Core Features Differentiate Dravet Syndrome from Febrile Seizures.

An 11-month-old girl with febrile seizures and first unprovoked seizures was evaluated in the hospital. Relevant history included developmental delay and strong family history of febrile seizures and migraines. A routine electroencephalogram was performed and was abnormal due to the presence of a slowed posterior dominant rhythm, generalized spike-wave discharges, and multifocal sharp waves. The findings were concerning for a developmental and epileptic encephalopathy. Given the concern for a developmental and epileptic encephalopathy, a next generation sequence epilepsy gene panel was ordered which identified a pathogenic variant in SCN1A. The clinical history, electroencephalogram, and pathogenic variant were compatible with a diagnosis of Dravet syndrome. This Grand Rounds manuscript highlights the thought process, evaluation, differential diagnosis, treatment, and prognosis in Dravet syndrome.

The Effect of Smartphone Video on Lead Time to Diagnosis of Infantile Spasms.

OBJECTIVE: To assess whether access to smartphone video capture of infantile spasms at initial presentation is associated with improved time to diagnosis and treatment. METHODS: We conducted a collaborative retrospective cohort study of 80 consecutive infants with confirmed infantile epileptic spasms syndrome initially presenting from 2015 to 2021 at 2 US pediatric centers. Statistical methods used included Mann-Whitney U test to assess the difference in lead times to electroencephalogram (EEG), diagnosis, and treatment between groups with and without video capture. A χ2 analysis was used to assess differences in demographics, clinical characteristics, and treatment outcomes between groups. Multivariate regression analysis was used to account for etiology types and infantile spasms capture on EEG. RESULTS: Patients with smartphone video infantile spasms capture initially presented a median of 9 days earlier (P = .02), had their first EEG 16 days earlier (P = .007), and were diagnosed and started treatment 17 days earlier (P = .006 and P = .008, respectively) compared with the nonvideo group. The video group had a 25% greater response to initial standard treatment (P = .02) and a 21% greater freedom from infantile spasms at long-term follow-up (P = .03), although this long-term outcome lost statistical significance after adjustment for etiology type (P = .07) and EEG capture of infantile spasms (P = .059). CONCLUSION: Our findings suggest a benefit of smartphone video capture of infantile spasms in reduced time to diagnosis and initial standard treatment, which are associated with improved treatment response rates. Substantial differences in lead times and treatment response highlight the clinical importance of pediatricians recommending caregivers to obtain smartphone video of events concerning for infantile spasms.

Clinical and Electroencephalographic Characteristics of Infantile-Onset Epilepsies Caused by Genetic Mutations.

OBJECTIVES: To determine whether certain characteristic electroencephalography (EEG) features are indicative of a genetic cause in early-life epilepsy. STUDY DESIGN: We enrolled a total of 100 patients with infantile-onset (<3 years) epilepsy due to known genetic cause (n = 50) and nongenetic cause (acquired, structural, or unknown, n = 50). The genetic group was classified into synaptopathies, channelopathies, mTOR (mammalian target of rapamycin)-opathies, and chromosomal abnormalities. The nongenetic group included epilepsy of unknown cause and structural abnormalities such as brain tumor, focal cortical dysplasia and encephalomalacia. The clinical features, magnetic resonance imaging, and video EEG obtained before 3 years of age and again at follow-up were reviewed. Specifically, the background rhythms and patterns of interictal epileptiform discharges were analyzed to define the EEG characteristics. RESULTS: The genetic group was more likely to have seizure recurrence beyond infancy and significant developmental delay (P <.01). The genetic and nongenetic groups showed different EEG patterns in the initial EEGs that persisted in follow-up EEGs. Diffuse slowing with pleomorphic focal/multifocal epileptiform discharges were present more often in the genetic (86%) compared with the nongenetic group (20%) in the initial EEGs (P <.01). The last available follow-up EEG features were similar (81% in genetic versus 17% in nongenetic) to the EEG performed prior to 3 years of age. CONCLUSIONS: Our findings suggest a simple guide for genetic screening in children with early-onset epilepsy. Genetic testing may be indicated and useful in infants with delayed development, no obvious cause, and significant EEG background slowing with pleomorphic focal or multifocal epileptiform discharges.

Response to treatment in a prospective national infantile spasms cohort.

OBJECTIVE: Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarrhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarrhythmia that was sustained at 3 months after first treatment initiation. Standard treatments of adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin were considered individually, and all other nonstandard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using chi-square tests and multivariate logistic regression models. RESULTS: Two hundred thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded, compared to only 9% who responded to nonstandard therapy (p < 0.001). Fifty-five percent of infants receiving ACTH as initial treatment responded, compared to 39% for oral corticosteroids, 36% for vigabatrin, and 9% for other (p < 0.001). Neither etiology nor development significantly modified the response pattern by treatment group. INTERPRETATION: Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies.

Risk factors for febrile status epilepticus: a case-control study.

OBJECTIVE: To identify risk factors for developing a first febrile status epilepticus (FSE) among children with a first febrile seizure (FS). STUDY DESIGN: Cases were children with a first FS that was FSE drawn from the Consequences of Prolonged Febrile Seizures in Childhood and Columbia cohorts. Controls were children with a first simple FS and separately, children with a first complex FS that was not FSE. Identical questionnaires were administered to family members of the 3 cohorts. Magnetic resonance imaging protocol and readings were consistent across cohorts, and seizure phenomenology was assessed by the same physicians. Risk factors were analyzed using logistic regression. RESULTS: Compared with children with simple FS, FSE was associated with younger age, lower temperature, longer duration (1-24 hours) of recognized temperature before FS, female sex, structural temporal lobe abnormalities, and first-degree family history of FS. Compared with children with other complex FS, FSE was associated with low temperature and longer duration (1-24 hours) of temperature recognition before FS. Risk factors for complex FS that was not FSE were similar in magnitude to those for FSE but only younger age was significant. CONCLUSIONS: Among children with a first FS, FSE appears to be due to a combination of lower seizure threshold (younger age and lower temperatures) and impaired regulation of seizure duration. Clinicians evaluating FS should be aware of these factors as many episodes of FSE go unnoticed. Further work is needed to develop strategies to prevent FSE.

Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study.

This prospective multicenter study of 200 patients with fever-associated status epilepticus (FSE), of whom 136 underwent a nontraumatic lumbar puncture, confirms that FSE rarely causes cerebrospinal fluid (CSF) pleocytosis. CSF glucose and protein levels were unremarkable. Temperature, age, seizure focality, and seizure duration did not affect results. CSF pleocytosis should not be attributed to FSE.