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CURRENT SCIENCE REVIEWS  By Joe Bruman  September 1999  P. 1 of 5

Caparros-Lefebvre D et al; Lancet, 24 July 1999:281-286:
They associate high incidence of levodopa-resistant atypical
parkinsonism and progressive supranuclear palsy (PSP) on the
tropical island of Guadeloupe, French West Indies, with neuro-
toxic alkaloids in herbal teas and fruits (e.g., custard apple)
from tropical plants of the Annonaceae family.

Lancet, 24 July 1999:263 (editorial):
Comment on the item above. Mention of the pawpaw, native to
North America, is confusing, might be a botanical error.

Mathias C, Kimber J; Lancet, 24 July 1999:339-340:
Continued debate (CSR AUG 97, JUN 99) over usefulness of
clonidine as a diagnostic test agent to identify PD.

Vale I; Lancet, 7 Aug 1999:511:
Comment on previous report (CSR JUL 99) that the glutamate
N-Methyl-D-Aspartate (NMDA) antagonist riluzole (Rilutek)
relieves levodopa-induced dyskinesia (LID) in some but not
all PD cases. In 1971 the weaker NMDA antagonist amantadine
(Symmetrel) was of most help in the 10%-25% of PD patients
whose memory and abstract thinking were also impaired.

Naumann R et al; Lancet, 14 Aug 1999:566 and
Benedetti F et al; Lancet, 14 Aug 1999:567:
Olanzapine (Zyprexa) was developed to replace the atypical
antipsychotic drug clozapine (Clozaril) but without the
latter's risk of agranulocytosis (white cell destruction) that
requires periodic blood testing. But in 2 patients who had
switched from clozapine because of that disorder, olanzapine
apparently caused a relapse.

Larner A, Farmer S; BMJ, 7 Aug 1999:362-366:
Tutorial review for nonspecialists on recent advances in
neurology, including a page about PD.

Hanakawa T et al; Brain 1999;122:1271-1282:
PET study of PD patients on a treadmill revealed abnormal
distribution of the brain activity involved in walking.

Ebersbach G et al; Brain 1999;122:1349-1355:
They compared physical parameters of walking gait in subjects
having different neurological disorders, including PD.

Saper C; Brain 1999;122:1401-1402 (editorial):
Comment on the extraordinary selectivity of degenerate areas in
PD, and two papers (below) addressing that problem.

Damier P et al; Brain 1999;122:1421-1436 and:
Damier P et al; Brain 1999;122:1437-1448:
They studied postmortem brain samples from 7 PD patients for
distribution of a stainable protein (calbindinD28K) that defines
a branched three-dimensional structure within the substantia
nigra. Then they looked within that calbindin-poor structure for
the distribution of dopamine neurons lost in PD. This protocol
for the first time shows the spatial progression of PD within the
substantia nigra, and perhaps a clue about what makes it happen.


CURRENT SCIENCE REVIEWS  By Joe Bruman  September 1999  P. 2 of 5

Piggott M et al; Brain 1999;122:1449-1468:
Meticulous study of postmortem brain samples from 25 dementia-
with-Lewy body (DLB) patients, 14 with PD, 17 with AD, and 20
non-diseased controls shows differences in distribution of
dopaminergic receptors as affected by the various diseases, and
may help to explain differences in their signs and symptoms.

Orimo S et al; J Neur N'surg Psych 1999;67:189-194:
Using a scan technique called I-MIBG myocardial scintigraphy,
they compared the proportion of cardiac sympathetic nerve
dysfunction in PD against other neurodegenerative diseases.

Ho A et al; J Neur N'surg Psych 1999;67:199-202:
The voice loudness of PD patients is diminished overall, but
its variation with distance to an interlocutor is normal.

Korczyn A et al; Neur 1999;53:364-370:
In a 3-year randomized trial of ropinirole (Requip) and
bromocriptine (Parlodel) in early-stage PD patients, both were
effective against motor symptoms but ropinirole was better. Of
335 subjects in all, 1/3 withdrew because of adverse effects.

Minagar A  et al; Neur 1999;53:453-454:
A patient at a moderate stage of PD applied a skin patch of
the anticholinergic sedative scopolamine, as protection against
seasickness on a planned cruise. She developed psychotic
hallucinations and delusions, that abated when the patch was
removed. Psychosis from scopolamine is not unknown, but perhaps
patients on PD medication are more susceptible.

Zappia M et al; Neur 1999;53:557-560:
The PDR article doesn't mention it, but levodopa (as in Sinemet)
has a long-duration response (LDR), that takes a few weeks to
establish, as well as the familiar response to individual doses.
The LDR develops sooner when dose intervals are shorter.

Kumar R et al; Neur 1999;53:561-566:
They compared bilateral against unilateral deep-brain stimulation
(DBS) of the subthalamic nucleus (STN) in 10 consecutive
recipients. Overall improvement was better with bilateral DBS.
STN DBS is as effective as DBS of the ventral intermediate
nucleus (Vim), or thalamotomy, against the tremor of PD.

Vieregge P et al; Neur 1999;53:566-572:
In 8-year followup of PD in 9 pairs of identical twins and 12
fraternal pairs, no additional members had developed motor
symptoms of PD, although some showed minor cognitive deficit.
Relatively similar concordance in the two classes suggests that
genetics aren't a major factor in motor symptoms of PD.

Barone P et al; Neur 1999;53:573-579:
A 3-month comparison of 53 early-PD patients given pergolide
(Permax) and 52 given placebo showed that pergolide monotherapy
may be effective and well-tolerated in early-stage PD.





CURRENT SCIENCE REVIEWS  By Joe Bruman  September 1999  P. 3 of 5

Defer G et al; Mov Disord 1999;14:572-584:
The Core Assessment Program for Surgical Intervention Therapies
in Parkinson's Disease (CAPSIT-PD) now covers pallidotomy and
DBS as well as neural transplants. A registry is proposed for
European PD patients receiving functional neurosurgery.

Stebbins G et al; Mov Disord 1999;14:585-589:
A 200-patient study confirms stability and internal consistency
of the motor section of the Unified Parkinson's Disease Rating
Scale (UPDRS) in both on- and off-state examinations.

Joost O et al; Mov Disord 1999;14:590-595:
Although mutations of the CYP2D6 gene have been suspected risk
factors for PD, a study of 7 different mutations in 109 PD
patients and 110 controls found no difference in frequency, nor
was there any link to family history, onset age, or environment.

Errea J et al; Mov Disord 1999;14:506-604:
A survey of hospital records and doctors' questionnaire response
showed PD prevalence in Lower Aragon, Spain about the same as
in other European regions.

Reardon K et al; Mov Disord 1999;14:605-611:
In a study of 34 PD patients for 6 years after start of drug
treatment, 18 developed dyskinesia after mean 15 months, 14
developed motor fluctuations after mean 25 months. Patients
with fluctuations had better response to levodopa, and less
disability in cranial and trunk muscles and gait.

Ebersbach G et al; Mov Disord 1999;14:619-625:
A study by means of a mechanical device of gait control in 22
early-PD patients and 22 controls, where subjects had to follow
changing frequency of a metronome, showed both groups having
irregular stride length, but only the PD group was less able to
follow the changing cadence.

Hardman C, Halliday G; Mov Disord 1999;14:626-633:
In (postmortem) study of tissue from patients with progressive
supranuclear palsy (PSP), PD, and controls, the external segment
of the globus pallidus had degenerated in PSP but not in PD.

Defebvre L et al; Mov Disord 1999;14:634-641:
A spatiotemporal study (using scalp electrodes) of event-related
desynchronization (ERD) in 10 PD or PSP patients and 10 controls
shows that motor programming is more affected in PSP than in PD.

Ondo W et al; Mov Disord 1999;14:664-668:
In tests on 10 advanced-PD patients of a novel apomorphine
preparation as sublingual tablets, motor symptoms improved,
levodopa requirement decreased, and "on" times increased.

Michel P et al; Clin Neuropharm 1999;22:137-150:
Review of apoptosis, its pharmacologic aspects, and its role
in neurodegenerative disease.

Shetty N et al; Clin Neuropharm 1999;22:207-212:
Literature study showed a placebo effect in PD patients, but it
wasn't correlated with any of several demographic factors.

CURRENT SCIENCE REVIEWS  By Joe Bruman  September 1999  P. 4 of 5

Bagheri H et al; Clin Neuropharm 1999;22:213-215:
PD patients often complain of excess salivation, but study of 83
patients and 65 controls showed it less, not more, than normal.

de la Fuente-Fernandez R; Clin Neuropharm 1999;22:216-219:
Patients whose dystonia responds to levodopa may, after chronic
treatment, develop dyskinesia. Likewise, chronic apomorphine
treatment may also result in dyskinesia.

Parkinson Study Group; Clin Neuropharm 1999;22:220-225:
The N-Methyl-D-Aspartate (NMDA) glutamate antagonist remacemide,
hoped to be neuroprotective, got an open-label test on 18 early-
stage PD patients. Its delay of levodopa absorption doesn't
preclude use of the two drugs together.

de la Fuente-Fernandez R et al; Clin Neuropharm 1999;22:226-230:
In a study of the apolipoprotein E epsilon 4 allele in 105 PD
patients, 17 who had that mutant gene were 3 times as likely as
the 88 who didn't have it to get drug-induced hallucinations.

Bourgoin S et al; Clin Neuropharm 1999;22:231-238:
Trying to learn how deep-brain stimulation (DBS) of the thalamus
ventral intermediate nucleus (VIM) relieves tremor of PD or
essential tremor, authors found opposing changes in levels of
dopamine metabolites and met-enkephalin in the cerebrospinal
fluid after 30 minutes of DBS.

Louis E; Arch Neur 1999;56:807-808:
Literature review, and musing on the possibility of gabapentin
(Neurontin), a chemical analog of the neurotransmitter gamma-
amino-butyric acid (GABA), as treatment for essential tremor
(ET). Past trial results (CSR JUN 99) have been mixed.

Kramer P et al; Ann Neur 1999;46:176-182:
Rapid-onset dystonia-parkinsonism (RDP), an autosomal-dominant
disorder characterized by sudden early onset and little or no
response to levodopa, is now linked to chromosome 19q13.

Ardouin C et al; Ann Neur 1999;46:217-223:
Thorough testing in 6-month followup of 62 consecutive PD
patients, who received bilateral deep-brain stimulation (DBS)
implants either in the internal globus pallidus or in the
subthalamic nucleus, showed no cognitive decline.

Pahapill P et al; Ann Neur 1999;46:249-252:
Using the opportunity of 6 essential tremor (ET) patients
receiving either thalamotomy or deep-brain stimulation (DBS)
implants, they tested the effect on tremor of minute amounts
of the gamma-aminobutyric acid (GABA) agonist muscimol, injected
into the ventral intermediate nucleus of the thalamus. Favorable
results suggest possible future use of muscimol as ET therapy.

Honey C et al; J Neurosurg 1999;91:198-201:
To test numerous anecdotal reports, a followup study of 21 PD
recipients showed that unilateral pallidotomy significantly
reduces pain attributable to PD.



CURRENT SCIENCE REVIEWS  By Joe Bruman  September 1999  P. 5 of 5

Lonser R et al; J Neurosurg 1999;91:294-302:
Although high-frequency electrical heating is the nearly
universal means of choice to destroy tissue in stereotactic
neurosurgery, it has some risks, and chemical ablation offers an
alternative. Authors injected a neurotoxin into the globus
pallidus internus of MPTP monkeys, depending upon convection to
spread it throughout that structure while sparing adjacent
tissue, and parkinsonian symptoms were dramatically improved.

Ghika J et al; J Neurosurg 1999;91:313-321:
While two unilateral pallidotomies separated by an interim of
several months are generally successful, doing both at once is
risky. Followup of 4 PD patients receiving contemporaneous
bilateral posteroventral pallidotomy revealed numerous and
serious motor, visual, cognitive and psychic problems.

Vidailhet M et al; Arch Neur 1999;56:982-989:
Patients following stroke may have dystonia related to loss
of dopaminergic neurons, and levodopa-responsive tremor. MRI and
PET imaging of 7 such patients revealed the distribution of
neuron loss.

Andres O et al; Arch Neur 1999;56:997-1003:
PET study during programmed movement tasks of 8 PD patient
recipients of deep-brain stimulation (DBS) of the subthalamic
nucleus (STN) demonstrated that DBS of the STN reduces movement-
related impairment of frontal motor association areas and
inappropriate motor cortex resting activity in PD.
--
J. R. Bruman   (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013