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CURRENT SCIENCE REVIEWS By Joe Bruman April 1999 Page 1 of 3 Limousin P et al; J Neur N'surg Psych 1999;66:289-296: Study of 111 patients treated at 13 European centers showed that thalamic stimulation (DBS) is an effective and relatively safe treatment for disabling parkinsonian or essential tremor. Vingerhoets G et al; J Neur N'surg Psych 1999;66:297-304: They studied cognitive consequences in 20 non-demented patients who received unilateral deep-brain stimulation (DBS) of the globus pallidus internus (GPi) for relief of motor symptoms. DBS is relatively safe, but older patients who needed high dosage of levodopa seemed more vulnerable to cognitive decline. Doder M et al; J Neur N'surg Psych 1999;66;380-385: Six weeks after a skull fracture, a 36-yr-old man developed parkinsonism unresponsive to levodopa. Neuroimaging showed traumatic infarction in the left caudate and lenticular nucleus. Parkinson Study Group; NEJM 1999;340:757-763: Drugs to control motor symptoms of PD often cause psychosis, and most antipsychotic drugs aggravate the motor symptoms. An exception, clozapine (Clozaril) does not affect motor symptoms but occasionally may cause potentially fatal agranulocytosis, if not detected early by weekly blood tests. A controlled trial in 60 psychotic PD patients at low dosage (about 1/10 of the usual dosage for schizophrenia) showed that clozapine, when accompanied by blood testing, is safe and effective against drug-induced psychosis without worsening parkinsonism. Cummings J; NEJM 1999;340:801-803: Editorial review of the clozapine article cited above. Gross R et al; J Neurosurg 1999;90:468=477: After using microelectrode guidance to select the best lesion site in 33 pallidotomy recipients, authors then used MRI to determine the locations relative to physical brain features, finding the distribution not random but highly correlated. Rezai A et al; J Neurosurg 1999;90:585-590: Functional magnetic resonance imaging (fMRI) during deep-brain stimulation (DBS) has much value for research, but possible risk due to induced current in the implanted wires. Authors did a number of such studies, with the simple precaution of prior inspection to ensure that insulation of the wires was intact. They report no resulting injury, and no ill effects of the stimulation current on image quality. Gregory R; Brain 1999;122:381-382: Editorial review of recent findings on unilateral pallidotomy for advanced Parkinson's disease: The most enduring effect is relief of dyskinesia, while off-state symptom benefits don't last. Gross R et al; Brain 1999;122:405-416: In 6- and 12-month followups of 33 microelectrode-guided globus internus (GPi) pallidotomy recipients, benefits were related to the lesion site. A more anterior position caused improvement in off-state rigidity and on-state dyskinesia, while more central location was better for akinesia and gait disturbance. CURRENT SCIENCE REVIEWS By Joe Bruman April 1999 Page 2 of 3 Samii A et al; Brain 1999;122:417-425: In a 2-year followup of 20 unilateral pallidotomy recipients, improvement in dyskinesa and tremor lasted, but that of other symptoms did not. Catalan M et al; Brain 1999;122:483-495: Positron-Emission Tomography (PET) imaging during repetitive finger motion tasks showed that in PD, cortical areas are recruited to compensate for loss of striatal function. Hanakawa T et al; Ann Neur 1999;45:329-336: Visual cues from transverse lines on the floor improved gait dysfunction of PD patients better than longitudinal lines. Single-Photon-Emission Computed Tomography (SPECT) during the tests revealed enhanced activity of the premotor cortex. [How did they do SPECT with the patient on a treadmill? JRB] Marder K et al; Neur 1999;52:719-724: Structured family history interviews of 146 non-demented PD patients, 120 demented ones, and 903 normal subjects showed that siblings of the demented patients were 3 times as likely to develop Alzheimer's disease, suggesting the possibility of a familial aggregation of AD and PD with dementia. Montgomery E et al; Neur 1999;52:757-762: A battery of tests including motor function, olfaction and mood, a highly specific and sensitive detector of presymptomatic PD, was given to 80 first-degree relatives of patients having more advanced PD impairment and 100 normal controls, and turned up a greater proportion of possible asymptomatic carriers among the relatives, particularly progeny whose fathers had PD. Zappia M et al; Neur 1999;52:763-767: Authors studied short- and long-duration response to levodopa in 17 PD patients, finding the latter diminished after a 1-yr interval, possibly indicating wearing-off as the source of motor symptom fluctuations. Ghabra M et al; Neur 1999;52:768-770: Testing to verify a prior finding failed to show that simultaneous repetitive transcranial magnetic stimulation (TMS) improved the fine movement speed of PD patients. Grondin R et al; Neur 1999;52:771-776: In dyskinetic MPTP monkeys, blockade of D1 receptors by various drugs improved levodopa-induced dyskinesia (LID) but worsened other PD symptoms. An exception was clozapine (Clozaril) at low dosage, which reduced LID without worsening the other symptoms. Ueda M et al; Neur 1999;52:777-781: Neuroleptic Malignant Syndrome (NMS) is a potentially fatal complication of antipsychotic therapy [or possibly, of abrupt withdrawal of dopaminergic therapy] which may result from dopamine receptor blockade. To evaluate susceptibility of elderly PD patients, authors measured various components of cerebrospinal fluid (CSF), concluding that levels of monoamine metabolites may provide a means to identify susceptible patients. CURRENT SCIENCE REVIEWS By Joe Bruman April 1999 Page 3 of 3 Weiner W et al; Neur 1999;52:873-874: Dopaminergic agents sometimes provide transient symptomatic improvement in Progressive Supranuclear Palsy (PSP), so authors tried pramipexole (Mirapex) on 6 PSP patients, without success. Turjanski N it al; Neur 1999;52:932-937: Restless Legs Syndrome (RLS) is a common disorder experienced by as much as 5% of the population. Positron Emission Tomography (PET) studies of striatal dopaminergic function in 13 RLS patients support the hypothesis of central dopaminergic dysfunction in RLS. Montplaisir J et al; Neur 1999;52:938-943: A controlled trial in 10 RLS patients of pramipexole (Mirapex), a new dopamine D3 agonist effective against PD, showed it to be the most potent therapeutic agent yet tested for RLS. Wetter T et al; Neur 1999;52:944-950: The long-acting D1 and D2 agonist pergolide (Permax) is already known to reduce RLS symptoms and subjectively to improve sleep quality. A formal crossover study in 30 patients confirmed that pergolide in low doses, combined with domperidone, is effective and well-tolerated treatment of sensorimotor symptoms and sleep disturbances in RLS. Tergau F et al; Neur 1999;52:1060-1063: They studied the effect of Transcranial Magnetic Stimulation (TMS) in 18 RLS patients and 17 controls, finding that the motor cortex is hyperexcitable in RLS, but suggesting that the origin of RLS is subcortical (supraspinal). Gemignani F et al; Neur 1999;52:1064-1096: Evaluating the frequency of RLS in 44 patients having Charcot- Marie-Tooth disease (a neuromuscular disorder) they found it in about 1/3 of those with CMT type 2, but nearly absent in other variants of CMT. They conclude that a disorder of sensory input plays a role in RLS. Chokroverty S, Jankovic J; Neur 1999;52:907-910 (editorial): Poor recognition, frequent misdiagnosis, and under-reporting have impeded studies of RLS. The agreed minimal diagnostic criteria are (1) intense, irresistible urge to move the legs, usually associated with peculiar sensation; (2) motor restlessness; (3) symptoms worse at rest and relieved by movement; and (4) symptoms worse in evening or at night. Movements during sleep are seen in about 80% of patients. Lancet, 6 March 1999:821 (news item): Confounding religious and moral objectors, Oregon's landmark Death With Dignity (doctor-assisted suicide) Act was invoked in only 15 of 30,000 total deaths, not the "hundreds of thousands" predicted, during its first year since becoming law. None of those expressed the objectors' predicted concern over becoming a financial burden, and only one cited fear of pain. The dire prediction of many more botched suicides also proved wrong, and contrary to the warnings of eugenic abuse, the subjects weren't poor, uneducated, or gender-biased. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013