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The phenotype of SCN8A developmental and epileptic encephalopathy

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  • Elena Gardella, Danish Epilepsy Centre, Dianalund, University of Southern Denmark
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  • Carla Marini, Università Degli Studi di Firenze
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  • Marina Trivisano, IRCCS Ospedale Pediatrico Bambino Gesù
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  • Mark P. Fitzgerald, Children’s Hospital of Philadelphia, The Pennsylvania State University
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  • Michael Alber, Universitätskinderklinik Tübingen
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  • Katherine B. Howell, Royal Children’s Hospital Melbourne, University Melbourne, Murdoch Children’s Research Institute
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  • Francesca Darra, University of Verona
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  • Sabrina Siliquini, Ospedale Pediatrico G. Salesi
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  • Bigna K. Bölsterli, University Children’s Hospital Zurich
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  • Silva Masnada, Università Degli Studi di Pavia
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  • Anna Pichiecchio, Neurological Institute IRCCS Mondino
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  • Katrine M. Johannesen, University of Southern Denmark, Royal Children’s Hospital Melbourne, University Melbourne, Murdoch Children’s Research Institute, Danish Epilepsy Centre, Dianalund
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  • Birgit Jepsen, Danish Epilepsy Centre, Dianalund
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  • Elena Fontana, University of Verona
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  • Gaia Anibaldi, Ospedale Pediatrico G. Salesi
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  • Silvia Russo, Ospedale Pediatrico G. Salesi, IRCCS Istituto Auxologico Italiano
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  • Francesca Cogliati, IRCCS Istituto Auxologico Italiano
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  • Martino Montomoli, Università Degli Studi di Firenze
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  • Nicola Specchio, IRCCS Ospedale Pediatrico Bambino Gesù
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  • Guido Rubboli, Danish Epilepsy Centre, Dianalund, University of Copenhagen
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  • Pierangelo Veggiotti, Struttura Complessa di Neurologia Pediatrica Ospedale Vittore Buzzi, Universita degli Studi di Milano
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  • Sandor Beniczky
  • Markus Wolff, Universitätskinderklinik Tübingen
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  • Ingo Helbig, Children’s Hospital of Philadelphia, The Pennsylvania State University
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  • Federico Vigevano, IRCCS Ospedale Pediatrico Bambino Gesù
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  • Ingrid E. Scheffer, University Melbourne, Royal Children’s Hospital Melbourne
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  • Renzo Guerrini, Università Degli Studi di Firenze
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  • Rikke S. Møller, University of Southern Denmark, Danish Epilepsy Centre, Dianalund

Objective To delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558). Methods Twenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment. Results Sixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at a median age of 4 months, followed by developmental slowing, pyramidal/extrapyramidal signs (22/22), movement disorders (12/22), cortical blindness (17/22), sialorrhea, and severe gastrointestinal symptoms (15/22), worsening during early childhood and plateauing at age 5 to 9 years. Death occurred in 4 children, following extreme neurologic deterioration, at 22 months to 5.5 years. Nonconvulsive status epilepticus recurred in 14 of 22 patients. The most effective antiepileptic drugs were oxcarbazepine, carbamazepine, phenytoin, and benzodiazepines. EEG showed background deterioration, epileptiform abnormalities with a temporo-occipital predominance, and posterior delta/beta activity correlating with visual impairment. Video-EEG documented focal seizures (FS) (22/22), spasm-like episodes (8/22), cortical myoclonus (8/22), and myoclonic absences (1/22). FS typically clustered and were prolonged (<20 minutes) with (1) cyanosis, hypomotor, and vegetative semiology, sometimes unnoticed, followed by (2) tonic-vibratory and (3) (hemi)-clonic manifestations ± evolution to a bilateral tonic-clonic seizure. FS had posterior-temporal/occipital onset, slowly spreading and sometimes migrating between hemispheres. Brain MRI showed progressive parenchymal atrophy and restriction of the optic radiations. Conclusions: SCN8A developmental and epileptic encephalopathy has strikingly consistent electroclinical features, suggesting a global progressive brain dysfunction primarily affecting the temporo-occipital regions. Both uncontrolled epilepsy and developmental compromise contribute to the profound impairment (increasing risk of death) during early childhood, but stabilization occurs in late childhood.

Original languageEnglish
JournalNeurology
Volume91
Issue12
Pages (from-to)E1112-E1124
Number of pages13
ISSN0028-3878
DOIs
Publication statusPublished - 18 Sep 2018

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