behavioral supersensitivity to dopamine agonists develops
following striatal dopamine denervation, imaging of neuroleptic binding sites on nondisrupted striatal tissue using radiolabeled spiperone has not yet provided insight into the mechanism responsible for such phenomena.

Refrences
1. Bennett JP Jr, Wooten G F Dopamine denervation does not alter

in vivo 3H-spiperone binding in rat stria-:
implications for
external imaging of dopamine receptors in Parkinson’s disease.
Ann Neurol 19378-383, 1986
2. Kuhar MJ, Murrin C, Malouf AT, Klemm N: Dopamine receptor binding in vivo. The feasibility of autoradiographic studies.
k f e Sci 22:203-2 10, 1978
3. Laduron PM, Janssen PFM, Leysen JE: Characterization of
specific in viva binding of neuroleptic drugs in rat brain. Life Sci
23:581-586, 1978
4. Leslie CA, Bennett JP Jr: jH-Spiperone binds selectively to
striatal D2 dopamine receptors in vivo: a kinetic and pharmacological analysis. Brain Res (in press)
5. Perlmutter JS, Raichle ME: In vitro or in vivo receptor binding:
where does the truth lie? Ann Neurol 1’9384-385, 1986

Naloxone in Gilles de la
Tourette’s Syndrome
We read with interest the letter by Sandyk [2] and would
like to add our experience. Dr. Sandyk has reported on
transient abatement of tics in a patient with Gilles de la
Tourette syndrome (GTS) treated with naloxone. Based on
observations from two patients [I, 21, he postulated the possible role of the endogenous opioid system in GTS. However, to quote Sandyk, “. . . both over- and underactivity of
the opioid system . . .” can account for the previous reports.
We studied a 26-year-old man with a 20-year history of
progressive multiple tics accompanied by vocalization,
echolalia, and coprolalia For the past 3 years, he has been
treated with haloperidol, clonidine, pimozide, tiapride HC1,
and carbamazepine, with only partial or transient relief. At
the time of examination he had been drug-free for several
months. Head shaking, facial tics, grimacing, lingua! protrusion, and vocalizations were evident and could be counted
easily. In a simple blind trial, 3 ml of saline or 3 ml of saline
containing 1.2 mg of naloxone was administered intraveEfect of Saline or Naloxone Administration
in Tourette’s Syndrome

No. of vocalizations
No. of head shaking
No. of facial tics, grimacing, or
lingual protrusion
Total

Department of Neurology
Beilinson Medical Center
Petah Tiqua 49 100
Israel
References
1. Gillman MA, Sandyk R Gilles de la Tourette syndrome-effect
of analgesic concentrations of nitrous oxide. Br Med J 288:114,
1984
2. Sandyk R: The effects of naloxone in Tourette’s syndrome. Ann
Neurol 18:367-368, 1985

Dysarthria-Clumsy Hand
Syndrome and Cerebellar
Hemorrhage

N. Gadoth, MD, C. R. Gordon, MD, DSc,
and J. Streifler, MD

Symptoms

nously. The patient‘s behavior was recorded on videotape,
and later the film was evaluated by three observers.
The number of vocalizations, head movement, facial
grimacing, and tongue protrusion was counted from the recordings for the 50-minute periods following the separate
saline and naloxone administrations. It can be seen from the
Table that, although there is some variation in the number of
a particular symptom between the naloxone and saline periods, the total number of tics was not affected by naloxone.
We observed no beneficial effect on the number or severity of tics in our patient with classic severe GTS.

Saline

Naloxone

333
235
607

133
165
962

1,175

1,260

E. P. Roy, 111, MD, Robert W. Keefover, MD,
Jack E. Riggs, MD, and Gary D. Marano, MD”
Initially described by Fisher 121 in 1967, the dysarthriaclumsy hand syndrome has been associated with lesions in
the pons [2, 4 ) and internal capsule [l, 31. A cerebellar
lesion producing this syndrome, though not previously reported, is not unexpected and was even predicted by Fisher.
We describe B patient with the dysarthria-clumsy hand syndrome associated with a small, deep cerebellar hemorrhage.
A 5 7-year-old right-handed hypertensive man was admitted with a one-day history of slurred speech and clumsiness of the right hand. On the evening prior to admission,
he noted the abrupt onset of slurred speech. There was no
associated alteration of consciousness, dizziness, nausea, dysphagia, visual changes, aphasia, weakness, or numbness. The
next morning, his speech remained slurred and he noticed
that hi5 right hand was clumsy while attempting to write.
O n admission, his blood pressure was 140/86. He was
alert with intact cognitive functioning. His speech was fluent
but dysarthric. There was no aphasia. Pupil responses; visual
fields; eye movements; facial strength and sensation; tongue,
palate, and swallowing movements; limb sensation; muscle
strength and tone; and deep tendon reflexes were normal.
There was no pronator drift. The right hand exhibited decreased facility with finger tapping and rapid alternating
movements. There was no extremity dysmetria or gait ataxia.
The toes were down-going on plantar stimulation.

Annals of Neurology

Vol 21 No 4

April 1987 415

Naloxone Reverses
the Inhibition by Sodium
Valtxoate of GABA
TrLnsport Across
the Deiters’ Neuronal
Plasma Membrane
H. Hydkn,* A. Cupello,t and A. Palm”

Unenhanced cranial computed tomographic scan demonstrating a
small, deep right cerebellar hematoma.

Cranial computed tomographic scan on admission demonstrated a small, deep right cerebellar hemorrhage (Figure).
Brainstem sections were normal. The patient was discharged
two days later, with mild improvement in his speech and
right hand function. Cranial magnetic resonance imaging
done 7% weeks later showed a small residual defect in the
same region of the cerebellum. Two months following admission, the patient’s speech remained d ysarthric but his
right hand symptoms had resolved.
This case further illustrates the concept that the dysarthriaclumsy hand syndrome is not a distinct clinicopathological
entity, but rather a clinical syndrome associated with pathological lesions at various sites, including the pons, internal
capsule, and cerebellum.

y-Aminobutyric acid (GABA) can diffuse through a GABAreceptive membrane such as that of the Deiters’ neuron in
the rabbit. This was assessed by our group by studying the
passage of GABA as a function of its “extracellular” concentration 141. This mechanism is extremely efficient, suggesting
that it may be mainly responsible for removal of GABA
from synaptic clefts 121. This process is inhibited (by 57%)
by the anticonvulsant drug sodium valproate (VPA) at concentrations higher than those corresponding to the therapeutic range 131 and also by met 5-enkephalin El}.
In a clinical case report, Steiman and associates [5l communicated that an accidental overdose of sodium valproate
was successfully treated with the opioid antagonist naloxone.
Our experimental data indicate that VPA and met 5-enkephalin have a similar effect on GABA diffusion through a
GABA-receptive membrane. The question thus arose: Do
they interact with the same site, in some way coupled to the
GABA postsynaptic diffusion mechanism Ill? If so, the site
should be an opioid receptor and the VPA effect should be
antagonized by low concentrations of naloxone. This mechanism might explain why naloxone was effective in the case
cited above.
To investigate this possibility, we used the experimental
model described in detail elsewhere 13,41, in which a single
Deiters’ neuronal membrane, microdissected from the rabbit
brainstem, separates two microchambers (MI and M2). We
studied the passage of f3H1GABA, 0.2 mM in Earle’s balEffects of Various Agents on GABA Diffusion
through the Rabbit Deiters’ Neamnal Membrane

Agent

Passage of GABA
(moles/pm2 x secPb
1.01 + 0.17 x 10-14
(7)
0.44 2 0.05 X
p‘ < 0.0001 (6)

Department of Neurology and “Radiology
West Virginia Univwsity MedicaL Center
Morgantwn, WV 26506

Control

Refeerences

0.85 0.08 X
NS‘; pd < 0.0001 ( 4 )
2.4 mM VPA + lo-’ M ndoxone 0.86 f 0.04 X lo-’*;
NS‘;pd < 0.0001 ( 3 )

1. Donnan GA, Tress BM, Bladin PF A prospective study of
lacunar infarction using computerized tomography. Neurology
32:49-56, 1982
2. Fisher CM: A lacunar stroke: the dysarthria-clumsy hand syndrome. Neurology 17:614-617, 1967
3. Spertell RB, Ransom BR. Dysarthria-clumsy hand syndrome
produced by capsular infarct. Ann Neurol6:263-265, 1979
4. Tuhrim S , Yang WC, Rubinowitz H, Weinberger J: Primary
hemorrhage and the dysarthria-clumsy hand syndrome. NeurolO ~ Y32:1027-10.28, 1982

416 Annals of Neurology Vol 21 No 4 April 1987

2.4 mM VPA
2.4 mMVPA 4- lO-’Mndoxone

*

”Number in parentheses refers to the number of experiments.
bAU values are rt standard deviation.
Compared with control.
dCompared with the 2.4 mM VPA value.

GABA = y-aminobutyric acid; VPA = sodium valproate; NS =
not significant.