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Carbamazepine and the heart.

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DCHS and HACP as two clinical variants of one and the
same syndrome: ataxic hemiparesis.
H6pital Rigional du Nord
Clinique Saint-Louis
Ettelbruck, Luxembourg
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Jerome H . Chin, MD, PhZ)
Adenosine and
Seizure Termination
M. Dragunow
I read with interest D r Chin’s article “Adenosine Receptors
in Brain: Neuromodulation and Role in Epilepsy” {l). However, I was disappointed that D r Chin did not mention perhaps the most important role for adenosine in epilepsy: its
role as a natural anticonvulsant to block seizure spread and
to terminate seizures C2). A growing body of data shows
convincingly that adenosine is released during seizure activity
[3] and that by activating theophylline-sensitive adenosine
A1 receptors it terminates seizures in animals [2, 4).In the
presence of a subconvulsive dose of the adenosine antagonists caffeine, theophylline, or 8-cyclopentyl-theophylline,
partial seizures that would normally last only a few seconds
are converted into fully generalized seizures that can last
many minutes [2,4].Caffeine and theophylline also prolong
the duration of seizures in humans [ 5 , 61. Conversely, adenosine agonists convert generalized seizures into partial seizures
[2, 71. These results strongly support our hypothesis that
endogenous adenosine inhibits seizure spread and terminates
seizure discharges in the brain {7]. Loss of this adenosine
anticonvulsant system leads to starus epilepticus in animals
and humans [ 5 , 7, 8), although it is not known if status epilepticus occurring spontaneously in humans also involves
adenosine loss.
Thus, adenosine is a powerful endogenous anticonvulsant
substance in the nervous system that terminates seizures arid
will no doubt become an important target for anticonvulsant
drug development.
Department of Pharmacology and Clinical Pharmacoloa
University of Auckland School of Medicine
Auckland, New Zealand
I appreciate Dr Dragunow’s interest in my article and in the
important role of adenosine as an endogenous neuromodulacor. D r Dragunow provides additional citations, including
some of his own, to support one of the central themes of my
review, namely, that adenosine may function as an endogenous anticonvulsant to inhibit seizure initiation and propagation. It is hoped that future research will substantiate this
proposal and result in pharmacological manipulation of adenosine systems for the treatment of epilepsy.
Department of Neurology
University of California
San Francisco. C A
Lar bamazepine
and the Heart
iMario Puletti, MD,” Cesare Iani, MD,t
Mario Curione, MD,” Massimo Trappolini, MD,*
and Mario Manfredi, MDP
Reports of sinoatrial or atrioventricular conduction disorders
in patients treated with carbamazepine have recently appeared {l-41. Given the widespread use of this drug, we
undertook systematic study of its cardiac effects. Two protocols were planned: the present one, which uses routine cardiological examination, and a second protocol now in development that requires Holter monitoring before and during
carbamazepine treatment. We report here on the results of
the first protocol.
Ninety-two patients with epilepsy (36 males and 56 females) were studied. Average age was 36.5 years (range 7 to
77 yr; 33 patients were over 40 yr). None had signs of cardiac
Annals of Neurology
Vol 29 No 5
May 1991 575
abnormality before treatment. The participants were taking
carbamazepine as monotherapy, at an average dose of 708
mgiday (from 200 to 1,400 mgiday) with serum levels below
toxic values. The duration of the treatment was on average
6 months (from 2 mo to 2 yr). Each patient underwent cardiological examination, standard EKG, and review of history
with the specific aim of uncovering possible syncopal episodes disguised by the underlying epileptic symptoms.
There were no suspected syncopal episodes in any patient.
Heart rates were between 60 and 100 beatsimin in 87 patients (mean age 40.2 yr), above 100 in 5 patients (mean age
18.6 yr), and in one patient 5 5 per minute (age 42 yr). None
of the participants showed relevant sinus arrhythmia. There
were no sinoatrial or atrioventricular conduction disorders,
and the PR intervals remained within normal limits. Seven
patients ( 2 males, 5 females, 24-43 yr, mean age 32.2 yr)
showed minor disturbances in right intraventricular conduction (rSR aspect in V1, with QRS lasting less than 0.10 sec).
An incomplete right bundle branch block was present in one
patient (male, aged 17 yr) and a left anterior hemiblock in 2
patients (1 male, 1 female, ages 19 and 63 yr). The QT
length was lower than normal in 8 2 patients. This effect was
probably caused by the reduced length of the action potential, experimentally observed by Steinert f53.
Although this study involved relatively young patients, we
feel safe in concluding that (1) the incidence of conduction
576 Annals of Neurology
Vol 29
No 5
May 1991
disorders is rare; (2) conduction disorders of clinical relevance do not occur in younger patients receiving carbamazepine; ( 3 ) however, any patient on carbamazepine who reports
changes in seizure type must be evaluated for cardiac conduction.
“II Clinica Medica
f Dipartimento di Scienze Neurologiche
V Clinica Neurologica
Universit2 di Roma “LaSapienza”
Rome, Italy
1. Gasparerti CM. Conduction abnormlties complicating carbamazepine therapy. Am J hied 1987;82:381
2. Benassi E, Bo GP, Cocito L, et al. Carbamazepine and cardiac
conduction disturbances. Ann Neurol 1987;22:280-281
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4. Takayanagi K, Yarnaguchi H , Hayashi T, et al. Carbamazepine
induced bradycardia-tachycardia syndrome with pharmacological
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5. Steinert C, Wit AL, Weiss MB, et al. The antiarrhythmic action
of carbamazepine (Tegretol). J Pharmacol Exp Ther 1970;173:
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