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vermis and neuroepithelial roof of the fourth ventricle in children It accounts for 20 percent of childhood brain tumors Rarely, it presents elsewhere in the cerebellum or other parts of the brain in adults (Peterson and Walker) The origin of this tumor remained in doubt for a long time Bailey and Cushing introduced the name medulloblastoma, although medulloblasts have never been identi ed in the fetal or adult human brain; nevertheless the term is retained for no reason other than its familiarity The current view of the tumor is that it originates from stem cells that have been prevented from maturing and differentiating to their normal growth-arrested state They retain their capacity to divide ad in nitum The tumor may differentiate uni- or pluripotentially, varying from case to case This accounts for the recognized histologic variants, ranging from the undifferentiated medulloblastoma to medulloblastoma with glial, neuronal, or even myoblastic components Rosette formation, highly characteristic of the below-described neuroblastoma is seen in half of medulloblastoma cases Molecular genetic qualities relate the medulloblastoma to retinoblastomas and certain pineal cell tumors and, rarely, to certain autosomal dominant diseases such as nevoid basal cell carcinoma The most common histologic variant, recognized by Hortega in his classic work on the histology of brain tumors, is the isomorphic glioblastoma, from which both astrocytes and oliogodendrocytes are derived Studies of cell lines from human medulloblastomas reveal a loss of genetic information on the distal part of chromosome 17 distal to the p53 region Schmidek has proposed that this accounts for the neoplastic transformation of cerebellar stem cells, at various stages of their differentiation, into tumor cells It is also notable that medulloblastomas are encountered in Gorlin syndrome, caused by mutations in the gene encoding patched, the receptor for sonic hedgehog ligand, and in Turcot syndrome, due to mutations in DNA repair genes (Louis et al) Another line of research has strongly implicated the JC virus, the same agent that causes progressive multifocal leukoencephalopathy (Chap 33) Genomic sequences from this virus have been found in 72 percent of tumors in some series (Khalili et al), and an experimental transgenic model in which the JC protein is expressed is characterized by a cerebellar tumor that resembles the medulloblastoma Neuroblastomas differ from medulloblastomas when analyzed for genetic markers, as indicated below The majority of the patients are children 4 to 8 years of age, and males outnumber females 3:2 or 3:1 in the many reported series As a rule, symptoms have been present for 1 to 5 months before the diagnosis is made The clinical picture is distinctive and derives from secondary hydrocephalus and raised intracranial pressure as a result of blockage of the fourth ventricle Typically, the child becomes listless, vomits repeatedly, and has a morning headache The rst diagnosis that suggests itself may be gastrointestinal disease or abdominal migraine Soon, however, a stumbling gait, frequent falls, and diplopia as well as strabismus lead to a neurologic examination and the discovery of papilledema or sixth nerve palsies Papilledema is present in all except a small proportion of patients by the time they come to the attention of the neurologist However, when the tumor is located in the lateral cerebellum or in the cerebrum, as it usually is in adults, signs of raised intracranial pressure may be delayed Dizziness (positional) and nystagmus are frequent A small proportion of these children have a slight sensory loss on one side of the face and a mild facial weakness Head tilt, the occiput being tilted back and away from the side of the tumor, indicates a developing cerebellar-foraminal herniation Rarely, signs of spinal root and subarachnoid metastases precede cerebellar.

Placed in this category are neuropathies that evolve over several weeks to months and, after reaching their peak of severity, tend to persist for a variable period Admittedly, the dividing line between such cases and those that evolve over somewhat shorter or longer periods is indistinct; there are diseases of nerve that overlap both the acute and the early chronic categories In contrast to the acute polyneuropathies, however, most of those that are subacute have prominent sensory features and are of axonal type The exception is a subacute in ammatory-demyelinative type, essentially a slow form of GBS, evolving over 4 to 8 weeks as described by Hughes and coworkers Similarly, some instances of diphtheritic neuropathy evolve subacutely Despite these quali cations, in the end, a symmetrical polyneuropathy syndrome of subacute type most often proves to be due to alcoholism and nutritional de ciency, to a remote effect of cancer (paraneoplastic, as described later), or to poisoning with arsenic, lead, or to the toxic effects of any number of drugs used for therapeutic purposes (cisplatin, nitrofurantoin, isoniazid, etc) Occasionally other drugs, metals, and industrial solvents are incriminated; these are discussed in Chap 43

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(See Chap 41) In the western world, nutritional polyneuropathy is usually associated with chronic alcoholism As indicated in page 989, all data point to the identity or at least close relationship between alcoholic neuropathy and neuropathic beriberi A nutritional factor is responsible for both, though in any given case it often remains unclear whether the de ciency is one of thiamine, nicotinic acid, pyridoxine, pantothenic acid, folic acid, or a combination of these B

On occasion, a vasculitic polyneuropathy associated with lupus erythematosus, polyarteritis nodosa, and related disorders may de-

vitamins We have not been persuaded of the existence of a form of polyneuropathy that is attributable solely to the direct toxic effect of alcohol, though claims of such an entity have been made Nutritional neuropathy and other forms of de ciency neuropathy (Strachan syndrome, pellagra, vitamin B12 de ciency, and malabsorption syndromes) are described fully in Chap 41

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