CURRENT SCIENCE REVIEWS  By Joe Bruman  December 1998  P. 1 of 3

Menegon A et al; Lancet, 24 Oct 1998:1344-1346:
In a study of 95 PD patients and 95 healthy controls, they found
PD strongly associated with the combination of factors implying
pesticide exposure and the genetic mutation of glutathione
S-transferase, an enzyme that normally destroys such neurotoxins.
This is the first plausible linkage of environment and heredity
as an origin of PD, explaining why some people are more
susceptible than others to the parkinsonism-inducing effects of
pesticides.

Golbe L; Lancet, 24 Oct 1998:1328-1329:
Besides commenting on the breakthrough discovery cited above, he
discusses the recent finding that a genetic mutation of alpha-
synuclein with a modified molecular "folding" pattern may
explain the clumping and formation of Lewy bodies in various
neurodegenerative diseases.

Collignon P et al; Lancet, 24 Oct 1998:1390-1391:
Debate over safety of pig cell transplants continues. Critics
are worried that some as yet undiscovered retrovirus may gain
a foothold in the human species, with disastrous results. Calmer
voices reply that careful search so far has found no such
interspecies infection, but concede that with the potential for
tens of thousands of transplants per year [for many conditions
besides PD], extreme caution is advisable.

Lancet, 7 Nov 1998:1529 (news item):
Comment on the neurogeneration discovery cited below.

Lancet, 7 Nov 1998:1529 (news item):
Comment on the alpha-synuclein report cited below. In a certain
familial variant of PD, the alpha-synuclein is a mutant form
which tends to clump into fibrils, which may have a role in PD.

BMJ, 7 Nov 1998:1272 (editorial):
More comment on the neurogeneration discovery cited below.

BMJ, 7 Nov 1998;1290 (editorial):
When the epidemic of bovine spongiform encephalitis (BSE) began
in England about 10 years ago, it leaped the species barrier to
cause a variant of Creutzfeldt-Jakob disease (CJD), with initial
symptoms easily mistaken for PD, in a few humans. CJD is quite
rare, but like BSE, almost invariably fatal, and the British
government didn't handle the episode very well.

Lancet, 7 Nov 1998:1529:
Brownell A et al; Nat Med 1998;4:1308-1312:
They gradually induced selective loss by oxidative stress of
nigrostriatal dopamine neurons in 5 macaque monkeys, through
repeated injection of the mitochondrial complex 1 inhibitor MPTP
during a period of 9 to 19 months. Then by a combination of
positron emission tomography (PET) and magnetic resonance
spectroscopy (MRS) imaging, they studied the progression and
persistence of regional changes in distribution of functional
brain neurochemicals, to better understand the mechanisms of PD.




CURRENT SCIENCE REVIEWS  By Joe Bruman  December 1998  P. 2 of 3

Eriksson P et al; Nat Med 1998;4:1313-1317:
Conventional wisdom, that adult mammal brain tissue cannot
regenerate, has been crumbling for the past few years (see,
for example, CSR JUN 98) as more highly developed species have
been found to do so. Here, authors demonstrate for the first
time, neurogenesis in the adult human brain.

Conway K et al; Nat Med 1998;4:1318-1320:
No one is sure if Lewy bodies are a cause, or effect, of PD, but
they do contain alpha-synuclein, and two mutant genes for alpha-
synuclein have been linked to an early-onset (familial) variant
of PD. So the authors studied folding and aggregation of the
mutant varieties in vitro, finding that they do indeed tend to
form fibrils and to clump into Lewy-body-like spheres.

Ghika J  et al; J Neurosurg 1998;89:713-718:
Six advanced PD patients with intractable fluctuations received
bilateral contemporaneous pallidal deep-brain-stimulation (DBS)
implants, and were followed for up to two years. Major
improvements in most motor and ADL scores persisted for about a
year, then began to diminish.

Pietz K et al; J Neur N'surg Psych 1998;65:709-716:
As an alternative to levodopa, they gave either injection or
continuous infusion of apomorphine to a total of 49 PD patients
in the fluctuating stage, over a period of up to 5 years. Both
groups had significant and persistent improvement of symptoms,
although psychiatric side effects and local inflammation of the
infusion site were common.

Graham J et al; J Neur N'surg Psych 1998;65:774-777:
In a trial on five PD patients having hallucinations due to
dopaminergic medications, they found that olanzapine controlled
the hallucinations but unacceptably worsened motor disability in
two of the five subjects.

Chan D et al; J Neur N'surg Psych 1998;65:781-784:
They surveyed 215 PD patients and 313 controls from a Chinese
population in Hong Kong, both for environmental factors and for
mutants of the CYP2D6 gene, which may impair resistance to
neurotoxins and are common in caucasians. They found several
environmental factors, for example that regular tea drinking is
protective, but the CYP2D6 mutations are so rare in Chinese
people that they are unlikely to be a genetic factor in PD for
that population.

Rinne U et al; Neur 1998;51:1309-1314:
They did a 6-month controlled study of the COMT inhibitor
entacapone (Comtan) in 171 PD patients at the fluctuation
stage, finding prolonged benefit. Entacapone acts to conserve
levodopa outside the brain, thereby allowing a greater fraction
of a given therapeutic dose to reach the brain.

Valldeoriola F et al; Neur 1998;51:1315-1320:
The startle reflex, an involuntary twitch in response to a
sudden noise, was timed in a cohort containing groups with
idiopathic PD, progressive supranuclear palsy, multisystem
atrophy, and normal controls. It is enhanced in PD and MSA
but not in PSP.
CURRENT SCIENCE REVIEWS  By Joe Bruman  December 1998  P. 3 of 3

Kunig G et al; Ann Neur 1998;44:758-762:
The used positron-emission tomography (PET) imaging to map the
activity of dopamine in 14 patients with dopa-responsive
dystonia (DRD), 16 levodopa-treated PD patients, and 26 healthy
controls. DRD includes some symptoms of PD, but is hereditary,
and onset often occurs in the first decade of life. Differences
in uptake distribution may help to understand both diseases.

Hammerstad J; Ann Neur 1998;44:843-844 (book review):
For $125, those interested may obtain a 286-page, hard-cover
summary of surgical treatment of PD, from a 1997 symposium.

Brotchie J; Mov Disord 1998;13:871-876:
Proposes several drugs that might help levodopa-induced
dyskinesia by manipulating non-dopaminergic systems.

Schrag A et al; Mov Disord 1998;13:885-894:
A long-term study of 10 juvenile (onset age < 21) and 139 young-
onset (21 < onset age < 40) PD patients. Half the juvenile group
had close relatives with PD. Mortality rate in both groups was
higher than in the normal population.

Tandberg E et al; Mov Disord 1998;13:895-899:
They surveyed 245 PD patients and two 100-member control groups,
and found that nearly 2/3 of the PD group reported sleep
disorders. Sleep disorders strongly correlated with depression.

O'Sullivan J et al; Mov Disord 1998;13:900-906:
Careful clinical measurement of gait parameters is a reliable
alternative to conventional PD rating scales for assessing the
response to levodopa.

Krack P et al; Mov Disord 1998;13:907-914:
Electrical stimulation of the subthalamic nucleus in 27
consecutive PD patients was effective against even severe high-
amplitude tremor, and offers an interesting alternative to
thalamotomy or pallidotomy.

Mov Disord 1998;13:Supp 3:1-125:
Reviews of various aspects of tremor, presented at a
workshop session of the 5th International Congress of
Parkinson's Disease and Movement Disorders, October 1998.

Science News, 28 Nov 1998:344 (news item):
Surgeons exploring a 65-year-old PD patient's brain with a
DBS electrode stimulated the substantia nigra and were startled
when she became severely depressed, returning to normal when
the stimulus was turned off. They repeated the stimulus to
confirm that it indeed caused instant and reversible depression.
--
J. R. Bruman   (818) 789-3694
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