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Drug error in anticonvulsant therapy.

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HLA in
Lowell L. Williams, M D
Variability in nerve conduction velocities, disease onset,
and rate of progression has been recorded in families with
Charcot-Marie-Tooth disease (CMT) [4]. Other factors
in addition to inherited susceptibility may play a role
in the clinical manifestations of this familial peripheral
neuropathy. Certain histocompatibility antigens (HLA)
have linked genetically susceptible individuals yith disease
states [l!. Inherirance of one o r more specific HLA.-antigens may be a factor controlling the p e n e r r m e abnormal pa_thology in CMT families.
To test this hypothesis, 31 A, B, and C HLA loci from
one afflicted member in each of 24 unrelated CMT families
were determined by standard microlymphocytotoxic
methods [2]. A normal control HLA incidence was comp i m m 1,255 persons who had been tested in the same
Red Cross facility in central Ohio over the preceding eight
years. Our control values were in agreement with the averages of six other published control populations with similar
racial distribution.
An increased incidence of two HLA loci, which reached
statistical significance. was found in the CMT probands.
was compared to controls by chi-square test
using the relative risk factor, RR, of Svejgaard [ 3 ]without
correction for the number of antigens tested.) .hcus 112
occurred i ! s % of CMT probands and 43% of controls
(RR = 2 . 6 4 , ~< 0.05);locus B12 (subtyped as Bw44) occurred in 42% of CMT pr=and
24.5% of controls
(RR = 2.23,p < 0.05). However, there did not appear to
be a correlation between this phenotype and the severity of
symptoms in these 24 probands.
For further evaluation of a link between an HLA locus
and CMT, the 31 antigens were determined in 16 additional at-risk family>,ers,
defining disease inheritance
as autosomal dominant. Some family members showed
symptoms, while ochers did not. Again, there was no distinct association between the A2-Bl2 p h e x p e , or any
other specific locus, and a p p a r e e s e manifestations. A
definitive haplotype linked with C M T disease penetrance,
t h e r z r e , could LoXe i d e n t i f i e d m c e A2 and
B12 are known^to be in linkage disequilibrium [l], their
high incidence in C M T patients suggests that the gene determining the disease in families lies close to either or both
of these loci o n c h r o z s o m e 6 .
Supported by Grant 92 from the Riverside Methodist Hospital
Research Foundation, Columbus, OH.
Appreciation is expressed to Dr George Paulson for helpful advice
and patient referral and to Mike Mason for technical aid.
Department of Pediatrirs
The Ohio State University
700 Children’s Dr
Columbus, OH 43205
Annals of Neurology
Vol 8 No
4 October 1980
VanRood JJ: The major histocompatibility complex:
genetics and biology. N Engl J Med 295:806-813, 872-878,
927-936, 1976
2. Mittal KK, Mickey MR, Singal DP, Terisaki PI: Seroryping for
homotransplantation. XVIII. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation 6 9 1 3-927, 1968
3. Svejgaard A, Jersiid C, Staub NL, Bodmer WF: HLA antigens
and disease. Statistical and genetical considerations. Tissue
Antigens 4:95-105, 1974
4. Thomas PK, Calne DB: Motor nerve conduction velocity in
peroneal muscular atrophy: evidence for genetic heterogeneity.
J Neurol Neurosurg Psychiatry 37:68-75, 1974
Drug Error in
Anticonvulsant Therapy
E. Wayne Massey, M D
The brief communication by Dr Cloyd et al, “Reduced seizure control due to spoiled phenytoin capsules” (Ann
Neurol 7:191-193, 1980), is interesting. We have had
difficulty with incorrect dispensing of carbamazepine,
which could have resulted in serious effects.
A 38-year-old mildly retarded woman had good seizure
control until suddenly she had five grand mal seizures over
three days. An immediate carbamazepine determination
indicated a blood level of less than 1 pglml. She assured us
that she was taking her medication; the family had been
reliable in previous years. Although no further seizures occurred in the next 48 hours and the dosage remained
unchanged, a repeat carbamazepine determination still
showed a blood level of less than 1 &mI. Results of ex-
The t w o drugr present in the patient’s prescription bottle: Tok i n (left) and Tegretol (right).
amination were as before except that no nystagmus was
present. H e r mother then examined the prescription bottle
and found two types of pills (Figure). One was truly carbamazepine (Tegretol), but the other was tolmetin sodium
(Tolectin). Both are white but of different size, and both
are 200 mg tablets; however, Tolectin has “200” written on
the tablet. T h e patient must have been taking some of each
tablet to explain the sudden failure of therapy and low
therapeutic levels.
This substitution of Tolectin for Tegretol has happened
more than once at our hospital over the last three years,
and discussion with colleagues at other institutions indicates that similar errors have occurred elsewhere. Being
alert to this possibility is important in managing patients
receiving carbamazepine.
Division of Neurology
Duke University Medical Center
Durham. N C 27710
Gilles de la Tourette
Syndrome and
Compressive Neuropathies
Christopher G. Goetz, MD, and Harold L. Klawans, M D
Gilles d e la Tourette syndrome is characterized by_multiple motor tics and involuntary vocalizations that b e G n
c w o d . Compressive neuropathy as a potential complication of Tourette syndrome has not previously been described. Its recognition allows for rapid diagnosis and potential reversibility through treatment of the underlying
movement disorder. Two patients are presented, one with
neck pain and hand wasting and one with a sciatic notch
A 16-yac-”old girl was evaluated for neck pain and left
hand weakness of six months’ duration. T h e patient had
been diagnosed as having Tourette syndrome at age 13.
H e r tics involved violent backward jerking of her head,
often several times in a row, and multiple less violent tics,
nose twitching, eye blinking, and jerking of both legs. Vocalizations included grunting noises and throat clearing but
no formed words or coprolalic speech. She was treated with
haloperidol, 1 to 5 mg per day, with abatement of all abnormal movements except the severe, neck-thrusting tics.
Six months earlier she had noted dysesthetic tingling sensations, lasting for seconds, that radiated from her neck
into her left arm and hand and were associated with neck
tics. Three months later she noted that her left arm became
fatigued during exercise and that her little finger was numb.
She also complained that her neck muscles ached and were
vaguely tender to touch.
The general physical and neurological examinations were
normal except for the described motor tics and the symptoms involving the left arm and hand. The reflexes were
symmetrical, although there was wasting of the first dorsal
interosseus muscle and weakness of the abductor pollicus
brevis on the left. Minimal weakness was also detectable in
the intrinsic hand muscles. Decreased pinprick sensation
was noted over the little finger and hypothenar region, extending slightly above the wrist. A clinical diagnosis of
C8-TI radiculopathy was made. Roentgenograms of the
cervical spine were normal. When the haloperidol dose was
increased, the tic became less frequent and the radicular
dysesthesias abated. A soft collar further improved the patient’s symptoms.
A 41-year-old man had had coprolalia and multifocal tics
since childhood. The most violent tic was a rapid abduction
of the left thigh with external rotation of the pelvis, creating an embarrassing and fleeting erotic posture. During the
hip-thrusting tic, the patient noted local buttock pain and
occasional unpleasant shooting dysesthesias down the back
of his leg. Gradually, he also noted difficulty walking and
visible wasting of his left calf. T h e general physical and
neurological examinations were normal except for the described tics and the abnormalities involving the left leg.
There was tenderness at the left sciatic notch and marked
wasting of the anterior and posterior calf compartments.
The ileopsoas and adductor muscles were strong. The
rectus femoris, biceps femoris, gastrocnemius, tibialis anterior, and intrinsic foot muscles tested 4/5. There were
occasional fasciculations in the gastrocnemius only. Left
knee and ankle jerks were diminished. Electromyographic
study confirmed the clinical impressions of disease at the
sciatic notch. After neurological therapy there was substantial relief of motor tics and vocalizations as well as disappearance of leg dysesthesias.
These two patients, clinically fitting the criteria for
Tourette syndrome, also suffered from symptoms of peripheral nerve or radicular in jury. T h e anatomical distribution of the neuropathy coincided well with the area of the
body involved by violent tics. Furthermore, pain, dysesthesias, and progression of weakness ceased coincident
with improved control of motor tics. These facts suggest
that the neuropathy was causally related to the tics. Rapid
recognition of the underlying cause of the neuropathy allowed its pathophysiological changes to be interrupted by
treatment of the primary movement disorder. The fact that
both patients complained of pain and sensory disturbances
weeks to months before noticeable weakness was detected
suggests that if the possibility of compressive neuropathy is
actively considered in such patients, the diagnosis may be
made at a time when changes are fully reversible. Furthermore, in a patient who is seemingly stable in frequency of
tics and vocalizations, the development of such complaints
would be an indication for more vigorous therapy against
tics than would otherwise be given. Since Tourette syndrome is treated primarily to prevent o r abate embarrassment and psychological disability, this instance would be a
specific neurological reason for treating the condition.
D r Goetz is the recipient of a NINCDS Teacher-Investigator
Rush-Presb?teriun S t . Luke’s Medical Center
1725 W Harrison S t
Chicugo, IL 60612
Letters 453
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drug, errors, anticonvulsant, therapy
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