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Multiple Sclerosis Multiple sclerosis is characterized by recurrent or chronically progressive neurologic dysfunction caused by lesions in the CNS. The CNS lesions are characterized by multiple areas of demyelination in the CNS. The brain, optic nerves, and spinal cord may be, sclorosis, MS Epidemiology Approximately 250,000 to 350,000 people in the United States have a diagnosis of MS; the prevalence is about 100 cases per 100,000 population. MS is more common in women than men by a ratio of 2:1. The onset of disease usually occurs between 20 and 50 years of age, with a peak at about 30 years of age. MS occurs in all major racial groups but is most common in whites, less common in blacks, and rare in Asians. The prevalence of MS varies widely Etiology The etiology of MS is unknown, but both genetic and nongenetic factors are important. The importance of genetic factors has been firmly established by the studies of familial MS. The contribution of nongenetic factors is demonstrated by the lack of concordance for Genetics The impression that susceptibility to MS is at least partly familial has been confirmed by extensive studies that found an increased prevalence of MS in close relatives of MS patients. In one study, the risk of MS in an identical twin of an MS patient was 31 percent, whereas the risk for a dizygotic twin was about five percent. Another study showed that the risk for a Diagnosis The diagnosis of MS is made on the basis of the clinical signs and symptoms, with magnetic resonance imaging and other laboratory tests playing a supporting role. The diagnosis of definite MS requires evidence for the dissemination of lesions in time and space Clinical Features Almost any neurologic deficit can occur in MS, but there are several signs and symptoms that are characteristic. None of these characteristic findings are pathognomonic for MS, but their presence should suggest MS as a possible diagnosis, particularly in a young adult. The typical findings include optic neuritis, internuclear ophthalmoplegia, heat sensitivity, and Lhermitte’s sign. About 20 percent of patients present with optic neuritis as their There are a number of other symptoms that are extremely common in MS but that also occur in many other disease processes. These include weakness, sensory loss, ataxia, and bowel and bladder symptoms. All these symptoms develop in the majority of patients during the Clinical Course The clinical course of MS varies greatly between people. The typical pattern of disease is Pathology and Pathogenesis Plaques, consisting of varying amounts of perivenular mononuclear cell inflammation, Laboratory Tests Magnetic resonance imaging MRI is the single most useful laboratory test in the diagnosis of MS. Most patients with MS have abnormalities that can be seen with MRI, and Cerebrospinal fluid Most CSF constituents are minimally affected in MS. A mild mononuclear cell pleocytosis can be found during acute relapses, but total cell counts Neurophysiology Slowing of conduction over demyelinated segments of axons or over incompletely remyelinated pathways provides a useful marker for identifying additional subclinical lesions in sensory pathways. Conduction can be measured along visual, auditory, Management of MS Treatment of MS can be broadly divided between management of acute relapses, prevention of relapses as modification of the disease process, and management of symptoms and fixed neurologic deficits. Acute relapse Management of relapses varies with the severity of the presenting signs and symptoms. Mild attacks that do not significantly alter the patient’s ability to function require no more than a supportive physician-patient relationship. High-dose corticosteroid Prevention of relapse In the past few years, three different medications that affect the long-term clinical course of MS have been approved. These include interferon beta-1b (IFN-–1b), interferon beta-1a (IFN-–1a), and glatiramer acetate (previously known as copolymer-1). When administered at regular intervals to patients with relapsing-remitting MS, The glycosylated IFN-–1a was tested in relapsing patients with little to mild disability at a single intramuscular dose of 6 million IU weekly. An overall reduction in the annualized attack rate of 18 percent was found when patients were followed for up to two years in a controlled trial; a 37 percent reduction in the proportion of all patients who showed sustained Glatiramer is a synthetic random polymer of four amino acids. Its mechanism of action is not definitively established, but it promiscuously binds to MHC class II antigen and induces Progressive MS In contrast to relapsing MS, no therapies have been shown definitively to be useful for progressive MS. Various aggressive immunosuppressive therapies have been tried, but most have been abandoned because of lack of efficacy, excessive side effects, or both. Cyclophosphamide, cladribine, methotrexate, azathioprine, and monthly high-dose corticosteroid treatment all have been advocated as treatment, but Symptomatic therapy Several of the common symptoms of MS respond to pharmacological treatment. Prominent among the most frequent symptoms of MS are depression and fatigue. Depression occurs in about 20 percent of MS patients, probably About 50 percent of patients with MS obtain at least partial relief by treatment with amantadine, but dosing late in the day, which may induce insomnia, should be avoided. When amantadine fails, pemoline, methylphenidate hydrochloride, or selective serotonin reuptake inhibitors may be useful. Spasticity is another common symptom that is amenable to treatment. The increased extensor tone in the lower extremities can to some extent compensate for associated weakness, but excessive spasticity is counterproductive to a fluid gait and may result in painful spasms or joint contracture. Centrally active g-aminobutyric acid (GABA) agonists, such as baclofen, often reduce spasticity but preserve functional gait or lower limb strength needed for transfer. Effective doses of baclofen vary from as little as 5 mg to 240 mg daily in Bladder dysfunction is also common in MS. The pathophysiology is complex; the symptoms, detrusor-sphincter dyssynergia, hyperactive detrusor function, and flaccid bladder, may occur individually or in various combinations, and often they fluctuate over time. Formal urodynamic studies are essential to delineate these various patterns and to Pain is not uncommon in MS. Often, it is secondary to unusual mechanical stress resulting from asymmetric weakness or spasticity. Appropriate orthotics, antispasmolytics, and self-performed exercise routines, supplemented by simple analgesics, are helpful. Paroxysmal pain syndromes, typified by trigeminal neuralgia, usually respond to low doses of carbamazepine or other antiepileptic drugs, particularly gabapentin. Distal dysesthetic sensations may also respond to these drugs. Low doses of tricyclic antidepressants may also Prognosis Although the course of MS varies from patient to patient, the effect of the disease in large
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