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If there is no evidence of upper or lower motor neuron disease but certain movements are nonetheless imperfectly performed, one should look for a disorder of position sense or cerebellar coordination or for rigidity with abnormalities of posture and movement due to disease of the basal ganglia (Chap. The common uncomplicated autosomal dominant form of disease has been linked to chromosomes 2p, 8q, 14q, and 15q, the 2p variety being most frequent; the recessive variety has been linked to 8p, 15q (the most frequent recessive type), and 16q. The inferior cerebellum is usually affected, causing vomiting, vertigo, and ataxia. One must always keep in mind that syndromes are not disease entities but rather abstractions set up by clinicians in order to facilitate the diagnosis of disease. Although the nervous system and musculature develop independently, muscle fibers continue to grow after birth only when they are active and under the influence of nerve. The peripheral extensions of these cells constitute the sensory nerves; the central projections of these same cells form the posterior (dorsal) roots and enter the spinal cord. In most cases, the cerebellar syndrome evolves over a period of several weeks or months, after which it remains unchanged for many years. Tumors of the pineal gland, which were not included in earlier classifications, comprise germ-cell tumors, the rare pineocytomas, and pineoblastomas. Under the electron microscope, the particles of stored material appear as membranous cytoplasmic bodies. Unexplained deafness or diabetes in family members might also raise the level of suspicion of a mitochondrial disorder. But in recent years, largely through the work of Ross, it has been shown that this deficit in prosody is also present in patients with strokes involving the territory of the right middle cerebral artery, i. Imaging studies of the brain had been thought until recently to be of little value, but up to 80 percent of cases show a subtle hyperintensity of the lenticular nuclei on T2-weighted images when the disease is fully established. Of all neuromuscular systems, the masseter innervation seems to be the most sensitive to the toxin. Proximal atrophy, weakness Weakness may be periodic, reflexes may be depressed or absent, rarely severe myoglobinuria Proximal muscle pain and weakness, sensorimotor neuropathy, cardiomyopathy 1. The latter disorder affects men and women alike, with onset in middle or late adult life. According to Erikson, the developmental challenge during the preschool period is autonomy versus shame and doubt c. This is an exception to the rule that organs innervated by the autonomic nervous system receive only postganglionic fibers. A slightly stooped posture, varying degrees of slowness and stiffness of walking, shortening of the stride, slight widening of the base, and a tendency to turn en bloc are the main objective characteristics. There are many other, less frequent lacunar syndromes, too numerous to tabulate here. This disorder was first described by Farmer and Mustian and more recently by Baloh and Winder, who have pointed out that both the episodic vertigo and ataxia are markedly reduced or abolished by the administration of acetazolamide. Curiously, in the extrapyramidal disorder of progressive supranuclear palsy, the dysarthria and dysphonia tend to be spastic in nature. The main output of the deep cerebellar nuclei is excitatory and is transmitted through mossy and climbing fibers. A second theory, the multifactorial theory of Thurstone, proposed that intelligence consists of a number of primary mental abilities such as memory, verbal facility, numerical ability, visuospatial perception, and capacity for problem solving, all of them more or less equivalent. Meningovascular syphilis and fungal and tuberculous meningitis and other forms of chronic basal meningitis are considerations in this age group; the strokes are usually of the cavitary lacunar type, resulting from infectious-inflammatory occlusion of small basal vessels. When present in an infant, it should suggest brachial plexus trauma from birth; in a child, poliomyelitis or other viral infection of the spinal cord; and in an adult, poliomyelitis, syringomyelia, amyotrophic lateral sclerosis, or a brachial plexus lesion. Demyelination of the intrapontine part of the facial nerve and possibly supranuclear disinhibition of the facial nucleus have been the postulated mechanisms. The radiologic picture consists of a series of transverse constrictions, giving the appearance of an irregular string of beads or a tubular narrowing; it is observed bilaterally in 75 percent of cases. Clinical Features Neurologic features of Williams syndrome include mild intellectual impairment, unusual behavior, and motor symptoms. These anatomic and biochemical properties of muscle also suggest some of the ways in which this tissue can be affected by disease. Forster has demonstrated that in certain types of reflex epilepsy, the repeated presentation of the noxious stimulus may eventually render the stimulus innocuous.

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Actually, most patients with high intracranial pressure complain of bioccipital and bifrontal headaches that fluctuate in severity, probably because of traction on vessels or dura. These symptoms may include a subjective sense of numbing, detachment or absence of emotional responsiveness, derealization, depersonalization, and dissociative amnesia. As little as 10 mg/kg per day may eliminate the movement disorder and permit normal functioning. Proprioception is diminished or lost in distal and, to some extent, proximal body parts, giving rise also to ataxic movements, often quite severe, and to pseudoathetosis. A second group of patients with color agnosia have no difficulty with color perception (i. The accumulation of plasma filtrate, with its high protein content, in the extracellular spaces and between the layers of myelin sheaths would be expected to alter the ionic balance of nerve fibers, impairing their function, but this has never been demonstrated satisfactorily. It has been suggested that this syndrome is due to occlusion of the labyrinthine division of the internal auditory artery, but so far anatomic confirmation has not been obtained. Tapping the chin with the jaw muscles relaxed stimulates proprioceptive afferents that terminate in the mesencephalic nucleus of the midbrain, which sends collaterals to the motor nucleus of the fifth nerve and causes the masseters to contract. An acute encephalitic, myelitic, or encephalomyelitic process of this type is observed in a number of clinical settings and is more common in children. Placing the patient prone or placing the limbs in abduction and extension facilitates the development of predominantly extensor postures. Stupor describes a state in which the patient can be roused only by vigorous and repeated stimuli, at which time he opens his eyes, looks at the examiner, and does not appear to be unconscious; response to spoken commands is either absent or slow and inadequate. The abnormality is sometimes less pronounced in recumbency and increased when the head is thrown forward. Usually the pain is located on one side of the head in carotid occlusion, at the back of the head, or simultaneously in forehead and occiput in basilar occlusion, and behind the ipsilateral ear or above the eyebrow in vertebral occlusion. Under the title of neck-tongue syndrome, Lance and Anthony have described the occurrence of a sharp pain and tingling in the upper neck or occiput on sudden rotation of the neck associated with numbness of the ipsilateral half of the tongue. Interferon, which has been effective in treating the hepatitis, may also ameliorate the neuropathy, but greater success has been achieved with cyclophosphamide. While well documented, this occurs rarely and only after an interval of many years. The headache can be expected to improve within a day or two of beginning treatment; failure to do so brings the diagnosis into question. Furthermore, it is not surprising that the participation of certain areas of the brain not primarily involved in memory function, particularly the language and visuospatial areas, are required for the performance of certain memory tasks. Neurocardiogenic Syncope this entity, a component or perhaps a subtype of vasodepressor syncope, has received attention as a cause of otherwise unexplained fainting in healthy and athletic children and young adults. They viewed function not as the direct property of a particular, highly specialized group of cells in one region of the cerebrum but as the product of complex, diffusely distributed activity by which sensory stimuli are analyzed and integrated at various levels of the nervous system and are united, through a system of temporarily acquired (experientially derived) connections, into a working mosaic adapted to accomplish a particular task. The attacks of vertigo usually cease when the hearing loss is complete, but there may be an interval of months or longer before this occurs. Usually this is the result of improper placement of retractors, which may compress the nerve directly or indirectly by undue pressure on the psoas muscle. Despite the fact that the disease is due to a transmissible agent, the lesions show no evidence of an inflammatory reaction and no viral particles are seen. The pathogenesis of the vascular lesion is unknown (both vasospasm and arteritis have been reported), and the same state occurs with cocaine, as described below. Seizures Following Stroke With the exception of infarction due to cerebral venous occlusion, epileptic seizures following stroke are not a great problem. Other Patterns of Evolution In addition to the special configurations discussed further on, there are many patterns of neuromuscular involvement other than the one just described. Furthermore, the concentration of these substances, which include methylguanidine and myoinositol, has been shown to correlate with the degree of neurotoxicity (Funck-Brentano et al). The releasing factors have overlapping functions, and the hypothalamic nuclei act on many parts of the brain in addition to the pituitary. The most distinctive members of this category of neurologic disease are the leukodystrophies and the so-called lysosomal storage diseases.

Syndromes

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In western Europe and the United States, the most common rabid species are raccoons, skunks, foxes, and bats among wild animals and dogs and cats among domestic ones. From the internal pallidum, two bundles of fibers reach the thalamus- the ansa lenticularis and the fasciculus lenticularis. There is no acoustic-induced startle or myoclonus, and head size is normal or slightly reduced. The spores may remain dormant for many months or years, but when they are introduced into a wound, especially if a foreign body or suppurative bacteria are present, they are converted into their vegetative forms, which produce the exotoxin tetanospasmin. In advanced cases, weakness or paralysis of voluntary movements of the face, tongue, larynx, and pharynx are added (bulbar spasticity or "pseudobulbar" palsy; see pages 426 and 445). Finally, it was Russell Brain, in 1948, who put cervical spondylosis on the neurologic map, so to speak. Intractable pain may be the leading symptom of both hysteria and compensation neurosis. The clinical picture will depend on the location and size of the infarct, which, in turn, relates to the site of the occlusion, the pattern of the circle of Willis, and the other ischemia-modifying factors mentioned earlier. For these reasons the current authors agree with Hughes in classifying this condition with the demyelinative diseases. In the twin brothers there were signs of Friedreich ataxia; postmortem examination of one showed a degeneration of the posterior columns and spinocerebellar tracts but not of the corticospinal tracts. In the veins, swelling of the endothelial cells and infiltration of the adventitia also occur. In the early and intermediate stages of the illness, special psychologic tests aid in the quantitation of some of these abnormalities, as indicated in the later part of this chapter. The presence of such a response indicates that the patient can at least perceive light, and if there is a claim to the contrary, the patient is either hysterical or malingering. Because of the danger of prolonged arterial spasm in patients who have vascular (particularly coronary) disease or are pregnant, the use of ergotamine is not advised. Treatment Once symptoms begin, it is doubtful if any treatment is of consistent value. It is preferable to first palpate the regions that are the least likely to evoke pain. Criteria suggest that the pain is significant enough to cause marked distress or impairment in social, occupational, or other important areas of functioning. The classification of seizures and of the epilepsies is constantly being modified. Etiology of Duchenne and Becker Dystrophies the most important development in our understanding of the Duchenne and Becker muscular dystrophies was the discovery by Kunkel of the abnormal gene on the X chromosome and of its gene product, dystrophin (Hoffman et al). Treatment consists of optimizing therapy for the medical condition and using standard mood disorder treatments. Some of these data come from studies of sheath fenestration for ischemic optic neuropathy, a condition not comparable to the disc swelling of pseudotumor. The pain has no specific features; it tends to be deep-seated, usually nonthrobbing (occasionally throbbing), and is described as aching or bursting. Baud and colleagues and more recently Brent et al and Jacobsen have advocated the use of intravenous 4-methylpyrazole (fomepizole), which is a far more effective inhibitor of alcohol dehydrogenase than is alcohol. To be distinguished also are the Tolosa-Hunt syndrome of ocular pain and ocular motor paralysis (see further on) and the paratrigeminal syndrome of Raeder, which consists of paroxysms of pain somewhat like that of tic douloureux in the distribution of the ophthalmic and maxillary divisions of the fifth nerve, in association with ocular sympathetic paralysis (ptosis and miosis but with preservation of facial sweating). Asymmetry in elicited eye movements remains a dependable sign of focal brainstem disease. This is probably due to the intrusion of brief sleep periods during the waking state and represents a sizable amount of time if summated (it is virtually impossible to deprive a human being or animal totally of sleep). Fields has elaborated a theoretical explanation of the overlap of pain and depression. A stereotyped episodic encephalopathy has been associated with bismuth intoxication, usually arising from the ingestion of bismuth subgallate.

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In addition to its generalized effects on the motor neurons of the spinal cord and brainstem, there is evidence that the toxin acts directly on skeletal muscle at the point where the axon forms the end plate (accounting perhaps for localized tetanus) and also upon the cerebral cortex and the sympathetic nervous system, in the hypothalamus. As the clonic lature is seized in a spasm and air is forcibly emitted through the phase asserts itself, the spikes become mixed with slow waves and closed vocal cords. The defects are in rocking the body from side to side, so that the feet can clear the floor, and in moving the legs quickly enough to overtake the center of gravity. Meningovascular Syphilis this form of neurosyphilis should always be considered when a young person has one or several cerebrovascular accidents, i. All ingested alcohol except that metabolized by alcohol dehydrogenase in the stomach wall is carried by the portal system to the liver. Minor degrees of visual impairment may be disclosed by alternately stimulating each eye with a bright white or colored object, enabling the patient to compare the intensity of vision in the two eyes. Emotional lability is a frequent accompaniment of diffuse cerebral diseases such as Alzheimer disease, but these diseases, of course, also involve the limbic cortex. The vertigo in these circumstances usually improves in a few days or weeks and is rarely accompanied by impairment of hearing- in distinction to the vertigo that follows fractures of the temporal bones (as described earlier in this chapter in the discussion of deafness). Although atheromatous plaques may narrow the lumen of an artery, causing stenosis, complete occlusion is nearly always the consequence of superimposed thrombosis ("atherothrombosis"). In the second type Many additional cases were soon uncovered, and by 1991, in a of case, in which there had been some type of seizure at an earlier publication devoted to this subject (edited by Andermann), Rasperiod, one should suspect a developmental disorder, parturitional mussen was able to summarize the natural history of 48 personally hypoxic-ischemic encephalopathy (birth injury), or one of the heobserved patients. Guerra and colleagues have reported on 57 such patients, mostly young adults, who underwent wide frontotemporal craniectomy, unilateral in 31 and bilateral in 26. These sensory defects tend also to be asymmetrical (it is noteworthy that symmetric sensory symptoms and signs of identical type are seen with subacute combined degeneration due to B12 deficiency. The cell death pathways differ in their triggering factors, temporal profile, biochemical mechanisms, and morphologic markers. Yet one observes particular patterns of disturbed higher cerebrocortical function with such regularity as to make them clinically useful in identifying certain diseases. Note that areas 41 and 42, the primary auditory receptive areas, are shown on the lateral surface of the temporal lobe but extend to its superior surface, deep within the sylvian fissure. Cisplatin and carboplatin provide similar marginal improvement in survival beyond that obtained by debulking and radiation therapy. The latter should be looked upon not as the sum of genetic and environmental factors but as the product of the two. The main object of treatment is to prevent respiratory depression and its complications as described in Chap. The interested reader will find further details concerning cerebellar influences on ocular movements in the monograph by Leigh and Zee and the review by Lewis and Zee. The most prominent neuronal changes are seen in the midbrain, spinal cord, and cerebellum. This is manifest by pupillary constriction on adduction of the eye or by retraction of the upper lid on downward gaze or adduction. Anoxic encephalopathy has been the most common cause, but a few cases have been attributed to drug overdose (Ropper 1981). In other cases it is not necessary to carry the clinical analysis beyond the stage of the anatomic diagnosis, which in itself may virtually indicate the cause of a disease. The prompt use of thiamine prevents progression of the disease and reverses those lesions that have not yet progressed to the point of fixed structural change. This may be difficult, for the lipoma may be fused with the dorsal surface of the spinal cord. Neoplastic transformation of abnormal glial cells, a not infrequent occurrence, usually takes the form of a large-cell astrocytoma, less often of a glioblastoma or meningioma. There is a fine reticulum reaction between the reticulum cells derived from fibroblasts and microglia or histiocytes. Cauda equina epidural abscess without neurologic signs may in many cases be treated solely with antibiotics, although some surgeons favor drainage, which must be undertaken in any case if osteomyelitis develops. Some children with fragile X syndrome, like children with other forms of developmental delays or learning disabilities, may benefit from medication designed to overcome attention-deficit/hyperactivity disorder or other disorders. These early symptoms may improve in response to antimicrobial agents, but within a few days or weeks, recurrent headache, slowness in mentation, focal or generalized convulsions, and obvious signs of increased intracranial pressure provide evidence of an inflammatory mass in the brain. Other vagal effects are perspiration, increased peristaltic activity, nausea, and salivation. The gait disorder may be accompanied by similarly exaggerated movements of the arms, as though to impress the observer with the great effort required to walk and maintain balance.

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Hallervorden-Spatz Disease this disease is also known as pigmentary degeneration of the globus pallidus, substantia nigra, and red nucleus. Its other characteristic feature is a nightly recurrence, between 1 and 2 h after the onset of sleep, or several times during the night; less often, it occurs during the day, unattended by aura or vomiting. In some cases the underlying disease is not apparent (this applies to about half of our cases), and the clonic movements may be mistaken for some type of slow tremor or extrapyramidal movement disorder. They may think about moral issues in terms of individual rights, the social contract, and universal principles. The glossopharyngeal, vagus, and spinal accessory nerves leave the skull together through the jugular foramen and are then distributed peripherally. They now assume greater importance in developed countries as the number of immunosuppressed persons increases. In all of these patients, following the initial period of stabilization, the matters of interest are the clinical and radiologic assessments, with the purpose of uncovering a surgically remediable lesion- namely a subdural or epidural hematoma- or a treatable intraparenchymal hematoma. An attack of tetanus does not confer permanent immunity, and persons who recover should be actively immunized. One notes in them a tendency to describe their pain vaguely and a preference to discuss the degree of their disability and their mistreatment at the hands of the medical profession. Weakness can be demonstrated by asking the patient to shrug his shoulders; the affected side will be found to be weaker, and there will often be evident atrophy of the upper part of the trapezius. In some, the abnormal movements are so mild as to be misinterpreted as restlessness or "the fidgets"; in others, every attempted voluntary act provokes violent involuntary spasms, leaving the patient nearly helpless. The electrical activity of various muscles is recorded both at rest and during active contraction by the patient. However, as for all the aforementioned tests, they must be interpreted in the context of the history and clinical examination; otherwise they are subject to overuse and overinterpretation. Discontinuation of medication, even after years of effective control, has resulted in relapse. Glucose is reduced to levels below 40 mg/dL but rarely to the very low values observed in pyogenic meningitis; the glucose falls slowly and a reduction may become manifest only several days after the patient has been admitted to the hospital. In such cases, the temporal horns tend to be enlarged more than the rest of the ventricular system, reflecting the disproportionate atrophy of the inferomedial temporal lobes. Ozeretzkii has combined these in a scale that often discloses arrests in motor development in the mentally retarded. A few observations indicate that it is short-term (retentive) memory, rather than immediate or long-term memory, that is impaired; this feature and the subsequent amnesia for the episode are somewhat reminiscent of the disorder known as transient global amnesia (page 379) but without the incessant questioning and competence in nonmemory mental activites that characterizes the latter. The first generation of these drugs were fungal metabolites (lovastatin, paravastatin, simvastatin) and were infrequently implicated in muscle damage, but the new synthetic ones (atorvastatin, fluvastatin, cerivastatin) are more frequently toxic, especially when given with gemfibrizil. 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). It has been stated that patients with discrete relapses have a better prognosis than those with a progressive course. In 1956 and 1957, three different laboratories isolated what has come to be called the human cytomegalovirus (see Weller). It is apparent from this overview that the clinical picture of brain abscess is far from stereotyped. The former is almost certainly of nutritional origin; in the latter a nutritionalmetabolic etiology seems likely but has not been established. Homonymous hemianopia may occur with posterior capsular lesions, but it must be distinguished from visual hemineglect of contralateral space. The neurons utilizing these substances and the manner in which they operate are just now being identified. Fibrillation potentials or positive sharp waves can be seen as early as 2 weeks after injury to a nerve and almost always by 21 days. Treatment Despite the incompleteness of our understanding of the role of disordered ammonia metabolism in the genesis of hepatic coma, an awareness of this relationship has provided the few effective means of treating this disorder: restriction of dietary protein; reduction of bowel flora by oral administration of neomycin or kanamycin, which suppress the urease-producing organisms in the bowel; and the use of enemas. Its most important adverse effects are neuropathy (see page 1133) and hepatitis, particularly in alcoholics. This condition occasionally occurs at higher levels and gives rise to a myelopathy. The major clinical manifestation is weakness that evolves more or less symmetrically over a period of several days to a week or two, or somewhat longer. The presenilins interact with or may be a component of secretase, the enzyme that produces the A 42 fragment.

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In other instances, cerebellar ataxia (Brownell-Oppenheimer variant) or visual disturbances (Heidenhain variant) precede the mental changes and may be the most prominent features for several months. Several conditions must be distinguished clinically from subdural empyema- a treated subacute bacterial meningitis, cerebral thrombophlebitis, brain abscess (see further on), herpes simplex encephalitis (page 638), acute necrotizing hemorrhagic leukoencephalitis (page 792), and septic embolism due to bacterial endocarditis (see further on in this chapter). Treatment of the pituitary adenoma and correction of the hormonal changes restores strength. Abnormal "Spontaneous" Activity With the muscle at rest, spontaneous activity of single muscle fibers and of motor units, known respectively as fibrillation potentials and fasciculation potentials, is abnormal. The cause of these lesions is not known, but they may represent a response to nonunion of fractures, taking the form of an excessive production of fibrous inflammatory tissue. A body of indirect evidence has been marshaled in support of this idea, based largely on alterations in humoral and cell-mediated immunity to viral agents (see reviews of R. Corticosteroids are added at any point as needed to control prominent neurologic symptoms. Complaints of weakness and fatigue, depression, anxiety, insomnia, nervousness, irritability, palpitations, etc. In addition, menstrual irregularities and polycystic ovarian syndrome may appear in young women taking the drug, perhaps as a consequence of the aforementioned weight gain. The development of adult gonadal function and the further evolution of psychosexual impulses create a bewildering array of new challenges in social adaptation. Role confusion A 25-year-old single man with a normal mood believes he is the incarnation of a great religious leader. Beyond these morphologic distinctions, the intrinsic organization of the neocortex follows a pattern elucidated by Lorente de No. However, under conditions of disease, motor or sensory functions may be affected independently. These sympathetically mediated effects are eliminated by sectioning of the cervical spinal cord and by alpha-adrenergic blockade. A decremental response to stimulation can usually be obtained from the facial, hand, or proximal limb muscles, which may or may not be clinically weak. Corticosteroids have been helpful in some of our patients with the lymphoid diseases; in others, the neuropathy resolves spontaneously or with radiation of the lymph nodes but otherwise progresses for months. The latter (type 2 fibers) fire in bursts and are utilized in quick phasic rather than sustained reactions. Occlusion of the anterior cerebral arteries is usually embolic, but atherothrombotic lesions are known and surgical instances have been described (occlusion with operations on anterior communicating aneurysms). Included in this category are polyarteritis nodosa, the Churg-Strauss syndrome (allergic bronchial asthma and eosinophilia), rheumatoid arthritis, lupus erythematosus, scleroderma, cryoglobulinemia, Wegener granulomatosis, and the aforementioned idiopathic variety of vasculitis that is confined to the cranial peripheral nerves and has no systemic manifestations. It is estimated that in one-quarter to one-third of all cases of paralysis of the recurrent laryngeal nerve no cause can be established, i. Differential Diagnosis Several problems arise in the diagnosis of spinal cord tumors in addition to those previously mentioned. Another inapparent or confounding stroke that may be mistaken for psychiatric disease is an attack of paraphasic speech from embolic occlusion of a branch of the left middle cerebral artery. This longitudinal fissuring and doubling of the cord are spoken of as diplomyelia. Widowers, in contrast to widows, are more likely to remarry and are more prone to early death. According to Finelli et al, neurologic abnormalities occur in approximately 10 percent of cases of adult celiac sprue. Damage to single peripheral nerves at the site of injection of heroin and from compression is a relatively common occurrence. The latter is said to interfere with the enunciation of any syllable of a word (not just the first), to favor involvement of grammatical and substantive words, and to be unaccompanied by anxiety and facial grimacing. With the arms at the sides, the shoulder on the affected side droops and the scapula is slightly winged; the latter defect is accentuated with lateral movement of the arm (with serratus anterior weakness, winging of the scapula is more prominent and occurs on forward elevation of the arm). Impairment of visual function and particularly of vestibular function with normal aging are important contributors. Finally, a paroxysm of myoglobinuria, due to an infection or a metabolic myopathy, especially if there has been unusually strenuous exertion, may be followed within hours by a rapidly developing paresis of limb muscles, usually in association with severe pain.

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Prophylaxis All household contacts of patients with meningococcal meningitis should be protected with antibiotic treatment. With a laterally situated disc protrusion between the fifth and sixth cervical vertebrae, the symptoms and signs are referred to the sixth cervical root. More recently a myxopapillomatous type, localized exclusively in the filum terminale of the spinal cord, has been identified (see Chap. In the past, they were used to assess for functional evidence of subclinical brainstem disease as another site of nervous system involvement in the evaluation of possible multiple sclerosis; neuroimaging has now replaced this indication. Mild grades of anemia are usually asymptomatic, and lassitude is far too often ascribed to it. A symmetrical sensory polyneuropathy or sensory ganglionopathy is the most common pattern. Another characteristic feature is the initiation of a jab or a series of jabs of pain by stimulation of certain areas of the face, lips, or gums, as in shaving or brushing the teeth, or by movement of these parts in chewing, talking, or yawning, or even by a breeze- the so-called trigger zones. Another pontine reflex that utilizes afferent trigeminal sensory nerves is the blink reflex. By intervening in what Vygotsky called the zone of proximal development (ie, the gap between actual and potential skill acquisition), sensitive and patient adults can provide the cognitive scaffolding needed for the child to progress. Of course, the solution to a clinical problem need not always be schematized in this way. In particular, hippocampal atrophy increases at the rate of less than 2 percent per year in healthy elderly people, in comparison to 4 to 8 percent a year in early Alzheimer disease. For example, a dissociation of mood and affect is characteristic of the aforementioned pseudobulbar state in which the patient displays extremes of easily precipitated and unexpected crying or laughing while reporting only slight alterations in subjective emotion. Most such cases turn out to have motor neuron disease, but rare instances of myasthenia gravis, acid maltase deficiency, polymyositis, nemaline myopathy, Lambert-Eaton syndrome, or chronic inflammatory demyelinating polyneuropathy may present in this way. These abnormalities are brought out by finger-to-nose or toe-to-finger movement, running the heel down the opposite shin, or tracing a square in the air with a hand or foot. A current speculation, shared with other degenerative disease, is that the absence of torsin A renders neurons unduly sensitive to oxidative stress (Walker and Shashidharan). Chronic atrophic rhinitis; sinusitis of allergic, vasomotor, or infective types; nasal polyposis; and overuse of topical vasocontrictors are other common causes. If respiration and motor function were normal (except for early decorticate posturing) and there was no extraneural trauma, 94 percent of the patients recovered. Pain is often dramatically relieved, but the sensorimotor defects improve only slightly. Usually, the polyneuropathy develops gradually, although in some patients it has a subacute onset or, after being established for some time, a tendency to worsen fairly abruptly. In both hypoparathyroidism and pseudohypoparathyroidism- the latter with characteristic skeletal abnormalities and, in some instances, mental slowness- the most important muscle abnormality is tetany. In some cases of impaired vision and photic epilepsy, eye rubbing or moving the fingers rhythmically across the field of vision is observed, especially in mentally retarded children. With posterior lesions, weakness is also less and is attended by sensory loss, hemianopia, impaired visual pursuit to the opposite side, Wernicke-type aphasia (leftsided lesions), and anosognosia (right-sided). 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. Irritation, redness, photophobia, pain, diplopia and strabismus, changes in pupillary size, and drooping or closure of the eyelids are another group of major ocular symptoms and signs. The symptoms must result in clinically significant distress and markedly interfere with normal functioning. Rarely, laughter may be the most striking feature of an automatism (gelastic epilepsy). When sound of intensity greater than 70 to 90 dB above threshold hearing reaches the inner ear, the stapedius muscles on both sides contract reflexly, relaxing the tympanum and offering impedance to further sound. Intramedullary lesions are usually gliomas, ependymomas, or vascular malformations or, in the context of a known carcinoma, intramedullary metastases. An approach to treating such patients is given further on, in the section on treatment, under "Patients with Only Transient Unconsciousness. The most important difference, of course, is that persons in sleep, when stimulated, can be roused to normal consciousness. The center of the abscess takes on the character of pus; at the periphery, fibroblasts proliferate from the adventitia of newly formed blood vessels and form granulation tissue, which is readily identified within 2 weeks of the onset of the infection.

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Hemifacial Spasm the facial muscles on one side may be involved in painless irregular clonic contractions of varying degree (hemifacial spasm). In getting up from a recumbent position, the patient turns his head and trunk and pushes himself sideways to a sitting position S. Aside from the hereditary spastic paraplegias, which may become evident in the second and third years, the common causes of weak spastic legs are prematurity and matrix hemorrhages. They produce a quadriparesis with pain in the back of the head and stiff neck, weakness and atrophy of the hands and dorsal neck muscles, marked imbalance, and variable sensory changes- or, if they spread intracranially, there may be signs of cerebellar and lower cranial nerve involvement. Chordoma this is a soft, jelly-like, gray-pink growth that arises from remnants of the primitive notochord. Some remarkable cases of meningioma have involved repeated transient attacks for decades. In others, the hands are stiff, movements are clumsy, and speech is mildly dysarthric. Also mentioned here is the distressingly painful compression of the plantar branches of the sciatic nerve. In the case of a unilateral phrenic nerve paralysis, there is mild dyspnea on exertion and one hemidiaphragm is found to be elevated on the chest film. It should be pointed out that all disorders of movement due to lesions of the extrapyramidal system have certain other attributes in common. As indicated earlier, knowledge of the anatomy of language has come almost exclusively from the postmortem study of humans with focal brain diseases. Another unusual syndrome consists of congenital absence of portions of the abdominal muscles ("prune belly"), often in association with arthrogryposis and a defect of ureters, bladder, and genital organs. Neurologic deficits were mainly sensorimotor and aphasic; only 6 patients had visual symptoms. In their initial report they described five patients, all with a rapid evolution of polyneuropathy and very slow and poor recovery. Empiric treatment with antidepressant medication or, failing this, with electroconvulsive therapy is one way out of the dilemma. Of the four cases, three also showed demyelination of the posterior columns of the spinal cord, no doubt an expression of the associated sensory polyradiculopathy. This biopathologic approach to stroke will likely guide the next generation of treatments and has already had a pronounced impact on the direction of research in the field. Release of oral behavior Depending on how this state is viewed, it may be interHypersexual behavior B preted as a heightened threshold to stimulation, inattentiveness Figure 25-3. Personality Changes in the Aged these are less easily measured than cognitive functions, but certain trends are nevertheless observable and may seriously disturb the lives of aged persons and those around them. The failure to conceive or formulate an action, either spontaneously or to command, was referred to by Liepmann as ideational apraxia. Various combinations of oculomotor palsies may follow as a result of tumor entry into the orbit via the infraorbital branch of the maxillary nerve. The virus or its nucleocapsid must be capable of penetrating the cell, mainly by the process of endocytosis, and of releasing its protective nucleoprotein coating. Some patients find the side effects more distressing than the myotonia and prefer not to take quinine except on occasions when the myotonia is troublesome in a particular activity. The experiments of Cannon and Bard demonstrated that emotional expression is possible in animals even after removal of both cerebral hemispheres provided that the diencephalon, particularly its hypothalamic part, remains intact. In addition to the patients initially reported by Rapin and coworkers, 24 similar cases have appeared in the medical literature, and we have personally observed examples. However, these explanations probably apply to only a minority of stutterers (Hecaen and de Ajuriaguerra). B, Tonic phase: interference pattern is due to continuous myogenic artifact and high-frequency seizure discharge. Executive functions have 4 components: 1) volition, 2) planning and decision making, 3) purposive action, and 4) effective performance.

Kabuki syndrome

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The tumor-like growths in different organs may include cells of more than one type. Full recovery is characterized by the realization that the voices were imaginary and by the ability to recall, sometimes with remarkable clarity, some of the abnormal thought content of the psychotic episode. In our experience, this syndrome is usually associated with other nutritional disorders, such as Wernicke disease and peripheral and optic neuropathy. Clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature. During and after the procedure, hypotension, hypoprothrombinemia with bleeding. The differential diagnosis includes pre-eruptive herpes zoster, sarcoid infiltration of nerve roots, and the rare entity of thoracic disc rupture. For details, see Volume 2, Chapter 71, "Neurological Development and Developmental Disabilities. Self-care is neglected, incentive to work wanes, sustained thought and action are interrupted by lapses of attention, judgment is impaired, and the subject becomes less and less inclined to communicate. Diseases of the urinary tract, diabetes mellitus or diabetes insipidus, epilepsy, sleep apnea syndrome, sickle cell anemia, and spinal cord or cauda equina disease must be excluded as causes of symptomatic enuresis. The African acute spastic paraplegia called "konzo" has a similar toxic pathogenesis; it is caused by cyanide-like compounds in flour made from cassava. A significant proportion of patients with this hyperproteinemia have a hyperviscosity state manifest by diffuse slowing of retinal and cerebral circulation- giving rise to episodic confusion, coma, impairment of vision, and sometimes strokes- (Bing-Neel syndrome). Confirmation of this relationship on pathologic grounds came much later (for further details, see the monograph by Victor et al). Blood cultures, sedimentation rate and chest x-ray are indispensable in the complete diagnosis of brain abscess, although it must be acknowledged that blood cultures are likely to be unrevealing except in cases of acute endocarditis. Associated Diseases A subset of these children are at increased risk for leukemia (acute myelogenous leukemia or acute lymphoblastic leukemia), but this risk is less than 1%. A clot 60 mL in volume is almost uniformly fatal if situated in the basal ganglia but may be more benign if located in the frontal or occipital lobe. Other Viral Myopathies In most patients with pleurodynia (epidemic myalgia, Bornholm disease), muscle biopsies disclose no abnormalities and there is no clear explanation of the pain. An absent or inadequate Moro response on one side is found in infants with hemiplegia, brachial plexus palsy, or a fractured clavicle. At operation, only part of the tumor can be removed; its multicentricity and diffusely infiltrative character defy the scalpel. They are unaware of much that goes on around them, are often disoriented in time and place, do not grasp their immediate situation, and may misidentify people or objects. Posterior Columns In the dorsal roots, the sensory fibers are first rearranged according to function. These images are not trustworthy for measuring luminal diameter because this measurement varies contingent on the chosen display thresholds; thus, the source images offer the most accurate representation of true vessel caliber. It occurs when the limb is in an attitude of repose and is suppressed or diminished by willed movement, at least momentarily, only to reassert itself once the limb assumes a new position. Abdominal pains or cramps, a sinking, rising, or gripping fully recovered, such a patient has no memory of any part of the feeling in the epigastrium, pallor or redness of the face, throbbing spell but knows that something has happened because of the strange headache, constipation, or diarrhea have also been given prodrosurroundings (in ambulance or hospital); the obvious concern of mal status, but we have not found them consistently enough to be those around him; and a sore, bitten tongue and aching muscles helpful. The central considerations in the diagnosis of brain death are (1) absence of cerebral functions; (2) absence of brainstem functions, including spontaneous respiration; and (3) irreversibility of the state. However, the suggestion that hypoglycemia results in a rapid depletion and inadequate production of high-energy phosphate compounds has not been corroborated; some other glucose-dependent biochemical process must be implicated. Familial amyloidosis with carpal tunnel syndrome (Swiss type) Falls and coworkers in 1955 and later Rukavina and associates described a large group of patients of Swiss stock living in Indiana who developed, in their fourth and fifth decades, a characteristic syndrome of acroparesthesias in the hands due to deposition of amyloid in the connective tissues and beneath the carpal ligaments. Also worthy of emphasis is the catastrophic syndrome of pituitary apoplexy discussed further on. However, neither plasma exchange nor immune globulin has been subjected to systematic study or comparison, and it should be emphasized that while these measures are invaluable in deteriorated patients or those in crisis, they offer only short-term benefit and are not used regularly in the treatment of most patients.

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In some cases, as in those of Leech and coworkers, one cannot ascertain the source of the bleeding, even at autopsy. It is also advisable to give B vitamins to alcoholic patients who are seen for other reasons in the emergency department. Both are particularly useful in the treatment of ovarian and breast cancer, but they have a wide range of antineoplastic activities. It can be administered in approximately 10 minutes and includes 5 sections with a total of 30 points: Orientation (10 points), Registration (3 points), Attention and Calculation (5 points), Recall (3 points), and Language (9 points). A modification of the classifications of Greenfield and of Harding, which is included in the introductory listing of the degenerative diseases (page 897) is used here. At the opposite end of the spectrum is an infantile myopathy in which weakness and lactic acidosis become evident in the first week of life and are fatal by 1 year. The brunt of the pathologic process in fatal cases, falls on the cervical portion of the spinal cord. With acute masses, a 3- to 5-mm horizontal displacement of the pineal calcification is associated with drowsiness; 5 to 8 mm, with stupor; and greater than 8 or 9 mm, with coma (Ropper, 1986). It was in relation to this disease that Oppenheim and Vogt, in 1911, introduced the term dystonia. Claude Bernard expressed this idea in more sardonic terms when he wrote, "nature thought it prudent to remove these important phenomena from the caprice of an ignorant will. Several such patients have nonetheless insisted that levodopa helps them in some nondescript way. These 2 modes of thalamocortical activity are mediated on the cellular level by specialized membrane properties involving a voltage-sensitive calcium current, known as the transient Ca2+ current, It. The rare appearance of this disorder with pontine infarctions has been mentioned (page 340). Tricyclics act on fast sodium channels and can cause adverse effects such as orthostatic hypotension, tachycardia, and cardiac conduction problems. In our clinical material and in reported series of cases, two types stand out- one that is due to hyperbilirubinemia or Rh incompatibility (kernicterus, see below) and the other due to hypoxic-ischemic encephalopathy. While familial cases are decidedly rare (Table 39-2), Golbe and colleagues advanced the understanding of the genetic underpinning of the disease by describing two large kindreds (probably related and originating from a small town in southern Italy) in which 41 patients in four generations were affected. Although this approach undoubtedly results in many negative spinal fluid examinations, it is preferable to the consequence of overlooking a bacterial meningitis. Once established, the syndrome is usually steadily progressive over a 1- to 15-month period (average survival of 6 months in the 42 cases analyzed by Lederman and Henry). Members of both groups of these so-called mildly retarded individuals exhibit a number of noteworthy features that have medical and social implications. Pathology In recent years, attention has been drawn to the presence of abnormal staining material in the cytoplasm of astroglia and oligodendrocytes and in some neurons as well. Bacteria, fungi, and fragments of echinococci and cysticerci can also be seen in cell-stained or Gram-stained preparations. Electrical discharge of neural and muscular tissue is predicated on a special property of excitable membranes- namely, that the permeability of the cell to Na is controlled by the electrical potential of the membrane. The median nerve is stimulated percutaneously (1) at the wrist and (2) in the antecubital fossa with the resultant compound muscle action potential recorded as the potential difference between a surface electrode over the thenar eminence (arrow) and a reference electrode (Ref. Autopsy material has usually disclosed no inflammatory changes in the peripheral nerves. This state of spontaneous and stimulus-sensitive myoclonus as well as persistent limb posturing usually presages a poor outcome. The monographs of Polyak and of Miller contain detailed information about the anatomy and physiology of this part of the brain. Rarely, it is affected with diabetes, polyarteritis nodosa, and osteitis pubis and by retroperitoneal spread of carcinoma of the cervix, uterus, and other tumors (Rogers et al). Invariably, the myelitic disease improves, sometimes to a surprising degree, but there are examples in which the sequelae have been severe and permanent. Examples are aminoglycoside antibiotics (vestibular damage); furosemide (cochlear damage); and nitrofurantoin, isoniazid, and hydralazine (peripheral nerve damage). Similar phenomena may occur as part of hypnologic hallucinations in the narcolepsy-cataplexy syndrome. Diplopia, paralysis of conjugate lateral and/or vertical gaze, internuclear ophthalmoplegia, horizontal and/or vertical nystagmus c. They become wasted as the proximal limb and axial muscles, including the diaphragm, fail to recover their power, even though the ocular and oropharyngeal muscles improve.

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