Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare early-onset developmental epileptic encephalopathy resistant to anti-epileptic drugs. The most common cause for EIMFS is a gain-of-function mutation in the KCNT1 potassium channel gene, and treatment with the KCNT1 blocker quinidine has been suggested as a rational approach for seizure control in EIMFS patients. However, variable results on the clinical efficacy of quinidine have been reported. In the present study, we provide a detailed description of the clinical, genetic, in vitro, and in vivo electrophysiological profile and pharmacological responses to quinidine of 2 EIMFS unrelated patients with a heterozygous de novo KCNT1 mutation: c.2849G>A (p.R950Q) in patient 1 and c.2677G>A (p.E893K) in patient 2. When expressed heterologously in CHO cells, KCNT1 channels carrying each variant showed gain-of-function effects, and were more effectively blocked by quinidine when compared to wild-type KCNT1 channels. On the basis of these in vitro results, add-on quinidine treatment was started at 3 and 16 months of age in patients 1 and 2, respectively. The results obtained reveal that quinidine significantly reduced seizure burden (by about 90%) and improved quality of life in both patients, but failed to normalize developmental milestones, which persisted as severely delayed. Based on the present experience, early quinidine intervention associated with heart monitoring and control of blood levels is among the critical factors for therapy effectiveness in EIMFS patients with KCNT1 gain-of-function mutations. Multicenter studies are needed to establish a consensus protocol for patient recruitment, quinidine treatment modalities, and outcome evaluation, to optimize clinical efficacy and reduce risks as well as variability associated to quinidine use in such severe developmental encephalopathy.

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Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis.

Summary Objective Pathogenic variants in SCN8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID) or movement disorders without epilepsy have been reported. The vast majority of the published SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A‐related epilepsies. Methods A cohort of 1095 patients were screened using a next generation sequencing panel. Further patients were ascertained from a network of epilepsy genetics clinics. Patients with severe DEE and BFIS were excluded from the study. Results We found 36 probands who presented with an SCN8A‐related epilepsy and normal intellect (33%) or mild (61%) to moderate ID (6%). All patients presented with epilepsy between age 1.5 months and 7 years (mean = 13.6 months), and 58% of these became seizure‐free, two‐thirds on monotherapy. Neurological disturbances included ataxia (28%) and hypotonia (19%) as the most prominent features. Interictal electroencephalogram was normal in 41%. Several recurrent variants were observed, including Ile763Val, Val891Met, Gly1475Arg, Gly1483Lys, Phe1588Leu, Arg1617Gln, Ala1650Val/Thr, Arg1872Gln, and Asn1877Ser. Significance With this study, we explore the electroclinical features of an intermediate SCN8A‐related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

Objective The objective of this study was to evaluate care needs, emotional and behavioral changes, and parental stress indices in a cohort of pediatric patients with epilepsy with neurocognitive and emotional comorbidities at the time of the coronavirus disease 2019 (COVID-19) pandemic. Methods This is a prospective observational study involving pediatric patients with epilepsy with neurocognitive and emotional comorbidities. Included patients were admitted to our hospital between August 2019 and February 2020 for epilepsy and neuropsychiatric assessment, and Child Behavior Checklist (CBCL) questionnaires were filled in by parents. Those patients and their families accepted to participate in a phone follow-up visit in April–May 2020 and to refill CBCL and Parenting Stress Index–Short Form (PSI-SF) questionnaires. Descriptive statistics for demographic and clinical data, CBCL questionnaire scores before and during the COVID-19 pandemic, and PSI-SF scores have been computed. Moreover, results of a short phone survey on the psychological burden during COVID lockdown have been reported. Results This study provides the parental-proxy report of emotional and behavioral profile changes of 23 pediatric patients with epilepsy and neurocognitive and emotional comorbidities during the COVID-19 pandemic. Concerns for therapy monitoring at the time of lockdown emerged in 43% of families, and 30% of patients showed worries for an altered contact with the referring medical team. Patients with neurocognitive comorbidities were more likely to exhibit behavioral problems, especially externalizing problems compared with patients with a diagnosis of anxiety/depression. Conclusion Our data suggest the importance to monitor disease trajectory and behavior and affective symptoms with telehealth strategies to provide effective care to patients and their families.

Introduction Glucose Transporter Type I Deficiency Syndrome ( GLUT 1 DS ) classical symptoms are seizures, involuntary movements, and cognitive impairment but so far the literature has not devoted much attention to the last. Methods In our retrospective study involving 25 patients with established GLUT 1 DS diagnosis, we describe the cognitive impairment of these patients in detail and their response to the ketogenic diet in terms of cognitive improvement. Results We outlined a specific cognitive profile where performance skills were more affected than verbal ones, with prominent deficiencies in visuospatial and visuomotor abilities. We demonstrated the efficacy of ketogenic diet ( KD ) on cognitive outcome, with particular improvement tin total and verbal IQ ; we found that timing of KD introduction was inversely related to IQ outcome: the later the starting of KD , the lower the IQ , more notable nonverbal scale (verbal IQ correlation coefficient −0.634, p ‐value = 0.015). We found a significant direct correlation between cognition and CSF /blood glucose ratio values: the higher the ratio, the better the cognitive improvement in response to diet (from T0–baseline evaluation to T1 on average 18 months after introduction of KD ‐: TIQ correlation coefficient 0.592, p ‐value = 0.26; VIQ correlation coefficient 0.555, p ‐value = 0.039). Finally, we demonstrated that a longer duration of treatment is necessary to find an improvement in patients with “severely low ratio.” Conclusion Our results were consistent with the hypothesis that timing of the diet introduction is a predictive factor of cognitive outcome in these patients, confirming that earlier initiation of the diet may prevent the onset of all GLUT 1 DS symptoms: epilepsy, movement disorders, and cognitive impairment.

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The classic ketogenic diet (cKD) requires constant nutritional monitoring over time both to ensure its effectiveness and to reduce the likelihood of short- and long-term adverse effects. We retrospectively described the use of remote monitoring by e-mail during the first year of follow-up on cKD in 34 children (47% males; age range: 2−17 years) diagnosed with drug-resistant epilepsy (DRE; n = 14) or glucose transporter type 1 deficiency syndrome (GLUT1-DS; n = 20). All the e-mails were evaluated analyzing their frequency and content at 3, 6 and 12 months. Three families never sent e-mails. A median of 36.0 (IQR 23.0–64.0) e-mails per family were sent during the 12 follow-up months by the 31 patients. GLUT1-DS patients sent a greater number of e-mails than the DRE group (median 39.0 (IQR 25.5–56.5) vs. median 26.0 (IQR 19.0–65.0)). At the end of the follow-up period, a greater number of e-mails had been exchanged between the nutritional team and the families belonging to the group that increased its linear growth (median 83.5; IQR 48.0–102.0), compared to the other ones. Constant remote monitoring by e-mail could be a feasible and effective way for a better cKD management.