillain-Barre syndrome, transverse myelitis, and acute encephalitis. The encephalitis is usually mild, often presenting as an aseptic meningi­tis, but occasionally a more severe parenchymal brain infection can occur. The prognosis is good in most cases, but fatalities have been reported. Infection with EBV has been related to primary CNS lymphoma in AIDS patients.

 

Diagnostic Procedures

1.  The blood shows an early leukopenia followed by leukocytosis with atypical lymphocytes.

2.  Lumbar puncture. There is a mild pleocytosis, ele­vated protein and IgG, and the presence of atypi­cal lymphocytes in the CSF.

3.  Liver function tests are abnormal.

4.  EBV DNA can be demonstrated by PCR.

 

Treatment Supportive. Antiviral agents are not ef­fective.

 

Prognosis Good, but fatigue, hepatomegaly, and splenomegaly may persist for many months.

 

Reye Syndrome

Reye syndrome is an acute encephalopathy that oc­curs predominantly in children and rarely in adults.

 

Etiology and Pathology Reye syndrome usually follows infection by influenza A or B, herpes zoster (chickenpox), herpes simplex, and paramyxoviruses. Other possible causes include the combined effect of a virus infection and the use of salicylates. However, the role of salicylates has not been established. There are characteristic pathological changes, including cerebral edema, proliferation of smooth endoplastic reticulum, and morphologically abnormal mitochon­dria, most marked in the neurons. The abdominal vis­cera and liver are heavily infiltrated with fat, and mi­tochondrial damage occurs in the liver cells. It is probable that the mitochondrial abnormalities affect­ing the brain and liver cells are the crucial pathologi­cal changes in Reye syndrome.

 

Clinical Features The onset is acute. The syn­drome usually presents in a child who is apparently re­covering from influenza, varicella, or an upper respira­tory infection. There are five stages:

1) onset with lethargy and protracted vomiting;

2) progressive im­pairment of consciousness with hallucinations, com­bative behavior, and hyperventilation; seizures may oc­cur;

3) coma with intermittent decerebrate rigidity occurring spontaneously or with minimal stimulation; brainstem reflexes are intact;

4) coma with decerebrate rigidity, hyperventilation and absence of brainstem re­flexes;

5) coma, respiratory failure, and death.

 

Diagnostic Procedures

1.    Liver function tests are abnormal, with ele­vation of serum aspartate transaminase (AST) and alanine transaminase (ALT).

2.    Serum glucose levels are low, and hypo­glycemia occurs in some cases.

3.    The plasma prothrombin time is prolonged.

4.     Serum ammonia levels are elevated about 50 mg/100 mL.

5.    The EEG shows symmetrical slowing. Se­rial records are useful in assessing the course of the illness.

6.    Either MRI or CT scanning shows evi­dence of cerebral edema with decreased density in the white matter in both hemispheres.

7.    There are no abnormalities in the CSF, but the glucose content may be low, in the presence of hypoglycemia. Lumbar puncture should not be per­formed in cases with suspected increased ICP.

8.    The diagnosis can be confirmed by liver biopsy, but this is usually not necessary.

 

Treatment When a child is arousable to verbal or painful stimuli, the following measures should be taken:

1.    The child should be intubated with a low-pressure nasotracheal tube and placed on a mechani­cal ventilator.

2.    The prothrombin time or partial thrombo­plastin time should be determined. If these times are prolonged, fresh frozen plasma should be given to re­duce the risk of bleeding, should an ICP monitor de­vice be inserted.

3.    A ventricular or subdural pressure monitor­ing device can be inserted, and ICP should be contin­uously recorded.

4.    If ICP exceeds 20 mmHg, mannitol 0.25 g/kg should be given intravenously.

5.    The  serum osmolality  should be main­tained between 300 and 320 mosmol/L and it should be measured q2h.

6.    A   neuromuscular   blocking   agent   such as  pancuronium  administered  under the  supervi­sion of an anesthesiologist is required if the ICP remains   elevated   or   the   patient   cannot   tolerate the ventilator. A neurological examination is per­formed immediately before the use of the neuromus­cular blocking agent, which can be discontinued briefly when further neurological assessment is performed.

7.    The body temperature is maintained below 30°C, using a refrigerator blanket.

8.    A Foley catheter should be inserted and the intake and output monitored.

9.    Fluid and electrolyte balance can then be maintained.

10.    The central venous pressure and arterial pressure are monitored through a central line.

11.    Hypertonic glucose 15% to 20% is in­fused intravenously to maintain the serum glucose level between 150 and 200 mg/dL.

12.    Insulin 1 unit per 10 g glucose should be infused q4h. The dose of insulin is regulated to main­tain glucose levels between 150 and 200 mg/dL. Glu­cose levels should be measured q4h.

13.    Neomycin enemas will help to reduce serum ammonia levels.

14.    The lungs are checked frequently. Pos­tural drainage and suctioning should be performed q2h or more frequently if necessary.

15.    A barbiturate coma should be considered in those rare cases when ICP cannot be controlled

 

Prognosis Children recovering from clinical stages 1, 2 or 3 are usually neurologically normal. Recovery from stages 4 and 5 may be followed by permanent neurological deficits, including spasticity, hemiparesis, dystonia, involuntary move­ments, and seizures. Recurrence of Reye syndrome is rare.

 

Subacute Herpes Simplex-6 Encephalitis

Involvement of the CNS by herpes simplex virus type 6 (HSV-6) has been reported by several sources and usually occurs in immunocompromised individuals with bone marrow transplants or AIDS. Infection ionimmunocompromised individuals can occur, however, producing a disease resembling acute dis­seminated encephalomyelitis in young children or severe acute multiple sclerosis. However, the role of HSV-6 in multiple sclerosis remains to be defined, although the virus has been demonstrated in multi­ple sclerosis plaques in some cases. A chronic myelopathy with predominantly white matter changes has been described. Thus, HSV-6 may produce an encephalopathy that shares clinical manifestations and demyelinative characteristics with multiple scle­rosis but may be etiologically distinct. Alterna­tively, HSV-6 may have a role in acute multiple scle­rosis, which is, as yet, undefined.

 

 

Arachnoiditis

Definition

Arachnoiditis is a chronic inflammation and fibrosis of the leptomeninges, usually occurring in the spinal canal and occasionally in the cranial cavity.

 

Etiology and Pathology

Arachnoiditis has been described following myelography using both water-soluble and oil contrast media. However, there is no doubt that the most common etiological factor in spinal varieties of arachnoiditis is surgical treatment of lumbar disc disease and the use of nonabsorbable oil-based contrast materials for myelography. The association of herniated lumbar intravertebral disc and arachnoiditis has been challenged recently. Chronic inflammation of the leptomeninges is more likely to occur after repeated myelographic studies, and it is possible that the injection of a mixture of contrast media and blood during a traumatic lumbar puncture increases the risk of arachnoiditis. There are also occasional reports of arachnoiditis following in­jection of antibiotics into the subarachnoid space and following spinal anesthesia. Arachnoiditis has been reported following trauma to the spinal column and spinal canal, and local arachnoiditis is not unusual at the site of a ruptured intravertebral disc. Chronic in­flammatory changes in the leptomeninges may follow an acute purulent meningitis or may be related to chronic infections, including syphilis, tuberculosis, sarcoidosis, and fungal meningitis. Localized arach­noiditis may occur at the site of tuberculosis of a ver­tebral body (Pott disease). Arachnoiditis has also been reported following subarachnoid hemorrhage.

Pathological changes consist of thickening of the leptomeninges and monocytic infiltration or gran­ulomatous inflammation with vascular proliferation. The blood vessels are involved by an arteritis or phlebitis. The presence of thickened leptomeninges may produce constriction of nerve roots or pressure on the spinal cord. This may be compounded by ischemia over the spinal cord, with circumscribed ar­eas of necrosis and fibrosis.

 

Clinical Features

The chief complaint is usually weakness of the lower limbs, which may progress to severe paraparesis or paraplegia. The appearance of weakness is followed by complaints of pain, which may be of two types, a burning pain in the distribu­tion of the affected nerve roots, or a more ill-defined pain below the level of the compression. In addition, patients may complain of numbness, “deadness,” and coldness in the lower limbs and trunk below the level of the arachnoiditis. Disturbances of micturition are early symptoms, and many patients develop complete incontinence. Examination shows the presence of spastic paraparesis with increased reflexes and exten­sor plantar responses. Sensation to pain and tempera­ture is impaired below the level of the cord compres­sion, and posterior column involvement produces impairment of vibration and position sense.

 

Diagnostic Procedures

1.    A CT scan of the spine may show the pres­ence of destruction of the vertebral bodies in cases of tuberculosis.

2.    The study of choice is MRI scanning. It is nontraumatic and is as effective as plain film myelog­raphy or CT myelography in the demonstration of lumbar arachnoiditis.

3. Lumbar puncture reveals a CSF of reduced pressure with a negative Queckenstedt test in cases of complete spinal block. The CSF is often xan­thochromic and the protein content is markedly ele­vated.

 

Treatment

1. Prophylactic

a.  Avoid the use of myelography when CT or MRI scans are unequivocally abnormal and in­dicate the presence of a herniated disc.

b.  If myelography is necessary, the latest type of water-soluble contrast media, which is quickly absorbed with the CSF, should be utilized.

Suspected infection should be effectively treated with antibiotics. Compression of the spinal cord or lumbosacral nerve roots can be relieved surgically in some cases by unroofing the dura mater and separating each nerve root one from the other. Patients with diffuse arachnoiditis may benefit from a course of corticosteroids, which may reduce the inflammatory response. Chronic cases are difficult to treat and may require pro­longed use of analgesic drugs. Transcutaneous stimu­lation may be useful in some cases. Direct cord stimulation using implanted electrodes has had some success.

 

Prognosis

Localized arachnoiditis treated by sur­gical resection of the leptomeninges usually shows good response to treatment. Patients with severe spinal cord damage can only hope to avoid further de­terioration and obtain relief from pain by appropriate use of analgesic medications.

 

Idiopathic Chronic Hypertrophic Craniocervical Pachymeningitis

Definition

This rare condition of chronic inflam­matory disease causes hypertrophy of the dura mater.

 

Etiology and Pathology

The etiology is un­known. It is possible that some cases represent occult tuberculous disease. There is diffuse thickening of the dura in the cervical and thoracic spinal cord or in the posterior fossa with involvement of the tentorium cerebelli and occasional extension forward into the middle and anterior cranial fossae with involvement of the falx cerebri. Microscopic examination shows dense fibrous tissue with an intermingled inflamma­tory exudate composed of lymphocytes, plasma cells, monocytes, and occasional multinucleated giant cells.

 

Clinical Features

The more frequently observed cervical pachymeningitis presents with back and neck pain followed by progressive spastic para­paresis, urgency of micturition and loss of bladder control associated with radicular pain due to progres­sive involvement of cervical and upper thoracic nerve roots.

The cranial form of the disease causes head­ache, cranial nerve palsies, cerebellar ataxia, and al­tered mentation with the development of hydro­cephalus.

 

Differential Diagnosis Other causes of pachy­meningitis must be considered, including tuberculo­sis, sarcoidosis, syphilis, Wegener granulomatosis, fungal or parasitic infections, and rheumatoid arthritis.

 

Diagnostic Procedures

1.    The CT scan shows a diffusely thickened hyperdense dura enhanced in the iodinated contrast study. The gadolinium-enhanced Tl-weighted MRI scan shows marked enhancement of the dural edge. The T2-weighted images show relative hypodensity of the thickened meninges with fine hyperintense edges, and there is homogenous enhancement of the thickened dura with gadolinium diethylenetriamine-pentaacetic acid.

2.    A thorough evaluation should be under­taken to exclude tuberculosis, sarcoidosis, syphilis, and other granulomatous conditions.

3.    The CSF is usually under an increased pressure and has an elevated protein content. The glu­cose content is normal and cultures are negative.

4.    Antibodies   to   herpes   simplex   may   be present.

 

Treatment

1.    There is usually a prompt but temporary re­sponse to corticosteroid therapy.

2.    Immunosuppression with azathioprine or cyclophosphamide or radiation therapy has inconsis­tent results.

3.    Surgical excision of the hypertrophied dura is mandatory to provide temporary decompression of the cervical cord and prevent paraplegia.

4.    A ventricular-atrial shunt procedure may be necessary in patients with hydrocephalus and papilledema.

5.    Treatment  with  acyclovir or famciclovir might benefit patients with elevated herpes simplex antibodies.

 

Poliomyelitis and the Post-Polio Syndrome

Epidemics of poliomyelitis occurred almost every year in the United States in the first half of the cen­tury, until the disease was practically eradicated by effective vaccination.

 

Etiology and Pathology

Poliomyelitis is caused by a virus that invades motor neurons in the spinal cord and brainstem. Neuronal death results in atrophy of muscle fibers supplied by the affected motor unit, unless there is a compensatory sprouting of new fibers by surviving axons that contact and innervate some of the newly denervated muscle fibers. How­ever, the overall effect is loss of muscle fibers, muscle wasting, and weakness.

Recovery from the acute phase of po­liomyelitis is related to the survival of neurons in the spinal cord and brainstem, and improvement could occur for as long as 2 years after the acute episode, with many patients showing residual but stable weakness. However, a number of people who survived acute poliomyelitis have had a further weakness of muscle, a condition of post-polio syndrome. This is believed to be the result of inability of the motor neuron to meet the metabolic demands of the enlarged motor unit and the atrophy of some of the distal nerve termi­nals. It is not due to reactivation of a latent polio virus infection.

Clinical Features Post-polio syndrome occurs in approximately 30 percent of patients who survive acute poliomyelitis. The condition tends to occur in patients who had severe, permanent impairment from acute poliomyelitis and is more common in women.¹⁴⁷ Patients report further muscle weakness, muscle pain, and unaccustomed fatigue. However, the deterioration is short-lived, and the condition stabilizes again, with an increased but stable residual weakness.

 

Diagnostic Procedures

Muscle biopsy will show recent and old denervation and reinnervation.

 

Treatment There is no effective treatment for post-polio syndrome.