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Once the memory disorder has become pronounced in the prototypic disorder, other failures in cerebral function become increasingly apparent. In the early phase of the illness other clinical signs of cerebellar disease are usually minimal or lacking; only a minority of cases show nystagmus or cerebellar ataxia of the limbs, although these signs must always be sought. There are no cutaneous mal formations but small vascular anomalies in the brain and elsewhere may accompany the cerebellar tumor as discussed in Chap. These agents were of interest because they can be admin istered up to several hours after the stroke (continuing for 72 h). About 2,000 cases occur yearly in the United States, accounting for approxi mately 10 percent of all cases of encephalitis. In addition, stature is apparently controlled by the nervous system, as shown by the fact that a majority of mentally retarded individuals are also stunted physically to a varying degree. Matters pertaining to spinal injuries, often coexistent with head trauma, are considered in Chap. As stated ear lier, the integration of these two systems is achieved pri marily in the hypothalamus. A similar "triple response" follows the release of histamine into the skin as the result of a scratch. The corrunon mode of expression of stroke is a relatively sudden occur rence of a focal neurologic deficit. This was appreci ated even in the time of Cicero, who, in his De Senectute, urged the practice of moderation in exercise and giving due attention to the mind, which must be kept active or, like a lamp that is not supplied with oil, it will grow dim. A more complete account of the disorders of the mitochondrial respiratory chain can be found in the review by Leonard and Schapira. The cell bodies of these sensory neurons lie in the posterior root sensory ganglia; some central axons of these ganglionic cells synapse with lateral hom cells of the spinal cord and subserve visceral reflexes; others syn apse in the dorsal hom and convey or modulate impulses for conscious sensation. The frequency of these changes is reported to be between 40 and 70 percent (see Chap. The meningitis may be preceded by respiratory symptoms, sometimes with pulmonary infiltrates. Furthermore, it should be kept in mind that the levels of proteins C and S and of anti thrombin are temporarily depressed after stroke, so that any detected abnormalities must be confirmed months later and in the absence of anticoagulation. In a subsequent review of the neuropathology, Kemper and Bauman concluded that three changes stood out: a curtailment of the normal development of neurons in the limbic system; a decrease in the number of Purkinje cells that appears to be con genital; and age-related changes in the size and number of the neurons in the diagonal band of Broca (located in the basal frontal and septal region), as well as in the cer ebellar nuclei and inferior olive. Signs of increased intracranial pressure appear late and have been present in fewer than 25 percent of our patients. Induced hypother mia limits the size of ischemic stroke, but it is technically difficult to administer and often has serious side effects. Gomez and colleagues suggested that the seizures damage the brain, a point with which we tend to agree in part. Resistant strains of tuberculous organisms are emerging, requiring the use of second-line drugs. The differential diagnosis of neurosarcoidosis is broad and includes multiple sclerosis as well as enti ties such as Sjogren syndrome, systemic lupus, lym phoma, lymphomatoid granulomatosis, cryptococcosis and other fungal infections that cause abscesses and chronic meningitis, syphilis, Wegener granulomatosis, Whipple disease, and, of course, tuberculosis. Vitiligo, cafe-au lait spots, loss of subcutaneous fat, and prema ture graying of hair are observed in some older patients. Every component of breathing-the lifelong automatic cycling of inspiration, the transmission of coordinated nerve impulses to and from the respiratory muscles, the transla tion of systemic influences such as acidosis to the neuro muscular apparatus of the diaphragm-is under neural control. With regard to the former group, having no obvious neurologic signs or physical stigmata, one should nevertheless initiate a search for the common metabolic, chromosomal, and infective diseases. The clinical state may also take the form of a parkinsonian syndrome or bilateral athetosis. In the summer of 1955, when New England experienced its last epi demic, 3,950 cases of acute poliomyelitis were reported in Massachusetts alone, and 2,771 were paralytic. The mechanism of the headache is not fully under stood and there may be more than one pathophysiology. Wholly extracranial anastomoses from muscular branches of the cervical arteries to vertebral and external carotid arteries are indicated in inset D. The factors that influence hypothalamic neurons have been reviewed in detail by Reichlin.

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About a dozen variants of globoid cell leukodys trophy have been reported, many of them allowing survival for years. For micturition to occur, the sphincters must relax, allowing the detrusor to expel urine from the blad der into the urethra. If the bifurcation is patent, few if any symptoms may result because retrograde flow from the external carotid maintains internal carotid flow and perfusion of the brain. The diagnostic criteria are based on the presence of two of more schwan nomas without vestibular nerve tumors in an individual older than age 18 years, as s umm arized in a thorough review by MacCollin and colleagues, and more recently by Plotkin and colleagues. Focal or focal and generalized sei zures occur in the early phase of the injury in some 15 to 20 percent of cases. For example, interference with synaptic signaling and dysfunction of supporting glia cells are equally important to morphologic neuronal death. Another recent patient with Kufs disease presented at age 51 with vague visual difficulty, which was followed by spasticity of the legs, behavioral disinhibition, and dementia spanning 6 years. The patient with a lacunar infarct usually fares well but may take months to improve to the maximum extent. These subsyndromes may consist of vertigo and ptosis, toppling and vertical diplopia, hoarseness and disequilibrium, or other combinations short of the entire syndrome. Any increase in headache, vomiting, or difficulty arous ing the patient should prompt a return to the emergency department. However, the main neurologic signs of a large intracranial mass, pupillary dilatation, abducens palsies, drowsiness, and the Cushing response, as discussed below and in Chaps. Animals are infected in the same way as humans, and the cycle can be repeated only if a new host ingests the encysted larvae. In addi tion to multiple sclerosis and traumatic and compres sive myelopathies, which are the most common causes, myelitis, neuromyelitis optica, spondylosis, dural arte riovenous fistula, syringomyelia, and tropical spastic paraparesis may cause a bladder disturbance of this type. There is no proven therapy, but liver transplantation could theoretically be effective. With the exception of urgent circumstances such as a mechanical heart valve that requires continu ous anticoagulation, current practice has been to delay instituting warfarin when the stroke is large, a definition that is admittedly difficult to quantify-perhaps greater than half or a third of the territory of the middle cerebral artery supply. Treatment Although natural isolates are sensitive to penicillin, bioengineered strains are resistant; therefore, combined treatment with ciprofloxacin with clindamy cin, rifampin, or meropenem has been recommended initially. The early manifestations are usually low-grade fever, malaise, headache (more than 50 percent of cases), lethargy, confusion, and stiff neck (75 percent of cases), with Kernig and Brudzinski signs. In some of these instances, it has been found to be caused by a defective ryanodine receptor. After it has been confirmed that the pressure is not elevated, these headaches may be treated in a man ner similar to the usual types of chronic headaches, as outlined in Chap. The controversies regarding the effects of prematurity, maternal hypertension, and eclampsia, which are often associated with neonatal cerebral pathol ogy and slowed psychomotor development, have been mentioned earlier in this chapter. The problem of a "traumatic tap" often clouds the early diagnosis, and several aids to detecting this mis leading laboratory result are discussed in Chap. The components of behavior that have been chosen as a frame of reference for neurological development are not likely to be of uniform physiologic value or of comparable complexity, and they have seldom been standardized on large populations drawn from different cultures. However, instances of encepha lopathy at lower pressures are common, especially if the rise in pressure has been abrupt (see below). Sometimes there are occult skull fractures, but more often, there is be evident on diffusion-weighted little or no direct cranial trauma. Characteristically, over a period of several days, there is partial or total loss of vision in one eye. Neurons are in disarray and some are enlarged; in some places the natural lamination of the cortex is effaced. All but the lowest concentration of saline require a central venous catheter to prevent sclerosis of veins. Biochemical studies may disclose a biotinidase defi ciency, methylmalonic aciduria, glutaric acidemia, meth ylglutaconic acidemia, or any number of other organic acid abnormalities. Because the benign nature of the illness has pre cluded extensive pathologic study, there is uncertainty regarding the infectious or postinfectious nature of these ataxic illnesses. Furthermore, certain epileptic states tend to occur only during certain epochs of life-one type of febrile seizure from 6 months to 6 years, generalized or temporal spike-wave activity with benign motor and complex partial seizures from 6 to 16 years, and juvenile myoclonic epilepsy in the mid- and late-adolescent years. Possibly an autosomal domi nant pattern of inheritance, with short stature of congenital hemihypertrophy (arm and leg on one side larger and longer), pseudohydrocephalic head (normal-sized cranium with small facial bones), abnormalities of genital development in one-third of cases, delay in closure of fontanels and in epiphy seal maturation, elevation of urinary gonadotropins.

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Some insight into the nature of swallowing dysfunction after stroke is provided by Hamdy and colleagues, who correlated the presence of dysphagia with a lesser degree of motor representation of pharyngeal muscles in the unaffected hemisphere, as assessed by magnetic stimula tion of the cortex. Benabdeljlil M, E l Alaoui Faris M, Kissani N, e t al: Troubles neuro psychologiques apres infarctus bi-thalamique par thrombose veineuse profonde. We have not had to resort to cranial subtemporal decompression, a procedure that was formerly used when vision was threatened. An accompany ing saccular aneurysm occurs in approximately 5 percent of cases of cerebral arteriovenous malformation, usually on the main feeding artery of the malformation. More generalized headaches may or may not be explained by the finding of a Chiari malformation and the advisability of a surgical treatment then depends on the degree of disability created by other aspects of the malformation. The B lymphocyte or lymphoblast is the tumor cell, whereas the fine reticulum and "microgliacytes" are secondary interstitial reactions. Acetazolamide and Osmotic Agents this approach has been considered the first step in treatment for patients who are not losing visual acuity rapidly. However, from the neuropathologic standpoint, the examination of the brains of the severely developmentally delayed by conventional histopathologic methods discloses lesions in approximately 90 percent, and in fully three-quarters of the entire group, an etiologic diagnosis can be determined or tentatively assigned. The Sneddon syndrome is an arteriopathy produc ing deep blue-red skin lesions of livedo reticularis and livedo racemosa in association with multiple ischemic strokes. There is both a deep and cutaneous sensory loss, usually severe in degree, of the opposite side of the body, including the trunk and face, sometimes accom panied by a transitory hemiparesis. Patients with mutations in these genes had better outcomes and slower tumor progression as presented by Yan and colleagues. There are often added compli cations: mental retardation, deafness, convulsions, and loss of sight secondary to papilledema. The more complex decision to apply stenting to the partial occlusion of the transverse sinus by generous pacchionian granulations should probably be guided by the same principles, i. In the untreated case, the dementia evolves, over a period of weeks or months; survival after the onset of dementia is generally 3 to 6 months but may be considerably longer if treatment is instituted. Granulovacuolar changes are a regular finding in aging hippocampi, regardless of the mental state of the individual. In general, In 1921, Loewi discov receptors mediate vasoconstriction, relaxation of the gut, and dilatation of the pupil; beta receptors mediate vaso dilatation, especially in muscles, relaxation of the bronchi, and an increased rate and contractility of the heart. By contrast, lesions that alter the blood-brain barrier cause rapid swelling of brain tissue. In the localization of an intracerebral hemorrhage, ocular signs may be particularly useful. Bacterial meningitis (except for that caused by Listeria monocytogenes, described below) is essentially a perinatal infection contracted during or immediately after parturi tion. Many patients are taking the higher dose levels for peripheral or coronary artery disease. Seizures and visual defects have also been observed, related to cerebral dys autoregulation. One issue with the longer term administration of interferon is the development of antibodies to the drug. Ampicillin should be added to the regimen in cases of suspected Listeria meningitis, particularly in an imrnu nocompromised patient. Third, there is an indication from sev eral series of concussions in National Collegiate Athletic Association and National Football League players that the number of recollected concussions is proportional to the degree of impairment on neuropsychologic tests (McCrea et al). The storage is, again, within lysosomes in the brain, spinal cord, heart, viscera, bone, and connective tissue. It can also be said that such changes are unrelated to Alzheimer Diminution in the sense of smell and, to a lesser extent, of taste (see Chap. It is worth while to quantify the speed and facility of gait two or three times before the lumbar puncture or drainage and to perform this testing at periodic intervals for several days after the procedure in order to be certain that improve ment is genuine. The sources of these social reactions are even more obscure than those of tem perament, character, and intelligence. If the brain is penetrated at the lower levels of the brainstem, death is instantaneous because of respiratory and cardiac arrest. The clinical picture is variable and combines features of infantile Gaucher disease-such as abducens palsies, dysphagia, trismus, rigidity of the limbs, and dementia with features of the late childhood-arly adult form, such as palsies of horizontal gaze, diffuse myoclonus, gener alized seizures, and a chronic course.

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As a consequence there is a conjunction of neurologic and skeletal abnormalities that is virtually unique. This notion was reinforced by Byrom, who demonstrated, in rats, a seg mental constriction and dilatation of cerebral and retinal arterioles in response to severe hypertension. The combination of surgery, radiation of the entire neur axis, and chemotherapy permits a 5-year survival in more than 80 percent of cases. With lesions in the upper thoracic cord, similar but lesser degrees of labile blood pressure are seen; in several of our patients with destructive myelitis, a viral infection of fever brought out episodes of a drop in blood pressure to approximately 80 I 60 mm Hg and a subsequent rapid rise to 190 / 110 mm Hg. The tumors at the base of the skull may destroy the clivus and bulge into the nasopharynx, causing nasal obstruc tion and discharge and sometimes dysphagia. These laboratory diagnostic issues are discussed and put in perspective by Golightly. Headache, at times severe, often occurs as a prodrome of a thrombotic stroke or subarachnoid hemorrhage; unless this is appreciated, a diagnosis of migraine may be made. Coma gradually follows the acute encephalitic symptoms and, with rare exceptions as noted below, death ensues within 4 to 10 days, or longer in the paralytic form. Sucking and swallowing are depressed or absent, but pupillary reactions and eye movements may at first be retained, only to be lost as the coma deepens. The profuse rete mirabile consists of a fine network of vessels over the basal surface of the brain (in the pia-arachnoid), which, according to Yamashita and coworkers, reveals microaneurysm for mation because of weakness of the internal elastic lamina and thinn ess of the vessel wall. Computerized methods of power spectral analysis may be used to express the variance in heart rate as a func tion of the beat-to-beat interval. Most impor tantly, in pyridoxine deficiency, the administration of 50 to 100 mg of vitamin B6 suppresses the seizure state, and daily doses of 40 mg permit normal development. Most patients recover completely, although myalgia may persist for several months. The seizures are treated with antiepileptic drugs, which may at first be held responsible for the ataxia. In addi tion to the sphingolipidoses, which are the lysosomal storage diseases most likely to be encountered in the first year of life, the table includes the storage diseases that may not appear clinically until a later age (in childhood and adolescence)-to be considered later in this chapter. Rutkowski and colleagues have reported some promising results, especially in those who had gross total tumor resection, but a large number nonethe less acquired a leukoencephalopathy that was said to be asymptomatic. With the most-severe neonatal type, the infant appears normal at birth, but toward the end of the first week, poor feeding, intermittent hypertonicity, opisthotonos, and respiratory irregularities appear. The combination of intracerebral hemorrhage and metaphysial bone spurs, which may be interpreted as "corner fractures," has led in some cases to the erroneous diagnosis of child abuse. This concept embodies an unproven hypothesis-that aging and degenerative changes of cells are based on the same process. This form of treatment has effected a 5-year survival without recurrence in approxi mately 80 percent of patients. Ruigrok symptomatic carotid artery stenosis in relation to clinical sub Rev Neurol 137:709, 1981. Occlusion of the distal intracranial portion of the internal carotid artery (the "T")-for example by an embolus to its distal part-produces a clinical picture like that of middle cerebral artery occlusion: contralateral hemiplegia, hemihypesthesia, and aphasia (with involve ment of the dominant hemisphere). Claims have also been made numerous times over the years for a viral cau sation of multiple sclerosis, amyotrophic lateral sclerosis, and other degenerative diseases, but the evidence in all instances has been questionable. These interrupt the venous portal transport of dopamine from the hypothalamus to the dopamine sensitive lactotrophs in the pituitary. The enlargement of the brain in this disease must be distinguished clinically from G M2 gangliosidosis, Alexander disease, Krabbe disease, and nonprogressive megalocephaly and pathologically from a variety of dis orders characterized by vacuolation of nervous tissue. This explains the rapid effects of intravenously injected hypotonic and hypertonic fluids. These data should inform the use of the long-term disease-modifying therapies dis cussed in a later section but, as pointed out by Sayao and colleagues, reliable criteria for identifying patients who are destined to accumulate minimal or no disability are not available but are being sought. In young children and infants, apathy, hyperirritability, vomiting, and seizures are the usual symptoms; however, stiff neck may not be prominent or may be absent altogether.

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Fortunately for the clinician, the most important of these diseases are expressed in several recognizable core syndromes and in a few variants thereof. Radiographs show beaking of the vertebral bodies and poor trabeculation of long bones. Psychiatric and social counseling may help the family to maintain gentle but firm support of the patient so that he can acquire, to the fullest extent pos sible, self-help skills, self-control, good work habits, and a congenial personality. It is well to remember that many of our ideas about the brain and the mind were shaped historically by this disease. Bailey A, LeCouteur A, Gottesman A, et al: Autism as a strongly genetic disorder: Evidence from a British twin study. Numerous hyphae are present within the thrombi and vessel wall, often invading the surrounding parenchyma. The stroke is then the result of occlusion of the vessel by a superimposed thrombus. Headaches, convulsions (either focal or generalized), and other cerebral signs appear; with lesions of larger size, papilledema may develop, simulating a brain tumor. After 6 to 18 months of normal development, motor skills and mental abilities seem slowly to regress. The incidence among adults, acquired from autopsy series and more recently, from incidentally discovered descent of the cerebellar tonsils on imaging procedures, is about If the patient survives to later childhood or adolescence, one of the syndromes that are more typical of the type I malformation may become manifest. The time required for the patient to pass through these stages of recovery may be only a few seconds or minutes, several hours, or possibly a limited number of days; but again, between these extremes there seem to be only quantitative differences. If disability by way of spasticity, ataxia, pain in the shoulders or arms, or lower cranial-nerve disease is increasing, upper cervical laminectomy and enlargement of the foramen magnum are indicated. Being a syn drome and not a disease, pseudotumor cerebri has a number of causes or pathogenetic associations. Differential Diagnosis of the Congenital Ataxias the congenital ataxias must be distinguished from the pro gressive hereditary ataxias. A precise rela tionship between motor hyperactivity and the inability to concentrate and stay focused on a series of tasks has not been established. There was an increased level of sulfite and thiosulfate and an abnormal amino acid, 5-sulfocysteine, in the blood. Between attacks, some patients with partial deficiency may be normal or show only a slight hyperbilirubinemia (DiMagno et al; Rowe et al). Well-studied cases of infarc tion in the territory of the anterior cerebral artery are not nwnerous; hence the syndromes have not been com pletely elucidated (see Brust for a review of the literature and a description of developmental abnormalities of the artery). The neurons in the penumbra are considered to be physiologically "stunned" by moderate ischemia and subject to salvage if blood flow is restored in a certain period of time. While a small, and not a random ized trial, surgical excision resulted in longer survival. Attempts to attain sitting balance early on reveal an unsteadiness that is not soon overcome, even with practice. Exceptionally, patients with meningomyelocele, and most of those with lumbar meningocele, are mentally normal. In the Traumatic Coma Data Bank, which included 1,030 gravely injured patients with Glasgow Coma Scale scores of 8 or less, 21 percent had subdural hematomas, 11 percent had intracerebral clots, and 5 percent had epidural hematomas. Individuals with systemic lupus erythematosus have an increased risk of aseptic men ingitic reactions to antiinflamatory medications. It is not known whether there is a characteristic brain pathology, but one 35-year-old patient examined by Golden and associates showed no cerebral abnormalities except for Alzheimer changes, mainly plaque formation in the entorhinal cortex and amygdala. Other character istics of mutational diseases are penetrance, a measure of the proportion of individuals with a given genotype who will show the phenotype, and expressivity, referring to the severity of disease in an affected individual. Histologically, this group of para neoplastic disorders is characterized by extensive loss of neurons, accompanied by microglial proliferation, small patches of necrosis, and marked perivascular cuffing by lymphocytes and monocytes. Other copper-dependent enzymes show impaired function, such as cytochrome oxidase. In almost all clinical and pathologic material, there has been a strong relationship between the lacunar state and chronic hypertension, but also diabetes and hyper lipidemia. Staphylococci also commonly cause brain abscess, but pneumococci, meningococci, and H. Most often they are generalized grand mal or partial types; typical petit mal probably does not occur.

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Occasionally one encounters a rhabdomyosarcoma, Ewing tumor, carcinoid, and others that have metastasized, but these have such low incidence that cerebral metastases seldom become a matter of diagnostic concern. Both types of intrasellar cysts may compress the pituitary gland and mimic the endocrine-suppressive effects of pituitary adenomas. Surrounding the necrotic tissue are macrophages, astroglia, microglia, and many small veins, some of which show endothelial hyperplasia, contain fibrin, and are cuffed with polymorphonuclear leukocytes. The main items are drawn from Gesell and Amatruda and from the Denver Developmental Test. Neurons are relatively resistant though they can be secondarily affected by loss of glial support as well as reduced tissue perfusion. Among the most important considerations in this disease is the cerebral arteritis caused by varicella zoster virus of the ophthalmic division of the trigeminal nerve; it simulates in radiographic appearance granulomatous arteritis and giant cell arteritis. In some of these cases, the metabolic or rhea logic change appears to have brought out symptoms of stenosis in a large or small vessel, but just as often the vasculature is normal. Little or no eye contact is made, and the child is no more interested in another person than in an article of furniture. Treatment 1his varies with the type and size of the pituitary tumor, the status of the endocrine and visual sys tems, and the age and childbearing plans of the patient. Exceptionally there are vascular lesions with infarction of central parts of the nerve. In some cases progression is slower, with acquisition of single words by the first year, bilateral corticospinal signs (Babinski signs and hyperactive tendon reflexes), persistent retro enlarged spleen flexion of the neck, and strabismus. Usually there is little or no evidence of any personality deviation before the onset of stuttering, and psychotherapy has not had a significant effect on the the school population. However, clouding the issue of causality is the absence of perinatal complications in a large number of children with cerebral palsy and the large number of normal babies who are born after complicated deliveries. The affected infant may be normal at birth or exhibit only mucocuta neous lesions, hepatosplenomegaly, lymphadenopathy, and anemia. Affected individuals should be advised not to have children, a precaution that may not be necessary because fertility, especially in males, seems to be reduced by the disease. The sedimentation rate is elevated, as are the rheumatoid and antiglobulin factors. Bilateral Babinski signs are found in the first few days following rupture if there is hydrocephalus. Epilepsy-that is, flexion spasms in infancy-and delay in psychomotor develop ment are by no means diagnostic of tuberous sclerosis, as they occur in many diseases. Emptying contractions are inadequate, and there is a large residual volume even after the Crede maneuver (manual abdomi nal compression) and strong contraction of the abdominal muscles. One of these special abilities may be observed in a child with a mild form of autism (Asperger syndrome, see Chap. Serologic surveys indicate that the exposure to toxo plasmosis in adults is widespread (approximately 40 per cent of American city dwellers have specific antibodies); cases of clinically evident active infection, however, are rare. Introductory Remarks Multiple sclerosis is a chronic condition characterized clinically by episodes of focal disorders of the optic nerves, spinal cord, and brain, which remit to a varying extent and recur over a period of many years and are usually progressive. This is an excep tion to the rule that organs innervated by the autonomic nervous system receive only postganglionic fibers. Radiation injury seems to be the most important factor, coupled with the age of the patient (most are younger than 5 years old). With blockage of the vertebral artery, the anastomotic flow may be via the deep cervical, thyrocervical, or occip ital arteries or retrograde from the other vertebral artery and again through the posterior communicating arteries. Whether such long term monitoring should be adopted in routine practice is not yet certain, but it is being increasingly added in the evaluation of "cryptogenic" stroke. Treatment within 3 h of the onset of symptoms led to a 30 percent increase in the number of patients who remained with little or no neurologic deficit when reexamined 3 months after the stroke; this benefit persisted when assessed 1 year later in the study by Kwiatkowski and associates. Much of the work in understanding the function of these two proteins and their role in tumor formation has been performed in Drosophila and are summarized in the extensive review by Crino and colleagues. As mentioned above, the histologic feature that unites mitochondrial myopathies is the presence of ragged red fibers. Furthermore, in some cases associated with Hodgkin disease, there has been spontaneous improvement of the cerebellar symptoms. Boto and colleagues found that basal ganglia hemorrhages were prone to enlarge in the day or two after closed head injury and that those greater than 25 mL in volume were fatal in 9 of 10 cases.

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Exceptionally, the localized adult type of encephalitis is caused by the type 2 virus and the diffuse neonatal encephalitis by type 1. Polymorphisms of the gene are found in children with a number of specific but seem ingly unrelated language deficits. Corneal, pharyngeal, and cutaneous reflexes, originally depressed, return, and the limbs withdraw from painful stimuli. It seems possible that these transient symptoms represent a direct localized concussive effect, caused either by indentation of the skull or by impact on these parts of the brain against the inner table of the skull, but a vascular mechanism cannot be excluded. A deficiency of several lysosomal enzymes required for the catabolism of mucopolysaccharides, glycolipids, and glycoproteins have been found. Ninety percent of meningiomas are supratentorial, and the majority of infratentorial meningiomas occur at the cerebellopontine angle. However, Blanc and colleagues studied a sample of 123 consecu tive patients with clinical signs of neurologic involve ment and found the sensitivity of the index was only 75 percent and the specificity was 97 percent. A rapid neurologic survey can then be made, with attention to the depth of coma, size of the pupils and their reaction to light, ocular movements, corneal reflexes, facial movements during grimace, swallowing, vocaliza tion, gag reflexes, muscle tone and movements of the limbs, predominant postures, reactions to pinch, and reflexes. Any given behavioral function, in order to be expressed, must await the development of its neural substrate. Pathologic studies have disclosed the central type of autonomic failure to be somewhat heterogeneous. Semin Verhaeghen P, Marcoen A, Goossens L: Facts and fiction about memory a ging: A quantitative integration of research findings. As common as intracranial metastases are, metastases to the vertebral column, which eventually cause compression of the spinal cord and nerve roots. Often, the diagnosis of cerebral embolism is made at autopsy with out finding a source. Morphologic peculiarities and genetic features separate a certain group called Pelizaeus-Merzbacher disease; other types have been artificially delineated; as a result, a rela tively meaningless terminology has been introduced. It may be difficult to differenti ate a long-standing subdural hematoma from hygroma, and some chronic subdural hematomas are probably the result of repeated small hemorrhages that arise from the membranes of hygromas. This region is supplied by the lenticulostriate, choroidal, and Heubner recurrent arteries and is drained by deep veins, which enter the vein of Galen. Hemiparesis, incomplete hemi anopia, and aphasia, any of which may fluctuate over days, are also characteristic according to Jacobs and col leagues. Neutrophils and lymphocytes migrate from the adventi tia to the subintimal region, often forming a conspicuous layer. Small numbers of gram-negative diplococci in leukocytes may be indistin guishable from fragmented nuclear material, which may also be gram-negative and of the same shape as bacteria. A dissociated sensory deficit over the ipsilateral face and contralateral half of the body usually indicates a lesion in the lower brainstem, while a hemisensory loss including the face and involving all modalities indicates a lesion in the upper brainstem, in the thalamus, or deep in the white matter of the parietal lobe. The diagnosis can also be confirmed by finding eosinophilic inclusions in the arterioles of a skill biopsy (osmophilic with electron microscopy). There is now a reasonably sound body of information about the natural history of these lesions. Stereotactic needle biopsy is the preferred method of establishing the histologic diagnosis in sporadic cases. From the third decade of life to the beginning of the tenth decade, the average decline in weight of the male brain is from 1,394 to 1,161 g, a loss of 233 g. The glioblastomas are largely defined by the features of necrosis and anaplasia of nonneural elements such as vascular proliferation and are set apart from anaplastic astrocytomas on the basis not only of their histology but also by a later age of onset than astrocytoma and a more rapid course. This assumes importance in patients who may have acquired the ill ness in another part of the world in whom the correct diagnosis may be missed if the specific antibody for the regional organism is not sought. A singular advance in this field has been the identification in recent years of large numbers of genetic defects that underlie disorders of neuronal migration. Several reviews of this subject have appeared subsequently (see especially those of Jenkyn, of Benassi, and of Kokmen [1977] and their associates). The incidence of encephalomyelitis was less following chickenpox and rubella, and much less follow g mumps (the latter never seen in our pathologic mate nal). The predilection of these lesions for the crowns of con volutions attests to their traumatic origin (being thrown against the overlying skull) and distinguishes them from cerebrovascular and other types of cerebral lesions. Some patients will be found to have evidence of spontaneous or traumatic dissection of multiple extracranial vessels; this also occurs as a consequence of dissection of the aortic arch from chest trauma. The last is believed to be caused by a coincidental folic acid deficiency, but in some cases it may have been caused by chronic phenytoin administration (Nishimura et al).

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Ohno T, Tsuchida H, Fukuhara N, et al: Adrenoleukodystrophy: A clinical variant presenting as olivopontocerebellar atrophy. In patients with relatively late onset, a progressive dementia is the cardinal manifestation. However, some metabolic diseases are of such slow progression that they appear almost stable, especially the late-onset ones, such as one type of metachromatic leukodystrophy, late-onset Krabbe leukodystrophy, adult adrenoleukodystrophy, and adult hexosaminidase defi ciency (see Chap. After a bite by a seemingly healthy animal, surveil lance of the animal for a 10-day period is necessary. It is likely that leukoara iosis exist in a continuum with Binswanger disease and many elderly individuals who have these changes show cognitive impairment as discussed below. A slight bewilder ment, slowness in comprehension, or loss of capacity for sustained mental activity may be the only deviations from normal, and signs of focal cerebral disease are wholly lacking. They have been attributed by Halliday and McDonald to ephaptic trans mission ("cross-talk") between adjacent demyelinated axons within a lesion. A much larger number of patients, however, are depressed, irritable, and short-tempered, sometimes as a reaction to the disabling features of the disease but also apparently as a primary effect of the brain disease; the incidence of depression has been estimated to be as high as 25 to 40 percent in some series. Initially there was a decline in proficiency at school, temper outbursts and other changes in personality, diffi culty with language, and loss of interest in usual activities. Their initial symptoms are vague, and not until some time has elapsed will signs of focal brain disease appear; when they do, they are not always of accurate localizing value. As a general rule, there is no progression of weakness after the tempera ture has been normal for 48 h. It is this failure of immune function that explains the development of a wide range of opportunistic infections and unusual neoplasms. There is a later-onset form of the disease in which the course is more protracted and the neurologic mani festations (rigidity and spasticity, cerebellar ataxia, and myoclonus) are more pronounced. Embolic occlusion limited to one of the distal branches of the superior division, perhaps the most common stroke seen in clinical practice, produces a more circumscribed infarct that further fractionates the above-described syn drome. In one of the cases we followed, several small lesions, presumably infarctions, were situated in the white matter and simulated multiple sclerosis. A lumbar puncture is often performed for diagnos tic purposes and the pressure measured carefully but here too, there is no uniformly agreed upon approach. There is also the possibility of ischemia in this territory from occlu sion of more proximal vessels, particularly the basilar artery, or infraction in the distal territory of the vessel as a result of global failure of cerebral perfusion, as in severe hypotension. The serum calcium levels in the aforementioned diseases are usually normal and there is no explanation of the calcification. 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. Headache, lethargy, and confusion are present in some cases and there are mild meningeal signs. This disease has similarities to juvenile dopa-responsive dystonia, which is exquisitely sensitive to L-dopa treat ment (as discussed in Chap. Cortical electrographic discharges were found to precede each myoclonic twitch (cortical myoclo nus). It should be mentioned that many patients, particularly children, hyperventilate spontaneously after head trauma. Age is an impor tant prognostic factor; fewer than 10 percent of patients older than age 60 years survive for 18 months, in com parison to two-thirds of patients younger than age 40 years. An extensive randomized study by Temkin and colleagues demonstrated that when administered within a day of injury and continuing for 2 years, phenytoin reduced the incidence of seizures in the first week, but not thereafter. Prevalence studies from Sweden indicate an occur rence of 1 per 1 0,000 girls; thus Rett syndrome is more com mon than phenylketonuria. The picture of total occlusion of the stem is one of contralateral hemiplegia (involving the face, arm, and leg as a result of infarction of the posterior limb of the inter nal capsule), hemianesthesia, and homonymous hemianopia (because of infarction of the lateral geniculate body), with deviation of the head and eiJeS toward the side of the lesion. Ependymitis, choroidal plexitis: it is doubtful if there are any recognizable clinical effects. It is as though the child were too hurried to take the trouble to pro nounce each word carefully and to compose sentences.

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In recent years, balloon angioplasty and stenting of the carotid artery have become increasingly popular as an alternative to surgery (see below). In some instances there is an evident disorder in the spatial arrangements of numbers that has been termed "anarithmetia" as noted in Chap. The only obstacle to eradication of the disease elsewhere is inadequate utilization of the vac cine. Possibilities to be remembered, particularly in cases of acute quadriplegia, is traumatic cord compres sion or the rarer cartilaginous embolism of the cervical cord (see "Fibrocartilaginous Embolism" in Chap. On occasion, brain swelling reaches a degree that requires specific therapy, as out lined in "Management of the Acutely Comatose Patient and Management of Raised Intracranial Pressure" in Chap. A broad classification of the infl ammatory demyelin demyelination has ating diseases is given in Table 36-1. The problem in interpreting these spells is their similarity to posttraumatic amnesia and the repetitive stereotyped questioning regarding orientation that is common to both processes. Erratic performance that is not the result of a defect in comprehension is also characteristic. Its pres ence at birth is disclosed by the lack of facial move ments and of full eye closure. In occlu sion of the internal carotid artery in the neck, there may be anastomotic flow through the anterior and posterior communicating arteries of the circle of Willis from the external carotid artery through the ophthalmic artery or via other smaller external-internal connections. Slotman B, Faivre-Finn C, Kramer G, et al: Prophylactic cranial irradiation in extensive small-cell lung cancer. However, mechanism of these disturbances is thought to be a displacement of the brain and tearing of the olfactory nerve filaments in or near the cribriform plate, through which they course, rather than being attributable to a fracture. Myelination of the anterior frontal and temporal lobes occurs later, during year, myelination of the cerebrum is largely complete. Collongues N, de Seze J: Current and future treatment approaches for neuromyelitis optica. It should be evident from the foregoing discussion that normal findings in any of these tests, including the muscle biopsy, do not exclude mitochondrial disease. Any pain in the globe is short lived and persistent pain should prompt an evaluation for local disease. Under the neu rosurgical conditions of four decades ago, with careful selection of cases, Rasmussen (also Penfield and Jasper) was able to eradicate seizures in 50 to 75 percent of cases by excision of the focus; the results currently are some what better. In this type, measles or exposure to measles precedes the encephalitis by 1 to 6 months. The effect of nerve root blocks is inconsistent, but this procedure may afford temporary relief. At that time, the incidence of this tumor, formerly called reticulum cell sarcoma, was negligible. Persistent cerebral ischemia and infarction may occasionally complicate migraine in young persons as dis cussed in Chap. Some patients with impending cerebellar-tonsilla r herniation are disinclined to sit and have vertical down beating nystagmus. The acute lesion is subtle; it is not a typical fibrinoid necrosis of the vessel wall, like that in hypertensive encephalopa thy, and there is no cellular infiltration. A number of studies have come to the conclu sion that delaying radiation in younger patients may avoid the consequences of dementia and hypopituitarism (Peterson and DeAngelis), but others have suggested that the tumor itself and antiepileptic drugs cause more diffi culty than high-dose radiation. Surgery seems preferable for the smaller lesions and embolization for larger and inaccessible ones. Some hereditary atax ias are intermittent or episodic, one of which is responsive to acetazolamide and is the result of an abnormality of the calcium channel as discussed in Chaps. Although the abruptness with which the stroke develops and the lack of prodromal symptoms point strongly to embolism, the diagnosis is based on the total clinical circumstances. The issue of the neurologic complications of cardiac sur gery may be summarized by noting that strokes originat ing from the aorta are the main cause of cognitive failure. The history usually discloses that menarche had occurred at the appropriate age; primary amenorrhea is rare. Close examina tion may also reveal an alteration in muscle tone and a slight degree of cerebellar ataxia.


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