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CURRENT SCIENCE REVIEWS By Joe Bruman June 1999 Page 1 of 5 Neurology 1999;52:Supplement 2: This hefty tome contains abstracts of several hundred papers offered at the 51st Annual Meeting of the American Academy Of Neurology at Toronto, Canada, April 17-24. I'll review 32 of those which seem relevant to PD or Essential Tremor, when time permits. Due to the number, and since the important ones will appear in regular issues of Neurology, I'll post separately. Baker M (ed) et al; Neur 1999;52S3:S1-S29: Reviews and commentary on depression, psychosis, and dementia in Parkinson's disease, by 7 members of a special panel session at the 12th International Symposium For Parkinson's Disease, held at London, 23 Mar 1977. A majority of the presentations deal with caregiving and impact on the family, and management recommendations variously include tricyclic antidepressants, selective serotonin reuptake inhibitors, electroconvulsive and light therapy, reduction or withdrawal of anticholinergic agents and dopamine agonists, and neuroleptics such as clozapine, quetiapine, or olanzapine. The selective serotonin antagonist ondansetron (Zofran) gets special mention, but its very high cost is a drawback. Ichise M et al; Neur 1999;52:1206-1214: Comparative scans of PD patients not yet started on levodopa and a healthy control group demonstrated that, using appropriate markers, single-photon-emission computed tomography (SPECT) can detect and map both presynaptic and postsynaptic dopaminergic alterations in L-dopa-untreated PD. Bower J et al; Neur 1999;52:1214-1220: A survey of patient records showed incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990, correlated to type of disease, age, and gender. Ilgin N et al; Neur 1999;52:1221-1226: Compared positron-emission tomography (PET) scans of PD patients, PSP patients, and healthy controls established that PET is useful in distinguishing PD from PSP. Goetz C et al; Neur 1999;52:1227-1229: To test the common belief that dopamine agonists in advanced PD must be switched slowly and carefully, they tried a switch from bromocriptine (Parlodel) or pergolide (Permax) to pramipexole (Mirapex), slowly in one group of patients and abruptly in another. If equivalent dosage is observed, rapid titration is quite safe and produces fewer adverse effects. Iwanaga K et al; Neur 1999;52:1269-1271: Microscopic examination of heart tissue from PD patients found both Lewy bodies and neurites positive for alpha-synuclein, showing that PD affects sympathetic and intrinsic heart neurons as well as those of the brain. CURRENT SCIENCE REVIEWS By Joe Bruman June 1999 Page 2 of 5 Saunders-Pullman R et al; Neur 1999;52:1417-1421: Review of chart data from women diagnosed less than 5 yr and who has not started levodopa showed that estrogen supplementation is associated with reduced severity of PD symptoms. Lee M et al; Neur 1999;52:1422-1426: Single-Photon Emission Computed Tomography (SPECT) study of 9 patients with only postural tremor, 6 with only postural and rest tremor, 11 with PD, and 21 healthy controls showed that essential tremor (ET) patients after some time may begin to lose substantia nigra neurons and develop parkinsonian symptoms. Bhatt M et al; Neur 1999;52:1467-1471: Reporting 5 cases of acute and reversible parkinsonism, unresponsive to levodopa, following brief exposure to organophosphate (OP) pesticide. From that, authors suspect that such pesticides may have a role in PD, and that there may be a factor of genetic susceptibility to OP pesticides in PD. Grondin R et al; Neur 1999;52:1672-1677: Searching for medication that might avoid the dyskinesia of levodopa, they tried a selective adenosine receptor agonist called KW-6002 on MPTP monkeys, with encouraging results. Griffiths P et al; Brain 1999;122:667-673: Postmortem x-ray and electron microscope study of brain tissue from PD patients and controls showed higher iron concentration in the substantia nigra and globus pallidus of the PD subjects. They suggest that increased ferritin, the normal brain iron storage protein, may increase the risk of free-radical damage. Clarke C et al; Lancet; 17 April 1999:1329-1330: Contrary to an earlier report (CSR AUG 97) that a differential response to the adrenoreceptor agonist clonidine could help to distinguish PD from multiple system atrophy (MSA), tests on 26 assorted patients failed to show any significant difference. Schrag A et al; Lancet, 1 May 1999:1498-1499: Suspecting that other tremor disorders are often mistaken for essential tremor (ET), they examined casenotes of 50 patients diagnosed with ET, and only half met established criteria. Wills A et al; J Neur N'surg Psych 1999;66:681-684: A patient with orthostatic tremor (a 14-16 Hz tremor causing unsteadiness in standing) after 9 years developed PD, whereupon treatment with levodopa relieved the orthostatic tremor as well. Therefore they tried it on 8 patients who had OT alone, with encouraging success. CURRENT SCIENCE REVIEWS By Joe Bruman June 1999 Page 3 of 5 Lieberman D et al; J Neurosurg 1999;90:928-834: In pallidotomy the conventional mode of ablation is electrical heating of the target site, which is nonselective and destroys nearby cells other than the target neurons. So they tried injecting a chemical (kainic acid) instead, which kills only neurons and spares other cells, on monkeys with MPTP-induced PD, finding that it permanently reversed the PD symptoms. They see potential value for both PD therapy and research. Lin J-J et al; J Neurosurg 1999;90:974-976: Simultaneous bilateral posteroventral pallidotomy in a 29-year- old man with cerebral palsy and disabling generalized dystonia produced slow but steady improvement in the dystonia. JAMA, 19 May 99:1784 (editorial): Reporting a paper at the AAN meeting (above) on followup of 40 PD patients in the first randomized controlled trial of fetal transplants (half given placebo surgery), motor symptom improvements were seen only in those under 60. Gironell A et al; Arch Neur 1999;56:475-480: Presently, only propranolol (Inderal) and primidone (Mysoline) are accepted medications for essential tremor (ET). A controlled trial of propranolol, placebo, and gabapentin (Neurontin) in 16 ET patients showed the latter to be as good as propranolol. Piccini P et al; Ann Neur 1999;45:577-582: They used positron emission tomography (PET) to study subclinical striatal dopaminergic dysfunction in 18 monozygotic (identical) and 16 dizygotic (fraternal) twin pairs, and found concordance only in the first class, 4 of whom eventually developed symptoms of PD. this result suggests that heredity plays a substantial role in sporadic Parkinson's disease. Ouchi Y et al; Ann Neur 1999;45:601-610: They used PET to study dopamine transporter alterations in regions other than the striatum, in early-stage PD patients. Results suggest the origins of mental and behavioral impairment seen in PD. Kruger R et al; Ann Neur 1999;45:611-617: Comparative study of polymorphism (mutation) in the genes for alpha-synuclein and for apolipoprotein E, in 193 German PD patients and 200 healthy controls, showed that those having both mutations were about 13 times more likely to develop PD. Nakao N et al; Ann Neur 1999;45:640-651: Using a mitochondrial toxin to destroy dopaminergic neurons in rats, they found that ablation of the subthalamic nucleus was neuroprotective. CURRENT SCIENCE REVIEWS By Joe Bruman June 1999 Page 4 of 5 Wang M et al; Ann Neur 1999;45:655-658: In a study of 160 sporadic PD patients and controls, they found a mutant allele of the "parkin" gene that seems to be a protective factor against PD. Karsenti D et al; BMJ; 1 May 1999:1179: Zolpidem (Ambien), a soporific that seemed to be effective against PD motor symptoms (CSR JUN 97, CSR AUG 97), was clearly identified as the cause of reversible liver injury in a patient taking it for insomnia. Neystat M et al; Mov Disord 1999;14:417-422: Looking for hereditary factors in PD, they found the gene for alpha-synuclein significantly reduced in the substantia nigra, but not the cortex, of PD patients compared with controls. Brown P, Marsden C; Mov Disord 1999;14:423-429: They used electroencephalography (EEG) in 12 PD patients to study the effect of levodopa upon bradykinesia. Barbiroli B et al; Mov Disord 1999;14:430-435: Using magnetic resonance spectroscopy (MRS) on patients having different movement disorders, they found that levels of certain phosphorus compounds may help to distinguish MSA from PD. Innis R et al; Mov Disord 1999;14:436-442: Single-photon-emission computed tomography (SPECT) mapping of dopamine transporter levels using the marker [1232I]beta-CIT doesn't require prior withdrawal of levodopa or selegiline treatment to be effective. Djaldetti R et al; Mov Disord 1999;14:443-447: The sometimes prominent stooped or bent-forward posture of PD patients doesn't always respond to levodopa treatment. Hagell P, Widner H; Mov Disord 1999;14:448-455: They invented a new clinical rating scale for dyskinesia in PD. Louis E et al; Mov Disord 1999;14:456-461: Family history data on essential tremor (ET) are unreliable, so clinical examination is the only valid determinant. Louis E et al; Mov Disord 1999;14:462-467: As part of a community-based study of ET, they compared the value of various bedside or clinical diagnostic tests. Ceravolo R et al; Mov Disord 1999;14:468-472: Clozapine (Clozaril), an atypical neuroleptic drug, was earlier reported to reduce postural tremor in PD. In a controlled trial on 15 patients having essential tremor (ET) resistant to other drugs, clozapine significantly reduced the symptoms. Benefit persisted in followup as long as 16 months. Merello M et al; Mov Disord 1999;14:491-483: During posteroventral pallidotomy procedure on a patient who had beginning-of-dose motor deterioration, they recorded firing rate of a single GPi cell following a dose of apomorphine. The rate increased and motor symptoms worsened before getting better, suggesting a role of the thalamus in beginning-of-dose effect. CURRENT SCIENCE REVIEWS By Joe Bruman June 1999 Page 5 of 5 Fernandez H et al; Mov Disord 1999;14:484-487: Quetiapine is an atypical antipsychotic having properties like clozapine, except for the dangerous side effect. They found it generally effective in a test on 35 PD patients with levodopa- induced psychosis, but some had trouble switching over from clozapine or olanzapine. -- J. R. 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