Recurrent schizophrenia-like psychosis as first manifestation of epilepsy: a diagnostic challenge in neuropsychiatry

Since the 1950s, several studies have been carried out to investigate the occurrence of schizophrenia-like psychoses in epilepsy. The psychopathological profile comprises symptoms from the affective, schizophrenic, and cognitive domains and the prevalence varies between 2% to 20%. Classification of such conditions is performed according to their temporal relationship with the seizure itself. Although it is well known that epilepsy may be associated with psychotic disorders, it is less widely recognized that relapsing psychotic phenomena may be the first and only symptom of epilepsy. In this research, two patients are described who were initially referred for recurrent episodes of bipolar affective disorder and schizophrenic psychosis, respectively. In both patients, a diagnosis of relapsing postictal psychotic states due to previously undiagnosed epilepsy was made and consequently, treatment with antiepileptics was started. During follow up over several months, they remained free of both epileptic and psychotic symptoms. Given the kaleidoscopic nature of the postictal psychosis and full recovery from this, such psychoses best meet the criteria for a cycloid psychosis. These observations illustrate diagnostic and therapeutic pitfalls due to the conceptual disintegration emerging from the inadequate separation between psychiatry and neurology. Therefore, the importance of a neuropsychiatric viewpoint should be promoted

Mortality in Dravet syndrome: A review

AbstractIntroductionPremature mortality is a major issue in Dravet syndrome (DS). To improve understanding of DS premature mortality, we conducted a comprehensive literature search with a particular emphasis on SUDEP.MethodsWe searched PubMed, Embase, Web of Science, Cochrane, CENTRAL, CINAHL, PsycINFO, Academic Search Premier, and ScienceDirect on the following terms: “Dravet syndrome”, “severe myoclonic epilepsy”, “SMEI”, “mortality”, “survivors”, “prognosis”, and “death”. DS cases or cohorts studies reporting mortality were included.ResultsThe search yielded 676 articles and 86 meeting abstracts. After removing duplicates and screening titles and abstracts, full text of 73 articles was reviewed. Only 28 articles and six meeting abstracts met inclusion criteria. Five articles and four meeting abstracts were excluded, as the case(s) were also described elsewhere. After checking the references, five additional studies were included. The 30 items reported 177 unique cases. Sudden unexpected death in epilepsy was the likely cause in nearly half of the cases (n=87, 49%), followed by status epilepticus (n=56, 32%). Drowning or accidental death was reported in 14 cases (8%), infections in 9 (5%), other causes in six (3%), and unknown in five (3%). Age at death was reported for 142 of the 177 cases (80%), with a mean age of 8.7±9.8years (SD); 73% died before the age of 10years.DiscussionDravet syndrome is characterized by high epilepsy-related premature mortality and a marked young age at death. Sudden unexpected death in epilepsy is the leading reported cause of death in DS, accounting for nearly half of all deaths. The cause of this excess mortality remains elusive but may be explained by epilepsy severity, as well as genetic susceptibility to SUDEP

NEXMIF encephalopathy:an X-linked disorder with male and female phenotypic patterns

Purpose Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. Methods Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. Results Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. Conclusion NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants

Recurrent schizophrenia-like psychosis as first manifestation of epilepsy: a diagnostic challenge in neuropsychiatry

Willem MA Verhoeven1,2, Jos IM Egger1,3, W Boudewijn Gunning4, Martijn Bevers1, Boudewijn JHB de Pont11Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands; 2Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, The Netherlands; 3Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; 4Epilepsy Centre Kempenhaeghe, Heeze, The NetherlandsAbstract: Since the 1950s, several studies have been carried out to investigate the occurrence of schizophrenia-like psychoses in epilepsy. The psychopathological profile comprises symptoms from the affective, schizophrenic, and cognitive domains and the prevalence varies between 2% to 20%. Classification of such conditions is performed according to their temporal relationship with the seizure itself. Although it is well known that epilepsy may be associated with psychotic disorders, it is less widely recognized that relapsing psychotic phenomena may be the first and only symptom of epilepsy. In this research, two patients are described who were initially referred for recurrent episodes of bipolar affective disorder and schizophrenic psychosis, respectively. In both patients, a diagnosis of relapsing postictal psychotic states due to previously undiagnosed epilepsy was made and consequently, treatment with antiepileptics was started. During follow up over several months, they remained free of both epileptic and psychotic symptoms. Given the kaleidoscopic nature of the postictal psychosis and full recovery from this, such psychoses best meet the criteria for a cycloid psychosis. These observations illustrate diagnostic and therapeutic pitfalls due to the conceptual disintegration emerging from the inadequate separation between psychiatry and neurology. Therefore, the importance of a neuropsychiatric viewpoint should be promoted.Keywords: postictal psychosis, epilepsy, classification, cycloid psychosis, neuropsychiatr

Value of re-interpretation of controversial EEGs in a tertiary epilepsy clinic

Objective Diagnostic value and efficacy of re-interpretation of previous EEGs in 100 patients admitted to a tertiary epilepsy center with EEG results conflicting with the clinical diagnosis after the first visit. Methods EEGs were reclassified. A matched control group was included to assess the efficiency of the re-interpretation process. Efficacy was assessed by questionnaires and costs as number of technician hours needed. Results In 85 patients the previous EEG conclusion was known. In 43 the conclusion was altered. In 23 the epileptic activity changed from positive to negative (17) or the reverse (6). In 15 the focus changed (7 originally classified as generalized epileptic activity). In 5 the syndrome changed. 57% of the re-interpretation group needed no extra EEG afterwards. 96% of the re-interpretations were considered useful by requesting and 72% by not involved neurologists. The average time per EEG technologist per patient was 8,81 h in controls and 5,40 in the re-interpretation group. Conclusions In 43 from the 85 patients (51%) re-interpretation of ‘controversial’ EEGs led to a different opinion. The re-interpretations were useful and less time consuming, compared to new EEGs in controls. Significance Re-interpretation of ‘controversial’ EEGs is useful and cost effective

Cardiac arrhythmias in Dravet syndrome: an observational multicenter study

Objectives: We ascertained the prevalence of ictal arrhythmias to explain the high rate of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome (DS). Methods: We selected cases with clinical DS, ≥6 years, SCN1A mutation, and ≥1 seizure/week. Home-based ECG recordings were performed for 20 days continuously. Cases were matched for age and sex to two epilepsy controls with no DS and ≥1 major motor seizure during video-EEG. We determined the prevalence of peri-ictal asystole, bradycardia, QTc changes, and effects of convulsive seizures (CS) on heart rate, heart rate variability (HRV), and PR/QRS. Generalized estimating equations were used to account for multiple seizures within subjects, seizure type, and sleep/wakefulness. Results: We included 59 cases. Ictal recordings were obtained in 45 cases and compared to 90 controls. We analyzed 547 seizures in DS (300 CS) and 169 in controls (120 CS). No asystole occurred. Postictal bradycardia was more common in controls (n = 11, 6.5%) than cases (n = 4, 0.7%; P = 0.002). Peri-ictal QTc-lengthening (≥60ms) occurred more frequently in DS (n = 64, 12%) than controls (n = 8, 4.7%, P = 0.048); pathologically prolonged QTc was rare (once in each group). In DS, interictal HRV was lower compared to controls (RMSSD P = 0.029); peri-ictal values did not differ between the groups. Prolonged QRS/PR was rare and more common in controls (QRS: one vs. none; PR: three vs. one). Interpretation: We did not identify major arrhythmias in DS which can directly explain high SUDEP rates. Peri-ictal QTc-lengthening was, however, more common in DS. This may reflect unstable repolarization and an increased propensity for arrhythmias

Photosensitivity in Dravet syndrome is under-recognized and related to prognosis

OBJECTIVE: To detect determinants for photoparoxysmal EEG response (PPR) in SCN1A-related Dravet syndrome (DS). METHODS: Data were studied from nationwide medical histories and EEGs of DS-patients (n=53; 31 males, age 2-19years). Detailed questionnaires on visual stimuli were completed by parents (n=49). RESULTS: PPR was found in 22 patients (42%; median age 1.25yr), and repeatedly in 17%. PPR (17% of 249 intermittent photic stimulation (IPS)-EEGs) occurred more often with optimal IPS protocols (OR 2.11 [95%CI 1.09-4.13]) and in EEGs showing spontaneous epileptiform abnormalities (OR 5.08 [95%CI 2.05-12.55]). PPR-positive patients tended to be younger at first (p=0.072) and second seizure (p=0.049), showed severe intellectual disability (p=0.042), and had more often spontaneous occipital epileptiform abnormalities (p<0.001). Clinical sensitivity was reported in medical files in 22% of patients and by parents in 43% (self-induction 24%). Clinical or EEG proven visual sensitivity was detected in 65% of cases. CONCLUSIONS: Sensitivity to visual stimuli is very common in DS and more often noticed by parents than confirmed by EEG. Detection of PPR improves with repetitive tests using accurate IPS protocols. SIGNIFICANCE: Photosensitivity is an important feature in DS and seems to be a marker of the severity of the disorder. Therefore repeated standardized IPS should be encouraged

Photosensitivity in Dravet syndrome is under-recognized and related to prognosis

OBJECTIVE: To detect determinants for photoparoxysmal EEG response (PPR) in SCN1A-related Dravet syndrome (DS). METHODS: Data were studied from nationwide medical histories and EEGs of DS-patients (n=53; 31 males, age 2-19years). Detailed questionnaires on visual stimuli were completed by parents (n=49). RESULTS: PPR was found in 22 patients (42%; median age 1.25yr), and repeatedly in 17%. PPR (17% of 249 intermittent photic stimulation (IPS)-EEGs) occurred more often with optimal IPS protocols (OR 2.11 [95%CI 1.09-4.13]) and in EEGs showing spontaneous epileptiform abnormalities (OR 5.08 [95%CI 2.05-12.55]). PPR-positive patients tended to be younger at first (p=0.072) and second seizure (p=0.049), showed severe intellectual disability (p=0.042), and had more often spontaneous occipital epileptiform abnormalities (p<0.001). Clinical sensitivity was reported in medical files in 22% of patients and by parents in 43% (self-induction 24%). Clinical or EEG proven visual sensitivity was detected in 65% of cases. CONCLUSIONS: Sensitivity to visual stimuli is very common in DS and more often noticed by parents than confirmed by EEG. Detection of PPR improves with repetitive tests using accurate IPS protocols. SIGNIFICANCE: Photosensitivity is an important feature in DS and seems to be a marker of the severity of the disorder. Therefore repeated standardized IPS should be encouraged