 |
 |
CURRENT SCIENCE REVIEWS By Joe Bruman December 1998 P. 1 of 3 Menegon A et al; Lancet, 24 Oct 1998:1344-1346: In a study of 95 PD patients and 95 healthy controls, they found PD strongly associated with the combination of factors implying pesticide exposure and the genetic mutation of glutathione S-transferase, an enzyme that normally destroys such neurotoxins. This is the first plausible linkage of environment and heredity as an origin of PD, explaining why some people are more susceptible than others to the parkinsonism-inducing effects of pesticides. Golbe L; Lancet, 24 Oct 1998:1328-1329: Besides commenting on the breakthrough discovery cited above, he discusses the recent finding that a genetic mutation of alpha- synuclein with a modified molecular "folding" pattern may explain the clumping and formation of Lewy bodies in various neurodegenerative diseases. Collignon P et al; Lancet, 24 Oct 1998:1390-1391: Debate over safety of pig cell transplants continues. Critics are worried that some as yet undiscovered retrovirus may gain a foothold in the human species, with disastrous results. Calmer voices reply that careful search so far has found no such interspecies infection, but concede that with the potential for tens of thousands of transplants per year [for many conditions besides PD], extreme caution is advisable. Lancet, 7 Nov 1998:1529 (news item): Comment on the neurogeneration discovery cited below. Lancet, 7 Nov 1998:1529 (news item): Comment on the alpha-synuclein report cited below. In a certain familial variant of PD, the alpha-synuclein is a mutant form which tends to clump into fibrils, which may have a role in PD. BMJ, 7 Nov 1998:1272 (editorial): More comment on the neurogeneration discovery cited below. BMJ, 7 Nov 1998;1290 (editorial): When the epidemic of bovine spongiform encephalitis (BSE) began in England about 10 years ago, it leaped the species barrier to cause a variant of Creutzfeldt-Jakob disease (CJD), with initial symptoms easily mistaken for PD, in a few humans. CJD is quite rare, but like BSE, almost invariably fatal, and the British government didn't handle the episode very well. Lancet, 7 Nov 1998:1529: Brownell A et al; Nat Med 1998;4:1308-1312: They gradually induced selective loss by oxidative stress of nigrostriatal dopamine neurons in 5 macaque monkeys, through repeated injection of the mitochondrial complex 1 inhibitor MPTP during a period of 9 to 19 months. Then by a combination of positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) imaging, they studied the progression and persistence of regional changes in distribution of functional brain neurochemicals, to better understand the mechanisms of PD. CURRENT SCIENCE REVIEWS By Joe Bruman December 1998 P. 2 of 3 Eriksson P et al; Nat Med 1998;4:1313-1317: Conventional wisdom, that adult mammal brain tissue cannot regenerate, has been crumbling for the past few years (see, for example, CSR JUN 98) as more highly developed species have been found to do so. Here, authors demonstrate for the first time, neurogenesis in the adult human brain. Conway K et al; Nat Med 1998;4:1318-1320: No one is sure if Lewy bodies are a cause, or effect, of PD, but they do contain alpha-synuclein, and two mutant genes for alpha- synuclein have been linked to an early-onset (familial) variant of PD. So the authors studied folding and aggregation of the mutant varieties in vitro, finding that they do indeed tend to form fibrils and to clump into Lewy-body-like spheres. Ghika J et al; J Neurosurg 1998;89:713-718: Six advanced PD patients with intractable fluctuations received bilateral contemporaneous pallidal deep-brain-stimulation (DBS) implants, and were followed for up to two years. Major improvements in most motor and ADL scores persisted for about a year, then began to diminish. Pietz K et al; J Neur N'surg Psych 1998;65:709-716: As an alternative to levodopa, they gave either injection or continuous infusion of apomorphine to a total of 49 PD patients in the fluctuating stage, over a period of up to 5 years. Both groups had significant and persistent improvement of symptoms, although psychiatric side effects and local inflammation of the infusion site were common. Graham J et al; J Neur N'surg Psych 1998;65:774-777: In a trial on five PD patients having hallucinations due to dopaminergic medications, they found that olanzapine controlled the hallucinations but unacceptably worsened motor disability in two of the five subjects. Chan D et al; J Neur N'surg Psych 1998;65:781-784: They surveyed 215 PD patients and 313 controls from a Chinese population in Hong Kong, both for environmental factors and for mutants of the CYP2D6 gene, which may impair resistance to neurotoxins and are common in caucasians. They found several environmental factors, for example that regular tea drinking is protective, but the CYP2D6 mutations are so rare in Chinese people that they are unlikely to be a genetic factor in PD for that population. Rinne U et al; Neur 1998;51:1309-1314: They did a 6-month controlled study of the COMT inhibitor entacapone (Comtan) in 171 PD patients at the fluctuation stage, finding prolonged benefit. Entacapone acts to conserve levodopa outside the brain, thereby allowing a greater fraction of a given therapeutic dose to reach the brain. Valldeoriola F et al; Neur 1998;51:1315-1320: The startle reflex, an involuntary twitch in response to a sudden noise, was timed in a cohort containing groups with idiopathic PD, progressive supranuclear palsy, multisystem atrophy, and normal controls. It is enhanced in PD and MSA but not in PSP. CURRENT SCIENCE REVIEWS By Joe Bruman December 1998 P. 3 of 3 Kunig G et al; Ann Neur 1998;44:758-762: The used positron-emission tomography (PET) imaging to map the activity of dopamine in 14 patients with dopa-responsive dystonia (DRD), 16 levodopa-treated PD patients, and 26 healthy controls. DRD includes some symptoms of PD, but is hereditary, and onset often occurs in the first decade of life. Differences in uptake distribution may help to understand both diseases. Hammerstad J; Ann Neur 1998;44:843-844 (book review): For $125, those interested may obtain a 286-page, hard-cover summary of surgical treatment of PD, from a 1997 symposium. Brotchie J; Mov Disord 1998;13:871-876: Proposes several drugs that might help levodopa-induced dyskinesia by manipulating non-dopaminergic systems. Schrag A et al; Mov Disord 1998;13:885-894: A long-term study of 10 juvenile (onset age < 21) and 139 young- onset (21 < onset age < 40) PD patients. Half the juvenile group had close relatives with PD. Mortality rate in both groups was higher than in the normal population. Tandberg E et al; Mov Disord 1998;13:895-899: They surveyed 245 PD patients and two 100-member control groups, and found that nearly 2/3 of the PD group reported sleep disorders. Sleep disorders strongly correlated with depression. O'Sullivan J et al; Mov Disord 1998;13:900-906: Careful clinical measurement of gait parameters is a reliable alternative to conventional PD rating scales for assessing the response to levodopa. Krack P et al; Mov Disord 1998;13:907-914: Electrical stimulation of the subthalamic nucleus in 27 consecutive PD patients was effective against even severe high- amplitude tremor, and offers an interesting alternative to thalamotomy or pallidotomy. Mov Disord 1998;13:Supp 3:1-125: Reviews of various aspects of tremor, presented at a workshop session of the 5th International Congress of Parkinson's Disease and Movement Disorders, October 1998. Science News, 28 Nov 1998:344 (news item): Surgeons exploring a 65-year-old PD patient's brain with a DBS electrode stimulated the substantia nigra and were startled when she became severely depressed, returning to normal when the stimulus was turned off. They repeated the stimulus to confirm that it indeed caused instant and reversible depression. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013