CURRENT SCIENCE REVIEWS By Joe Bruman July 1998 Page 1 of 3 Verhagen Metman L et al; Neur 1998;50:1323-1326: N-methyl-D-aspartate (NMDA) is one of several glutamates, enzymes normally present in the brain but toxic to neurons. Amantadine (Symmetrel) inhibits NMDA, and also is known to reduce levodopa-induced dyskinesia (LID). A double-blind controlled trial, on 18 patients with late-stage PD, confirmed that the reduction was accomplished without losing any of the symptomatic benefits of levodopa. This result also suggests that LID is somehow related to NMDA. Factor S et al; Neur 1998;50:1456-1458: Still mysterious: Amantadine (Symmetrel), developed decades ago as an antiviral agent and introduced in 1968 as PD therapy, is beneficial against PD symptoms at all stages. Recently it was found to protect against neurodegeneration, and also to prolong the life-span of PWP. But in 3 elderly patients, its withdrawal after long-term (4 to 18 years) use caused acute delirium and other psychoses, that were relieved only by resuming its use. As with many other drugs, it's unknown precisely how or why Amantadine acts against PD. Goetz C; Neur 1998;50:1211-1212 (editorial): Summary of present knowledge about Amantadine, and comment on the articles cited above. Laments the trend of research focus on new drugs, instead of refining knowledge about old ones. Growdon J et al; Neur 1998;50:1327-1331: Of 800 PD subjects of the DATATOP study, 387 reached the point where they required levodopa to cope with symptoms. They were given a battery of cognitive tests then, and after 6 months of levodopa therapy. Results showed that levodopa doesn't affect cognition, and is unrelated to hallucinations, delusions, or depression that may appear in the later stages of PD. Hogl B et al; Neur 1998;50:1332-1339: Some PD patients feel better and have fewer motor symptoms on waking in the morning, despite the prolonged deprivation of levodopa, while others do not. To study this, they gave motor tests to 10 patients with sleep benefit and 10 without. The former group, as expected, did better on the morning motor tests but was more susceptible to "off" spells between levodopa doses. Matsumine H et al; Neur 1998;50:1340-1345: In the rare Early-onset Parkinsonism with Diurnal Fluctuation (EPDF), symptoms improve after sleep. EPDF also differs from the usual PD in its lack of Lewy bodies. Hoping to find a genetic site for PD, they studied 53 cases in 17 EPDF family clusters, and found the gene site for EPDF to be the same as that for autosomal-recessive juvenile parkinsonism (ARJP), suggesting that the two disorders are closely related. Gorell J et al; Neur 1989;50:1346-1350: In a questionnaire study of 144 Detroit PD patients and 464 controls, they found PD associated with farming, herbicides, and insecticides. The risk of farming exceeded that of the combined pesticide exposure alone, indicating an additional factor at work. CURRENT SCIENCE REVIEWS By Joe Bruman July 1998 Page 2 of 3 Louis E et al; Neur 1998;50:1351-1357: Although essential tremor (ET) is the most common adult movement disorder, the importance of genetic factors is unknown. To refine incidence study methods, they compared a screening interview with a neurological examination, in a large sample of Manhattan residents. Interviews alone missed a significant number of mild ET cases that were discovered by examination. Checkoway H et al; Neur 1998;50:1458-1461: Monoamine oxidase B (MAO-B) is an ubiquitous enzyme that both destroys dopamine and activates MPTP, the drug that causes PD-like symptoms. Smokers are less likely to have PD (or PWP are less likely to be smokers), but only if they share one of two alternative forms of the gene that encodes MAO-B. In subjects having the other form, the effect is just opposite, and PD risk for smokers is higher. The gene polymorphism is distributed about 50-50 in the white population, and its peculiar relation to MAO-B and the risks of smoking begs for explanation. Logroscino G et al; Mov Disord 1998;13S1:13-16: PD is linked to elevated iron in the substantia nigra but not, in their survey, to dietary iron intake. But diet high in animal fat, combined with certain defects in iron metabolism, does impute higher risk of PD. Jenner P; Mov Disord 1998:13S1:24-34: Survey of possible mechanisms of oxidative stress in PD. Hirsch E, Faucheux B; Mov Disord 1998;13S1:39-45: Possible relation of iron metabolism to oxidative stress and PD. Shoulson I; Mov Disord 1998;13S1:46-48: Current state of knowledge about neuroprotection in PD. Lapchak P; Mov Disord 1998;13S1:49-54: Development of Glial cell line-Derived Neurotrophic Factor (GDNF) for treatment of PD. Kang U; Mov Disord 1998;13S1:59-72: Potential of gene-transfer therapy for PD. Kumar R et al; Mov Disord 1998;13S1:73-82: Compares long-term results of 40 pallidotomies and 8 DBS implants. After pallidotomy, levodopa-resistant "on" period symptoms didn't improve, and some "off" improvements faded in a year or two. Conclusions about DBS are conjectural. Lindvall O; Mov Disord 1998;13S1:83-87: Up to 6 yr after fetal transplant in 13 with idiopathic PD and 3 with MPTP-induced PD, most of those whose grafts survived had "therapeutic" (less medication needed?) benefit but "incomplete" symptomatic relief. Trosch R et al; Mov Disord 1998;13:377-382: Reviewed records of 172 PD patients treated with clozapine show it as generally tolerable and effective against several kinds of late-stage symptoms. CURRENT SCIENCE REVIEWS By Joe Bruman July 1998 Page 3 of 3 Kordower J et al; Mov Disord 1998;13:383-393: Postmortem study of a fetal graft recipient who died of unrelated causes revealed that the observed clinical benefits were accompanied by survival of the graft. Potagas C et al; Mov Disord 1998;13:394-399: PD patients could discriminate between odors, but had trouble identifying them, compared to normal control subjects. Verhagen Metman L et al; Mov Disord 1998;13:414-417: In open-label trial followed by controlled double-blind trial, the NMDA (glutamate) antagonist dextromethorphan was helpful against motor response complications of PD. Marti-Masso J, Poza J; Mov Disord 1998;13:453-456: Parkinsonism induced by the (in Europe) prescription drug cinnarizine may persist a year or more after withdrawal. Pahwa R et al; Mov Disord 1998;13:465-467: Of 20 essential tremor patients in a double-blind trial of gabapentin, only one had marked improvement. Merello M et al; Mov Disord 1998;13:533-535: During pallidotomy surgery on 6 consecutive PD patients, they injected apomorphine to see if the lesion just made would prevent drug-induced dyskinesia, as a test of success. O'Sullivan J, Hughes A; Mov Disord 1998;13:536-539: Apomorphine restored penile erection in 5 PD patients, and authors think the mechanism is similar to that of other dopamine agonists and of levodopa. Speelman J, Bosch D; Mov Disord 1998;13:582-588: Historical review of pallidotomy and deep-brain stimulation implant surgery. Piercey M; Clin Neuropharm 1998;21:141-151: The D3 agonist pramipexole (Mirapex) alone may control PD symptoms for several years following diagnosis, and now is seen as a useful adjuvant to levodopa in later stages of the disease. van Laar T et al; Clin Neuropharm 1998;21:152-158: Apomorphine is effective against PD symptoms but in excess will cause dyskinesia, and dosage must be adjusted because response varies widely between patients. Authors tested 8 patients by stepwise increase at regular intervals and found the mean plasma concentration for symptom control was 2.7 ng/ml, and for onset of dyskinesia it was 8.5 ng/ml. They recommend the calibration protocol to determine optimum dosage for each patient. Schrag A et al; Clin Neuropharm 1998;21:164-175: In beginning tests of the agonist ropinirole involving 1364 patients, its safety profile was similar to other agonists. Long-term safety and efficacy remain to be determined. Muenter M et al; Ann Neur 1998;43:768-781: Detailed study of 13 cluster members having an autosomal- dominant form of parkinsonism-dementia showed several significant differences from classic (idiopathic) PD. J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013