Post: 007812 008091

Olanow, C. et al: Ann Neur 1995; 38:771-777:
A careful new placebo-controlled study of 101 patients with mild (early) PD seems to show that Deprenyl (Eldepryl, selegiline) retards the progress of PD symptoms after all. This is the latest round in a controversy which has gone on for several years, and it looks convincing. Symptoms were evaluated by the UPDRS, primarily a measure of motor function. While the precise action of Deprenyl remains unknown, the study seems to indicate a true neuroprotective effect and not just symptomatic relief. The effect is suspected to be a counter to oxidative stress, which in turn may be due to cytotoxic free radicals caused by levodopa therapy. (Incidentally, Olanow's institution, Mount Sinai Medical Center in New York City, is beginning a trial of an alternative to Deprenyl, which is also a MAO-B inhibitor but does not metabolize to amphetamine- see my post on PDF of 5 Dec 95)

Morrish, P. et al: J Neur Neurosurg Psych 1995; 59:597-600:
27 recent-onset PD patients were studied via FD PET to check validity of that technique for early diagnosis. Authors found FD PET to be accurate, but the disease has a highly variable rate of progression, and the preclinical period is short (on the order of 2 years).

Avorn, J. et al: JAMA 1995; 274:1780-1782:
Authors tested the effect of metaclopramide (Reglan), a drug commonly used in elderly patients for gastric problems, on subsequent misdiagnosis of PD, as indicated by administration of levodopa. In a large sample of Medicaid patients, those getting Reglan were three times more likely to begin using levodopa, suggesting that Reglan side effects are commonly misdiagnosed as PD. (I'm not sure I follow the logic of that conclusion.)

Sandyk, R.: Int J Neur 1994; 69:125-130 (from fall 1995 APDA newsletter):
50% to 80% of PD patients have abnormal glucose tolerance (diabetes) which may be aggravated by levodopa therapy, and may reduce the efficacy of that therapy against PD symptoms. Author therefore recommends that PD patients should be routinely screened for glucose intolerance. (Might this also suggest that perhaps diabetes may predispose to PD?)

Lees A: BMJ 16 Dec 95; 1602-1607:
The debate rages on! Snapping at the heels of Olanow's recent report (see Part 1) comes a UK study showing not only that selegiline (Deprenyl, Eldepryl) is of no benefit in PD, but also that mortality of participants during the 5-6 year follow-up was an alarming 60% higher among those given selegiline plus levodopa (about 1/3 of the total 520) than the others. Ages and causes of death were not specified. The study conclusions attack a) the free radical hypothesis and b) the oxidative stress hypothesis of PD etiology. The three trial groups got respectively, levodopa alone, levodopa plus selegiline, and bromocriptine (Parlodel) alone. The UK report also faults conclusions of the earlier US DATATOP study as subjective. (All the trials thus far seem to rely on clinical evaluation of psychological performance. Results might be better defined if a trial were based on more "tangible" evidence, such as FD PET scans of each participant.)

Calne D: BMJ 16 Dec 95; 1584:
Commentary on the article reviewed above, with rather scathing remarks about earlier trials which were claimed to indicate a neuroprotective effect. Some curious discrepancies regarding medication protocol and number of subjects, but otherwise a fair representation of the UK study results. Especially unkind treatment of W. Birkmayer, developer of selegiline. (I note that most of the respondents in the current informal parkinsn survey seem to be taking selegiline along with levodopa and other medications. At this point, patients taking selegiline must be wondering, what to do and whom to believe. We all can offer opinions, but with consequences so serious I hesitate to do so.)

Jacobs D. M. et al: Neur 1995;45:1691-1696:
Impaired verbal fluency may offer a preclinical sign of PD dementia.

Jacobs D. H. et al: Neur 1995;45:1696-1702:
PD patients are poor not only at expressing emotion facially, but also at perceiving facial expression of others.

Maricle R et al: Neur 1995;45:1757-1760:
Mood elevation and anxiety reduction following levodopa dosing are true pharmacologic, not placebo, effects.

Carrero-Valenzuela R et al: Neur 1995;45:1760-1763:
Gene mutations have been linked to several neural diseases, but the suspect mutation was not found in the case of PD.