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Objective: Data on COVID-19 outcomes in persons with epilepsy (PWE) are scarce and inconclusive. We aimed to study the risk of hospitalization and death for COVID-19 in a large cohort of PWE from March 1, 2020 to October 31, 2021. Methods: The historical cohort design (EpiLink Bologna) compared adult PWE grouped into people with focal epilepsy (PFE), idiopathic generalized epilepsy (PIGE), and developmental and/or epileptic encephalopathy (PDEE), and a population cohort matched (ratio 1:10) for age, sex, residence, and comorbidity (assessed with the multisource comorbidity score), living in the local health trust of Bologna (approximately 800 000 residents). Clinical data were linked to health administrative data. Results: In both cohorts (EpiLink: n=1575 subjects, 1128 PFE, 267 PIGE, 148 PDEE, 32 other; controls: n=15 326 subjects), 52% were females, and the mean age was 50 years (SD=18). Hospital admissions for COVID-19 in the whole period were 49 (3.1%) in PWE and 225 (1.5%) in controls. The adjusted hazard ratio (aHR) in PWE was 1.9 (95% confidence interval [CI] = 1.4–2.7). The subgroups at higher risk were PFE (aHR=1.9, 95% CI=1.3–2.8) and PDEE (aHR=3.9, 95% CI=1.7–8.7), whereas PIGE had a risk comparable to the controls (aHR=1.1, 95% CI =.3–3.5). Stratified analyses of the two main epidemic waves (March–May 2020, October 2020–May 2021) disclosed a higher risk of COVID-19-related hospitalization during the first epidemic wave (March–May 2020; aHR=3.8, 95% CI=2.2–6.7). Polytherapy with antiseizure medications contributed to a higher risk of hospital admission. Thirty-day risk of death after hospitalization was 14% in both PWE and controls. Significance: During the first 20 months since the outbreak of COVID-19 in Bologna, PWE had a doubled risk of COVID-19 hospital admission compared to a matched control population. Conversely, epilepsy did not represent a risk factor for COVID-19-related death.

ObjectiveTo evaluate the long-term outcomes of patients with epilepsy and malformations of cortical development (MCD).MethodsWe conducted a historical cohort study of patients with epilepsy and MCD due to impaired neuronal migration and postmigration organization with a follow-up period of ≥5 years. For each patient, MCD was classified after accurate neuroimaging reappraisal by an expert neuroradiologist. The primary outcome was remission, defined as a period of seizure freedom ≥5 years at any time from epilepsy onset. We used Kaplan-Meier estimates for survival analysis and univariate and multivariate Cox regression analyses to evaluate baseline variables as possible factors associated with remission.ResultsThe cohort included 71 patients (M/F 31/40) with a 17-year median follow-up (1,506 person-years). About half (49.3%) had heterotopia, 35.2% polymicrogyria, 7% lissencephaly, and 8.5% the combination of 2 MCD. The mean age at seizure onset was 12.4 ± 7.2 years. Intellectual disability and neurologic deficits were observed in 30.4% and 40.9%, respectively. More than 60% of patients had refractory epilepsy. In 3 patients who underwent epilepsy surgery, MCD diagnosis was confirmed by histology. At the last visit, 44% of patients had been seizure-free during the previous year, but none of them had stopped antiseizure medication. Thirty patients achieved remission (42.2%) at some point in their disease history, whereas 41 individuals (57.8%) had never been in remission for ≥5 years. The cumulative remission rate was 38% by 20 years from inclusion. In the Cox model, unilateral distribution of MCD (hazard ratio [HR] 2.68, 95% CI 1.04–6.92) and a low seizure frequency at onset (HR 5.01, 95% CI 1.12–22.5) were significantly associated with remission.DiscussionPatients with epilepsy and MCD showed a remission rate of 38% by 20 years from onset. Unilateral distribution of the MCD is associated with a 3-fold probability of achieving remission. About 40% of patients showed a drug-sensitive condition with risk of relapse during their epilepsy course.Classification of EvidenceThis study provides Class II evidence that in patients with epilepsy and MCD, unilateral MCD and low seizure frequency at onset are associated with achieving epilepsy remission.

The study aims to characterize the epilepsy phenotype of maternally inherited Leigh's syndrome (MILS) and neuropathy, ataxia, retinitis pigmentosa (NARP) due to mutations in the mitochondrial ATP6 gene and to correlate electroclinical features with mutant heteroplasmy load (HL). We investigated 17 individuals with different phenotype, from asymptomatic carriers to MILS: 11 carried the m.8993T>G mutation, 5 the m.8993T>C and one the novel, de novo m.8858G>A mutation. Seizures occurred in 37.5% of patients, EEG abnormalities in 73%. We ranked clinical and EEG abnormalities severity and performed quantitative EEG to estimate Abnormality Ratio (AR) and Spectral Relative Power (SRP). Spearman’s rho and Kruskal–Wallis test were used for correlation with heteroplasmy load (HL). HL correlated with disease severity (Rho=0.63, P=0.012) and was significantly higher in patients with seizures or EEG abnormalities (P=0.014). HL correlated with EEG severity score only for the m.8993T>G (Rho=0.73, P=0.040), showing a trend toward a positive correlation with AR and delta SPR, irrespective of the mutation.

We describe a case of epileptic encephalopathy in a young woman with undiagnosed medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD), who presented with an early-onset focal motor status epilepticus (SE) then followed by permanent left hemiplegia and drug-resistant epilepsy with neurodevelopmental delay. Throughout her clinical history, recurrent episodes of lethargy, feeding difficulties, and clustering seizures occurred, progressing into a super refractory SE and death at the age of 25 years. Although epilepsy is not a distinctive feature of MCADD, we advise considering this metabolic disease as a possible etiology of epileptic encephalopathy and hemiconvulsion-hemiplegia-epilepsy syndrome of unknown origin, on the chance to provide a timely and targeted treatment preventing development delay and evolution to SE. Adult patients with epilepsy of unknown etiology not screened at birth for inborn errors of metabolism, such as MCADD, should be promptly investigated for these treatable conditions.

Many aspects of epilepsy in mitochondrial disorders (MDs) need to be further clarified. To this aim, we explored retrospectively a cohort of individuals with MDs querying the “Nationwide Italian Collaborative Network of Mitochondrial Diseases” (NICNMD) database (1467 patients included since 2010 to December 2016). We collected information on age at epilepsy onset, seizure type and frequency, genetic findings, and antiepileptic drugs (AEDs). At the time of our survey, 147/1467 (10%) patients in the NICNMD database had epilepsy. Complete information was available only for 98 patients, 52 males and 46 females, aged 5–92years (mean age 40.4 ± 18.4; 14/98 children/teenagers and 84 adults). Epilepsy was the presenting feature of MD in 46/98 (47%) individuals, with onset at a median age of 19years (range, 0.2–68; < 3years in 14/97 (14%), 3–19years in 36/97 (37%), > 19years in 47/97 (49%)). Moreover, 91/98 patients (93%) displayed multiple seizures, with daily or weekly frequency in 25/91 (28%). Interictal EEG was abnormal in 70/78 (90%) patients, displaying abnormal background (47/70; 67%) and/or interictal paroxysms (53/70; 76%). Eighty of 90 patients (89%) displayed a 50–100% reduction of seizures on AEDs; levetiracetam was the most commonly used. Forty-one patients (42%) carried the m.3243A>G mutation, 16 (16%) the m.8344A>G, and 9 (9%) nuclear DNA (nDNA) mutations. Individuals with early-onset seizures mainly carried nDNA mutations and had a more severe epilepsy phenotype, higher seizure frequency, and disorganized background EEG activity. A better definition of epilepsy in MDs may foster the diagnostic workup, management, and treatment of affected patients, and allow more homogeneous patient stratification.

Paroxysmal nonepileptic events are time-limited behavioral, cognitive, motor, sensory, and/or vegetative alterations, which, unlike epilepsy, do not depend on abnormal and excessive cortical activity. The two conditions posing the major issues of differential diagnosis with epilepsy are syncope and psychogenic seizures.

Glucose transporter type 1 (GLUT1) deficiency due to SLC2A1 mutations causes a wide spectrum of neurologic disorders ranging from severe encephalopathy with developmental delay, epilepsy, ataxia, and acquired microcephaly to atypical less severe variants. Early diagnosis is crucial for prompt initiation of a ketogenic diet. Recognizing GLUT1 deficiency syndrome (GLUT1DS) may be challenging and results in delayed diagnosis. Here we describe the clinical and molecular findings of patients with SLC2A1 mutations referred to our adult Epilepsy Center. Patients with a clinical history suggestive of GLUT1DS were screened for SLC2A1 mutations. Blood samples were collected from probands and first-degree relatives. A lumbar puncture was performed in two patients in fasting state, and cerebrospinal fluid and blood glucose measurement were undertaken at the same time. Since 2010, 19 GLUT1DS probands have been screened for SLC2A1 mutations. We identified four different SLC2A1 mutations in three sporadic cases and one family. Three mutations (c.130_135delTACAAC, c.342_343insA, and c.845A > G) were novel, whereas one was previously reported in the literature associated with a different phenotype (c.497_499delTCG). Here we describe a small case series of patients with sporadic and familial GLUT1DS presenting with a broad phenotypic heterogeneity which is likely to be responsible for the considerable delay in diagnosis.

Highlights • We assessed sudden unexpected death in epilepsy in nocturnal frontal lobe epilepsy. • The incidence of SUDEP in NFLE was no higher than that of other epilepsy populations. • The lower than expected risk of SUDEP might reflect a low occurrence of GTCS in NFLE., Objective Most cases of sudden unexpected death in epilepsy (SUDEP) follow a seizure, and most deaths occur while people are in bed, presumably sleeping. Nocturnal seizures are reported to be a risk factor for SUDEP. People with nocturnal frontal lobe epilepsy (NFLE) have seizures predominantly or exclusively during sleep, often many times per night. The present study aimed to assess whether NFLE represents a high-risk condition for SUDEP. Methods The present study retrospectively assessed the incidence of SUDEP in a cohort reconstructed from a dedicated database of consecutive patients referred to the Epilepsy and Sleep Centres of the Institute of Neurological Sciences of Bologna from 1980 to 2012 with: (1) a diagnosis of NFLE, (2) at least 90% of seizures during sleep, and (3) at least one-year of follow-up. Results One hundred and three people were included. The median time from seizure onset to last observation was 26 years, equal to a follow-up of 2789 person-years. One person died of SUDEP during the follow-up period. The incidence rate of SUDEP was 0.36 per 1000 person-years (95% CI 0.01 to 2.0). Conclusions The incidence of SUDEP in the participant population was not higher than the rates previously reported in prevalent epilepsy populations (0.4 to 2.3 per 1000 person-years). The low prevalence of SUDEP might reflect the low occurrence of generalised tonic-clonic seizures in people with NFLE.

Objective:To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).Methods:We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.Results:We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR.Conclusions:Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.

The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case–control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group.

The clinical spectrum of epilepsy related to celiac disease (CD) ranges from benign syndromes to intractable epilepsy with evolution to a severe encephalopathy, including progressive myoclonic epilepsy (PME). A more specific syndrome characterised by the association of CD, epilepsy, and occipital calcifications (CEC) has also been reported. This study describes the clinical, neuroradiological and neurophysiological features of eight consecutive epileptic patients with a diagnosis of CD confirmed by laboratory tests and duodenal biopsy, referring to our Epilepsy Centre. Despite its small size, this series reflects the broad spectrum of the association between the two diseases, since it includes four cases of CEC and a more heterogeneous group of patients without cerebral calcifications comprising one case of limbic encephalitis and a case of PME. Our cohort suggests that more complex pathogenic mechanisms may be involved in the association between epilepsy and CD, and that CD should be included in the screening for PME etiology. Our data also confirm the major involvement of the occipital lobe, and minimise both the importance of calcifications in epileptogenesis and folic acid deficit in the development of calcifications.

Summary Purpose: Retrospective observations disclosed an overlap between parasomnias and nocturnal frontal lobe epilepsy (NFLE) not only in patients but also in their relatives, suggesting a possible common pathogenetic mechanism. This study aimed to verify whether relatives of patients with NFLE have a higher frequency of parasomnias, namely arousal disorders, and thereby shed light on the still unknown pathophysiologic mechanisms underlying NFLE. Methods: We undertook a case–control family study in which we recruited NFLE probands and healthy controls, matched for age, sex, education, and geographic origin. At least four relatives were included for each proband and control. Each subject underwent a standardized interview, with application of the International Classification of Sleep Disorders–Revised (ICSD-R 2001) minimal criteria to diagnose the lifetime prevalence of the main parasomnias. Results: Four hundred fifty-eight individuals were recruited: 33 NFLE probands, 200 relatives of probands, 31 controls, and 194 control relatives. All NFLE probands but one have sporadic NFLE. The lifetime prevalence of the following parasomnias differed in proband relatives versus control relatives: arousal disorders [odds ratio (OR) 4.7, 95% confidence interval (CI) 2.0–11.6; p

n.a.

Paroxysmal kinesigenic dyskinesia is a neurological condition characterised by brief attacks of involuntary movements triggered by sudden voluntary movements.We describe the clinical, polygraphic, and genetic features of an Italian family with paroxysmal kinesigenic dyskinesia.Paroxysmal kinesigenic dyskinesia manifested as brief choreoathetosic-dystonic attacks precipitated by sudden movements, varying in severity and frequency, amongst the four affected family members. The disorder follows an autosomal dominant transmission and affects female members. Mutation of SLC2A1, MR1, CACNA1A, and ATP1A2 genes was excluded by direct sequencing. Mutation analysis of the PRRT2 gene revealed a single nucleotide duplication, c.649dupC, resulting in the frameshift mutation p.Arg217Profs*8 in all affected members.Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. We describe a family with paroxysmal kinesigenic dyskinesia associated with PRRT2 gene mutation, mild intrafamilial clinical heterogeneity, and benign course. [Published with video sequences].

Seizure response and alerting behaviour may spontaneously develop in dogs living with children or adults with epilepsy. Some dogs can also be reliably trained to respond and anticipate seizures. We describe the case of a dog, not previously trained for assistance work, showing complex seizure response behaviour. This is the first release of a home video recording of a dog reacting to its owner's seizure.