Sleep spindles are the hallmark of N2 sleep and are attributed a key role in cognition. Little is known about the impact of epilepsy on sleep oscillations underlying sleep-related functions. This study assessed changes in the global spindle rate in patients with epilepsy, analysed the distribution of spindles in relation to the epileptic focus, and performed correlations with neurocognitive function. Twenty-one patients with drug-resistant focal epilepsy (12 females; mean age 32.6 ± 10.7 years [mean ± SD]) and 12 healthy controls (3 females; 24.5 ± 3.3 years) underwent combined whole-night high-density electroencephalography and polysomnography. Global spindle rates during N2 were lower in epilepsy patients compared to controls (mean = 5.78/min ± 0.72 vs. 6.49/min ± 0.71, p = 0.02, d = − 0.70). Within epilepsy patients, spindle rates were lower in the region of the epileptic focus compared to the contralateral region (median = 4.77/min [range 2.53–6.18] vs. 5.26/min [2.53–6.56], p = 0.02, rank biserial correlation RC = − 0.57). This decrease was driven by fast spindles (12–16 Hz) (1.50/min [0.62–4.08] vs. 1.65/min [0.51–4.28], p = 0.002, RC = − 0.76). The focal reduction in spindles was negatively correlated with two scales of attention (r = − 0.54, p = 0.01; r = − 0.51, p = 0.025). Patients with focal epilepsy show a reduction in global and local spindle rates dependent on the region of the epileptic focus. This may play a role in impaired cognitive functioning. Future work will show if the local reduction in spindles can be used as potential marker of the epileptic focus.
Memantine is an N-methyl-D-aspartate receptor antagonist, approved for dementia treatment. There is limited evidence of memantine showing benefit for pediatric neurodevelopmental phenotypes, but no randomized placebo-controlled trials in children with developmental and epileptic encephalopathy. In this randomized double-blind placebo-controlled crossover trial (Trial registration: https://clinicaltrials.gov/ct2/show/NCT03779672), patients with e developmental and epileptic encephalopathy received memantine and placebo, each for a 6-week period separated by a 2-week washout phase. Electroencephalography, seizure diary, patient caregivers’ global impression, serum inflammatory markers, and neuropsychological evaluation were performed at baseline and after each treatment phase. The primary outcome measure was classification as a “responder,” defined as ≥ 2 of: > 50% seizure frequency reduction, electroencephalography improvement, caregiver clinical impression improvement, or clear neuropsychological testing improvement. Thirty-one patients (13 females) enrolled. Two patients withdrew prior to initiating medication and two (twins) had to be removed from analysis. Of the remaining 27 patients, nine (33%) were classified as responders to memantine versus two (7%) in the placebo group (p < 0.02). Electroencephalography improvement was seen in eight patients on memantine compared to two on placebo (p < 0.04). Seizure improvement was observed in eight patients on memantine and two on placebo (p < 0.04). Caregivers reported overall clinical improvement in 10 patients on memantine compared to seven on placebo (not significant). Statistical analysis of neuropsychological evaluation suggested improvements in symptoms of attention deficit hyperactivity disorder and autism. Memantine is a safe and effective treatment for children with developmental and epileptic encephalopathy, having the potential to improve both seizure control and cognitive function.
Background Cerebral palsy (CP) is the most common motor impairment in childhood and often accompanied by a broad spectrum of comorbidities. Data are sparse concerning visual impairment (VI) and functional classification among CP children. Objective The objective of this study was to analyze the prevalence of VI among children with CP and to investigate a possible association between VI and Gross Motor Function Classification System (GMFCS) and the Bimanual Fine Motor Function (BFMF). Methods In this hospital-based study, records of 200 children with CP aged 2 to 17 years were reviewed. Results Overall, VI was found in 59.5% of children with CP. Prevalence of VI was higher when compared with non-CP children. A correlation between GMFCS as well as BFMF and severity of VI was found. Children with severe CP were at greater risk for severe VI, especially cerebral VI compared with children with mild CP. Conclusion VI is a significant problem in children with CP and is correlated with motor function. Children with CP should undergo detailed ophthalmologic and orthoptic assessment to enable early intervention.
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.
Objective: The aim of this study was to examine a possible association of HbA1c, quality of life (QoL), fitness, and electrophysiological parameters in children with type 1 diabetes mellitus (T1DM). Methods: The study population (n = 34) consisted of patients with T1DM (n = 17) and an age-, sex-, and BMI-matched healthy control group (n = 17). HbA1c was obtained from patients with T1DM at time of diagnosis (T0), at 6 months (T6), at 12 months (T12), and at time of study inclusion (Tstudy). QoL was determined with a standardized questionnaire (KINDL-R). All children completed a 6-min walk test (6MWT) to evaluate their fitness level. Electrodiagnostic studies established upper and lower limb motor and sensory nerve conduction velocities (NCV). Results: Higher HbA1c (Tstudy) was associated with lower QoL showing in the subscales self-esteem, friends, and school. Higher HbA1c at (T6) and (T12) was associated with lower QoL in the subscale self-esteem. Based on various subscales, perceived problem areas differed significantly between children and their parents. No differences in fitness level and NCV were found between patients and controls except for a significantly slower median motor NCV in patients. HbA1c was not associated with NCVs at this early stage of disease. Conclusions: Good metabolic control reflected by adequate HbA1c values seems to be important for a good QoL in children with T1DM. Early HbA1c might be associated with QoL during follow-up.
Study Objectives Whereas there is plenty of evidence on the influence of epileptic activity on non-rapid eye movement (NREM) sleep macro- and micro-structure, data on the impact of epilepsy on rapid eye movement (REM) sleep remains sparse. Using high-density electroencephalography (HD-EEG), we assessed global and focal disturbances of sawtooth waves (STW) as cortically generated sleep oscillations of REM sleep in patients with focal epilepsy. Methods Twenty-two patients with drug-resistant focal epilepsy (13 females; mean age, 32.6±10.7 years; 12 temporal lobe epilepsy) and 12 healthy controls (3 females; 24.0±3.2 years) underwent combined overnight HD-EEG and polysomnography. STW rate, duration, frequency, power, spatial extent, IED rates and sleep homeostatic properties were analysed. Results STW rate and duration were reduced in patients with focal epilepsy compared to healthy controls (rate: 0.64/min±0.46 vs. 1.12/min±0.41, p=0.005, d=-0.98; duration: 3.60s±0.76 vs. 4.57±1.00, p=0.003, d=-1.01). Not surprisingly given the fronto-central maximum of STW, the reductions were driven by extratemporal lobe epilepsy patients (rate: 0.45/min±0.31 vs. 1.12/min±0.41, p=0.0004, d=-1.35; duration: 3.49s±0.92 vs. 4.57±1.00, p=0.017, d=-0.99) and more pronounced in the first vs. the last sleep cycle (rate: d=-0.90 vs. d=-0.62, duration: d=-1.01 vs. d=-0.80). There was no regional decrease of STWs in the region with the epileptic focus vs. the contralateral side (all ps>0.5). Conclusion Patients with focal epilepsy and in particular extratemporal lobe epilepsy show a global reduction of STW activity in REM sleep. This may suggest that epilepsy impacts cortically generated sleep oscillations even in REM sleep when epileptic activity is low.
Ketogenic diet (KD) and pulsatile dexamethasone therapy (PDT) are commonly used in the treatment of children with drug resistant epilepsy. Potential side effects of the KD are hypoglycemia, whereas PDT might lead to hyperglycemia. One practical option to measure glucose concentrations regularly is the flash glucose monitoring system (FGM). In this single-center study in Germany, two pediatric patients with epilepsy (age: 6.0 and 6.8 years) received FGM from the beginning of the KD over six months, in the year 2020, and one patient (9.8 years) was observed for one month on PDT and switched to the KD thereafter. Glucose concentrations were measured by using an FGM system and capillary blood measurement. Seizure frequency, changes in cognition, motor performance, social behavior, and sleep quality were evaluated. The mean hypoglycemia rate per day (65 mg/dL and lower) declined significantly in patient 1 and 2 after three months. Patient 3 showed in total seven hyperglycemic events during PDT. Patient 1 became seizure free. Improvement of attention and memory performance were reported. FGM during the KD as a treatment for drug resistant epilepsies in childhood is a practical option to explore and to avoid hypoglycemia during the KD and hyperglycemia during PDT.
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