Cardiac manifestations of complex partial seizures

Cardiac manifestations of complex partial seizures

Cardiac Manifestations of Complex Partial Seizures ORRIN DEVINSKY, M.D.* BRUCE H. PRICE, M.D. STAFFORD I. COHEN, M.D. Boston, Massachusetts Six pat...

978KB Sizes 2 Downloads 7 Views

Cardiac Manifestations of Complex Partial Seizures

ORRIN DEVINSKY, M.D.* BRUCE H. PRICE, M.D. STAFFORD I. COHEN, M.D. Boston,

Massachusetts

Six patients with complex partial seizures in whom the first or most prominent manifestation was cardiovascular are described. “Angina1 pain,” which was usually atypical, developed in five patients (mean age 34), although three were admitted to coronary care unitq sinus tachycardia developed in one, sinus bradycardia leading to syncope developed in one, and a cluster of symptoms suggestive of pheochromocytoma developed in one. The causal relationship between complex partial seizures and these symptoms is based on clinical history, electrodiagnostic studies indicating epilepsy (in five of six cases) without changes of myocardial &hernia, and response to anticonvulsant but not antianginal medications. Complex partial seizures that present with cardiovascular and other visceral symptoms represent an underdiagnosed, treatable disorder. Visceral symptoms, especially abdominal discomfort, are a relatively common manifestation of complex partial seizures. Rarely, visceral symptoms may masquerade as cardiac or metabolic dysfunction, resulting in misdiagnosis and mismanagement. We have encountered six patients in whom the most prominent symptom of complex partial seizures was cardiovascular. These included chest discomfort simulating angina, palpitations from sinus tachycardia, symptoms suggestive of pheochromocytoma, and syncope resulting from sinus bradycardia or arrest. An analysis of the pathophysiology in the subjects in this report and previously reported cases of complex partial seizures with autonomic symptoms suggests diagnostic and therapeutic approaches.

CASE REPORTS

From the Departments of Medicine and the Section of Neuroscience and Behavioral Neurology, Charles A. Dana Research institute, Beth Israel Hospital, Boston, Massachusetts. Manuscript accepted February 25, 1985. Current address and address for reprint requests: Department of Neurology, The New York Hospital-Cornell Medical Center, 526 East 68th Street, New York, New York 10021. l

Patient 1. A 42-year-old woman with mild hypertension was admitted to the coronary care unit after 30 minutes of severe substernal chest pressure associated with radiation to the jaws, nausea, diaphoresis, and shortness of breath. The episode occurred while she was walking and resolved spontaneously. She had a history of intermittent abdominal pains of variable quality (crampy, stabbing, gripping, pressure, burning) for which no source was found despite extensive investigation. Frequent use of antacids provided minimal relief. Results of general medical and neurologic examinations were normal. Myocardial infarction was ruled out by serial electrocardiography and determination of cardiac isoenzymes. Electrocardiography revealed persistent T wave flattening and inversion in leads Ill and aVF, respectively. Several episodes of “angina” occurred during hospitalization; findings on electrocardiography during and after pain were unchanged. Neither nitrates nor calcium channel antagonists were effective in preventing or relieving chest discomfort. Hyperventilation did not reproduce symptoms. Results of an exercise tolerance test with thallium imaging were normal; a maximal

February

1986

The American

Journal

of Medicine

Volume

80

195

CARDIAC

MANIFESTATIONS

OF COMPLEX

PARTIAL

SEIZURES-DEVINSKY

heart rate of 175 beats per minute and work load of 150 watts were achieved without symptoms. Erythrocyte sedimentation rate, thyroid function test results, and findings on echocardiography were normal. Several months after discharge, the diagnosis of complex partial seizures was suspected because of increased emotionality and a long history of abdominal symptoms with several gastrointestinal work-ups that showed no abnormalities. Electroencephalography revealed bursts of high amplitude spikes and slow wave activity in both temporal regions and an independent focus in the right frontal region. Results of head computed tomography with and without contrast medium were normal. Phenytoin administration resulted in complete resolution of chest pressure and its associated symptoms as well as a greater than 90 percent reduction in the frequency of abdominal pain. Several months later, the patient discontinued phenytoin because of dizziness and noted the recurrence of paroxysmal chest pressure and abdominal pain. Treatment with carbamazepine was then begun, and she has remained symptom-free during the following seven months. Patient 2. A 54-year-old woman was admitted for management of chest pains. The quality and duration of the pains varied but included many episodes of chest pressure lasting 60 to 120 minutes, which radiated to the left shoulder, neck, and the fourth and fifth digits of the left hand. The first episode occurred at age six during a church service. No precipitating factors were identified; some episodes woke her from sleep. Episodes of severe chest pain led to almost 40 admissions at a community hospital for possible acute myocardial infarction. Levels of cardiac enzymes (and in later admissions, isoenzymes) were normal, electrocardiography revealed no changes from the baseline with T wave inversion in lead aVL. Episodes of pain were not associated with electrocardiographic changes. Sublingual nitroglycerin, beta blockers, calcium channel blockers, and antacids had no effect in relieving or preventing symptoms. Cardiac catheterization performed at age 48 revealed normal coronary arteries and hemodynamics. Results of echocardiography, 24-hour Holter monitoring, and upper gastrointestinal series were normal. The only cardiac risk factor was a 60-pack-a-year cigarette smoking habit. The past history was remarkable for paroxysmal hallucinations of a bad odor between ages four and six. Syncopal episodes, unassociated with convulsive movements, began at age 14. After IO syncopal episodes in the next two years, she underwent neurologic evaluation. Despite a normal result of routine electroencephalography, the patient began to receive phenytoin and had only one syncopal episode during the next five years, at which time she discontinued phenytoin. Several years later, because of an increased frequency of syncope (up to two times per week) and chest pain, treatment with phenytoin was resumed. There was no significant resolution in either symptom despite therapeutic phenytoin levels. She had chronic depression (attempted suicide several times) and experienced paroxysmal feelings of profound unhappiness, following episodes of chest pain. Normal results of medical and neurologic examination

196

February

1966

The American

Journal

of Medicine

Volume

ET AL

were recorded on admission. Values of cardiac isoenzymes were normal and electrocardiographic findings during episodes of chest pain were unchanged. Admission medication included sublingual nitroglycerin as needed, nifedipine IO mg four times a day, cimetidine 300 mg at bedtime, phenytoin 100 mg three times a day, and imipramine 25 mg four times a day. Nifedipine and nitroglycerin were discontinued without apparent change in frequency or duration of chest pain. Results of thyroid function tests and 24-hour symptom-free Holter monitoring were normal. Findings on head computed tomography without contrast medium were normal. Routine electroencephalography several months prior to admission showed slowing and rare sharp transients in the temporal areas. During hospitalization, sleep electroencephalography with sphenoidal electrodes revealed frequent bursts of paroxysmal epileptic activity in both temporal areas, but predominantly on the left. Carbamazepine was added, and after three months of combined anticonvulsant therapy, she has had only one episode of syncope compared with five during the month prior to admission and has enjoyed greater than 90 percent reduction in frequency and severity of chest pain. Patient 3. A 31-year-old man was admitted to the coronary care unit with one hour of atypical chest pain believed to be consistent with angina, although the results of electrocardiography were normal. He was in good health until six years prior to admission, when he began experiencing stereotyped spells consisting of the abrupt onset of bilateral tinnitus immediately followed by stabbing, throbbing pressures and pain in the left precordium radiating to the left axilla, neck, and medial left arm and into the fourth and fifth digits. Simultaneously, he noted palpitations, diaphoresis, nausea, facial flushing, a diffusely throbbing headache, fear, and sense of impending doom. Episodes were intermittently accompanied by visual illusions that included micropsia and macropsia. The episodes occurred one to three times per day and lasted from two to 30 minutes. Atypical features associated with chest pain were not fully described on admission. During the preceding five years, the patient had been hospitalized many times for extensive noninvasive evaluations and had received diagnoses such as neuritis and hysteria. The past history was unremarkable: his only cardiac risk factor‘was family history of early myocardial infarction. Following admission, normal findings on physical and neurologic examinations were recorded. Myocardial infarction was ruled out by serial cardiac isoenzyme determinations and electrocardiography. Results of chest radiography, erythrocyte sedimentation rate, results of thyroid function tests, findings on electrocardiography, and a 24-hour urine vanillylmandelic acid measurement were normal. Results of electrocardiography during and after chest pain were normal. Neither nitrates nor calcium-channel blockers were effective in preventing or relieving chest discomfort. An exercise tolerance test revealed no ischemic changes. Twenty-four hour Holter monitoring revealed two episodes of sinus tachycardia up to 180 beats per minute, which correlated with the patient’s symptoms of rapid heart action, chest pressure and pounding, tinnitus, nausea, and’ diaphoresis. Sleep-deprived electroencephalography with

60

CARDIAC

nasopharyngeal leads demonstrated a left medial temporal epileptic focus with rare right-sided discharges. An isolated generalized epileptiform discharge was also seen. Results of computed tomography of the head with contrast medium were unremarkable. Carbamazepine was administered with diminished frequency of spells. Mephobarbital was then added for six weeks without benefit. When mephobarbital was replaced by valproic acid, there was a 90 percent reduction of episodes during a follow-up period of 10 months’ duration. Patient 4. A 53-year-old man with borderline hypertension was evaluated for palpitation and dizziness with near syncope, and chest discomfort with left arm radiation. Atria] fibrillation was diagnosed at an outside hospital three years earlier, and he had been treated with digoxin and atenolol since that time. One year later, he presented to us with dizziness and near syncope. Results of medical examination and electrocardiography were normal. Meclizine had no effect on dizziness. Several months later, he had a IO-minute visual illusion while reading, with words rising above the line. He then looked at a wall picture, and he noted that the upper right corner was missing. He had no march of visual symptoms or headache. Palpitations then became the most prominent symptom: however, self-monitoring of pulse during these episodes revealed no change from baseline. Twenty-fourhour Holter monitoring revealed a four-beat run of ventricular or supraventricular tachycardia (rate 155 beats per minute) that was not associated with symptoms. He was later admitted to the hospital because of frequent palpitations of two to four minutes’ duration that were sometimes associated with chest discomfort and left arm radiation. Several episodes observed by physicians revealed no change in vital signs or electrocardiographic findings. The patient denied emotional changes during these episodes. Normal studies included electrocardiography, exercise tolerance test (work load 150 watts), and noninvasive carotid scanning (B mode) and direct Doppler. Echocardiography revealed a dilated left atrium (5.2 cm) but no source of emboli. Repeated Holter monitoring showed one ventricular couplet and a three-beat run of supraventricular tachycardia. Neither coincided with symptomatic periods. The presence of complex partial seizures in one son (and possibly another) together with the clinical features and negative results of cardiac work-up suggested complex partial seizures. A neurologic consultation was obtained in which an additional history and examination revealed frequent, brief paroxysmal episodes of everything receding into the distance since early childhood. Slight hypoplasia of the left face, hand, and foot, and increased left upper extremity deep tendon reflexes were noted. Electroencephalography demonstrated bilateral central suprasylvian isolated epileptic discharges and r/ght temporal slowing. Results of head computed tomography without contrast medium were normal. Phenytoin has led to greater than 90 percent reduction in the frequency of episodes of palpitation, dizziness, and resolution of chest pain. (Duration of treatment was six months.) Patient 5. A 19-year-old man complained of syncope, which had occurred at six-month to two-year intervals since

February

MANIFESTATIONS

OF COMPLEX

PARTIAL

SEIZURES-DEVINSKY

ET AL

age 12. The episodes were not associated with tonic or clonic movements or incontinence. In early childhood, he had dizzy spells, hypersensitivity to noises, and manic episodes. Experiences of “knowing the future” and deja vu, fear of open spaces, and hypergraphia (tendency for extensive writing) have been present for the past five years. One year prior to entry, syncopal episodes increased in frequency and were accompanied by tingling of the tongue, pupillary dilation, frontal head pressure, and crampy sensations in the chest that were not associated with radiation or shortness of breath. Confusion and behavioral withdrawa, for about two hours followed these episodes. Two months prior to admission, mononucleosis developed with an Epstein-Barr virus titer of 1: 1,024. During this illness, violent outbursts occurred for the first time. These behaviors were not temporally related to ictal events. When he was admitted for evaluation of syncope, results of general physical and neurologic examinations were normal. Results of electrocardiography were normal, but Holter monitoring showed sinus pauses of 1.6 to 2.4 seconds and rare Wenckebach second-degree block during sinus tachycardia. Results of head computed tomography without contrast medium were normal, and electroencephalography revealed bifrontal spiking. Therapy with carbamazepine has led to resolution of syncopal episodes and chest discomfort for eight months. Patient 6. A 62-year-old man was first evaluated 14 years ago for syncope, which followed an aura of “not being there and then seeing an incredibly clear image of a fence.” In the hospital, a similar aura was followed by syncope with sinus bradycardia at a rate of 20 beats per minute. Results of general physical and neurologic examinations were unremarkable; laboratory data, including conventional electroencephalography, brain scanning, and lumbar puncture, were normal. Electrocardiography demonstrated left ventricular hypertrophy by voltage criteria. The patient was discharged receiving a long-acting muscarinic blocker, but was readmitted two months later for pacemaker placement after another aura and syncopal episode. After pacemaker placement, auras continued to occur with associated weakness but without syncope. During one such episode, a relative who was a nurse felt a weak pulse at the pacemaker’s rate. Administration of phenytoin was then begun with cessation of 811spells. Primidone was substituted for phenytoin after a rash developed. Fourteen years later, with pacemaker revisions and primidone therapy, he has had rare auras without syncope only when primidone levels were low. COMMENTS Complex partial seizures can mimic angina, primary cardiac arrhythmias, and a cluster of symptoms suggestive of pheochromocytoma (Patient 3). These disorders have received little attention, but the condition of Patients 1 to 5 were newly diagnosed on the medicine service at the Beth Israel Hospital during an 18-month period. The causal relationship between complex partial seizures and these symptoms is based on clinical history, electrodiagnostic studies indicating epilepsy (in five of six cases) without

1988

The American

Journal

of Medicine

Volume

80

197

CARDIAC

MANIFESTATIONS

TABLE I Reference This

198

report

February

OF COMPLEX

PARTIAL

SEIZURES-DEVINSKY

ET AL

“Angina1 Pain” with Complex Partial Seizures Patient 1

1988

Age and Sex

Chest Pain Pattern

Diagnostic Studies

Treatment/Response

42F

Substernal chest pressure. Radiation to jaw. Associated with diaphoresis, shortness of breath. Episodes lasted 30 to 60 seconds, occurred one to four times each week

EKG at rest and with chest pain showed T wave flattening inferiorly. ETT with thallium showed normal results. EEG showed bitemporai and right frontal epileptic activity. Result of head CT was normal EKG at rest and with pain showed T wave inversion in lead aVL. Results of coronary arteriography, echocardiography, 24-hour Holter monitoring, upper gastrointestinal series, and head CT were normal. EEG showed bitemporal (left predominant) epileptic activity Result of EKG at rest and with chest pain was normal. Result of ETT was normal. Results of echocardiography, 24-hour urine vaniiiylmandelic acid determination, and head CT were all normal. EEG showed bitemporai epileptic activity Result of EKG at rest and with pain was normal. Twenty-four-hour Hoiter monitoring showed one four-beat run of ventricular tachycardia (?) or supraventricular tachycardia (155 beats per minute); repeated monitoring showed ventricular couplet and threebeat supraventricular tachycardia. Echocardiography showed enlarged left atrium without embolic source. Resuits of ETT, noninvasive carotid studies, and head CT were normal. EEG showed bilateral suprasylvian epileptic discharges and right temporal slowing. Results of EKG and head CT were normal. EEG showed bifrontal spikes

Sublingual nitroglycerin and sublingual nifedipine had no effect. Phenytoin and carbamazepine each produced complete resolution

2

54F

Variable quality and frequency; included chest pressure with left arm radiation lasting 60 to 120 minutes; sometimes followed by depression

3

31M

4

53M

Bilateral tinnitus. Stabbing, throbbing, and pressure pain in left arm, associated with nausea, diaphoresis, tachycardia, flushing, and headaches. Episodes lasted two to 90 minutes and occurred one to three times each day Poorly characterized chest discomfort with left arm radiation and palpitations lasting two to four minutes

5

19M

The American

Crampy sensation in chest with mydriasis, headache, and syncope followed by confusion. Episodes lasted two to 30 seconds and occurred one to two times each week

Journal

of Medicine

Volume

80

Sublingual nitroglycerin and nifedipine did not relieve pain. Oral cimetidine, beta blockers, and nifedipine did not prevent pain. Phenytoin and carbamazepine led to a 90 percent reduction

Sublingual nitroglycerin, sublingual nifedipine, and intravenous morphine had no effect. Phenytoin and valproic acid produced 90 percent reduction of episodes

Phenytoin led to 90 percent reduction in palpitations and cessation of chest pain

Carbamazepine produced complete resolution of chest pain and syncopal episodes

CARDIAC

TABLE I (cont’d) Reference

“Angina1 Patient

Pain” with Complex

Age and Sex

[41

6

44M

141

7

26M

151

a

34M

151

9

57F

1'31

10

39M

EKG = electrocardiography;

ETT = exercise

MANIFESTATIONS

Partial

Chest Pain Pattern

test;

Diagnostic

February

SEIZURES-DEVINSKY

ET AL

Studies

Treatment/Response

EEG showed generalized dysrhythmia, not diagnostic of epilepsy. EKG not reported

Phenobarbital led to complete resolution for one year

EEG showed generalized dysrhythmia, not diagnostic of epilepsy. EKG not reported

Phenobarbital led to complete resolution for six months

Results of EKG were normal. EEG not reported. Pneumoencephalography showed left frontal mass

Not reported

Results of skull radiography were normal. Results of EEG were diffusely abnormal. EKG not reported.

Not reported

Results of EKG at rest were normal. EEG showed bilateral high voltage.

No response to vasodilators. Phenytoin led to complete resolution of episodes

EEG = electroencephalography;

changes of myocardial ischemia, and response to anticonvulsant but not antianginal medications. “Heart pain” as a manifestation of epilepsy was recognized as early as 500 A.D. in the Brahminic book Sushruta [I]. Hughlings Jackson [2] described a patient with “severe oppression across the chest” and “fear of some impending catastrophe.” Cowers [3] listed “cardiac sensation,” which included pain, palpitation, and vague discomfort, as the 14th of 17 most frequent symptoms of minor seizures. More recently, chest discomfort simulating angina has been reported in five patients with complex partial seizures, but none had epileptic activity on electroencephalography [4-61. The clinical features of these patients and the five subjects with chest pain in our report are summarized in Table I. Eight of the 10 were male. The average age of presentation was 34 (range six to 56),

PARTIAL

Seizures

Severe left chest and precordial pain associated with fear of death. Episodes at rest and with exertion. Occurred two to three times each week Severe substernal chest pain associated with tachycardia, diaphoresis, and flushing. Episodes lasted less than 1.5 seconds, occurred at intervals of three days to three months Epigastric and substernal crushing pressure lasting seconds; then eye blinking and loss of consciousness; then dull precordial pain radiating to left arm and headache. Hyperventilation reproduced symptoms Epigastric and thoracic pressure followed by a generalized tonic-clonic seizure. Episodes occurred 0 to two times each week Nausea and substernal chest pain radiating to left arm; precipitated by activity, stress, and large meals. Episodes lasted 20 to 30 seconds, occurred two to three times each week tolerance

OF COMPLEX

CT = computed

tomography.

which is young for onset of angina.‘Episodes of pain typical of myocardial ischemia were present in four patients. Chest pains were associated with radiation to the jaw or left arm, nausea, diaphoresis, or dyspnea in five patients. However, “angina1 pain” was associated with factors that increase myocardial oxygen demand in only one case. Atypical features were present in seven patients. These included a stabbing or crampy quality of pain, onset of pain in the upper abdomen, tinnitus, and the sensation of mind-body dissociation. Hyperventilation reproduced symptoms in one patient but was without effect in our patients. In addition to our four patients, nitrates were used in one prior case without effect. All six patients treated with phenytoin, phenobarbital, valproic acid, carbamazepine, or a combination of these drugs had a dramatic response. Electrocardiography was performed

1988

The American

Journal

of Medicine

Volume

80

199

CARDIAC

MANIFESTATIONS

OF COMPLEX

PARTIAL

SEIZURES-DEVINSKY

in eight patients during episodes of chest pain; results were normal in six, and baseline nonspecific ST-T wave abnormalities were shown in two. Cardiac catheterization was performed in one patient and showed normal findings. Exercise tolerance tests showed no abnormalities in the five patients in whom they were performed. Three previously described patients had abnormal but nondiagnostic results of electroencephalography. In the two patients’ in whom electroencephalography was not performed, chest pressure was followed by eye blinking and loss of consciousness in one and a tonic-clonic seizure in the other [5]. Tachyarrhythmias, and less commonly bradyarrhythmias, have been reported with complex partial seizures [5,7-121. Holter monitoring in Patient 5 revealed sinus tachycardia with rates of up to 180 beat8 per minute during his auras. Palpitations resolved with anticonvulsant therapy. Marshall et al [ 121 described 12 patients with complex partial seizures in whom seizure activity on electroencephalography preceded the onset of tachycardia by four to eight seconds. Pritchett et al [IO] described a one-year-old child with complex partial seizures and paroxysmal supraventricular tachycardia. The arrhythmia did not respond to.digoxin, propranolol, quinidine, or combinations of these drugs, although carbamazepine led to resolution of neurologic symptoms and arrhythmias. Sinoatrial node dysfunction resulting in syncope may follow a complex partial seizure. Patient 8 had an aura of a complex visual hallucination, which was followed by sinus bradycardia at a rate of 20 beats per minute and syncope. A normal result of electroencephalography (while the patient was awake and without special leads) led physicians to discount epilepsy. The patient received a pacemaker, which prevented bradycardia and syncope, but auras persisted. Primidone led to resolution of the auras. Phizackerley et al [9] observed a 7%year-old woman in whom an epigastric aura and intense apprehension were followed by asystole of up to eight seconds and loss of consciousness. Electroencephalography revealed spike activity in the right temporal lobe. Treatment with tincture of belladonna prevented syncope but not the aura. Paroxysmal signs and symptoms of complex partial seizures may be indistinguishable from those of pheochromocytomas and include headache, hypertension, palpitations, flushing, diaphoresis, mydriasis, tremor, and apprehension. Both disorders often present between five and 25 years of age. Our Patient 3, as well as previously described patients, had a pheochromocytoma included in the differential diagnosis [7,11,13]. However, appropriate studies excluded this diagnosis, and electroencephalography revealed epileptic activity in the temporal lobes. There was a good response to anticonvulsant medication. The mechanisms by which complex partial seizures cause autonomic symptoms are complex. Limbic areas, in which complex partial seizures arise, are richly con-

200

February

1988

The American

Journal

of Medicine

Volume

ET AL

netted with the hypothalamus, the principal regulatory center of the autonomic nervous system. Effects on hypothalamic activity are probably responsible for many complex partial seizure-induced visceral symptoms. In addition, subjective visceral sensations may occur without autonomic changes in the viscera. Therefore, complex partial seizures may cause autonomic changes, which then lead to symptoms or cause “referred visceral syrnptoms.” A spectrum of autonomic signs and symptoms have been recorded during complex partial seizures and electrical stimulation of limbic structures in humans and animals [4-191. These include changes in heart rate and rhythm, blood pressure, respiratory rate and pattern, pupillary size, vasomotor and sudomotor activity, gastrointestinal tract motility, and gastric acid secretion. Similar effects follow hypothalamic stimulation and suggest that arrhythm,ias and the autonomic episodes (as in Patient 3) may result from hypothalamic stimulation by a limbic discharge. The pathophysiologic complexity is illustrated by Patient 8, who presented with syncope from sinus bradycardia. However, complex partial seizures, not bradycardia, was the primary disorder. The high incidence of unexpjained sudden death in young epileptic patients [20-231 may be related to autonomic changes during seizures, which may cause arrhythmias and neurogenic pulmonary edema [24-281. These patients usually have subtherapeutic anticonvulsant levels and approximately 50 percent die in their sleep without evidence of status epilepticus. Necropsy rarely reveals the cause of death. Perhaps a representative example is the case of an 1 l-year-old girl who had recurrent episodes of an aura followed by syncope. When the aura came, she would rush to sit down. One day after she immediately sat down in response to the aura, her body stiffened and she suddenly died [2 11. Chest discomfort associated with complex partial seizures and electrical stimulation of limbic areas in humans does not appear to result from myocardial ischemia. The lack of electrocardiographic changes or elevation of levels of cardiac isoenzymes in Patients 1, 2, and 4 does not suggest that ischemia induced chest pain. Similarly, Dodge et al [27] reported a case in which three episodes of left-sided epilepsia partialis continua were preceded by severe substernal chest pain thought to represent myocardial infarction despite normal results of serial electrocardiography. Postmortem examination five years later revealed a large old infarct of the right temporal lobe, whereas the heart was “normal in all respects.” “Angina1 pain” has also been reported as a symptom of migraine [28,29]. Sacks [29] observed this manifestation in only two of his more than 1,000 patients with migraine. In one of his patients, the chest tightness was associated with left arm radiation, and lasted two to three hours. Result8 of electrocardiography were normal during the episode,

80

CARDIAC

MANIFESTATIONS

which responded to ergotamine, rather than to nitroglycerin. As with complex partial seizures, diagnosis may be difficult since this complaint may not be accompanied by more usual symptoms during some episodes. Certain visceral sensations may first be perceived in limbic structures. Thus, discharges in these areas may produce visceral sensations without physiologic changes in the viscera. It is of interest that the feeling of impending doom that accompanies myocardial infarction also occurs with complex partial seizures. It should be noted, however, that neurogenic factors may cause myocardial ischemia. Intracranial hemorrhage in humans and animals can result in electrocardiographic and pathologic changes of myocardial infarction [30,31]. Similar observations have been made in animals following electrical stimulation of hypothalamic and limbic areas [32]. These studies suggest that myocardial ischemia could result from complex partial seizures. The diagnosis of complex partial seizures may be difficult. lctal manifestations such as confusion or blank stare with subsequent amnesia and motor automatisms (e.g., lip smacking and chewing) are likely to attract attention, but are not always present. Directed questions often elicit less subtle symptoms. These include hallucinations and illusions that may occur in any sensory modality; emotional experiences, most commonly fear; “psychic” phenomena such as dreamlike states, mind-body dissociation, and “religious experiences”; deja vu and jamais vu; and visceral (autonomic) symptoms, which have been reported in 40 percent of patients with complex partial seizures [5]. Evaluation and treatment of complex partial seizures have recently been reviewed [33-351. It is important to note that patients with complex partial seizures may have normal results of electroencephalography. Complex partial seizures arise from limbic areas of the temporal and frontal lobes, which are located deep in the hemispheres: epileptic activity in these areas may be seen with intracerebral electrodes whereas simultaneous recordings from surface electrodes reveal no abnormality [36]. Prolonged monitoring with the use of nasopharyngeal, nasoethmoidal, or sphenoidal leads, and activation procedures such as sleep, sleep deprivation, and hyperventilation can increase the yield from electroencephalography [35,37]. Computed tomographic head scanning may reveal a structural abnormality (e.g., tumor, stroke, or vascular malformation), but shows normal findings in most patients. Abnormal results of computed tomographic scanning are more likely in those with seizure onset after adolescence and focal findings on neurologic examination. Anticonvulsant medication is the primary approach in the management of complex partial seizures. Carbamazepine, phenytoin, primidone, and phenobarbital are the principal anticonvulsants used in complex partial seizures

February

OF COMPLEX

PARTIAL

SEIZURES-DEVINSKY

ET AL

[33]. Many patients require two or more medications for adequate seizure control, and some show refractoriness to medical therapy and may be candidates for neurosurgical intervention [34,35]. Therapy for cardiac manifestations of complex partial seizures has not been well studied. “Anginal” pain and arrhythmias induced by complex partial seizures have responded to a variety of anticonvulsants, as just described. Phenytoin is useful in the treatment of digitalisinduced arrhythmias and less so in certain ventricular arrhythmias [37]. In experimental studies of cardiac arrhythmias produced by hypothalamic stimulation, phenytoin acts centrally to depress hyperactivity in cardiac sympathetic nerves and to abolish arrhythmias [38-401. Thus, phenytoin may be particularly useful in the treatment of arrhythmias associated with complex partial seizures. Carbamezepine has been implicated in the development of asystole, sinoatrial, and atrioventricular block and decreased Purkinje automaticity in eight elderly patients with trigeminal neuralgia [4 l-451. This association is supported by the findings that carbamazepine prolongs atrioventricular node conduction time and suppresses ventricular ectopy in dogs [46]. Carbamazepine should probably not be used as the drug of first choice for complex partial seizures in patients with bradyarrhythmias or abnormal cardiac conduction systems. Complex partial seizures that present with visceral symptoms are probably underdiagnosed. Chest discomfort masquerading as typical or more commonly atypical angina, arrhythmias that can produce syncope, and symptoms suggestive of pheochromocytoma may all result from complex partial seizures. Correct diagnosis and treatment with appropriate anticonvulsant medication can alleviate symptoms and possibly prevent seizure-induced arrhythmias, neurogenic pulmonary edema, or death. In addition, autonomic manifestations of complex partial seizures may be particularly hazardous in patients with known cardiovascular disease. If other diagnoses for these autonomic symptoms are not supported by the history, laboratory data, or medication response, physicians should investigate the possibility of complex partial seizures by a careful review of the clinical history and by performing electroencephalography. However, a normal electroencephalographic finding does not rule out the possibility of complex partial seizure disorder. If there is a strong clinical suspicion, an empiric trial of anticonvulsants is warranted. ACKNOWLEDGMENT

We thank Drs. Ken Silverman, James Morgan, and Michael Ronthal for their assistance in providing information on Patients 2 and 4 under their care. We also thank Dr. Jerome Posner for his critical review of this manuscript, and Ms. Pauline Kehm and Ms. Shawn D. Bartley for their generous secretarial assistance.

1988

The American

Journal

of Medicine

Volume

80

201

CARDIAC

MANIFESTATIONS

OF COMPLEX

PARTIAL

SEIZURES-DEVINSKY

ET AL

REFERENCES 1. 2.

3. 4. 5. 6. 7.

8. 9. 10. Il.

12.

13. 14. 15.

16.

17.

18.

19. 20. 21. 22.

23. 24.

202

Pirkner EH: Epilepsy in the light of history. Ann Med Hist 1929; 1: 453-480. Jackson JH: On right- and left-sided spasm at the onset of epileptic paroxysms, and on crude sensation warnings and elaborate mental states. Brain 1886; 3: 192-206. Gowers WR: A manual of diseases of the nervous system. Philadelphia: Blakiston, Son and Co., 1888; 1090-1091. Winans HM: Epileptic equivalents, a cause of somatic symptoms. Am J Med 1949; 7: 150-152. Mulder DW, Daly D, Bailey AA: Visceral epilepsy. Arch Intern Med 1951; 93: 481-493. Janjigian ER: Cardiac epilepsy simulating the angina1 syndrome. Am J Med 1953; 110: 34-40. Metz SA, Halter JB, Porte D, Robertson RP: Autonomic epilepsy: clonidine blockade of paroxysmal catecholamine release and flushing. Ann Intern Med 1978; 88: 188-193. Van Buren JM: Some autonomic concomitants of ictal automatism. Brain 1958; 81: 505-529. Phizackerley PJR, Poole EW, Whitty CWM: Sinoauricular heart block as an epileptic manifestation. Epilepsia 1954; 3: 89-91. Pritchett ELC, Minamara JO, Gallagher JJ: Arrhythmogenic epilepsy: a hypothesis. Am Heart J 1980; 100: 683-687. Devinsky 0, Bear D: Varieties of aggressive behavior in temporal lobe epilepsy. Am J Psychiatry 1984; 141: 651-656. Marshall DW, Westmoreland BF, Sharbrough FW: lctal tachycardia during temporal lobe seizures. Mayo Clin Proc 1983; 58: 443-446. Brown RW, McLeod WR: Sympathetic stimulation with temporal lobe epilepsy. Med J Aust 1973; 2: 274-276. Delago JMR: Circulatory effects of cortical stimulation. Physiol Rev 1960; 40 (suppl 4): 146-171. Van Buren JM: Sensory, motor and autonomic effects of mesial temporal lobe stimulation in man. J Neurosurg 1961; 18: 278-288. Chapman WP: Depth electrode studies of temporal lobe epilepsy. In: Ramey ER, O’Doherty DS, eds. Electrical studies on the unanesthetized brain. New York: Hoebner Inc., 1960; 334-350. Pool JL, Ransohoff H: Autonomic effects on stimulating the rostra1 portion of the cingulate gyri in man. J Neurophysiol 1949; 12: 385-392. Smith WK: The functional significance of the rostra1 cingular cortex as revealed by its response to electrical stimulation. J Neurophysiol 1945; 8: 241-255. Ward AA: The cingular gyrus. J Neurophysiol 1948; 11: 13-23. Krohn W: Causes of death among epileptics. Epilepsia 1963; 4: 315-321. Hirsh CS, Martin DL: Unexpected death in young epileptics. Neurology 1971; 21: 682-690. Terrence CF, Wisotzkey HM, Perper TA: Unexpected, unexplained death in epileptic patients. Neurology 1975; 25: 594-598. Jay FW, Leestma JE: Sudden death in epilepsy. Acta Neurol Stand 1981; 63 (suppl82): l-166. Terrence CF, Rao GR, Perper TA: Neurogenic pulmonary

February

1986

The American

Journal

of Medlclne

25.

26. 27.

28. 29. 30.

31.

32.

33. 34. 35. 36.

37. 38.

39. 40.

41. 42. 43. 44. 45.

46.

Volume

80

edema in unexpected unexplained death of epileptic patients. Ann Neurol 1981; 9: 456-464. Darwell JC, Jay SJ: Recurrent postictal pulmonary edema: a case report and review of the literature. Epilepsia 1982; 23: 71-83. Lown B, Verner RI: Neural activity and ventricular fibrillation. N Engl J Med 1976; 294: 1165-l 170. Dodge PR, Richardson EP, Victor M: Recurrent convulsive seizures as a sequel to cerebral infarction: a clinical and pathological study. Brain 1954; 77: 610-638. Fitz-Hugh J: Precordial migraine: an important form of “angina innocens.” New Int Clin Series 3, 1940; 1: 141-147. Sacks OW: Migraine. Berkeley: University of California Press, 1970; 58-59. Weidler DJ: Myocardial damage and cardiac arrhythmia after intracranial hemorrhage. A critical review. Stroke 1974; 5: 759-763. Melville KI, Blum B, Shister H, Silver MD: Cardiac ischemic changes and arrhythmias induced by hypothalamic stimulation. Am J Cardiol 1963; 12: 781-791. Hall RE, Cornish K: Role of the orbital cortex in cardiac dysfunction in unanesthetized Rhesus monkey. Exp Neurol 1977; 56: 289-297. Woodbury DM, Penry JK, Pippenger GE: Antiepileptic drugs: mechanism of action. New York: Raven Press, 1982. Delgado-Escueta, Treiman AV, Walsh GO: The treatable epilepsies. N Engl J Med 1983; 308: 1508-1514. Schemer DL: Current concepts in neurology: partial epilepsy. N Engl J Med 1983; 309: 535-536. Lieb JP, Walsh GO, Babb TL, Walter RD, Crandall PH: A comparison of EEG seizure patterns recorded with surface depth electrodes in patients with temporal lobe epilepsy. Epilepsia 1976; 17: 137-160. Gilman AG, Goodman LS, Gilman A: Pharmacological basis of therapeutics. New Yqrk: Macmillan, 1980; 769. Gillis RA, McClellan JR, Sauvci TS: Depression of cardiac sympathic nerve activity by diphenylhydantoin. J Pharmacol Exp Ther 1971; 173: 599-610. Evans DE, Gillis RA: Effect of diphenylhydantoin and lidoCaine on cardiac arrhythmias induced by hypothalamic stimulation. J Pharmacol Exp Ther 1974; 191: 506-517. Evans DE, Gillis RA: Effect of oubain and its interaction with diphenylhydantoin on cardiac arrhythmias induced by hypothalamic stimulation. J Pharmacol Exp Ther 1974; 195: 577-586. Beerman B, Edhag 0, Vallin H: Advanced heart block aggravated by carbamazepine. Br Heart J 1975; 37: 668-671. Herzberg L: Carbamazepine and bradycardia. Lancet 1978; 1: 1097-1098. Hamilton DR: Carbamazepine and heart block. Lancet 1978; I: 1365. Adverse drug reactions advisory committee: Carbamazepine. Med J Aust 1979; 1: 574. Ladefoged SD, Mogelrang JC: Total atrioventricular block with syncopes complicating carbamazepine therapy. Acta Med Stand 1982; 212: 185-186. Steiner C, Wit Al, Weiss MP, Damato AN: The antiarrhythmic action of carbamazepine (Tegretol). J Pharmacol Exp Ther 1980; 173: 323-335.