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CURRENT SCIENCE REVIEWS By Joe Bruman October 1999 P. 1 of 4 Hely M et al; J Neur N'surg Psych 1999;67:300-307: A 10-year followup of trial comparing bromocriptine (Parlodel) against levodopa-carbidopa as opening therapy in 149 PD patients showed that neither the increased mortality risk of PD in general nor the rate of disease progression was affected by treatment. Poewe W; J Neur N'surg Psych 1999;67:280-281(editorial): Analytical comment on item above. Caparros-Lefebvre D et al; J Neur N'surg Psych 1999;67:308-314: Comparing effects of deep-brain stimulation (DBS) implants in the thalamus ventral intermediate nucleus (VIM) of two patient cohorts by surgical teams using slightly different site location protocols, they found tremor well suppressed in both groups, but levodopa-induced dyskinesia (LID) was also improved only when the DBS site was on average 2.9mm deeper, more posterior, and medial than the nominal VIM site. Durif F et al; J Neur N'surg Psych 1999;67:315-321: Six month followup of deep-brain stimulation (DBS) implants in the globus pallidus internus (GPi) of 6 advanced-PD patients showed the treatment to be safe and of lasting benefit but the precise location within the GPi makes a big difference. Aziz T, Bain P; J Neur N'surg Psych 1999;67:281(editorial): Comment on the two items above, and differences from results previously (CSR MAR 98) reported. Dujardin K et al; J Neur N'surg Psych 1999;67:323-328: A battery of executive function (cognition) tests on 41 first- degree relatives of familial-PD patients and 39 controls turned up impairment in 15 of the relatives, even though they had not yet been diagnosed (per motor symptoms) with PD. Gentil M et al; J Neur N'surg Psych 1999;67:329-333: Mechanical measurement of speech organ (lips and tongue) response in 10 PD patients having deep-brain stimulation (DBS) of the subthalamic nucleus (STN) implants, and 14 controls, showed that STN DBS improves the neural control involved in speech. Bateman D et al; J Neur N'surg Psych 1999;67:384-385: Some patients wake in the morning "off", while those with sleep benefit wake "on". Previous reports were inconclusive, so they studied 20 hospital inpatients and (by questionnaire) 150 outpatients, in various stages of PD. About half wake "on", with sleep benefit that persists without medication for an average of about 1-1/2 hours before reverting to "off". Walker Z et al; Lancet, 21 August 1999:646-647: Single-photon-emission computed tomography (SPECT) of a patient later found by necropsy to have had dementia with Lewy bodies (DLB) showed severe degeneration of the nigrostriatal dopamine pathway, like that in PD but not like the pattern of AD. Lancet, 21 August 1999:654(news item): DNA analysis in 160 subjects up to 8 years after receiving transplants of pig cells showed that the cells survived, but no evidence of the porcine endogenous retrovirus was found. CURRENT SCIENCE REVIEWS By Joe Bruman October 1999 P. 2 of 4 Science News, 4 September 1999:149(news item): Mice genetically altered to have more than usual receptor capacity for the glutamate neurotransmitter N-methyl-D-aspartate (NMDA) learn, adapt, and remember better than normal mice. (But glutamates are considered harmful to those neurons whose failure causes PD, so PD researchers are testing NMDA antagonists such as amantadine (Symmetrel) and riluzole (Rilutek) in PD patients). Grunblatt E et al; Mov Disord 1999;14:612-618: The mechanism of MPTP in causing parkinsonism involves generation of oxygen free-radical oxidative stress. R-apomorphine is a potent radical scavenger and iron chelator, and is found to be neuroprotective against damage by MPTP, in mice. Karp B et al; Mov Disord 1999;14:652-657: In open-label trial on 5 patients with severe (non-PD) dystonia, clozapine was effective and the side effects tolerable in most. Cummings J, Masterman D; Int J Ger Psych 1999;14:711-718: Review of depression in PD, with advice against tricyclics (e.g., Norpramin, Sinequan), and for SSRIs (e.g., Paxil, Prozac). Fails to mention possibly mistaking dopamine mood swings as depression. Moriyama E et al; Neur Med Chir 1999;39:350-356: Followup as long as 11 yr of 53 thalamotomy recipients confirms that improvements in tremor and rigidity are long-lasting, bbut that patients with akinesia are unpromising candidates. Menza M et al; Ann Clin Psych 1999;11:141-144: They successfully switched 3 PD patients with dopamine-related psychotic symptoms from clozapine (Clozaril) to quetiapine (Seroquel), better tolerated and no need for blood monitoring. Kumar R et al; Neur 1999;53:871-874: Inspired by striking benefit of bilateral pallidotomy against generalized dystonia, they tried deep-brain stimulation (DBS) of the internal globus pallidus (GPi) in one such patient, with equally good results. By positron-emission tomography (PET) scanning, they also were able to study the underlying mechanism. Tedroff J et al; Ann Neur 1999;46:359-365: Using positron-emission tomography (PET), they confirmed that in early-stage PD, the brain attempts to compensate for dopaminergic loss in one area by increase in another. Markopoulou K et al; Ann Neur 1999;46:374-381: Members of a certain familial PD cluster have reduced expression of one mutant gene for alpha-synuclein. Kordower J et al; Ann Neur 1999;46:419-424: One aspect of the current trials of Glial-Cell-Line-Derived Neurotrophic Factor (GDNF) is its delivery to the desired site within the brain. Death from unrelated causes of one PD patient who received monthly injections into the right lateral ventricle permitted a detailed postmortem study. His PD symptoms had not improved, and there was no evidence either of neuroregeneration or of GDNF diffusing into relevant brain structures, so they need to find a better delivery scheme. CURRENT SCIENCE REVIEWS By Joe Bruman October 1999 P. 3 of 4 Rakshi J et al; Brain 1999;122:1637-1650: By Positron-Emission Tomography (PET) they compared regional dopaminergic function in patients with early and advanced PD, and normal controls. Boeker H et al; Brain 1999;122:1651-1665: They used positron-emission tomography (PET) to compare the regional anatomy of sensory processing in groups of Huntington's patients, PD patients, and healthy controls. Basal ganglia sensory dysfunction was found to be important in both diseases. Bronstein J et al; Arch Neur 1999;56:1064-1069: Report of an international workshop on pallidotomy for PD, with consensus recommendations on various issues for providers. Weiner W; Mov Disord 1999;14:716-724: Suspecting that levodopa is toxic or harmful, some therapists prefer to postpone its use in early PD, but there is little supporting evidence for that choice. Montastruc J et al; Mov Disord 1999;14:725-730: New dopamine agonists are as effective as levodopa in early PD, and offer the possibility of delaying levodopa-induced motor side effects later on, if treatment begins with only an agonist. Henry B et al; Mov Disord 1999;14:744-753: In monkeys with MPTP-induced parkinsonism, the adrenergic receptor agonist idazoxan alone was of no benefit, but it enhanced benefits of levodopa and reduced dyskinesia. Burkhard P et al; Mov Disord 1999;14:754-763: They describe a novel measuring system that permits dyskinesia in PD to be quantified. Barbanti P et al; Mov Disord 1999;14:764-771: Dopamine receptors like those in the brain are found on peripheral blood lymphocytes (PBL). In a comparative assay of subjects with PD and several other neurodegenerative diseases, only those with PD had increased expression of the receptors on PBL. de Boer A et al; Mov Disord 1999;14:772-779: They studied 225 PD patients to learn how well their use of health care services can be predicted by various factors. Junque C et al; Mov Disord 1999;14:780-789: They studied cognitive and behavioral effects of pallidotomy in 15 recipients. Several functions are worse immediately following surgery, but most return to normal within 3 months. Fernandez H, Friedman J; Mov Disord 1999;14:836-838: They observed 3 PD patients in a sort of compulsive behavior that consists of repeated handling or manipulation of selected small objects. They call this "punding" and think it is related to dopaminergic drug therapy. CURRENT SCIENCE REVIEWS By Joe Bruman October 1999 P. 4 of 4 Koller W et al; Mov Disord 1999;14:847-850: Having established previously that deep-brain stimulation (DBS) of the thalamus ventral intermediate nucleus (VIM) alleviates essential hand tremor, they found it also beneficial in 38 patients with disabling essential head tremor. Shetty N et al; Clin Neuropharm 1999;22:207-212: It's common for subjects in a drug trial who receive only placebo but aren’t told, to report some benefit anyhow. To measure this effect, authors searched literature from various controlled studies of PD drugs, attempting to correlate "positive" response among the placebo subjects with various aspects of personal status such as age, race, gender, education, etc., but didn't find any. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013