Summary Objective PCDH19‐related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever‐induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19‐related epilepsy and better define the epileptic phenotype, genotype‐phenotype correlations, and related outcome‐predicting factors. Methods We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19‐related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. Results At last follow‐up (median = 12 years, range = 1.9‐42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure‐free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty‐six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). Significance We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long‐term follow‐up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.

New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic–clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies.

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Background: Obesity is associated with lower serum vitamin D (25(OH)D) levels through several mechanisms. The aim of the study was to examine the possibility of a negative association between fat mass and 25(OH)D levels in a cohort of otherwise healthy overweight and obese subjects, independently of age, sex, blood pressure levels and anthropometric and metabolic parameters. Materials and Methods: 147 overweight and obese subjects (106 women and 41 men), aged between 18 and 69 years, were enrolled into the study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, insulin, glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. The season in which the blood samples were collected was autumn. Insulin resistance was assessed by using the Homeostasis Model Assessment (HOMA-IR). Body composition parameters (Fat Mass [FM], Fat Free Mass [FFM], body cell mass [BCM], Total Body Water [TBW]) were measured by electrical Bioimpedance Analysis (BIA). Lastly, demographic, anthropometric and clinical parameters (age, Body Mass Index [BMI], Waist Circumference [WC], Systolic (SBP) and Diastolic (DBP) blood pressure) were also assessed. Results: 25(OH)D levels were significantly and negatively correlated with BMI (P <0.001), WC (P <0.01), DBP (P <0.05), insulin (P <0.001), HOMA-IR (P <0.01), triglycerides (P <0.01), and fat mass (P <0.001). A multivariate regression analysis was performed by considering 25(OH)D levels as the dependent variable and sex, waist circumference, fat mass, DBP, triglycerides, and insulin (or HOMAIR) as the independent ones, and 25(OH)D levels maintained a significant and independent relationship only with fat mass (negative) (P <0.01). Conclusion: This study clearly shows that 25(OH)D circulating levels are progressively lower with the increase of fat mass, independently of sex, body fat distribution, blood pressure and insulin and metabolic parameters. These data strongly show that adipose tissue accumulation per se is absolutely the main factor responsible factor for lower 25(OH)D levels in obese subjects, possibly through sequestration of fat soluble 25(OH)D in fat mass.

Background Lafora disease (LD) is a rare, lethal, progressive myoclonus epilepsy for which no targeted therapy is currently available. Studies on a mouse model of LD showed a good response to metformin, a drug with a well known neuroprotective effect. For this reason, in 2016, the European Medicines Agency granted orphan designation to metformin for the treatment of LD. However, no clinical data is available thus far. Methods We retrospectively collected data on LD patients treated with metformin referred to three Italian epilepsy centres. Results Twelve patients with genetically confirmed LD (6 EPM2A , 6 NHLRC1 ) at middle/late stages of disease were treated with add-on metformin for a mean period of 18 months (range: 6–36). Metformin was titrated to a mean maintenance dose of 1167 mg/day (range: 500–2000 mg). In four patients dosing was limited by gastrointestinal side-effects. No serious adverse events occurred. Three patients had a clinical response, which was temporary in two, characterized by a reduction of seizure frequency and global clinical improvement. Conclusions Metformin was overall safe in our small cohort of LD patients. Even though the clinical outcome was poor, this may be related to the advanced stage of disease in our cases and we cannot exclude a role of metformin in slowing down LD progression. Therefore, on the grounds of the preclinical data, we believe that treatment with metformin may be attempted as early as possible in the course of LD.