CURRENT SCIENCE REVIEWS By Joe Bruman February 1999 P.1 of 4 Schierle G et al; Nat Med 1999;5:97-100: Apoptosis, or programmed cell death, is the natural process by which an organism gets rid of weak or superfluous cells, but sometimes it is unwelcome. Authors' rat studies indicated that only 5%-10% of grafted embryonic cells survive longer than one week, and that most of the loss is by apoptosis. Certain modified peptides known as "caspase inhibitors" have been found in other paradigms to block apoptosis, so they tried one, Ac-YVAD-cmk (don't ask), on rat fetal cells in vitro, and then on cells transplanted stereotactically in the substantia nigra of live rats that had chemically-induced parkinsonism. They found that the pretreatment significantly improved survival in vitro, and that it mediated substantial functional recovery in the parkinsonian rats, corroborated by examination of the brains after the subjects were sacrificed. Ekblom J et al; Pharmacol Toxicol; 1998:83:194-199: Experimenting with cultured rat brain cells subjected to ischemic insult, they found that pre-treatment with deprenyl or tolcapone may reduce the resulting stroke damage. diPierro C et al; J Neurosurg 1999;90:95-100: They report 62 stereotactic pallidotomies or thalamotomies guided by MRI imagery of the anterior commissure-posterior commissure line, claiming results just as good as those guided by microelectrode recording. Shaunak S et al; J Neur N'surg Psych 1999;66:79-81: Serosal (membrane) fibrosis is an occasional adverse effect of other dopamine agonists, but rarely reported from pergolide (Permax). They report 3 PD patients on Permax for average 2 years, at dosage from 1mg/day to 3mg/day, who respectively developed potentially life-threatening retroperitoneal, pleural, and pericardial fibrosis, that in all cases required surgical intervention. They advise regular monitoring of Permax users. Groth C; Lancet, 1998 Review:26: Although no such infection has been found in about 60 human recipients of various pig cell transplants, at least one porcine endogenous retrovirus (PERV) can infect cultured human cells in vitro, prompting government authorities in the U.S. and UK to set up various precautionary controls of such transplants. De Palma G et al; Lancet, 19 December 1998:1986-1987: In 100 PD patients and 200 controls, they studied genes related to free radicals and oxidative stress, and history of exposure to environmental hazards, finding positive correlation in PD of mutations with such factors as rural living and well water. Lancet, 19 December 1998:1992 (news item): Good news: Chocolate may be addictive. Bad news: Its content of cannabinoid (marijuana-like) substance is way too small to be a significant cause. CURRENT SCIENCE REVIEWS By Joe Bruman February 1999 P. 2 of 4 Altschuler E, Bonelli R et al; Lancet, 16 January 1999:240-241: Discussing functional improvement by certain drugs in a patient with Huntington's Disease, they speculate that lesion of the globus pallidus as in pallidotomy for PD might also provide such improvement. They note however that the principal benefit of pallidotomy for PD, namely reduction of L-dopa-induced dyskinesia (LID), is unexplained by the current model of basal ganglia organization. Gorell J et al; Neur 1999;52:115-119: There has always been suspicion that the negative correlation of smoking and PD may be due merely to aversion to smoking in persons susceptible to PD. Authors put that to rest by study comparing heavy smokers and light smokers and the time elapsed after quitting, if applicable. They found a distinct dose-related effect, showing that smoking is indeed neuroprotective. Ekesbo A et al; Neur 1999;52:120-125: It is well-known that levodopa therapy, effective in early stages of PD, seems to lose that effectiveness in more advanced stages. By means of PET imagery and standardized levodopa and apomorphine protocol, authors mapped the effects of apomorphine on regional levodopa uptake in early-stage and advanced-stage PD patients (the strong dopaminergic effect of apomorphine normally inhibits levodopa uptake). They found this inhibition in early-stage PD but not in advanced stages. The explanation is that a function which regulates dopamine activity is lost as the nigrostriatal degeneration of PD progresses. Averbuch-Heller L et al; Neur 1999;52:185-188: Square-wave jerks (SWJ) are brief saccades that divert the eye from its target and return it after about 200 msec, thereby interfering with activity such as reading. They studied three advanced-stage PD patients who had received pallidotomies, and found the frequency of SWJs substantially above normal. Gottlieb S; BMJ, 12 December 1998:1616: Postmortem study of 43 various brains from Alzheimer's, PD, schizophrenic, and normal subjects showed signs of oxidative stress in Alzheimer's subjects but not in the others. Miles J; BMJ, 12 December 1998:1658-1659: Citing a defect rate in one (un-named) maker's implantable neurostimulators of over 50%, he strongly advocates national registry in the U.S. and UK. Wang W et al; Arch Neur 1998;55:1521-1523: In 44 familial PD patients and 29 with sporadic PD, not of Greek or Italian ancestry, search for the mutant alpha-synuclein gene (CSR DEC 96) drew a blank. At least 5 searches of various other population samples (CSRs JUL 97, MAR 98, MAY 98, JAN 99) were likewise unsuccessful. Louis E et al; Arch Neur 1998;55:1553-1559: They examined 54 subjects diagnosed with essential tremor (ET), finding mild assymetry to be a fundamental property of ET, with tremor less severe in the dominant arm. CURRENT SCIENCE REVIEWS By Joe Bruman February 1999 P. 3 of 4 Blanchet P et al; Clin Neuropharm 1998;21:339-343: A double-blind controlled trial in 4 PD patients of the D-1 agonist Dihydrexidine, given iv at various dosage, showed a plasma half-life less than 5 minutes and marginal value. Deuschl G et al; Mov Disord 1998;13S3:2-23: (see CSR DEC 98 P.3) Proposes tremor classifications: rest, postural, simple kinetic, and intention (during target-directed movement). Rothwell J; Mov Disord 1998;13S3:24-28: Possible oscillating circuits in the CNS that could cause tremor. Bergman H et al; Mov Disord 1998;13S3:29-34: Rhesus monkeys given MPTP develop only infrequent short episodes of high-frequency tremor, whereas vervet monkeys have many prolonged episodes of low-frequency tremor. Elble R; Mov Disord 1998;13S3:35-39: Various animal models of action tremor are needed to define the apparently universal involvement of the cerebellum and ventral intermediate nucleus of the thalamus in human tremor disorders. Hua S et al; Mov Disord 1998;13S3:40-42: Role of the thalamus and basal ganglia in parkinsonian tremor. Hallet M; Mov Disord 1998;13S3:43-48: The normal 8-12 Hz central oscillator may contribute to physiologic tremor. Essential tremor is easily influenced by sensory input, while the rest tremor of PD is less affected by sensory input but more so by transcranial magnetic stimuli. Vidailhet M et al; Mov Disord 1998;13S3:49-54: Symptomatic tremors most often arise from lesion in the cerebello-thalamo-cortical or the dentato-rubro-olivary pathway. The role of the basal ganglia is poorly understood. Brin M, Koller W; Mov Disord 1998;13S3:55-63: Essential tremor is one of the most common movement disorders, but the epidemiology, genetics, and pathogenesis are unknown. Boecker H, Brooks D; Mov Disord 1998;13S3:64-72: Review of functional imaging by MRI and PET, and the insights into the pathology of tremor that are provided. Volkmann J; Mov Disord 1998;13S3:73-76: Review of magnetoencephalography in study of human tremors. Bain P; Mov Disord 1998;13S3:77-80: Clinical methods of tremor measurement. Spicker S et al; Mov Disord 1998;13S3:81-84: Long-term ambulatory electromyography can distinguish essential tremor from that of PD. Pullman S; Mov Disord 1998;13S3:85-89: A new digitizing tablet records features of a hand-drawn spiral in 3 dimensions. It is safe, fast, portable, and cheap to use. CURRENT SCIENCE REVIEWS By Joe Bruman February 1999 P. 4 of 4 Wasielewski P et al; Mov Disord 1998;13S3:90-100: Beta-adrenergic blockers [e.g., propranolol] and primidone (Mysoline) remain the mainstays of drug treatment for ET, while carbidopa/levodopa [Sinemet] and anticholinergics are best for the tremor of PD. Pogarell O, Oertel W; Mov Disord 1998;13S3:101-102: Literature review indicates no special improvement in PD tremor from fetal tissue transplant. However, PD patients whose tremor is the main symptom normally are not selected for transplant, so the effect of fetal transplant upon PD rest tremor is unknown. Speelman J et al; Mov Disord 1998;13S3:1903-106: Review of thalamotomy for tremor. Chronic thalamic stimulation seems promising, but cost-effectiveness remains to be proven. Lozano A et al; Mov Disord 1998;13S3:107-110: Microelectrode-guided pallidotomy produces striking improvement in off-period contralateral tremor of PD. The benefit has persisted 2 years or more, despite reduction of medication dose and progression of the disease. Rodriguez M et al; Mov Disord 1998;13S3:111-118: Following evidence that the subthalamic nucleus in MPTP monkeys was a source of tremor, they implanted stimulators in that region of 12 PD patients and ablated it in 7 others. In all cases, tremor was significantly improved or wholly suppresed. Benabid A et al; Mov Disord 1998;13S3:119-125: Reviews 8 years' experience with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim), successful in a variety of patients and configurations. PD tremor was suppressed for up to 11 years, but ET benefit declined with time in about a third of recipients. Other dyskinesias were much less influenced. More recently, DBS of the subthalamic nucleus (STN) has had spectacular success on akinesia and rigidity. DBS of the globus pallidus (GPi) has effects similar to pallidotomy, in suppressing dyskinesia. Tanner C et al; JAMA, 27 Jan 1999:341-346: In the first big test of the heredity factor in PD, they used VA records to find and screen 19842 male twins, finding 268 with parkinsonism. Concordance data show some genetic influence when disease appears before age 50, but none in cases of later onset. Cummings J; JAMA, 27 Jan 1999:376-378: Possibly inspired by recent publicity about celebrities with PD, a pretty good tutorial on recent developments in the knowledge and treatment of PD. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013