 |
 |
All you wanted to know about dyskinesia, and then some, probably is in Annals Of Neurology;2000:Volume 47:Supplement 1:S1-S203, which appears in print this month. About 60 prominent researchers met in Bermuda on 20-22 November 1998, to summarize their current work in 22. All are cited, with abstracts available, in PubMed. But the gains in knowledge in the mere 18 months since then make some of the presented ideas and theories seem almost quaint. For my own reference files, I've done reviews like those in the monthly Current Science Reviews; but because of the number, they are collected here as a separate document and omitted from the CSR. BTW, I see in my files a previous document on dyskinesia, about 3 pages including several reviews of earlier published articles, dated August 1999, but I can't remember if I posted it in the PIE forum or not. If anyone wants it, ask offlist. The Bermuda reviews (3 pages) follow: Olanow C et al;Ann Neur 2000;47S1:S1: "Foreword" Fahn S;Ann Neur 2000;47S1:S2-S11: "The Spectrum of Levodopa-Induced Dyskinesias" Chorea and dystonia often are intermixed, occurring mostly soon after a dose of levodopa, when brain concentration of levodopa and dopamine is highest; thus called peak-dose dyskinesias. Sealfon S;Ann Neur 2000;47S1:S12-S21: "Dopamine Receptors and Locomotor Responses: Molecular Aspects" Response to drugs acting upon dopamine receptors depends on the type of receptor, but drugs having highly specific targets aren't available, so workers resort to a molecular genetic approach. Obeso J et al;Ann Neur 2000;47S1:S22-S34: "Pathophysiology of Levodopa-Induced Dyskinesias in Parkinson's Disease: Problems With the Current Model" The current model for organization of the basal ganglia explains fairly well the motor features of PD, but not the differences in symptoms and responses to treatment between different patients. A new model should include the recent suggestion that LID results from pulsatile stimulation of dopamine receptors, which disrupts firing pattern of downstream neurons. Filion M;Ann Neur 2000;47S1:S35-S41: "Physiologic Basis of Dyskinesia" Suggests improved basal ganglia model to include important inputs from cortex and thalamus, and that dyskinesia may result from imbalance between them, i.e., selection and attention. Gerfen C;Ann Neur 2000;47S1:S42-S52: "Dopamine-Mediated Gene Regulation In Models Of Parkinson's Disease" When dopamine in the brain is depleted by PD, striatal D1 neurons become supersensitive to dopamine agonists. Gene expression is a useful tool to study this and other effects. Dyskinesia-Bermuda (p. 2) Canales J, Graybiel A;Ann Neur 2000;47S1:S53-S59: "Patterns of Gene Expression and Behavior Induced by Chronic Dopamine Treatments" Chronic dopamine treatment causes persistent changes in gene regulation. Calabresi P et al;Ann Neur 2000;47S1:S60-S69: "Levodopa-Induced Dyskinesia: A Pathological Form of Striatal Synaptic Plasticity?" Could be. Calon F et al;Ann Neur 2000;47S1:S70-S78: "Molecular Basis of Levodopa-Induced Dyskinesias" Levodopa-induced dyskinesias may be a form of pathological learning which results from deficient gating by dopamine of glutamatergic inputs to the striatum. Langston J et al;Ann Neur 2000;47S1:S79-S89: "Investigating Levodopa-Induced Dyskinesia in the Parkinsonian Primate" Two-thirds of PD patients given levodopa develop treatment- related motor complications within 6 years, that usually become a dose-limiting factor. Jenner P;Ann Neur 2000;47S1:S90-S104: "Factors Influencing the Onset and Persistence of Dyskinesia in MPTP-Treated Primates" Intermittent periodic dosage of fast-acting agonists is more likely to cause dyskinesia than treatment having longer-lasting effect of more continuous receptor stimulation. Brotchie J;Ann Neur 2000;47S1:S105-S114: "The Neural Mechanisms Underlying Levodopa-Induced Dyskinesia in Parkinson's Disease" LID may be due to abnormalities in basal ganglia output, either the average firing rate or the patterns of cell-cell communication within subregions of the basal ganglia. Hirsch E;Ann Neur 2000;47S1:S115-S121: "Nigrostriatal System Plasticity in Parkinson's Disease: Effect of Dopaminergic Denervation and Treatment" Reviews data suggesting that dopaminergic denervation and treatment induce profound changes in the nigrostriatal system. Chase T, Oh J;Ann Neur 2000;47S1:S122-S130: "Striatal Mechanisms and Pathogenesis of Parkinsonian Signs and Motor Complications" Evidence suggests that intermittent stimulation of dopamiergic receptors indirectly sensitizes NMDA receptors to glutamtergic input from the cortex. Dyskinesia-Bermuda (p.3) Vitek J, Giroux M;Ann Neur 2000;47S1:S131-S140: "Physiology of Hypokinetic and Hyperkinetic Movement Disorders: Model for Dyskinesia" Postulates that dyskinesias result from combination of reduced mean discharge rate, altered patterns and increased synchronism of neurons in the globus pallidus internus. Lozano A et al;Ann Neur 2000;47S1:S141-S146: "Neuronal Recordings in Parkinson's Disease Patients with Dyskinesias Induced by Apomorphine" Recordings during GPi or STN surgery on 17 advanced-PD patients suggest that drug-induced dyskinesias result from a large decrease in GPi firing. Hallett M;Ann Neur 2000;47S1:S147-S153: "Clinical Physiology of Dopa Dyskinesia" The blink rate is reduced in PD but increased with dopamine treatment, and more so in patients having levodopa-induced dyskinesias. Brooks D et al;Ann Neur 2000;47S1:S154-S159: "Neuroimaging of Dyskinesia" PET studies of patients with and without dyskinesias suggest that dyskinesias result from overactivity of basal-ganglia frontal projections. Nutt J;Ann Neur 2000;47S1:S160-S166: "Clinical Pharmacology of Levodopa-Induced Dyskinesia" Dyskinesia represents sensitization to levodopa after chronic repetitive use. Once developed, the duration of LID, but not its severity, is dose-responsive. Olanow C, Obeso J;Ann Neur 2000,47S1:S167-S178: "Preventing Levodopa-Induced Dyskinesias" Various strategies of drug treatment to avoid pulsatile stimulation of dopamine receptors. Rascol O;Ann Neur 2000;47S1;S179-S188: "Medical Treatment of Levodopa-Induced Dyskinesias" Reviews possibilities of DBS, embryonic transplants, or non- dopaminergic agents such as amantadine. Benabid A et al;Ann Neur 2000;47S1:S189-S192: "Dyskinesias and the Subthalamic Nucleus" Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves all types of LID, particularly off-period dystonia. Lang A;Ann Neur 2000;47S1:S193-S202: "Surgery for Levodopa-Induced Dyskinesias" Reviews effectiveness of pallidotomy, great promise of STN DBS, dubious benefit of transplants, and poor prospects of gamma- knife surgery. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013