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CURRENT SCIENCE REVIEWS By Joe Bruman November 1998 P. 1 of 3 Calabrese V et al; Mov Disord 1998;13:768-774: The novel soluble D2 agonist N-0923 given intravenous to 9 PD subjects was fast-acting, and fast-fading when stopped, suggesting use where oral medication is impractical. It was well tolerated in therapeutic amounts, although higher dosage caused nausea and vomiting. Skalabrin E et al; Mov Disord 1998;13:775-781: They studied response to levodopa challenge in 9 advanced PD cases, before and after unilateral posteroventral pallidotomy. Some but not all symptoms were helped. The main benefit was significant widening of the therapeutic levodopa window. Dewey R et al; Mov Disord 1998;13:782-787: In a double-blind controlled crossover study of 9 advanced PD patients, they tested apomorphine by nasal spray as a rescue from the "off" state. On average it worked within 11 minutes and lasted 50 minutes, but nasal irritation was "disabling" in 3 subjects and mild in 2 others. Ryoo H et al; Mov Disord 1998;13:788-797: There are several types of dopamine receptors, in different neural pathways and affected differently by agonists. Here, authors analyzed postmortem tissue from 9 PD patients and 8 non-PD controls. In the striatum of long-term PD patients, D3 receptors are decreased and D2 receptors are increased. Blanchet P et al; Mov Disord 1998;13:798-802: They tested the glutamate NMDA receptor channel blocker amantadine (Symmetrel) on four levodopa-primed parkinsonian monkeys. Combined with a relatively low dose of levodopa, it markedly suppressed dyskinesia but reduced the effect on other PD symptoms. More levodopa controlled those, while dyskinesia still was partly suppressed. This confirms that glutamate receptors are a factor in levodopa-induced dyskinesia. Louis E et al; Mov Disord 1998;13:803-808: Study of essential tremor is difficult, because those affected hardly ever seek treatment. Here they did a formal examination of 73 suspected cases, finding the kinetic component more severe than the postural component. During M et al; Nat Med 1998;4:1131-1135: The first successful gene therapy (in a non-PD animal model) to be administered by mouth, avoiding the usual difficulties. Limousin P et al; NEJM 1998;16:1105-1111: They followed 24 advanced PD recipients of subthalamic nucleus stimulator implants (STN DBS) for up to a year, finding general improvement in symptoms, and reduction by half of dopaminergic drug requirement. Janava J, Aminoff M; J Neur N'surg Psych 1998;65:436-445: Review of systemic dystonia (cramps) and chorea (dyskinesia), discussing specific neural pathways and etiologies. One hypothesis is selective circulation impairment (ischemia) in parts of the basal ganglia, another is greater vulnerability of the striatum due to its high oxygen metabolism. CURRENT SCIENCE REVIEWS By Joe Bruman November 1998 P. 2 of 3 Bennett K et al; J Neur N'surg Psych 1998;65:479-487: They tested kinematics of reach-to-grasp movement in 4 patients before and after pallidotomy, finding some effects beneficial, some not. Blackwood S et al; J Neur N'surg Psych 1998;65:531-546: They compared effects of vigorous exercise on cognitive and motor function in 10 patients with chronic fatigue syndrome, 10 with clinical depression, and 10 healthy controls. The CFS group had impaired attention and/or working memory capacity. Racette B, Perlmutter J; J Neur N'surg Psych 1998;65:577-579: The first case report, including MRI and DNA analysis, of a HD patient who also presented levodopa-responsive parkinsonism. Behrman A et al; J Neur N'surg Psych 1998;65:580-582: Testing speed and spatial gait variables in 8 PD patients and 8 controls, they found that the former could reduce impairment by means of attention to arm swing, stride length, tempo, etc. Bhatia K et al; J Neur N'surg Psych 1998;65:604-605: In a case report, long-standing attacks of paroxysmal dystonia induced by exercise were helped by posteroventral pallidotomy. Onofrj M et al; J Neur N'surg Psych 1998;65:605-606: Case reports of two elderly rural patients who had reached PD stage IV before diagnosis or treatment. After levodopa was begun their PD symptoms improved, but they quickly developed severe dyskinesia-dystonia and fluctuations. Lieberman A et al; Neur 1998;51:1057-1062: A 6-month controlled trial of ropinerole (Requip) as adjunct to L-dopa in advanced PD with fluctuations showed benefit due to reduced need for L-dopa. Ondo W et al; Neur 1998;51:1063-1069: They report results of motor function rating in 14 ET and 19 PD patients before and 3 months after thalamic DBS implantation, concluding that it is safe and effective against tremor from either source, but should be limited to patients whose tremor is disabling. Contin C et al; Neur 1998;51:1076-1089: Long-term followup, noting duration of response to standard levodopa challenge in 34 patients, showed it be useful in estimating progression rate of PD and cheaper than PET imaging. Observing the decay of plasma concentration, they found the half-life of a levodopa dose averaged 37 minutes in PD patients at H-Y stage 1, and 6.5 minutes at stage 3. The half-life declines faster in the initial stages of PD. Dewey R et al; Arch Neur 1998;55:1320-2323: Levodopa may be effective in generalized dystonia as well as in PD. Those patients perceived motor fluctuations as in PD, but objective tests failed to confirm it. CURRENT SCIENCE REVIEWS By Joe Bruman November 1998 P. 3 of 3 Hutchison W et al; Ann Neur 1998;44:622-628: In determining position of the subthalamic nucleus (STN) for implantation of DBS electrodes, they find microelectrode recording preferable to electrical stimulation. Findings in monkeys and 8 human subjects suggest that STN neuronal activity is elevated in PD. Friedberg G et al; Clin Neuropharm 1998;21:280-284: They applied their Parkinson Psychosis Rating Scale (PPRS) for assessing levodopa-induced psychosis in PD patients, to 29 psychotic subjects before and after a standardized treatment, finding it reliable, relevant, valid, and easily administered. Friedman J et al; Clin Neuropharm 1198;21:285-288: About 5-8% of PD patients on dopaminergic medication eventually develop psychosis. Clozapine (Clozaril) is effective and well- tolerated remedy, but hard to use because it requires weekly monitoring for agranulocytosis, a rare but dangerous side effect. Risperidone was tried as a substitute but is poorly tolerated. So they tested the new antipsychotic olanzapine on 12 patients, but 9 quit because it worsened their PD symptoms. Diederich N et al; Clin Neuropharm 1998;21:289-295: To study the relation between visual hallucinations and impaired discrimination of color and contrast, they tested 14 PD patients with visual hallucinations and 21 without, finding all subjects impaired but hallucinators more so. Colm H, Wilson J; Lancet, 27 June 1998:1995-1996: Three elderly patients with long-standing PD became confused when started on tolcapone (Tasmar) but returned to normal when it was stopped. Kuhn W et al; Lancet, 17 Oct 1998:1313-1314: They speculate that since COMT has a useful role in eliminating certain toxins, the COMT inhibitor tolcapone (Tasmar) might have a neurotoxic effect, despite its benefit of conserving levodopa. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013