CURRENT SCIENCE REVIEWS   By Joe Bruman  June 1998  Page 1 of 4

Quinn N, Bhatia K: BMJ;25 April 1998:1259-1260:
Summarizes status of pallidotomy, thalamotomy, and deep brain
stimulation implants. Suggests comparing long-term effects with
those of fetal-cell grafts or continuous apomorphine infusion.

Berger A; BMJ;9 May 1998:1407:
A simplified description of the complex process to obtain
cloned bovine dopamine-producing neurons (cf. Zawada et al, below)
for transplantation in PD patients. (The firm which developed
it has just received a broad and extremely valuable patent-JRB)

Brashear A et al; Ann Neur 1998;43:521-526:
Rapid-onset dystonia-parkinsonism (RDP) develops full symptoms
within as little as one day. Analyzing cerebrospinal fluid (CSF) of
members of two familial clusters, they found that decreased level
of the dopamine metabolite homovanillic acid is a weak diagnostic
predictor.

Uhl G; Ann Neur 1998;43:555-560:
Dopamine is produced and used by neurons in several parts of the
brain, but the loss of neurons in PD is highly selective. By the
time overt motor symptoms appear, the part of the substantia
nigra that connects to the putamen and caudate nuclei has lost
about 80% of its neurons. The ventral tegmental area of the
midbrain that innervates the cortex and limbic forebrain (higher
mental sites) has lost 40% to 60%. While the arcuate nucleus of
the hypothalamus, which controls endocrine secretions of the
pituitary, has lost none at all. The mystery of this selectivity
may hold a key to understanding, and possibly curing, PD. He
thinks it is the dopamine transporters, chemicals which carry
dopamine to its various application sites, and whose local
concentration correlates with the degree of neuron loss.

Murer M et al; Ann Neur 1998;43:561-575:
In rats with induced PD, prolonged levodopa therapy not only is
not toxic for remaining dopamine neurons, but instead promotes
their recovery.

Fahn S; Ann Neur 1998;43:551-554: The opposing side in the long
debate over levodopa toxicity remains unconvinced. A controlled
clinical trial, conducted by the Parkinson Study Group (who did
the DATATOP study) and funded by NIH, is planned.

Mercuri N et al; Ann Neur 1998;43:613-617:
In vitro and in rats, large doses of selegiline (Eldepryl)
greatly enhanced and prolonged the function of levodopa therapy,
suggesting its use in human patients to reduce the dosage needed.

Inzelberg R et al; J Neur N'surg Psych 1998;64:533-535:
Auditory hallucinations may occur with visual ones, but not alone,
in PD, and most often in patients with cognitive impairment.

Ko K; J Neurosurg 1998;88:777-781:
The rigid stereotactic frame now required to guide such surgery
as pallidotomy may become unnecessary, upon refinement of a CAT-
scan-derived 3-dimensional holographic technique now being tried.



CURRENT SCIENCE REVIEWS   by Joe Bruman  June 1998  Page 2 of 4

Merello M et al; J Clin Neuropharm 1998;21:135-138:
Acute L-dopa challenge in 6 patients after unilateral posteroventral
pallidotomy (PVP) showed that while improvement of cardinal symptoms
by PVP was contralateral, the effect of L-dopa remained symmetrical.

Lyons K et al; J Clin Neuropharm 1998;21:118-121:
Looking for gender difference of motor and cognitive PD symptoms in
630 local patients, they found that as PD advances, men have worse
motor impairment, while women have more levodopa-induced dyskinesia.

Bedard N et al; J Clin Neuropharm 1998;21:108-117:
Attention deficit occurring in PD may be due to depletion of
catecholamine. In standard tests on 9 patients, they found that the
selective noradrenergic agonist Naphtoxazine partly reversed it.

Brooks D et al; J Clin Neuropharm 1998;21:101-107:
In a double-blind controlled efficacy and safety trial, Ropinirole
alone significantly improved motor symptoms of early-stage PD.

Sternic N et al; J Clin Neuropharm 1998;21:93-96:
In 20 PD patients who had developed levodopa-induced complications,
the MAO-A inhibitor Moclobemide was well tolerated and effective.

Baas A et al; J CLin Neuropharm 1998;21:86-92:
In 10 late-stage PD patients with end-of-dose motor fluctuations,
a double-blind trial tested interaction of levodopa and apomorphine.
Apomorphine improved "on" duration, but not the degree, of motor
response due to levodopa.

Majsak M et al; Brain 1998;121:755-766:
They measured bradykinesia by asking 6 PD and 6 control subjects to
reach as fast as possible and grasp an object. The PD subjects were
slower when the object was stationary but not when it was moving.
PD impairs internally controlled but not visually controlled motion.

Johnson K et al; Brain 1998;121:743-753:
They tested bimanual coordination of 16 PD patients and 16 controls
in repetitive crank turning. An external timing cue helped the PD
subjects when the required motions were in phase, but worsened
their inability to coordinate out-of-phase motions. Bimanual
coordination therefore is thought to involve the basal ganglia.

Alberts J et al; Brain 1998;121:725-742:
Performance of PD and control subjects in simultaneous bimanual
motion tasks showed that the PD group did poorly when the tasks
were unsymmetrical, i.e., reduced control of multiple degrees of
freedom. PD subjects also were less able to make the transition
from movement control to force control.

Scott R et al; Brain 1998;121:659-675:
Intellectual, psychological, and functional outcomes were compared
in 20 PD patients, following either unilateral or simultaneous
bilateral pallidotomy. All had improvement of motor symptoms and
some reduction in categorical verbal fluency, while only the
bilateral group lost some phonemic verbal fluency.




CURRENT SCIENCE REVIEWS   By Joe Bruman  June 1998   Page 3 of 4

Rogers R et al; Brain 1998;121:815-842:
To explore the mechanism of executive behavior control, they
compared 12 PD patients with 12 who had focal damage of the
frontal cortex, in a battery of tests requiring subjects to
switch from one task to another. In addition to the left frontal
cortex, they found that dopaminergic transmission along the
nigrostriatal pathway may also be involved in that cognitive
process.

Owen A et al; Brain 1998;121:949-965:
Using Positron Emission Tomography (PET) to map cerebral blood
flow in subjects while they worked on a series of mental tasks,
They compared 6 PD patients against 6 healthy controls, finding
that depletion of dopamine in the basal ganglia due to PD
affects higher frontal-lobe functions as well as motor control.

Nutt J; Lancet, 25 April 1998:1221-1222:
While the most effective agent against PD symptoms, levodopa has
the problem of rapid loss once taken. To avoid dyskinesia from
excessive concentration in the blood plasma, patients must take
frequent small doses. Controlled-release (CR) formulation has a
lower peak, but less reliable action and less bioavailabiity. An
important levodopa antagonist is the ubiquitous enzyme catechol-
O-methyl transferase (COMT). Two new drugs inhibit COMT and hence
prolong availabilty of levodopa, thereby smoothing out its motor
symptom fluctuations and permitting less-frequent dosage. Newly
approved tolcapone (Tasmar) can enter the brain, but works mainly
outside the brain to preserve levodopa in the plasma. By itself
it has no effect on PD symptoms, and doesn't need gradual increase
to the optimum dosage. Its main side effect is indirect, namely
dyskinesia which results if levodopa dosage is not simultaneously
reduced. Approval of a second COMT inhibitor, entacapone (Comtan
in the US, Comtess in Europe) is expected shortly.

Agid Y; Neur 1998;50:858-863:
PD seems prone to stir up sometimes heated scientific debate. One
such topic is levodopa toxicity, and the choice of frugality and
deferred use versus the most effective relief of PD symptoms. The
author here argues that all the imputed adverse effects are
reversible, and that levodopa does not accelerate progress of PD.

Marder K et al; Neur 1998;50:1138-1140:
Suspecting iron concentration as a factor in PD, they measured 6
different indicators of iron metabolism in a longitudinal study
of 103 PD patients and 353 healthy controls. Of the 6, transferrin
receptor concentration was strongly associated with mortality in
the PD group but not the controls.

Marder K et al; Neur 1998:50:1141-1143:
In study of 87 women with PD but not dementia, 80 with PD and
dementia, and 989 healthy nondemented women, estrogen replacement
therapy was protective against dementia but not incidence of PD.

Neur 1998:50 (advertisement)
The implanted Medtronic device for deep-brain stimulation to
suppress tremor is being marketed as "Activa" tremor therapy.



CURRENT SCIENCE REVIEWS   By Joe Bruman   June 1998  Page 4 of 4

Kempermann G, Gage F; Nat Med 1998;4:555-557:
Many adult animals can regenerate brain tissue, but conventional
belief holds that humans and other mammals cannot. Reversal came
a step closer, with discovery of such regeneration in marmosets.

Zawada W et al; Nat Med 1998;4:569-574:
The quest for an alternative to human fetal transplant tissue
for PD gets complicated. Starting with bovine embryonic cells,
by gene-transfer they cultured cells that produce dopamine.
From those they cloned embryos to implant in host cows. After
6 to 7 weeks the embryos were aborted, and they implanted
mesencephalic cells from those into the brains of immuno-
suppressed parkinsonian rats, resulting in improved motor
performance.

Martin W et al; Mov Disord 1998;13:281-286:
Free iron in the brain contributes to formation of free
radicals, which cause oxidative stress, which damages neurons,
possibly resulting in PD. Using magnetic resonance technique,
authors surveyed 20 healthy volunteers ranging in age from 24 to
79. They found that free iron increases with age in the putamen
and caudate, but not in the globus pallidus or thalamus.

Goldman W et al; Arch Neur 1998;55:674-680:
They gave a battery of cognitive tests to 22 PD patients with
questionable dementia, 53 without dementia, and 43 healthy
controls, finding the first group slightly impaired, the second
group less so, suggesting that PD may predispose to cognitive
impairment. They propose longitudinal follow-up, to see if PD
patients who eventually become demented can be identified ahead
of time.
--
J. R. Bruman   (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013