CURRENT SCIENCE REVIEWS   By Joe Bruman    August 1997   p. 1 of 4

Polymeropoulos M et al; Science, 27 Jun 97:2045:
Announcing the identification of a mutant gene that encodes
alpha-synuclein, in members of several family clusters of PD cases.
It created a wave of optimistic comment as a major step in the path
to understanding and possibly cure for PD.

Science News; 28 Jun 97:396 (news item):
By diligent analysis of genetic makeup in several large families
having multiple members with PD, workers found a mutant gene
associated with at least that variant of the disease. The gene*
encodes the protein alpha-synuclein, thought to be one of 50 or so
neurotransmitters in the brain, whose function is still unknown.
*Not entirely clear whether they mean normal or mutant. The latest
flyer from NPF seems to imply that the normal gene encodes just
plain synuclein, while the mutant encodes alpha-synuclein. Exactly
why the latter may trigger PD and its normal relative doesn't
should be interesting, since nobody knows much about either one.

Kordower J et al; Exp Neur 1997;144:41-46:
Fifteen years of experience with tissue transplants for PD allow
comparison of adrenal medulla and fetal mesencephalon as sources,
mainly by means of postmortem study. Adrenal cells survive poorly,
although they do induce sprouting of host neurons. Fetal cells,
however, thrive and produce major restoration of striatal tissue
lost in PD.

Mytilineou C et al; J Neurochem 1997;68:33-39:
Lab study of cultured fetal cells showed that selegiline (Deprenyl)
prevents cell death independently of its MAO-B inhibition; notably
death otherwise due to NMDA, a normally present glutamate known to
be neurotoxic.

Mytilineou C et al; J Neurochem 1997;68:434-436:
Following the work above, they tested desmethylselegiline (DMS), a
metabolite of selegiline found in the gastrointestinal tract,
showing that it protects neurons against NMDA even better than
selegiline. Therefore they think DMS is the active agent in
neuroprotection by selegiline.

Kimber J et al; Lancet, 28 Jun 97:1877-1881:
As a side effect, the antihypertensive clonidine causes increase
of growth hormone in healthy persons and PD patients, but not in
those with MSA, often confused with PD. Thus a clonidine test may
be a useful diagnostic tool.

Lavoisy J, Marsac J; Lancet, 5 Jul 97:74:
They dispute the value of zolpidem in PD (CSR Jun 97) for a rather
weak reason: a soporific, it may increase risk to PWP of falling.

Kopyov O et al; J Neurosurg 1997;87:52-59:
Reports success of 29 microelectrode-guided pallidotomies done by
the Good Samaritan Hospital (L.A.) team over the course of a year.

Parkinson Study Group; JAMA, 9 Jul 97:125-130:
In a 1994 randomized dose-ranging study of 264 early-PD patients
not on levodopa or on other DA agonists, Pramipexole was found
to be safe and effective monotherapy.


CURRENT SCIENCE REVIEWS    by Joe Bruman   August 1997  p 2 of 4

Jost W et al; Mov Disord 1997;12:423-425:
Cisapride (Propulsid) usually given for gastric reflux, works by
stimulating gut muscles, so they tried it for constipation in PD.
At first it reduced colon transit time from 5 days to 3, but after
a year the benefit had virtually disappeared.

Lipinski J et al; Mov Disord 1997:12:402-407:
They tried the dopamine agonist pergolide (Permax) on 19 young
people with Gilles de Tourette syndrome, finding marked benefit,
especially in those also having restless leg syndrome.

Hubble J et al; Mov Disord 1997;12:337-341:
Study of deep-brain stimulation in 10 patients with PD and 19 with
essential tremor showed about equal reduction of tremor and of
self-rated disability, with best results against postural tremor.

Johnston B et al; Mov Disord 1997;12:322-327:
They compared swallowing impairment in 7 PD patients and 7 with
PSP, finding it about equal, except in the oral phase where it was
more severe in the PSP patients.

Abbruzzese G et al; Mov Disord 1997;12:315-321:
They compared the response to transcranial magnetic stimulation
of sensory and motor evoked potential, in 15 patients with
multiple system atrophy, 20 PD patients, and 20 healthy controls,
finding no differences of diagnostic value.

Muller V et al; Mov Disord 1997;12:306-314:
They gave behavioral treatment of postural and gait problems to
l5 PD patients and nonspecific psychological treatment to 14
others, finding the behavioral treatment measurably helpful.

Giladi N et al; Mov Disord 1997;12:302-305:
They found the "freezing" phenomenon in 158 out of 347 patients
with parkinsonism other than idiopathic PD. It was most common in
those with neurodegenerative diseases and absent in drug-induced
parkinsonism. It was significantly associated with dementia,
incontinence, and tachyphemia*.

Andreu N et al; Mov Disord 1997;12:293-296:
A dose-ranging study in 4 groups of 6 PD patients established that
20 mg/week of selegiline is the minimum needed to induce maximal
(>95%) and lasting inhibition of platelet MAO-B.

Nutt J et al; Mov Disord 1997;12:285-292:
Motor fluctuations, evaluated by tapping tests in 11 PD patients,
continued even though they were on constant-rate levodopa infusion,
with no ready explanation.

Gomez Arwvalo G et al; Mov Disord 1997;12:277-284:
Retrospective analysis and acute levodopa challenge in 34 early-
onset PD patients and 34 late-onset revealed differences in mode
of onset and degree of initial improvement, and a stronger,
shorter response to the levodopa challenge by the early-onset
group.



*Gotcha! "Tachyphemia" = pathologically rapid speech
CURRENT SCIENCE REVIEWS   by Joe Bruman    August  1997   p 3 of 4

Wenning G et al; Ann Neur 1997;42:95-107:
They tracked 6 PD recipients of fetal tissue grafts for between 10
and 72 months. PET scans at 8 to 12 months revealed increased
dopaminergic activity in the putamen but not a secondary site, the
caudate. Four of the six showed significant clinical improvement,
the other 2 only modest. One was able to drop levodopa at 32 months
and still showed normal activity in the putamen at 72 months.

Samuel M et al; Brain 1997;120:963-976:
A PET study of PD patients and controls during assigned one-hand
and two-hand movement tasks showed that in PD there is a compen-
satory switch from striato-mesial frontal premotor circuits to
parietal-lateral circuits during complex finger movement.

Rickards C, Cody F; Brain 1997;120:997-990:
Electromyography during standardized arm movement tasks in 29 PD
patients and 23 controls showed that proprioceptive (internal
origin) guidance of movement is impaired in PD.

Science News, 19 Jul 97:36 (news item):
Johns Hopkins researchers report survival in vitro of human stem
cells, the embryonic cells which have the ability to diversify into
any of the numerous types of cells, including neurons, in the
final developed organism. Discovery of how to cultivate the cells,
which now are obtained from fetuses, would offer hope of a cure for
many degenerative diseases, including PD.

Stern M et al; Neur 1997; 49:Supp.1:S1-S62:
Comprehensive review of current strategy and controversy in drug
treatment of PD. Issues still moot are: neurotoxicity of levodopa;
oxidative stress as a root of PD; slowing of progression by
selegiline; delayed onset of motor fluctuation and diskinesias by
continued dopamine receptor stimulation; and differing clinical
effects of various dopamine agonists. Pallidotomy mentioned only
as a "last resort" in drug-resistant dyskinesia.

Lieberman A et al; Neur 1997;49:162-168:
Reporting the large-scale multicenter trial of pramipexole, in
181 PD patients and 179 controls, finding that pramipexole is
safe, effective, and tolerable in both early and late stages of
PD. They also noted that it allays a distinctive PD mood disorder
that includes anxiety, apathy, attention span, and anhedonia.

Sathian K et al; Neur 1997;49:168-177:
In controlled trials, PD impaired tactile spatial acuity
(discrimination of a standard grating roughness and orientation).

Pahwa R. et al; Neur 1997;49:249-253:
In 3-month followup of 5 PD recipients of DBS implants, they
conclude that chronic stimulation of the globus pallidus is safe
and effective againist motor fluctuations and dyskinesias. (There
appears to be some confusion about "high" frequency of the
stimulation pulses; I've heard some lecturers talk of 100 KHz,
whereas the frequency of choice is actually about 100 Hz, near the
lower limit of the audible range.)

Logroscino G et al; Neur 1997;49:310-311:
Debate between conductors of two different surveys, about whether
the increased appetite observed in PD is a cause or effect.
CURRENT SCIENCE REVIEWS   By Joe Bruman   August 1997   p. 4 of 4

Fink D, Glorioso j; Nat Med 1997;3:357-359
Suggests that herpes simplex virus may be "engineered" as a gene
transfer vector for brain disorders because of its unique affinity
for neurons.

Kennedy G; Brain 1997;120:1245-1259:
Review of potential for gene transfer therapy of neurological
disorders. Herpes simplex virus is a favored transmission vector
because it readily infects neurons.

Nagaratnam N, Kalasabail G: J Neurol Sci 1997;149(2):195-196:
They report an elderly patient with long-standing essential tremor,
who after a stroke in one side of the pons, found the tremor gone
on the opposite side, yielding a clue to the neural pathway
involved in that disorder. (This is analogous to the incident some
years ago that led to discovery of pallidotomy as an effective
treatment for PD.)

Deacon T et al; Nat Med 1997;3:350-353:
Histological study following unrelated death of a PD patient 7
months after transplant of fetal pig neural cells showed that they
had thrived.