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CURRENT SCIENCE REVIEWS By Joe Bruman August 1997 p. 1 of 4 Polymeropoulos M et al; Science, 27 Jun 97:2045: Announcing the identification of a mutant gene that encodes alpha-synuclein, in members of several family clusters of PD cases. It created a wave of optimistic comment as a major step in the path to understanding and possibly cure for PD. Science News; 28 Jun 97:396 (news item): By diligent analysis of genetic makeup in several large families having multiple members with PD, workers found a mutant gene associated with at least that variant of the disease. The gene* encodes the protein alpha-synuclein, thought to be one of 50 or so neurotransmitters in the brain, whose function is still unknown. *Not entirely clear whether they mean normal or mutant. The latest flyer from NPF seems to imply that the normal gene encodes just plain synuclein, while the mutant encodes alpha-synuclein. Exactly why the latter may trigger PD and its normal relative doesn't should be interesting, since nobody knows much about either one. Kordower J et al; Exp Neur 1997;144:41-46: Fifteen years of experience with tissue transplants for PD allow comparison of adrenal medulla and fetal mesencephalon as sources, mainly by means of postmortem study. Adrenal cells survive poorly, although they do induce sprouting of host neurons. Fetal cells, however, thrive and produce major restoration of striatal tissue lost in PD. Mytilineou C et al; J Neurochem 1997;68:33-39: Lab study of cultured fetal cells showed that selegiline (Deprenyl) prevents cell death independently of its MAO-B inhibition; notably death otherwise due to NMDA, a normally present glutamate known to be neurotoxic. Mytilineou C et al; J Neurochem 1997;68:434-436: Following the work above, they tested desmethylselegiline (DMS), a metabolite of selegiline found in the gastrointestinal tract, showing that it protects neurons against NMDA even better than selegiline. Therefore they think DMS is the active agent in neuroprotection by selegiline. Kimber J et al; Lancet, 28 Jun 97:1877-1881: As a side effect, the antihypertensive clonidine causes increase of growth hormone in healthy persons and PD patients, but not in those with MSA, often confused with PD. Thus a clonidine test may be a useful diagnostic tool. Lavoisy J, Marsac J; Lancet, 5 Jul 97:74: They dispute the value of zolpidem in PD (CSR Jun 97) for a rather weak reason: a soporific, it may increase risk to PWP of falling. Kopyov O et al; J Neurosurg 1997;87:52-59: Reports success of 29 microelectrode-guided pallidotomies done by the Good Samaritan Hospital (L.A.) team over the course of a year. Parkinson Study Group; JAMA, 9 Jul 97:125-130: In a 1994 randomized dose-ranging study of 264 early-PD patients not on levodopa or on other DA agonists, Pramipexole was found to be safe and effective monotherapy. CURRENT SCIENCE REVIEWS by Joe Bruman August 1997 p 2 of 4 Jost W et al; Mov Disord 1997;12:423-425: Cisapride (Propulsid) usually given for gastric reflux, works by stimulating gut muscles, so they tried it for constipation in PD. At first it reduced colon transit time from 5 days to 3, but after a year the benefit had virtually disappeared. Lipinski J et al; Mov Disord 1997:12:402-407: They tried the dopamine agonist pergolide (Permax) on 19 young people with Gilles de Tourette syndrome, finding marked benefit, especially in those also having restless leg syndrome. Hubble J et al; Mov Disord 1997;12:337-341: Study of deep-brain stimulation in 10 patients with PD and 19 with essential tremor showed about equal reduction of tremor and of self-rated disability, with best results against postural tremor. Johnston B et al; Mov Disord 1997;12:322-327: They compared swallowing impairment in 7 PD patients and 7 with PSP, finding it about equal, except in the oral phase where it was more severe in the PSP patients. Abbruzzese G et al; Mov Disord 1997;12:315-321: They compared the response to transcranial magnetic stimulation of sensory and motor evoked potential, in 15 patients with multiple system atrophy, 20 PD patients, and 20 healthy controls, finding no differences of diagnostic value. Muller V et al; Mov Disord 1997;12:306-314: They gave behavioral treatment of postural and gait problems to l5 PD patients and nonspecific psychological treatment to 14 others, finding the behavioral treatment measurably helpful. Giladi N et al; Mov Disord 1997;12:302-305: They found the "freezing" phenomenon in 158 out of 347 patients with parkinsonism other than idiopathic PD. It was most common in those with neurodegenerative diseases and absent in drug-induced parkinsonism. It was significantly associated with dementia, incontinence, and tachyphemia*. Andreu N et al; Mov Disord 1997;12:293-296: A dose-ranging study in 4 groups of 6 PD patients established that 20 mg/week of selegiline is the minimum needed to induce maximal (>95%) and lasting inhibition of platelet MAO-B. Nutt J et al; Mov Disord 1997;12:285-292: Motor fluctuations, evaluated by tapping tests in 11 PD patients, continued even though they were on constant-rate levodopa infusion, with no ready explanation. Gomez Arwvalo G et al; Mov Disord 1997;12:277-284: Retrospective analysis and acute levodopa challenge in 34 early- onset PD patients and 34 late-onset revealed differences in mode of onset and degree of initial improvement, and a stronger, shorter response to the levodopa challenge by the early-onset group. *Gotcha! "Tachyphemia" = pathologically rapid speech CURRENT SCIENCE REVIEWS by Joe Bruman August 1997 p 3 of 4 Wenning G et al; Ann Neur 1997;42:95-107: They tracked 6 PD recipients of fetal tissue grafts for between 10 and 72 months. PET scans at 8 to 12 months revealed increased dopaminergic activity in the putamen but not a secondary site, the caudate. Four of the six showed significant clinical improvement, the other 2 only modest. One was able to drop levodopa at 32 months and still showed normal activity in the putamen at 72 months. Samuel M et al; Brain 1997;120:963-976: A PET study of PD patients and controls during assigned one-hand and two-hand movement tasks showed that in PD there is a compen- satory switch from striato-mesial frontal premotor circuits to parietal-lateral circuits during complex finger movement. Rickards C, Cody F; Brain 1997;120:997-990: Electromyography during standardized arm movement tasks in 29 PD patients and 23 controls showed that proprioceptive (internal origin) guidance of movement is impaired in PD. Science News, 19 Jul 97:36 (news item): Johns Hopkins researchers report survival in vitro of human stem cells, the embryonic cells which have the ability to diversify into any of the numerous types of cells, including neurons, in the final developed organism. Discovery of how to cultivate the cells, which now are obtained from fetuses, would offer hope of a cure for many degenerative diseases, including PD. Stern M et al; Neur 1997; 49:Supp.1:S1-S62: Comprehensive review of current strategy and controversy in drug treatment of PD. Issues still moot are: neurotoxicity of levodopa; oxidative stress as a root of PD; slowing of progression by selegiline; delayed onset of motor fluctuation and diskinesias by continued dopamine receptor stimulation; and differing clinical effects of various dopamine agonists. Pallidotomy mentioned only as a "last resort" in drug-resistant dyskinesia. Lieberman A et al; Neur 1997;49:162-168: Reporting the large-scale multicenter trial of pramipexole, in 181 PD patients and 179 controls, finding that pramipexole is safe, effective, and tolerable in both early and late stages of PD. They also noted that it allays a distinctive PD mood disorder that includes anxiety, apathy, attention span, and anhedonia. Sathian K et al; Neur 1997;49:168-177: In controlled trials, PD impaired tactile spatial acuity (discrimination of a standard grating roughness and orientation). Pahwa R. et al; Neur 1997;49:249-253: In 3-month followup of 5 PD recipients of DBS implants, they conclude that chronic stimulation of the globus pallidus is safe and effective againist motor fluctuations and dyskinesias. (There appears to be some confusion about "high" frequency of the stimulation pulses; I've heard some lecturers talk of 100 KHz, whereas the frequency of choice is actually about 100 Hz, near the lower limit of the audible range.) Logroscino G et al; Neur 1997;49:310-311: Debate between conductors of two different surveys, about whether the increased appetite observed in PD is a cause or effect. CURRENT SCIENCE REVIEWS By Joe Bruman August 1997 p. 4 of 4 Fink D, Glorioso j; Nat Med 1997;3:357-359 Suggests that herpes simplex virus may be "engineered" as a gene transfer vector for brain disorders because of its unique affinity for neurons. Kennedy G; Brain 1997;120:1245-1259: Review of potential for gene transfer therapy of neurological disorders. Herpes simplex virus is a favored transmission vector because it readily infects neurons. Nagaratnam N, Kalasabail G: J Neurol Sci 1997;149(2):195-196: They report an elderly patient with long-standing essential tremor, who after a stroke in one side of the pons, found the tremor gone on the opposite side, yielding a clue to the neural pathway involved in that disorder. (This is analogous to the incident some years ago that led to discovery of pallidotomy as an effective treatment for PD.) Deacon T et al; Nat Med 1997;3:350-353: Histological study following unrelated death of a PD patient 7 months after transplant of fetal pig neural cells showed that they had thrived.