CURRENT SCIENCE REVIEWS By Joe Bruman MAY 1997 p. 1 of 3 Allen G et al; Science, 28 Mar 1997:1940-1943: The cerebellum (Latin: "little brain") is usually known as a center for motor control. Authors demonstrated, by MRI scan of volunteers performing tasks designed to separate cognition from motor control, that the cerebellum also functions in attention and other nonmotor activity. Taha J et al;J Neurosurg 1997;86:642-647: Until now, the usual choice in ablative surgery for PD has been: thalamotomy for tremor, pallidotomy for other symptoms (rigidity, drug-induced dyskinesia, etc.). But this team using microrecording in 44 routine pallidotomies found, in some patients, cells firing in time with observed tremor. Extending the lesion to those cells greatly reduced the tremor, in addition to the other complaints. McKay R; Science, 4 Apr 1997:66-71: Comprehensive review of work to date on "stem" cells of the CNS. Every embryo begins with a single cell, that divides and differentiates to create the multitude of cellular forms and functions in the eventual organism. Stem cells, present in both embryo and adult CNS, are "precursors" of "progenitor" cells that can differentiate into neurons and other CNS cells, and multiply fast enough to create the huge number of cells in the infant CNS. Arcane detail, but understanding is the key to transplant therapy. Zetterstrom R et al; Science, 11 Apr 1997:248-250: Working with newborn and embryonic mice, authors found a protein, Nurr-1, which appears in cells before they develop into dopamnin- ergic neurons, and regulates production of dopamine in adult mice. Mice bred to lack Nurr-1 didn't develop the neurons (corresponding to the substantia nigra pars compacta) and died soon after birth. Authors hope this may lead to better understanding, treatment, and prevention of PD. Science; 11 Apr 1997:202:editorial) Comment on above report, in slightly simpler language. Too little dopamine causes PD; too much may lead to schizophrenia; Nurr-1 regulates it throughout life. Finding the molecule that binds Nurr-1, or ways to control its expression via gene transfer, or a toxin that disables it, may become important breakthroughs in PD. Science; 11 Apr 1997:196-198 (news report): MRI and PET scans of the living brain in action have become basic neuroscience tools, but they imply the assumption that oxygen metabolism is a key measure of neural activity. Now two mavericks claim it's not so, that some neural activity is anaerobic, and a debate over the meaning of the imagery has arisen. BMJ; 5 Apr 1997:997 (news item): Two French professors surveyed 1777 people over 65, beginning in 1988 and, contrary to common belief, found that moderate wine drinkers (3 to 4 glasses/day) were only about 1/3 as likely as non-drinkers or light (2 glasses/day) drinkers to develop dementia, including AD. By sheer coincidence, locale of the survey was Bordeaux, France's premier wine district. Rioux L et al; Movem't Dis 1997;12:148-158: In MPTP monkeys, chronic levodopa treatment led to dyskinesia via enhanced production of D1 receptors in striatal output to the Gpi. CURRENT SCIENCE REVIEWS by Joe Bruman May 1997 p. 2 of 3 Dziewczapolski G et al; Movem't Dis 1997;12:159-166: In mice, the atypical neuroleptic clozapine, besides its anti- psychotic effect, relieved the "super-off" motor phenomenon by, they think, blocking some D2 receptors. Avissar S et al; Movem't Dis 1997;12:167-174: Seeking a diagnostic marker for PD, they found reduction of certain proteins in mononuclear leukocytes (MNLs) of PD patients. Larsen J et al; Movem't Dis 1997;12:175-182: In a 5-year double-blind controlled study of selegiline (Eldepryl) plus levodopa in 163 PD patients, the former reduced the need for long-term levodopa dosage and may have delayed disability. LeWitt P et al; Movem't Dis 1997;12:183-189: In re-analysis of DATATOP data, trying to define the "end point" (where need for levodopa became apparent) using such established disabilty scales as UPDRS, they could not reproduce it reliably, although the DATATOP conclusions were reasonably consistent. Scheider W et al; Movem't Dis 1997;12:190-196: By questionnaire survey of 57 PD patients and 50 controls, they found that dietary antioxidants were not protective. Melcon M et al; Movem't Dis 1997;12:197-205: Controlled random survey of 7765 people over 40, in a city of about 75,000 in an agricultural region of Argentina, turned up 51 PD cases, or 657 per 100,000 population. Burleigh-Jacobs A et al; Movem't Dis 1997;12:206-215: The "freezing" phenomenon in PD is improved both by external stimuli and by levodopa. Lieberman A; Movem't Dis 1997:12:239-240: Study of many film clips showing Adolf Hitler revealed no obvious signs of PD up to 1932, but left arm immobility by 1933 and tremor by 1944 or 1945. Author suggests that Hitler's awareness of his PD may have influenced his principal wartime strategy decisions. Sano M et al; NEJM, 14 Apr 1997:1216-1222: Selegiline, but not Vitamin E, is believed to slow progression of PD. To test the free-radical/oxidative-stress hypothesis in Alzheimer's Disease, they gave either, both, or neither to 341 AD patients for 2 years in a double-blind controlled trial, and found that both slow progression of AD. Jobst E et al; Arch Neur 1997;54:450-454: Ten PD patients did less well than ten controls in a movement test requiring kinesthesia without visual clues. Miller G et al; Ann Neur 1997;41:530-539: Highly specific monooclonal antibodies help to localize dopamine transporter protein, a reliable marker for PD. Brashear A et al; Neur 1997;49:1066-1069: Rapid-onset dystonia-parkinsonism, a variant of PD, can develop full-blown symptoms in a few days or in an hour, resists levodopa therapy, autosomal-dominant. Authors found a second familial cluster of this unusual disease. CURRENT SCIENCE REVIEWS By Joe Bruman May 1997 p. 3 of 3 Richard I et al; Neur 1997;48:1070-1077: To check a claim that selegiline (Eldepryl) combined with an antidepressant may cause a serious reaction called the serotonin syndrome, authors surveyed 47 investigators who had so treated a total of 4568 patients, and conclude it is too rare for concern. Friedman J et al; Neur 1997;48:1077-1081: In a double-blind crossover trial of clozapine compared with the standard antitremor drug benztropine for tremor in 22 PD patients, they found it equally effective and recommend it as a fallback. Cerbo R et al; Clin Neuropharm 1997;20:36-41: Dopamine is thought to be involved in migraine. Using the dopamine agonist apomorphine as a test on 35 migraine sufferers and 20 controls, they found that DA receptors in migraine are hyper- sensitive. Gimenez-Roldan S et al; Clin Neuropharm 1997;20:67-76: In a 44-month test of combined levodopa and bromocryptine, they found it beneficial but can't explain just why. Ghika J et al; Clin Neuropharm 1997;20:130-139: A 14-week open-label study on 61 PD patients at various stages confirmed that a new dual-release formulation of levodopa/ benserazide combines the advantages of standard and sustained- release formulations. Courty E et al; Clin Neuropharm 1997;20:140-147: Self-administered apomorphine for severe on-off motor fluctuations in 4 male PD patients led to psychotic increase of libido and consequent erratic behavior, as well as desire for greater dosage and probable psychologic dependence on the drug. Merello M et al; Clin Neuropharm 1997;20:165-167: In 12 PD patients alternately given subcutaneous apomorphine or Dispersible Madopar (benserazide) in a double-blind trial, the former gave faster relief of sudden "offs". Adler C; Clin Neuropharm 1997;20:148-151: In preliminary open-label trial on 8 patients, gabapentin was effective against Restless Legs Syndrome, and a controlled trial is recommended. Stocchi F et al; Clin Neuropharm 1997;20:95-115: Review of treatment strategies for fluctuations and dyskinesias in advanced PD. 146 references. Mercuri N et al; J Neurosci 1997;17:2267-2272: Persistent effect of MAO inhibition on response to dopamine. Connerl J et al; J Neurosci 1997;17:2295-2313: Mapping of brain-derived neurotrophic factor in rat CNS. Moghaddam B et al; J Neurosci 1997;17:2921-2927: Effect of a NMDA (glutamate) antagonist on psychic state in rats. Paus T et al; J Neurosci 1997;17:3178-3184: PET study aided by transcranial magnetic stimulation (TMS). J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks CA 91403