Tonic and myoclonic seizures in lennox-gastaut syndrome mistaken as complex partial seizures

] Epilepsy 1991;41,211-215

© 1991 Demos ~ n s

Tonic and Myoclonic Seizures in Lennox-Gastaut Syndrome Mistaken as Complex Partial Seizures Warren D. Lo, Jane F. Donat, and Francis S. Wright

Five children with the Lennox-Gastaut syndrome had seizures consisting of staring, mental status change, and automatic movements associated with subtle repetitive motor jerks. Based on the clinical history and observations, the seizures were classified as complex partial seizures. Because of poor responses to treatment directed toward complex partial seizures, time-locked video/EEG evaluations were performed and correctly identified the seizures as clusters of generalized myoclonic or tonic seizures. These observations demonstrate that patients with Lennox-Gastaut syndrome may develop series of brief, repeated tonic or myoclonic seizures in which the behavioral phenomena are more pronounced than the motor activity. Successful treatment of seizures in patients with LennoxGastaut syndrome may require careful differentiation between seizure types. Key Words: Lennox-Gastaut syndrome--Pediatric epilepsy--Video/EEG--Complex partial seizures--Myoclonic seizures.

The seizure disorder found in Lennox-Gastaut synd r o m e (LGS) is often difficult to control and can include several types of seizures (1,2). An e r r o n e o u s characterization of the seizures may hinder effective treatment. We report five patients with LGS w h o were diagnosed as having complex partial seizures based on descriptions given by family members, nurses, and physicians. These patients u n d e r w e n t intensive video/EEG monitoring because of failure to respond to anticonvulsant medication given for complex partial seizures. The monitoring d e m o n s t r a t e d the seizures to be series of tonic or myoclonic seizures accompanied by i m p a i r m e n t in the patients' level of consciousness rather than complex partial seizures. The observers noted and described the Received February 19, 1991; accepted June 3, 1991. From the Departments of Pediatrics and Neurology, The Ohio State University, Columbus, OH, U.S.A. This paper was presented in part at the 42nd Annual Meeting of the American Academy of Neurology, Miami, FL, May 1990. Address correspondence and reprint requests to Dr. W. D. Lo at Children's Hospital, 700 Children's Drive, Columbus, OH 43205, U.S.A.

obvious confusional state that occurred during the flurries of seizures, but the less striking m o t o r components of the seizures were mislabeled as automatisms or were not observed. This mistake in diagnosis in LGS has received little attention in the literature.

Patients The patients, two boys and three girls, ranged in age from 4 to 15 years at the time of diagnosis. All five patients were mentally retarded or developmentally delayed. The LGS was thought to be idiopathic in four patients and secondary to cranial irradiation in one patient. The patients were k n o w n to have additional types of seizures: three had tonic-clonic seizures and one had absence seizures. Interictal EEGs in all patients s h o w e d generalized (<2.5 Hz) slow spike-and-wave discharges consistent with LGS (1,2). All five had seizures that were incompletely controlled despite treatment with combinations of phenobarbital (four patients), phenytoin (three patients), carbamazepine (five patients), valproic acid (four patients), clonazepam (four patients), and clorazepate (two patients) p u s h e d to toxicity. J EPILEPSY, VOL. 4, NO. 4, 1991

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Four patients had previous routine wake and sleep EEGs, during which the presumed complex partial seizures were not recorded. The clinical diagnosis of complex partial seizures in each patient was based on the descriptions of the seizures provided by observers. The descriptions included staring, unresponsiveness, confusion, change in affect, and automatisms that included picking, clapping hand movements, and walking about the room. The seizures lasted from seconds to 20 min.

Methods Because of poor response to treatment for complex partial seizures, the children u n d e r w e n t time-locked video/EEG evaluation for identification of their seizures. All patients u n d e r w e n t 1-2-h 21-channel video/EEGs performed according to American Eiectroencephalographic Society guidelines (3). Three children also u n d e r w e n t 6-h video/EEGs or 12-48-h remote video/EEG telemetries using 16-channel recordings. Parents or caretakers observed the children during the EEG recordings and identified what they considered to be the seizures by using a microphone, event marker, or manual recordings on a seizure log. Findings on videotape and simultaneous EEGs were evaluated by an electroencephalographer (J.D.); clinical histories and examinations were evaluated by two pediatric neurologists (W.L. and F.W.). A seizure was considered to be myoclonic if it consisted of a single abrupt jerk-like muscle contraction. A seizure was considered to be tonic if the movement was less abrupt in onset and sustained longer than a myoclonic seizure (4). Responsiveness, while difficult to assess in mentally retarded patients, was determined by inattention, cessation of activity, and impaired responsiveness to observers' questioning.

Results The seizures in all five patients consisted of series of myoclonic jerks or brief tonic stiffenings, each lasting a second or less, that involved the whole body (one patient) or just the upper body and facial musculature (four patients) (Table 1). Patients were awake and sitting or standing at the time of the seizures. Each jerk or stiffening was separated from the next by 3-30 s and usually included upward eye deviation or blinking, facial grimacing, hunching of the shoulders, or an outward flare of the arms. The head or torso jerked or bobbed forward or back in three patients. In many instances, the motor activity was subtle and the patients were usually able to continue to maintain the

212 J EPILEPSY, VOL. 4, NO. 4, 1991

sitting or standing posture throughout the series of seizures. During the series of seizures, the patients ceased their activities and were unable to talk or communicate. The patients stared or appeared unresponsive between jerks or tonic stiffenings. Symptoms included inappropriate grinning, laughter, drooling, automatic hand movements, and the appearance of unhappiness or distress. If the patient was sitting, the head and body drooped; when standing, one patient wandered about the room. These changes in behavior continued for the duration of the series of motor jerks and were punctuated by the repeated motor jerks. On the EEG, each generalized jerk or tonic stiffening in the series was accompanied by a generalized sharp or slow-wave transient followed by a generalized decrement. This pattern occurred repeatedly during the series (Fig. 1). One patient also had partial motor seizures recorded on the same video/EEG. The tonic and myoclonic seizures in these five patients were difficult to control. In one child, the addition of valproate was followed by a partial reduction in the frequency of her seizures. Another child's seizures came under transient control after she underwent a total corpus callosotomy. The other three continue to have poorly controlled seizures.

Discussion These five patients had seizures that consisted of generalized myoclonic or tonic seizures that occurred in series. During the series, the patients appeared confused and displayed automatic behavior. The brief, quickly repeated jerks of the myoclonic and tonic seizures were so physically unimpressive in comparison to the obvious behavioral changes that the motor activity was misidentified or ignored by the clinical describers. The observers' descriptions of the seizures led to the erroneous clinical diagnoses of and unsuccessful treatment of the episodes as complex partial seizures. Time-locked video/EEG monitoring was needed to correctly categorize the seizures as generalized rather than complex partial seizures. Brief motor seizures are characteristic of LGS and may be tonic, atonic, or myoclonic (1,2). What is not commonly realized is that these brief motor seizures may occur repetitively. In 1980, Kurokawa et al. (5) reported that 6.6% of LGS patients had clusters of motor seizures, but they did not describe the clusters or the seizures further. Recently, Donat and Wright (6) described the EEG features in LGS patients who have clusters or series of brief motor seizures. In that

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report, the repeated myoclonic jerks or tonic stiffenings were each associated with a generalized sharp or slow-wave transient and followed by a generalized decrement of the cerebral activity. A striking aspect of the patients comprising the current report is that the clinically apparent p h e n o m e n a were the behavioral or mental status changes and automatic movements occurring between the motor jerks rather than the repeated motor jerks themselves. Although Niedermeyer (7) noted that psychomotor automatisms occur in LGS, he did not indicate how frequently psychomotor automatisms occur. Psychomotor automatisms and complex partial seizures seem to occur infrequently in LGS. Gastaut and colleagues reported in a series of 100 LGS patients that psychomotor attacks occurred in 7% of cases (8). Chevrie and Aicardi reported in a series of 80 children with LGS that 10% had psychomotor seizures. The pathophysiological mechanisms underlying the behavioral changes and automatisms are uncertain. We speculate that the confusion, unresponsiveness, and other behavioral changes in our patient are due to a combination of phenomena. Postictal disorientation, confusion, and motor automatisms may occur following generalized tonic-clonic seizures, 214 J EPILEPSY, VOL. 4, NO. 4, 1991

and appear to be release p h e n o m e n a due to cortical suppression (10). Postictal behavioral changes usually follow prolonged generalized tonic-clonic seizures and have not been described following brief myoclonic or tonic seizures. It is possible, however, that the serial, quickly repeating motor seizures in our patients, although each seizure was brief, may result in an analogous "interictal" or "peri-ictal" confusionai state. Alternatively, it is possible that our patients' behavioral symptoms might be caused by repeated brief atypical absence seizures following each motor seizure. Atypical absence seizures in LGS patients may be associated with generalized decrements or generalized slow spike-and-wave discharges, and the behavioral and mental status changes in our patients not only coincided with the generalized electrodecremental episodes but also continued when periods of generalized slow spikeand-wave activity briefly resumed before the next motor seizure in the series (11). Several authors have reported, in abstracts or a case report, p h e n o m e n a that appear similar to our observations. Bladin et al. (12) reported 11 patients with LGS whose tonic seizures were mistaken for complex partial seizures. These investigators described two

SERIAL TONIC AND MYOCLONIC SEIZURES electroclinical patterns. One pattern, similar to that of our patients, consisted of runs of "microtonic" seizures accompanied by a p r o m i n e n t confusional state. The other pattern consisted of a single tonic seizure followed by a postictal confusional state, during which the patients displayed automatisms. Details of the clinical and EEG features were not given in this abstract. Somerville and Bruni (13) described a single 17year-old patient, not identified as having LGS, w h o presented in a confusional state during a prolonged episode of tonic status epilepticus. The patient had subtle tonic seizures in which the m o t o r activity was missed for the m o r e obvious confusional state. The tonic seizures occurred every 45 s and lasted 3-10 s, but the seizures were not evident without the aid of concurrent EEG monitoring. Oller-Daurella reported six adult patients w h o had "tonic-automatic" seizures (14). Bilateral tonic muscle contractions were preceded or interrupted by a masticatory or gestural automatisms. The tonic phen o m e n a coincided with a 10-Hz high-voltage recruiting rhythm on EEG, and the automatisms coincided with bilateral slow waves or spike-and-waves. OllerDaurella did not describe series or clusters of seizures, and the EEG features appear to be different from our patients. In an earlier report, Bladin, (15) indicated that tonic seizures in LGS can a p p e a r clinically like complex partial seizures. In a survey of 25 patients, presenting at an average age of 20 years, 16 had features of psyc h o m o t o r seizures, but p r o v e d to have tonic seizures on video/EEG monitoring. In this report, Bladin did not c o m m e n t on series of microtonic seizures as he did in his subsequent abstract (12). O u r observations, together with the reports of Bladin and colleagues, suggest that the frequency of complex partial seizures in LGS may be lower than has been reported. Video/EEG monitoring of patients with LGS w h o are suspected of having complex partial seizures m a y demonstrate that the p r e s u m e d complex partial seizures actually are series of myoclonic or tonic seizures. Such a recognition will help in the selection of suitable antiepileptic drugs. Furthermore, studies of antiepileptic drugs in patients with LGS should distinguish series of subtle m y o clonic or tonic seizures from complex partial seizures for the accurate assessment of treatment efficacy.

Conclusions The five patients with LGS reported here develo p e d a confusional state during series of repeated, brief myoclonic or tonic seizures that was described

in such a m a n n e r that the clinician was led to a mistaken diagnosis of complex partial seizures. Video/ EEG monitoring identified the repeated, subtle m o t o r jerks and established the correct diagnosis. Because LGS patients m a y have multiple types of seizures, precise characterization of the seizure type with intensive video/EEG monitoring is essential whenever seizures are difficult to control.

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