Neurology_Adams

Neurology_Adams. Ependymoma of the Fourth Ventricle Ependymomas, as pointed out earlier in this chapter, arise from the lining cells in the walls of the ventricles. Approximately 70 percent of them originate in the fourth ventricle, according to Fokes and Earle (Fig. 30-13). Postmortem, some of these tumors, if small, are found protruding into the fourth ventricle, never having produced local symptoms. Whereas the supratentorial ependymoma occurs at all ages, fourth ventricular ependymomas appear mostly in childhood. In the large series of Fokes and Earle (83 cases), 33 developed in the first decade of life, 6 in the second decade, and 44 after the age of 20 years. Males have been affected almost twice as often as females.


Neurology_Adams

Neurology_Adams. Cerebral ependymomas usually arise from the floor of the fourth ventricle and extend through the foramina of Luschka and Magendie. They may later invade the medulla. These tumors produce a clinical syndrome much like that of the medulloblastoma except for their more protracted course and lack of early cerebellar signs. The histologic features of this tumor were described earlier in this chapter. The degree of anaplastic change varies and has prognostic significance. The most anaplastic form is the ependymoblastoma, a highly aggressive tumor that falls within the spectrum of primitive neuroectodermal tumors (see the following text).


Neurology_Adams

Neurology_Adams. Symptoms may be present for 1 or 2 years before diagnosis. About two-thirds of the patients come to notice because of increased intracranial pressure; in the remainder, vomiting, difficulty in swallowing, paresthesia of the extremities, abdominal pain, vertigo, and neck flexion or head tilt are prominent manifestations. Some patients with impending cerebellar–tonsillar herniation are disinclined to sit and have vertical downbeating nystagmus. Surgical removal offers the only hope of survival. The addition of radiation therapy and sometimes ventriculoperitoneal shunting of CSF may prolong life. Myxopapillary ependymomas of the spinal cord and filum are discussed with the spinal cord tumors further on and in Chap. 42.


Neurology_Adams

Neurology_Adams. Papillomas of the choroid plexus are about one-fifth as frequent as ependymomas. They arise mainly in the lateral and fourth ventricles, occasionally in the third. Two authoritative studies (Laurence et al; Matson and Crofton) give the ratios of lateral/third/fourth ventricular locations as 50:10:40. The tumor, which takes the form of a giant choroid plexus, has as its cellular element the cuboidal epithelium of the plexus, which is closely related embryologically to the ependyma. An oncogene T (tumor) antigen of the SV40 virus is possibly involved in tumor induction (see Schmidek). Essentially, these are tumors of childhood. Fully 50 percent cause symptoms in the first year of life and 75 percent in the first decade. In the younger patient, hydrocephalus is usually the presenting syndrome, sometimes aggravated acutely by hemorrhage; there may be papilledema, an unusual finding in a hydrocephalic infant with enlarging head. Headaches, lethargy, stupor, spastic weakness of the legs,


Neurology_Adams

Neurology_Adams. sometimes aggravated acutely by hemorrhage; there may be papilledema, an unusual finding in a hydrocephalic infant with enlarging head. Headaches, lethargy, stupor, spastic weakness of the legs, unsteadiness of gait, and diplopia are more frequent in the older child. Tumors that arise from the choroid plexus and project into the lateral recess of the fourth ventricle may present with a syndrome of the cerebellopontine angle (see in the following text). One consequence of the tumor (rather uncertain or inconsistent) may be increased CSF formation, which contributes to the hydrocephalus. Some of the tumors acquire more malignant attributes (mitoses, atypia of nuclei) and invade surrounding brain. They have the appearance of a carcinoma and may be mistaken for an epithelial metastasis from an extracranial site.


Neurology_Adams

Neurology_Adams. Treatment by surgical excision is usually curative, but palliative ventricular shunting may be needed first if the patient’s condition does not permit surgery. The prognosis of the rare choroid plexus carcinomas is poor.


Neurology_Adams

Neurology_Adams. This term was introduced by Hart and Earle in 1973 to describe tumors that have the histologic features of medulloblastoma but occur supratentorially. Various poorly differentiated or embryonal tumors of infancy and childhood were in the past included in this group: medulloblastoma, neuroblastoma, retinoblastoma, ependymoblastoma, and pineoblastoma (described further on). Subsequent authors have broadened the category of PNETs to include all CNS neoplasms of neuroectodermal origin. With the advent of immunohistochemical techniques, many of these poorly differentiated neoplasms of infancy came to be recognized as small cell gliomas (Friede et al); others, after ultrastructural study, could be classified as other types of primitive neoplasms. To some pathologists, the term primitive neuroectodermal tumors has appeal but has added little to our understanding of their undifferentiated embryonal origin. Current classifications have again grouped these with embyronal tumors, the group


Neurology_Adams

Neurology_Adams. tumors has appeal but has added little to our understanding of their undifferentiated embryonal origin. Current classifications have again grouped these with embyronal tumors, the group containing medulloblastoma. In practical terms, the prognosis and treatment of all these tumors are much the same, regardless of what they are called (see Duffner and Cohen). Certain patterns of gene expression are used to distinguish this group of tumors from histologically similar medulloblastomas.


Neurology_Adams

Neurology_Adams. Hemangioblastoma of the Cerebellum This tumor is referred to most often in connection with von Hippel-Lindau disease, of which it is the essential element. Dizziness, ataxia of gait or of the limbs on one side, symptoms and signs of increased ICP from compression of the fourth ventricle, and in some instances an associated retinal angioma or hepatic and pancreatic cysts (disclosed by CT or MRI) constitute the von Hippel-Lindau syndrome. There is a tendency later for the development of malignant renal or adrenal tumors. Many patients have polycythemia as a result of elaboration of an erythropoietic factor by the tumor. The age of onset is usually between 15 and 50 years. Blacks, whites, and Asians are equally affected. The dominant nature of the inheritance of von Hippel-Lindau disease is well known. Seizinger and coworkers, in cases associated with renal cell carcinoma and pheochromocytoma, localized a defect in a tumor suppressor gene (termed VHL; see Chap. 37).


Neurology_Adams

Neurology_Adams. The diagnosis can be deduced from the appearance on CT or MRI of a cerebellar cyst containing an enhancing nodular lesion on its wall. Often, the associated retinal hemangioma will be disclosed by the same imaging procedure. The angiographic picture is also characteristic: a cluster of small vessels forming a mass 1.0 to 2.0 cm in diameter (Fig. 30-14). Craniotomy with opening of the cerebellar cyst and excision of the mural hemangioblastomatous nodule is usually curative, but there is a high rate of recurrence if the entire tumor, including the nodule, is not completely removed. In the series of Boughey and colleagues, the lesion was successfully excised in 80 percent of patients; 15 percent of patients, who had only partial resection of an isolated cerebellar lesion, developed recurrent tumors. More recently, several groups have used endovascular embolization of the vascular nodule prior to surgery, but it is not clear if this reduces the incidence of recurrence. Treatment with


Neurology_Adams

Neurology_Adams. tumors. More recently, several groups have used endovascular embolization of the vascular nodule prior to surgery, but it is not clear if this reduces the incidence of recurrence. Treatment with focused radiation is also being undertaken, particularly for multifocal or surgically inaccessible lesions, and several case series using either stereotactic radiosurgery, or external or proton beam radiation indicate results that may be comparable to conventional treatment.


Neurology_Adams

Neurology_Adams. Hemangioblastomas of the spinal cord are frequently associated with a syringomyelic lesion (greater than 70 percent of cases); such lesions may be multiple and are located mainly in the posterior columns. A retinal hemangioblastoma may be the initial finding and leads to blindness if not treated. New retinal lesions continue to be formed over a period of years while the patient is under observation. The children of a parent with a hemangioblastoma of the cerebellum should be examined regularly for an ocular lesion and renal cell carcinoma and genetic testing is appropriate in some instances. There has been uncertainty as to the proper classification of pineal tumors. Originally they were all thought to be composed of pineal cells; hence they were classified as true pinealomas, a term suggested by Krabbe. Globus and


Neurology_Adams

Neurology_Adams. Silbert believed that these originated from embryonic pineal cells but Russell later pointed out that some tumors in the pineal region are really atypical teratomas resembling the seminoma of the testicle. Four types of pineal tumors are now recognized: germinoma, nongerminatous germ cell tumors, pinealoma (pineocytoma, atypical pineocytoma, and pineoblastoma), and a glioma originating in astroglial cells of the pineal body. Some would include teratomas in this group. Currently, they are assigned a category of their own with 4 subtypes ranging from grade I (pineocytoma) to IV (pineoblastoma). Of the four groups of pineal tumors, approximately 50 percent are germinomas. The pinealomas, pineoblastomas, and gliomas are less frequent. Children, adolescents, and young adults—males more than females—are affected. Only rarely does one see a patient with a pineal tumor that has developed after the 30th year of life.


Neurology_Adams

Neurology_Adams. The pineal germinoma has its origin in germinal cells and is therefore classified separately from tumors that arise in pineal cells (pineocytoma and pineoblastoma). It is a firm, discrete mass that usually reaches 3 to 4 cm in greatest diameter. It compresses the superior colliculi and sometimes the superior surface of the cerebellum and narrows the aqueduct of Sylvius. Often it extends anteriorly into the third ventricle and may then compress the hypothalamus. A germinoma may also arise in the suprasellar area. Microscopically, these tumors are composed of large, spherical epithelial cells separated by a network of reticular connective tissue and containing many lymphocytes.


Neurology_Adams

Neurology_Adams. The pineocytoma, atypical pineocytoma, and pineoblastoma reproduce the normal structure of the pineal gland. These tumors enlarge the gland, are locally invasive, and may extend into the third ventricle and seed along the neuraxis. Cytologically, the pineocytoma is a moderately cellular tumor with none of the histologic attributes of anaplasia. The tumor cells tend to form circular arrangements, so-called pineocytomatous rosettes. Pinealocytes may be impregnated by silver carbonate methods, and some contain the retinal S antigen of photoreceptor cells. Pineoblastomas are highly cellular and composed of small, undifferentiated cells bearing some resemblance to medulloblasts.


Neurology_Adams

Neurology_Adams. Teratoma and dermoid and epidermoid cysts of the pineal body have no special features—some are quite benign. Gliomas of the pineal have the usual morphologic characteristics of an astrocytoma of varying degrees of malignancy. In some cases, the clinical syndrome of the several types of pineal tumors consists solely of symptoms and signs of increased intracranial pressure. Beyond this, the most characteristic localizing signs are an inability to look upward and slightly dilated pupils that react on accommodation but not to light (Parinaud syndrome). Sometimes ataxia of the limbs, choreic movements, or spastic weakness appears in the later stages of the illness. It is uncertain whether the ocular and motor signs are caused by neoplastic compression of the brachia conjunctivae and other tegmental structures of the upper midbrain or to hydrocephalus (dilatation of the posterior part of the third ventricle). Probably both mechanisms are operative.


Neurology_Adams

Neurology_Adams. Precocious puberty occurs in males who harbor a germinoma. Although the pineal gland is the source of melatonin, sleep is not affected to any important degree in patients with these tumors, as discussed in “The Pineal Gland and Melatonin” in Chap. 26. Measurement of CSF or serum melatonin is useful mainly in the detection of tumor recurrence after surgical extirpation. In patients with a germ cell tumor, the CSF or serum may show elevations of beta-human choriogonadotropin or alpha-fetoprotein. The diagnosis is made by neuroimaging (Fig. 30-15). The CSF may contain tumor cells and lymphocytes but may also be entirely normal.


Neurology_Adams

Neurology_Adams. Treatment Pineal lesions were formerly judged to be inoperable. However, the use of the operating microscope now makes it possible to excise them by a supracerebellar or transtentorial approach. Operation for purposes of excision and histologic diagnosis is advised because each type of pineal tumor must be managed differently. Moreover, one may occasionally find an arachnoidal cyst that needs only excision. The germ cell tumors should be removed insofar as possible and the ventricular region radiated for germinomas, and the whole neuraxis is treated in the case of nongerminomatous lesions. The use of chemotherapy in addition to or instead of cranial irradiation is still being evaluated. Several of our patients have survived more than 5 years after the removal of a pineal glioma. Neuroepithelial Tumors (DNET), Germinomas, Gangliocytomas, Mixed Neuronal-Glial Tumors, and Lhermitte-Duclos Disease


Neurology_Adams

Neurology_Adams. Neuroepithelial Tumors (DNET), Germinomas, Gangliocytomas, Mixed Neuronal-Glial Tumors, and Lhermitte-Duclos Disease Malignant germ cell tumors occurring in locations other than the pineal body are usually found in the suprasellar space and rarely in the roof of the third ventricle. Germinoma, mentioned above, is the most common of this rare group of neoplasms, which also includes choriocarcinoma, embryonal cell carcinoma, endodermal sinus tumors, and malignant teratomas. Certain biochemical markers of these tumors are of interest and of clinical utility, because they may be detected in samples of the blood and CSF. The beta subunit of human chorionic gonadotropin (hCG) is elaborated by choriocarcinoma and alpha-fetoprotein, and by endodermal sinus tumors and immature teratomas. Typical germinomas have shown little elevation of either. Most often these markers indicate the presence of complex mixed germ cell tumors.


Neurology_Adams

Neurology_Adams. Gangliogliomas and mixed neuronal–glial tumors are special tumor types, more frequent in the young and of variable but usually low-grade malignancy. They are composed both of differentiated glial cells, usually astrocytes, and of neurons in various degrees of differentiation. The latter, which may resemble glial cells, can be identified by Nissl stains, silver stains, and immunochemical reactions for cytoskeletal proteins. Inflammation is common in the parenchyma and adjacent to these tumors; this has led to the erroneous diagnosis of a nonneoplastic inflammatory condition if only limited biopsy samples are taken. Some of these developmental tumors are difficult to separate from hamartomas or from the tubers of tuberous sclerosis. In the case of hamartomas, it may be difficult to determine if the tumor or the associated developmental abnormality is the cause of seizures. Some of these tumors take the form of large, slowly growing cystic lesions.


Neurology_Adams

Neurology_Adams. The best characterized, albeit rare, type in this group is the gangliocytoma, a tumor that occurs in the adrenal gland, retroperitoneal and thoracic sympathetic chain, internal auditory canal, and in the spinal cord. One form is the dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). This is a slowly evolving lesion that forms a mass in the cerebellum; it is composed of granule, Purkinje, and glia cells. Reproduced therein, in a disorganized fashion, is the architecture of the cerebellum with no clear plane from normally structured cerebellar tissue. The importance of distinguishing this disease from other cerebellar tumors is its lack of growth potential and favorable prognosis. It is, however, excised if symptomatic. The appearance on imaging is highly characteristic; a cerebellar hemisphere is occupied with an indistinct mass of “tiger stripe” appearance as a result of alternating layers of dysmorphic cerebellar cells (Fig. 30-16). Interest in this entity derives


Neurology_Adams

Neurology_Adams. a cerebellar hemisphere is occupied with an indistinct mass of “tiger stripe” appearance as a result of alternating layers of dysmorphic cerebellar cells (Fig. 30-16). Interest in this entity derives from its association with a germ line mutation in the PTEN gene that relates the disease to other gangliocytomas and to Cowden syndrome of multiple skin hamartomas and cancers of the gynecologic, breast, and thyroid glands (and which may include Lhermitte-Duclos as a component). Mice with PTEN knocked-out have abnormal synaptic structure and dysplasia of the cerebellar granule cells.


Neurology_Adams

Neurology_Adams. Other forms of gangliogliomas include the desmoplastic infantile ganglioglioma, some of the xanthoastrocytomas, and the dysembryoplastic neuroepithelioma tumor (DNET), not all of which are included in newer classifications.


Neurology_Adams

Neurology_Adams. This last of these tumors, DNET, is worthy of comment as it often causes seizures that may be difficult to control in children. We have encountered them mostly in young adults after a single seizure or as an incidental finding on MRI. Although the tumors may be located in any part of the brain, there is a proclivity for the superficial (juxtacortical or intracortical) lateral or medial temporal lobe. The radiologic appearance is usually of a nodule or small cyst, or more specific to this entity, a cluster of several adjacent small cystic lesions, generally not enhancing and hyperintense on T2-weighted MRI (Fig. 30-17). The lesion is very slow growing and, if appropriately situated, may remodel the bone of the orbital roof or calvarium. The tumors originate from dysplastic cells in the germinal matrix that become arrested during migration toward the cortex; they are often associated with an adjacent region of cortical heterotopia. The histologic appearance varies but has as its main


Neurology_Adams

Neurology_Adams. matrix that become arrested during migration toward the cortex; they are often associated with an adjacent region of cortical heterotopia. The histologic appearance varies but has as its main element a collection of neuroepithelial cells and clusters of oligodendrocytes with multinodular architecture that create mucinous cysts in some cases. When the lesion is single and has a nonspecific radiologic appearance, a biopsy or resection is required to differentiate it from a low-grade glioma or oligodendroglioma. Biopsy alone may be misleading in showing only the adjacent inflammation, at times prominent enough to appear almost granulomatous. Resection is curative and often eliminates the seizures but it is not clear what the best course of action is for asymptomatic lesions.


Neurology_Adams

Neurology_Adams. Another tumor that may be considered in this group is the subependymal giant cell astrocytoma that is found in up to 20 percent of patients with tuberous sclerosis. These are very slowly growing tumors that arise mostly near the foramen of Munro. Repeated resection is sometimes required to treat the hydrocephalus caused by the location of the tumor at the point of egress of CSF from the lateral ventricle. Krueger and colleagues, and subsequently others, have reported that everolimus, an inhibitor of the mTOR complex, which is disrupted in this phakomatosis, reduces the size of the tumor and ameliorates seizures. The remaining tumors mentioned earlier are rare and affect children mostly; therefore, they are not discussed further. Descriptions are to be found in the monographs of Russell, of Rubinstein (1972), of Levine (both articles from 1993), and of Schmidek, and in the article by Zentner and coworkers. Colloid Cyst and Other Tumors of the Third Ventricle


Neurology_Adams

Neurology_Adams. Colloid Cyst and Other Tumors of the Third Ventricle The most important of these is the colloid tumor, which is derived from ependymal cells of a vestigial third ventricular structure known as the paraphysis. The cysts formed in this structure are always situated in the anterior portion of the third ventricle between the interventricular foramina and are attached to the roof of the ventricle (Fig. 30-18). They vary from 1 to 4 cm in diameter, are oval or round with a smooth external surface, and are filled with a gelatinous material containing a variety of mucopolysaccharides. The wall is composed of a layer of epithelial cells, some ciliated, surrounded by a capsule of fibrous connective tissue. Although congenital, the cysts practically never declare themselves clinically until adult life, when they block CSF outflow through the foramen of Monro and produce an obstructive hydrocephalus.


Neurology_Adams

Neurology_Adams. Suspicion of this tumor is occasioned by intermittent, severe bifrontal–bioccipital headaches, sometimes modified by posture (“ball valve” obstruction) or with crises of headache and obtundation, incontinence, unsteadiness of gait, bilateral paresthesias, dim vision, and weakness of the legs, with sudden falls but no loss of consciousness (“drop attacks”). Stooping may result in an increase or onset of headache and loss of balance. However, this intermittent obstructive syndrome has been infrequent in our experience. More often the patient has no headache and presents with the symptoms comparable to those of normal-pressure hydrocephalus or, as frequently, the tumor is found incidentally on CT or MRI. On CT and MRI, the lesion density depends on the hydration state of the mucopolysaccharides. These lesions do not restrict diffusion or enhance with contrast. Subtle behavioral changes are common and a few patients, as emphasized by Lobosky and colleagues, experience mild confusion and


Neurology_Adams

Neurology_Adams. These lesions do not restrict diffusion or enhance with contrast. Subtle behavioral changes are common and a few patients, as emphasized by Lobosky and colleagues, experience mild confusion and changes in personality that may reach the extreme of psychotic behavior. We have no experience with this constellation and find it difficult to understand from the location of the lesion or from hydrocephalus; in our experience, chronic headache or gait difficulty is usually present.


Neurology_Adams

Neurology_Adams. The treatment for many years has been surgical excision, which carries some risk, far less than in the past, but satisfactory results have also been obtained by ventriculoperitoneal shunting of the CSF, leaving the cyst untouched. Decompression of the cyst by aspiration under stereotactic control has also become a popular procedure. Other tumors found in the third ventricle and giving rise mainly to obstructive symptoms are craniopharyngiomas (see later), papillomas of the choroid plexus, and ependymomas (discussed earlier).


Neurology_Adams

Neurology_Adams. This CSF-filled lesion, which is probably congenital, presents clinically at all ages but may become evident only in adult life, when it gives rise to symptoms of increased intracranial pressure and sometimes to focal cerebral or cerebellar signs, simulating intracranial neoplasm. Seizures may occur but are not characteristic. In infants and young children, macrocrania and extensive unilateral transillumination are characteristic features. Usually these cysts overlie the sylvian fissure or temporal pole; occasionally they are interhemispheric under the frontal lobes or lie in the pineal region or under the cerebellum. They may attain a large size, to the point of enlarging the middle cranial fossa and remodeling and elevating the lesser wing of the sphenoid, but they do not communicate with the ventricles. Rarely, one of these cysts may cover the entire surface of both cerebral hemispheres and create a so-called external hydrocephalus.


Neurology_Adams

Neurology_Adams. The cysts are readily recognized (often accidentally) on unenhanced CT or MRI, showing a circumscribed tissue defect filled with fluid that has the density of CSF (Gandy and Heier). If these cysts are completely asymptomatic, they should be left alone; if symptomatic, additional MRI studies are indicated, so as not to overlook a chronic subdural hematoma, which is often associated and may not be visualized on the unenhanced CT. Suprasellar arachnoid cysts are discussed further on, under “Empty Sella Syndrome.” The treatment of enlarging and symptomatic cysts is marsupialization or, less preferably, by shunting from the cyst to the subarachnoid space.


Neurology_Adams

Neurology_Adams. The treatment of enlarging and symptomatic cysts is marsupialization or, less preferably, by shunting from the cyst to the subarachnoid space. Skull Base and Other Regional Intracranial Tumor Syndromes (Vestibular Schwannoma, Other Tumors of the Cerebellopontine Angle, Craniopharyngioma, Pituitary, Meningioma of the Sphenoid Ridge and Olfactory Groove, Glioma of the Optic Nerve, Pontine Glioma, Chordoma Chondrosarcoma, Glomus Jugulare and Carotid Body Tumors, Nasopharyngeal Carcinoma)


Neurology_Adams

Neurology_Adams. In this group of tumors, symptoms and signs of general cerebral impairment and increased pressure occur late or not at all. Instead, special syndromes referable to particular intracranial loci arise and progress slowly. One arrives at the correct diagnosis by localizing the lesion accurately from the neurologic findings and by reasoning that the etiology must be neoplastic because of an afebrile and steadily progressive nature. Investigation by CT, MRI, and other special studies will usually confirm the clinical impression. The tumors that most often produce these unique intracranial syndromes are the ones listed above as well as a number of other erosive tumors at the base of the skull. The aforementioned medulloblastoma, hemangioblastoma, and ependymoma of the fourth ventricle may have a similar regional clinical signature.


Neurology_Adams

Neurology_Adams. This tumor was first described as a pathologic entity by Sandifort in 1777, diagnosed clinically by Oppenheim in 1890, and recognized as a surgically treatable disease in the early 1900s. Cushing’s monograph (1917) was a milestone, and the papers of House and Hitselberger and of Ojemann and colleagues provide valuable descriptions of from the era before modern imaging.


Neurology_Adams

Neurology_Adams. Approximately 3,000 new cases of acoustic neuroma are diagnosed each year in the United States (incidence rate of 1 per 100,000 per year). The tumor occurs occasionally as part of von Recklinghausen neurofibromatosis, in which case it takes one of two forms. In classic von Recklinghausen disease (peripheral or type 1 neurofibromatosis), a schwannoma may sporadically involve the eighth nerve, usually in adult life, but it may involve any other cranial (particularly trigeminal) or spinal nerve root. Rarely, if ever, do bilateral acoustic neuromas occur in this form of the disease. However, bilateral acoustic neuromas are the hallmark of the genetically distinct neurofibromatosis type 2 (NF2), in which they practically always occur before the age of 21 and show a strong (autosomal dominant) heredity (Fig. 30-19). Schwannomas are distinguished from neurofibromas (composed of both Schwann cells and fibroblasts) found in peripheral nerves of type 1 von Recklinghausen disease. A small


Neurology_Adams

Neurology_Adams. heredity (Fig. 30-19). Schwannomas are distinguished from neurofibromas (composed of both Schwann cells and fibroblasts) found in peripheral nerves of type 1 von Recklinghausen disease. A small percentage of neurofibromas become malignant, a phenomenon that is highly unusual in schwannomas.


Neurology_Adams

Neurology_Adams. In this context, a rare form of familial schwannomatosis should be mentioned, characterized by multiple schwannomas without vestibular tumors, which maps genetically to chromosome 22 but is distinct from NF2. The primary gene defect in this familial schwannomatosis has not been defined (MacCollin et al), although mutations in the SMARCB1 gene on chromosome 22 locus have been identified in some patients.


Neurology_Adams

Neurology_Adams. The typical vestibular schwannoma in adults presents as a solitary tumor. Being a schwannoma, it originates in nerve. The examination of small tumors reveals that they practically always arise from the vestibular rather than the cochlear division of the eighth nerve, just within the internal auditory canal (Fig. 30-19). As the eighth nerve schwannoma grows, it extends into the posterior fossa to occupy the angle between the cerebellum and pons (cerebellopontine angle). In this lateral position, it is so situated as to compress the seventh, fifth, and less often the ninth and tenth cranial nerves, which are implicated in various combinations. Later it displaces and compresses the pons and lateral medulla and obstructs the CSF circulation; very rarely, it is a source of subarachnoid hemorrhage.


Neurology_Adams

Neurology_Adams. Certain biologic and clinical data assume clinical importance. The highest incidence is in the fifth and sixth decades of life, and the sexes are equally affected. Familial occurrence is a mark, usually, of von Recklinghausen disease. The earliest symptom reported by the 46 patients in the decades-old but instructive series of Ojemann and coworkers was loss of hearing (33 of 46 patients); headache (4 patients); disturbed sense of balance (3 patients); unsteadiness of gait (3 patients); and facial pain, tinnitus, and facial weakness, each in a single case. Some patients sought medical advice soon after the appearance of the initial symptom, some later, after other symptoms had occurred. One-third of the patients were troubled by vertigo associated with nausea, vomiting, and pressure in the ear. The vertiginous symptoms differed from those of Ménière disease in that discrete attacks separated by periods of normalcy were rare. The vertigo coincided more or less with hearing loss and


Neurology_Adams

Neurology_Adams. the ear. The vertiginous symptoms differed from those of Ménière disease in that discrete attacks separated by periods of normalcy were rare. The vertigo coincided more or less with hearing loss and tinnitus (most often a unilateral high-pitched ringing, sometimes a machinery-like roaring or hissing sound, like that of a steam kettle). Some of our patients ignored their deafness for many months or years; often the first indication of the tumor in such patients is a shift to the unaccustomed ear (usually right to left) in the use of the telephone. Others neglected these symptoms to a point where they presented with impaired mentation, imbalance, and sphincteric incontinence because of brainstem compression and secondary hydrocephalus.


Neurology_Adams

Neurology_Adams. The neurologic findings at the time of examination in the series mentioned above were as follows: eighth nerve involvement (auditory and vestibular; 45 of 46 patients), facial weakness including disturbance of taste (26 patients), sensory loss over the face (26 patients), gait abnormality (19 patients), and unilateral ataxia of the limbs (9 patients). Inequality of reflexes and 11thand 12th-nerve palsies were present in only a few patients. Signs of increased intracranial pressure appear late and have been present in fewer than 25 percent of our patients. These findings are comparable to those reported by House and Hitselberger many years ago and, more contemporarily, by Harner and Laws. With the shift in recent years to fairly routine investigation of unilateral hearing loss by cerebral imaging, it is common to find these tumors at a far earlier stage, if as an incidental finding on cerebral imaging, well before the tumor becomes symptomatic.


Neurology_Adams

Neurology_Adams. The contrast-enhanced CT will detect practically all vestibular schwannomas that are larger than 2.0 cm in diameter and project further than 1.5 cm into the cerebellopontine angle. Much smaller intracanalicular tumors (i.e., restricted to within the internal acoustic canal) can be detected reliably by MRI with gadolinium (Fig. 30-20). Specialized thin-slice MRI sequences such as steady-state free precession can accurately define anatomic relationships between the tumor and adjacent cranial nerves and vessels with high resolution.


Neurology_Adams

Neurology_Adams. Audiologic and vestibular evaluation includes the various tests described in Chap. 14, the brainstem auditory evoked response probably being the most sensitive to the presence of acoustic schwannoma. In combination, they permit localization of the deafness and vestibular disturbance to the cochlear and vestibular nerves rather than to their end organs. The CSF protein is raised in two-thirds of the patients (greater than 100 mg/dL in one-third); a clinically inevident acoustic schwannoma is one of the causes of an unexpectedly elevated CSF protein when a lumbar puncture is performed for other reasons.


Neurology_Adams

Neurology_Adams. Treatment The preferred treatment in most symptomatic cases has been surgical excision. Neurosurgeons who have had a lot of experience with these tumors favor a microsurgical suboccipital transmeatal approach (Martuza and Ojemann). The facial nerve can usually be preserved by intraoperative monitoring of brainstem auditory responses and facial nerve electromyography (EMG); in experienced hands, hearing can be preserved in approximately one-third of patients with tumors smaller than 2.5 cm in diameter. If no attempt is to be made to save hearing, small tumors can be removed safely by the translabyrinthine approach.


Neurology_Adams

Neurology_Adams. An alternative to surgery is focused radiation, which controls the growth of many of the smaller tumors. In a large series of patients treated with radiosurgery, facial motor and sensory functions were preserved in 75 percent of cases and, after 28 months of observation, no new neurologic deficits were detected (Kondziolka et al). This approach is favored in older patients with few symptoms but is being adopted increasingly for others. The rates of hearing loss and facial numbness and weakness are comparable or lower than with surgery, but the follow-up period in most series is less than 5 years (Flickinger et al). Focused radiation with the Gamma Knife or proton beam also appears to be preferable to surgery in cases of recurrent tumor. The antiangiogenic agent, bevacizumab, in preliminary reports has reduced the size of these tumors in patients with NF2 (Plotkin et al).


Neurology_Adams

Neurology_Adams. There is no consensus on the management of an incidentally identified tumor but it is reasonable to follow these with audiograms and serial imaging. Some authoritative sources suggest that half of lesions smaller than 2 cm in diameter will not progress, or do so slowly enough that hearing and balance are not impaired. However, lesions larger than this size are associated with more surgical complications and make sparing of hearing less likely. Other Tumors of the Cerebellopontine Angle


Neurology_Adams

Neurology_Adams. Neurinoma or schwannoma of the trigeminal (gasserian) ganglion or neighboring cranial nerves and meningioma of the cerebellopontine angle may, in some instances, be indistinguishable from a vestibular schwannoma. Fifth cranial nerve tumors should always be considered if deafness, tinnitus, and lack of response to caloric stimulation (“dead labyrinth”) are not the initial symptoms of a cerebellopontine angle syndrome. A true cholesteatoma (epidermoid cyst) is a relatively rare tumor that is most often located in the cerebellopontine angle where it may simulate an acoustic neuroma but usually causes more severe facial weakness. Spillage of the contents of the cyst may produce intense chemical meningitis. Other disorders that enter into the differential diagnosis are glomus jugulare tumor (see later), metastatic cancer, neoplastic meningitis (especially lymphomatous), syphilitic meningitis, arachnoid cyst, and epidural plasmacytoma of the petrous bone. All these disorders may produce a


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Neurology_Adams. later), metastatic cancer, neoplastic meningitis (especially lymphomatous), syphilitic meningitis, arachnoid cyst, and epidural plasmacytoma of the petrous bone. All these disorders may produce a cerebellopontine angle syndrome consisting of imbalance and unilateral hearing loss, but they are more likely to cause multiple lower cranial neuropathies and their temporal course differs from that of vestibular schwannoma. Occasionally, a tumor that originates in the pons or in the fourth ventricle (ependymoma, astrocytoma, papilloma, medulloblastoma) or a nasopharyngeal carcinoma may present as a cerebellopontine angle syndrome.


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Neurology_Adams. Craniopharyngioma (Suprasellar Epidermoid Cyst, Rathke Pouch or Hypophyseal Duct Tumor, Adamantinoma) This is a histologically benign epithelioid tumor, generally assumed to originate from cell rests (remnants of the Rathke pouch [or adenohypophyseal diverticulum]) at the junction of the infundibular stem and pituitary gland. By the time the tumor has attained a diameter of 3 to 4 cm, it is almost always cystic and partly calcified. Usually it lies above the sella turcica, compressing and elevating the optic chiasm and extending up into the third ventricle. Less often it is subdiaphragmatic, that is, within the sella, where it compresses the pituitary body and erodes one part of the wall of the sella or a clinoid process; seldom it balloons the sella like a pituitary adenoma. Large tumors may obstruct the flow of CSF.


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Neurology_Adams. The tumor is oval, round, or lobulated and has a smooth surface. The wall of the cyst and the solid parts of the tumor consist of cords and whorls of epithelial cells (often with intercellular bridges and keratohyalin) separated by a loose network of stellate cells. If there are bridges between tumor cells, which have an epithelial origin, the tumor had in the past been classed as an adamantinoma, a term not used in recent classifications. The cyst contains dark albuminous fluid, cholesterol crystals, and calcium deposits; the calcium can be seen in plain films or CT of the suprasellar region in 70 to 80 percent of cases. The sella beneath the tumor tends to be flattened and enlarged. The majority of the patients are children, but the tumor is not infrequent in adults, and we have encountered patients up to 60 years of age.


Neurology_Adams

Neurology_Adams. The presenting syndrome may be one of increased intracranial pressure, but more often it takes the form of a combined pituitary-hypothalamic-chiasmal derangement. The symptoms are often subtle and long standing. In children, visual loss and diabetes insipidus are the most frequent findings, followed in a few cases by adiposity, delayed physical and mental development, headaches, and vomiting. The visual disorder takes the form of dim vision, chiasmal field defects, optic atrophy, or papilledema, as emphasized long ago by Kennedy and Smith. In adults, waning libido, amenorrhea, slight spastic weakness of one or both legs, headache without papilledema, failing vision, and mental dullness and confusion are the usual manifestations. One of the most remarkable cases in our experience was a middle-aged nurse who became distractible and ineffective at work and was thought for many months to be simply depressed. Often it is observed that drowsiness, ocular palsies, diabetes insipidus, and


Neurology_Adams

Neurology_Adams. middle-aged nurse who became distractible and ineffective at work and was thought for many months to be simply depressed. Often it is observed that drowsiness, ocular palsies, diabetes insipidus, and disturbance of temperature regulation (indicating hypothalamic involvement) occur later. Spontaneous rupture of the cystic lesion can incite severe aseptic meningitis, at times with depressed glucose in the CSF, a syndrome similar to that caused by rupture of the earlier described cholesteatoma.


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Neurology_Adams. In the differential diagnosis of the several craniopharyngioma syndromes, a careful clinical analysis is often more informative than laboratory procedures. Among the latter, MRI is likely to give the most useful information. Often, because of the cholesterol content, the tumor gives an increased signal on T1-weighted images. Usually, the cyst itself is isointense, like CSF, but occasionally it may give a decreased T2 signal.


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Neurology_Adams. Treatment Modern microsurgical techniques, reinforced by corticosteroid therapy before and after surgery and careful control of temperature and water balance postoperatively, permit successful excision of all or part of the tumor in the majority of cases. Although smaller tumors can be removed by a transsphenoidal approach, attempts at total removal require craniotomy and remain a challenge because of frequent adherence of the mass to surrounding structures (Fahlbusch et al), as well as the potential for postoperative chemical meningitis from cyst contents. Partial removal practically ensures recurrence of the tumor, usually within 3 years, and the surgical risks of reoperation are considerable (10 percent mortality in large series). Stereotactic aspiration is sometimes a useful palliative procedure, as are focused radiation therapy and ventricular shunting in patients with solid, nonresectable tumors. Endocrine replacement is necessary for an indefinite time. We have several times


Neurology_Adams

Neurology_Adams. procedure, as are focused radiation therapy and ventricular shunting in patients with solid, nonresectable tumors. Endocrine replacement is necessary for an indefinite time. We have several times seen a syndrome of prolonged but reversible delirium after tumor resection.


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Neurology_Adams. Glomus jugulare tumor This tumor is relatively rare but of interest to neurologists. It is one of the paragangliomas, so classified because of their location in the paraganglia of the sympathetic nervous system, thereby relating it to the carotid body tumor discussed next. It is a purplish red, highly vascular tumor composed of large epithelioid cells, arranged in an alveolar pattern and possessing an abundant capillary network. The tumor is thought to be derived from minute clusters of nonchromaffin paraganglioma cells (glomus bodies) found mainly in the adventitia of the dome of the jugular bulb (glomus jugulare) immediately below the floor of the middle ear, as well as in multiple other sites in and around the temporal bone. These clusters of cells are part of the chemoreceptor system that also includes the carotid, vagal, ciliary, and aortic bodies. Individuals living at high altitudes have a higher incidence than those at sea level owing to stimulation of the chemoreceptors from


Neurology_Adams

Neurology_Adams. that also includes the carotid, vagal, ciliary, and aortic bodies. Individuals living at high altitudes have a higher incidence than those at sea level owing to stimulation of the chemoreceptors from hypoxia. About one-quarter are familial, several genes having been identified.


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Neurology_Adams. The fully developed syndrome consists of partial deafness, facial palsy, dysphagia, and unilateral atrophy of the tongue combined with a vascular polyp in the external auditory meatus and a palpable mass below and anterior to the mastoid eminence, occasionally with a bruit that may be audible to the patient (“self-audible bruit”). Other neurologic manifestations are phrenic nerve palsy, numbness of the face, a Horner syndrome, cerebellar ataxia, and temporal lobe epilepsy. As with vestibular schwannoma, the availability of MRI has led to the earlier discovery of these tumors.


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Neurology_Adams. The jugular foramen is eroded and CSF protein may be elevated. Women are affected more than men, and the peak incidence is during middle adult life. The tumor grows slowly over a period of many years, sometimes 10 to 20 or more. Treatment in the past has consisted of radical mastoidectomy and removal of as much tumor as possible, followed by radiation. The combined intracranial and extracranial two-stage operation has resulted in the cure of many cases (Gardner et al). Embolization prior to resection is now also employed. A detailed account of this tumor can be found in the article by Kramer.


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Neurology_Adams. Carotid body tumor This is a generally benign but potentially malignant tumor originating in a small aggregate of paraganglioma cells of neuroectodermal type. The normal carotid body is small (4 mm in greatest diameter and 10 mg in weight) and is located at the bifurcation of the common carotid artery. The cells are of uniform size, have an abundant cytoplasm, are rich in substance P, and are sensitive to changes in Po2, Pco2, and pH (i.e., they are chemoreceptors, not to be confused with baroreceptors). The tumors that arise from these cells are identical in appearance to tumors of other chemoreceptor organs such as the glomus jugulare neoplasm described in the preceding section (paragangliomas). Interestingly, they are many times more frequent in individuals living at high altitudes.


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Neurology_Adams. The usual presentation is of a painless mass at the side of the neck below the angle of the jaw; thus it must be differentiated from the branchial cleft cyst, mixed tumor of the salivary gland, and carcinomas and aneurysms in this region. As the tumor grows (at an estimated rate of 2.0 cm in diameter every 5 years) it may implicate the sympathetic, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves (syndrome of the retroparotid space; see Chap. 47). Hearing loss, tinnitus, and vertigo are present in some cases. Tumors of the carotid body have been a source of transient ischemic attacks in 5 to 15 percent of the 600 or more reported cases. One of the most interesting presentations has been with sleep apnea, particularly with bilateral tumors (see later); respiratory depression as well as lability of blood pressure are common postoperative problems. Malignant transformation occurs in 5 percent of cases.


Neurology_Adams

Neurology_Adams. A similar paraganglioma of the vagus nerve has been reported; it occurs typically in the jugular or nodose ganglion but may arise anywhere along the course of the nerve. These tumors may also undergo malignant transformation in about 5 percent of cases, metastasize, or invade the base of the skull. Carotid body tumor has been seen in combination with von Recklinghausen neurofibromatosis type 1 (NF1) and in von Hippel-Lindau disease. Familial cases are known, especially with bilateral carotid body tumors (about 5 percent of these tumors are bilateral). The treatment is surgical excision with or without prior intravascular embolization; radiation therapy has not been advised. Pituitary Adenoma (See Also “Pituitary Insufficiency” in Chap. 26)


Neurology_Adams

Neurology_Adams. Pituitary Adenoma (See Also “Pituitary Insufficiency” in Chap. 26) Tumors arising in the anterior pituitary are of considerable interest to neurologists because they often cause visual and other symptoms related to involvement of structures bordering upon the sella turcica, before an endocrine disorder becomes apparent. Pituitary tumors are age-linked; they become increasingly numerous with each decade. By the eightieth year, small adenomas are found in more than 20 percent of pituitary glands. In some cases, an apparent stimulus to adenoma formation is endocrine end-organ failure, as occurs, for example, with ovarian atrophy that induces a basophilic adenoma. Only a small proportion (6 to 8 percent) enlarge the sella, that is, most are “microadenomas,” as discussed below.


Neurology_Adams

Neurology_Adams. On the basis of conventional hematoxylin-eosin-staining methods, cells of the normal pituitary gland were for many years classified as chromophobe, acidophil, and basophil, these types being present in a ratio of 5:4:1. Adenomas of the pituitary are most often composed of chromophobe cells (4 to 20 times as common as acidophil cell adenomas); the incidence of basophil cell adenomas is uncertain. Histologic study is now based on immunoperoxidase-staining techniques that define the nature of the hormones within the pituitary cells—both of the normal gland and of pituitary adenomas. These methods have shown that either a chromophobe or an acidophil cell may produce prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH), whereas the basophil cells produce adrenocorticotropic hormone (ACTH), β-lipotropin, luteinizing hormone (LH), and follicle- stimulating hormone (FSH).


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Neurology_Adams. The development of sensitive methods for the measurement of pituitary hormones in the serum has made possible the detection of adenomas at an early stage of their development and the designation of several types of pituitary adenomas on the basis of the endocrine disturbance. Hormonal tests for the detection of pituitary adenomas, preferably carried out in an endocrine clinic, are listed in Table 30-4. Between 60 and 70 percent of tumors in both men and women are prolactin secreting. About 10 to 15 percent secrete growth hormone, and a smaller number secrete ACTH. Tumors that secrete gonadotropins and TSH are quite rare. These tumors may be monohormonal or plurihormonal and approximately one-third are composed of nonfunctional (null) cells.


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Neurology_Adams. Pituitary tumors usually arise as discrete nodules in the anterior part of the gland (adenohypophysis). They are reddish gray, soft (almost gelatinous), and often partly cystic, with a rim of calcium in some instances. The adenomatous cells are arranged diffusely or in various patterns, with little stroma and few blood vessels; less frequently the architecture is sinusoidal or papillary in type. Variability of nuclear structure, hyperchromatism, cellular pleomorphism, and mitotic figures are interpreted as signs of malignancy, which is exceedingly rare. Tumors less than 1 cm in diameter are referred to as microadenomas and are at first confined to the sella. As the tumor grows, it first compresses the pituitary gland; then, as it extends upward and out of the sella, it compresses the optic chiasm; later, with continued growth, it may extend into the cavernous sinus, third ventricle, temporal lobes, or posterior fossa. Recognition of an adenoma when it is still confined to the sella is


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Neurology_Adams. chiasm; later, with continued growth, it may extend into the cavernous sinus, third ventricle, temporal lobes, or posterior fossa. Recognition of an adenoma when it is still confined to the sella is of considerable practical importance, since total removal of the tumor by transsphenoidal excision or some form of stereotactic radiosurgery is possible at this stage with prevention of further damage to normal glandular structure and the optic chiasm. Penetration of the diaphragm sellae by the tumor and invasion of the surrounding structures make treatment more difficult.


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Neurology_Adams. Pituitary adenomas come to medical attention because of endocrine or visual abnormalities. Headaches are reported by nearly half of patients with macroadenomas but are not clearly part of the syndrome. The visual disorder usually proves to be a complete or partial bitemporal hemianopia, which has developed gradually and may not be evident to the patient (see the description of the chiasmatic syndromes in “Neurologic Causes of Reduced Vision” in Chap. 12). Early on, the upper parts of the visual fields may be affected predominantly, since those fibers run along the inferior optic nerve and chiasm. A small number of patients will be almost blind in one eye and have a temporal hemianopia in the other. Bitemporal central hemianopic scotomata are a less-frequent finding. A postfixed (situated relatively posteriorly) chiasm may be compressed in such a way that there is an interruption of some of the nasal retinal fibers, which, as they decussate, project into the base of the opposite optic


Neurology_Adams

Neurology_Adams. relatively posteriorly) chiasm may be compressed in such a way that there is an interruption of some of the nasal retinal fibers, which, as they decussate, project into the base of the opposite optic nerve (Wilbrand knee); the controversy regarding the validity of this projection in humans is mentioned in Chap. 12. This results in a central scotoma on one or both sides (junctional syndrome) in addition to the classic temporal field defect (see Fig. 12-3).


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Neurology_Adams. If the visual disorder is longstanding, the optic nerve heads are atrophic. In 5 to 10 percent of cases, the pituitary adenoma extends into the cavernous sinus, causing some combination of ocular motor palsies as well as potential compression of the cavernous segment of the internal carotid artery. Other neurologic abnormalities, rare to be sure, are seizures from indentation of the medial temporal lobe, CSF rhinorrhea from erosion of the sella, and diabetes insipidus, hypothermia, and somnolence from hypothalamic compression.


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Neurology_Adams. With regard to differential diagnosis, bitemporal hemianopia with a normal-size sella indicates that the causative lesion is probably a saccular aneurysm of the circle of Willis or a meningioma of the tuberculum sellae; multiple sclerosis may simulate this pattern and eventration of a greatly hydrocephalic third ventricle is an uncertain cause (see Chap. 12). The idiopathic syndrome of an “empty sella” also can cause bitemporal hemianopia and is discussed further on.


Neurology_Adams

Neurology_Adams. The major endocrine syndromes associated with pituitary adenomas are described briefly in the following pages. Their functional classification can be found in the monograph edited by Kovacs and Asa. A detailed discussion of the diagnosis and management of hormone-secreting pituitary adenomas is given in the reviews of Klibanski and Zervas and of Pappas and colleagues; recommended also is an article that details the neurologic features of pituitary tumors by Anderson and colleagues. Worthy of emphasis is the catastrophic syndrome of pituitary apoplexy discussed further on.


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Neurology_Adams. Amenorrhea-galactorrhea syndrome As a rule, this syndrome becomes manifest during the childbearing years. The history usually discloses that menarche had occurred at the appropriate age; primary amenorrhea is rare. A common history is that the patient took birth control pills, only to find, when she stopped, that the menstrual cycle did not reestablish itself. On examination, there may be no abnormalities other than galactorrhea. Serum prolactin concentrations are increased (usually in excess of 100 ng/mL). In general, the longer the duration of amenorrhea and the higher the serum prolactin level, the larger the tumor (prolactinoma). The elevated prolactin levels distinguish this disorder from idiopathic galactorrhea, in which the serum prolactin concentration is normal.


Neurology_Adams

Neurology_Adams. Males with prolactin-secreting tumors rarely have galactorrhea and usually present with a larger tumor and complaints such as headache, impotence, and visual abnormalities. In normal persons, the serum prolactin rises markedly in response to the administration of chlorpromazine or thyrotropin-releasing hormone (TRH); patients with a prolactin-secreting tumor fail to show such a response. With large tumors that compress normal pituitary tissue, thyroid and adrenal function will also be impaired. It should be emphasized that large, nonfunctioning pituitary adenomas also cause modest hyperprolactinemia by distorting the pituitary stalk and reducing dopamine delivery to prolactin-producing cells.


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Neurology_Adams. Acromegaly This disorder consists of acral growth and prognathism in combination with visceromegaly, headache, and several endocrine disorders (hypermetabolism, diabetes mellitus). The highly characteristic facial and bodily appearance, well known to all physicians, is caused by an overproduction of GH after puberty; prior to puberty, an oversecretion of GH leads to gigantism. In a small number of acromegalic patients, there is an excess secretion of both GH and prolactin, derived apparently from two distinct populations of tumor cells. The diagnosis of this disorder, which is often long delayed, is made on the basis of the characteristic clinical changes, the finding of elevated serum GH values (0.10 ng/mL), and the failure of the serum GH concentration to decline in response to the administration of glucose or TRH. The new growth hormone-receptor antagonist pegvisomant was introduced to reduce many of the manifestations of acromegaly (see the review by Melmed).


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Neurology_Adams. Cushing disease Described in 1932 by Cushing, this condition is only about one-fourth as frequent as acromegaly. A distinction is made between Cushing disease and Cushing syndrome, as indicated in Chap. 26. The former term is reserved for cases that are caused by the excessive secretion of pituitary ACTH, which, in turn, causes adrenal hyperplasia; the usual basis is a pituitary adenoma. Cushing syndrome refers to the effects of cortisol excess from any one of several sources—excessive administration of steroids (the most common cause), adenoma of the adrenal cortex, ACTH-producing bronchial carcinoma, and, very rarely, other carcinomas that produce ACTH. The clinical effects are the same in all of these disorders and include truncal obesity, hypertension, proximal muscle weakness, amenorrhea, hirsutism, abdominal striae, hyperglycemia, osteoporosis, and in some cases a characteristic mental disorder (see “Cushing Disease and Corticosteroid Psychoses” in Chap. 49).


Neurology_Adams

Neurology_Adams. Although Cushing originally referred to the disease as pituitary basophilism and attributed it to a basophil adenoma, the pathologic change may consist only of hyperplasia of basophilic cells or of a nonbasophilic microadenoma. Seldom is the sella turcica enlarged: Consequently, visual symptoms or signs as a result of involvement of the optic chiasm or nerves and extension to the cavernous sinus are rare. The diagnosis of Cushing disease is made by demonstrating increased concentration of plasma and urinary cortisol; these levels are not suppressed by the administration of relatively small doses of dexamethasone (0.5 mg qid), but they are suppressed by high doses (8 mg daily). A low level of ACTH and a high level of cortisol in the blood, increased free cortisol in the urine, and nonsuppression of adrenal function after administration of high doses of dexamethasone are evidence of an adrenal source of the Cushing syndrome—usually a tumor and less often a micronodular hyperplasia of


Neurology_Adams

Neurology_Adams. of adrenal function after administration of high doses of dexamethasone are evidence of an adrenal source of the Cushing syndrome—usually a tumor and less often a micronodular hyperplasia of the adrenal gland.


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Neurology_Adams. Diagnosis of pituitary adenoma This is virtually certain when a chiasmal syndrome is combined with an endocrine syndrome of either hypopituitary or hyperpituitary type. Laboratory data that are confirmatory of an endocrine disorder, as described above, and sometimes a ballooned sella turcica on plain films of the skull are occasionally found. Patients who are suspected of having a pituitary adenoma should be examined by MRI with gadolinium; this procedure will visualize pituitary adenomas as small as 3 mm in diameter and show the relationship of the tumor to the optic chiasm (Fig. 30-21). This also provides the means of following the tumor’s response to therapy. It should be kept in mind that pituitary tissue normally enhances on CT and MRI, revealing small tumors as relatively hypoenhancing nodules.


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Neurology_Adams. Tumors and lesions other than pituitary adenomas may sometimes expand the sella. Enlargement may be the result of an intrasellar craniopharyngioma, meningioma, carotid aneurysm, or cyst of the pituitary gland. Intrasellar epithelium-lined cysts are rare lesions. They originate from the apex of the Rathke pouch, which may persist as a cleft between the anterior and posterior lobes of the hypophysis. Rarer still are intrasellar cysts that have no epithelial lining and contain thick, dark brown fluid, the product of intermittent hemorrhages. Both types of intrasellar cysts may compress the pituitary gland and mimic the endocrine-suppressive effects of pituitary adenomas. Neoplasms originating in the nasopharynx or sinuses may invade the sella and pituitary gland, and sarcoid lesions at the base of the brain may do the same. Also, the pituitary gland and the infundibulum (and the chiasm) may be the site of metastases, most of them from the lung and breast (Morita et al); they give rise to


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Neurology_Adams. of the brain may do the same. Also, the pituitary gland and the infundibulum (and the chiasm) may be the site of metastases, most of them from the lung and breast (Morita et al); they give rise to diabetes insipidus, pituitary insufficiency, or orbital pain, and rarely may be the first indication of a systemic tumor.


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Neurology_Adams. Empty sella syndrome More common than the aforementioned conditions is a nontumorous enlargement of the sella (“empty sella”). This results from a defect in the dural diaphragm, which may occur without obvious cause or with states of raised intracranial pressure, such as pseudotumor cerebri (see Chap. 29) or hydrocephalus, or may follow surgical excision of a pituitary adenoma or meningioma of the tuberculum sellae or pituitary apoplexy (see later). The arachnoid covering the diaphragm sellae will bulge downward through the dural defect, and the sella then enlarges gradually, presumably because of the pressure and pulsations of the CSF acting on its walls. In the process, the pituitary gland becomes flattened, sometimes to an extreme degree; however, the functions of the gland are usually unimpaired. Flattening of the pituitary gland precedes bony expansion of the sella in many cases. Erosion or dishiscence of the sellar floor does not occur and the appearance of these changes


Neurology_Adams

Neurology_Adams. usually unimpaired. Flattening of the pituitary gland precedes bony expansion of the sella in many cases. Erosion or dishiscence of the sellar floor does not occur and the appearance of these changes implicates another type of lesion. Downward herniation of the optic chiasm occurs occasionally and may cause visual disturbances simulating those of a pituitary adenoma (Kaufman et al). As mentioned earlier, a bitemporal hemianopia with a normal-sized sella is usually caused by a primary suprasellar lesion (saccular aneurysm of the distal carotid artery, meningioma, or craniopharyngioma).


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Neurology_Adams. Treatment This varies with the type and size of the pituitary tumor, the status of the endocrine and visual systems, and the age and childbearing plans of the patient. The administration of the dopamine agonist bromocriptine (which inhibits prolactin) in a beginning dosage of 0.5 to 1.25 mg daily (taken with food) may be the only therapy needed for small or even large prolactinomas, and is a useful adjunct in the treatment of the amenorrhea–galactorrhea syndrome. The dose should be slowly increased by 2.5 mg or less every several days until a therapeutic response is obtained. Under the influence of bromocriptine, the tumor decreases in size within days, the prolactin level falls, and the visual field defect improves.


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Neurology_Adams. Some cases of acromegaly also respond to the administration of bromocriptine but even better to octreotide, an analogue of somatostatin. The initial dose of octreotide is 200 mg/d, increased in divided doses to 1,600 mg by increments of 200 mg weekly. In Lamberts’ series of acromegaly patients, the growth hormone levels returned to normal and tumor size was reduced in 12 of 15 cases. Treatment with bromocriptine and octreotide must be continuous to prevent relapse. Newer slow-release somatostatin analogues and long-acting dopamine agonists such as cabergoline have been developed for use in patients who do not respond to the conventional agents (Colao and Lombardi).


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Neurology_Adams. If the patient is intolerant of medication (or, in the case of acromegaly, to octreotide and newer drugs), the treatment is surgical, using a transsphenoidal microsurgical approach, with an attempt at total removal of the tumor and preservation of normal pituitary function. Unfortunately, approximately 15 percent of GH-secreting tumors and prolactinomas will recur at 1 year. For this reason, incomplete removal or recurrence of the tumor (or tumors that are unresponsive to hormonal therapy) should be followed by radiation therapy. Alternative primary treatment for intrasellar tumors is forms of stereotactic radiosurgery, provided that vision is not being threatened and there is no other urgent need for surgery. These forms of radiation can be focused precisely on the tumor and will destroy it. Kjellberg and Kliman in past decades using proton beam radiation, in the past treated more than 1,100 pituitary adenomas without a fatality and with few complications (Kliman et al).


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Neurology_Adams. Kliman in past decades using proton beam radiation, in the past treated more than 1,100 pituitary adenomas without a fatality and with few complications (Kliman et al). A single brief exposure was all that was necessary. An endocrine deficit will follow in most instances and must be corrected by hormone replacement therapy. Several equivalent methods (Gamma Knife, Cyberknife) are more accessible and have become widely used. The advantage of these radiotherapeutic methods is that tumor recurrence is rare. A disadvantage is that the radiation effect is obtained only after several months. Estrada and colleagues have also reported that external beam-radiation therapy may be employed after unsuccessful transsphenoidal surgery for Cushing disease. After approximately 3.5 years following radiation, 83 percent of their patients showed no signs of tumor growth. There are a few reports, however, of a decline in memory ability after radiation treatment of all types.


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Neurology_Adams. Large extrasellar extensions of a pituitary growth must be removed by craniotomy, usually with a transfrontal approach, followed by radiation therapy. Visual field defects often remain, but some improvement in vision can be anticipated.


Neurology_Adams

Neurology_Adams. Pituitary apoplexy This syndrome, described originally by Brougham and colleagues, occurs as a result of infarction of an adenoma that has outgrown its blood supply. It is characterized by the acute onset of severe headache that may be retro-orbital, frontal, bitemporal, or generalized ophthalmoplegia; bilateral visual loss; and in severe cases, drowsiness or coma, with either subarachnoid hemorrhage or pleocytosis and elevated protein in the CSF. The CT or MRI shows infarction of tumor, often with hemorrhage in and above an enlarged sella. Pituitary apoplexy may threaten life unless the acute addisonian state is treated by hydrocortisone. Blindness is the other dreaded complication. If there is no improvement after 24 to 48 h, or if vision is markedly affected, transsphenoidal decompression of the sella is indicated. Factors that may precipitate the necrosis or hemorrhage of a pituitary tumor are anticoagulation, pituitary function testing, radiation, bromocriptine treatment, and


Neurology_Adams

Neurology_Adams. of the sella is indicated. Factors that may precipitate the necrosis or hemorrhage of a pituitary tumor are anticoagulation, pituitary function testing, radiation, bromocriptine treatment, and head trauma; most cases, however, occur spontaneously. Some pituitary adenomas have been cured by this accident.


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Neurology_Adams. Ischemic necrosis of the pituitary, without the presence of a tumor followed by hypopituitarism, occurs under a variety of circumstances, the most common being in the partum or postpartum period (Sheehan syndrome). Meningioma of the Sphenoid Ridge


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Neurology_Adams. This tumor, mentioned earlier in the chapter, is situated over the lesser wing of the sphenoid bone. As it grows, it may expand medially to involve structures in the wall of the cavernous sinus, anteriorly into the orbit, or laterally into the temporal bone. Fully 75 percent of such tumors occur in women, and the average age at onset is 50 years. Most prominent among the symptoms are a slowly developing unilateral exophthalmos, slight bulging of the bone in the temporal region, and radiologic evidence of thickening or erosion of the lesser wing of the sphenoid bone. Variants of the clinical syndrome include anosmia; oculomotor palsies; painful ophthalmoplegia (sphenoidal fissure and Tolosa-Hunt syndromes; see Table 44-2); blindness and optic atrophy in one eye, sometimes with papilledema of the other eye (Foster Kennedy syndrome); mental changes; seizures (“uncinate fits”); and increased intracranial pressure. Rarely, a skull bruit can be heard over a highly vascular tumor. Sarcomas


Neurology_Adams

Neurology_Adams. of the other eye (Foster Kennedy syndrome); mental changes; seizures (“uncinate fits”); and increased intracranial pressure. Rarely, a skull bruit can be heard over a highly vascular tumor. Sarcomas arising from skull bones, metastatic carcinoma, orbitoethmoidal osteoma, benign giant cell bone cyst, tumors of the optic nerve, and angiomas of the orbit must be considered in the differential diagnosis. Neuroimaging with contrast provides the definitive diagnosis. The tumor is resectable without further injury to the optic nerve if the bone has not been invaded.


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Meningioma of the Olfactory Groove

Neurology_Adams. Meningioma of the Olfactory Groove


Neurology_Adams

Neurology_Adams. This tumor originates in arachnoidal cells along the cribriform plate. The diagnosis depends on the finding of ipsilateral or bilateral anosmia or ipsilateral or bilateral blindness—often with optic atrophy and mental changes. The tumors may reach enormous size before coming to the attention of the physician but as many are small and found incidentally with cerebral imaging (see Fig. 30-7B). If the anosmia is unilateral, it is rarely if ever reported by the patient. The unilateral visual disturbance may consist of a slowly developing central scotoma. Abulia, confusion, forgetfulness, and inappropriate jocularity (witzelsucht) are the usual psychic disturbances from compression of the inferior frontal lobes (see Chap. 21). The patient may be indifferent to or joke about his blindness. Usually there are radiographic changes along the cribriform plate. MRI with gadolinium is diagnostic. Except for the largest and most invasive tumors, surgical removal is possible.


Neurology_Adams

Neurology_Adams. Meningioma of the Tuberculum Sella Cushing was the first to delineate the syndrome caused by this tumor. All of his 23 patients were female. The presenting symptoms were visual failure—a slowly advancing bitemporal hemianopia with a sella of normal size. Often the field defects are asymmetrical, indicating a combined chiasmal–optic nerve involvement. Usually there are no hypothalamic or pituitary deficits. If the tumor is not too large, complete excision is possible. If removal is incomplete or the tumor recurs or undergoes malignant changes, radiation therapy of one type or another is indicated. The outlook is then guarded; several of our patients succumbed within a few years. Glioma of the Brainstem


Neurology_Adams

Neurology_Adams. Astrocytomas of the brainstem are relatively slow-growing tumors that infiltrate tracts and nuclei. They produce a variable clinical picture depending on their location in the medulla, pons, or midbrain. Most often, this tumor begins in childhood (peak age of onset is 7 years), and 80 percent appear before the 21st year. Symptoms have usually been present for 3 to 5 months before coming to medical notice. In most patients the initial manifestation is a palsy of one or more cranial nerves, usually the sixth and seventh on one side, followed by long tract signs—hemiparesis, unilateral ataxia, ataxia of gait, paraparesis, and hemisensory and gaze disorders in addition to pseudobulbar dysarthria and palsy. In the remaining patients the symptoms occur in the reverse order—that is, long tract signs precede the cranial nerve abnormalities. Patients in the latter group survive longer than those whose illness begins with cranial nerve palsies. Headache, vomiting, and papilledema may occur,


Neurology_Adams

Neurology_Adams. signs precede the cranial nerve abnormalities. Patients in the latter group survive longer than those whose illness begins with cranial nerve palsies. Headache, vomiting, and papilledema may occur, usually late in the illness. The course is slowly progressive over several years unless some part of the tumor becomes more malignant (anaplastic astrocytoma or glioblastoma multiforme) or, as rarely happens, spreads to the meninges (meningeal gliomatosis), in which instance the illness may terminate fatally within months.


Neurology_Adams

Neurology_Adams. The main problem in diagnosis is to differentiate this disease from a pontine form of multiple sclerosis, a vascular malformation of the pons (usually a cavernous hemangioma), or brainstem encephalitis, and to distinguish the focal from the diffuse type of glioma (see in the following text). The most helpful procedure in diagnosis and prognosis is contrast-enhanced MRI (Fig. 30-22).


Neurology_Adams

Neurology_Adams. A study of 87 patients by Barkovich and coworkers emphasized the importance of distinguishing between diffusely infiltrating and focal nodular tumors. In the more common diffuse type, there is mass effect with hypointense signal on T1-weighted MRI and heterogeneously increased T2 signal, which reflects edema and tumor infiltration. These diffusely infiltrating tumors, usually showing an asymmetrical enlargement of the pons, have a poorer prognosis than the focal or nodular tumors, which tend to occur in the dorsal brainstem and often protrude in an exophytic manner. In a few instances of diffuse brainstem glioma, surgical exploration is necessary to establish the diagnosis (inspection and possibly biopsy). However, the histologic characteristics of a minute biopsy specimen of the tumor are not particularly helpful in determining prognosis or treatment and the general practice is to avoid surgery unless the tumor exhibits unusual clinical behavior or does not conform to the typical MRI


Neurology_Adams

Neurology_Adams. not particularly helpful in determining prognosis or treatment and the general practice is to avoid surgery unless the tumor exhibits unusual clinical behavior or does not conform to the typical MRI appearance of the diffuse type.


Neurology_Adams

Neurology_Adams. Treatment The treatment of the diffuse infiltrative type is radiation, and if increased intracranial pressure develops as a result of hydrocephalus, ventricular shunting of CSF becomes necessary. Adjuvant chemotherapy has not been helpful. A series of 16 patients treated by Pollack and colleagues emphasizes that the focal and exophytic brainstem tumors are almost all low-grade astrocytomas; these tumors, in contrast to the more diffuse type, usually respond well to partial resection and permit long-term survival because they recur only slowly and do not undergo malignant transformation. Gangliocytomas or mixed astrogangliocytomas are rare imitators of nodular glioma in the brainstem. The rarer cystic glioma of the brainstem (see Fig. 30-22), a pilocytic tumor like its counterpart in the cerebellum, is treated by resection of the mural nodule and, as mentioned earlier, has an excellent prognosis. Landolfi and colleagues emphasized the longer survival in adults with pontine glioma


Neurology_Adams

Neurology_Adams. the cerebellum, is treated by resection of the mural nodule and, as mentioned earlier, has an excellent prognosis. Landolfi and colleagues emphasized the longer survival in adults with pontine glioma (median 54 months) as compared to children. Most of the patients with pontine tumors with which we are familiar proved to have malignant gliomas.


Neurology_Adams

Glioma of the Optic Nerves and Chiasm

Neurology_Adams. Glioma of the Optic Nerves and Chiasm


Neurology_Adams

Neurology_Adams. This tumor, like the brainstem glioma, occurs most frequently during childhood and adolescence. In 85 percent of cases, it appears before the age of 15 years (average 3.5 years), and it is twice as frequent in girls as in boys (Cogan). The initial symptoms are dimness of vision with constricted fields, followed by bilateral field defects of homonymous, heteronymous, and sometimes bitemporal type and progressing to blindness and optic atrophy with or without papilledema. Ocular proptosis from the orbital mass is the other main feature. Hypothalamic signs (adiposity, polyuria, somnolence, and genital atrophy) occur occasionally as a result of proximal tumor extension. CT, MRI, and ultrasonography will usually reveal the tumor, and radiographs will show an enlargement of the optic foramen (greater than 7.0 mm). This finding and the lack of ballooning of the sella or of suprasellar calcification will exclude pituitary adenoma, craniopharyngioma, Hand-Schüller-Christian disease, and


Neurology_Adams

Neurology_Adams. (greater than 7.0 mm). This finding and the lack of ballooning of the sella or of suprasellar calcification will exclude pituitary adenoma, craniopharyngioma, Hand-Schüller-Christian disease, and sarcoidosis. In adolescents and young adults, the medial sphenoid, olfactory groove, and intraorbital meningiomas (optic nerve sheath meningioma) are other tumors that cause monocular blindness and proptosis. If the entire tumor is prechiasmatic (the less-common configuration), surgical extirpation can be curative. For tumors that have infiltrated the chiasm or are causing regional symptoms and hydrocephalus, partial excision followed by radiation is all that can be offered. Both gliomas and nontumorous gliotic (hamartomatous) lesions of the optic nerves may occur in von Recklinghausen disease; the latter are sometimes impossible to distinguish from optic nerve gliomas and should be followed closely.


Neurology_Adams

Neurology_Adams. This is a soft, jelly-like, gray-pink growth that arises from remnants of the primitive notochord. It is located most often within the clivus (from dorsum sellae to foramen magnum) and in the sacrococcygeal region. It affects males more than females, usually in early or middle adult years and is one of the rare causes of syndromes involving multiple cranial nerves or the cauda equina. Approximately 40 percent of chordomas occur at each of these two ends of the neuraxis; the rest are found at any point in the vertebral bodies in between. The tumor is made up of cords or masses of large cells with granules of glycogen in their cytoplasm and often with multiple nuclei and intracellular mucoid material. Chordomas are locally invasive, especially of surrounding bone, but they do not metastasize.


Neurology_Adams

Neurology_Adams. The cranial neurologic syndrome caused by this tumor is remarkable in that all or any combination of cranial nerves from the 2nd to 12th on one or both sides may be involved. Associated signs in the series of Kendall and Lee were facial pain, conductive deafness, and cerebellar ataxia, the result of pontomedullary and cerebellar compression. A characteristic feature is neck pain radiating to the vertex of the skull on neck flexion. The tumors at the base of the skull may destroy the clivus and bulge into the nasopharynx, causing nasal obstruction and discharge and sometimes dysphagia. Extension to the cervical epidural space may result in cord compression. Thus, chordoma is one of the lesions that may present both as an intracranial and extracranial mass, the others being meningioma, neurofibroma, glomus jugulare tumor, and carcinoma of the sinuses or pharynx. CT of the skull base is useful for defining the bony margins of the tumor, and MRI can identify involved and adjacent neural


Neurology_Adams

Neurology_Adams. glomus jugulare tumor, and carcinoma of the sinuses or pharynx. CT of the skull base is useful for defining the bony margins of the tumor, and MRI can identify involved and adjacent neural and vascular structures. Midline (Wegener) granulomas, histiocytosis, Erdheim-Chester disease, and sarcoidosis also figure in the differential diagnosis. Chondrosarcoma of the clivus produces a similar syndrome.


Neurology_Adams

Neurology_Adams. Treatment of the chordoma is surgical excision and radiation (focused radiation). This form of treatment has effected a 5-year survival without recurrence in approximately 80 percent of patients. Nasopharyngeal Growths That Erode the Base of the Skull (Nasopharyngeal Transitional Cell Carcinoma, Schmincke Tumor)


Neurology_Adams

Neurology_Adams. These are seen regularly in a general hospital; they arise from the mucous membrane of the paranasal sinuses or the nasopharynx near the eustachian tube, that is, the fossa of Rosenmüller. In addition to symptoms of nasopharyngeal or sinus disease, which may not be prominent, facial pain and numbness, abducens, and other cranial nerve palsies may occur. Diagnosis depends on inspection and biopsy of a nasopharyngeal mass or an involved cervical lymph node and radiologic evidence of erosion of the base of the skull. Bone scans and CT are helpful in diagnosis (see Fig. 44-5). The treatment is surgical resection and radiation but chemotherapy is increasingly being included. Carcinoma of the ethmoid or sphenoid sinuses and postradiation neuropathy, coming on years after the treatment of a nasopharyngeal tumor, may produce similar clinical pictures and are difficult to differentiate. The syndromes resulting from nasopharyngeal tumors are discussed in Chap. 47, under “Diseases of the Cranial


Neurology_Adams

Neurology_Adams. tumor, may produce similar clinical pictures and are difficult to differentiate. The syndromes resulting from nasopharyngeal tumors are discussed in Chap. 47, under “Diseases of the Cranial Nerves.”


Neurology_Adams

Other Tumors of the Base of the Skull

Neurology_Adams. Other Tumors of the Base of the Skull


Neurology_Adams

Neurology_Adams. In addition to meningioma, nasopharyngeal tumors, and the other tumors enumerated earlier, there are a large variety of tumors, rare to be sure, that derive from tissues at the base of the skull and paranasal sinuses, ears, and other structures and give rise to distinctive syndromes. Included in this category are osteomas, chondromas, ossifying fibromas, giant cell tumors of bone, lipomas, epidermoids, teratomas, mixed tumors of the parotid gland, and hemangiomas and cylindromas (adenoid cystic carcinomas of salivary gland origin) of the sinuses and orbit; sarcoid granulomas may produce the same effect. Most of these tumors are benign, but some have a potential for malignant change. To the group must be added the esthesioneuroblastoma (of the nasal cavity) with anterior fossa extension and, perhaps most common of all of these, the systemic malignant tumors that metastasize to basal skull bones (prostate, lung, and breast being the most common sources), or involve them as part of a


Neurology_Adams

Neurology_Adams. and, perhaps most common of all of these, the systemic malignant tumors that metastasize to basal skull bones (prostate, lung, and breast being the most common sources), or involve them as part of a multicentric neoplastic process, for example, primary lymphoma, multiple myeloma, plasmacytoma, and lymphocytic leukemia.


Neurology_Adams

Neurology_Adams. Suprasellar arachnoid cysts also occur in this region. CSF flows upward from the interpeduncular cistern but is trapped above the sella by thickened arachnoid (membrane of Liliequist). As the CSF accumulates, it forms a cyst that invaginates the third ventricle; the dome of the cyst may intermittently block the foramina of Monro and cause hydrocephalus (see Fox and Al-Mefty). Children with this condition exhibit a curious to-and-fro bobbing and nodding of the head, like a doll with a weighted head resting on a coiled spring. This has been referred to as the “bobble-head doll syndrome” by Benton and colleagues; it can be cured by emptying the cyst. Seesaw and other pendular and jerk types of nystagmus may also result from these suprasellar lesions.


Neurology_Adams

Neurology_Adams. Tables 30-5 and 44-1, adapted from Bingas’ large neurosurgical service in Berlin, summarize the facts about the focal syndromes of the skull base; his authoritative article and the more recent one by Morita and Piepgras, both in the Handbook of Clinical Neurology, are recommended references.


Neurology_Adams

Neurology_Adams. Modern imaging techniques now serve to clarify many of the diagnostic problems posed by these tumors. MRI is particularly helpful in delineating structures at the base of the brain and in the upper cervical region. CT is also capable of determining the absorptive values of the tumor itself and the sites of bone erosion. When the lesion is analyzed in this way, an etiologic diagnosis often becomes possible. For example, the absorptive value of lipomatous tissue is different from that of brain tissue, glioma, blood, and calcium. Bone scans (technetium and gallium) display active destructive lesions with remarkable fidelity, but in some cases, even when the tumor is seen with various studies, it may be difficult to obtain a satisfactory biopsy. Tumors of the Foramen Magnum


Neurology_Adams

Neurology_Adams. Tumors of the Foramen Magnum Tumors in the region of the foramen magnum are of particular importance because of the need to differentiate them from diseases such as multiple sclerosis, Chiari malformation, syringomyelia, and bony abnormalities of the craniocervical junction. Failure to recognize these tumors is a consequential matter because the majority are benign and extramedullary, that is, potentially resectable and curable. If unrecognized, they terminate fatally by causing medullary and high spinal cord compression. Although these tumors are not common (approximately 1 percent of all intracranial and intraspinal tumors) sizable series have been collected by several clinicians (see Meyer et al for a complete bibliography). In all series, meningiomas, schwannomas, neurofibromas, and dermoid cysts are the most common types; others, all rare, are teratomas, dermoids, granulomas, cavernous hemangiomas, hemangioblastomas, hemangiopericytomas, lipomas, and epidural carcinomas.


Neurology_Adams

Neurology_Adams. Pain in the suboccipital or posterior cervical region, mostly on the side of the tumor, is usually the first and by far the most prominent complaint. In some instances the pain may extend into the shoulder and even the arm. The latter distribution is more frequent with tumors arising in the spinal canal and extending intracranially than the reverse. For uncertain reasons, the pain may radiate down the back, even to the lower spine. Both spine and root pain can be recognized, the latter because of involvement of either the C2 or C3 root or both.


Neurology_Adams

Neurology_Adams. One pattern is weakness of a shoulder and arm progressing to the ipsilateral leg and then to the opposite leg and arm (“around-the-clock” paralysis) as discussed in Chap. 3. Another configuration is triplegia that is a characteristic but not invariable sequence of events, caused by the encroachment of tumor upon the decussating corticospinal tracts at the foramen magnum. Occasionally, both upper limbs are involved alone; surprisingly, there may be atrophic weakness of the hand or forearm or even intercostal muscles with diminished tendon reflexes well below the level of the tumor, an observation made originally by Oppenheim. Involvement of sensory tracts also occurs; more often it is posterior column sensibility that is impaired on one or both sides, with patterns of progression similar to those of the motor paralysis. Sensation of intense cold in the neck and shoulders has been another unexpected complaint, and also “bands” of hyperesthesia around the neck and back of the head.


Neurology_Adams

Neurology_Adams. to those of the motor paralysis. Sensation of intense cold in the neck and shoulders has been another unexpected complaint, and also “bands” of hyperesthesia around the neck and back of the head. Segmental bibrachial sensory loss has been demonstrated in a few of the cases and a Lhermitte sign (really a symptom) of electric-like sensations down the spine and limbs upon flexing the neck has been reported frequently. The cranial nerve signs most frequently conjoined and indicative of intracranial extension of a foramen magnum tumor are dysphagia, dysphonia, dysarthria, and drooping shoulder (because of vagal, hypoglossal, and spinal accessory involvement); included less often are nystagmus and episodic diplopia, sensory loss over the face and unilateral or bilateral facial weakness, and a Horner syndrome.


Neurology_Adams

Neurology_Adams. The clinical course of such lesions often extends for years, with deceptive and unexplained fluctuations. The important diagnostic procedure is contrast-enhanced MRI (Fig. 30-23). With dermoid cysts of the upper cervical region, as in the case reported by Adams and Wegner, complete and prolonged remissions from quadriparesis may occur. Tumors of the foramen magnum, as mentioned, should be differentiated from spinal or brainstem- cerebellar multiple sclerosis, Chiari malformation with syrinx, and bony compression. Persistent occipital neuralgia with a foramen magnum syndrome is particularly suggestive of a tumor at that site. The early occipitonuchal pain must be differentiated from mundane cervical osteoarthritis. Treatment is surgical excision (Hakuba et al) followed by focused radiation if the resection is incomplete and the tumor is known to be radiosensitive.


Neurology_Adams

Neurology_Adams. In the past 50 years a group of neurologic disorders has been delineated that occur in patients with systemic neoplasia even though the nervous system is not the site of metastases or direct invasion or compression by the tumor. These so-called paraneoplastic disorders are not specific or confined to cancer, but the conditions are linked far more frequently than could be accounted for by chance. They assume special importance because in many cases the neurologic syndrome becomes apparent before the underlying tumor is found. The great variety of clinical presentations of paraneoplastic neurological disease can be appreciated from early series reported by Graus and colleagues of 200 patients: sensory neuropathy, 54 percent; cerebellar ataxia, 10 percent; limbic encephalitis, 9 percent; and others, including multiple sites, in 11 percent. Some of the paraneoplastic disorders that involve nerve and muscle—namely, polyneuropathy, polymyositis, and the myasthenic-myopathic syndrome of


Neurology_Adams

Neurology_Adams. and others, including multiple sites, in 11 percent. Some of the paraneoplastic disorders that involve nerve and muscle—namely, polyneuropathy, polymyositis, and the myasthenic-myopathic syndrome of Lambert-Eaton—are described in later chapters on these subjects. Here we present the paraneoplastic processes that involve the spinal cord, cerebellum, brainstem, and cerebral hemispheres.


Neurology_Adams

Neurology_Adams. Comprehensive accounts of the paraneoplastic disorders may be found in the writings of Darnell and Posner, and Dalmau and Rosenfeld. Many are associated with immunoglobulin G (IgG) autoantibodies, but it should be remarked that although certain antibodies are associated with specific syndromes, they are not invariably linked to particular cancers and vice versa. Furthermore, the same syndromes and antibodies occur sometimes without an evident tumor, and in some cases multiple autoantibodies are present. This was emphasized in the survey by


Neurology_Adams

Neurology_Adams. Pittock and colleagues at the Mayo Clinic, who found that one-third of sera from patients with paraneoplastic neurologic disorders had more than one antibody. They have suggested that this reflects the numerous immunogenic onconeural proteins that are expressed by tumors. Consequently, the relationships between particular antibodies and a clinical syndromes listed in Table 30-6 should be taken as approximate, or nonexclusive. The presence of an autoantibody does not necessarily implicate a role in neuronal dysfunction and certain autoantibodies may be present in the serum of healthy individuals (see Dahm et al). Nonetheless, certain syndromes seem to occur disproportionately often with particular antibodies. Small cell cancer of the lung (see Gozzard et al), adenocarcinoma of the breast and ovary, thymoma (see Evoli and Lancaster), and Hodgkin disease are the tumors most often associated with these disorders, but the paraneoplastic neurologic syndromes occur in only a very small


Neurology_Adams

Neurology_Adams. and ovary, thymoma (see Evoli and Lancaster), and Hodgkin disease are the tumors most often associated with these disorders, but the paraneoplastic neurologic syndromes occur in only a very small proportion of patients with these tumors.


Neurology_Adams

Neurology_Adams. The mechanisms by which tumors produce their remote effects are incompletely understood. Perhaps the most plausible theory, as intimated above, is that they have an autoimmune basis. According to this theory, antigenic molecules are shared by certain tumors and central or peripheral neurons. The immune response is then directed to the shared antigen in both the tumor and the nervous system. The evidence for such an autoimmune mechanism is most clearly exemplified by the Lambert-Eaton syndrome, in which an antibody derived from a tumor binds to voltage-gated calcium channels at neuromuscular junctions (see Chap. 46).


Neurology_Adams

Neurology_Adams. Furthermore, in some types of paraneoplastic disorders, there is provocative evidence that the inciting tumor has antigen on its surface and self-binding of the antibody may inhibit tumor growth. This may account for the difficulty in detecting diminutive small cell lung cancers that underlie some of the paraneoplastic syndromes. It should be noted, however, that there is no evidence that suppressing or removing the antibody leads to growth of the tumor.


Neurology_Adams

Neurology_Adams. The occurrence of regional and bilateral encephalomyelitic changes in association with carcinoma has been described by several authors (Corsellis et al; Henson and Urich; Posner, 1995). In most of the reported cases, the encephalitic process has been associated with carcinoma of the bronchus, usually of the small cell type, but all types of neoplasms, including Hodgkin disease, have been implicated. Histologically, this group of paraneoplastic disorders is characterized by extensive loss of neurons, accompanied by microglial proliferation, small patches of necrosis, and marked perivascular cuffing by lymphocytes and monocytes. Foci of lymphocytic infiltration have been observed in the adjacent leptomeninges as well. These pathologic changes may involve the brain and spinal cord diffusely, but more often they predominate in a particular part of the nervous system, notably in the medial temporal lobes and adjacent nuclei (“limbic encephalitis,” Fig. 30-24), the brainstem, the cerebellum


Neurology_Adams

Neurology_Adams. but more often they predominate in a particular part of the nervous system, notably in the medial temporal lobes and adjacent nuclei (“limbic encephalitis,” Fig. 30-24), the brainstem, the cerebellum (see earlier), or the gray matter of the spinal cord. The symptoms will, of course, depend on the location and severity of the inflammatory changes and may overlap. Most cases are subacute, meaning specifically a progression over a few weeks or months, but often the main symptoms in mild form become apparent in a matter of days. Rare instances of remission have been reported.


Neurology_Adams

Neurology_Adams. The most distinctive features of paraneoplastic limbic encephalitis consists of a confusional–agitated state, memory defect (Korsakoff syndrome), seizures, hallucinations, and dementia—singly or in various combinations and evolving subacutely (Gultekin et al); an amnestic component is almost universal and the central feature in most cases.


Neurology_Adams

Neurology_Adams. Vertigo, nystagmus, ataxia, nausea and vomiting, and a variety of ocular and gaze palsies reflect a different process of paraneoplastic brainstem encephalitis. As indicated above, these symptoms may be joined with cerebellar ataxia, and another group has an additional sensory neuropathy. We have seen instances of this condition involving only the midbrain and others involving only the medulla, the latter with unusual breathing patterns including gasping, inspiratory breath holding, and vocal–respiratory incoordination, and yet others with chorea and additional basal ganglionic features. Pathologic studies have partially clarified this form of paraneoplastic disorder. In some cases, few changes were demonstrable in the brain, even though there had been a prominent dementia during life. Contrariwise, widespread inflammatory changes may be found without clinical abnormalities having been recorded during life.