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