CURRENT SCIENCE REVIEWS By Joe Bruman March 1998 P. 1 of 4 Piccini P et al; Ann Neur 1997;42:720-726: Pursuing the idea that levodopa-induced dyskinesia (LID) in PD patients is related to dysfunction of striatal opioid receptors, they used positron emission tomography (PET} scan technique to map the uptake distribution of a known opioid ligand, in PD patients both with and without dyskinesia problems. They found significantly less striatal and thalamic binding in the dyskinetic group, suggesting a further look at possible use of opioids in management of LID. Baker M et al; Ann Neur 1997;42:794-798: "Frontotemporal dementia with parkinsonism" is the collective term for a group of autosomal-dominant presenile dementias that lack distinctive features. Genetic analysis of 28 affected individuals in an Australian family revealed a common gene, in chromosome 17q21-22. Marder K et al; Neur 1998:50:279-281: They surveyed environmental risk factors for 89 non-demented PD patients and 188 controls from an urban multiethnic community. Correlation of PD with area farming and well water was positive for African-Americans, but negative (protective) for Hispanics. Samuel M et al; Brain 1998;121:50-75: They carefully assessed clinical outcome of unilateral ventral microelectrode-guided medial pallidotomy in 26 recipients who had marked levodopa-induced dyskinesia (LID) and poor response of other motor symptoms. Generally there was dramatic abatement of dyskinesia (permitting some to increase levodopa dosage) but no significant improvement in parkinsonism. Two patients died as a result, four had major complications, and ten had minor complications. Therefore they believe that, given the risks,the principal indication for pallidotomy is LID. Praamstra P et al; Brain 1998;121:167-177: In 7 PD patients and 7 controls, they studied the mechanism underlying increased reliance by PD patients on external (visual) cues for movement initiation. It may be a compensatory strategy that bypasses the basal ganglia, or it may be related to excitability changes in the motor cortex that are intrinsic to PD. Bach F et al; Nat Med 1998;4:141-144: After recent success with pig cells for PD, government agencies such as the National Research Council and the FDA are concerned about ethical aspects of xenotransplantation; specifically, the unknown risk of retroviral infection that might spread to the entire human species. Authors propose a moratorium until some unspecified but general public review takes place. Hetts S; JAMA; 28 Jan 1998;300-307: Animal cells die in either of two ways: necrosis, due to trauma or toxic insult, or apoptosis, where the cell kills itself. Virtually all animal cells contain the means for apoptosis, and the strictly regulated process is essential to growth and survival of any organism. This article reviews in detail the molecular basis of apoptosis and its role in disease, with several examples including PD. Understanding how apoptosis is regulated might soon lead to better diagnosis, prognosis, and therapy of many diseases. CURRENT SCIENCE REVIEWS By Joe Bruman March 1998 p. 2 of 4 Lancet; 31 Jan 1998;343 (news item): The US Public Health Service plans to regulate xenotransplantation by means of a standing advisory committee, registry of trials and recipients, specimen repository, possible post-trial monitoring. Penn R et al; Lancet, 31 Jan 1998, 341-342: Before completing a unilateral pallidotomy they used the probe to inject the GABA agonist muscimol at the chosen site, observing improvement in rigidity and bradykinesia. Nat Med 1998;4:242-243 (book review): The new "Home Edition" of the Merck Manual, a watered-down version about the same price and half the size as the continuing professional edition, got enthusiastic praise. Louis E et al; Mov Disord 1998;13:5-10: Although Essential Tremor (ET) is the most common adult movement disorder, maybe 20 times as prevalent as PD, knowledge is poor. They reviewed 19 published surveys, with estimates ranging from 0.08 per thousand to 220 per thousand persons. Among the 4 most reliable (age-stratified) surveys, estimates for age 60 and over range from 13.0 to 50.5 cases per 1000 persons. Blandini F et al; Mov Disord 1998;13:11-15: To explain reported reduced activity of the mitochondrial enzyme Complex I (NADH-ubiquinone oxidoreductase) in the substantia nigra of PD patients, they studied platelets of 16 PD patients and 16 controls, with inconclusive results. Schwarz J et al; Mov Disord 1998;13:16-19: Single-photon-emission computed tomography (SPECT) studies followed up to 56 months in 65 newly diagnosed parkinsonism cases, using the marker 123I-iodobenzamide (123I-IBZM), distinguished those who responded to L-dopa and developed fluctuations (the likely PD cases) from those who turned out to have MSA, PSP, or CBGD. Carter J et al; Mov Disord 1998;13:20-28: A questionnaire to 380 spousal PD caregivers showed that strain, depression, and other decrements of their lifestyle got worse as the disease progressed. Starkstein S et al; Mov Disord 1998;13:29-33: In comparison of 78 patients with classic PD (tremor plus rigidity and/or bradykinesia) against 34 with the akinetic-rigid variant, they found dysthymia (lassitude, ennui) about the same in both groups, but major depression strongly linked to the akinetic-rigid type of PD. Hagell P et al; Mov Disord 1998;13:34-38: Pregnancy is rare in PD, and to evaluate their own case of a healthy uncomplicated birth to a patient taking levodopa, they reviewed literature about possible effects of PD or its medications. Amantadine (Symmetrel) was teratogenic in rats, and some unspecified complications occured when it was used in human patients. Selegiline had other adverse effects in rats. They think that PD may possibly be aggravated by pregnancy alone. CURRENT SCIENCE REVIEWS By Joe Bruman March 1998 P. 3 of 4 Rascol O et al; Mov Disord 1998;13:39-45: In a 6-month preliminary result of a 5-year study, ropinirole equaled levodopa against motor symptoms in new PD patients, but was less effective in advanced stages of the disease. Korczyn A et al; Mov Disord 1998;13:46-51: In a 6-month preliminary report of a 3-year comparison of ropinirole vs. bromocriptine, with and without selegiline, selegiline enhanced the effect of bromocriptine but not of ropinirole. Ropinirole alone was better against the symptoms of PD than bromocriptine alone. van Laar T et al; Mov Disord 1998;13:52-55: One clinical formulation of apomorphine contains sodium edetate (EDTA) to prevent oxidation of apomorphine. A test in 4 patients caused severe subcutaneous allergic reaction, which disappeared on removal of the EDTA. They recommend its exclusion from apomorphine formulations. Brown P et al; Mov Disord 1998;13:56-60: Action tremor contributes to weakness of wrist and elbow joints in PD, observed in physical and electromyographic (EMG) records. Antiparkinsonian drugs reduced tremor of wrist but not elbow. Morris M et al; Mov Disord 1998;13:61-69: They measured walking stride length, when paced by a metronome between 40 and 180 steps per minute, in 20 PD patients and 20 controls. The PD stride was shorter, but improved with levodopa. Hariz G et al; Mov Disord 1998;13:78-83: Chronic thalamic stimulation (CTS, variant of DBS) is known to relieve tremor of PD and ET. Psychologic follow-up assessment showed that performance of instrumental activities of daily living (IADL) is improved as well. Chaudhuri K, Clough C; BMJ, 28 Feb 1998:641 (editorial): Apomorphine, which may be injected by the PD patient or taken by several other means such as a skin patch, is as good as levodopa against most PD symptoms and especially levodopa-induced dyskinesia. Its quick response (3-20 min) and short duration (20-40 min) make apomorphine valuable as a "rescue" from sudden unpredictable "off" periods that are characteristic of late-stage levodopa therapy. Krack P et al; Ann Neur 1998;43:180-192: Experiments with pallidal stimulation (DBS) at different sites showed nearly opposite effects. DBS at the ventral (lowest) site stopped levodopa-induced dyskinesia, while at the dorsal (upper) boundary it sometimes worsened dyskinesia. Authors conclude there may be two or more functional zones in the globus pallidus. Jenner P; Ann Neur 1998;43:202-203 (ad): and Arch Neur 1998;55:142-143 (ad): Agonist stimulation of both D1 and D2 receptors is better in PD than either one alone. These authoritative short essays are sponsored by Athena Neurosciences, related to the mail-order drug firm Athena. CURRENT SCIENCE REVIEWS By Joe Bruman March 1998 p. 4 of 4 Naoi M et al; Ann Neur 1998;43:212-216: The natural enzyme N-methyl(R)salsolinol, known to be toxic to dopaminergic neurons, is now found to be significantly more active in lymphocytes of PD patients than in control subjects. Trojanowski J, Lee V; Arch Neur 1998;55:155ff: Alpha-synuclein is a major conponent of the Lewy bodies which are always present in the substantia nigra of PD patients and also elsewhere in the brains of patients with other diseases, but their pathological significance is still enigmatic. Hoehn M, Yahr M; Neur 1998:50:318ff: Celebrating 50 years of the American Academy of Neurology this landmark article from 1967, with retrospective commentary by one author, is reproduced. Study of 856 parkinsonian patients led to the Hoehn-Yahr PD staging classification and many other insights, e.g., poorer prognosis for PD patients with balance problems. Shannon K et al; Neur 1998;50:434-438: Stereotactic microelectrode-guided pallidotomy in 26 PD patients was effective against intractable dyskinesia and severe "off" motor disability, but had major adverse effects, including one fatality, in 8 of the patients. Chan P et al; Neur 1998;50:513-514: Intense study of the large Contursi kindred containing at least 60 PD cases led to last year's sensational report of an autosomal- dominant factor, namely an alpha-synuclein gene mutant, in its members. However, comparable study of 100 unrelated young-onset PD patients found no examples of the mutant gene, suggesting that familial PD and sporadic PD are quite distinct. Goetz C et al; Neur 1998;50:515-517: In 5 advanced-PD patients having daily visual hallucinations, acute challenge by intravenous levodopa established that the drug was not responsible. Imaiso Y et al; Neur 1998;50:517-519: Levodopa has uses other than PD. A case of hereditary progressive dystonia responded remarkably well to low (100mg/day) dosage. Ballard C, McKeith I; Neur 1998;50:573: Clinical depression occurs with parkinsonism in Diffuse Lewy Body Disease (DLBD) as it does in PD. They suspect that levodopa may be a contributing factor. Colosimo C, Metman V et al; Neur 1998;50:573: (correspondence) Through acute challenge by levodopa and by apomorphine in PD patients at various stages of the disease, they concluded that levodopa-induced motor complications in PD may stem in part from postsynaptic pharmacodynamic effects, rather than from presynaptic pharmacokinetic effects. J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013