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CURRENT SCIENCE REVIEWS By Joe Bruman July 1999 Page 1 of 2 Merims D et al; Lancet: 22 May 1999:1764-1765: In a preliminary open-label trial, the NMDA inhibitor riluzole (Rilutek) in 6 patients having advanced PD was well tolerated and effectively reduced dyskinesia. Gwinn-Hardy D et al; Lancet: 29 May 1999:1850-1851: For input to the long debate over levodopa toxicity, they studied records of 12 members of a familial cluster of autosomal-dominant L-dopa-responsive PD patients. Seven who died before 1969 got no levodopa, and lived an average 7 years after diagnosis, to age 43. Levodopa therapy began on the 5 survivors in 1969, who lived an average ll years following diagnosis (including 3 still living). Hoehn-Yahr staging estimates for that group showed slower progression of PD symptoms as well. French Clozapine PD Study Group; Lancet: 12 June 1999:2041-2: To augment the sole previous controlled study, they tested clozapine (Clozaril) against drug-induced psychosis in 60 PD patients, concluding that it is well tolerated, effective, and safe, if periodic blood tests are done as long as it is used. Lancet: 12 June 1999:2043 (news item): Nine PD patients, who had caused traffic accidents by falling asleep while driving, were surveyed. They had normal skills and excellent records, but 4 of the 9 reported previous incidents of irresistibly falling asleep, suddenly and without warning. One had been taking ropinirole (Requip) and the other eight were on pramipexole (Mirapex). No such episode occurred before starting, and none occurred after stopping, the agonist involved. Kimber T et al; Brain 1999:122:895-906: Followup of 17 pallidotomy recipients who had advanced PD confirmed the informal impression that pallidotomy improves bradykinesia, but the mechanism is unclear. Hagell P et al; Brain 1999;122:1121-1132: Five recipients of unilateral fetal tissue grafts received second grafts on the opposite side, some months later. PD symptoms improved markedly in two patients and moderately in another. Sequential transplantation seems not to compromise survival or function of either graft. Krack P et al; Brain 1999;122:1133-1146: In 8 PD patients with implanted deep-brain stimulation (DBS) of the subthalamic nucleus (STN), authors studied effects of varying the power. Normal voltage reduced off-period dystonia as well as levodopa-induced dyskinesia, but higher power made both symptoms worse. They identify several kinds of dystonia in a continuous spectrum which seems to reflect the degree of STN activity, as affected by the amount either of levodopa given or of STN stimulation. Generally, DBS of the STN seems to mimic the effects of levodopa, thereby permitting reduced dosage of that drug. Yokoyama T et al; J Neurosurg 1999:90:1005-1010: About a third of PD patients develop dementia, even in the early stages. Thorough cognitive function testing of 25 posteroventral pallidotomy recipients revealed that the degree of cognitive dysfunction follows the Hoehn-Yahr stage of PD progression, but is unaffected by pallidotomy. CURRENT SCIENCE REVIEWS By Joe Bruman July 1999 Page 2 of 2 Zirh A et al; J Neur N'surg Psych 1999;66:772-775: A blinded study of 21 patients who received thalamotomy for intractable essential tremor (ET) shows that, like deep-brain stimulation (DBS) of the ventral intermediate nucleus (Vim) of the thalamus, unilateral thalamotomy is safe and effective treatment for ET. Anderson J et al; J Neur N'surg Psych 1999;66:776-778: Developmental stuttering of a patient who also was taking levodopa for PD was worse during "on" periods of PD medication, suggesting that the stuttering is related to excessive dopamine. Miyagi Y et al; J Neur N'surg Psych 1999;66:794-796: A vigorous postural tremor induced by 7 years of toluene abuse (glue sniffing) was abolished by ablation of the contralateral ventral intermediate nucleus (Vim) of the thalamus (thalamotomy). Elbaz A et al; Neur 1999;52:1876-1882: In a European population-based control study comparing 219 PD patients and 657 healthy subjects, a first-degree relative with PD was found 3 times as often in the PD group as in the controls. The association with younger members of that group was about 5 times as strong as with the older patients. Familial factors, either genetic or environmental, play a role in PD. Frucht S et al; Neur 1999;52:1908-1910: The sudden-sleep article reported in Lancet (above). BMJ; 12 June 1999:1575 (news item): Transplanted stem cells, unlike fetal tissue transplants that for some years have shown promise for PD, are able to migrate via cerebrospinal fluid to any location where replacement may be needed, and to evolve through reproductive growth to the specific type of neural cell that is deficient. Researchers injected stem cells into the cranial cavity, or ventricle, of mice which had been genetically altered to have a disorder causing severe tremor, and found that the infusion of stem cells improved the condition. Yandava B et al; Proc Natl Acad Sci USA 1999;96:7029-7034: (PMID 10359833) The article on neural stem cell transplantation reported in BMJ (above). This was the first success in treating neurodegeneration that was widespread, rather than localized, in the brain (see also CSR MAY 97). J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013