Elsevier

Epilepsy Research

Volume 65, Issue 3, July 2005, Pages 161-168
Epilepsy Research

Neonatal seizures with tonic clonic sequences and poor developmental outcome

https://doi.org/10.1016/j.eplepsyres.2005.05.009Get rights and content

Abstract

Seizures consisting of a tonic followed by a clonic phase have rarely been described in neonates and are not included in the current classifications of neonatal seizures. Our video archive of 105 neonates with seizures or suspected seizures revealed six neonates with such tonic clonic or tonic myoclonic sequences. Two of those neonates had pyridoxine dependent seizures. The other four neonates had drug refractory seizures and demonstrated similarities in electro-clinical pattern, clinical course and outcome. Their seizures started with tonic posturing and after 10–20 s tonic posturing was superimposed by focal or multifocal cloni or myocloni. Ictal EEG started with voltage attenuation followed by bilateral or alternating focal epileptic discharges. The interictal EEG was abnormal. One child died, while the other three children became seizure free but had severe motor delay and mental retardation. In one of those three children, a de novo missense mutation was detected in the voltage gated potassium channel gene KCNQ2, indicating a genetic relationship between drug refractory neonatal seizures of unknown etiology with tonic clonic or myoclonic sequences and the well-known syndrome of benign familial neonatal convulsions (BFNC).

Introduction

Tonic clonic seizures are “a sequence consisting of a tonic followed by a clonic phase” (Blume et al., 2001). Such sequences are commonly seen in children and adults but have been rarely described in neonates. Neither Volpe (2001) nor Mizrahi and Kellaway (1998) include tonic clonic or tonic myoclonic seizures in their neonatal seizure classification. However, tonic clonic sequences have been reported in infants with benign familial neonatal convulsions (BFNC) (Ronen et al., 1993). Similar to other neonatal seizure types, the presentation of tonic clonic or tonic myoclonic sequences differed from those observed in older children. The reason for this difference is most likely related to the immature status of neuroanatomical and neurophysiological development in the neonatal period (Volpe, 2001).

Screening our video archive of 105 neonates with seizures or suspected seizures we identified six patients with tonic clonic or tonic myoclonic sequences. Two of those had known pyridoxine dependent seizures (PDS) but the etiology of the seizures in the remaining four patients was unknown. We analyze the electro-clinical patterns, the clinical course and neurodevelopmental outcome in the two groups of patients and demonstrate a possible genetic relationship between BFNC and the second group through the identification of a formerly unknown ion channel mutation.

Section snippets

Methods and subjects

The patients were selected from all neonates hospitalized in the Intensive Care Units of the University Children's Hospital, Zurich between 1991 and 2004. Most children were outborn and transferred for tertiary level neonatal care. Neonates (age 1–28 days) with suspected seizures underwent one or more EEG examinations, most of them with simultaneous video-recording. One hundred and five neonates were identified as having seizures or suspected seizures during the video-EEG. We reviewed all

Results

We identified seven children with tonic clonic or mixed tonic myoclonic seizure sequences. One child was excluded because the tonic sequence could not be differentiated from movements at awakening.

Discussion

We could identify two types of neonatal seizures with tonic myoclonic or tonic clonic sequences. One type showed mixed seizures with erratic or generalized myoclonic jerks, associated intermittent tonic posturing or spasms, eye deviations and abnormal oral and mimic movements. These seizures were long-lasting (>10 min) and did not coincide with ictal EEG changes. The other seizure type was better structured, started with slowly progressing bilateral tonic posturing of the trunk and limbs

Acknowledgment

We thank Stephanie Stücheli for her detailed neurodevelopmental examination. This work was supported by a grant from the Nationales Genomforschungsnetz 2 (NGFN2) to OKS.

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