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Treatment is symptomatic and may need to be continued indefinitely Haloperidol is generally regarded as the drug of choice It is started in a low daily dose (025 mg) that is gradually increased (by 025 mg every 4 or 5 days) until there is maximum benefit with a minimum of side effects or until side effects limit further increments A total daily dose of between 2 and 8 mg is usually optimal, but higher doses are sometimes necessary Treatment with clonazepam (in a dose that depends on response and tolerance) or clonidine (2 5 mcg/kg/d) may also be helpful, and it seems sensible to begin with one of these drugs in order to avoid some of the longterm extrapyramidal side effects of haloperidol Phenothiazines, such as fluphenazine (2 15 mg daily), have been used, but patients unresponsive to haloperidol are usually unresponsive to these as well Pimozide, an oral dopamine-blocking drug related to haloperidol, may be helpful in patients who cannot tolerate or have not responded to haloperidol Treatment is started with 1 mg daily and the daily dose increased by 1 2 mg every 10 days; the average dose is between 7 and 16 mg daily Injection of botulinum toxin type A at the site of the most distressing tics is sometimes worthwhile Treatment with risperidone, calcium channel blockers, tetrabenazine, clomipramine, or metoclopramide has yielded mixed results or encouraging findings in preliminary studies that require confirmation Bilateral high-frequency thalamic stimulation has been helpful in some, otherwise intractable, cases and is currently under study

Albin RL et al Recent advances in Tourette syndrome research Trends Neurosci 2006 Mar;29(3):175 82 [PMID: 16430974]

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This common neurologic disorder, which probably has an autoimmune basis, has its greatest incidence in young adults Epidemiologic studies indicate that multiple sclerosis is much more common in persons of western European lineage who live in temperate zones No population with a high risk for multiple sclerosis exists between latitudes 40 N and 40 S Genetic, dietary, and climatic factors cannot account for these differences Nevertheless, a genetic susceptibility to the disease is likely, based on twin studies, familial cases, and an association with specific HLA antigens (HLA-DR2) Pathologically, focal often perivenular areas of demyelination with reactive gliosis are found scattered in the white matter of brain and spinal cord and in the optic nerves

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The common initial presentation is weakness, numbness, tingling, or unsteadiness in a limb; spastic paraparesis; retrobulbar neuritis; diplopia; disequilibrium; or a sphincter disturbance such as urinary urgency or hesitancy Symptoms may disappear after a few days or weeks, although examination often reveals a residual deficit Several forms of the disease are recognized In most patients, there is an interval of months or years after the initial episode before new symptoms develop or the original ones recur (relapsing-remitting disease) Eventually, however, relapses and usually incomplete remissions lead to increasing disability, with weakness, spasticity, and ataxia of the limbs, impaired vision, and urinary incontinence The findings on examination at this stage commonly include optic atrophy, nystagmus, dysarthria, and pyramidal, sensory, or cerebellar deficits in some or all of the limbs In some of these patients, the clinical course changes so that a steady deterioration occurs, unrelated to acute relapses (secondary progressive disease) Less commonly, symptoms are steadily progressive from their onset, and disability develops at a relatively early stage (primary progressive disease) The diagnosis cannot be made with confidence unless the total clinical picture indicates involvement of different parts of the central nervous system at different times A number of factors (eg, infection, trauma) may precipitate or trigger exacerbations Relapses are also more likely during the 2 or 3 months following pregnancy, possibly because of the increased demands and stresses that occur in the postpartum period

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

Example A-61. The solution to Exercise 20-3 (continued)

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

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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