The phenotype of SCN8A developmental and epileptic encephalopathy

Elena Gardella; Carla Marini; Marina Trivisano; Mark P Fitzgerald; Michael Alber; Katherine B Howell; Francesca Darra; Sabrina Siliquini; Bigna K Bölsterli; Silva Masnada; Anna Pichiecchio; Katrine M Johannesen; Birgit Jepsen; Elena Fontana; Gaia Anibaldi; Silvia Russo; Francesca Cogliati; Martino Montomoli; Nicola Specchio; Guido Rubboli; Pierangelo Veggiotti; Sandor Beniczky; Markus Wolff; Ingo Helbig; Federico Vigevano; Ingrid E Scheffer; Renzo Guerrini; Rikke S Møller

doi:10.1212/WNL.0000000000006199

The phenotype of SCN8A developmental and epileptic encephalopathy

Elena Gardella^*, Carla Marini, Marina Trivisano, Mark P Fitzgerald, Michael Alber, Katherine B Howell, Francesca Darra, Sabrina Siliquini, Bigna K Bölsterli, Silva Masnada, Anna Pichiecchio, Katrine M Johannesen, Birgit Jepsen, Elena Fontana, Gaia Anibaldi, Silvia Russo, Francesca Cogliati, Martino Montomoli, Nicola Specchio, Guido RubboliPierangelo Veggiotti, Sandor Beniczky, Markus Wolff, Ingo Helbig, Federico Vigevano, Ingrid E Scheffer, Renzo Guerrini, Rikke S Møller

^*Corresponding author af dette arbejde

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Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

Abstract

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.

Originalsprog	Engelsk
Sider (fra-til)	e1112-e1124
Tidsskrift	Neurology
Vol/bind	91
Udgave nummer	12
DOI	https://doi.org/10.1212/WNL.0000000000006199
Status	Udgivet - 18 sep. 2018

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10.1212/WNL.0000000000006199

Citationsformater

Gardella, E., Marini, C., Trivisano, M., Fitzgerald, M. P., Alber, M., Howell, K. B., Darra, F., Siliquini, S., Bölsterli, B. K., Masnada, S., Pichiecchio, A., Johannesen, K. M., Jepsen, B., Fontana, E., Anibaldi, G., Russo, S., Cogliati, F., Montomoli, M., Specchio, N., ... Møller, R. S. (2018). The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology, 91(12), e1112-e1124. https://doi.org/10.1212/WNL.0000000000006199

@article{0a7f7d096ead4edea51e2a1386e19571,

title = "The phenotype of SCN8A developmental and epileptic encephalopathy",

abstract = "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.",

keywords = "Adolescent, Child, Child, Preschool, Developmental Disabilities/complications, Electroencephalography, Female, Humans, Infant, Male, Mutation, NAV1.6 Voltage-Gated Sodium Channel/genetics, Spasms, Infantile/complications, Young Adult",

author = "Elena Gardella and Carla Marini and Marina Trivisano and Fitzgerald, {Mark P} and Michael Alber and Howell, {Katherine B} and Francesca Darra and Sabrina Siliquini and B{\"o}lsterli, {Bigna K} and Silva Masnada and Anna Pichiecchio and Johannesen, {Katrine M} and Birgit Jepsen and Elena Fontana and Gaia Anibaldi and Silvia Russo and Francesca Cogliati and Martino Montomoli and Nicola Specchio and Guido Rubboli and Pierangelo Veggiotti and Sandor Beniczky and Markus Wolff and Ingo Helbig and Federico Vigevano and Scheffer, {Ingrid E} and Renzo Guerrini and M{\o}ller, {Rikke S}",

note = "{\textcopyright} 2018 American Academy of Neurology.",

year = "2018",

month = sep,

day = "18",

doi = "10.1212/WNL.0000000000006199",

language = "English",

volume = "91",

pages = "e1112--e1124",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "12",

}

Gardella, E, Marini, C, Trivisano, M, Fitzgerald, MP, Alber, M, Howell, KB, Darra, F, Siliquini, S, Bölsterli, BK, Masnada, S, Pichiecchio, A, Johannesen, KM, Jepsen, B, Fontana, E, Anibaldi, G, Russo, S, Cogliati, F, Montomoli, M, Specchio, N, Rubboli, G, Veggiotti, P, Beniczky, S, Wolff, M, Helbig, I, Vigevano, F, Scheffer, IE, Guerrini, R & Møller, RS 2018, 'The phenotype of SCN8A developmental and epileptic encephalopathy', Neurology, bind 91, nr. 12, s. e1112-e1124. https://doi.org/10.1212/WNL.0000000000006199

TY - JOUR

T1 - The phenotype of SCN8A developmental and epileptic encephalopathy

AU - Gardella, Elena

AU - Marini, Carla

AU - Trivisano, Marina

AU - Fitzgerald, Mark P

AU - Alber, Michael

AU - Howell, Katherine B

AU - Darra, Francesca

AU - Siliquini, Sabrina

AU - Bölsterli, Bigna K

AU - Masnada, Silva

AU - Pichiecchio, Anna

AU - Johannesen, Katrine M

AU - Jepsen, Birgit

AU - Fontana, Elena

AU - Anibaldi, Gaia

AU - Russo, Silvia

AU - Cogliati, Francesca

AU - Montomoli, Martino

AU - Specchio, Nicola

AU - Rubboli, Guido

AU - Veggiotti, Pierangelo

AU - Beniczky, Sandor

AU - Wolff, Markus

AU - Helbig, Ingo

AU - Vigevano, Federico

AU - Scheffer, Ingrid E

AU - Guerrini, Renzo

AU - Møller, Rikke S

PY - 2018/9/18

Y1 - 2018/9/18

N2 - 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.

AB - 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.

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Developmental Disabilities/complications

KW - Electroencephalography

KW - Female

KW - Humans

KW - Infant

KW - Male

KW - Mutation

KW - NAV1.6 Voltage-Gated Sodium Channel/genetics

KW - Spasms, Infantile/complications

KW - Young Adult

U2 - 10.1212/WNL.0000000000006199

DO - 10.1212/WNL.0000000000006199

M3 - Article

C2 - 30171078

SN - 0028-3878

VL - 91

SP - e1112-e1124

JO - Neurology

JF - Neurology

IS - 12

ER -

The phenotype of SCN8A developmental and epileptic encephalopathy

Abstract

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