Bryan Courtney Batch, MD

• Associate Professor of Medicine

https://medicine.duke.edu/faculty/bryan-courtney-batch-md

For example gastritis diet ����������� generic 10mg motilium with visa, we have observed unexpected sudden remissions and severe relapses gastritis yahoo answers generic 10mg motilium with mastercard, as well as resistance to medications gastritis que es bueno order motilium 10 mg free shipping. The brain and spinal cord are normal unless damaged by hypoxia and hypotension from cardiorespiratory failure gastritis medicina natural purchase motilium cheap online. Furthermore gastritis symptoms mayo clinic buy motilium online from canada, the m uscle fibers are generally intact gastritis ulcer medicine order motilium online, although in fatal cases with extensive paralysis, isolated fibers of esopha geal, diaphragmatic, and eye muscles may undergo segmental necrosis with variable regeneration (Russell). Scattered aggregates of lymphocytes (lymphorrhages) are also observed, as originally noted by Buzzard, but none of these changes in muscle explains the widespread and severe weakness. Engel and associates (1976, 1977, 1987), consist of a reduction and simplification in the surface area of the postsynaptic membrane (sparse, shallow, abnormally wide, or absent secondary synaptic clefts) and a widening of the synaptic cleft. The observation of regenerating axons near the junction, the many simplified junctions, and the absence of nerve terminals supplying some postsynaptic regions suggested to Engel and coworkers (1976, 1977, 1987) that there was an active process of degeneration and repair of the neuromuscular junction, particularly of the postsynaptic side. Although not directly relevant to myasthenia, it is of interest that a number of curious neurologic disorders occur in association with thymoma. Among our own patients were 2 with "limbic encephalitis" with memory loss and confusion that could not be differentiated from the paraneoplastic variety of encephalitis (see Chap. Such cases appear in the literature, and all are considered to have a humoral immune basis. The terminal axon contains abundant presynaptic vesicles, but the post synaptic folds are wide and there are few secondary folds. Thyrotoxicosis with periodic paralysis (5 percent of myasthenic patients; see further on and Chap. A proportion of young women with myasthenia have moderately elevated titers of antinuclear antibody without the clinical manifestations of systemic lupus. Lennon and colleagues recognized this model as being similar to that of myasthenia gravis. These observations were followed by the creation of an experimental model of the disease and the demonstration that experimen tally induced myasthenia had clinical, pharmacologic, and electrophysiologic properties identical with those of human myasthenia gravis (Engel et al, 19 76). Thus, the accu mulated evidence satisfied the criteria for the diagnosis of an autoantibody-mediated disorder (Drachman, 1990). The present view is that myasthenic weakness and fatigue are a result of the failure of effective neuromus cular transmission on the postsynaptic side. Blocked transmission at many endplates results in a reduction in the contractile power of the mus cle. This deficiency is reflected first in the ocular and cra nial muscles that thymus (according to Schluep et al). Another suggested pathogenesis, yet unconfirmed, is that a virus with a tropism for thymic cells might alter such cells and induce antibody formation. A viral infection might at the same time have a potential for oncogenesis, accounting for thymic tumors, but this is all speculative. Diag nosis In patients who present with a changeable, specifically fatigable, diplopia or ptosis and the typical myasthenic facies-unequally drooping eyelids, relatively immobile mouth turned down at the corners, a smile that looks more like a snarl, a hanging jaw supported by the hand the diagnosis can hardly be overlooked. Ptosis, diplopia, difficulty in speaking or swallowing, or weakness of the limbs is at first mild and inconstant and may be mistaken for a cerebrovascular disease. However, the finding that sustained activity of small cranial mus cles results in weakness. Several special clinical problems and associated conditions are summ arized further on. The presence of receptor antibodies has proved to be a reasonably sensitive and reliable test of the disease, as discussed later. Neuromuscular transmission is therefore impaired in several ways: to the has been shown to induce an increase in the degradation antibodies to cross-link the receptors; folds (Engel and Arahata). Although the evidence that an autoimmune mecha nism is responsible for the functional disorder of muscle in myasthenia gravis is incontrovertible, the source of the autoimmune response has not been established. Because most patients with myasthenia have thymic abnormali ties and a salutary response to thymectomy; it is logical to implicate the lymphoid reaction in this gland in the pathogenesis of the disease. It is not known with certainty that thymic myoid cells are the source of immunologic stimulation in myasthenia gravis. Reversal of this response by neostigmine or edrophonium has been a reliable confirmatory finding in most cases. A deere mental response to stimulation can usually be obtained most often from the proximal limb muscles followed by the facial and, to a lesser extent, the hand muscles, which may or may not be clinically weak. During a pro gressive phase of the disease or during corticosteroid therapy, a slight initial incrementing response may be obtained, not to be confused with the marked increment ing response after voluntary contraction that character izes the Lambert-Eaton syndrome (see further on). This technique demonstrates an inconstancy of the normally invariant interval between the firing of muscle fibers connected to the same motor unit ("jitter"-see "Single-Fiber Electromyography" in Chap. It is also possible to detect such pairs of fibers by electrical stimulation of a nerve. Nerve conduction velocities and distal motor latencies are normal unless there is a coincident polyneuropathy. Neostigmine Test Almost as valuable as electrophysi ologic testing is testing with the anticholinesterase inhibi tors neostigmine and in the past, edrophonium a more rapidly acting agent. Edrophonium is not easily available in the United States at the time of this writing but neostigmine affords a longer time for observation, as noted in the next para graph. After the estimation of strength in a cranial (usually the levator palpebrae or an extraocular muscle) or limb mus cle (by dynamometry), or vital capacity, neostigmine is injected intramuscularly in a dose of 1. After intramuscular injection of neostigmine, objective improve ment occurs within 10 to 15 min reaches its peak at 20 min and lasts up to 1 h, allowing for careful verification of the neurologic improvement. Many neurologists perform this test twice, once with an injection of saline as a control. The mild muscarinic effects of edropho nium are blocked by pretreatment with atropine 0. The clinical effect of improved ptosis, extraocular movements, oropharyngeal function, arm and shoulder abduction, or vital capacity persists for no more than 5 min with edrophonium and 60 min with neostigmine. One caution: with either drug, some patients deterio rate immediately, but briefly, as a result of an increase in pulmonary secretions. A positive test consists of visible (objective) improvement in muscle contractility, fusion of diplopia, or resolution of fatigable ptosis. Dynamometry and measurement of forced vital capacity serve as more objective markers of improvement, or lack of effect. A negative test with an anticholinesterase agent does not entirely exclude myasthenia gravis but is a strong point against the diagnosis. Finally, the anticholinesterase-inhibiting drugs carry a small risk of inducing ventricular fibrillation and cardiac arrest so that testing should be carried out where emergency support is accessible. Serum antibodies are found in 80 to 90 percent of patients with generalized myas thenia gravis and in approximately 60 percent of those whose sy. Interestingly, the antibody titers usually remain elevated during clini cal remissions. Instances of "seronegative" disease are sometimes due to antibody production against unusual muscle epitopes that are located on or near the acetylcholine receptor; their detection requires a special panel of tests. Others have reported a differ ent pattern of mainly neck and proximal weakness that simulates a typical myopathy. Many of these patients are inadequately responsive to anticholinesterase treatment. Also of interest, but not currently used in routine diag nosis, is the presence of antibodies directed against striated m uscle in almost half of myasthenic patients and an even higher incidence (stated to be 85 percent) in patients who also have a thy. Each of the commonly used diagnostic tests, elec trophysiology, edrophonium, and antibodies, proves to be about equally reliable. Kelly and coworkers obtained positive results with single-muscle-fiber recording in 79 percent, with the antireceptor antibody test in 71 percent, and with the edrophonium test in 81 percent. Combined, they confirmed the diagnosis in 95 percent of clinically suspected cases. Progressive external ophthalmoplegia and other restricted has not been as consistently evident, but it may be a use ful adjunctive test. It should be emphasized that the extraocular muscles and levator palpebrae may be permanently damaged by myasthenia and cease to respond to neo stigmine. Another possibility is that restricted ocular myasthenia may not respond to anticholinesterase drugs from the beginning and the diagnosis of myas thenia is erroneously excluded. One must then turn to other muscles for clinical and electromyographic and serologic confirmation of the diagnosis. Testing with an anticholines terase inhibitor, single-fiber and repetitive stimulation recording, and measurement of antibodies usually clarifies the matter. Thyrotoxicosis may produce a characteristic ocular myopathy and there is a tentative relation to peri odic paralysis as indicated in Chap. There is no certain evidence that thyrotoxicosis aggravates myasthenia gravis; some have even observed an inverse relationship between the severity of the two conditions. The ophthalmoplegia of thyrotoxicosis can usually be distinguished by the presence of an associated exophthalmos (early in the disease, exophthalmos may be absent), lack of ptosis, and the lack of definitive response to neostigmine. Polymyositis and inclusion body myopathy are dif ferentiated from myasthenia by lack of involvement of extraocular muscles, but they may affect oropharyn geal muscles, as does myasthenia. Finding the signs of these diseases in combination with those of myas thenia indicates a concurrence of two independent autoimmune diseases. The initial manifestations of botulism may be mistaken for myasthenia gravis of acute onset. The neurasthenic or depressed patient who complains of weakness when actually referring to fatigability. Intoxication with organophosphate insecticides, because no ptosis, strabismus, or dysphagia, though an anx ious individual may complain of diplopia (usually of momentary duration when drowsy) and also of tightness in the throat (globus hystericus). A number of such patients claim improvement with neostig mine but objective and reversal is always uncertain. Conversely, myasthenia is as often mistaken for hysteria or other emotional illness, mainly because the physician is unfamiliar with myasthenia (or with hysteria) and has been overly impressed with the precipitation of the illness by an emotional crisis. Furthermore, fatigability is a feature of all of these conditions, but only in the psychiatric ones does it extend to the sphere of mental endurance. Those with myasthenia do not usually complain of fatigue of the mind, whereas these are frequent complaints in psychiatric conditions. Certain other small clinical points may be helpful in differentiating myasthenia from other diseases that affect the cranial musculature. The question of midbrain stroke as a consequence of basilar artery occlusion arises in a case with total ophthalmoplegia; it should be recalled that the level of consciousness is usually reduced if vertical gaze and pupillary reactions are lost in cases of basilar artery stroke; such is not the case in neuromuscular diseases. The myasthenic syndrome of Lambert-Eaton, discussed further tified by its other clinical and electrophysiologic features. Ocular paresis, as may occur in nemaline polymyopathy, on, only occasionally affects the ocular muscles, but is iden A similar problem arises frequently on our services in judging breathless ness due to anxiety or cardiopulmonary disease in a patient with presumed myasthenia. On occasion, the eye movements in myasthenia simulate an internuclear ophthalmoplegia or other "central" sign, even to the extent of including nystag mus in an abducting eye. Anticholinesterase Drugs the two drugs that give the best results in ameliorating myasthenic weak ness are neostigmine (Prostigmin) and pyridostigmine (Mestinon), the latter being preferred by most clinicians and patients. The usual dose of pyridostigmine is 30 to 90 mg given every 6 h (typically a 60-mg pill is tried first); the oral dose of neostigmine ranges from 7. Extended-action forms of both drugs are available but are given at bedtime mainly to patients who complain of weakness during the night or early morning hours. The dosage of these drugs and their fre quency of administration vary considerably from patient to patient, but we agree with Drachman (2003) that the maximal useful dosage of pyridostigmine rarely exceeds 120 mg given every 3 h. For mild cases, for patients in partial remission after thymectomy, and for purely ocular myasthenia, the use of anticholinesterase drugs may be the only form of therapy necessary for some period of time (ocular myasthenia often responds well to small doses of corticosteroids as noted further on). Although these drugs seldom relieve symptoms completely (the response of ocular symptoms is typically incomplete), most such patients are able to function well. Corticosteroids For the patient with moderate to severe generalized weakness who is responding inad equately to anticholinesterase drugs, the long-term administration of corticosteroids is the most consistently effective form of treatment, as described in a large series of patients by Pascuzzi and colleagues. Small doses of corticosteroids (prednisone 15 to 25 mg daily) alone or in combination with azathioprine (see later) are also often adequate to control ocular myasthenia. However, one must be prepared to contend with the side effects of long term corticosteroid therapy and we hesitate to undertake such a program in children or patients with severe dia betes or other diseases that are likely to be aggravated. Because recent experience with the newer immunosup pressive agents was not incorporated into most prior series, the uniform use of steroids might not be correct. The usual form of corticosteroid therapy is predni sone (or corresponding doses of prednisolone), beginning with 15 to 20 mg/ d and increasing the dose gradually until a satisfactory clinical response is obtained or until a daily dose of 50 to 60 mg is reached. With higher doses or more rapid elevations of the doses, worsening of weakness in the first weeks may occur and hospitalization and careful observation for respiratory difficulty may be advisable. Once the maximal effect from predni sone has been attained, the dosage can be reduced gradu ally over months to the lowest point at which it is still effective. Our practice has been to then attempt to insti tute an alternate-day schedule, which diminishes the side effects; some patients have done better with a modest difference in dose from one day to the next, rather than omitting a dose entirely on alternate days. Potassium supplements and antacids should be prescribed liberally if needed, as with any chronic corticosteroid regime and consideration should be given to prophylaxis with anti biotics for Pneumocystis infection, and bisphosphonate for osteoporosis if long-term treatment is anticipated. At the outset of steroid therapy, anticholinesterase drugs are given simultaneously; as the patient improves, the dos age of the latter may be adjusted downward. Azathioprine and Other Immunosuppressive Drugs Azathioprine is a useful adjunct to steroids in patients who cannot tolerate or fail to respond to prednisone. It has been possible to manage the disease reasonably well in a few of patients with azathioprine alone, but there is no study to support this practice (see Palace et al, 1998). Treatment typically begins with 50 mg (1 tablet) bid for a few days; if this is tolerated, the dosage is raised to 2 to 3 mg/ kg/d (150 to 250 mg daily). However, improvement occurs much more slowly than with corticosteroids and a significant response may not be evident for many months to a year (Witte et al). The Myasthenia Gravis Clinical Study Group found that the most severe forms of the disease, particularly those resistant to either prednisone or azathioprine alone, benefit from the combi nation of the two medications. Approximately 3 per 1 00,000 persons are deficient in the enzyme, for which reason, some clinicians measure its level before ini tiating azathioprine in order to avoid bone marrow toxic ity; it has not been our practice to do so. Cyclosporine is another immunosuppressive drug that has shown benefit in clinical trials (T mdall et al). It is given in 2 divided doses daily, to a total of 6 mg/kg, but not often used currently because of serious side effects (hypertension, nephrotoxicity) and its high cost.

The sensory features and pain in particular may be slower to recover gastritis diet �� motilium 10 mg discount, having taken over a year in one of our recently observed patients gastritis diet ������ motilium 10 mg online. The slowness of recovery creates a special problem for the alcoholic patient gastritis diet ����������� buy motilium 10mg low cost, in whom the great danger to continued recovery is the resumption of drinking and inadequate diet gastritis diet 5 2 safe motilium 10mg. Serum creatine phosphate was normal in these individuals gastritis omeprazole purchase motilium 10mg visa, but carnitine was reduced gastritis diet apples buy motilium 10mg otc. The oral administration of 200 mg of riboflavin and 4 g of carnitine per day relieved the symptoms. Since 1940, it has diminished greatly because of the general practice of enriching bread with niacin. Nevertheless, among the vegetarian, maize eating people of underdeveloped countries, and among the black population of South Africa, pellagra is still a common disease (Bomb et al; Shah et al; Ronthal and Adler). In developed countries, pellagra is practically confined to alcoholics (Ishii and Nishihara; Spivak and Jackson; Serdaru et al). In the past, there were claims that glossitis, cheilosis, and neuropathy were caused by riboflavin deficiency, but its effects were never isolated. It is a component of general malnutrition, mak ing it difficult to separate the cause of various disorders. Antozzi and coworkers reported that a metabolic disorder similar to the Reye syndrome can be caused by riboflavin deficiency and is correctable by administration of riboflavin alone. The affected infants in their studies were hypoglycemic, hypotonic, and episodically weak and unresponsive. Generally, 15 mg per day in divided doses is used for replacement, but restoration of a normal diet is paramount. Antozzi and colleagues also recorded instances of disease in older children and adults, manifesting as a type of lipid storage polymyopathy as a result of either In its fully developed form, pellagra affects the skin, alimentary tract, and hematopoietic and nervous sys tems. Insomnia, fatigue, nervousness, irritability, and feelings of depression are common com plaints; taken together they have the character of neur asthenia. Pellagra may not only produce mental impairment but occasionally result from it, by virtue of anorexia and refusal of food. The dermatologic feature, often the aspect that permits one to make a confident diagnosis, is a scaly dermatitis in sun-exposed areas, followed by hyperpig mentation of these areas. Diarrhea and glossitis or other forms of mucous membrane disorder may be accompani ments (hence the alliterative triad dementia-dermatitis diarrhea; the "3 Ds"). Signs of peripheral neuropathy are relatively less common and are indistinguishable from those of neuropathic beriberi. However, in the pathologic material presented by Hauw and associates, these chro matolytic changes were most pronounced in the brainstem nuclei (upper reticular and pontine) and not in the Betz cells. They concluded that the neuronal changes were not caused by a retrograde axonal lesion but did not comment on the status of the spinal cord or nerves. The few studies of the peripheral nerves in pellagra have disclosed changes like those in alcoholics and other patients with nutritional deficiency. The spinal cord lesions in pellagra take the form of a symmetrical degeneration of the dorsal columns, espe cially of Goll, and to a lesser extent of the corticospinal tracts. The posterior column degeneration is likely to be secondary to degeneration of the dorsal root ganglion cells or posterior roots. Many years before, Goldberger had demonstrated the curative effects of dietary protein and proposed that pellagra was caused by a lack of specific amino acids (see Terris). Now it is known that pellagra may result from a deficiency of either nicotinic acid or tryptophan, the amino acid pre cursor of nicotinic acid. One milligram of nicotinic acid is formed from 60 mg of tryptophan, a process for which pyridoxine is essential. The relationship of niacin to tryp tophan metabolism explains the frequent occurrence of pellagra in persons who subsist mainly on corn, which contains only small amounts of tryptophan and niacin, some of the niacin being in bound form and unavailable for absorption. It should be pointed out that in experimental sub jects, only the cutaneous-gastrointestinal-neurasthenic manifestations of pellagra have been produced by diets that are tryptophan or niacin deficient; neurologic abnor malities have not resulted from these diets (Goldsmith). As a corollary, only the dermal, gastrointestinal, and neurasthenic manifestations respond to treatment with niacin and tryptophan; neurologic disturbances in pel lagrins have proved to be recalcitrant to prolonged treat ment with the vitamin, although the peripheral nerve disorder may subsequently respond to treatment with thiamine. In monkeys, degeneration of peripheral nerves and the cerebrocortical changes of pellagra were induced by a deficiency of pyridoxine (Victor and Adams, 1 956). Swank and Adams described degeneration of the periph eral nerves in pyridoxine- and pantothenic acid-deficient swine, and Vilter and colleagues produced polyneu ropathy in human subjects rendered pyridoxine deficient; these subjects also showed seborrheic dermatitis and glossitis (indistinguishable from that of niacin deficiency) and the cheilosis and angular stomatitis that are usually attributed to riboflavin deficiency. The foregoing obser vations indicate that certain lingual and cutaneous mani festations of pellagra may be produced by a deficiency of pyridoxine or other B vitamins, and that the neurologic manifestations of pellagra are most likely caused by pyri doxine deficiency. In the special case of Hartnup disease in infants (which resembles pellagra in most respects including the dermatitis), a secondary niacin deficiency is believed to result from the high excretion of indicans and indole metabolites (see Chap. Treatm ent the administration of niacin 500 mg per day for approxi mately 3 weeks reverses the process. If the patient is unable to take oral medications, intravenous doses of 100 mg per day for 5 to 7 days are utilized. Nicoti nic Acid-Deficiency Encephalopathy Under this title, Jolliffe and coworkers, in 1940, described an acute cerebral syndrome in alcoholic patients consist ing of clouding of consciousness, progressing to extrapy ramidal rigidity and tremors ("cogwheel" rigidity) of the extremities, uncontrollable grasping and sucking reflexes, and coma. Some of their patients showed overt manifes tations of nutritional deficiency, such as Wernicke disease, pellagra, scurvy, and polyneuropathy. These authors concluded that the encephalopathy represented an acute form of nicotinic acid deficiency, as most of their patients recovered when treated with a diet of low vitamin B con tent supplemented by intravenous glucose and saline and large doses of nicotinic acid. Sydenstricker and colleagues (1938) had previously reported the salutary effects of nic otinic acid on the unresponsive state observed in elderly undernourished patients, and Spillane (1947) described a similar syndrome and response to nicotinic acid in the indigent Arab population of the Middle East. The clinical, nutritional, and pathologic features were never delineated precisely. Serdaru and associates reported 22 presumed examples of this syn drome in the alcoholic population of the Salpetriere clinic in Paris, all diagnosed retrospectively after the finding in postmortem material of pellagra-like changes in nerve cells. The prominent features were confusional states, paratonic rigidity, ataxia, and polymyoclonia, a picture somewhat like that described by Jolliffe and cowork ers. We have not encountered identical cases among the undernourished patients in the alcoholic population. Botez and colleagues have described a group of 10 patients with sensorimotor polyneuropathy (4 also had spinal cord disease) presumably because of intestinal malabsorption; all the patients improved over several months while receiving large doses of folic acid. The possible role of folate deficiency in the pathogenesis of spinal cord disease was mentioned previously in relation to vitamin B 1 2 deficiency, and its putative role in psychiatric disease has been discussed by Carney. In such cases of folate deficiency, if subacute combined degeneration or mental changes occur, they must be rare. The folate deficiency of pregnancy is a special case that is known to increase the incidence of neural tube defects. For nutritional folate deficiency, difficult to separate from the lack of other vitamins, replacement is with 1 mg per day. The neuropathy responds favorably to discontinuation of the drug and the administration of pyridoxine. Pyridoxine deficiency also leads to homocystinemia because the vitamin is a coenzyme for the conversion of homocystine to cystathionine. This was first observed in swine by Swank and Adams, and later in infants who were maintained on a milk formula lacking in pyridoxine. A pyridoxine-responsive seizure disorder (pyridoxine depen dency) of the neonatal period is discussed in Chap. In pregnant women, higher doses are used, sepa rately from a multivitamin preparation in order to avoid vitamin A toxicity. When a folate antagonists is the under lying cause, folinic acid (leukovorin, citrovorum factor) 15 mg orally is given every 6 h for 10 doses starting after methotrexate infusion. Pa ntothenic Acid Deficiency A predominantly sensory neuropathy also has been induced, again in swine, by Swank and Adams, and later in humans by a deficiency of pantothenic acid (a constituent of coenzyme A [CoAl), as reported by Bean and colleagues. Treatm e nt For pyridoxine deficiency caused by malnutrition, the treatment is 50 mg per day orally for several weeks, fol lowed by 2 mg per day and resumption of a normal diet. Treatment for the inherited form with convulsions is discussed in the section on neonatal seizures in Chap. In some patients, the administration of pantothenic acid has reportedly reversed the painful dys esthesias of the "burning foot" syndrome. Lifelong supplementation is required after the seizures are aborted with a large intravenous dose of the vitamin. The the spinal cord, brain, optic nerves, and peripheral spinal cord is usually affected first and often exclusively. The term Pyridoxine Toxicity Paradoxically, the consumption of large amounts ofpyridoxine (mainly by vitamin faddists) may also cause a sensory peripheral neuropathy or ganglionopathy (Schaumburg et al; Albin et al). There is no weakness; the symptoms, including ataxia and areflexia, are purely sensory and can be quite disabling. Improvement is the rule when the drug is of pyridoxine on dorsal root ganglion cells. Whether a peripheral neuropathy is a pri mary component of the disease or is secondary to dam age of the posterior root fibers of entry in the dorsal cord has been debated, but the available pathologic evidence favors the latter, except perhaps for a few advanced cases, in which other nutritional deficiencies could have been responsible. The hematologic effects of vitamin B 1 2 deficiency, when they result from pernicious anemia, are distinctive insofar as they usually result not from a dietary lack of vitamin B1 2 but from the failure to transfer minute amounts of this nutrient across the intestinal mucosa, "starvation in the midst of plenty," as Castle aptly put it. Folate (B9 Deficiency) Despite the frequency of folic acid deficiency and its hematologic effects, its role in the pathogenesis of ner vous system disease has not been established beyond doubt (see reviews by Crellin et al and by Carney). However, folate antagonists such as methotrexate are known to cause a neuropathy that is probably predicated on the vitamin deficiency. This is referred to as a conditioned deficiency, as it is conditional on the lack of an intrinsic factor. It was Castle, experimenting on himself, who iso lated the "intrinsic factor" that facilitates absorption of the vitamin. The hematologic and neurologic manifestations of vitamin B 1 2 deficiency often complicate many of the malabsorptive disorders, including poor nutrition in the elderly, especially those with atrophic gastritis, but also individuals of any age with celiac sprue; gastric or ileal resections; overgrowth of intestinal bacteria in "blind loops," anastomoses, diverticula, and other con ditions resulting in intestinal stasis; and infestation with cobalamin-metabolizing fish tapeworm (Diphyllobothrium latum). Uncommon instances of vitamin B1 2 deficiency are observed in lactovegetarians and in infants nursed by mothers deficient in vitamin B1 2; vitamin B1 2 deficiency may also be a result of a rare genetic defect of methylmal onyl-CoA mutase as discussed further on. It should be further commented that interference with methionine synthetase, a methylcobalamin-depen dent enzyme, can be produced by exposure to nitrous oxide. Chronic exposure can produce the entire subacute combined syndrome but more often, an individual is marginally deficient, often but not always elderly, and even short exposure may then induce symptoms. This illness, cleverly named "anesthesia paresthetica" by Kinsella and Green, arises in operating room personnel (we have seen it in several anesthesia nurses), occasionally in dentists, and in abusers of the gas (whippets) to obtain a "high. The patient first notices mild general weakness and paresthesias consisting of tingling, "pins and needles" feelings, or other vaguely described sensations. The paresthesias involve the hands and feet, more often and first in the hands, and tend to be constant and steadily progressive and the source of much distress. As the illness progresses, the gait becomes unsteady and stiffness and weakness of the limbs, especially of the legs, develop. If the disease remains untreated, an ataxic paraplegia evolves with variable degrees of spasticity. Early in the course of the illness, when only pares thesia is present, there may be no objective sign. Later, examination discloses a disorder of the posterior and lateral columns of the spinal cord, predominantly of the former. Loss of vibration sense is the most consistent sign; it is more pronounced in the feet and legs than in the hands and arms and frequently extends over the trunk Position sense is usually impaired in parallel. The motor signs, usually limited to the legs, include a mild symmetrical loss of strength in proximal limb muscles, spasticity, enhanced tendon reflexes, clonus, and extensor plantar responses. At first, the patellar and Achilles reflexes are diminished as frequently as they are increased; they may even be absent. This is most likely the result of a neuropa thy due to multiple vitamin deficiencies as cases of pure cobalamin loss, for example due to nitrous oxide, almost never obliterate the tendon reflexes. Loss of superficial sensation below a segmental level on the trunk should suggest an alternative diagnosis involving the spinal cord. However, 2 of our patients have described a band-like sensation around the thorax. A defect of cutaneous sensation may take the form of impaired tactile, pain, and thermal sensation over the limbs in a distal distribution, implicating the small fibers of the peripheral nerves or the spinothalamic tracts, but such findings are relatively uncommon. The Lherrnitte phenomenon (paresthesia down the spine or across the shoulders induced by rapid flexion of the neck) may be found if sought but is a sign more often allied with multiple sclerosis. Cognitive symptoms and signs are frequent, ranging from irritability, apathy, somnolence, suspiciousness, and emotional instability to a marked confusional or depres sive psychosis or dementia. Lindenbaum and coworkers have reported cases in which neuropsychiatric symp toms, responsive to vitamin B 1 2, were present without spinal cord or peripheral nerve abnormalities. In our clinical material, symptoms of dementia or psychosis have not been frequent and always followed the spinal cord disorder. Visual impairment caused by optic neuropathy occa sionally may be an early or sole manifestation of perni cious anemia; examination discloses roughly symmetrical centrocecal scotomata and optic atrophy in the most advanced cases. That visually evoked potentials may be abnormal in vitamin B 1 2 -deficient patients without clinical signs of visual impairment suggests that the visual pathways are affected more often than is evident from the neurologic examination alone. A small number of patients have symptoms of autonomic dysfunction, including urinary sphirtcteric symptoms and impotence. The nerve conduction studies may show slowing of sensory conduction or reduced amplitude sensory potentials, but they are as process, the former more obviously and perhaps earlier and more severely than the latter. There is relatively little fibrous gliosis in the early lesions, but in more chronic ones, particularly those in which considerable tissue is destroyed, the gliosis is pronounced. The changes begin in the posterior columns of the lower cervical and upper thoracic segments of the cord and spread from this region up and down the cord as well as forward into the lateral and anterior columns. The lesions are not limited to systems of fibers within the posterior or lateral columns but are scattered irregularly through the white matter, thereby representing a myelinopathy. Frequently, according to Hemmer and colleagues, somatosensory evoked potentials are delayed or absent; these changes are known to recover with treat ment.

In a few person ally observed patients this was the main abnormality gastritis y dolor de espalda purchase motilium 10mg online, but there was also a sensory loss in the radial territory of the hand gastritis diet food recipes order motilium australia. Less commonly gastritis peptic ulcers symptoms buy motilium cheap online, there is foot-drop occurring alone or in combination with weakness of the proximal arm and shoulder girdle muscles antral gastritis diet chart discount 10mg motilium. Although the neuropathy has been known since ancient times gastritis symptoms fever buy motilium 10mg on line, details of the pathobiology are still obscure diet bei gastritis 10 mg motilium. Axonal degeneration with secondary myelin change and swelling and chro matolysis of anterior horn cells has been described. Lead accumulates in the nerve and may be toxic to Schwann cells or to endothelial capillary cells, causing edema. The diagnosis is established by the history of lead exposure, the predominant and restricted motor involve ment, associated medical findings (anemia, basophilic stippling of red blood cell precursors in the bone marrow, a "lead line" along the gingival margins, colicky abdomi nal pain, and constipation), and the urinary excretion of lead and coproporphyrins. Coproporphyrin in the urine is abnormal in any amount, but it may also be found in porphyria, alcoholism, iron deficiency, and other disor ders as well as in lead intoxication. Treatment consists of terminating the exposure to lead and eliminating lead from the bloodstream and the bones by chelation as discussed in Chap. Su bacute Toxic Neuropath ies Arse n ica l Po lyneu ropathy Of the neuropathies caused by metallic poisoning, that caused by arsenic is particularly well characterized. In cases of chronic poisoning, the neuropathic symptoms develop rather slowly, over a period of several weeks or months and have the same sensory and motor distribution as the nutritional polyneuropathies. Gastrointestinal symptoms, the result of ingestion of arsenic compounds, may precede the polyneuropathy, which is nearly always associated with anemia, jaundice, brownish cutaneous pigmentation, hyperkeratosis of palms and soles, and later with white transverse banding of the nails (Mees lines). Pathologically, this form of arsenical neuropathy is catego rized as of the dying-back (axonal degeneration) type. In patients who survive the ingestion of a single massive dose of arsenic, a more rapidly evolving poly neuropathy may appear after a period of 8 to 21 days as discussed earlier. A predominantly motor neuropathy is induced by occupational exposure to metallic mercury and mercury vapor but any connection to the mercury content in dental amalgam has little cred ibility. The devastating encepha lopathy of organic mercury toxicity does not, to our knowledge, cause neuropathy. Most often the cumu lative dose of gold had exceeded 1 g but in a few instances the neuropathy occurred with 0. Painful distal burning is the initial complaint with weakness and wasting follow ing. A distal, symmetrical sensorimotor (predominantly sensory) neuronopathy may follow exposure to certain hexacarbon industrial solvents. Operating room nurses may be affected by the latter when the agent is absorbed through the skin, leaving a characteristic rash at exposed sites (usually the wrists, where a surgical gown ends). Nurses are also subject to a risk of nitrous oxide neurotoxicity and this usually takes the form of a myelopathy similar to that seen with cobalamin deficiency. As with vitamin B-12 deficiency, the syndrome may be mistaken for a neu ropathy but nerve conduction studies fail to demonstrate one. The associated macrocytic anemia is reversed by the administration of B12, but the neurologic illness may be less responsive as discussed in Chap. Both of these drugs cause a dying-back polyneuropathy with axonal degeneration and have been used experimentally to produce this effect. Vacor, a phenylnitrosourea rodenticide, taken as a suicidal agent, gives rise to a profound sensory and autonomic neuropathy with abdominal pain and hyperglycemia caused by acute pancreatitis. Detailed accounts of the clinical and experimental neurotoxicology of these agents can be found in the monograph by Spencer and colleagues. Most are dose-dependent and are therefore more or less predict able after large cumulative doses of the drug have been given. A more complete list than can be compiled here can be found in the review by England and Asbury. Some patients develop acrodynia and episodic color changes in the fingertips and toes suggesting that autonomic nerves are also involved; in severe cases there is sensory ataxia and pseudoathetosis. The severity of histopathologic changes in the peripheral nervous system corresponds to the concentration of platinum in these tissues, the highest being found in dorsal root ganglia. Secondary degenera tion in the posterior columns is the basis for a Lherrnitte symptom reported by some patients. The taxanes paclitaxel and the more potent docetaxel, both cited as inhibitors of the depolymerization of neu rotubules, are used mainly in the treatment of ovarian cancer. Pathologic studies have shown a neuronopathy and distal axonopathy affecting mainly large fibers. For decades it has been known that peripheral neu ropathy commonly complicates the use of vincristine, an antineoplastic agent most widely used in treatment of the lymphomas and leukemia. Paresthesias are the most common early symptom, and loss of ankle jerks is an early sign. Some degree of weakness usually precedes objective sensory loss; the extensor muscles of the fingers and wrists are affected; later the dorsiflexors of the toes and feet causing foot-drop or, more often in our experi ence, foot-drop may appear first. With the dose regimens currently used, the weakness is usually mild, but in the past, some patients became quadriparetic and bedbound. Adults are more severely affected than are children, as are persons with preexisting polyneuropathies. The neu ropathy is strictly dose-related and reduction in dosage is followed by improvement of neuropathic symptoms although this may take several months. Many patients are then able to tolerate vincristine in low dosage, such as 1 mg every 2 weeks, for many months. Symptoms of neuropathy appeared between 3 and 35 weeks after treatment was begun and affected approximately 10 percent of patients receiving therapeutic doses in the upper range (10 mg/kg daily). The initial symptoms are symmetrical numbness and tingling of the toes and feet spreading, if the drug is continued, to the knees and occasionally to the hands. Isoniazid produces its effects on the peripheral nerves by interfering with pyridoxine metabolism, per haps by inhibiting the phosphorylation of pyridoxine (the collective name for the B6 group of vitamins) and decreasing the tissue levels of its active form, pyridoxal phosphate. The administration of 150 to 450 mg of pyri doxine daily in conjunction with the isoniazid completely prevents the neuropathy. The same mechanism is prob ably operative in the neuropathies that occasionally complicate the administration of the isoniazid-related substances such as ethionamide, used sometimes in the treatment of tuberculosis and the now little-used antihy pertensive agent use of disulfiram in the treatment of alcoholism. Pathologic data, although scant, tend to discredit this notion, insofar as disulfiram evokes a wallerian type of axonal degeneration, whereas carbon disulfide neuropathy is characterized by swollen (giant) axons that are filled with neurofilaments (Bouldin et al). Some patients who have taken phenytoin for decades may lose ankle and patellar reflexes and acquire mild distal sy. Paradoxically, the taking of extremely high doses of pyridoxine over a prolonged period 1983). A relatively mild sensory neuropathy (acral paresthe may actually cause a disabling, predominantly sensory ganglionopathy (Schaumburg et al, statin drugs have been tentatively sia) associated with optic neuropathy occasionally compli cates chloramphenicol therapy. The chronic administration of metronidazole may have the same effect (and can produce lesions in the deep cerebellum). The newer antimicrobial, linezolid, has been associated with a fairly severe sensory neuropathy in a few cases after prolonged use. A pre dominantly motor neuropathy has been reported with the chronic administration of implicated in a painful, paresthetic distal axonal polyneu ropathy with retained reflexes (Gaist et al). The frequency of polyneuropathy is low but, if no other expla nation is identified, it may be advisable to discontinue the drug. Colchicine has long been known to cause a myopathy, but a few cases of predominantly axonal sensory neuropa thy have also been reported dapsone, a sulfone used to treat (neuromyopathy). Stilbamidine, used in the treatment of kala azar, may also induce a purely sensory neuropathy with a propensity to affect the the introduction, in 1952, of nitrofurantoin for the treat ment of bladder infections was soon followed by reports of trigeminal nerves. Among various other agents that cause neuropathy are hydroxychloroquine and colchicine are known to cause a toxic neuropathy. The anesthetic agent ethylene, predilection for cranial nerves, particularly the fifth. The neurotoxicity is apparently caused by dichloroacetylene, as with the aforementioned stilbamidine, has a If the drug is not discontinued, the disorder progresses to a toms are pain and tingling paresthesias of the toes and feet, followed shortly by similar sensations in the fingers. Patients with chronic renal failure are particularly prone to neuro toxicity from nitrofurantoin because of diminished drug excretion resulting in high tissue levels. To make matters more complex, the uremic state itself may be responsible for a polyneuropathy so that the distinction between ure mic and nitrofurantoin neuropathy may be impossible. The neuropathologic studies of Lherrnitte and colleagues disclosed an axonal degeneration in peripheral nerves and sensory roots. There may be an eosinophilic infiltrate in nerves, but the neuropathy is probably the result of a direct toxic mechanism. A sensory neuropathy, resulting from excessive Cardiac Drugs Amiodarone, a drug used for treat ing recalcitrant ventricular tachyarrhythmias, induces a motor-sensory neuropathy in about 5 percent of patients pyridoxine ingestion after several months of treatment. Perhexiline maleate for the treatment of angina pectoris may also cause a generalized, predomi nantly sensory polyneuropathy in a small proportion of patients. Patients taking alluded to earlier, is still seen among individuals who take huge doses of vitamin supplements. Amitriptyline is capable of producing paresthesias, but the effect seems to be idiosyncratic and infrequent. We are referring mainly cholesterol levels may experience distal and truncal paresthesias, but an associated neuropathy has been identified. In recent years, attention has also been directed to a possible association between a nondescript sensory polyneuropathy and impaired glucose tolerance, even without manifest diabetes, per sistent hyperglycemia, or an elevation of hemoglobin A1 c. The survey by Sumner and colleagues makes a case for such an association, but we remain uncertain about the relationship between glucose intolerance alone and polyneuropathy. By statistically adjusting for relevant factors such as glycemic control and glycosylated hemo globin, Tesfaye and colleagues have suggested that some cardiovascular risk factors subsumed under the term "metabolic syndrome" (triglyceride levels, body mass, hypertension) are themselves risk factors for diabetic polyneuropathy. Approximately Most of the syndromes listed here are likely to be a result of ischemia or infarction of nerves or nerve fas cicles, because of a diabetic microvasculopathy. In recent years, an inflammatory process has been postu lated as yet another mechanism of peripheral nerve dam age. The main complaints are persistent and often distressing numbness and tingling, usually confined to the feet and lower legs and worse at night. As a rule, sensory loss is confined to the distal parts of the lower extremities, but in severe cases the hands are involved and the sensory loss may even spread to the anterior trunk, simulating a sensory level of spinal cord disease (Said et al, 15 percent of patients with diabetes have symptoms and signs of polyneuropathy, but nearly 50 percent of cross-sectional population samples have evidence of peripheral nerve damage as judged by nerve conduction abnormalities. Fewer than 10 percent of patients have clinically evident polyneuropathy at the time of discovery of diabetes, but this figure rises to 1983). Trophic changes in the form of deep ulcerations and neuropathic degeneration of the joints (Charcot joints) are encountered in the most severe and long-standing cases, presumably as a result of sensory analgesia, trophic changes, and repetitive injury. In another group of patients with diabetic polyneu ropathy the clinical picture may be dominated instead by loss of deep sensation, ataxia, and atony of the bladder, with only slight weakness of the limbs, in which case it resembles tabes dorsalis (hence the term 50 percent after 25 years. The presence of diabetic retinopathy is associated with higher incidences of neu ropathy. It is not surprising, therefore, that neuropathy is most common in diabetics older than 50 years; it is 30 years and is rare in childhood. Dyck and colleagues (1993) studied diabet infrequent in those younger than age ics in Rochester, Minnesota, and found that 54 percent with type 1 (insulin-deficient) and 45 percent with type 2 (insulin-resistant) had polyneuropathy. The percent ages were lower when patients were selected on the basis of clinical symptoms alone rather than on the presence of changes in nerve conduction; close to 15 percent at the time of diagnosis in both groups. In the syndromes described further on, both type 1 and type 2 diabetic patients are susceptible, the duration of diabetes being a major factor. Several fairly distinct clinical syndromes of diabetic neuropathy have been delineated: diabetic pseudota if lan bes). The similarity to tabes dorsalis is even closer (1) the most common (2) acute ophthal cinating pains in the legs, unreactive pupils, abdominal pains, and neuropathic arthropathy are present. It commonly presents as isolated, painful third nerve palsy with sparing of pupillary function. In the first autopsied patient reported by Dreyfus and colleagues, there was an ischemic lesion in the center of the retroor bital portion of the third nerve. Isolated involvement of practically all the major peripheral nerves has been described in diabetes, but the ones most frequently affected are the femoral, sci trunk including a painful thoracolumbar radicu lopathy; (4) an acute or subacute painful, asymmetrical, predominantly motor, multiple neuropathy affecting the upper lumbar roots and the proximal leg muscles ("diabetic amyotrophy"); (5) a more symmetrical, proxi mal motor weakness and wasting, usually without pain and with variable sensory loss, pursuing a subacute or chronic course; and (6) an autonomic neuropathy involv ing bowel, bladder, sweating and circulatory reflexes. These forms of neuropathy often coexist or overlap, par ticularly the autonomic and distal symmetrical types and the subacute proximal neuropathies. A syndrome of painful unilateral or asymmetrical mul tiple neuropathies tends to occur in older patients with relatively mild or even unrecognized diabetes. Multiple nerves are affected in a random distribution (mononeu ropathy multiplex). The mononeuropathies often emerge during periods of transition in the diabetic illness, for example, after an episode of hyper- or hypoglycemia, when insulin treatment is initiated or adjusted, or when there has been rapid weight loss. Pain, which can be severe, begins in the low back or hip and spreads to the thigh and knee on one side; the dis comfort has a deep, aching character with superimposed lancinating jabs and there is a propensity for pain to be most severe at night. Weakness and later atrophy are evi dent in the pelvic girdle and thigh muscles, although the distal muscles of the leg may also be affected. Curiously, we have found the opposite patellar reflex to be absent in some patients without explanation. Deep and superficial sensation may be intact or mildly impaired, conforming to either a mul tiple nerve or multiple adjacent root distribution. Motor recovery is the rule although months and even years may elapse before it is complete. The same syndrome may recur after an interval of months or years in the opposite leg. This form of neuropathy has been referred to as diabetic amyotrophy, a term that draws attention to one facet of the syndrome. Clinical expe rience has shown that an identical painful lumbofemoral neuropathy may develop in nondiabetics; possibly this form is also vasculopathic or vasculitic. While lumbar disc herniation, retroperitoneal hematoma compressing upper lumbar roots, carcinomatous meningeal seeding, and neoplastic and sarcoid infiltration of the proximal lumbar plexus enter into the differential diagnosis, the diabetic type is usually so distinctive as to permit rec ognition on clinical grounds alone.

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Syndromes

• Eat foods rich in antioxidants, like green leafy vegetables.
• Continues to cause pain even after self care, such as wearing wide-toed shoes
• Waxy casts can be found in persons with advanced kidney disease and chronic kidney failure.
• Delirium
• Traumatic brain injury
• Rate of cell division or how quickly the tumor is growing
• Decerebrate posture -- the arms and legs are out straight and rigid, the toes point downward, and the head arches backward
• Stress
• Sudden falling

The pathologic effects of isch emic brain injury from systemic hypotension differ from those caused by pure anoxia gastritis symptoms treatment buy motilium no prescription. Under conditions of tran sient ischemia gastritis symptoms how long does it last purchase motilium cheap online, one pattern of damage takes the form of incomplete infarctions in the border zones between major cerebral arteries (Chap gastritis diet vegetables motilium 10 mg cheap. With predominant anoxia gastritis diet soy milk discount motilium amex, neurons in portions of the hippocampus and the deep folia of the cerebellum are particularly vulnerable gastritis diet 2012 order 10 mg motilium mastercard. More severe degrees of either ischemia or hypoxia gastritis no symptoms generic 10 mg motilium otc, or the combina tion, lead to selective damage to certain layers of cortical neurons, and if more profound, to generalized damage of all the cerebral cortex, deep nuclei, and cerebellum. The nuclear structures of the brainstem and spinal cord are relatively resistant to anoxia and hypotension and stop functioning only after the cortex has been badly damaged. The cellular pathophysiology of neuronal damage under conditions of ischemia is discussed in Chap. One mechanism of injury is an arrest of the aerobic metabolic processes necessary to sustain the Krebs (tricarboxylic acid) cycle and the electron transport system. Neurons, if completely deprived of their source of energy; are unable to maintain their integrity and undergo necrosis. The most acute forms of cell death are character ized by massive swelling and necrosis of neuronal and nonneuronal cells (cytotoxic edema). Short of immediate ischemic necrosis, a series of internally programmed cel lular events may also propel the cell toward death in a delayed fashion, a process for which the term apoptosis has been borrowed from embryology. There is experimental evidence that certain excitatory neurotransmitters, par ticularly glutamate, contribute to the rapid destruction of neurons under conditions of anoxia and ischemia (Choi and Rothman); the pertinence of these effects to clinical situations is uncertain. Ultimately; this process may be affected by massive calcium influx through a number of different membrane channels, which activates various kinases that participate in the process of gradual cellular destruction. Free radical generation appears to play a role in membrane dissolution as a result of these processes. There is also a poorly understood phenomenon of delayed neurologic deterioration after anoxia; this may be a result of the blockage or exhaustion of some enzymatic process during the period when brain metabolism is restored. These observations make the point that profound anoxia may be well tolerated if arrived at gradually. For example, we have seen several patients with advanced pulmonary disease who were fully awake when their arterial oxygen pressure was in the range of 30 mm Hg. An important derivative observation is that degrees of hypoxia that at no time abolish consciousness rarely, if ever, cause per manent damage to the nervous system. In the circumstances of severe global ischemia with prolonged loss of consciousness, the clinical effects can be quite variable. Following cardiac arrest, for example, consciousness is lost within seconds but recovery can be complete if breathing, oxygenation, and cardiac action are restored within 3 to 5 min. Clinically, however, it is often difficult to judge the precise degree and duration of ischemia, because slight heart action or an impercep tible blood pressure may have served to maintain the circulation to some extent. Hence some individuals have made an excellent recovery after cerebral ischemia that apparently lasted 8 to 10 min or longer. Subnormal body temperatures, as might occur when the body is immersed in ice-cold water, greatly prolong the tolerable period of hypoxia. This has led to the successful application of moderate cooling after cardiac arrest as a technique to limit cerebral damage (see further on in Treatment of Hypoxic-Ischemic Encephalopathy section). Conversely, the absence of these brainstem reflexes even after circulation and oxygenation have been restored, particularly pupils that fail to react to light, implies a grave outlook as elaborated further on. If the damage is almost total, coma persists, decerebrate postures may be present spontaneously or in response to painful stimuli, and bilateral Babinski signs can be evoked. In the first 24 to 48 h, death may terminate this state in a setting of rising temperature, deepening coma, and circulatory collapse, or the syndrome of brain death intervenes, as discussed below. Most patients who have suffered severe but lesser degrees of hypoxia will have stabilized their breathing and cardiac activity by the time they are first examined; yet they are comatose, with the eyes slightly divergent and motionless but with reactive pupils, the limbs inert and flaccid or intensely rigid, and the tendon reflexes dimin ished. Within a few minutes after cardiac action and breathing have been restored, generalized convulsions and isolated or grouped myoclonic twitches may occur. Tragically, the individual may survive for an indefinite period in a state that is variously referred to as cortical death, irreversible coma, or persistent vegetative state (see discussion of these subjects in Chap. Some patients remain mute, unresponsive, and unaware of their envi ronment for weeks, months, or years. Long survival is usually attended by some degree of improvement but the patient appears to know nothing of his present situation and to have lost all past memories, cognitive function, and capacity for meaningful social interaction and inde pendent existence (a minimally conscious state, actually a severe dementia; see Chap. With lesser degrees of anoxic-ischemic injury, the patient improves after a period of coma lasting hours or less. Some of these patients quickly pass through this acute post-hypoxic phase and proceed to make a full recov ery; others are left with varying degrees of permanent disability. The most common early change in cases of severe injury is a loss of the distinction between the cerebral gray and white matter. With less severe and predominantly hypotensive-ischemic events such as cardiac arrest, watershed infarctions become evident in the border zones between the anterior, middle, and posterior cere bral arteries. Natural res piration cannot be sustained; only cardiac action and blood pressure are maintained. At autopsy one finds that most, if not all, the gray matter of cerebral, cerebel lar, and brainstem structures-and in some instances, even the upper cervical spinal cord-has been severely damaged. Watershed infarction between the middle and poste rior cerebral arteries after brief cardiac arrest. Visual agnosias including Balint syndrome and cortical blindness (Anton Syndrome) (see Chap. Proximal a rm and shoulder weakness, sometimes accom panied by hip weakness (referred to as a "man-in the-barrel" syndrome), reflecting infarction in the territory between the middle and anterior cerebral arteries. These patients are able to walk, but their arms dangle and their hips may be weak. The interested reader may consult the appropriate chapter in the text on neurologic intensive care by Ropper and col leagues for further details. Myoclonus is a grave sign in most cases but it generally recedes after several hours or a few days. The pallidum is spared, in contrast to typical cases of car bon monoxide poisoning. Delayed Posta noxic Enceph a lopathy and Leu koencephalopathy this is a relatively uncommon and unexplained phe nomenon. Initial improvement, which appears to be complete, is followed after a variable period of time (1 to 4 weeks in most instances) by a relapse, characterized by time the results of toxic screening also become avail able. In exceptional cases, however, the provision of adequate fluid, vasopressors, and respiratory support allows preservation of the body in a comatose state for longer periods. Most patients survive this second episode, but some are left with serious mental and motor disturbances (Choi; Plum et al). In still other cases, there appears to be progression of the initial neurologic syndrome with additional weakness, shuffling gait, diffuse rigidity and spasticity, sphincteric incontinence, coma, and death after 1 to 2 weeks. Exceptionally; there is yet another syndrome in which an episode of hypoxia is followed by slow dete rioration, which progresses for weeks to months until the patient is mute, rigid, and helpless. Instances have followed cardiac arrest, drown ing, asphyxiation, and carbon monoxide poisoning. A mitochondrial disorder has been suggested, on uncertain grounds, as the under lying mechanism. All of them incor porate simple clinical features involving loss of motor, ver bal, and pupillary functions in various combinations. The neurologist can be expected to state the level and degree of brain damage, its cause, and the prognosis based on his own and published experience. One pru dently avoids heroic, lifesaving therapeutic measures once the nature of this state has been determined with certainty. The absence of neurologic function in any of these spheres at 1 day after cardiac arrest, unsurprisingly, was associated with an even poorer outcome. Similarly, Booth and colleagues analyzed previously published studies and determined that 5 clinical signs at 1 day after cardiac arrest predicted a poor neurologic outcome or death: (1) absent corneal responses, (2) absent pupillary reactivity, (3) no withdrawal to pain, and (4) the absence of any motor response. The use of somatosensory evoked potentials in the prognostication of coma is discussed in Chaps. Most workers in the field of coma studies have been unable to establish signs that confidently predict a good outcome. The role of somatosensory evoked potentials in prognosis of coma has been addressed in Chap. The question of what to do with patients in such states of protracted coma is a societal as much as a medical Treatment is directed initially to the prevention of further hypoxic injury. A clear airway is secured, cardiopulmo nary resuscitation is initiated, and every second counts in their prompt utilization. Oxygen may be of value during the first hours but is probably of little use after the blood becomes well oxygenated. Once cardiac and pulmonary function are restored, there is experimental and clinical evidence that reducing cerebral metabolic requirements by inducing hypothermia may have a slight beneficial effect on outcome and may prevent the delayed worsen ing referred to above, though a recent clinical trial brings this into question (see further on). Much attention was drawn to the randomized trials conducted by Bernard and colleagues and by the Hypothermia After Cardiac Arrest Study Group, of mild hypothermia applied to unconscious patients immediately after cardiac arrest. Both trials demonstrated improved survival and bet ter cognitive outcome in survivors, compared to leav ing the patient in a normothermic state and this led to the development of guidelines and a change in clinical practice in the U. Implementing and sustaining hypothermia, either by external cooling, infusion of cooled normal saline, or intravenous cooling devices is difficult, and the iatrogenic problems of hypotension, bleeding, ventricular ectopy and infection have some times arisen, although this mild degree of temperature reduction is usually well tolerated. The results of this third study are still being discussed and it is not clear if it should be interpreted as demonstrating that hypothermic treatment is ineffective or if the avoid ance of even mild hyperthermia, observed in the con trol groups of previous trials, was the important factor in improving outcome. At the time of this writing, it seems to us that induced hypothermia is not obligatory after cardiac arrest but that attempts should be made to keep the body temperature from rising above normal. Vasodilator drugs, glutamate blockers, opiate antag onists, and calcium channel blockers have been of no proven benefit despite their theoretical appeal and some experimental successes. Corticosteroids ostensibly help to allay brain (possibly cellular) swelling, but, again, their therapeutic benefit has not been evident in clinical trials. If convulsions are severe, continuous, and unresponsive to the usual medications, continuous infusion of a drug such as midazolam or propofol, and eventually the suppression of convulsions with neuro muscular blocking agents may be required. For the latter, clonazepam, 8 to 12 mg daily in divided doses may be useful but the commonly used antiepileptic drugs have little effect. A state of spontane ous and stimulus-sensitive myoclonus as well as persis tent limb posturing usually presages a poor outcome. The striking disorder of delayed movement-induced myoclo nus and ataxic tremor that appear after the patient awak ens from an anoxic episode (Lance-Adams myoclonus) is a special issue, which is discussed in Chap. Fever is treated with antipyretics or a cooling blanket combined with neuromuscular paralyzing agents. The effects on the brain for the most part simulate those caused by cardiac arrest. Early symptoms include headache, nausea, dyspnea, confusion, dizziness, and clumsiness. These occur when the carboxyhemoglobin level reaches 20 to 30 percent of total hemoglobin. A cherry-red color of the skin may appear, but is actu ally an infrequent finding; cyanosis is more common. Only if there has been associated hypo tension does one see the same types of vascular border zone infarctions that appear after cardiac arrest. The common feature among the delayed-relapse patients is a prolonged period of pure anoxia (before the occurrence of ischemia). Headache, anorexia, nausea and vomiting, weakness, and insomnia appear at alti tudes above 8,000 ft; on reaching higher altitudes, there may be ataxia, tremor, drowsiness, mild confusion, and hallucinations. At 16,000 ft, according to Griggs and Sutton, 50 percent of individuals develop asymptomatic retinal hemorrhages, and it has been suggested that such hemorrhages also occur in the cerebral white mat ter. With more prolonged exposure at these altitudes or with further ascent, affected individuals suffer mental impairment that may progress to coma. Hypoxemia at high altitudes is intensified during sleep, as ventilation normally diminishes and also by pulmo nary edema, another manifestation of mountain sick ness. Reference was made earlier to the observation of Hornbein and colleagues of a mild, but possibly lasting, memory impairment even in acclimated mountaineers who had been exposed to extremely high altitudes for several days. Chronic mountain sickness, also called Monge disease (after the physician who described the condition in Andean Indians of Peru), is observed in long-term inhab itants of high-altitude mountainous regions. Pulmonary hypertension, cor pulmonale, and secondary polycythe mia are the main features. There is usually hypercarbia as well, with the expected degree of mild mental dullness, slowness, fatigue, nocturnal headache, and, sometimes, papilledema (see below). Thomas and colleagues have called attention to a syndrome of burning hands and feet in Peruvians at high altitude, apparently a maladaptive response to chronic hypoxia. Sedatives, alcohol, and a slightly elevated Pco2 in the blood all reduce tolerance to high altitude. Dexamethasone and acetazolamide prevent and counteract mountain sickness to some extent. The most effective preventive measure is acclimatization by a 2- to 4-day stay at inter mediate altitudes. Hyperca pnic Pu lmonary Disease Chronic obstructive pulmonary disease such as emphy sema, fibrosing lung disease, neuromuscular weakness, and, in some instances, inadequacy of the medullary respiratory centers each may lead to persistent respi ratory acidosis, with elevated of Pco 2 and reduced in arterial Po 2. The complete clinical syndrome of chronic hypercapnia described by Austen, Carmichael, and Adams comprises headache, papilledema, mental dullness, drowsiness, confusion, stupor and coma, and asterixis. The headache tends to be generalized, frontal, or occipital and can be quite intense, persistent, steady, and aching in type; nocturnal occurrence is a feature of some cases. The papilledema is bilateral but may be slightly greater in one eye than in the other, and hemorrhages may encircle the choked disc (a later finding). Intermittent drowsiness, inattentiveness, reduction of psychomotor activity, inability to perceive all the items in a sequence of events, and forgetfulness constitute the more subtle man ifestations of this syndrome and may prompt the family to seek medical help.