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Dementia, the symptom complex of progressive global impairment of intellectual function, is a major medical, social, and economic problem that is worsening as the number of elderly people in the general population increases It is discussed in 4, and the only point to be reiterated here is the importance of recognizing early any treatable or reversible causes of dementia, such as normal-pressure hydrocephalus, intracranial mass lesions, vascular disease, hypothyroidism, thiamine or vitamin B12 deficiency, Wilson s disease, hepatic or renal failure, neurosyphilis, and the chronic meningitides
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Episodic neurologic symptoms Patient usually under 55 years of age at onset Single pathologic lesion cannot explain clinical findings Multiple foci best visualized by MRI
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MRI of the brain or cervical cord is often helpful in demonstrating the presence of a multiplicity of lesions CT scans are less helpful In patients presenting with myelopathy alone and in whom there is no clinical or laboratory evidence of more widespread disease, myelography or MRI may be necessary to exclude a congenital or acquired surgically treatable lesion The foramen magnum region must be visualized to exclude the possibility of Arnold-Chiari malformation, in which parts
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of the cerebellum and the lower brainstem are displaced into the cervical canal and produce mixed pyramidal and cerebellar deficits in the limbs
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C Laboratory and Other Studies
A definitive diagnosis can never be based solely on the laboratory findings If there is clinical evidence of only a single lesion in the central nervous system, multiple sclerosis cannot properly be diagnosed unless it can be shown that other regions are affected subclinically The electrocerebral responses evoked by monocular visual stimulation with a checkerboard pattern stimulus, by monaural click stimulation, and by electrical stimulation of a sensory or mixed peripheral nerve have been used to detect subclinical involvement of the visual, brainstem auditory, and somatosensory pathways, respectively Other disorders may also be characterized by multifocal electrophysiologic abnormalities There may be mild lymphocytosis or a slightly increased protein concentration in the cerebrospinal fluid, especially soon after an acute relapse Elevated IgG in cerebrospinal fluid and discrete bands of IgG (oligoclonal bands) are present in many patients The presence of such bands is not specific, however, since they have been found in a variety of inflammatory neurologic disorders and occasionally in patients with vascular or neoplastic disorders of the nervous system
It can only be prescribed under a risk management plan because of rare reports of progressive multifocal leukoencephalopathy developing in patients while receiving treatment Several studies have suggested that immunosuppressive therapy with cyclophosphamide, azathioprine, methotrexate, cladribine, or mitoxantrone may help arrest the course of secondary progressive multiple sclerosis The evidence of benefit is incomplete, however There is little evidence that plasmapheresis is helpful in multiple sclerosis Intravenous immunoglobulins (IVIGs) may reduce the clinical attack rate in relapsing-remitting disease, but the available studies are inadequate to permit treatment recommendations Statins may have immunomodulatory effects, and their possible role in the treatment of multiple sclerosis is being studied Treatment for spasticity (see below) and for neurogenic bladder may be needed in advanced cases Excessive fatigue must be avoided, and patients should rest during periods of acute relapse
Fox EJ Management of worsening multiple sclerosis with mitoxantrone: a review Clin Ther 2006 Apr;28(4):461 74 [PMID: 16750460] Goodin DS Magnetic resonance imaging as a surrogate outcome measure of disability in multiple sclerosis: have we been overly harsh in our assessment Ann Neurol 2006 Apr;59(4): 597 605 [PMID: 16566022] Polman CH et al A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis N Engl J Med 2006 Mar 2;354(9):899 910 [PMID: 16510744]
D Diagnosis
Multiple sclerosis should not be diagnosed unless there is evidence that two or more different regions of the central white matter have been affected at different times A diagnosis of clinically definite disease can be made in patients with a relapsing-remitting course and evidence on examination of at least two lesions involving different regions of the central white matter The diagnosis is probable in patients with multifocal white matter disease but only one clinical attack, or with a history of at least two clinical attacks but signs of only a single lesion
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