Theme:

Theme: Cerebral and Spinal Cord tumors

Epilepsy and convulsive syndromes. Classification and diagnosis of epileptic attack and convulsive syndromes

 

      The incidence of brain tumors is 4 – 6 persons per 100 000 people. Brain tumors account for 6 % of malignances and in 1 – 1.5 % of all cases are the reason of patho – anatomical sections. Brain tumors also account 4 – 5 % of all organic diseases of the brain.

      

There are several classifications of brain tumors. The last one was proclaimed by World Health Organization in 1993. According to this classification all the brain tumors are divided into 10 groups.

I.    Epithelium tissue tumors. 

1.    Astrocytomas

2.    Oligodendrogliomas 

3.    Ependymomas, subependymomas

4.    Mixed gliomas (oligoastrocytomas)

5.    Choroid plexus tumors

6.    Neuroepithelium tumors of unknown origin (spongioblastoma, glioblastoma)

7.    Neuronal  – gangliomas, gangliocytomas

8.    Pineal region tumors (pinealoma, pineoblastoma)

9.    Embryonal tumors (meduloblastoma)

II.   Tumors of spinal and cranial nerves (neurinomas, neurofibromas)  

III.    Tumors of the meninges  

IV.   Lymphomas and tumor of hematogenic tissue.

V.     Tumors from embryo cells (chorion  – carcinoma, teratoma, embryo carcinoma)

VI.   Cysts and tumors – like processes (dermoid cyst, epidermoid cyst)

VII.  Tumors of Turkish saddle region (adenoma of Hypophysis region, carcinoma of hypophysis region)

VIII. Tumors that are expanding from neighbour’s territory

IX.          Metastasis tumors 

X.           Non classified tumors

Epithelium tissue tumors are the most common ones (50 – 60 % of all cases). Tumors of the meninges account about 20 % of all brain tumors.

 

Clinical classification of brain tumors

According to the cerebellar tentorium the tumors are divided into

·         Above tentorial (they are located in the base of anterior and middle cranial fossa)

·         Under tentorial (these ones are located in the cerebellum region, IV–th ventricle and medulla oblongata).

According to the brain tissue the tumors are divided into

·         Out of brain tumors (meningeomas and neurinomas can be treated in radical way)

·         Intra brain tumors (gliomas)

 

 

 

 

The typical features of brain tumors

1.    Astrocytoma (15%) is a benign slowly progressive tumor located in frontal, temporal, parietal lobes or in brain stem.

2.    Oligodendroglioma (8%) is a benign intra brain slowly progressive tumor. It is hardly differentiated from brain tissue. It has petrifactions that are seen at craniogram. It is localized in large hemispheres.

3.    Ependymoma (3%) is usually found in the region of ventricles (the central canal of spinal cord and the IV – th ventricle)

4.    Glioblastoma (15%) or spongioblastoma is a very malignant intra brain tumor located in temporal lobe or even sometimes in both hemispheres. It has a rapid growth with expressed intoxication and metastasis along CSF pathways.

5.    Meduloblastoma (4%) is a very malignant tumor located in cerebellum, the IV–th ventricle or in brain stem in children at the age of 1 – 10 years. It gives rapid metastasis along CSF pathways.

6.    Angioreticuloma (2%) – gemangioblastoma – is a benign slowly progressive tumor. It consists of multiple cysts of different sizes and is well separated from the brain tissue. It is often located in cerebellum.

7.    Meningeoma (15%) – is a benign out of brain tumor. There are basal and convexial meningeomas. Convexial ones are often located parasagitally and basal ones are mostly located in the region of Turkish saddle.

8.    Neurinoma (8%) – is a benign tumor from the covers of cranial (VIII, V) and spinal nerves.

9.    Pinealoma is a benign tumor located in brain stem or posterior parts of ventricles’. It is characterized by secondary malignization.

10. Adenoma of hypophysis (10%) can be hormonally active or non active. There are adenomas with increased production of Prolactinum, Somatotropinum, ACTH, Tyriotropic hormone with typical clinical picture. Hormonally active tumors can expand into the neighbouring regions. Microadenomas in the Turkish saddle do not show clinical picture.

11. Craniopharyngioma is a tumor that grows from Ratke pocket. It is inborn benign one with great number of cysts and petrifactions.

12. Metastasis (8%). Usually nervous system metastasis originates from lung, breast, kidneys, and stomach cancer. The main way of metastasis is haematogenous.

 

 

 

 

 

Etiology and pathogenesis Polyetiologic and dysontogenic theory.

 

Clinical picture

The clinical picture of brain tumors is associated with the following factors:

1.    The direct influence of tumor on the brain tissue.

2.    Increased intra cranial pressure

3.    Dislocation of different parts of the brain

 

There are 4 groups of clinical symptoms in case of brain tumors.

I.    The symptoms associated with increased intra cranial pressure – hypertension or general – cerebral symptoms.

II.    Focal symptoms as a result of tumor’s direct influence on brain tissue.

III. Neighbour symptoms as a result of brain edema, blood circulation disturbances.

IV.Distance symptoms as a result of increased intra cranial pressure and dislocation of some parts of the brain.

 

The clinical picture of tumor can consist of focal or general cerebral symptoms according to its location. If the tumor is far from the SCF pathways then focal symptoms dominate in clinical picture. If the tumor is close to the CSF pathways then the symptoms of hypertension dominate in clinical picture.

 

I. General – cerebral (hypertensive) syndromes are the result of increased intra cranial pressure.

The main reasons of increased intra cranial pressure are:

• The tumor mass

• Brain edema

• Blood and CSF drain disturbances

• CSF absorption disturbances

 

Brain edema is developed as a result of:  

• Mechanical influence of tumor

• The influence of the substances that are created in course of tumor metabolism that leads to the additional production of CSF

• Ischemia of brain tissue as a result of vessels pressure

• Venous drain disturbances and blood stagnation

 

Blood and CSF drain disturbances are observed when the tumor is located near large veins and venous collectors. The blood content in cranial cavity is increased. There is blood stagnation in cranial cavity. That causes increased secretion of CSF by choroids plexuses and leads to the increased intra cranial pressure. At the same time there are disturbances of CSF absorption that also leads to the increased intra cranial pressure.

 

The main clinical signs of intra cranial hypertension

1.    Headache

2.    Vomiting

3.    Choked disks of II CN

4.    Pulse, AP and breathing disturbances

5.    Epileptic attacks

6.    Psychiatric disorders

7.    CSF changes

8.    Craniogram changes

 

The first three symptoms are most frequent but they are observed only in 50% of all patients.

1.    Headache – is usually in the morning. It is puffed one. It is increased in case of coughing or physical exercises and it is decreased after vomiting. The main reason of headache is irritation of receptors as a result of increased intra cranial pressure. Headache is associated with painful trigeminal points, Bechterev’s cheekbone phenomena.

2.    Vomiting – is usually in case of severe headache and it is not associated with eating. The main reason of vomiting is irritation of Vagus nerve endings as a result of increased intra cranial pressure. It is a late symptom of tumor. Only in case of IV–th ventricle tumor it is an early symptom.

3.    Choked disks of optic nerve and visual disorders – are associated with venous drain disturbances. Especially often this symptom is observed at tumors in posterior cranial fossa, cerebellar tumors, tumors of temporal lobe, IV–th ventricle. Choked disks of optic nerves lead to the low visual acuity and atrophy of optic nerve disks. There is the symptom of Foster – Kennedy atrophy of optic nerve disk on the side of tumor and choked disks on the opposite side.

4.    Pulse, AP, breathing disturbances – are late symptoms of CSF hypertension. Pulse changes are due to the irritation of Vagus Nerve endings stimulation. Tachycardia is the result of brain stem pressure. Arythmia and AP changes are the results of increased intra cranial pressure.

5.    Epileptic attacks – are also the results of increased intra cranial pressure. Sometimes they are the first sign of cortical tumor.

6.    Psychiatric disorders – are memory disturbances, loss of orientation, inhibition, sometimes even sopor and coma.

7.    CSF changes – are increased CSF pressure, CSF is transient, with increased protein content at normal cytosis (protein – cellular dissociation). The most expressed CSF changes are at basal tumors (basal meningiomas), neurinomas. CSF changes at convexital tumors are less significant.

8.    Craniogram changes – are observed in a month after increased intra cranial pressure. They are osteoporosis of Turkish saddle, well expressed digital depressions, well expressed vessels picture, unclosed cranial sutures, osteoporosis of pyramids of temporal bone and edge of occipital foramen, increased skull sizes and thin skull bones.

II. Focal symptoms.

Frontal lobe tumors

1.    Frontal psychiatric disorders – decreased attention, critics, behavioral changes, speech and motor depression, the loss of social and professional skills, untidiness, excitement, aggression, low mental activity, rude humor.

2.    In case of anterior central gyrus lesion – there are central hemiparesis with domination in one extremity and facial paresis on the opposite side.

3.    In case of irritation of anterior central gyrus there are epileptic attacks like “Motor Jackson “.

4.    In case of irritation of anterior adversive region there are adversive attacks. They start with gaze and head turning into the opposite direction.  

5.    Frontal ataxia – which can later cause astasia – abasia. It is characterized by standing and walking disturbances with tendency to falling down into the opposite direction.

6.    Catching phenomena of Yanishevskyy.

7.     Hypoosmia and anosmia (at olfactory meningiomas)

8.    Motor aphasia – when the process is localized in posterior part of lower frontal gyrus. Agraphy and gaze paresis is observed at tumor in posterior part of middle frontal gyrus.

9.    Foster – Kennedy symptom – is the result of direct influence of tumor on optic nerve or increased intra cranial pressure.

10. If the tumor is localized in paracentral lobe there is lower paraparesis, urination central disorders.

 

Parietal lobe tumors

1.    In case of irritation of posterior central gyrus there are sensory Jackson attacks with parasthesia sensation in one of the extremity.

2.    In case of posterior central gyrus lesion there is loss of sensation according to the cortical monotype.

3.    The loss of deep sensation in the extremities or afferent paresis of the opposite side extremity.

4.    Autotopognosia, anosognosia, pseudomelia, astereognosia. (At right – side localization)

5.    Alexia, acalculia, agraphia. (At left – side localization)

6.    Apraxia (at tumors of gyrus supramarginalis )

 

Temporal lobe tumors

1.    Epileptic attacks with auditory, olfactory, gustatory, visual and visceral hallucinations. The patients complain often on unpleasant internal sensations, depressions with time and space loss of orientation (especially when the tumor is localized between the temporal and parietal lobe)

2.    Olfactory, auditory, gustatory agnosia

3.    Homonimic hemianopsy (when the tumor is deep in the posterior part)

4.    Sensory aphasia

5.    Amnestic aphasia

6.    Pseudocerebellar ataxia

7.    Vestibulo – cochlear dizziness.

8.    Memory disorders on current events at mediobasal parts lesion

9.    Psycho – motor automatisms.

 

Those tumors very quickly lead to

1.    Dislocation symptoms and cutting  – in

2.    Increased intra cranial pressure (headache, vomiting, choked disks of optic nerves)

3.    The symptoms of III and V CN’s lesion

 

Occipital lobe tumors (They are very rare)

1.    Simple visual hallucinations or photopsy (light, flash)

2.    Homonimic hemianopsy (this symptoms appears at destruction of cortical neurons).

3.    Colour vision disturbances (dyschromatopsy)

4.    Visual agnosia

5.    Optic metamorphopsy

6.    Central gaze paralysis

7.    Quadrant hemianopsy

General cerebral symptoms at occipital lobe tumors are very early.

 

Subcortical structures tumors

1.    They are located very close to the CSF pathways

2.    Hypertension and dislocation develop very early

 

Clinical picture

1.    Hyperkinesis

2.    Amyostatic syndrome with plastic hypertonus

3.    Hemiplegia, hemianesthesia, hemianopsy – capsule syndrome

 

Thalamus tumors

There are hemianesthesia on the opposite side with burning – like unpleasant pains.

 

Corpus Callosum tumors

1.    Psychiatric disorders with memory disturbances on current and past events

2.    Dementia

3.    Apraxia

4.    One or two – side paralysis

 

Third ventricle tumors

1.    Hormonal disorders (Non sugar diabetes, obesity)

2.    The attacks of general weakness with muscle tone disorders

3.    Headaches with autonomic reactions

4.    Occlusive – hypertensive syndrome with memory disorders and psychiatric disturbances

 

Chiasma and saddle tumors

Usually there are basal meningiomas, hypophysis adenomas, chiasmatic gliomas, optic nerve gliomas.

1.    Endocrine disorders

2.    Primary atrophy of optic nerve disk

3.    Bitemporal hemianopsy

4.    III, IV, VI, V CN’s lesion

5.    Foster – Kennedy syndrome

6.    Local hyperostosis or osteolysis in case of tumor’s expansion into the base of the skull

 

Posterior fossa tumors (tumors of cerebellum and IV – th ventricle and brain stem tumors).

    In this case hypertension increases very quickly. There are radicular and nuclei lesions of CN’s and alternating brain stem syndromes, bulbar syndrome and brain stem nystagmus.

    At cerebellar tumors there are muscular hypotonia, coordination disorders, ataxia, enforced head position (the patient is lying on the tumor), occipital headache, asynergy, adiadochokinesis. There are early symptoms of increased intracranial pressure.

 

Fourth ventricle tumors (ependimomas)

These tumors are mainly developed in young persons. In elderly ones there is metastasis of bronchial cancer into the fourth ventricle. There are 3 main symptoms:

1.    Headaches with irradiation into the neck and shoulder

2.    Morning vomiting because of IV – th ventricle irritation

3.    Dizziness and nystagmus

All these symptoms are united into the Bruns attacks (severe headache, vomiting, skin autonomic reaction, breathing disorders, arythmic pulse, enforced head position). The main reason is– acute occlusion of IV – th ventricle exit.

    Sometimes it is associated with:

1.  Neck’s muscles tension

2.  Coordination disorders

3.  Tonic attacks, tachycardia, brain stem breathing disorders, hiccup.

    Sadden death is very common in this case.

 

Brain stem tumors.

They are gliomas (benign tumors) and sarcomas (malignant tumors) or metastasis in brain stem.

1.    At midbrain tumors there are peduncle alternating syndromes of Veber, Benedict

2.    At pons tumors there are alternating syndromes of Fovil, Miyar – Hubler

3.    At medulla oblongate there are syndromes of Jackson, Avelis, Shmidt, Valenberg – Zaharchenko

Heart – vascular and breathing disorders are often joined.

 

The tumors of pontine – cerebellar angle (neurinoma of VII CN)

These tumors mainly appear at the age of 40 – 50 years. The typical signs are:

1.    Slow growth.

2.    Early focal signs

3.    Late increased cranial pressure.

The first signs of neurinoma are:

1.    Progressive hearing loss (otiatric stage)

2.    Dizziness and nystagmus

3.    The symptoms of V, VI, VII, XIII CN’s lesion and cerebellar disorders (otoneurologic stage).

4.    IX, X, XI, XII CN’s lesion.

5.    Enlargement of internal auditory pathway and osteoporosis of the top of temporal bone pyramid.

 

III. Neighbour regions syndromes.

These are developed because of the lesion of neighbouring regions, such as edema and blood circulation disturbances. These symptoms can regress while usage of dehydration therapy. Sometimes when the tumor is localized in the so-called “ mute parts of the brain” these symptoms can manifest as focal ones that complicates the diagnostics of tumor’s localization.

 

IV.  Distance syndromes (dislocation and cutting – in)

The most common are temporal tentorial and axial occipital cutting – in.

   The reasons and mechanisms of cutting – in:

Cranial cavity is divided by cerebellar tentorium and falx cerebri into several parts (right and left hemisphere, above and under tentorial parts). In case of tumor in one of these parts the pressure in cranial cavity is increased and brain mass is dislocated in the direction where the pressure is lower. This leads to the dislocation of other parts of the brain and cutting – in of brain stem, corpus callosum.

     At temporo – tentorial cutting – in gyrus parahypocampalis is cutted – in Bisha hole. That clinically manifests as brain stem syndromes with downwards dynamics. At first the symptoms of brain peduncles appear, then pons and oblongate brain are involved, later decerebrative rigidity and disorders of consciousness, heart – vascular and breathing activity are joined.

At axial occipital cutting – in there is cutting – in of cerebellum into the foramen occipital magnum. That clinically manifests as occipital headache, neck – stiffness, enforced head position, later bulbar disturbances and cyanosis, breathing and heart – vascular disorders are joined. That often leads to death.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Tumors diagnostics

1.    Neurological examination

2.    Ophtalmological examination with eye ground, visual fields and visual acuity examination

3.    Otoneurological examination (hearing, taste, smell and vestibular sensation)

4.    Craniogram in two projections. If necessary it can be associated with additional pictures in special positions. On X–ray examination can be found the signs of intracranial hypertension, local hyperostosis, local bone defects, enlargement of physiological holes

5.    Echo-EG finds dislocation of middle structures or wideness of ventricles at hemisphere localization of the tumor

6.    CT and MRI give us information about the tumor’s localization and its sizes

7.    Lumbar puncture is used rarely as it can cause cutting – in syndrome

8.    EEG finds the focus of pathologic activity

9.    PET finds the changes of blood circulation and metabolism in the region of brain where the tumor is localized

 

Craniopharyngeoma                                                                                                   Glioma

 

 

 

Treatment

1.     Surgical

2.     Surgical with next radiation therapy.

3.     Medicines.

    In case of most tumors the treatment is surgical. Before the surgery it is necessary to take into consideration all the indications and contraindications. During the surgery we can do complete radical extraction of tumor or partial extraction of tumor. Sometimes we use palliative surgery in order to improve CSF drainage. In case of cutting of cerebellum in order to save patient’s life surgeon makes a hole with side ventricle’s horn puncture. This decreases intra cranial pressure and compensates patient’s state.

Recently bone – plastic skull trepanation is used. Almost all extra brain tumors are extracted without brain incision. Hypophysis tumors can be extracted through the nose, small neurinomas can be extracted through the labyryntis of temporal bone. Partially internal brain tumors are extracted.

    Palliative operations are used when the direct operation is impossible. To palliative operations belong decompressive skull trepanation, perforation of IV- th ventricle ground, drainage.

   Radiation therapy When it is established that the tumor is sensitive to radiation therapy, surgical treatment is associated with radiation therapy. It is made in two ways:

1.    Radio-therapeutic treatment is made by means of distant radiation therapy – γ – therapy, X – ray therapy and proton radiation (at the tumors in the base of the skull, brain stem, gliomas, medulloblastomas, and metastasis).

2.    Radio – surgical treatment is made by means of radio – pharmaceutical medication introduction. This method is used at endocrine tumors – hypophysis adenomas, craniopharyngiomas, and tumors in the base of the skull.

Medicines are used mostly symptomatically in order to

·         Decrease intra cranial pressure and brain edema (diuretics, steroids)

·         Anti-seizures medications

·         Nootrops (in postoperative period)

·         Analgesics

·         Chemotherapy

 

Spinal tumors 

They are less common then brain tumors. They take about 12% of all tumors of central nervous system. They are usually diagnosed at the age of 30 to 50 years.

 

Classification

According to the growth of the tumors they are classified into 2 groups:

I – extramedullar (out of spinal cord. To them belong neurinomas, meningiomas).

II – intramedullar (within the spinal cord. To them belong ependimomas, astrocytomas, oligodendrogliomas).

The correlation between extra – and intra – medullar tumors is 1:4. Extra- medullar tumors amount about 80% and intra- medullar tumors about 20% of all spinal tumors. The most common are tumors of thoracic part of spinal cord (66%), there are also cervical (18%) and lumbar (15%) tumors.

There are primary and secondary (metastasis) spinal tumors. Metastasis usually originates from breast, esophagus, thyroid gland and prostate cancer.

 

Clinical features

Extra – medullar tumors

There are 3 stages:

1.    Radix – associated – not well expressed

2.    Stage of Brown – Sequard syndrome.

3.    Stage of complete spinal cord diameter lesion.

 

Intra – medullar tumors  

There are 3 stages:

1.    Segmental (segmental – dissociative disorders)

2.    Stage of complete spinal cord diameter lesion.

3.    Radix – associated

At extra – medullar tumors superficial sensory disorders are slowly moving upwards, while at intra – medullar tumors these disorders are slowly moving downwards.

In order to localize the tumor we should pay attention at:

• The symptom of spinal process (pain in case of hammer percussion)

• Radix- associated pain

 

 

 

 

 

 

 

 

Diagnosis

1.    Lumbar puncture with CSF – dynamic tests and CSF – examination.

2.    X- ray of spinal cord. There are such symptoms:

·         Widened between vertebra spaces.

·         Osteoporosis of the base of vertebra’s arches radixes and widened central canal (the symptom of Elsberg – Dayke)

·         Destruction of vertebra’s bodies.

3.    CT and MRI

4.    Myelography with contrast usage (omnopack, dimmer, conrey) gives us possibility to refine the presence of tumor and its level.

 

Treatment.

It is only surgical. Extra – medullar tumors and some of intra – medullar tumors (ependimomas, astrocytomas) are extracted radically.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TUMORS

 

Neoplasia can affect the central nervous system (CNS) in three ways. Primary tumors may develop in the brain, spinal cord, or surrounding structures; metastatic tumors may spread to the CNS from pri­mary cancer elsewhere; or the brain and spinal cord may be damaged indirectly by the presence of a tu­mor elsewhere in the body. This latter condition is discussed under the remote effects of cancer.

Tumors arising within the CNS or from sur­rounding structures, including the meninges, blood vessels, embryonic cell rests, and bone, constitute ap­proximately 10 percent of all tumors and account for 1.7 percent of deaths from cancerous tumors.

Approximately 80 percent of all tumors are pri­mary tumors; 20 percent are metastatic. The gliomas are the most common tumor type with astrocytomas and glioblastoma multiforme exceeding the oligo­dendrogliomas and ependymomas in frequency. Nongliomatous tumors consist of meningiomas (10 percent), pituitary adenomas (10 percent), and acous­tic neuromas (5 percent), with a large group of mis­cellaneous tumors making up another 5 percent. There is some difference in the frequency and distrib­ution of tumors affecting the brain and spinal cord. The gliomas are the most common brain tumors, fol­lowed by meningiomas and pituitary adenomas. In contrast, neuromas are the most common tumors af­fecting the spinal cord, followed by meningiomas and gliomas.

In general, tumors that arise from embryonic tissue such as the primitive neuroectodermal tumors tend to occur early in life, but identification may be delayed until adolescence or adult life in some cases. Gliomas occur at all ages with increasing frequency up to 65 years of age. Metastatic tumors are usually seen among older patients with a steady increase in incidence after the age of 50.

 

ETIOLOGY

It is not possible to identify etiological factors in the great majority of brain tumors. Heredity plays a rela­tively minor role, although there are occasional re­ports of gliomas, meningiomas, and medulloblastomas in siblings. There is an increased incidence of brain tumors in neurofibromatosis and tuberous scle­rosis, but these conditions are relatively uncommon. Congenital abnormalities, particularly incorporation of embryonic tissue in the developing brain or cranial cavity, are believed to be responsible for cranio­pharyngiomas, chordomas, colloid cysts of the third ventricle, and some pineal tumors. Inclusion of der­mal elements may be followed by the development of dermoid and epidermoid tumors. The effects of trauma, infection, and carcinogenic viruses or agents are unclear, and there is little evidence that they play a major role in the development of brain tumors. Ra­diation treatment for scalp ringworm or malignant brain tumors in children is, however, associated with an increased rate of developing brain or spinal cord¹ tumors including meningiomas later in life.

Genetic factors appear to play a key role in the development of primary brain tumors. At the present time, it is believed that cell nuclei contain genes that regulate cell proliferation. Amplification of these genes can lead to excessive production of positive regulators or proto-oncogenes with conversion into oncogenes. The presence of oncogenes within a cell leads to nuclear proliferation, which, if unchecked, becomes a neoplastic process. There are, however, tu­mor suppressor genes that inhibit cellular division. The loss of tumor suppressor gene activity by muta­tion, deletion, or reduced expression is associated with an imbalance of the normal equilibrium that ex­ists between proto-oncogenes and tumor suppressor genes, thus disturbing the balance of cell integrity in favor of uninhibited growth and neoplastic prolifera­tion. Primary glioblastomas occurring in older pa­tients exhibit epidermal growth factor complication. Secondary glioblastomas developing from astrocy­tomas contain p53 mutations and both types show deletions of chromosome 10. Oligodendrogliomas have genetic abnormalities involving chromosomes lp and 19q. Meningiomas exhibit loss of chromo­some 22q and mutations of the neurofibromatosis type 2 gene with loss of chromosome 14q and lOq in malignant transformation. Primitive neuroectodermal tumors are associated with an abnormality i (17q). Oncogenesis can then be regarded as a blocking or short-circuiting of the differentiation process in adult glial progenitor cells or a dedifferentiation of previ­ously mature cells.

 

ASTROCYTOMAS

Definition Astrocytomas are neoplasms of astro­cytic origin and are the most common type of in­tracranial tumor in children and in patients who are between 20 and 40 years of age. Although slow grow­ing, they are not benign, because of their invasive quality and location within the confines of the bony calvarium. Anaplastic astrocytomas are found in in­creasing numbers in patients between 30 and 50 years of age and glioblastoma multiforme, the most malig­nant astrocytoma, predominates in patients 50 years and older but can be encountered at any age.

There have been several attempts to classify as­trocytomas based on the histological subtypes of the astrocyte that normally exists. However, some astro­cytomas cannot be categorized in this fashion because they contaiot only several histological subtypes of astrocytes but also other glial cells, particularly oligo­dendrocytes. It is probably better, therefore, to base a description of astrocytomas on their location within the CNS.

 

Pilocytic Astrocytoma

This tumor is the most benign form of astrocytoma. It occurs predominantly in children and young adults involving the cerebellar hemisphere, third ventricle, hypothalamic region, or optic pathway. Pi­locytic astrocytomas may be solid or cystic struc­tures with a mural nodule. The tumor is composed of loosely interwoven astrocytes with a fine fibril­lary background and very few mitoses. There may be microcysts and Rosenthal fibers. This tumor is well circumscribed and should be treated by total re­section whenever possible. This procedure is usually curative with a survival rate approximating 100 per­cent. When it is only possible to perform a partial or incomplete resection, patients can be followed with regular magnetic resonance imaging (MRI) scans to detect any further growth. If this occurs, a second partial resection should be followed by radiation therapy. Tumors of the optic nerve, optic chiasm, and hypothalamus should be treated with systemic chemotherapy.

 

Cerebral Astrocytoma

Pathology The tumor presents as a solid, slightly discolored yellow or gray mass with indistinct bound­aries, often blurring the discrete junction between cerebral white matter and gray matter. Microscopic examination shows the presence of fibrillary astro­cytes with a glassy eosinophilic cytoplasm and cell processes. Cells with unusually plump cytoplasm are occasionally encountered and are termed gemistocytes. Mitotic figures, vascular endothelial prolifera­tion, and necrosis are absent, but microcalcification occurs in 15 percent of cases. The spectrum of differ­entiation runs from well-differentiated tumors to more anaplastic tumors. Astrocytomas may undergo a malignant transformation to glioblastoma multiforme at any time.

 

Clinical Features The peak incidence of cere­bral astrocytomas occurs during the third and fourth decades of life, but astrocytomas can also develop in childhood. The frontal lobes are the most common site for astrocytomas, followed by the temporal lobes (Fig. 15-1), parietal lobes, basal ganglia, and occipital lobes, in decreasing order of frequency. Thalamic astrocytomas are occasionally seen in children.

The patient often complains of unilateral or fo­cal headache that becomes generalized with the de­velopment of papilledema indicating increased in­tracranial pressure (ICP) (Fig. 15-1). Some cases present with focal or generalized seizures. Other signs depend on the location of the tumor (Fig. 15-2 and Table 15-1).

 

Diagnostic Procedures An MRI scan with dem­onstration of the tumor in axial coronal and sagittal planes is the method of choice in cases of suspected astrocytoma. An MRI gives a more accurate delin­eation of tumor boundaries than CT, and regular MRI scans can be obtained in follow-up, without risk to the patient (Fig. 15-3). With CT scanning, astrocytomas usually present as areas of increased density and show enhancement after infusion of contrast material. Displacement of midline structures and effacement of the wall of the lateral ventricle on the side of the tumor are seen.

 

Treatment Astrocytoma should be surgically ex­cised whenever possible. Radiation therapy is advised when total excision cannot be accomplished, or when the tumor recurs.

The pathology of deep nonresectible tumors can be established using an MRI or CT-guided stereo­tactic biopsy. A low-grade astrocytoma can then be treated by partial resection, removing as much tumor as possible and any epileptogenic foci without caus­ing neurological deficits. However, patients who are neurologically intact, with well-controlled seizures, can be monitored without surgery, with the intention to intervene surgically if the tumor shows progression symptomatically or by serial imaging.

 

Prognosis Approximately 40 percent of adults with cerebral astrocytoma are alive 10 years after total excision of the tumor. Children have a survival rate of 85 percent 10 years after surgery.

 

Figure 15-2

A. Axial and B. Coronal views. MRI scan showing an astrocytoma mesial mid-temporal region right tem­poral lobe.

 

Table 15-1

Signs associated with localized lesions

Location of lesion	Associated signs
Prefrontal area	Loss of judgment, failure of memory, inappropriate behavior, apathy, poor attention span, easily distractible, release phenomena
Frontal eye fields	Failure to sustain gaze to opposite side, saccadic eye movements, impersistence, seizures with forced deviation of the eyes to the opposite side
Precentral gyrus	Partial motor seizures, jacksonian seizures, generalized seizures, hemiparesis
Superficial parietal lobe	Partial sensory seizures, loss of cortical sensation including two-point discrimination, tactile localization, stereognosis and graphism
Angular gyrus	Agraphia, acalculia, finger agnosia, allochiria (right-left confusion) (Gerstmann syndrome)
Broca’s area	Motor dysphasia
Superior temporal gyrus	Receptive dysphasia
Midbrain	Early hydrocephalus; loss of upward gaze; pupillary abnormalities; third nerve involvement—ptosis, external strabismus, diplopia; ipsilateral cerebellar signs; contralateral hemiparesis; parkinsonism; akinetic mutism
Cerebellar hemisphere	Ipsilateral cerebellar ataxia with hypotonia, dysmetria, intention tremor, nystagmus to side of lesion
Pons	Sixth nerve involvement—diplopia, internal strabismus; seventh nerve involvement— ipsilateral facial paralysis; contralateral hemiparesis; contralateral hemisensory loss; ipsilateral cerebellar ataxia; locked-in syndrome
Medial surface of frontal lobe	Apraxia of gait, urinary incontinence
Corpus callosum	Left-hand apraxia and agraphia, generalized tonic-clonic seizures
Thalamus	Contralateral “thalamic pain,” contralateral hemisensory loss
Temporal lobe	Complex partial seizures, contralateral homonymous upper quadrantanopsia
Paracentral lobule	Progressive spastic paraparesis, urgency of micturition, incontinence
Deep parietal lobe	Autotopagnosia, anosognosia, contralateral homonymous lower quadrantanopsia
Third ventricle	Paroxysmal headache, hydrocephalus
Fourth ventricle	Hydrocephalus, progressive cerebellar ataxia, progressive spastic hemiparesis or quadriparesis
Cerebellopontine angle	Hearing loss, tinnitus, cerebellar ataxis, facial pain, facial weakness, dysphagia, dysarthria
Olfactory groove	Ipsilateral anosmia, ipsilateral optic atrophy, contralateral papilledema (Foster-Kennedy syndrome)
Optic chiasm	Incongruous bitemporal field defects, bitemporal hemianopsia, optic atrophy
Orbital surface frontal lobe	Complex partial seizures, Paroxysmal atrial tachycardia
Optic nerve	Visual failure of one eye, optic atrophy
Uncus	Partial complex seizures with olfactory hallucinations (uncinate fits)
Basal ganglia	Contralateral choreoathetosis, contralateral dystonia
Internal capsule	Contralateral hemiplegia, hemisensory loss, and homonymous hemianopsia
Pineal gland	Loss of upward gaze (Parinaud syndrome), early hydrocephalus, lid retraction, pupillary abnormalities
Occipital lobe	Partial seizures with elementary visual phenomena, homonymous hemianopsia with macular sparing
Hypofhalamus/pituitary	Precocious puberty (children), impotence, amenorrhea, galactorrhea, hypothyroidism, hypopituitarism, diabetes insipidus, cachexia, diencephalic autonomic seizures

 

Anaplastic Astrocytoma

The growth and histologic appearance of the anaplas­tic astrocytoma is similar to that of a low-grade astro­cytoma. However, there is increased cellularity with pleomorphism, hyperchromatic nuclei, and occa­sional mitoses, but no evidence of necrosis in the tu­mor. In some cases, astrocytes present with abundant eosinophilic cytoplasm and small nuclei. The pres­ence of more than 20 percent of these cells, termed gemistocytes, is indicative of a poorer prognosis. Another feature of the anaplastic astrocytoma is mi­crovascular proliferation of vascular endothelium in blood vessel walls, often obliterating the lumen.

 

Cerebellar Astrocytoma

Cerebellar astrocytomas are the most common in-fratentorial tumors in childhood and carry a more fa­vorable prognosis than most brain tumors because these neoplasms are usually histologically benign and amenable to extensive resection. The classical juve­nile pilocytic astrocytoma tends to arise within the cerebellar hemisphere, presenting as a cyst with a mural nodule or as a solid tumor. The diffuse fibril­lary astrocytoma usually occurs in the vermis.

Pathology The pilocytic astrocytoma is composed of loosely interwoven astrocytes with a fine fibrillary background and has few mitoses. There may be mi-crocytes and Rosenthal fibers. The diffuse fibrillary astrocytoma resembles the low-grade astrocytoma of the cerebral hemisphere.

Clinical Features The hemispheric pilocytic as­trocytoma presents with a slowly progressive unilat­eral cerebellar ataxia involving limbs and trunk, fol­lowed by increased ICP caused by displacement and obstruction of the fourth ventricle. The diffuse fibril lary astrocytoma situated in the midline results in a truncal ataxia followed by increased ICP.

Diagnostic Procedures The MRI and CT scans will reveal a cystic cerebellar mass (Fig. 15-4) in one cerebellar hemisphere or a solid midline tumor. The much greater detail of the MRI scan is an advantage in delineating the boundaries of the cystic mass and the mural nodule, which may appear in the CT scan only after contrast enhancement. The use of gadolin­ium enhancement with the MRI scan provides even better definition of tumors and their anatomic rela­tionship. The hemispheric pilocytic tumor should be excised whenever possible, because virtually 100 per­cent of patients are alive 10 years after total re­moval. The midline astrocytoma should also be ex­cised whenever possible, but tumors showing anaplasia tend to disseminate in the neuraxis, and fur­ther treatment ranging from local radiation therapy to craniospinal radiation therapy plus chemotherapy has been recommended.

 

Glioblastoma Multiforme

This tumor is the highest grade malignant tumor of the astrocytic line, accounting for 20 percent of in­tracranial tumors and 50 percent of those of astrocytic origin. Although it is possible that some glioblas­tomas arise from oligodendrogliomas, the majority develop by transformation of astrocytes through pro­gressively higher grades of malignancy from low-grade astrocytoma to glioblastoma multiforme. How­ever, direct malignant transformation from astrocytes is possible.

Pathology The brain is swollen and the neoplasm appears as a pinkish gray, well-demarcated mass with scattered areas of hemorrhage within its substance. Ar­eas of cystic degeneration and a central area of creamy necrosis may be present. Microscopically, the tumor is characterized by hypercellularity and pleomorphism, and the cells show hyperchromatic nuclei and occa­sional mitoses. Multinucleated giant cells are a feature of the more anaplastic tumors. There are few normal astrocytes. The numerous blood vessels show endothe­lial proliferation. Despite the presence of a well-de­marcated border, the tumor infiltrates the surrounding brain and is associated with considerable edema.

Clinical Features Glioblastoma multiforme oc­curs most commonly in the fifth and sixth decades and is somewhat more common in men. The inci­dence is increasing in the elderly. The tumor is found most frequently in one frontal lobe and may spread through the corpus callosum to the opposite side. Glioblastomas also occur in the temporal, pari­etal, and occipital lobes and in the basal ganglion and thalamus. The tumor is the most common glioma of the pons.

Signs and symptoms usually progress rapidly. The patient may present with unilateral headache over the site of the tumor, but this is rapidly followed by generalized headache, indicating an increase in ICP due to tumor mass, edema, or hydrocephalus (Fig. 15-5). Onset with focal or generalized seizures or the development of seizures early in the course of the illness is not unusual. Additional signs and symp­toms depend on the location of the neoplasm (see Table 15-1).

 

 

Diagnostic Procedures

1.    The MRI scan is the most sensitive imag­ing technique in the detection of glioblastoma multi­forme and the delineation of the boundaries of the tu­mor (Fig. 15-6). The volume of the tumor is usually greater than that identified by the MRI scan.

2.    The CT scan shows a mass with irregular margins containing areas of high and low density. There are usually significant mass effects and marked surrounding edema. There is usually a homogeneous irregular or ring pattern of enhancement following in­fusion of contrast material. Calcification occurs in about 15 percent of cases, and there may be areas of cystic, necrotic, or hemorrhagic change within the tu­mor substance.

3.    MR spectroscopy  produces  a distinctive pattern  differentiating  tumor from infarction,  de-myelination, or radiatioecrosis.

 

Treatment

Preoperative Treatment

1.    Dexamethasone 4 mg q6h to reduce cere­bral edema.

2.    Hyperosmolar  agents   such   as   mannitol may be required to reduce ICP if the patient is show­ing signs of rapid progression.

3.    Seizures should be controlled with a load­ing dose of 1 g phenytoin by intravenous piggyback (IVPB) at 50 mg/min followed by 500 mg ql2h IVPB until free Dilantin level is 2 μg/mL. At that juncture, the dose can be adjusted to maintain a thera­peutic level at 2 μg/mL.

Biopsy    Indications for biopsy of a suspected malignant glioma include:

1.    Diagnosis in doubt despite adequate MRI studies.

2.    Medical and anesthetic risks too great to permit craniotomy.

3.    Lesion  located  in  the  corpus  callosum, thalamus, hypothalamus, brainstem, or cerebellar pe­duncles.

4.    To distinguish between radiatioecrosis and tumor recurrence.

5. To verify tumor progression in a known low-grade glioma when there are signs of change in serial imaging studies.

Closed biopsy is intended to obtain a small sample with minimal risk to the patient, the greatest risk being hemorrhage.

Techniques for closed biopsy include CT guid­ance, ultrasound localization, and the use of CT- or MR-coupled stereotactic frames.

 

Angiosarcoma

Primary or metastatic angiosarcoma is a rare malig­nant tumor that usually arises from endothelial cells of arteries or lymphatics in the skin or superficial tis­sues. There are few reports of primary or metastatic brain involvement. The tumor presents as a unilateral mass, producing a contralateral hemiparesis with hyperreflexia and an extensor plantar response. Clini­cally, the tumor resembles a glioblastoma.

The CT scan demonstrates an enhancing mass resembling meningioma; MRI scanning will show low-intensity extra-axial tumor on T2-weighted imag­ing, with marked surrounding edema.

Treatment consists of excision followed by ra­diotherapy. Prognosis is poor.

Radical Tumor Resection

The role of surgery in the treatment of glioblastoma multiforme is controversial, particularly in the extent of tumor removal. It is clear that cytoreductive proce­dures are indicated to alleviate increased ICP or to re­duce mass effect, producing focal neurological deficits. However, attempts at total tumor removal are hampered by the definition of boundaries, despite ad­vances in imaging techniques. Nevertheless refine­ment in surgical technique suggests that gross total re­section can be performed in many cases one considered inoperable with acceptable neurological deficits.¹⁸ Refinement in procedures such as neurophysiological mapping of the adjacent brain reduces postoperative deficits while electrocorticography will define seizure foci that should be resected. Enhanced optic imaging using a contrast enhancing dye provides a means of differentiating betweeormal brain and tumor tissue at the resection margins. A gadoliniumenhanced MRI scan should be obtained within 3 days postoperatively after attempting complete extirpation of a glioblastoma multiforme or anaplastic astrocy­toma. This study permits the detection of any residual tumor and is valuable in planning additional therapy. All patients will require postoperative radiation ther­apy and chemotherapy after tumor resection.

Postoperative Management

Following surgery, all patients with an uncomplicated course should be transferred from the postoperative recovery area to an intensive care unit for 48 h. Dexamethasone should be maintained at 4 mg q4h then tapered slowly, depending on the clinical findings and residual mass effect on the postoperative scan. Antiepileptic drugs should be maintained at a high normal therapeutic level. Antibiotics should be given for a 48-h period to minimize infection. Although craniotomy is not usually a painful procedure, pa­tients may have pain for other reasons and may re­quire treatment with intramuscular codeine 60 mg q4h p.r.n. or morphine sulphate 10 mg q4-q6h p.r.n. Insomnia can be a problem and will respond to a short-acting benzodiazepine preparation.

Reoperative Procedures

Although most patients with cerebral gliomas have a poor prognosis following all modalities of treatment, including surgical excision, radiation therapy, and chemotherapy, there does appear to be a limited place for further surgical treatment in some cases (Fig. 15-7). The single factor when considering retreatment is im­provement of quality of life, and careful selection of cases may attain this goal. Currently, retreatment may be of benefit when neurological deterioration is re­lated to pressure effects. This situation may be im­proved by debulking of recurrent tumor, cyst evacua­tion, or ventricular atrial shunting. Chemotherapy is of questionable value, but brachytherapy may extend survival.

Chemotherapy

Chemotherapy provides limited improvement in sur­vival following surgical excision of a glioblastoma multiforme and radiation therapy.²³ The addition of chemotherapy to surgical excision and radiation im­proves the median survival from 9.4 to 12 months.²⁴ This is, in part, due to the integrity of the blood-brain barrier, which limits passage of water-soluble com­pounds or compounds bound to plasma proteins into the brain.

The limited effect of intermittent systemic chemotherapy has led to the development of a number of techniques to increase drug concentration within the brain. These techniques include continuous infusion chemotherapy, high-dose chemotherapy with stem cell rescue, autogenous marrow transplantation, intra­ventricular or intrathecal therapy intra-arterial chemotherapy, intra-arterial chemotherapy with blood-brain barrier disruption, interstitial chemotherapy and techniques to modify the blood-brain barrier or blood tumor barrier to improve delivery of agents to the brain. Despite these advances, improvement in chemotherapy is likely to be limited by the fact that malignant cells are dispersed far beyond the bound­aries of a glioblastoma multiforme, having tracked along white matter tracts to other areas of the brain, in­cluding the noninvolved hemisphere. The challenge would appear to be the development of chemothera-peutic methods to treat the entire brain and meninges without diffuse neurotoxicity.

Radiotherapy

Treatment of glioblastoma multiforme and anaplastic astrocytoma with postoperative radiation therapy pro­duces a modest improvement in survival, compared to surgery alone. Median survival is 14 to 22 weeks postoperatively for those treated with excision of the tumor and 36 to 47 weeks for patients receiving surgery followed by external beam conventional irra­diation. However, the median survival time for pa­tients with glioblastoma multiforme is only 10 months, whereas the median survival time for those with anaplastic astrocytoma is 36 months. Although studies have clearly demonstrated the benefit of radia­tion therapy, the results are far from satisfactory. Research into several innovative techniques indicates that the prognosis can be expected to improve. Pro­posed therapeutic approaches include combining radiation therapy and chemotherapy, which may in­crease survival by 10 percent at 1 year. However, this is only a modest improvement. Consequently, several other strategies are under investigation, in­cluding hyperfractionation, brachytherapy, stereotac­tic radiosurgery using gamma knife units of multiple cobalt beams, and three-dimensional conforma­tional photon radiation therapy. Additional tech­niques, based on the assumption that tumor cells in glioblastoma multiforme are hypoxic include the use of hypoxic cell sensitizers such as nitroimidazole compounds. However, evidence suggests that whole brain irradiation can produce diffuse neuronal dam­age with impairment of cognitive functioning, includ­ing memory. This crucial adverse effect imposes un­questionable caution in the development of newer techniques.

 

Oligodendrogliomas

Definition Oligodendrogliomas constitute approx­imately 5 percent of all gliomas. These tumors usu­ally occur in adults and are located predominantly in the cerebral hemispheres. More than half the patients with oligodendroglioma fail to live for more than 5 years after surgery.

Pathology The neoplasm presents as a gray-pink to red cystic area in the brain. Microscopic examina­tion reveals a honeycomb appearance at low power caused by the presence of fibrovascular stroma. At higher power, the cells have a uniform appearance with a central nucleus surrounded by clear cytoplasm. The presence of some mitoses is not unusual. Ap­proximately 70 percent of these tumors show some evidence of calcification. The neoplasm expands to­ward the cortex and may spread through it to eventu­ally attach to the dura.

Clinical Features Oligodendrogliomas are more common during the third and fourth decades and usu­ally occur in the frontal lobes. Chronic headaches and partial or generalized seizures often constitute the only complaints for several years. Additional signs and symptoms depend on the location of the tumor (Table 15-1).

Diagnostic Procedures

1.    The MRI scan will clearly define the oligo­dendroglioma and its boundaries. The nonenhanced CT scan shows clusters of dense calcification lying within an area of decreased density. There are some surrounding  edema  and  ventricular  displacement. There may be little change on contrast enhancement or slight enhancement of the surrounding area.

2.    Tissue diagnosis  can be  established by stereotactic tumor biopsy.

Treatment Because the boundaries of the tumor can often be defined by MRI scanning in three planes, resection may be possible by stereotactic ra­diosurgery.

Prognosis With the standard procedure, a partial resection followed by irradiation therapy, the mean postoperative survival is between 5 and 7 years. Pa­tients undergoing complete resection have survived beyond 10 years.

 

Ependymoma

Definition Ependymomas are neoplasms derived from the ependymal cell lining of the ventricular sys­tem and the central canal of the spinal cord. These tu­mors are common in childhood and have a 50 per­cent, 5-year survival rate.

Pathology Ependymomas are usually reddish, lobulated, and well-circumscribed tumors said to resemble a cauliflower in shape. There are two histological types. Epithelial ependymomas contain ependymal cells that form true rosettes. This histo­logical type is most common in tumors involving the cerebral hemispheres and posterior fossa. Papillary ependymomas consist of ependymal cells that resemble simple epithelium or glial fibrillary stroma arranged in papillary configuration. This type is most common in the spinal cord and filum terminale. There may be cystic areas and calcifica­tion within the tumor. The tumor is usually benign, but 10 to 20 percent are malignant, with a tendency toward extension and spread through the subarach­noid space.

Clinical Features Ependymomas are the third most frequent posterior fossa neoplasm in childhood. Supratentorial ependymomas are usually found in the parietal occipital area and are more aggressive tumors often growing to a considerable size before detection. Ependymomas of the third ventricle are rare tumors with presenting symptoms of headache, ataxia, ver­tigo, hydrocephalus, and Parinaud syndrome.

Posterior fossa ependymomas arise in three lo­cations: midline tumors arising from the caudal half of the fourth ventricle and extending through the foramen of Magendie to the upper cervical region; laterally located tumors arising in the lateral recess and extending inferiorly and laterally; and roof tu­mors arising from the inferior medullary velum. Spinal cord ependymomas commonly involve the lumbosacral area and filum terminale and are often relatively benign.

The signs and symptoms of this neoplasm de­pend on the location. Ependymomas involving the fourth ventricle are likely to be detected in an early stage because of the signs and symptoms of increased ICP, including headache, nausea, vomiting, and pap­illedema, followed by lower cranial nerve involve­ment and cerebellar ataxia.

Diagnostic Procedures The MRI and CT scans show displacement, distortion, or obliteration of the fourth ventricle by a mass that may show cystic areas and foci of calcification (Fig. 15-8). However, the boundaries of the mass are shown in much greater de­tail by the MRI scan. Supratentorial ependymomas have features similar to those of the glioblastoma multiforme.

Treatment The treatment of choice is resection with removal of as much of the tumor as possible, followed by radiation therapy. Third ventricular tu­mors are treated by microsurgical resection followed by radiation therapy. Hydrocephalus should be treated by a ventricular shunting procedure.

Prognosis The mean survival rate is 62 percent at 5 years postoperatively for ependymomas of the fourth ventricle. Patients with tumors arising in the lateral re­cess have a poorer survival rate at 5 years than those with midline tumors. Supratentorial ependymomas carry a poor prognosis.

 

CHOROID PLEXUS PAPILLOMA

The choroid plexus papilloma is a low-grade neo­plasm of the choroid plexus that bears a close struc­tural resemblance to normal choroid plexus. This is a rare neoplasm and is usually found in children, where it is often associated with overproduction of cere­brospinal fluid (CSF) and hydrocephalus. The hydro­cephalus and the tumor can be demonstrated by MRI or CT scan (Fig. 15-9).

The papilloma can usually be completely re­moved with subsequent resolution of the hydro­cephalus.

CHOROID PLEXUS CARCINOMA

Choroid plexus carcinoma is the malignant counter­part of the choroid plexus papilloma. This tumor, which is usually found in children, grows rapidly, producing macrocrania, a bulging fontanelle, and hy­drocephalus. Treatment consists of partial tumor re­section and placement of a ventricular peritoneal shunt. This should be followed by chemotherapy and delayed radiation therapy.

 

INTRAVENTRICULAR MASS LESIONS

Many masses impinge on or appear to arise within the ventricular system. When extraventricular, intra­ventricular masses are excluded, those arising entirely

within the ventricular system constitute a variety of conditions, of which the colloid cyst of the third ven­tricle is the most common often presenting with episodic headache and subtle signs of increased in­tracranial pressure³⁸ (Table 15-2). Correlation of pa­tient age and classical features with a CT scan and MRI appearance will frequently narrow the differen­tial diagnosis. Meningioma is the most common cause of a mass in the area of the trigone after the first decade of life, with the highest incidence in the fifth decade. However, many tumors can present as intraventricular mass lesions.

 

Table 15-2

Intraventricular mass lesions

1.  Cysts

a.  Colloid cyst

b.  Intraventricular CSF cyst

c.  Epidermoid cyst

d.  Dermoid cyst

2.  Tumors of the choroid plexus

a.  Choroid plexus papilloma

b.  Choroid plexus carcinoma

3.  Meningioma

4.  Lipoma choroid plexus

5.  Glial tumors

a.  Ependymoma

b.  Astrocytoma

6.  Other tumors

a.  Neurocytoma

b.  Neuroblastoma

c.  Primitive neuroectodermal tumor

d.  Lymphoma

e.  Hemangioblastoma

f.  Intraventricular craniopharyngioma

7.  Metastatic tumor

a.  Lung

b.  Breast

c.  Melanoma

d.  Gastrointestinal

e.  Genitourinary

8.  Malformations

a.  Arteriovenous malformations

b.  Cavernous malformation

c.  Tuberous sclerosis

9.  Nonneoplastic cysticercosis

 

PRIMITIVE NEUROECTODERMAL TUMORS

Meduiiobiastoma

Definition Primitive neuroectodermal tumors (PNETs) include the meduiiobiastoma, retinoblas­toma, pinealoblastoma, and cerebral neuroblastoma,⁴⁰ all of which have common microscopic features and are probably derived from neoplastic transformation occurring within a primitive undifferentiated neuroec­todermal cell. The PNETs are the most common malignant primary posterior fossa tumor of child­hood, constituting 13 to 20 percent of pediatric brain tumors and 33 percent of posterior fossa tumors in childhood. About 50 percent of PNETs occur in the first decade of life. These tumors are highly malig­nant, usually develop in the vermis of the cerebellum, and exert pressure on or occlude the fourth ventricle.

Pathology The PNETs present as well-circum­scribed soft reddish-gray tumors. Microscopic exami­nation reveals closely packed cells with deeply stained nuclei and scant cytoplasm. The cells occur in random formation but occasionally form pseudorosettes or ap­pear in rows. The tumor is highly vascular and there is a higher incidence of systemic metastasis with PNETs than other gliomas. Seeding into the subarachnoid space is a frequent complication.

Clinical Features The PNETs are more common in males with a male: female ratio of 2:1 to 3:1. The tumors usually develop in the cerebellar vermis but have been described in other sites, including the retina, pineal gland, cerebral hemispheres, brainstem, and cerebellar hemispheres. The younger the patient, the more aggressive the tumor and the higher the inci­dence of metastasis at presentation.⁴³ The presence of a PNET close to the fourth ventricle results in the early development of hydrocephalus with signs of in­creased ICP (headache, vomiting, ataxia), accompa­nied by cerebellar dysfunction, usually presenting as truncal ataxia (Fig. 15-10).

 

 

Diagnostic Procedures

1.  The CT scan shows a well-defined homoge­neous mass with moderate uniform contrast enhance­ment. Ten percent show cystic change or calcifica­tion.

2.  The MRI scan is clearly superior to CT scanning in demonstrating the posterior fossa mass with distortion and compression of the fourth ventri­cle (Fig. 15-11). The tumor is usually hypointense on Tl-weighted   images   and   hyperintense   on   T2-weighted images, with uniform enhancement with gadolinium.

3.  A lumbar puncture should be performed with examination of the CSF for cells indicating dis­semination of the PNET throughout the subarachnoid space.

4.  A contrast-enhanced craniospinal MRI scan, which includes the whole of the neuraxis, is neces­sary to detect metastatic spread through the subarach­noid space.

Treatment The tumor should be resected com­pletely if possible. This should be followed by cra­niospinal radiotherapy and chemotherapy.

Prognosis The postoperative survival is 6 to 12 months for patients treated by surgery alone. Com­bined surgery and radiation therapy has a 10-year sur­vival rate of 40 to 50 percent. The addition of chemotherapy increases the 5-year rate of survival. Reoperation of recurrent tumors is a useful proce­dure. Deficiencies of growth hormone and thy­rotropin induced by chemotherapy should be cor­rected by replacement therapy.

 

Pinealoma

Definition Pinealomas are a heterogeneous group of tumors found in the area of the pineal gland. True neoplasms of the pineal gland constitute less than 1 percent of all intracranial tumors.

Pathology A large number of tumors arise in the pineal area, including benign cysts (dermoid, glial, epidermoid, arachnoid, colloid), hamartomas (lipoma, arteriovenous malformation, cavernous angioma), ter­atomas, pinealocytoma, astrocytoma, meningioma, oligodendroglioma, granuloma, germinoma, embry­onic carcinoma, yolk sac tumor, and pinealoblastoma. Pinealocytomas are soft masses that replace the pineal gland and are often the site of necrosis, hemor­rhage, or cyst formation. Pinealocytomas consist of cells resembling normal pineal tissue. Pinealoblastomas have an appearance similar to primitive neu­roectodermal tumors (medulloblastomas). Teratomas contain mixtures of hair, bone, cartilage, and muscle and are the most common brain tumor presenting or producing symptoms at birth occurring in supratento-rial locations frequently, but not exclusively, in the pineal region. Germinomas have the microscopic appearance of germinomas of the testes.

 

 

Clinical Features Pineal tumors produce symp­toms due to pressure on the midbrain at the level of the quadrigeminal plate. Symptoms of increased ICP, including occipital headache, nausea and vomiting, appear at an early stage, because of distortion of the cerebral aqueduct and resultant hydrocephalus. Ex amination frequently shows the loss of vertical upward gaze (Parinaud syndrome) due to pressure on the superior colliculi. Other signs include lid retraction and pupillary abnormalities such as poor reaction to light or Argyll Robertson pupils when there is pretectal involvement. More severe com­pression of the midbrain causes ataxia and nystag­mus. There may be bilateral signs of corticospinal tract involvement caused by forward displacement of the midbrain with compression of the cerebral peduncles.

Diagnostic Procedures

1.    A chest film should be obtained to exclude metastasis from germinoma, pinealoblastoma, chorio­carcinoma, or malignant teratoma.

2.    Lumbar puncture with examination of the CSF for cytology, chemistry, and tumor markers is in­dicated in all malignant tumors of the pineal region.

3.    Some tumor markers (human chorionic go­nadotropin, α-fetoprotein) may be present.

4.    Yolk sac tumors are associated with ele­vated levels of α-fetoprotein in serum and CSF.

5.    The MRI scan shows the presence of a pineal tumor in multiple planes and demonstrates the precise anatomical relationships of the tumor, includ­ing vascular structures such as the internal cerebral veins, vein of Galen, and straight sinus. The presence of fat within the tumor, shown by MRI or CT scan, suggests the presence of a teratoma or epidermoid or dermoid tumor and excludes germinoma.

6.    Arteriography. With the demonstration of vascular structures by MRI scanning, arteriography is necessary only if it is believed that the mass is a vas­cular tumor.

Treatment Mature teratomas, pinealocytomas, der­moid or epidermoid cysts, low-grade astrocytomas, oligodendrogliomas, meningiomas, and well-differ entiated ependymomas should be resected. Partially resected benign tumors require long-term observa­tion without further treatment, unless recurrence develops.

Isolated pineal germinoma with suprasellar in­volvement requires excision followed by local radiation therapy. More extensive germinomas and pinealblastomas will require excision followed by whole brain ra­diation and craniospinal radiation therapy in cases with dissemination in the spinal fluid. Teratomas, embryonic carcinoma, yoke sac tumors, and choriocarcinomas are more malignant and should be treated with subtotal re­section, radiation therapy, and chemotherapy.

Prognosis Shunting and radiation therapy are as­sociated with 60 to 70 percent 5-year survival for ger­minomas. The more malignant tumors, such as yolk sac tumor, have a very poor prognosis.

 

Brainstem Glioma

Brainstem gliomas constitute approximately 20 per­cent of all posterior fossa tumors in children.

Pathology The majority of brainstem gliomas are diffuse infiltrative lesions arising in the pons. These tumors are low-grade gliomas containing foci of more anaplastic gliomas.

A second type of low-grade, often indolent, glioma occurs in the upper midbrain and grows very slowly.

About 10 percent of brainstem gliomas arise in the cervical medullary region and extend dorsally into the cerebellum.

Clinical Features The pontine gliomas present with sixth and seventh cranial nerve palsies followed by involvement of lower cranial nerves. Hydro­cephalus is a later development. Midbrain gliomas in­volve the tectum, producing hydrocephalus as the first symptom. Cervical medullary tumors are associ­ated with ataxia and later development of lower cra­nial nerve symptoms.

Diagnosis is established by MRI.

Treatment Cervical medullary tumors can be ex­cised in some cases. Midbrain gliomas require ven­tricular peritoneal shunting procedures. Diffuse pon­tine gliomas should be treated by hyperfractionated radiotherapy, but the overall survival rate is less than 10 percent in pediatric patients with infiltrating brain­stem gliomas at 3 years posttreatment.

 

Diencephalic Gliomas

Gliomas affecting the optic nerve, optic chiasm, hy­pothalamus, or thalamus constitute 20 percent of pe­diatric low-grade gliomas. A large number of children with neurofibromatosis have visual pathway gliomas demonstrated by MRI. These tumors are asympto­matic or have apparently static visual impairment. Low- or high-grade diencephalic gliomas occurring in adults are rare.

Pathology Most diencephalic gliomas in children consist of fibrillary or pilocytic astrocytomas. Despite their low-grade state, the proximity of the ventric­ular system permits dissemination throughout the subarachnoid space in some cases. Adult tu­mors, which include anaplastic astrocytoma and glioblastoma multiforme, can develop in the optic pathways and infiltrate the hypothalamus or adjacent structures.

Diagnostic Procedures

1.    The MRI scan readily demonstrates di­encephalic tumors. Pilocytic astrocytomas may be quite large and show marked  enhancement  with gadolinium.   Cystic   components   and   calcification may be present in the tumor. Thalamic tumors show clear separation from the optic chiasm. Bilateral optic nerve  involvement  usually  indicates   a  chiasmatic tumor.

2.    Hypothalamic tumors are associated with hypertension, euphoria, hyperkinesis, hypoglycemia, hyperhidrosis, and failure to thrive, with elevation of growth hormone levels and corticotropin.

3.    Optic chiasmatic involvement produces in­congruous  field defects.  The  classical bitemporal hemianopia is a late phenomenon.

Treatment Children with low-grade gliomas with bulky necrotic or cystic components can be managed with partial resection and observation. Patients with rapidly progressive disease should be treated with ra­diation therapy. However, the effect of radiation on the surrounding brain limits radiation therapy in young children, who may have better results with chemotherapy.

 

PITUITARY ADENOMA

Definition Pituitary adenomas are tumors derived from cells of the anterior portion of the pituitary gland and represent approximately 10 to 15 percent of all intracranial tumors.

Pathology Pituitary tumors can be classified as follows:

Stage 1: Microadenoma—a tumor less than 10 mm in diameter confined to the pituitary fossa

Stage 2: Macroadenoma—a tumor greater than 10 mm in diameter confined to the pituitary fossa

Stage 3: Macroadenoma with extracellular ex­tension outside the pituitary fossa by invasion of the floor of the sella or by suprasellar extension.

Clinical Features

Symptoms may be produced by:

1. The mass of the tumor.

a. Suprasellar extension often causes compression of the optic chiasm and visual field defects.

b. Midline extension may produce hypothalamic dysfunction with hyperphagia, weight gain, ab­normal temperature regulation, and somnolence. There may be damage to gonadotrophin-releas-ing cells in the hypothalamus or interference with the delivery of gonadotrophic releasing hormones through the hypophyseal portal sys­tem.

c. Tumor growth into the third ventricle results in hydrocephalus.

d. Caudal extension can produce pressure on the brainstem.

e. Lateral extension can involve the cavernous si­nus and the third, fourth, fifth, and sixth cranial nerves.

f. Temporal lobe involvement produces complex-partial seizures.

g. Acute  hemorrhage  into  a  pituitary  adenoma causes pituitary apoplexy with acute swelling of the tumor, producing severe headache, vomit­ing, impaired consciousness, ophthalmoplegia, pupillary   abnormalities,   visual   disturbance, meningismus,  and occasionally,  subarachnoid hemorrhage. Symptoms vary. Transient hypopi­tuitarism is common and pituitary function may improve.⁵⁵ h. Intracranial and spinal dissemination is a rare

complication of a pituitary tumor. 2. Oversecretion of pituitary hormones. Excess hor­mone production occurs in 75 percent of pituitary adenomas.

a. Prolactin-secreting tumors are the most common hormone-producing adenomas. Symptoms consist of galactorrhea, amenorrhea, anovula­tion,  and infertility in women,  and hypogo­nadism, depressed libido, impotence or infertil­ity in men.

b. Growth hormone-secreting tumors produce gi­gantism in the adolescent and acromegaly in the adult. Acromegaly is characterized by hypertro­phy of bone and connective tissue, producing progressive enlargement of the hands, feet, tho­rax, skull, and jaw, leading to “coarsening” of the features.

c. Corticotrophin overproduction results in Cushing syndrome. This condition is characterized by hypertension, facial and truncal obesity, osteo­porosis,   abnormal   carbohydrate   metabolism, muscle weakness, menstrual abnormalities, and hirsutism.

d. Thyrotropin-secreting  hormones  present  with hyperthyroidism.

e. Leutinizing   hormone   and   follicle-stimulating hormone adenomas do not produce symptoms, but many of the clinically nonfunctioning tu­mors are gonadotrophin producing.

Patients who are found to have a pituitary ade­noma should be investigated for the multiendocrine adenoma (MEA1) syndrome, a genetically deter­mined syndrome of pituitary adenoma, pancreatic tu­mor, and hyperparathyroidism.

Diagnostic Procedures

1. The MRI or CT scan in the axial, coronal, and sagittal planes will display pituitary adenomas and the relationship of the tumor to the surround­ing structures—cavernous sinus, optic chiasm, carotid arteries, hypothalamus, and third ventricle (Fig. 15-12). The majority of microadenomas are re­vealed by MRI with contrast enhancement, which shows a focal signal abnormality in the pituitary. De­tection may be increased using three-dimensional gradient echo acquisition sequences. Asymptomatic nonsecreting tumors should have repeated MRI stud­ies at 6 months, and 1, 3, and 5 years.

2.  Because pituitary adenoma is the most com­mon tumor in the sella, all patients should be evalu­ated endocrinologically for hypersecretion or hyper-function. This will entail determination of prolactin, growth hormone, corticotropin, thyrotropin, luteiniz­ing hormone, and follicle-stimulating hormone.

3.  Patients with tumors greater than 1 cm in di­ameter require visual field determination.

Treatment Prolactin-secreting tumors of all sizes can be treated with bromocriptine, the dopamine ago­nist, 1.25 mg q.h.s., increasing to 2.5 mg q8h. Macroadenomas with visual field defects often shrink with   improvement   in   visual   field   abnormalities.

 

 

Bromocriptine therapy may be continued indefinitely. Dopamine receptor agonist-resistant tumors are occa­sionally encountered.

Other hyperfunctioning adenomas should be treated surgically. Small and medium-sized tumors can be removed by the transphenoidal route. Larger tumors may require a transfrontal approach.

Some clinically nonfunctioning tumors respond to bromocriptine with shrinkage of the mass. If visual field defects persist, the tumor should be removed surgically. Those without visual field defects usually follow a benign course and can be followed with re­peated MRI studies at 1, 2, and 5 years.

Postoperative complications include CSF rhi-norrhea, hypopituitarism, diabetes insipidus, perma­nent visual field defects, and cranial nerve palsies.

Hypopituitarism can be treated with appropriate replacement therapy.

Clinical Features Meningiomas constitute 10 percent of intracranial tumors. They are most com­mon in the latter years of life and are more frequent in women, particularly in those who have breast can­cer. Sex hormones stimulate the growth of menin­giomas, which may progress more rapidly in the sec­ond half of pregnancy. Meningiomas can be found wherever arachnoid cap cells or connective tissue portions of arachnoid are located. These areas include the convexity of the cerebral hemispheres, the basal skull areas, sphenoid ridge, olfactory groove, sella and parasellar areas, tentorium cerebelli, posterior fossa, choroid plexus, and, rarely, the spinal canal. Because meningiomas are slow-growing tumors pro­ducing compression of the brain, abnormal signs and symptoms may evolve over a period of many years. Neurological abnormalities depend on the location of the tumor (see Table 15-1).

 

MENINGIOMA

Definition Meningiomas are benign, slow-growing tumors that are believed to be derived from the cells and vascular elements of the meninges. Evidence in­dicates that development of a meningioma is related to loss of function of a tumor suppressor gene located on chromosome 22.

Pathology The majority of meningiomas are of four basic types. Meningothelial meningiomas are de­rived from arachnoid cap cells and are composed of sheets of cells with large vesicular nuclei. Fibrous meningiomas are derived from connective tissue ele­ments of the arachnoid and consist of strands of inter­lacing spindle cells with long fibrils. Psammomatous meningiomas consist of whorls of spindle cells with a central area that degenerates, calcifies, and forms a concretion or psammoma body. Angiomatous menin­giomas contaiumerous vascular spaces lined by en­dothelial cells. Many meningiomas undergo secondary xanthomatous or myxomatous change, whereas others calcify or contain melanin, bone, or cartilage. Most meningiomas grow as well-capsulated tumors, but others develop in relatively thin sheets along the dura. The latter type of tumor has been termed “menin­gioma en plaque.”

Diagnostic Procedures

1.  Skull films. Changes in the skull are not in­frequent, due to the proximity of the tumor to the in­ner table of the skull. Radiographic abnormalities consist of thinning or thickening of bone and widen­ing of vascular bone shadows. The tumor may con­tain calcification in 30 to 60 percent of cases.

2.  On MRI scanning, the tumor usually ap­pears as a dense, sharply demarcated mass located near the bone or in close relationship to the falx or tentorium cerebelli. The majority exhibit a heteroge­neous intensity pattern that may be related to the presence of calcification, areas of necrosis or hemor­rhage, cyst, or tumor vascularity⁶⁶ (Fig. 15-13). There is dense enhancement following infusion of contrast material (Fig. 15-14).

Treatment Meningiomas should be excised. Com­plete removal offers the greatest likelihood of cure.

Prognosis Complete removal is usually followed by resolution of neurological deficits and permanent recovery. Tumor recurrence is not unusual following incomplete excision, and a second operation may be necessary several years later. Radiation therapy pre­vents or delays recurrence of tumor in most cases.

 

 

 

 

NEUROMA

(NEURINOMA; SCHWANNOMA)

Definition Neuromas are slow-growing benign tu­mors that originate from Schwann cells and most commonly develop on the vestibular portion of the eighth cranial nerve (acoustic neuroma). There are between 2000 and 3000 new cases of acoustic neuro­mas in the United States each year. Acoustic neuro­mas also account for 90 to 95 percent of neoplasms in the cerebellopontine angle.

Pathology Grossly, the tumor is thickly encapsu­lated and lobulated. Microscopic examination shows that it consists of spindle-shaped cells with rod-shaped nuclei that often lie in parallel rows. The tu­mor is often highly vascular and may contain areas of cystic granulation or loose reticular tissue. Axons are found only in the capsule of this tumor, in contrast to the neurofibroma, where axons are often contained in the substance of the tumor.

Clinical Features The acoustic neuroma is the most common cerebellopontine angle tumor. It pre­sents with the following symptoms, in order of de­creasing frequency: progressive hearing loss, tinnitus, ataxia, vertigo, headache, trigeminal nerve dysfunc­tion including hyperesthesia, paresthesias or facial pain, and progressive facial weakness.

Neuromas are often found attached to other cra­nial nerves and to nerve roots of the spinal nerves, usu­ally in the thoracic area, where they are subdural in lo­cation and involve the dorsal sensory nerve root. These tumors may grow out of the intervertebral foramen into the mediastinum in so-called dumbbell fashion.

Bilateral acoustic neuromas are occasionally encountered in patients with the subcutaneous nod­ules and cafe au lait lesions of neurofibromatosis.

 

Diagnostic Procedures

1. Audiologic tests show a high-tone hearing loss and impaired speech discrimination.

2.  Impedance audiometry is abnormal, with ab­sence of the acoustic reflex on the affected side.

3.  Brainstem auditory evoked potentials are ab­normal, with absence of wave 1 or prolongation of all absolute latencies.

4.  Caloric tests show diminished or absent re­sponse on the affected side.

5.  The MRI scan clearly outlines even the smallest tumor in axial, coronal, and sagittal planes. The MRI scan is particularly useful for the diagnosis of intracanalicular tumors (Fig. 15-15).

6.  Polytomes of the skull may reveal enlarge­ment of the internal auditory meatus. Polytomes of the thoracic vertebrae may reveal enlargement of the intervertebral foramina in the case of a neuroma de­veloping on a spinal nerve root.

7.  A CT scan with enhancement reveals a sharply marginated homogeneous, dense mass in the cerebellopontine angle. Hydrocephalus is often pres­ent in long-standing tumors.

Treatment Surgical removal using a suboccipital transmeatal approach is the treatment of choice in most cases. The tumor has a tendency to recur un­less there has been complete removal. Stereotactic ra­diosurgery is an effective alternative, which has less morbidity with better preservation of hearing and fa­cial nerve function. Transtemporal access is another technique favored by some surgeons.

Elderly patients with minimal symptoms and small tumors can be followed annually with MRI studies. The minority, who develop symptoms of brainstem or cerebellar involvement, can be treated by subtotal resection or cyst drainage.

CRANIOPHARYNGIOMA

Definition The craniopharyngioma is a tumor of congenital origin that develops from remnants of Rathke’s pouch. It is histologically benign and occurs most commonly in the suprasellar region in children and adults.

Etiology and Pathology The neoplasm is be­lieved to develop from squamous cell remnants of Rathke’s pouch. The tumor is yellow-brown in color, encapsulated, nodular in appearance, and frequently cystic. Microscopically, it is characterized by inter­lacing trabeculae of squamous epithelial cells with a peripheral layer of palisading columnar epithelial cells. Keratinization results in formation of squamous “horny pearls” that frequently calcify. Cystic compo­nents are lined by stratified squamous epithelium and the contents are oily brown in consistency and con­tain cholesterol crystals. There is intense gliosis in the surrounding brain.

Clinical Features The craniopharyngioma is the most common supratentorial tumor of childhood, some 55 percent occurring in children, 45 percent af­ter the age of 20 years. The tumor accounts for 2 to 3 percent of all intracranial tumors. It occurs in a 3:2 male: female ratio. Clinically, the tumor can present with a variety of signs and symptoms. These include increased ICP, visual field defects, headache, and neuroendocrine disorders resulting in diabetes in­sipidus, short stature, delayed sexual development, and hypogonadism. Larger tumors may produce hy­pothalamic involvement, cranial nerve palsies, hydro­cephalus because of pressure on the third ventricle, and progressive dementia. There may be evidence of recurrent aseptic chemical meningitis, where the cys­tic contents are discharged into the subarachnoid space. Diabetes insipidus may precede the appear­ance of other symptoms for some years in children with occult craniopharyngiomas, pituitary tumors, or hypothalamic tumors.

 

       

 

Diagnostic Procedures

1.    Skull films may reveal thickening, erosion, or enlargement of the sella. There may be evidence of bony invasion. Suprasellar calcifications are present in 80 percent of children with craniopharyngiomas but only in 40 to 50 percent of adult patients with this tumor.

2.    The MRI scan with contrast medium en­hancement will clearly delineate the tumor in axial, coronal, and sagittal planes (Fig. 15-16).

3.    The CT scan is characterized by the pres­ence of a calcified high-density mass or an isodense lesion in the case of intrasellar craniopharyngiomas.

Cystic tumors show a well-defined capsule containing high-density areas of calcification surrounding a low-density core. The capsule often shows dense contrast enhancement. Hydrocephalus may be present if the tumor extends into the area of the third ventricle.

4.    Endocrine studies should be obtained to es­tablish the function of the pituitary and hypothala­mus. A moderate hyperprolactinemia is not uncom­mon. Levels greater than 150 ng/mL (normal 1 to 25 ng/mL) suggest the presence of associated pituitary microadenoma.

5.    Arteriography is useful in the preoperative period to delineate the blood supply to the tumor.

6.    Lumbar puncture is indicated in patients with clinical evidence of meningeal involvement. The CSF shows a polymorphonuclear leukocytosis. Glu­cose content is normal or slightly decreased and pro­tein content is elevated.

Treatment The treatment of choice is surgical re­moval of all neoplastic tissue. However, total removal is not always feasible because of adherence to vital structures such as the optic chiasm, hypothalamus, and circle of Willis. In these cases, as much tumor as possible is removed, the cystic contents are aspirated, and the patient is treated with postoperative radiother­apy. Some patients may require repeated stereotactic percutaneous drainage of cysts. Others may be treated by insertion of an Ommaya reservoir for intermittent aspiration of cysts. Gross total resection is associated with a less than 20 percent recurrence, whereas more than 50 percent recur after subtotal resection.

Prognosis The overall 10-year survival rate is ap­proximately 60 percent. The rate is higher in the pedi­atric population than in adults. Death is the result of tumor recurrence, which seems to be low in those who survive more than 10 years. Hormone deficien­cies may be permanent and should be corrected by appropriate substitution therapy.

 

RATHKE’S CLEFT CYSTS

Rathke’s cleft cysts arise from a remnant of the sto-modeum and are enlarged by an accumulation of mu cus secreted by cyst wall cells. Small, asymptomatic Rathke’s cleft cysts are occasionally found by CT or MRI scanning. Symptomatic Rathke’s cleft cysts are rare and can compress the pituitary gland, optic chi­asm, and hypothalamus and must be distinguished from cystic pituitary adenomas or craniopharyn­giomas. One fact that helps differentiate Rathke’s cleft cysts is that the pituitary fossa is not enlarged on plain radiographs. The MRI scans usually show high-intensity Tl- and T2-weighted images.

Treatment is by resection of symptomatic cleft cysts.

 

HEMANGIOBLASTOMA

Definition The hemangioblastoma is believed to be a tumor of capillary endothelial origin and is com­monly located in the cerebellum.

Etiology and Pathology The tumor is most fre­quently located in the cerebellar hemisphere or ver­mis. It may also develop in the brainstem or in the spinal cord,⁷⁷ where it may be associated with a sy­rinx formation or supratentorially, where it is fre­quently attached to the dura. The association of a cerebellar hemangioma with angiomas and cysts of the liver, pancreas, and kidney, and occasionally with tumors of the kidney, epididymis, or adrenals, has been termed Lindau syndrome. The association of a retinal angioma and Lindau syndrome is often re­ferred to as the von Hippel-Lindau syndrome. He-mangioblastomas are yellowish red in color, well cir­cumscribed, lobulated, and cystic in appearance. Small mural nodules of tumor may be located in the cyst walls. Microscopically, the tumor is composed of an endothelial portion and a stromal portion, which is frequently distended with lipid. Reticular fibers sepa­rate the two portions. Polycythemia secondary to tu­mor production of erythropoietin can occur.

Clinical Features Hemangioblastomas usually develop during the third or fourth decade in men and frequently present as a posterior fossa mass with evi­dence of increased ICP and signs of cerebellar dys­function.  Brainstem involvement produces  cranial

nerve palsies and long tract signs. Polycythemia or evidence of von Hippel-Lindau syndrome may be present. Cerebellar tonsillar herniation can cause sud­den death. Subarachnoid hemorrhage is a rare com­plication of hemangioblastoma.

Diagnostic Procedures

1.  The MRI or CT scan reveals a well-circum­scribed, solid or cystic mass in the posterior fossa, which may contain calcifications (Fig. 15-17). Solid tumors show enhancement after injection of contrast material.

2.  Arteriography usually shows the presence of abnormal blood supply to the vascular nodule in cys­tic tumors.

Treatment In the case of cystic hemangioblas­tomas, the cyst and mural nodule should be removed because this is usually curative. Solid tumors can only be partially resected. Multiple tumors or inac­cessible tumors may benefit from radiotherapy or ra­diosurgery.

choice is total surgical removal. If this is not possible, the cyst may be drained stereotactically or a bilateral ventricular shunting procedure may be necessary.

     

 

COLLOID CYSTS OF THE THIRD VENTRICLE

A colloid cyst is a rare congenital lesion derived from an outpouching of the ependyma at the site of the pa-raphysis. The cyst enlarges and contains a clear gelatinous substance. Symptoms occur when the cyst causes intermittent obstruction of the flow of CSF through the third ventricle. The patient experiences intermittent headache that is relieved by change in posture. Sudden death may occur.

An MRI or CT scan will show the presence of a midline cystic lesion in the third ventricle with asso­ciated hydrocephalus (Fig. 15-18). The treatment of

 

DERMOIDS AND EPIDERMOID CYSTS (PEARLY TUMORS)

Dermoids and epidermoid cysts are believed to result from incorporation of a portion of the ectoderm in the developing neural tube. The cysts have a thin capsule of epidermis or dermis and enlarge when desquama­tion occurs. Dermoid cysts may contain hair or seba­ceous glands and are often calcined. They are usually associated with a dermal sinus or an occipital bone defect. The cysts are located in the midline in the pos­terior fossa, or in the cerebellar pontine angle, intra-and suprasellar region, or the lumbosacral region. Dermoid cysts occasionally develop in the temporal lobe of the brain. These tumors present as a slowly growing intracranial mass, producing partial or gen­eralized seizures, and increased ICP. Cerebellopon­tine angle cysts present with symptoms suggesting an acoustic neuroma. Intra- and suprasellar dermoid cysts may compress the pituitary gland and cause hy­popituitarism. An MRI scan is the procedure of choice. The CT scan shows a cystic lesion, often with negative density values. Peripheral calcification may be present. Total excision should be attempted when­ever possible, but dermoid and epidermoid cysts should be excised with care because contamination of the subarachnoid space can result in a severe chemi­cal meningitis, which may be fatal.

 

CHORDOMA

Definition A chordoma is a congenital neoplasm that may arise wherever notochordal tissue is present during embryonic development.

Etiology and Pathology The chordoma is be­lieved to arise from remnants of notochordal tissue and is most commonly located in the sacrococcygeal area or in the vicinity of the clivus. A rare variant of an intradural chordoma, arising from ectopic noto­chordal tissue, can occur in the prepontine region.

The tumor appears as a whitish or reddish brown lobulated structure containing gelatinous material. In some areas, the cells are grossly distorted by vacuo-lation and have indistinct boundaries. These have been termed physaliphorous cells. This tumor has local invasive tendencies, and rarely metastasizes to the lung.

Clinical Features The chordoma is most fre­quently encountered in the third to seventh decades and is twice as common in men. Signs and symptoms depend on the site of the tumor. When the tumor is in the area of the clivus, it may extend forward to the suprasellar region to involve the optic chiasm or later­ally into the middle cranial fossa. There may be pro­gressive cranial nerve involvement, usually beginning with the sixth cranial nerve and followed by hemi-paresis or quadriparesis.

Diagnostic Procedures

1.  Skull films may reveal sella enlargement, bony erosion, or calcification in the area of the tumor. Separation of the cranial sutures and enlargement of the skull can occur in children.

2.  MRI and CT scans are required to clearly delineate the boundaries of the chordoma and to as­sist in the planning of radiation therapy.

Treatment Most tumors cannot be resected and should be treated by radiation therapy in an attempt to slow tumor growth. Partial resection by the transpharyngeal route, combined with retromastoid craniotomy, may be possible in selected cases. This should be followed by charged particle radiation ther­apy, which is only available in major centers. Com­bined treatment produces a local control rate of 63 percent at 5 years.

 

ARACHNOID CYSTS

Definition Arachnoid cysts are encapsulated cysts containing CSF lying within the arachnoid space. The cysts may cause compression of the brain or spinal cord.

Etiology and Pathology The majority of arach­noid cysts are of developmental origin and result from failure of fusion of the two layers of the arach­noid in early fetal life, followed by accumulation of CSF and cyst formation. Between 20 and 30 percent of arachnoid cysts are associated with other congenital abnormalities, including aqueductal steno­sis, agenesis of the corpus callosum, and hamar­tomas. A number of cases follow head trauma with herniation of the arachnoid between the two layers of the dura, resulting in cyst formation. It is also possible that arachnoid cysts develop after sub­arachnoid inflammation and the formation of arach­noid adhesions.

Arachnoid cysts are thin-walled structures bounded by arachnoid. The cyst compresses the brain or spinal cord, producing deformity and atrophy.

Clinical Features Arachnoid cysts are more com­mon in infants and young children and may present with a local bulging of the skull. The cysts may occur in any part of the cranial cavity but are somewhat more common in the posterior fossa. Older children and adults usually complain of increasing headache and other symptoms suggesting an expanding in­tracranial mass lesion.

Arachnoid cysts of the spinal canal are usually located posteriorly and produce progressive parapare­sis without pain. Examination shows a well-demar­cated sensory level at the site of compression.

Diagnostic Procedures

1.  Radiography of the skull may reveal asym­metry and local bulging and thinning of the bone.

2.  The MRI and CT scans reveal a lucent area with the density of CSF and a clearly defined border (Fig. 15-19).

3.  Arachnoid cysts in infants may be demon­strated by ultrasound.

Treatment Treatment consists of cyst peritoneal shunting when cyst compression is present. Many cases require a ventricular peritoneal shunting proce-1 dure because of associated hydrocephalus.

 

LYMPHOMA

Primary lymphoma of the CNS has increased in inci­dence in the last decade. This increase can be explained in part by the rising number of immunosuppressed indi­viduals who are receiving immunosuppressant drugs af­ter organ transplantation or from infection by the hu­man immunodeficiency virus.

Pathology Most primary CNS lymphomas are al­most exclusively large B-cell lymphomas.

Clinical Features Most primary lymphomas of the CNS are parenchymal lesions that involve the deep white matter and basal ganglia and are a fre­quent complication of HIV-1 infection in children and adults with AIDS.⁸⁵ These lesions are often periven­tricular and may be multifocal. Posterior fossa in­volvement occurs in approximately 15 percent of pa­tients and isolated spinal cord lymphoma is rare.⁸⁶ Leptomeningeal involvement occurs in 42 percent of cases.

Diagnostic Procedures

1.  The MRI scan shows isointensity on Tl- and T2-weighted images with intense enhancement after intravenous administration of gadolinium.

2.  The CT scan shows an intensely enhancing parenchymal mass.

3.  The CSF contains a mononuclear pleocy-tosis and increased protein content. The fluid should be examined by flow cytometry for the presence of abnormal lymphocytes. The fluid should also be examined for tumor markers, including β₂– micro­globulin.

Treatment Short intensive primary chemotherapy, followed by whole brain radiation therapy, is recom­mended.

 

 

METASTATIC BRAIN TUMOR

Definition More than 100,000 cancer patients de­velop brain metastases each year in the United States. The most common primary site is the lung and 10 percent of bronchial carcinomas present with neuro­logical symptoms before evidence of lung involve­ment appears. Other common primary sites for brain metastasis are cancer of the breast and malignant melanoma. Metastatic brain tumors are most frequent in the sixth and seventh decades.

Etiology and Pathology The great majority of metastases reach the CNS through the arterial system. A smaller number arise by direct extension from ex­tracranial sites such as the pharynx, neck, or paranasal sinuses. There is a theoretical pathway from the pelvis through the vertebral venous plexus, but it is doubtful that metastases in the brain originate in this manner. Most metastatic tumors develop in the cerebral hemispheres in the distribution of the middle cerebral artery at the junction of the gray and white matter. Approximately 35 percent of metastatic brain tumors arise from a primary lung tumor, 20 percent are associated with carcinoma of the breast, and 10 percent from melanomatous tumors of the skin, with a further 10 percent from gastrointestinal carcinoma, 5 percent from carcinoma of the kidney, and the re­mainder from the genitourinary system and the en­docrine glands. Most metastases present as multiple spherical gray-pink tumors with sharply defined mar­gins but without encapsulation, and are typically as­sociated with large areas of edema in the surrounding brain (Fig. 15-20). It is not unusual to see a small tu­mor measuring 1 cm in diameter associated with massive cerebral edema. This edema is believed to arise as a transudate from abnormal capillaries within the tumor. Massive hemorrhage into tumors is rare and usually occurs with melanoma.

It is not always possible to determine the loca­tion of the primary lesion from the study of histologi­cal characteristics of a metastatic tumor.

Clinical Features Most metastatic tumors present with headache and partial or generalized seizures. Other signs and symptoms depend on the location of the tumor and the rapidity of development of the t mor (Table 15-1).

Diagnostic Procedures

1.    An MRI scan is the procedure of choice metastatic disease (Fig. 15-21). The MRI scan more sensitive than the CT scan and will often rev< multiple metastases that have escaped detection CT scanning (Fig. 15-22).

2.    A CT scan should be performed with be nonenhancing and contrast-enhanced studies. If oi one scan can be performed, a contrast-enhanced sc is recommended, although it is not possible to diff entiate between hemorrhage or tumor enhancement contrast-enhanced scans. Metastatic tumors most ten  appear  as  high-density  nodular  or  spheri masses, often surrounded by frond-like areas of cency representing edema. There is increased dens on contrast enhancement, often appearing as a rii shaped area.

3.    Radiographs of the chest will reveal one more lesions indicating the presence of primary metastatic tumors in the lung, in most cases.

4.    The presence of carcinoembryonic antij (CEA) in the CSF in a patient with a solitary mass sion in the brain suggests the tumor is metastatic in origin.

 

   

 

 

 

 

 

Treatment

1.    Edema can be controlled by corticosteroids such as dexamethasone (Decadron) 12 mg initially followed by 4 mg q6h. A more rapid reduction of ICP using intravenous mannitol is indicated when there is marked shift of the midline structures with the possi­bility of herniation.

2.    Solitary metastasis can be excised when the primary lesion can be successfully treated or when the symptoms produced by the lesion are inca­pacitating.

3.    Stereotactic radiosurgery is the treatment of choice in asymptomatic or mildly symptomatic pa­tients with small, solitary lesions. This should be followed by whole brain radiation.

4.    Whole brain radiation therapy is the treatment of choice for multiple metastases because many 1 are sensitive to radiation. Symptoms usually improve after radiation therapy and survival time may increase.

5.    Chemotherapy will frequently produce regression of brain metastasis in chemosensitive tu­mors.

Prognosis Current available treatments produce effective palliation of neurological symptoms and ex­tension of life and most patients do not die of their brain metastases.

 

MENINGEAL CARCINOMATOSIS

Meningeal carcinomatosis is the least common form of intracranial metastatic disease and is usually asso­ciated with a well-differentiated primary carcinoma of breast or lung. The remaining cases are usually as­sociated with carcinoma of the lung, stomach, and pancreas and malignant melanoma.

The meninges appear dull, gray, and hazy and show the presence of numerous tumor cells and an in­flammatory reaction.

Clinical Features The disorder is uncommon but not rare. Symptoms include headache, changes in mentation, signs of meningeal irritation, and cranial nerve palsies, particularly paralysis of the ocular, mo­tor, and facial nerves. Spinal cord involvement with radicular pain or paresthesias is an occasional presen­tation.

Diagnostic Procedures

1.    Lumbar puncture usually reveals a clear CSF under increased pressure with a slight lympho­cytic pleocytosis, moderately elevated protein con­tent, and a marked reduction of glucose content. The presence of tumor cells can be demonstrated by a fil­ter technique. The CEA level in the CSF is elevated in patients with meningeal carcinomatosis due to can­cer of the breast, lung, alimentary tract, and geni­tourinary tract. The CEA level may be of value in monitoring response to treatment and relapse.

2.    The CSF lactate dehydrogenase levels of­ten show marked elevation in meningeal carcino­matosis.  Similar elevation can occur in bacterial meningitis, but the test may be useful in suspected cases of meningeal carcinomatosis.

3.    The MRI scan is usually normal but may show some enhancement of the meninges in some cases and is probably more useful for detecting the presence of unsuspected metastatic lesions elsewhere in the neuraxis.

Differential Diagnosis Meningeal carcinomato­sis must be differentiated from all forms of chronic meningitis, including tuberculous meningitis, fungal meningitis, syphilis, sarcoidosis, and lymphoma in­volving the CNS.

Treatment Irradiation and intrathecal methotrexate are the only available means of treating meningeal carcinomatosis. Most patients show progressive dete­rioration, but adequate treatment may provide a pe­riod of useful remission. Corticosteroids may provide some symptomatic improvement.

 

TUMORS OF THE SPINAL CORD AND SPINAL CANAL

Tumors of the spinal cord and spinal canal are un­common, with an annual incidence of between 0.9 to 2.5/100,000 population. The most common tumor is the neuroma, followed by meningioma, glioma, and arteriovenous malformation. Approximately 25 percent of tumors arise in the cervical canal, 55 per­cent originate in the area of the thoracic canal, and 25 percent arise in the lumbosacral area. Twenty percent are extradural, 50 percent are extradural and in­tradural, and 30 percent are intradural. Tumors occur at all ages, but congenital tumors tend to occur with increasing frequency in infants and children.

Clinical Features

1. Pain. Most patients with spinal cord tumor present with pain caused by nerve root irritation. This is particularly common in extradural tumors and is frequently misdiagnosed as cervical spondylosis or herniated intravertebral disc. The pain is frequently exacerbated by coughing, sneezing, or straining. Root pains are less common with intramedullary tumors but have been reported. The association of root pain with asymmetry of reflexes and insidious onset is strongly suggestive of spinal cord tumor.

2.    Motor weakness. Root pains may be fol­lowed by the development of weakness and wasting of the muscles supplied by the affected nerve root. Extension of an extramedullary tumor may produce pressure on the anterior horn cells at several segments in the spinal cord, with gradual increase in focal mus­cle weakness, wasting, and fasciculations. Compres­sion of the corticospinal tracts produces weakness and spasticity below the level of the lesion. This usu­ally takes the form of progressive spastic paraparesis. However, tumors of the cervical medullary junction may present with an ascending flaccid paralysis re­sembling the Guillain-Barre syndrome.

3.     Sensory change. Many patients experience a dysesthesia in the limbs below the level of the le­sion. This is often described as a feeling of tempera­ture change, particularly a feeling of cold. Examina­tion   shows  a  dissociated  sense  of loss  in  about one-third of cases. This type of sensory loss is likely to occur in intramedullary tumors but is not confined to this type and can be seen with extramedullary tu­mors.

4.    Sphincter disturbances.  Tumors affecting the cervical, thoracic, and upper lumbar spinal cord produce early symptoms of sphincter dysfunction with increasing frequency and urgency of micturition. Rectal disturbances tend to occur somewhat later in most cases. Tumors of the lower lumbar cord and the conus medullaris destroy the parasympathetic neu­rons responsible for bladder control. This results in retention of urine with overflow incontinence. The development of sphincter disturbances is frequently followed by impotence in men.

5.     Syringomyelia.   Some intramedullary tu­mors, particularly ependymomas and hemangioblas-tomas, are associated with syringomyelia. Astrocy­tomas are less likely   to present  in  this  fashion. Intramedullary spinal cord metastases are a relatively rare cause of syringomyelia.⁹⁷ The tumor is likely to lie above rather than below the syrinx and the higher the spinal cord level of involvement, the more likely the presence of the syrinx.⁹⁸ The tumor or syrinx may produce destruction of the decussating lateral spinal thalamic fibers in the center of the spinal cord, with loss of pain and temperature sensation below the level of the lesion on one or both sides of the body. This is often coupled with pressure on the descending corti­cospinal tracts and progressive spastic paraparesis. Anterior extension of the tumor involves the anterior horn cells at the level of the lesion and results in mus­cle weakness, wasting, and fasciculations in the muscles supplied by the anterior horn cells.

6.    Brown-Sequard-like   symptoms.   Involve­ment of one-half of the spinal cord produces a char­acteristic constellation of symptoms known as the Brown-Sequard syndrome. This consists of progres­sive weakness, increased tone, clonus, increased re­flexes, and an extensor plantar response on the same side below the level of the lesion. Dissociated sensory loss occurs on the contralateral side with impairment of pain and temperature sensations. Posterior com­mon involvement produces ipsilateral loss of vibra­tion and position sense. The Brown-Sequard syn­drome is  much more  common  in  extramedullary tumors, which are usually benign and operable.

7.    Papilledema. Some cases of spinal cord tu­mor are associated with papilledema. The reason for this development is not clear. It has been postulated that the high protein content of the CSF stimulates in­creased production of CSF, resulting in papilledema, but this cannot be the sole explanation for this phe­nomenon. Papilledema is more likely to occur in spinal cord ependymomas but has been described with both intramedullary and extramedullary tumors of other types. The occurrence of papilledema is much more common with tumors of the thoracic and lumbosacral regions.

8.    Subarachnoid hemorrhage. Most cases of spinal subarachnoid hemorrhage are secondary to an arteriovenous malformation. The second most likely cause is bleeding from an ependymoma. Spinal hemangioblastomas are a rare cause of subarachnoid I hemorrhage because hemangioblastoma is rarely encountered in the spinal cord, but 50 percent can cause I  subarachnoid hemorrhage.”

9.    Intramedullary hemorrhage. Intramedullary hemorrhage is usually a complication of an arteriovenous malformation and is a rare event in spinal cord tumors, including astrocytomas, ependymomas, and hemangioblastomas. The majority present as a subarachnoid hemorrhage, but intramedullary hemorrhage from a hemangioblastoma may present with acute paraplegia.

The clinical features of spinal cord tumors at different levels include:

1.    Upper cervical cord. There is usually in­volvement of the lower cranial nerves if the tumor ex­tends up through the foramen magnum. A progressive spastic quadriparesis and a positive Lhermitte’s sign may be seen. Nystagmus is not unusual, due to in­volvement  of the  medial  longitudinal  fasciculus, which descends from the medulla into the upper cer­vical cord. Pressure on the vertebral arteries as they ascend over the ventral surface of the medulla may lead to intermittent symptoms of vertebral basilar in­sufficiency. Patients may experience pain and stiff­ness of the neck with an abnormal posture of the head. Obstruction of the flow of the CSF at the level of the foramen magnum can lead to hydrocephalus and raised ICP with papilledema.

2.    The lower cervical cord. Atrophy of the small muscles of the hand caused by an anteriorly placed meningioma has been reported in tumors at the level of the foramen magnum, due to pressure on the anterior spinal artery, with ischemia of the ante­rior  horn cells  in the   lower  cervical  cord.   In­tramedullary and extramedullary tumors of the lower cervical area produce weakness and increased tone below the level of the tumor, often presenting with progressive spastic paraparesis associated with in­creased sphincter disturbances. Sensory examination may show the presence of abnormal sensation up to the level of the tumor on both sides of the body. Ex­tramedullary   tumors   tend   to  produce   a   Brown-Sequard syndrome and unilateral Horner syndrome due to involvement of the sympathetic outflow from the lower cervical and upper thoracic cord.

3.    Thoracic cord lesions. Most thoracic cord tumors produce severe root pain that radiates in a gir­dle fashion around the chest or upper abdomen. This is associated with progressive spastic paraparesis and bladder dysfunction. Examination may show a sen­sory level and Horner syndrome with lesions of the upper thoracic cord.

4.    Lumbosacral tumors. Tumors in this area usually present with severe root pain followed by sphincter disturbances of the bladder and rectum. Men are impotent. Examination shows the presence of flaccid paralysis in the lower extremities with loss of tendon reflexes. There may be sensory loss in the “saddle” area. Tumors in the lumbosacral area can mimic a herniated lumbar disc with production of typical sciatic pain. This occurs with neuromas, meningiomas, and gliomas in the lower lumbosacral cord. Intramedullary lesions of the lumbar portion of the cord may produce flaccid paralysis on one side and evidence of spasticity with increased tendon re­flexes and an extensor plantar response on the oppo­site side.

 

 

Diagnostic Procedures

1.    The MRI scan is the method of choice in the diagnosis of tumors involving the spinal cord and spinal canal. The extraordinary detail obtained in the sagittal axial or coronal sections of the spinal canal and spinal cord has replaced other procedures or rele­gated them to second choice (Fig. 15-23). Both un-enhanced and enhanced scans should be obtained in all patients with spinal cord tumor. Intramedullary ependymomas   and  hemangioblastomas   show  iso-dense or slightly hyperintense Tl-weighted images, but T2-weighted images are hyperintense for heman-gioblastoma; ependymomas do not exhibit enhance­ment. High-resolution imaging of the spinal cord in multiple planes, using Tl- and T2-weighted images and  gadolinium enhancement,  clearly  defines  in­tradural extramedullary  lesions.  Neuromas  appear isointense on Tl-weighted images, hyperintense on T2-weighted images, and give an intense homoge­nous signal after gadolinium infusion. Meningiomas appear isointense to the spinal cord on Tl- and T2-weighted images but show increased intensity after gadolinium fusion. Axial MRI scans are essential in determining  the  relationship  of the  tumor to  the spinal cord

2.    Radiography  of the  cervical  spine.  The presence of spinal cord tumor may lead to widening of the spinal canal and extramedullary tumors may erode the posterior aspect of the vertebral bodies. Neuromas may produce unilateral enlargement of the intravertebral foramina; neuromas, meningiomas, and metastatic tumors frequently erode the pedicles and

laminae. Congenital tumors in children are frequently accompanied by abnormal curvature of the spine. Calcification is unusual but may occasionally occur in some spinal cord tumors. Malignant extradural tu­mors frequently produce bone destruction, but more benign tumors, such as meningioma, rarely produce new bone formation, unlike meningiomas in the era-1 nial cavity.

3.    Myelography. In most cases, a myelogram will locate a spinal cord tumor and differentiate be­tween an intramedullary and extramedullary tumor. The combination of CT and myelography using a wa­ter-soluble contrast material is particularly helpful in the diagnosis of spinal cord tumors.

4.    Electromyography. Extramedullary tumors tend to be associated with unilateral denervation, which can be detected by electromyography. Bilateral denervation at the same level suggests the presence of I an intramedullary tumor.

5.    Angiography. Selective angiography of the spinal arteries is particularly useful in the diagnosis of arteriovenous malformations. Arteriography is not usually required for the diagnosis of other tumors.

6. Lumbar puncture. This procedure has be­come redundant in most cases because of MRI scan­ning but is used for the introduction of contrast mate­rial for myelography when the following observations can be made. Extramedullary and intramedullary tu­mors are likely to produce some change in pressure dynamics, ranging from a slow rise in pressure fol­lowing insertion of the needle to a failure to register any increase in pressure, and a negative Queckenstedt test (see Chap. 16) indicating a block in the spinal subarachnoid space. In these cases, the fluid is likely to be xanthochromic and the protein content markedly elevated. It is usual, however, to find some increase in the protein content of the CSF even when there is no obstruction of the spinal subarachnoid space.

Differential Diagnosis There are no clinical signs exclusively found with intramedullary tumors rather than extramedullary tumors. The presence of root pain and ascending segmental sensory loss oc­curs more often with extramedullary tumors than with intramedullary tumors. Fasciculations and de­scending dissociate sensory loss are more characteris­tic of an intramedullary tumor.

The association of root pain with hyperesthesia to pinprick and weakness of muscles supplied by the same nerve root is strongly suggestive of a neuroma. Meningiomas tend to produce bilateral root pain and paresthesias, followed by unilateral then bilateral mo­tor disturbances.

Treatment Extramedullary tumors should be re­moved surgically with total excision, if possible. Pa­tients with intramedullary astrocytomas have a 10-year survival rate of 50 percent, whether treated by gross to­tal resection or subtotal resection, or biopsy followed by postoperative radiation therapy in each category.¹⁰² Pilocytic astrocytomas have a better prognosis than nonpilocytic astrocytomas.¹⁰³ Spinal ependymomas are usually tumors of low malignancy that can be totally removed. Malignant spinal ependymomas are unusual but carry a poor prognosis. Recurrent low-grade ependymomas should be treated by further surgical ex-

cision and radiotherapy, but recurrence carries a poor prognosis. Surgery has little impact on the course and poor prognosis for anaplastic gliomas.¹⁰⁴ Heman-gioblastomas should be removed totally whenever pos­sible, using microsurgical techniques.¹⁰⁵

Prognosis The prognosis of spinal cord tumors varies according to the histologic type and the degree of malignancy. If all spinal cord tumors are consid­ered, approximately 66 percent of the patients survive 5 years following diagnosis and treatment. Most neu­romas and meningiomas can be excised, and patients have a life expectancy corresponding to that of the general population.¹⁰⁶ However, 80 percent of pa­tients have residual complaints following excision of a neuroma, including local pain, radiating pain, para­paresis, sensory deficits, and impaired bladder func­tion. Congenital tumors in children, including der­moids, epidermoids, lipomas, and teratomas, have a good prognosis, although residual neurological deficits, including muscle wasting and weakness of lower limbs and urinary incontinence, persist.

 

 

Epilepsy and convulsion syndromes

 

Epilepsy is a chronic disorder, which is characterized by the presence of:

·        Epileptic focus

·        Recurrent attacks with various clinical signs

·        Personality disorders between attacks

·        Some specific paraclinical signs

 

Epidemiology

      The prevalence of epilepsy is 0.8 – 1.2%. About 40 million people are affected worldwide. Among them 6 million people live in Europe. In men the incidence of epilepsy is 1.5 times higher than in women. The disease begins at the age under 10 – in 31 %; 20 – in 29 %; 30 – in 30 %; 40 – in 14 %; elder – in 6  %. About 200 billions of Euro are spent for the treatment of epilepsy in Europe.

 

Epilepsy as a disease should be differentiated from:

·        Epileptic reaction

·        Epileptic syndrome

 

Epileptic reaction – is the response of the brain to the strong external and internal damaging factors (such as electro – shock, insulin shock, brain hypoxia, severe alcohol intoxication and so on). The main clinical features of epileptic reaction are abortive seizures or general tonic – clonic seizures.

 

Epileptic syndrome – is characterized by recurrent epileptic attacks on the background of pathologic focus in brain. The attacks are variable and depend on the localization of focus. Focal symptoms are obligatory in this case.

 

Risk factors

1.   Inheritance

2.   Organic brain diseases

·        Prenatal (infections – cytomegalovirus, rubella, toxoplasmosis, toxicosis of pregnancy, diet disturbances)

·        Perinatal (physical trauma, child birth anoxia, metabolic disorders, neonatal infection)

·        Postnatal (infections, trauma, dehydration, toxins)

3.   Disorders of brain function. Sleep disorders.

4.   Paroxysmal states in childhood

·        Newborns seizures

·        Febrile seizures

·        Affective – respiratory seizures

 

Pathology

There are such changes:

·        The results of organic diseases

·        The results of epileptic process

Each epileptic attack causes hypoxic changes in brain and leads to the development of encephalopathy.

 

Pathologic physiology

1.   There is a group of neurons with pathologic activity, which is called epileptic focus

2.   There is the ability to enforce and spread the activity

3.   Weakness of anti – epileptic protection. (It is provided by caudal parts of the brain)

 

Neurochemistry of epilepsy

1.   Disorders of balance between glutamate (exciting neurotransmitter), GABA (inhibitory neurotransmitter

 

Immunology of epilepsy

     There is increasing content of anti–brain antibodies. The primary attack causes disturbances of HEB. Immune system butts into strange to it nervous system. The result is production of antibodies and CIC that are fixed in brain tissue and favour its damage iew places.

 

Classification of epileptic attacks

I.   Partial epileptic

1.   Simple

a.   Simple motor

·        Focal motor without march

·        Focal motor with march

·        Adversive

·        Postural

·        Phonatory simple

b.   Simple sensory

·        Somatosensory (with and without march)

·        Visual, acoustical, gustatory, smell)

c.   Simple autonomic – visceral

d.   Simple with psychiatric disorders

·        Aphatic

·        Dysmnestic

·        With thinking disturbances (ideatory)

·        Emotional – affective

·        Hallucinatory

2.   Complex

a.   Temporal pseudoabsance

b.   Automatisms

3.   Simple with generalization (secondary general)

II.           General attacks

1.   Absance

·        Typical

·        Atypical

2.   Myoclonic

3.   Tonic – clonic

4.   Tonic

5.   Clonic

6.   General atonic

III.          Non classified

IV.         Epileptic status

 

Clinical features

I.             A. General seizures.

Epileptic general tonic – clonic attack (grandmal) usually begins with short initial stage that lasts several seconds. The last can manifest as:

·        Bilateral general muscle jerks

·        Loss of consciousness

·        Autonomic changes

·        Enlargement of pupils

Karlov called this stage initial one.

 

The tonic stage lasts about 10 – 20 seconds. During this stage seizures involve all the muscles. Usually seizures dominate in the extensors but at the beginning flexors are even more involved. The eyes are opened and are looking upwards. Mouth is opened too. Seizures start from axial muscles and then involve extremities. Shoulders are lifted and adducted. Muscles of lower extremities are seldom involved. Opistotonus and “obstetrician arm” are often observed. Extension of great toe is a common symptom in this case. Because of the diaphragm muscles contraction epileptic shouting is often associated with the attack.

      Then tonic stage is converted in clonic one. That means that on the background of tonic muscles straining there is trembling of the muscles. Then between the muscles straining relax pause appear. This stage is often associated with tongue biting, clonic vocalization. This phase lasts 30–40 seconds. During the tonic–clonic attack there are severe autonomic disorders – apnoe, cyanosis, small skin hemorrhages, pulsation of carotic arteries. Pulsation is frequent, AP is increased. There is also midriasis with pupils areflexia, hypersalivation that usually manifest as bloody foam. After attack the next stage can be divided into early and late ones.

 

Early stage lasts 1 – 5 min and is characterized by: after the last clonic attack a new phase of tonic contraction appears. The last is very similar to the one at the beginning. But the seizure dominates in the face, especially in chewing muscles and causes trismus. Usually the extremities aren’t involved. The eyes are looking upwards. There is midriasis. This stage is finished by muscles atonia that leads to involuntary urination. Corneal reflexes are absent. Deep reflexes are increased. There is loss of consciousness. And that means that the patient is in coma.

        Late after attack (recovery) stage is characterized by decreasing of midriasis, normal superficial reflexes, decreased deep reflexes and Babinski sign. The behavior of the patient is often automatic. When the patients are conscious they can complain on headache, muscles pain and complete amnesia. This period lasts 5 – 15 min.

        There can be different types of general tonic – clonic attack because of the age of the patient. In children tonic stage can last longer than clonic one. In newborn babies there is often difference between right and left hemisphere seizures. Sometimes in children general tonic – clonic attacks are associated with vomiting and feces incontinence.

        Tonic attacks are seldom in grown – ups. In children tonic attacks are often associated with atypical absentia epileptica.

There are three types of epileptic tonic attacks:

1. Axial – body and facial muscles are involved in attack. There is spasm of respiratory muscles and breathing stop at expiration.

2. The same signs plus less involvement of extremities muscles.

3. Global means involvement of body and extremities muscles in the same way.

These attacks are associated with loss of consciousness. There is midriasis, tachycardia, increased AB and so on.

     General tonic – clonic attacks are very dangerous for the patient. They can cause trauma, aggression and sudden death as a result of autonomic disorders and respiratory disturbances, acute suprarenal insufficiency.

 

Clonic epileptic attacks

General typical clonic attacks are often observed iewborn babies. There is loss of consciousness, autonomic disorders, rhythmic clonic seizures. Between the attacks of clonic muscles jerks there is muscle hypotonia.

       If the attacks last 1–2 min the consciousness recovers quickly. But these attacks can last 4–5 min and even more. Then after the attack coma can be developed.

 

B. Without seizure attacks

      Absentia epileptica are characterized by sudden and short – lasting (2–30 sec) loss of consciousness and EEG – peculiarities. They are associated with absent gaze, interruption of patient’s activity, autonomic disorders (paleness or hyperemia of face, midriasis). The attack is finished suddenly. The patient doesn’t remember anything about it. This picture is typical for simple attack, when motor activity, seizures or loss of muscles tonus are absent.

       If absentia is associated with any motor component it is called complex absentia.

Complex absentia can be divided into myoclonic, atonic, tonic and with automatisms.

      Myoclonic absentia is characterized by loss of consciousness, rhythmic bilateral myoclonus in face and upper extremities. There are jerks of eyelids, periorbital muscles, mouth edges, eye bulbs. The patient can loose some objects he is holding in his arms.

      Atonic absentia is characterized by decreasing of postural tonus, hanging head and sudden drops.

      Tonic absentia is associated with looking of eyes upwards. There is domination of either extensor or flexor component, symmetric or asymmetric.

      Absentia with automatism can be the sign of focal attack and absentia. The main condition for automatism is incomplete loss of consciousness. Differential diagnosis in this case is very complicated. That’s why EEG should be made for such patients.

       Typical absentia are associated with bilateral symmetric complexes “top – waves” with frequency 3 per sec in frontal – central lobe.

        Typical absentia are much more common in children and can be caused by hyperventilation or light. They are very refractory to the antiepileptic drugs.

Atypical absentia are associated with such EEG changes:

1. Bilateral symmetric complex of “top – wave” which are rhythmically repeated with frequency 2 per sec.

2. Epileptic rhythm of gathering with frequency 10 per sec.

3.  Epileptic rhythm of gathering with frequency 20 per sec.

4. Complex of multiple spikes – waves with frequency 4 – 6 per sec.

Atypical absentia are resistant to hyperventilation and paroxysmal light.

II.           Focal attacks

       Focal attacks are those that clinically and on EEG manifest as the beginning of activation of neuron system of certain part of brain hemisphere.

There are three groups of focal attacks:

1.   Simple focal

2.   Complex focal

3.   Focal attacks with secondary generalization.

     The main differential feature of complex focal attacks from simple ones is loss of consciousness.

      Focal attacks are characterized by different symptoms – motor, sensory, autonomic or psychiatric that depends on focus localization and the peculiarities of morpho–functional organization of epileptic system. Motor attacks are caused by discharges in certain part of motor cortex. Somato–motor or motor Jackson attacks are seizures in certain muscle group according to the focus localization. They can be local or involve other group of muscles according to the topical localization in the brain cortex.

     In case of epileptic discharges in motor speech center speech disorders or involuntary vocalization – involuntary repetition of words are observed.

     Sensory attacks manifest as simple or complex  sensory disorders, such as somatosensory, visual, acoustical, olphactory, taste attacks and epileptic attacks of dizziness.

     Somatosensory Jackson attacks are associated with numbness, tingling in some part of the body. They can be localized or involve other parts of the body. They are caused by epileptic discharges in Post – Rollandic region. Very often the attack begins as somatosensory and then converts into somatomotor.

      As for visual, acoustical, olphactory, taste attacks and epileptic attacks of dizziness they can manifest as simple disorders or complex illusion or hallucinations.

 

Treatment

The main principals of epilepsy treatment should be – emergency, accordance to stages, following.

On the way to hospital:

1.   To release breathing air ways

2.   Digitalis drugs

3.   Sibazonum 0.01g

In ambulance:

a)   Tracheobronchial tree drain

1. Sibazonum 30 ml in 150 ml of physiological solution, in 10 min we add the medication up to 100 – 120 mg

2. Magnesiii sulfas 25% 10.0 in glucose 40 %

3. Anesthesia with nitrous oxide

4. Dosed anesthesia

5. Aminazinum 25% 1-2 ml

6. Atropinum 0.1% 1.0 s/c

7. Cardiac, antihistamine, diuretics

8. Natrii tiopentali 1g in 10 ml of physiological solution

 

Epileptic status

·        To provide permeability of respiratory airways

·        To evaluate the function of heart – vascular and respiratory systems

·        To provide free way to veins

·        Lorazepam 4mg i/v or Diazepam 10 mg

 

In the hospital

·        To take blood for analysis

·        % of urea, electrolytes

·        liver function

·        % of glucose

·        % of blood gas

·        etiology of attack – hypoglycemia – 50% solution of glucose 50 mg

–         at alcohol abuse – Tiaminum

 

Next half an hour:

§  to introduce the medication through the naso – gastral probe

§  Fenitoin 18 mg per kg or Phenobarbitalum 15 mg per kg i/v by drop 100 mg per kg

 

In 30 minutes:

§  General anesthesia

§  EEG

 

Surgical methods of treatment:

1.   Resections

§  Anterior temporal lobectomy

§  Selective amygdalohypocampoectomia

§  Calosotomia

§  Hemisphereectomia

2.   Stereotaxic

§  Destruction of deep temporal structures. This procedure on lateral part normally decreases seizures, on medial ones – aggression.

3.   Radio – surgical with γ – knife. γ – waves from 201 sources are focused on certain aims. The effectiveness of this procedure is 70 – 80 %.

4.   Electrostimulative – stimulation of certain structures:

§  Nucleus dentatus, the caput of nucleus caudatus (the price is 3.5 – 3 000 $)

§  Stimulation of n. vagus – this method is one of the newest one. It is indicated at partial seizures with secondary generalization.

Students’ practical Study Program.

 

Step I. Aim: to put of the clinical diagnosis. For this purpose it is necessary:

1. To examine the patient (history, somatic-neurological state).

2. To use the results of the laboratory investigation (general and biochemical blood and urine analyses, EEG, craniography, CT –scan tomography).

3. To make the differential diagnosis using the algorithm.

4. To make the clinical diagnosis.

Step II. Aim: To prescribe adequate treatment.

The treatment of patients with convulsive seizure can be divided into four parts:

1.    Elimination of the factors of importance in the causation or precipitation of attacks

2.    General mental and physical hygiene

3.    Medical therapy directed toward elevation of the convulsive threshold and thus the prevention of the attacks

4.    Surgical therapy in carefully selected patients with focal epilepsy

Elimination of the factors of importance in the causation or precipitation of attacks – requires treatment of all underlying physiologycal or structural abnormalities which have been discovered in the examination of the patient. This includes surgical removal of operable tumors of the brain, evacuation of the brain abscess, treatment of infections or endocrine abnormalities, and the correction of the physical defects

General mental and physical hygiene – Patients must be encouraged to use all of their resources to overcome their feelings of inferiority and self-consciousness resulting from the attacks. Adults should be assisted in obtaining productive work which will occupy their time and give them remuneration. Children should be kept in school unless the frequency of attacks unduly disturbs the routine of the classroom, or unless mental deficiency requires special facilities.

Physical activity of the patient should be regulated so that there is a set time for eating and sleeping and regular exercises every day. Alcoholic beverages are to be avoided. Special activities, such as parties, dancing, moving pictures, and so on, should be encouraged. Swimming, horseback riding and otherwise dangerous sports can be permitted when there are proper safeguards.

Medical Therapy. They should be given an adequate, thorough trial in each individual patient.

Anticonvulsive drags:

1.    Barbiturats (Phenobarbital (max 240 mg), Bensonal

2.    Phenylhydantoin (Diphenin)

3.    Trimethdione (Trimetin)

4.    Ethosuximide

5.    Carbamazepine (Tegretol, Finlepsin)

6.    Depakin, Convulex

7.    Diacarb

8.    Bromides

Phenobarbital is the drag of choice in the treatment of patients with grand mal seizures because of their high therapeutic index. A combination of phenytoin with Phenobarbital is often more effective than any one these drugs when used alone. In patients with psychomotor-temporal lobe or psychic equivalent seizures, carbamasepine is the drags of choice.

For petit mal seizures, ethosuximide is the drags of choice. If the patients are subject to petit ml seizures and grand mal or psychomotor attacks, one of the «anti petit mal» drugs shhould be given in combination with phenytoin sodium, Phenobarbital.

Surgical Treatment. Whenever convulsive seizures are associated with a surgically removable lesion of the brain, such as tumor or abscess, removal of.

Step III. Aim: Preventive determination.

Prognostic examination is determined according the clinical diagnosis and effectiveness of the treatment. To make the prognosis to live, to recover, to work, make a complex of the preventive measures.