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Eur. Neurology 28: 139-141 (1988)

Phenobarbital-Induced Buccolingual Dyskinesia in Oral Apraxia
Gian Pietro Sechi, Maria Rita Piras, Giulio Rosati, Marco Zuddas, Renat o Ortu, Salvatore Tanca, Virgilio Agnetti
Department of Neurology, University of Sassari, Italy

Key Words. Phénobarbital • Buccolingual dyskinesia • Oral apraxia

Introduction
Orofacial dyskinesia has been described after admin­
istration of several drugs, including the anticonvulsants
phenytoin, primidone, carbamazepine and phénobarbi­
tal at toxic levels [1-4], The occurrence of buccolingual
dyskinesia in a neurologically impaired child, soon after
the intake of low phénobarbital (PB) doses has recently
been reported [5]. We studied a similar case in which, in
addition, oral apraxia and a well defined brain lesion on
CT scan were documented. Such an association has not
been reported previously.

Case Report
A 25-year-old woman with a third-grade education was admitted
to this neurological ward in December 1985 for epileptic generalized
seizures. She was right-handed, but ambilaterality was present in a
sister. Neurological examination showed a normally alert and co­
operative patient. Mild left hemiparcsis and nonfluent aphasia were
present, likely due to tubercular meningoencephalitis contracted
when she was 7 years old. The optic fundi showed no abnormality
and no other neurological abnormalities were recorded. Laboratory
findings including urea, glucose, electrolytes, EEG, chest X-ray,
liver and thyroid function tests were within normal limits. A CT
scan performed without contrast in January 1985 showed a lowdensity area in the right frontal region involving both cortical and
subcortical areas (fig. I). The lesion was evident in the low- and

high-ventricular slices as well as in the supraventricular ones. More
precisely, the following subcortical structures seemed involved in
the low-ventricular slices: putamen and head of the caudate nucleus
(small calcifications were found in both) and part of the anterior
limb of the internal capsule with extension into paraventricular
white matter deep into area 44. The lesion extended superiorly into
the paraventricular white matter corona radiata deep in the precen­
tral gyrus area representing the lower part of the face at high-ven­
tricular slices. Areas 44. 6 and, possibly, part of area 4, were
involved at the cortical level. Neuropsychological examination was
carried out in December 1985. Mental status examination showed a
fully alert patient. IQ performance scale was 52. Raven’s progressive
matrices were 36.11 % (13/36). The patient’s speech was not fluent:
the expression was low with articulation difficulties. Agrammatism
was present. The patient series speech, counting and reciting the
months were performed with difficulty. The result of the repetition
tasks was poor. There were 90% errors for letters, syllables and
100% errors for words. The phonemic paraphasia impaired any
attempt to repeat phrases or sentences. She was aware of errors
which she attempted to correct, and often exhibited catastrophic
depressive reactions. Verbal comprehension, assessed with the
token test was relatively good (25/36). The patient had difficulty in
reading aloud single letters and syllables, but more so with single
words, owing to frequent paralexia. She could not carry out written
commands. Spontaneous writing, performed with the right hand,
was poor. On dictation of words, most of her recordings were incor­
rect due to numerous omissions. Copy was performed better (20%
errors). Movements of the face and buccorespiratory apparatus were
performed with difficulty on verbal command (2/20) and imitation
(2/20). The patient was started with PB 100 mg daily after the neu­
ropsychological examination was performed. Six hours after the first
dose, she suddenly developed continuous perioral muscle spasms

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Abstract. A young woman with oral apraxia and a well-defined brain lesion on CT scan developed buccolingual
dyskinesia lasting 40 days after low phénobarbital (PB) doses. Disruption of the corticostriatal glutamatergic path­
way from areas 6 and 4 may have been important both in causing oral apraxia and in lowering the threshold for
PB-induced buccolingual dyskinesia.

Scchi/Pi ras/Rosati/Zuddas/Oriu/Tanca/Agnctt i

140

and dystonic lingual movements. After 12 days of PB therapy (blood
level = 16 pg/ml), she could not chew, or swallow because of contin­
uous oromandibular dystonic spasms with involontary jaw opening,
protrusion of the tongue and blowing movements of the cheeks. The
movements stopped in sleep and were not associated with EEG epi­
leptiform activity. When the PB dose was reduced to 50 mg daily for
2 weeks there was a moderate improvement of dystonic movements
and the drug was discontinued. The oromandibular movements
abated 40 days later. After 45 days, PB 50 mg daily was restarted
with recurrence of buccolingual dyskinesias after 1 day (blood level
= 6 pg/ml). Sodium valproate was substituted for PB. The dyskine­
sia abated 10 days later.

Discussion
Our case confirms that PB may induce orofacial dys­
kinesia at low therapeutic dosages in the presence of a
preexistent cerebral injury [5], In addition, it poses the
question whether oral apraxia may lower the threshold
for PB-induced buccolingual dyskinesia. Apraxia, which
is defined as a defect in motor performance and behavior
without concomitant relevant paresis, ataxia, incoordi­
nation or dystonic dyskinesia [6], may be due to lesions
in some parts of the cerebral cortex (both left and right
hemisphere), corpus callosum with its radiation, basal
ganglia and/or thalamus [7-9], In particular it appears
that the cerebral cortex alone cannot execute a coordi­
nated skilled movement [9], and that the integrity of sub­
cortical circuits and structures (e.g. corticostriate and
thalamostriate pathways) may be crucial for perfor­

mance [10, 11]. In our case, several cortical and subcor­
tical connections and structures are disrupted. However,
as documented by the limited lesion on CT scan, the
corticostriatal glutamatergic pathway from areas 6 and
4, which is excitatory to the small 'spiny' neurons in the
caudate and putamen [ 12] seems mainly involved. In our
opinion, the disruption of this pathway might play a role
both in the pathophysiology of oral apraxia and in low­
ering the threshold for PB-induced buccolingual dyski­
nesia. The loss of cortical control on the striatum reduces
the inhibitory GABA-ergic tone of the striatopallidal
neuronal chain [12], which in turn leads to a disinhibition of the pallidum [12], Interestingly, a frequently
obtained effect of stimulation of the pallidum in freely
moving cats (Hess technique) is licking [10], In this pre­
disposing condition small PB doses might induce dys­
tonic movements through a further selective depression
of the depolarization elicited by glutamate in the stria­
tum [13] and/or affecting the function of other neuro­
transmitter likely involved in the pathophysiology of
cranial dystonia such as GABA and acetylcholine [1416]. Our patient developed PB-induced buccolingual
dyskinesias only, while Wiznitzer and Younkin’s [5]
patient also had cervical dystonia and blepharospasm.
This is likely due to the limited brain lesion observed on
CT scan in the former case (where a corticosubcortical
somatotopic organization involving oral structures
seems affected), with respect to the diffuse cortical and
subcortical lesions observed in the later. In both cases.

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Fig. 1. CT scan without contrast. A low-density area in the right frontal region involving both cortical and subcortical regions is
evidenced in the low-ventricular (a), high-ventricular (b) and supraventricular (c) slices.

141

Phénobarbital Dyskinesias in Oral Apraxia

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Received: June 20, 1987
Accepted: August 24, 1987
Dr. Gian Pietro Sechi
Clinica Neurologica
Viale S. Pietro. 10
1-07100 Sassari (Italy)

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the PB-induced buccolingual dyskinesias persisted for
40 days although negligible drug levels were found in the
blood. This may be due either to a pharmacokinetic phe­
nomenon, by accumulation and persistence of PB in the
brain [17, 18] or to a pharmacodynamic one by the
effects of PB on specific biochemical processes in the
brain (e.g. reduction of the synthesis and central release
of acetylcholine) [ 13].