CURRENT SCIENCE REVIEWS  By Joe Bruman  February 1999   P.1 of 4

Schierle G et al; Nat Med 1999;5:97-100:
Apoptosis, or programmed cell death, is the natural process by
which an organism gets rid of weak or superfluous cells, but
sometimes it is unwelcome. Authors' rat studies indicated that
only 5%-10% of grafted embryonic cells survive longer than one
week, and that most of the loss is by apoptosis. Certain
modified peptides known as "caspase inhibitors" have been found
in other paradigms to block apoptosis, so they tried one,
Ac-YVAD-cmk (don't ask), on rat fetal cells in vitro, and then
on cells transplanted stereotactically in the substantia nigra
of live rats that had chemically-induced parkinsonism. They
found that the pretreatment significantly improved survival in
vitro, and that it mediated substantial functional recovery in
the parkinsonian rats, corroborated by examination of the brains
after the subjects were sacrificed.

Ekblom J et al; Pharmacol Toxicol; 1998:83:194-199:
Experimenting with cultured rat brain cells subjected to
ischemic insult, they found that pre-treatment with deprenyl
or tolcapone may reduce the resulting stroke damage.

diPierro C et al; J Neurosurg 1999;90:95-100:
They report 62 stereotactic pallidotomies or thalamotomies
guided by MRI imagery of the anterior commissure-posterior
commissure line, claiming results just as good as those guided
by microelectrode recording.

Shaunak S et al; J Neur N'surg Psych 1999;66:79-81:
Serosal (membrane) fibrosis is an occasional adverse effect of
other dopamine agonists, but rarely reported from pergolide
(Permax). They report 3 PD patients on Permax for average 2
years, at dosage from 1mg/day to 3mg/day, who respectively
developed potentially life-threatening retroperitoneal, pleural,
and pericardial fibrosis, that in all cases required surgical
intervention. They advise regular monitoring of Permax users.

Groth C; Lancet, 1998 Review:26:
Although no such infection has been found in about 60 human
recipients of various pig cell transplants, at least one porcine
endogenous retrovirus (PERV) can infect cultured human cells in
vitro, prompting government authorities in the U.S. and UK to
set up various precautionary controls of such transplants.

De Palma G et al; Lancet, 19 December 1998:1986-1987:
In 100 PD patients and 200 controls, they studied genes related
to free radicals and oxidative stress, and history of exposure
to environmental hazards, finding positive correlation in PD of
mutations with such factors as rural living and well water.

Lancet, 19 December 1998:1992 (news item):
Good news: Chocolate may be addictive. Bad news: Its content of
cannabinoid (marijuana-like) substance is way too small to be
a significant cause.






CURRENT SCIENCE REVIEWS  By Joe Bruman  February 1999  P. 2 of 4

Altschuler E, Bonelli R et al; Lancet, 16 January 1999:240-241:
Discussing functional improvement by certain drugs in a patient
with Huntington's Disease, they speculate that lesion of the
globus pallidus as in pallidotomy for PD might also provide
such improvement. They note however that the principal benefit
of pallidotomy for PD, namely reduction of L-dopa-induced
dyskinesia (LID), is unexplained by the current model of basal
ganglia organization.

Gorell J et al; Neur 1999;52:115-119:
There has always been suspicion that the negative correlation
of smoking and PD may be due merely to aversion to smoking in
persons susceptible to PD. Authors put that to rest by study
comparing heavy smokers and light smokers and the time elapsed
after quitting, if applicable. They found a distinct dose-related
effect, showing that smoking is indeed neuroprotective.

Ekesbo A et al; Neur 1999;52:120-125:
It is well-known that levodopa therapy, effective in early
stages of PD, seems to lose that effectiveness in more advanced
stages. By means of PET imagery and standardized levodopa and
apomorphine protocol, authors mapped the effects of apomorphine
on regional levodopa uptake in early-stage and advanced-stage
PD patients (the strong dopaminergic effect of apomorphine
normally inhibits levodopa uptake). They found this inhibition
in early-stage PD but not in advanced stages. The explanation
is that a function which regulates dopamine activity is lost
as the nigrostriatal degeneration of PD progresses.

Averbuch-Heller L et al; Neur 1999;52:185-188:
Square-wave jerks (SWJ) are brief saccades that divert the eye
from its target and return it after about 200 msec, thereby
interfering with activity such as reading. They studied three
advanced-stage PD patients who had received pallidotomies, and
found the frequency of SWJs substantially above normal.

Gottlieb S; BMJ, 12 December 1998:1616:
Postmortem study of 43 various brains from Alzheimer's, PD,
schizophrenic, and normal subjects showed signs of oxidative
stress in Alzheimer's subjects but not in the others.

Miles J; BMJ, 12 December 1998:1658-1659:
Citing a defect rate in one (un-named) maker's implantable
neurostimulators of over 50%, he strongly advocates national
registry in the U.S. and UK.

Wang W et al; Arch Neur 1998;55:1521-1523:
In 44 familial PD patients and 29 with sporadic PD, not of Greek
or Italian ancestry, search for the mutant alpha-synuclein gene
(CSR DEC 96) drew a blank. At least 5 searches of various other
population samples (CSRs JUL 97, MAR 98, MAY 98, JAN 99) were
likewise unsuccessful.

Louis E et al; Arch Neur 1998;55:1553-1559:
They examined 54 subjects diagnosed with essential tremor (ET),
finding mild assymetry to be a fundamental property of ET, with
tremor less severe in the dominant arm.


CURRENT SCIENCE REVIEWS  By Joe Bruman  February 1999  P. 3 of 4

Blanchet P et al; Clin Neuropharm 1998;21:339-343:
A double-blind controlled trial in 4 PD patients of the D-1
agonist Dihydrexidine, given iv at various dosage, showed a
plasma half-life less than 5 minutes and marginal value.

Deuschl G et al; Mov Disord 1998;13S3:2-23: (see CSR DEC 98 P.3)
Proposes tremor classifications: rest, postural, simple kinetic,
and intention (during target-directed movement).

Rothwell J; Mov Disord 1998;13S3:24-28:
Possible oscillating circuits in the CNS that could cause tremor.

Bergman H et al; Mov Disord 1998;13S3:29-34:
Rhesus monkeys given MPTP develop only infrequent short episodes
of high-frequency tremor, whereas vervet monkeys have many
prolonged episodes of low-frequency tremor.

Elble R; Mov Disord 1998;13S3:35-39:
Various animal models of action tremor are needed to define the
apparently universal involvement of the cerebellum and ventral
intermediate nucleus of the thalamus in human tremor disorders.

Hua S et al; Mov Disord 1998;13S3:40-42:
Role of the thalamus and basal ganglia in parkinsonian tremor.

Hallet M; Mov Disord 1998;13S3:43-48:
The normal 8-12 Hz central oscillator may contribute to
physiologic tremor. Essential tremor is easily influenced by
sensory input, while the rest tremor of PD is less affected
by sensory input but more so by transcranial magnetic stimuli.

Vidailhet M et al; Mov Disord 1998;13S3:49-54:
Symptomatic tremors most often arise from lesion in the
cerebello-thalamo-cortical or the dentato-rubro-olivary pathway.
The role of the basal ganglia is poorly understood.

Brin M, Koller W; Mov Disord 1998;13S3:55-63:
Essential tremor is one of the most common movement disorders,
but the epidemiology, genetics, and pathogenesis are unknown.

Boecker H, Brooks D; Mov Disord 1998;13S3:64-72:
Review of functional imaging by MRI and PET, and the insights
into the pathology of tremor that are provided.

Volkmann J; Mov Disord 1998;13S3:73-76:
Review of magnetoencephalography in study of human tremors.

Bain P; Mov Disord 1998;13S3:77-80:
Clinical methods of tremor measurement.

Spicker S et al; Mov Disord 1998;13S3:81-84:
Long-term ambulatory electromyography can distinguish essential
tremor from that of PD.

Pullman S; Mov Disord 1998;13S3:85-89:
A new digitizing tablet records features of a hand-drawn spiral
in 3 dimensions. It is safe, fast, portable, and cheap to use.


CURRENT SCIENCE REVIEWS  By Joe Bruman  February 1999  P. 4 of 4

Wasielewski P et al; Mov Disord 1998;13S3:90-100:
Beta-adrenergic blockers [e.g., propranolol] and primidone
(Mysoline) remain the mainstays of drug treatment for ET, while
carbidopa/levodopa [Sinemet] and anticholinergics are best for
the tremor of PD.

Pogarell O, Oertel W; Mov Disord 1998;13S3:101-102:
Literature review indicates no special improvement in PD tremor
from fetal tissue transplant. However, PD patients whose tremor
is the main symptom normally are not selected for transplant,
so the effect of fetal transplant upon PD rest tremor is unknown.

Speelman J et al; Mov Disord 1998;13S3:1903-106:
Review of thalamotomy for tremor. Chronic thalamic stimulation
seems promising, but cost-effectiveness remains to be proven.

Lozano A et al; Mov Disord 1998;13S3:107-110:
Microelectrode-guided pallidotomy produces striking improvement
in off-period contralateral tremor of PD. The benefit has
persisted 2 years or more, despite reduction of medication dose
and progression of the disease.

Rodriguez M et al; Mov Disord 1998;13S3:111-118:
Following evidence that the subthalamic nucleus in MPTP monkeys
was a source of tremor, they implanted stimulators in that
region of 12 PD patients and ablated it in 7 others. In all
cases, tremor was significantly improved or wholly suppresed.

Benabid A et al; Mov Disord 1998;13S3:119-125:
Reviews 8 years' experience with deep brain stimulation (DBS) of
the thalamic ventral intermediate nucleus (Vim), successful in
a variety of patients and configurations. PD tremor was
suppressed for up to 11 years, but ET benefit declined with time
in about a third of recipients. Other dyskinesias were much less
influenced. More recently, DBS of the subthalamic nucleus (STN)
has had spectacular success on akinesia and rigidity. DBS of the
globus pallidus (GPi) has effects similar to pallidotomy, in
suppressing dyskinesia.

Tanner C et al; JAMA, 27 Jan 1999:341-346:
In the first big test of the heredity factor in PD, they used VA
records to find and screen 19842 male twins, finding 268 with
parkinsonism. Concordance data show some genetic influence when
disease appears before age 50, but none in cases of later onset.

Cummings J; JAMA, 27 Jan 1999:376-378:
Possibly inspired by recent publicity about celebrities with PD,
a pretty good tutorial on recent developments in the knowledge
and treatment of PD.

--
J. R. Bruman   (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013