Hippocampal Sclerosis in Severe Myoclonic Epilepsy in Infancy: A Retrospective MRI Study

Siegler, Zsuzsanna; Barsi, Péter; Neuwirth, Magdolna; Jerney, Judit; Kassay, Mária; Janszky, József; Paraicz, Éva; Hegyi, Márta; Fogarasi, András

doi:10.1111/j.1528-1167.2005.41604.x

Cited by 53 publications

(47 citation statements)

References 30 publications

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“…The SCN1A + surgical case had unilateral hippocampal sclerosis. Previous studies have shown that in a small proportion of patients with Dravet syndrome, hippocampal sclerosis is observed (Striano et al ., 2007 a ), and this may not be present in the early childhood scans (Siegler et al ., 2005). Prospective MRI studies in Dravet syndrome are required.…”

Section: Discussionmentioning

confidence: 99%

Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

Catarino¹,

Liu²,

Liagkouras³

et al. 2011

Brain

189

212

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Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy.

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Section: Discussionmentioning

confidence: 99%

Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

Catarino¹,

Liu²,

Liagkouras³

et al. 2011

Brain

189

212

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“…Neuroradiological studies are normal in most patients (Guerrini and Dravet, 1997) but structural abnormalities such as cerebral or cerebellar atrophy of various degree and focal arachnoid cysts have been anecdotically reported (Dalla Bernardina et al, 1982; Reiner and Renkawek, 1990; Guerrini and Dravet, 1997; Ohki et al, 1997; Dravet et al, 2005). However, only one study systematically investigated structural abnormalities on MRI and found evidence of hippocampal sclerosis (HS) in 10 out of the 14 children with a clinical diagnosis of SMEI (Siegler et al, 2005). Among these, six who had been reported to have normal initial MRI developed HS during the course of the disorder (Siegler et al, 2005).…”

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confidence: 99%

Brain MRI Findings in Severe Myoclonic Epilepsy in Infancy and Genotype–Phenotype Correlations

et al. 2007

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Summary: Introduction:To determine the occurrence of neuroradiological abnormalities and to perform genotype-phenotype correlations in severe myoclonic epilepsy of infancy (SMEI, Dravet syndrome).Patients and Methods: Alpha-subunit type A of voltage-gated sodium channel (SCN1A) mutational screening was performed by denaturing high-performance liquid chromatography (DH-PLC) and multiplex ligation probe amplification (MLPA). MRI inclusion criteria were: last examination obtained after the age of 4 years on 1.5-T systems; hippocampal cuts acquired perpendicular to the long axis of the hippocampus; qualitative assessment was performed on T 1 -weighted, T 2 -weighted, proton density, and 1-3 mm thick coronal FLAIR images.Results: We collected 58 SMEI patients in whom last MRI was performed at or later than 4 years of age. SCN1A mutations occurred in 35 (60%) cases. Thirteen (22.4%) out of 58 patients showed abnormal MRIs. Eight patients showed cortical brain atrophy of which 3 associated to ventricles abnormalities, 1 to cerebellar atrophy, 1 to white matter hyperintensity; 3 patients had ventricles enlargement only; 1 patient showed hippocampal sclerosis (HS); 1 had focal cortical dysplasia. Genotypephenotype analysis indicated that abnormal MRIs occurred more frequently in patients without SCN1A mutations (9/23; 39.1%) compared to those carrying SCN1A mutations (4/35; 11.4%) (p = 0.02).Conclusion: Different brain abnormalities may occur in SMEI. Only one case with HS was observed; thus, our study does not support the association between prolonged febrile seizures and HS in SMEI. Abnormal MRIs were significantly more frequent in patients without SCN1A mutations. Prospective MRI studies will assess the etiological role of the changes observed in these patients. Key Words: Severe myoclonic epilepsy of infancy-Dravet syndrome-MRI-SCN1A-Genotype-phenotype correlations.

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“…11,19,20 Unilateral or bilateral hippocampal sclerosis is an increasingly recognized finding in patients with Dravet syndrome and/or SCN1A mutations and may develop after an initially normal MRI. 5,19,22 abbreviations EEG = electroencephalography; GEFS+ = generalized epilepsy with febrile seizures plus; ILAE = International League Against Epilepsy; MCD = malformation of cortical development; MTS = mesial temporal sclerosis; SMEI = severe myoclonic epilepsy of infancy. However, other authors have hypothesized that SCN1A mutations may actually protect from hippocampal sclerosis.…”

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confidence: 99%

Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy

Skjei

Church

Harding

et al. 2015

PED

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obJect Mutations in the sodium channel alpha 1 subunit gene (SCN1A) have been associated with a wide range of epilepsy phenotypes including Dravet syndrome. There currently exist few histopathological and surgical outcome reports in patients with this disease. In this case series, the authors describe the clinical features, surgical pathology, and outcomes in 6 patients with SCN1A mutations and refractory epilepsy who underwent focal cortical resection prior to uncovering the genetic basis of their epilepsy. methods Medical records of SCN1A mutation-positive children with treatment-resistant epilepsy who had undergone resective epilepsy surgery were reviewed retrospectively. Surgical pathology specimens were reviewed. results All 6 patients identified carried diagnoses of intractable epilepsy with mixed seizure types. Age at surgery ranged from 18 months to 20 years. Seizures were refractory to surgery in every case. Surgical histopathology showed evidence of subtle cortical dysplasia in 4 of 6 patients, with more neurons in the molecular layer of the cortex and white matter. conclusions Cortical resection is unlikely to be beneficial in these children due to the genetic defect and the unexpected neuropathological finding of mild diffuse malformations of cortical development. Together, these findings suggest a diffuse pathophysiological mechanism of the patients' epilepsy which will not respond to focal resective surgery. However, other authors have hypothesized that SCN1A mutations may actually protect from hippocampal sclerosis.2 Few pathological cases of Dravet syndrome have been published to date. 3,5,13,15,18 Most were case reports of autopsy specimens, and many had not undergone SCN1A testing. In this study, we review the clinical features and surgical pathology in 6 patients with treatment-resistant epilepsy who underwent surgery for intractable focal seizures and were later found to have presumed pathogenic mutations in SCN1A. We also review their outcomes and seek to draw conclusions regarding surgical evaluation and management. methodsThe medical records of 6 children with SCN1A mutations who underwent epilepsy surgery for medically refractory epilepsy were reviewed retrospectively. Patients were identified at the Children's Hospital of Philadelphia by surveying the epilepsy group to identify patients who had undergone epilepsy surgery and were later found to have SCN1A mutations. An additional patient was identified at the Cincinnati Children's Hospital. Data extracted included age at seizure onset, initial seizure types, clinical course, and neuroimaging and electroencephalography (EEG) reports. Surgical outcomes were classified using the International League Against Epilepsy (ILAE) surgical outcome scale as of their last follow-up visit. 24SCN1A mutation testing was done at commercially available laboratories (Athena and Transgenomics). A mutation was considered pathogenic if it was previously described as such, was a truncation mutation, or was a novel mutation with predicted pathogenicity (based o...

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Hippocampal Sclerosis in Severe Myoclonic Epilepsy in Infancy: A Retrospective MRI Study

Cited by 53 publications

References 30 publications

Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

Brain MRI Findings in Severe Myoclonic Epilepsy in Infancy and Genotype–Phenotype Correlations

Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy

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