Abstracts

Rationale: Lissencephaly is a well-described entity that encompasses a broad range of malformations of cortical development that share characteristics of broad or absent normal cerebral gyri, thickened cortical tissue, and abnormal neural histopathology.¹ This spectrum consists of varying degrees of agyria, pachygyria, and subcortical band heterotopia (SBH). On electroencephalography (EEG), a specific interictal pattern in lissencephaly was first described by Hakamada et al. of bilaterally synchronous high amplitude discharges.^2,3 At least 17 causative genes have been implicated in lissencephaly, with PAFAH1B1 formerly known as LIS1 being the most well-known.¹ Various EEG patterns have been described based on structural pathology.^2-4 The authors present a case series of lissencephaly of various genetic mutations and their interictal phenotypes. 

Methods: Chart review was performed on the following patients. 

Results: Eight patients were identified with malformations of cortical development with known pathogenic mutations. Median age was 4.5 years (1-15 years with five males and three females. Median age of seizure onset was 5.5 months (0-60 months). 5/8 patients had a history of infantile spasms. Seizure types included spasms (5/8), tonic (2/8), myoclonic (2/8), atonic (2/8), focal (4/8), and tonic clonic (3/8). Four had pathogenic mutations in PAFAH1B1, three in DCX, and one in DYNC1H1. Neuroimaging showed lissencephaly and pachygyria (4/8), SBH (2/8), and lissencephaly and partial SBH (2/8). Interictal EEG pattern for the four patients with PAFAH1B1 mutations showed high amplitude rhythmic activity, bilaterally synchronized spike waves, and prominent fast activity. One patient with a large deletion including DCX showed generalized polyspike and slow waves. Two patients with DCX point mutations showed unilateral focal discharges. One patient with DYNC1H1 mutation had multifocal sharp waves.

Conclusions: In this case series, the authors present eight patients with severe malformations of cortical development within the lissencephaly spectrum with various EEG patterns correlated with known pathogenic mutations. Interestingly, the four patients with PAFAH1B1 mutations consistently show the characteristic interictal pattern historically identified. However, three patients with DCX mutations and one patient with DYNC1H1 show different EEG patterns. Despite significant structural phenotype overlap, this may suggest that the underlying genetic etiology is involved in the electrographic phenotype.  

References:

¹ Koenig, M., Dobyns, W. B., & Di Donato, N. (2021). Lissencephaly: Update on diagnostics and clinical management. European Journal of Paediatric Neurology, 35, 147-152. ² Hakamada, S., Watanabe, K., Hara, K., & Miyazaki, S. (1979). The evolution of electroencephalographic features in lissencephaly syndrome. Brain and Development, 1(4), 277-283.  ³ Quirk, J. A., Kendall, B., Kingsley, D. P. E., Boyd, S. G., & Pitt, M. C. (1993). EEG features of cortical dysplasia in children.  Neuropediatrics, 24(04), 193-199. ⁴ Grant, A. C., & Rho, J. M. (2002). Ictal EEG patterns in band heterotopia. Epilepsia, 43(4), 403-407.