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http://www.ucsf.edu/brain/pdcenter/AtypicalPDforMDs.htm Recognizing Other Causes of Parkinsonism Although the symptoms and signs of Parkinson's disease (PD) are fairly specific, a significant fraction of patients with parkinsonism do not have PD. Indeed an epidemiologic study of patients with parkinsonism found that 65% had PD, 18% had drug-induced parkinsonism, 7% had vascular parkinsonism; 6% had atypical but non-specific features, 2% had dementia with parkinsonism, 2.5 % had progressive supranuclear palsy, and 1.7 % had multiple system atrophy (Schrag et al, 2000). Identifying patients with atypical parkinsonism is important since these patients respond less reliably to dopaminergic agents, do not respond favorably to surgical treatments of PD, and often develop additional clinical problems. Atypical parkinsonism should be considered particularly in patients with poor dopamine responsiveness, early loss of balance, prominent dementia, rapid onset or progression, prominent autonomic dysfunction, and little or no tremor. Medication-induced Parkinsonism Although tremor and postural instability may be less prominent, this condition may be indistinguishable from PD. Medications frequently associated with the development of parkinsonism include: antipsychotics, metaclopramide, reserpine, tetrabenazine and some calcium-channel blockers (especially cinnarizine and flunarizine). The parkinsonism usually resolves within weeks to months after discontinuing the offending medication. Progressive Supranuclear Palsy (PSP) Early onset of imbalance, frequent falls, axial rigidity, and (eventually) eye movement problems characterize PSP. Symptoms usually begin after age 50 and progress more rapidly than with Parkinson's disease. The most characteristic eye movement abnormality is of a vertical gaze paresis, however, a slowing of vertical saccadic movements may often be appreciated first (Vidailhet et al, 1994). Dementia develops later in the disease. There is no specific treatment for PSP. Dopaminergic treatment should be tried but often offers little benefit. Supportive measures such as speech therapy, physical therapy and antidepressants may help. Corticobasal Degeneration (CBD) CBD is the least common of the atypical causes of parkinsonism and often affects patients quite asymmetrically and progresses more rapidly than PD. The initial symptoms of CBD usually develop after age 60 and include: asymmetric bradykinesia, rigidity, limb dystonia, and postural instability. Additional features such as ideomotor apraxia, alien limb phenomenon, progressive aphasia or the development of contractures are typical of CBD (Stover and Watts, 2001). There is no specific treatment for CBD. Supportive treatment such as botulinum toxin for dystonia, antidepressants as well as speech and physical therapy may help. Levodopa and dopamine agonists seldom offer benefit Multiple System Atrophy (MSA) MSA is a sporadic neurodegenerative disease of unknown cause. The mean age of onset is 54 and median survival is 6 years (Ben-Shlomo et al, 1997). Clinically, it presents with bradykinesia, cerebellar ataxia, autonomic dysfunction, and pyramidal signs. The term "multiple system atrophy" encompasses the three presentations of the illness that have overlapping clinical and pathological findings: striatonigral degeneration (parkinsonian presentation), olivopontocerebellar atrophy (ataxic presentation), and Shy-Drager syndrome (autonomic presentation). While at initial presentation a patient may have a rather pure phenotype, as the condition progresses other symptoms and signs develop that reflect involvement of a different system. Patients with the parkinsonian presentation typically have an asymmetrical tremor, bradykinesa, rigidity and postural instability. Men often develop impotence; both men and woman often experience urinary urgency and incontinence. Although 30% of patients obtain a definite but short lived benefit from levodopa and dopamine agonists, the parkinsonism is typically poorly responsive to medications. Dyskinesias and dystonia emerge in half of treated patients. There is not much experience using deep brain stimulators (DBS) for MSA, however, Visser-Vandewalle and colleagues (2003) found a modest benefit of subthalamic DBS that persisted over 2 years in 4 patients. Vascular Parkinsonism Multiple small strokes, particularly if located adjacent to the internal capsule, can cause parkinsonism. Winikates and Jankovic (1999) found that patients with this disorder are more likely to present with gait difficulty than tremor and are more likely to have symptoms that are worse in the lower extremities than upper extremities. Some will also report an abrupt onset of symptoms. Signs on neurological exam may include bilateral slowing, impaired fine movements, increased tone, and a gait disturbance. Treatment for this condition is the same as for PD. Dementia with Lewy Bodies (DLB) This disorder is characterized by early dementia, prominent hallucinations, fluctuations in cognitive status, and parkinsonism. In a study comparing DLB with PD, the absence of resting tremor, the presence of myoclonus, the symmetry of the extrapyramidal symptoms, and the lack of response to levodopa were more common in DLB (Louis et al, 1997). The neuropsychological profile is characterized by deficits in attention, executive function and visuospacial function (Hansen et al, 1990). Clock drawing is often helpful in demonstrating the visuospacial deficit. Treatment with cholinesterase inhibitors may reduce delusions, apathy, agitation and hallucinations (McKeith et al, 2000). A severe extrapyramidal reaction to antipsychotic medication is another feature of this disease. If behavioral problems do not respond to cholinesterase inhibitors, low-dose treatment with atypical antipsychotic medications (quitiapine or clozapine) may be considered (Swanberg, 2002). Although motor symptoms may respond to levodopa, treatment may be limited by hallucinations. References: Ben-Shlomo Y, Wenning GK, Tison F, Quinn NP. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis. Neurology 1997; 48:384-93. Hansen L, Salmon D, Galasko D, Masliah E, et al. The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology 1990; 40:1-8. Louis ED, Klatka LA, Liu Y, Fahn S. Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson's disease. Neurology 1997; 48:376-80. McKeith I, Del Ser T, Spano P, Emre M, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000; 356:2031-6. Schrag A, Ben-Shlomo Y, Quinn NP. Cross sectional prevalence survey of idiopathic Parkinson's disease and Parkinsonism in London. BMJ 2000; 321:21-2 Swanberg MM, Cummings JL. Benefit-risk considerations in the treatment of dementia with Lewy bodies. Drug Saf 2002; 25:511-23. Stover NP, Watts RL. Corticobasal degeneration. Semin Neurol 2001; 21:49-58. Vidailhet M, Rivaud S, Gouider-Khouja N, Pillon B, et al. Eye movements in parkinsonian syndromes. Ann Neurol 1994;35:420-6. Visser-Vandewalle V, Temel Y, Colle H, van der Linden C. Bilateral high-frequency stimulation of the subthalamic nucleus in patients with multiple system atrophy--parkinsonism. Report of four cases. J Neurosurg 2003; 98:882-7. Winikates J, Jankovic J. Clinical correlates of vascular parkinsonism. Arch Neurol 1999; 56:98-102. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn