Elsevier

Brain and Development

Volume 23, Issue 7, November 2001, Pages 736-748
Brain and Development

Review article
Severe myoclonic epilepsy in infants – a review based on the Tokyo Women's Medical University series of 84 cases

https://doi.org/10.1016/S0387-7604(01)00276-5Get rights and content

Abstract

Severe myoclonic epilepsy in infants (SME) is one of the most malignant epileptic syndromes recognized in the latest classification of epileptic syndromes. The clinical details and electroencephalographic (EEG) characteristics have been elucidated by Dravet et al. The diagnosis of SME depends largely on the combination of clinical and EEG manifestations at different ages, of which the presence of myoclonic seizures appears to be the most important. However, because of the inclusion of different types of myoclonic attack and the lack of strict criteria for diagnosing SME, there has been some confusion as to whether patients without myoclonic seizures or myoclonus should be classified as SME, despite other identical clinical symptoms (SME borderlands (SMEB) group). Among the various clinical manifestations characterizing SME, special attention has been paid to seizures easily precipitated by fever and hot baths in Japan. We have demonstrated that the onset of myoclonic attack in these patients is very sensitive to the elevation of body temperature itself rather than its etiology. Using simultaneous EEG and rectal temperature monitoring during hot water immersion, we showed that epileptic discharges increased in frequency, and eventually developed into seizures at temperatures over 38°C. We believe that the unique fever sensitivity observed in SME is similar to, but more intense than that of febrile convulsions. We have also identified a group of cases who have had innumerous myoclonic and atypical absence seizures daily which were sensitive to the constant bright light illumination. In these cases, spike discharges increased or decreased depending on the intensity of constant light illumination. Although these cases form the most resistant SME group, they lost the constant light sensitivity with increasing age, leaving only relatively common types of fever-sensitive grand mal seizures (FSGM) at the age of around 5 years. In the long run, only convulsive seizures continue, while myoclonic or absence seizures and photosensitivity disappear with advancing age, thus it is conceivable that SMEB constitutes a basic epileptic condition underlying SME. There is a clinical continuum that extends from the mildest end of SMEB to the severest end of SME with constant light sensitivity, with intermediates of frequent or infrequent myoclonic and absence seizures in-between. This spectrum concept appropriately explains the clinical variabilities between SME and SMEB during early childhood.

Introduction

Severe myoclonic epilepsy in infants (SME) is one of the most malignant epileptic syndromes and was first described and characterized by Dravet et al. [1], [2]. Since then, SME has been gradually recognized as an independent epileptic syndrome with many characteristic features. SME has been studied intensively not only in Europe but also in Japan [3], [4], [5], [6], [7], [8], [9]. However, diagnosis of SME in the early stage of clinical course inevitably remains equivocal because of the current diagnostic criteria, which places more importance on the characteristic clinical course rather than the specific seizure or electroencephalographic (EEG) manifestations. The term ‘SME’ may wrongly suggest that it is the severest form of myoclonic epilepsy or epilepsy with intractable myoclonic seizures. However, the myoclonic seizures of SME are usually only seen between 1 and 4 years of age and may not be the predominant seizure type [10]. Patients with SME characteristically have multiple seizure types including generalized or unilateral clonic convulsions, alternating hemiconvulsions, and simple or complex partial seizures (CPS), which manifest more often than the myoclonic seizures throughout the clinical course. Accordingly, the term of ‘polymorphous epilepsy’ was once proposed instead of SME [11]. Furthermore, in Japan, several investigators became aware of the existence of a distinct group of patients who closely resemble SME clinically by sharing most of characteristic features of SME in common, but who do not fulfill an essential item of diagnostic criteria for typical SME, that is, myoclonic seizures, so that other designations such as SME borderland or the peripheral type of SME had tentatively been offered [4], [11], [12], [13], [14]. The causal relationship between hot water bathing and the precipitation of seizures has provoked a keen interest among Japanese investigators also [3], [4], [15], [16]. In this article, the authors will present an overview of Japanese research works ever made on SME and related conditions, including a summary of serial studies of the authors' own.

Section snippets

Diagnostic criteria

The International Classification of Epilepsies and Epileptic Syndromes [17] employs the following six clinical and EEG characteristics for assisting a diagnosis of SME: (1) a high incidence of family history of epilepsy or febrile convulsions (FC); (2) normal development before onset; (3) seizures beginning during the first year of life in the form of generalized or unilateral febrile and afebrile clonic seizures, secondary appearance of myoclonic jerks, and often partial seizures; (4) EEGs in

Subjects

The authors recruited 39 patients with SME and 45 with SMEB who were followed-up for at least 1 year and who were more than 4 years old, including the 22 reported in 1987 by Sugama et al. and other cases previously described [19], [25], [26]. The authors adhered to the international classification system [27] to diagnose the seizure type as accurately as possible, and as a consequence, myoclonus and massive myoclonia were distinguished from myoclonic seizures. Massive myoclonia was observed

Seizures susceptible to fever and Japanese style hot water immersion

All patients in our series experienced frequent seizures triggered by fever and by Japanese style hot water immersion. Convulsive seizures during such episodes tended to become prolonged or even status convulsivus. In the SME and SMEB patients, the epileptic seizures were always provoked whenever fever went up over 38°C, despite an AED medication. Thus, the authors paid special attention to the precipitation of seizures due to fever and hot water immersion [16]. It was unclear, however, which

Therapy

The responses of SME patients to AEDs for seizure control has been disappointing [6], [8], [10], [37]. Okada et al. [37] retrospectively studied the efficacy of various treatments in the present 27 children with SME. Among them, the medium-chain triglyceride (MCT) ketogenic diet treatment was most effective, bringing an excellent reduction in both intensity and frequency in all seizure types in four out of ten patients (40%) while the diet was maintained. The efficacy of adinocorticotropic

Prognosis

The intellectual and seizure outcome for SME patients is generally poor [10]. The mortality is high due to status convulsivus, and sometimes due to other sudden unexpected reasons [44]. In the Dravet series, ten out of 63 or 15.9% of SME patients died. In the present study, 12 out of 85 children with SME (n=7) and SMEB (n=5) died at a mean age of 65±23 months (Fig. 9). Seven patients died of status convulsivus, and three died unexpectedly from unknown causes. In addition, one patient died of

Etiology and nosological situation

The 84 patients with SME and SMEB did not show any pre- or perinatal abnormality except for premature delivery or small for date baby (SFD) in a few children. In addition, the authors could not identify any abnormality from laboratory examinations of amino acids, organic acids, lactic acid, or muscle biopsies from one patient. In a neuroimaging study including magnetic resonance imaging (MRI), we did not identify any specific abnormality. However, incidence of the family history of convulsive

Acknowledgements

This research was carried out on the basis of data accumulated from patients, who were intensively studied physically, neurologically, and electro-encephalographically with great difficulty by many medical staff in the pediatric department of Tokyo Women's Medical University from 1968. We thank all the medical staff for their devoted effort.

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