CURRENT SCIENCE REVIEWS By Joe Bruman December 2000 P. 1 of 4 Ceravolo R et al; Neur 2000;55:1216-1218: Testing suggestion that selective serotonin reuptake inhibitor (SSRI) antidepressants may worsen motor function in PD, an open- label trial of paroxetine (Paxil) on 33 patients having confirmed depression and under dopaminergic drug therapy showed no general change in UPDRS scores, except for reversible worsening of tremor in one of the subjects. Lai E et al; Neur 2000;55:1218-1222: In extended followup of 89 unilateral posteroventral pallidotomy (PVP) recipients, 82% reported moderate or marked improvement in their parkinsonian symptoms. Schrag A et al; Neur 2000;55:1239-1240 (letters): Discussing the value of magnetic resonance imaging (MRI) in diagnosis of atypical parkinsonian syndromes such as PSP, MSA, or CBGD. (cf. CSR MAR 00) Karlsen K et al;J Neur N'surg Psych 2000;69:584-589: In a 4-year followup examination of 111 patients, health-related quality of life (HRQL) was substantially reduced by impact of PD. Clarke C, Davies P: J Neur N'surg Psych 2000;69:590-594: Thirteen studies found in a literature search indicate that the common test involving acute levodopa and apomorphine challenge is no better than that of chronic levodopa therapy for diagnosis of idiopathic PD, while it may cause significant adverse events and added cost. Lancet, 21 October 2000:1416 (news item): In the continuing debate over levodopa vs agonist as initial treatment for PD, a blinded trial of levodopa/carbidopa (Sinemet) vs. pramipexole (Mirapex) in 151 PD patients showed significantly fewer motor complications, but less improvement in movement ability and greater risk of somnolence and hallucinations, in the latter group. Lancet, 21 October 2000:1416 (news item): Initiation of dopamine agonist therapy in patients with PD may trigger acute orthostatic hypotension, and therefore should be supervised by a physician or nurse. Lancet, 28 October 2000:1498 (news item): The first human trial of glial cell-line derived neurotrophic factor (GDNF) was abandoned last year by Amgen because when injected into a ventricle (fluid space) of the brain, it failed to reach the site where it was needed, in the substantia nigra. But a new trick that works in monkeys offers some hope: instead of GDNF, they injected a virus genetically altered to express GDNF, that would directly affect the nigrostriatal system. One remaining problem is possible overproduction of dopamine. CURRENT SCIENCE REVIEWS By Joe Bruman December 2000 P. 2 of 4 Lancet, 28 October 2000:1500 (editorial): Stem cells in a developing infant have the ability, as they reproduce, to turn into any of the myriad variety of cells (such as neurons) needed in the adult organism. But there must be a means of telling each stem cell just which type it is supposed eventually to become. One clue is the nearby presence of the desired type, say heart muscle. But in the lab all they got was an amorphous mass of heart cells, not muscle. However, when they added a microscopic "scaffold" mimicing the arrangement of real muscle cells, the stem cells took the cue and also grew into muscle tissue. Lancet, 4 November 2000:1579 (news item): Creutzfeldt-Jakob disease (CJD) is unrelated to PD, except only that its symptoms at onset may be mistaken for those of PD. But it is closely related to bovine spongiform encephalopathy (BSE) or "mad cow disease" epidemic in Britain about 10 years ago, and the 16-volume report of the subsequent inquiry is a cautionary lesson for those who would rely on their government to solve problems of any kind. Lancet, 11 November 2000:1659 (news item): In experiments with rat models of PD, the common pesticide rotenone was found to be a risk factor. [but since rotenone is so ubiquitous it must be accompanied by another, such as a gene mutation, otherwise everyone would have PD.] Schrag A, Quinn N; Brain 2000;123:2297-2305: A community-based study of 124 PD patients revealed that motor fluctuations are most strongly related to disease duration and levodopa dosage, while dyskinesias are related to duration of levodopa treatment. Science News, 25 November 2000:344 (news item): Following reports that heavy drinkers of coffee are less likely to have PD, researchers gave caffeine to rats with MPTP-induced PD, and found true neuroprotection, not mere aversion to coffee. Poewe W, Wenning G; Mov Disord 2000;15:789-794: Apomorphine taken orally causes nausea, but by subcutaneous injection it is virtually as effective against PD symptoms as levodopa, while lacking the latter's adverse effects, therefore authors advocate wider use. Rodriguez M et al; Mov Disord 2000;15:795-803: Electrophysiological study in rats shows association of dopamine cell degeneration with increased excitatory response in the striatonigral pathway, a possible clue to the origin of PD. Treseder S et al; Mov Disord 2000;15:804-812: Studies in rats suggest that dopamine agonists get less effective as PD progresses, because endogenous dopaminergic tone is lost. CURRENT SCIENCE REVIEWS By Joe Bruman December 2000 P. 3 of 4 Buervenich S et al; Mov Disord 2000;15:813-818: In a study of 78 PD patients and 130 healthy controls, mutation of the alcohol dehydrogenase gene (ADH4) was found to be associated with PD, but not strongly enough to cause symptoms by itself alone. Bower J et al; Mov Disord 2000;15:819-825: A community-based records study showed that perceived incidence of PD depends upon the rigor of diagnostic criteria applied. Larsen J et al; Mov Disord 2000;15:826-829: In a community-based study of 245 PD patients, most didn't have motor fluctuations, but motor disabilities and neuropsychriatric problems are important. Morita H et al; Mov Disord 2000;15:830-834: Study of 17 PD patients and 36 controls showed that presynaptic inhibition (PSI) is impaired in PD and probably responsible for disturbance of walking gait. Hozumi A et al; Mov Disord 2000;15:835-842: In a study of 15 PD patients and 13 controls, event-related potential topography produced by novel and target stimuli was used to detect dysfunction of mental switching (perseveration) in PD. This cognitive impairment is related to learning disabil- ities based upon dysfunction of the frontal lobe and basal ganglia. Nutt J et al; Mov Disord 2000;15:843-849: Alternate tapping speed, widely used as a measure of bradykinesia in PD, is affected by age, hand dominance, and practice. But procedural (motor) learning from practice is impaired in PD. Tonolli I et al; Mov Disord 2000;15:850-861: In 10 PD patients and 6 controls, they found that the task of maintaining postural equilibrium while raising one or the other foot to one side is an effective test for PD impairment. Reuter I et al; Mov Disord 2000;15:862-868: To study the relation in PD between therapeutic levodopa dosage and physical exertion, they tested 12 patients uniformly, but results were generally inconclusive. Molina J et al; Mov Disord 2000;15:869-872: In a population of 250 PD patients, 12 were pathologic gamblers; 10 of those began gambling only after onset of PD symptoms and the start of levodopa therapy. Luginger E et al; Mov Disord 2000;15:873-878: A 5-week double-blind crossover trial confirmed previous reports that the NMDA receptor antagonist amantadine (Symmetrel) significantly diminishes levodopa-induced dyskinesias in PD. CURRENT SCIENCE REVIEWS By Joe Bruman December 2000 P. 4 of 4 Marchese R et al; Mov Disord 2000;15:879-883: A single-blind study in 20 PD patients showed that external sensory cues confer added benefit to the physical therapy rehabilitation protocol. Hayashi S et al; Mov Disord 2000;15:884-888: Autosomal-recessive juvenile parkinsonism (AR-JP) has been associated in epidemiologic studies with a mutation of the "parkin" gene. The death at age 70 of one such patient permitted a detailed pathologic examination which confirmed that finding. Kimber T, Thompson P; Mov Disord 2000;15;982-985: Observed blink rate in 17 of 25 PD patients in "off" periods was reduced, as expected, and restorable by levodopa. But in the other 8, blink rate was high, returning to normal with levodopa. Authors suggest the latter effect may be a new form of "off"- period dystonia. Tesei S et al; Mov Disord 2000;15:986-989: Since tricyclic antidepressants may aggravate symptoms of PD, they tried instead the selective serotonin reuptake inhibitor (SSRI) paroxetine (Paxil) on 65 depressed PD patients, finding it to be effective against depression and acceptably tolerable in its motor symptom effects. Piccini P et al; Ann Neur 2000;48:689-695: Positron-emission tomography (PET) study of movement-related cortical function in 4 recipients of fetal tissue transpants for PD shows that it improves significantly, but somewhat later than the improvement of motor symptoms alone. Thyagarajan D et al; Ann Neur 2000;48:730-736: In a patient with levodopa-responsive parkinsonism and other neurologic symptoms, they found a specific mutation in mitochondrial, rather than nuclear, DNA, which appears to be responsible. Rana M et al; Ann Neur 2000;48:774-781: Laboratory studies of a patient with parkinsonism, associated with mutation in mitochondrial DNA. BMJ, 11 November 2000:1175 (news item): The widely used and ubiquitous agricultural pesticide rotenone (see Lancet item above) causes the equivalent of PD in rats. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013