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ory, a global dementia with deteriorated executive function, or a confusional-psychotic state also occur in the advanced stages of the disease The cognitive impairment is more in keeping with what has been ascribed to subcortical dementia (page 372) Symptoms of bladder dysfunction including hesitancy, urgency, frequency, and incontinence occur commonly with spinal cord involvement Urinary retention, due to affection of sacral segments, is less frequent (Fig 26-5) In males, these symptoms are often associated with impotence, a symptom that the patient may not report unless speci cally questioned in this regard Abrupt attacks of neurologic de cit, lasting a few seconds or minutes and sometimes recurring many times daily, are a relatively infrequent but well-recognized feature of MS (see Osterman and Westerbey) Usually the attacks occur during the relapsing and remitting phase of the illness, rarely as an initial manifestation These clinical phenomena are referable to any part of the CNS but tend to be stereotyped in an individual patient The most common phenomena are dysarthria and ataxia, paroxysmal pain and dysesthesia in a limb, ashing lights, paroxysmal itching, or tonic seizures, taking the form of exion (dystonic) spasm of the hand, wrist, and elbow with extension of the lower limb The paroxysmal symptoms, particularly the tonic spasms, may be triggered by sensory stimuli or can be elicited by hyperventilation On a few occasions we have seen dystonic hand and arm spasms as the rst symptoms; an acute plaque was detected in the opposite internal capsule In advanced cases, the spasms may involve all four limbs and even a degree of opisthotonos The cause of paroxysmal phenomena is uncertain They have been attributed by Halliday and McDonald to ephaptic transmission ( cross-talk ) between adjacent demyelinated axons within a lesion Carbamazepine is usually effective in controlling such attacks These transitory symptoms appear suddenly, may recur frequently for several days or weeks, sometimes longer, and then remit completely, ie, they exhibit the temporal pro le of a relapse or an exacerbation It is sometimes dif cult to determine whether they represent an exacerbation or a new lesion Years ago, Thygessen pointed out, in an analysis of 105 exacerbations in 60 patients, that there were new symptoms in only 19 percent; in the remainder there was only a recurrence of old symptoms Another problem is that the original lesion may have been asymptomatic This is most obviously re ected in the many patients who are found to have impaired visual evoked responses but have never had symptomatic visual changes Thus, new symptoms and signs may be manifestations of previously formed but asymptomatic plaques However, the observations of Prineas and Connell indicate that symptoms and signs may progress without the appearance of new plaques These and other factors need to be taken into consideration in evaluating the clinical course of the illness and the effects of a therapeutic program (see Poser) Unusually severe fatigue is another peculiar symptom of MS; it is often transient and more likely to occur when there is fever or other evidence of disease activity, but it can be a persistent complaint and a source of considerable distress Depression may play a role in these recalcitrant cases, although the response to pharmacologic agents suggests that these two aspects of the disease are dissociable Thus, antidepressants often do not improve fatigue, while drugs that alleviate fatigue, such as moda nil and amantadine, do not function as antidepressants A number of other interesting manifestations of MS have come to our attention over the years and have given rise to dif culties in diagnosis The occurrence of typical tic douloureux in.

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young patients has already been mentioned; only their young age and the bilaterality of the pain in some of them raised the suspicion of MS, con rmed later by sensory loss in the face and other neurologic signs It is notable, however, that facial palsy along the lines of Bell s palsy is almost never a sign of MS Brachial, thoracic, or lumbosacral pain consisting mainly of thermal and algesic dysesthesias, was a source of puzzlement in several other patients until additional lesions developed Other types of pain in MS have been addressed earlier In two of our cases, the relatively acute occurrence of a right hemiplegia and aphasia rst raised the probability of a cerebrovascular lesion; in still others, a more slowly evolving hemiplegia had led to an initial diagnosis of a cerebral glioma The dystonic and paroxysmal symptoms are mentioned above; they do not typically bring the diagnosis of MS to mind Approximately 3 percent of patients reportedly have focal seizures, but it should be emphasized that this is usually in relation to an obvious cerebral lesion and advanced disease of many years duration Seizures at an early stage of illness are almost always attributable to previous head injury, idiopathic epilepsy, or as in a recent case, withdrawal of sleep medication Several times we have seen coma during relapse of MS, and in each instance it continued to death In one case it occurred in a 64-year-old woman who had had two previous episodes of nondisabling spinal MS at 30 and 44 years of age A confusional psychosis with drowsiness was the initial syndrome in another patient whom we saw later with a relapse involving the cerebellum and spinal cord Another unusual syndrome is one of slow intellectual decline with slight cerebellar ataxia A 10-year, slowly progressive cerebellar ataxia in an adolescent girl was perplexing until she later developed internuclear ophthalmoplegia A rapid onset of ascending paralysis of legs, bladder and bowel, and trunk with severe pain in sacral parts, are exia, and a mononuclear pleocytosis of 1600 cells per cubic millimeter occurred in another of our patients and lasted 2 years before she began to walk again; earlier she had had diplopia and retrobulbar neuritis Cases similar to these develop a necrotic myelopathy that is similar to Devic disease and there is little recovery As mentioned in the chapter on spinal cord disease, some instances of MS in late adult life take the form of a slowly progressive cervical myelopathy There is also certainly a form of spinal MS without cerebral involvement, as noted further on Seemingly more frequently in recent years, we have observed patients whose illness satis ed all the clinical criteria for the diagnosis of MS except for the onset of symptoms in the sixth or seventh decade Presumably we were witnessing the late deteriorative phase of the illness, earlier symptoms having been forgotten or having never been recognized Contrariwise, in our pathologic material (and increasingly with the ubiquitous use of MRI scans), we have several times found a few typical lesions of MS to which the clinical records make no reference.

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Several variants of MS merit more extended discussion They are acute MS, neuromyelitis optica, acquired Schilder disease, and the conjunction of MS and polyneuropathy The chronic progressive variety of MS presents special problems that are addressed in a later section on Clinical Course and Prognosis Acute Multiple Sclerosis Rarely, MS takes a rapidly progressive and highly malignant form; Marburg s name has been attached to this variant A combination of cerebral, brainstem, and spinal man-

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