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CURRENT SCIENCE REVIEWS By Joe Bruman August 1999 Page 1 of 3 J Neur N'surg Psych 1999;67:(advertisement): This ad implies that the catechol-0-methyl transferase (COMT) inhibitor entacapone (Comtess) is now approved for treatment of PD in the UK. Like tolcapone (Tasmar), entacapone prolongs the bioavailability of levodopa by slowing its breakdown, thereby permitting lower dosage of levodopa for equivalent benefit; less potent than tolcapone, but requires no blood tests. The makers claim it will be available in the U.S. "later this year". Hu M et al; J Neur N'surg Psych 1999;67:20-26: Neuropsychological study of 17 PD patients and 10 controls showed that PD subjects, even though not clinically demented, had some cognitive impairment. Concurrent magnetic resonance spectroscopy (MRS) imaging proved able to locate the site of cortical dysfunction in the PD subjects before they had reached the stage of clinical dementia. Stuerenburg H, Schoser B; J Neur N'surg Psych 1999;67:22-24: A 76-yr-old, taking 600 mg/day of levodopa (3x50/200 Striaton) for mild Parkinson's syndrome without much effect, attempted suicide by taking a 10-day supply at once. Within 1/2 hour he developed various psychotic symptoms such as anxiety, crying without reason and depression but, except for fully dilated and light-unresponsive pupils, no peak-dose dyskinesia or other motor symptoms. Authors suggest the blood concentration of 3-0-methyldopa as a test for acute overdose of levodopa. Sommer M et al; J Neur N'surg Psych 1999;67:27-34: Neuropsychological testing of PD subjects and controls showed that the former were impaired in complex learning tasks requiring alertness, but not in simple learning tasks such as eyeblink conditioning. de Bie R et al; J Neur N'surg Psych 1999;67:124-125: Of 60 successive pallidotomy recipients, 7 shortly afterward experienced intermittent bouts of hiccups, lasting for hours. In 6 patients the bouts abated within 3 days, but in the 7th they persisted for 6 months. Kostic V et al; Neur 1999;52:1916: After an educated guess and success with rat models of PD, they tried the adenosine antagonist theophylline (commonly prescribed for asthma symptoms) on patients at various stages of PD. By itself theophylline has little anti-PD effect, but combined with dopaminergic therapy it significantly increases the ratio of "on" to "off" period duration, without worsening dyskinesia. Moro E et al; Neur 1999;53:85-90: Seven recipients of bilateral deep-brain stimulation (DBS) implants in the subthalamic nucleus (STN) in general had improvements in rigidity, tremor, and bradykinesia, as well as nonclinical signs such as sleep and ADL quality, which were reflected as reduced need for anti-PD medication. Jarman P, Wood N; BMJ;19 Jun 1999:1641-1642 (editorial): So far, 3 different genes have been associated with PD, in various familial clusters. With extensive discussion of possible etiology, they hope that more knowledge of those relations will lead to better understanding of the more common sporadic PD. CURRENT SCIENCE REVIEWS By Joe Bruman August 1999 Page 2 of 3 Richard I et al; Clin Neuropharm 1999;22:172-175: The male aphrodisiac yohimbine (Yocon; predates Viagra) may cause panic attack in users who are clinically depressed. PD patients in a small trial, even those without history of depression or anxiety, were also susceptible to yohimbine-induced panic attack. Azulay J-P et al; Brain 1999;122:111-120: In a controlled study of visual cues as aids to walking gait in PD, lines on the floor helped in normal lighting, but not when lit by strobe flash, which made them look motionless. Floor markings help only if perceived to move in the visual field. Taha J et al; J Neurosurg 1999;91:68-72: From experience with 23 assorted recipients of deep-brain stimulation (DBS) of the thalamus, either contralateral to previous thalamotomy or bilateral, they conclude that (1) both procedures are safe; (2) staging doesn't reduce risk of speech or gait impairment; and (3) primary indications for bilateral thalamus DBS (Vim-Stim) are head and voice tremor. Honey C et al; J Neurosurg 1999;91:109-113: In experiment with rats to compare survival of fetal transplants under two alternative means of immunosuppression, they found that a short course of the monoclonal antibody anti-CD25 was as good as a long course of cyclosporin. Mehler M, Kessler J; Arch Neur 1999;56:780-784: A tutorial review for nonspecialists of "progenitor" neurons, which from early stages of embryonic development can evolve into any of the many types of adult neurons, and their potential as transplant material for treatment of PD. The recent discovery that such cells also exist in the adult brain is encouraging. Jankovic J; Arch Neur 1999;56:785-790: Tutorial review for nonspecialists of new and emerging therapies for PD. Discusses recent advances and promise in neuroprotection, dopaminergic therapy, and neurosurgery; thorough and up-to-date. Louis E et al; Arch Neur 1999;56:841-846: Feeling that diagnosis of essential tremor (ET) by questionnaire or interview is unreliable, they devised a performance-based functional test, and tried it on 50 ET patients and 51 normal controls to confirm its accuracy. Muller T et al; Lancet, 10 July 99:126: PD patients on dopamineregic therapy are at greater than usual risk of atherosclerosis (coronary or other vascular blockage). In a controlled study of 45 subjects, those taking levodopa for PD had elevated plasma level of homocysteine, a natural product known to be a major risk factor. Authors recommend that such therapy should be supplemented by folic acid, which occurs in green leafy vegetables and fruits, and lowers homocysteine. Shinotoh H et al; Ann Neur 1999;46:62-69: Comparison by positron emission tomography (PET) of 16 PD patients, 12 progressive supranuclear palsy (PSP) patients, and 23 matched controls showed that acetylcholinesterase activity is distributed differently, therefore may be useful in diagnosis. CURRENT SCIENCE REVIEWS By Joe Bruman August 1999 Page 3 of 3 Muriel M-P et al; Ann Neur 1999;46:103-111: Microscopic examination of brain cells from 5 PD patients and 4 controls showed that levodopa alters distribution of D1 dopamine receptors at both the cellular and subcellular level, offering a possible explanation of symptom fluctuations and loss of efficacy in advanced stages of the disease. Deuschl G et al; Ann Neur 1999;46:126-128: Frequency and other features of hand tremor may be important in diagnosis. A man who had a unilateral cerebellectomy (to remove a tumor) developed PD 17 years later, identified partly by the classic (and disabling) 4.3-hz resting tremor and by favorable response to levodopa. Hence, authors think that the cerebellum may play an important role in PD. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013