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 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 SE in twenty-eight patients, by a mean of six 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 hyper-intense 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 auto-antibodies was inconclusive, though in 7 of 11 patients had CSF lymphocytic pleocytosis and three 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 homogeneous condition with defined clinical features and a presumed but unidentified autoimmune aetiology. A better characterization of de novo SE is mandatory for the search of specific etiologies.

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. We retrospectively collected data on LD patients treated with metformin referred to three Italian epilepsy centres. 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. 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.

Background: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS‐associated neurological phenotypes and outcome. Methods and Results: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short‐ and long‐term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in‐hospital stay (8 [interquartile range, 5–12] versus 6 [interquartile range, 5–9] days; P <0.01) and more often experienced in‐hospital complications (27% versus 16%; P =0.01) mainly driven by cardiogenic shock and in‐hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P <0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long‐term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P <0.01). Neurological disorder was an independent predictor of both the 60‐day and long‐term mortality rate (odds ratio, 1.78 [95% CI, 1.07–2.97]; P =0.02; hazard ratio, 1.72 [95% CI, 1.33–2.22]; both P <0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long‐term mortality rates, 29.2% and 9.7%, respectively). Conclusions: Neurological disorders identify a high‐risk TTS subgroup for enhanced short‐ and long‐term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.