Managing Status Epilepticus in a Child with Dravet Syndrome: How Difficult It Could Be?

Previously known as severe myoclonic epilepsy of infancy, Dravet syndrome is characterized by febrile or afebrile prolonged hemiconvulsive seizures or generalized status epilepticus in an infant with previously normal development. Immediate management of status epilepticus is critical in these patients. Early control of status epilepticus prevents further brain damage; however, there is no consensus regarding the management of status epilepticus in children with Dravet syndrome, as many conventional antiseizure medications that are recommended in the management of status epilepticus worsen the seizures in these patients. A 2.5-year-old girl was referred due to status epilepticus which was refractory to antiseizure medications. Sodium valproate, nitrazepam, ketogenic diet, intravenous phenytoin, and midazolam continuous infusion were administered. After controlling status epilepticus, the probable diagnosis of Dravet syndrome was proposed and confirmed by a mutation in SCN1A. As previously stated in numerous case reports, phenytoin worsens seizures in patients with Dravet syndrome. Therefore, it seems logical that in every infant with status epilepticus and probable Dravet syndrome, the practicing physician considers administering intravenous valproate or even midazolam continuous infusion instead of intravenous phenytoin.

7q35 Microdeletion and 15q13.3 and Xp22.33 Microduplications in a Patient with Severe Myoclonic Epilepsy, Microcephaly, Dysmorphisms, Severe Psychomotor Delay and Intellectual Disability

Copy number variations (CNVs) play a key role in the pathogenesis of several diseases, including a wide range of neurodevelopmental disorders. Here, we describe the detection of three CNVs simultaneously in a female patient with evidence of severe myoclonic epilepsy, microcephaly, hypertelorism, dimorphisms as well as severe psychomotor delay and intellectual disability. Array-CGH analysis revealed a ~240 kb microdeletion at the 7q35 inherited from her father, a ∼538 kb microduplication at the 15q13.3 region and a ∼178 kb microduplication at Xp22.33 region, both transmitted from her mother. The microdeletion in 7q35 was included within an intragenic region of the contactin associated protein-like 2 (CNTNAP2) gene, whereas the microduplications at 15q13.3 and Xp22.33 involved the cholinergic receptor nicotinic α 7 subunit (CHRNA7) and the cytokine receptor-like factor 2 (CRLF2) genes, respectively. Here, we describe a female patient harbouring three CNVs whose additive contribution could be responsible for her clinical phenotypes.

Accuracy of Flash Glucose Monitoring in a Patient with Dravet Syndrome on a Ketogenic Diet

We herein report the case of a 3-year-old girl with severe myoclonic epilepsy of infancy known as Dravet syndrome (DS) on a ketogenic diet (KD) whose glucose concentrations were controlled by using a flash glucose monitoring system. Two-hundred ninety-three events of moderate hypoglycemia with a minimum of 45 mg/dL, not related to day or night, were recorded during the observational period. Hypoglycemia rate declined from 24.5% of all measurements to 11.8% over time; one hypoglycemia-associated seizure and one seizure due to ketone concentrations below the therapeutic range were observed. In summary, this case report broadens our understanding of hypoglycemia risk in patients with DS on a KD. Especially in childhood, the painless and easy detection of low glucose concentrations might lead to improved cognitive performance, and the reduction of hypoglycemia-induced seizures.

Dravet Syndrome in Lebanon: First Report on Cases with SCN1A Mutations

Dravet syndrome, also known as severe myoclonic epilepsy in infancy, is a rare disease characterized by the appearance of different types of seizures in a healthy baby, triggered by various factors and stressful events. We report 8 Lebanese cases referred for molecular analysis of the SCN1A gene. Results were positive in 7 cases and revealed de novo variants at the heterozygous state in different exons of the gene for all except one, where the variant was intronic. Four variants were novel. Confirmation of Dravet syndrome is important for a better follow-up and treatment, preventing the occurrence of status epilepticus and severe neurological deterioration.

Identification of a Novel Nonsense Variant in the SCN1A Gene that Causes Febrile Seizure Disorder

The SCN1A gene, encoding for the voltage-gated sodium channel Nav1.1, is the most clinically relevant epilepsy gene, with most mutations having been documented in a spectrum of epilepsy syndromes, ranging from the relatively benign generalized epilepsy with febrile seizures plus (GEFS+) to severe myoclonic epilepsy in infancy (SMEI), and other rare febrile seizure disorders. To date, more than 1,250 mutations in SCN1A have been linked to epilepsy. In this case, we describe a novel nonsense pathogenic variant (NM_001202435.1; c.327C > G) in SCN1A in a 10-month Moroccan infant with febrile seizure disorder.

Vagus Nerve Stimulation in Intractable Epilepsy Associated With SCN1A Gene Abnormalities

Mutations in the SCN1A gene cause a spectrum of epilepsy syndromes. There are 2 syndromes that are on the severe end of this spectrum. The classic severe form, Dravet syndrome, is an epileptic encephalopathy of childhood, causing cognitive decline as well as intractable seizures. Severe Myoclonic Epilepsy of Infancy–Borderline (SMEIB) is a term used to include cases with similar severities as those with Dravet syndrome, but lacking a single feature of classic severe myoclonic epilepsy of infancy. Vagus nerve stimulation is a nonpharmacologic treatment for intractable epilepsy. A retrospective review was conducted of patients with deleterious SCN1A mutations who had vagus nerve stimulation placement for treatment of their intractable epilepsy. These children had onset of their epilepsy between 3 and 29 months of age. Seizure control was assessed 6 months after implantation. Twenty patients are included in the study, with 12 implanted at our institution. Nine of the 12 patients implanted at our institution, who had confirmed pre- and post-implantation seizure assessments, showed improvement in seizure control, which was defined as >50% reduction in generalized tonic-clonic seizures, and 4 of those 12 reported improvement in cognitive or speech development. Seven of the 8 patients not implanted at our institution reported subjective benefit, with 4 relating “marked improvement” or seizure freedom. Vagus nerve stimulation appears to impart a benefit to children with deleterious SCN1A gene abnormalities associated with intractable epilepsy.