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

Krauss J et al; Arch Neur 1997;54:1026-1029;
In a patient whose levodopa-resistant symptoms presumably arose=20
from peripheral trauma rather than idiopathic PD, unilateral
microelectrode-guided pallidotomy induced marked and lasting=20
improvement.

Samuel M et al; Brain 1997;120:1301-1313:
Studying the effect of pallidotomy on selective impairment of=20
voluntary movement, they did PET scans on 6 off-medication PD=20
patients performing standardized motor tasks, before the=20
surgery and 3-4 months afterward. Improvements in UPDRS score=20
and response time were associated with increased activity in the
supplementary motor area and the dorsal prefrontal cortex.

Eidelberg D et al; Brain 1997;120:1315-1324:
They used PET to study glucose metabolism of the pallidum and=20
thalamus in 42 awake and unmedicated PD patients, before and
during pallidotomy, to assess the effect of PD on the pathway
relation between the two areas.

Soliveri P et al; Brain 1997;120:1325-1337:
Learning new motor (tracking) skills is impaired by PD. By testing
PD patients both on and off medication, they found that PD affects
internal (kinesthetic) guidance more than visual guidance.

Cunnington R et al; Brain 1997;120:1339-1353:
To clarify whether PD impairment of voluntary movement occurs
mainly in preparation or in execution, they recorded movement-
related EEG potential in 14 PD patients and 10 healthy controls,=20
while they either performed or imagined standard motor tasks.=20
Later-stage PD patients were impaired more in the preparation or=20
tne termination phase, rather than in the execution phase.

Wascher E et al; Brain 1997;120:1355-1375:
To distinguish cognitive defects from those of activation in the
motor impairment of PD, they measured response force and EEG
potentials in 15 PD patients and 15 healthy controls, while
performing tests of either timing or recognition. In both cases
the PD patients were slower.

Krauss J et al; J Neurosurg 1997 Sep,87(3):358-367:
They report good and lasting results of microelectrode-guided
pallidotomy in 34 out of 36 advanced PD patients, besides some
history and details of technique. Optimal location for the lesion
(region to be destroyed) is still being refined. The initial=20
lesion size in this series averaged 18 cubic mm (less than a small
grape seed). Various methods for creating the lesion: cutting,=20
freezing, radioactive implants, electrical resistance heating,=20
balloons, or injected poison such as alcohol, are now more or less
superseded by radiofrequency heating, which permits the best
precision and control. Followup MRIs confirmed the value of=20
microelectrode recording to ensure accuracy of lesion placment.

Ansorge O et al; Neur 1997 Aug,49(2):610-613:
Problems of water excretion and blood pressure adaptation in PD
suggest impaired function of the hypothalamus. So they studied
(postmortem) neural tissue of the supraoptic nucleus (SON) of the
hypothalamus, in PD patients and controls. The expected loss of
neurons was associated with enlargement of the remaining ones.
CURRENT SCIENCE REVIEWS   By Joe Bruman   October 1997   p. 2 of 4

Ellis C et al; Neur 1997 Aug,49(2):438-444:
By proton magnetic resonance spectroscopy they studied the effect
of levodopa on the ratio of n-acetylaspartate to choline in the=20
putamen of 9 levodopa-na=EFve PD patients, 7 advanced PD patients
under levodopa treatment, and 11 healthy controls. Compared with
controls, the ratio was reduced in the drug-naive group but not=20
in those getting levodopa, suggesting use of the measurement as
a reversible marker of striatal dysfunction.

Wermuth I et al; Neur 1997 Aug,49(2):426-432:
In a statistical survey of 43,709 Faroe Islands residents,=20
they found 82 (0.2%) with confirmed PD, an incidence about 60%
higher than a similar group on the mainland. They believe the=20
anomaly may be due to earlier diagnosis but not to earlier onset
or longer duration.

Grondin R et al; Neur 1997 Aug,49(2):421-426:
In tests on induced-PD monkeys they are studying therapeutic
potential of the D1 agonist A-86929 and other DA agonists.

Adler C et al; Neur 1997 Aug,49(2):393-399:
A prospective, randomized, placebo-controlled, double-blind,
parallel-group, 6-month study of the nonergoline D2-dopamine=20
agonist ropinirole as monotherapy in 241 early-PD patients=20
showed it to be effective, safe, and well-tolerated.

Isacson O, Breakfield X; Nature Medicine 1997 Sep;3(9):964-969:
Comprehensive review of benefits/risks in animal-tissue CNS
grafts. Detailed analysis of 2 examples: replacement of dopamin-
ergic neurons lost in PD, and apoptosis-gene transfer for
suppression of brain tumors. Fetal transplants for PD, either
human or animal, risk transmitting infection. An impediment to
use of human tissue is the need to pre-screen the prospective
mother's blood. Pig fetal cells may carry retroviruses (agents
that subvert host nucleic DNA) dangerous to humans. The safest
prospect is cells cultured and well-screened in the laboratory.

Holtzman D, Deshmukh M; Nature Medicine 1997 Sep;3(9):954-955:
The role of apoptosis (programmed cell death) in neurodegenerative
diseases such as PD is uncertain. But workers find that PCD is
mediated by enzymes called caspases. In mice with artifical ALS,
a caspase inhibitor slowed progress of the disease.

Agid Y et al; Lancet, 6 Sep 97:712:
They did an 8-week, open-label, multicenter study on 146 PD=20
patients who were at the stage of motor fluctuations, to compare
the COMT inhibitor tolcapone against bromocriptine as adjunctives
to levodopa therapy. Tolcapone was better at increasing "on" time,
reducing "off" time, and reducing levodopa requirement. More of the
bromocriptine subjects required domperidone to manage peripheral
dopaminergic adverse effects.

Beric A et al; J Neur N'surg Psych 1997;63:159-162:
During pallidotomy surgery on 73 PD patients, they measured the
stimulus required at an electrode in the globus pallidus to
excite limb muscle contraction. The threshold was lower when
applied on the dominant side (i.e. left side in right-handed=20
patient).

CURRENT SCIENCE REVIEWS   by Joe Bruman   October 1997   p. 3 of 4

Churchyard A et al; J Neur N'surg Psych 1997;63:228-234
The team that reported signs of shorter lifespan among selegiline
recipients has found a new worry about the drug. In 9 of 16 such
recipients, tilting the head up to an angle of 45 deg caused severe
hypotension, to the point where 2 of them fainted.

Reuneveld J et al; J Neur N'surg Psych 1997;63:258:
After a third tetanus shot, an otherwise healthy worker developed
severe parkinsonism. The syndrome abated dramatically with levodopa
therapy, but they don't say if continued maintenance was required.
SPECT imaging revealed a pattern similar to that of progressive
supranuclear palsy or multiple system atophy.

Goto S et al; Neur 1997;49:707-710:
After surgery involving general anesthesia, a patient suffered an
ischemic/hypoxic stroke, and in the 6 months following recovery
developed severe parkinsonism symptoms, which were markedly
alleviated by staged bilateral posteroventral pallidotomy.

Metman L et al; Neur 1997;49:711-713:
A dosage-range trial of levodopa on 25 cases of advanced PD showed
similar threshold for relief of parkinson symptoms and onset of
dyskinesia, i.e. the therapeutic window was zero. Rather than=20
smaller and more frequent doses, in such cases they suggest that
the fuller response and longer duration of bigger doses may be
of benefit.

Logroscino G et al; Neur 1997;49:714-717:
Concentration of iron in the substantia nigra of PD patients has
been suspected to produce free radicals and neuron death. But
surprisingly, serum concentration of iron and iron-related=20
compounds in 104 patients was lower than in the controls, implying=20
a systemic defect in iron metabolism related to PD.

Turjanski N et al; Neur 1997;49:717-723:
Suspecting the source of peak-dose levodopa-induced dyskinesia in
advanced PD to be in supersensitized striatal D1 and D2 receptors,
they did comparative PET studies on treated vs untreated patients,
finding no significant difference in receptor binding.

Shannon K et al; Neur 1997;49:724-728:
Although other dopamine agonists usually require levodopa as an
adjunct, a double-blind test of pramipexole alone on 335 early-PD
patients for 31 weeks showed it to be safe and effective therapy.

Limousin P et al; Ann Neur 1997;42:283-291:
By PET mapping of cerebral blood flow during performance of=20
assigned movement tasks, they compared the value of the internal
pallidum with that of the sub-thalamic nucleus as sites (6 PD=20
patients each) for deep-brain stimulation, finding the STN to be=20
the more effective.

Koller W et al; Ann Neur 1997;42:292-299:
Assessing up to a year of unilateral deep-brain stimulation at=20
the ventral intermediate nucleus (VIM) of the thalamus in 29=20
essential tremor patients and 24 PD patients, they found it
highly effective for reducing tremor in both groups. (Note: The
term "high-frequency" in the title is misleading, it means 120
to 180 Hz, compared with the effective minimum of about 50 Hz.)=20
CURRENT SCIENCE REVIEWS   By Joe Bruman   October 1997  p. 4 of 4

Durso R et al; Ann Neur 1997;42:300-304:
Using tagged samples to measure central metabolism of levodopa
in 8 PD patients of varying status, they found no significant
correlation of levodopa-related benefit with duration of the=20
disease or with prior levodopa experience.

Nutt J et al; Ann Neur 1997;42:349-355:
Using tapping speed ability in 18 previously untreated PD patients=20
as an index of long-duration (baseline) response or short-duration
(after infusion) response to levodopa, they conclude that both LDR
and SDR continue to improve during the first year. They also found
a pattern of poorer response in late afternoon or evening.=20

Buee-Scherer V et al; Ann Neur 1997;42:356-359:
Three patients who contracted encephalitis during the epidemic of
the 1920s at age 8 to 10 developed parkinsonism at age 20 to 30,
which responded to levodopa when it became available in the 1970s=20
but persisted until their deaths 60 or so years later. Postmortem
analysis of neurofibrillary tangles in all three showed a chemical
distinction from those of progressive supranuclear palsy or
corticobasal degenerstion.

Ghika J, Bogousslavsky J; Arch Neur 1997;54:1104-1108:
Survey of 893 patients with parkinsonism of various causes
showed that presymptomatic hypertension is a major feature in
diagnosis of progressive supranuclear palsy.

Jenner P; Arch Neur 1997;54(8)Aug (ad):
Attempt to sort out the relative benefits of D1 vs D2 receptor=20
agonists in PD, and the various available examples. They=20
represent two different pathways and components of the motor
system. D1 stimulation in some respects is better than D2, but
a combination of both (as in pergolide) may be better yet.=20
--=20
J. R. Bruman   (818) 789-3694
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