Ketone Supplementation: Meeting the Needs of the Brain in an Energy Crisis

Diverse neurological disorders are associated with a deficit in brain energy metabolism, often characterized by acute or chronic glucose hypometabolism. Ketones serve as the brain's only significant alternative fuel and can even become the primary fuel in conditions of limited glucose availability. Thus, dietary supplementation with exogenous ketones represents a promising novel therapeutic strategy to help meet the energetic needs of the brain in an energy crisis. Preliminary evidence suggests ketosis induced by exogenous ketones may attenuate damage or improve cognitive and motor performance in neurological conditions such as seizure disorders, mild cognitive impairment, Alzheimer's disease, and neurotrauma.

Epilepsy and other seizure disorders in acute psychiatric inpatients

Background It is well known that patients with epilepsy have a high rate of psychiatric comorbidity. However, studies exploring epilepsy in psychiatric cohorts are scarce. The aim of this study was to examine the prevalence of seizure disorders in acute psychiatric inpatients. Methods This is a cross-sectional study performed in a catchment-area based acute psychiatric department. All patients (age > 18) admitted during September 2011 - March 2012 were eligible for inclusion. Consenting patients were screened for a life-time history of epilepsy or seizures using self-reported questionnaire data and diagnostic codes for epilepsy in hospital and National registries. Patients scoring positive to one or more of these screening criteria underwent a thorough diagnostic validation (chart review), and the seizure disorders were classified as epilepsy, acute symptomatic seizures and/or psychogenic non-epileptic seizures according to current definitions. Results A total of 380 out of 591 (64.3%) consecutively admitted patients consented to participate in the study. Eighty-nine patients (23.4%) scored positive to one or more screening criteria. Fifteen (3.9%) were classified with epilepsy, 21 (5.5%) with acute symptomatic seizures and 9 (2.4%) with psychogenic non-epileptic seizures. Conclusions This is the first study to report on the prevalence of seizure disorders in acute psychiatric inpatients. The life-time prevalence of epilepsy in this cohort of patients is five – six times as high as reports in the general population. These findings underscore the need for the clinical psychiatrist to have comprehensive knowledge on the interface between epileptology and psychiatry. Trials registration ClinicalTrials.gov identifier NCT01415323.

Approach to Neurological Channelopathies and Neurometabolic Disorders in Newborns

Ion channel disorders (channelopathies) can affect any organ system in newborns before 2 months of life, including the skeletal muscle and central nervous system. Channelopathies in newborns can manifest as seizure disorders, which is a critical issue as early onset seizures can mimic the presentation of neurometabolic disorders. Seizures in channelopathies can either be focal or generalized, and range in severity from benign to epileptic encephalopathies that may lead to developmental regression and eventually premature death. The presenting symptoms of channelopathies are challenging for clinicians to decipher, such that an extensive diagnostic survey through a precise step-by-step process is vital. Early diagnosis of a newborn’s disease, either as a channelopathy or neurometabolic disorder, is important for the long-term neurodevelopment of the child.

Epilepsy and ADHD

Epilepsy encompasses a set of heterogeneous seizure disorders, with various clinical characteristics that exclude a unique etiological mechanism. Individuals with this disease have a significantly higher rate for the development of psychiatric and neurological conditions. Children with epilepsy have two to three times increased risk of developing ADHD when compared to healthy individuals, while one in five epileptic adults have ADHD symptoms. In children with epilepsy, the severity and frequency of seizures and an earlier age at the onset of seizures are common risk factors for ADHD. A narrative review of the literature was carried out and articles published in the period between 2003 and 2021 in digital databases of the health area (LILACS, Medline, Web of Science, SciELO and PubMed) were selected. The review showed that epilepsy can increase the risk of developing ADHD in children, and that benign rolandic epilepsy is the most diagnosed type in these children, which even has a high rate of neurobehavioral disorders with associated ADHD symptoms. Early diagnosis and appropriate management lead to a better prognosis in this group of patients.

Seizure disorders in pregnancy: an insight beyond eclampsia and epilepsy

Background: Seizures in pregnancy contribute to poor maternal and perinatal outcome. Though eclampsia and epilepsy are common causes of seizures in pregnancy but there are several other conditions apart from eclampsia and epilepsy which give rise to convulsions. Objective of this study was to evaluate fetomaternal outcome in patients with seizure disorders as well as to analyze the other causes of seizures in pregnancy apart from eclampsia and epilepsy.Methods: This prospective study was conducted in Shri. Guru Ram Rai institute of medical and health sciences, Dehradun, India over a period of 39 months from January 2017to March 2020, in all pregnant women with seizure disorders delivered in this hospital. In all cases demographic characteristics, causes of seizure with special attention on noneclamptic, non-epileptic conditions, maternal complications, mode of delivery and fetal outcome were noted.Results: Total 97 cases with seizure disorders were included in the study. Mostly seizures were due to eclampsia and epilepsy in 91.75% cases. Among other causes neurocysticercosis, cerebral malformation, posterior reversible encephalopathy syndrome, brain tumor, and cerebral infarcts contributed to seizures in pregnancy in 8.25%cases. Maternal complications were premature rupture of membranes, gestational diabetes mellitus, hypothyroidism, anaemia, jaundice and abruption observed in37.11% cases. Live birth rate was 76.28%, prematurity was present in 27.83% cases and fetal growth restriction was seen in 7.21% neonates. There were 5 (5.15 %) neonatal deaths.Conclusions: Seizure disorders in pregnancy are associated with significant increase in maternal and fetal risk. Maternal complications, cesarean section rate and neonatal complications are increased. Several other conditions apart from eclampsia, need to be considered in patients without epilepsy presenting with convulsions in pregnancy.

Compound Heterozygote of Point Mutation and Chromosomal Microdeletion Involving OTUD6B Coinciding with ZMIZ1 Variant in Syndromic Intellectual Disability

The OTUD6B and ZMIZ1 genes were recently identified as causes of syndromic intellectual disability (ID) with shared phenotypes of facial dysmorphism, distal limb anomalies, and seizure disorders. OTUD6B -and ZMIZ1 -related ID are inherited in autosomal recessive and autosomal dominant patterns, respectively. We report a 5-year-old girl with developmental delay, facial phenotypes resembling Williams syndrome, and cardiac defects. The patient also had terminal broadening of the fingers and polydactyly. Cytogenomic microarray (CMA), whole exome sequencing (WES), and mRNA analysis were performed. The CMA showed a paternally inherited 0.118 Mb deletion of 8q21.3, chr8:92084087–92202189, with OTUD6B involved. The WES identified a hemizygous OTUD6B variant, c.873delA (p.Lus291AsnfsTer3). The mother was heterozygous for this allele. The WES also demonstrated a heterozygous ZMIZ1 variant, c.1491 + 2T > C, in the patient and her father. This ZMIZ1 variant yielded exon 14 skipping, as evidenced by mRNA study. We suggest that Williams syndrome-like phenotypes, namely, periorbital edema, hanging cheek, and long and smooth philtrum represent expanded phenotypes of OTUD6B -related ID. Our data expand the genotypic spectrum of OTUD6B - and ZMIZ1 -related disorders. This is the first reported case of a compound heterozygote featuring point mutation, chromosomal microdeletion of OTUD6B, and the unique event of OTUD6B, coupled with ZMIZ1 variants.

Electroencephalographic Findings in a Cohort of Egyptian Systemic Lupus Erythematosus Patients with Neuropsychiatric Manifestations

Background and Objective Neuropsychiatric manifestations are frequently reported in 75% of Systemic Lupus Erythematosus (SLE) patients and that varied from mild subtle signs: headache or mood disturbance to life threatening conditions: acute confusional state, major fits, stroke or transverse myelitis. Electroencephalography (EEG) was used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in SLE patients or not. So, this study was done to describe EEG findings in a cohort of Egyptian SLE patients with Neuropsychiatric SLE (NPSLE), its possible correlation with any of the disease activity parameters and comparing them to patients with Non-NPSLE. Patients and Methods This case-control study was conducted on 60 SLE patients who fulfilled the 2015 ACR/SLICC Classification Criteria for SLE. They were classified into 2 groups: 30 patients with NPSLE as cases and 30 patients without NPSLE (Non-NPSLE) as controls. All patients were subjected to detailed medical history taking together with full clinical examination and calculations of SLE disease activity using the SLE disease activity index (SLEDAI) score. Laboratory investigations including CBC, ESR, CRP, BUN, creatinine, urine analysis, P/C ratio, C3, C4, Lupus Anticoagulant (LAC) and Anticardiolipin (ACL) antibodies and EEG were done for all patients. MRI brain was done for patients with NPSLE. Results There were 6 neuropsychiatric manifestations in the NPSLE group; the commonest was seizure disorders (43.3%), followed by psychosis (20.0%), cerebrovascular disease (16.7%), acute confusional state (13.3%), headache (10.0%) and lastly demyelinating syndrome (6.7%). SLEDAI score was higher in NPSLE group (Median=16) than nonNPSLE group (Median=4) (P < 0.01). ACL IgM positivity was higher in NPSLE group (P < 0.05). 53.3% of NPSLE group had abnormal MRI brain findings, the most common finding was periventricular white matter lesion (23.3%), followed by infarction (13.3%), subcortical white matter lesion and demyelinating lesion (6.7%). Lastly was sinus thrombosis, cerebral edema and encephalomalacia (3.3% each). 12 patients out of 30 (40.0%) with NPSLE had EEG abnormalities, while all 30 patients with non-NPSLE had no EEG abnormalities. The most common EEG abnormalities in NPSLE group were diffuse slowing (20.0%), followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7% each). 50% of patients with abnormal EEG had normal MRI. 13 patients out of 30 with NPSLE had seizure disorders (43.3%), 8 of them had abnormal EEG (61.5%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in diagnosing and studying the different manifestations of NPSLE especially seizure disorder and acute confusional state, but it cannot be used as a screening test alone for detecting NPSLE and must be supplemented by neuroimaging studies.

Psychogenic non-epileptic seizures (PNES) in the context of concurrent epilepsy – making the right diagnosis

Epilepsy is a risk factor for the development of psychogenic non-epileptic seizures (PNES) and comorbid epilepsy is recognized as a comorbidity in about 10–30% of patients with PNES. The combination of epileptic and nonepileptic seizures poses a particular diagnostic challenge. In patients with epilepsy, additional PNES may be suspected on the basis of their typical semiology. The possibility of additional PNES should also be considered if seizures fail to respond to antiepileptic drug treatment, in patients with frequent emergency admissions with seizures and in those who develop new types of seizures. The description of semiological details by patients and witnesses can suggest additional PNES. Home video recordings can support an initial diagnosis, however, especially in patients with mixed seizure disorders it is advisable to seek further diagnostic confirmation by capturing all habitual seizure types with video-EEG. The clinical features of PNES associated with epilepsy are similar to those in isolated PNES disorders and include longer duration, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, persistently closed eyes and mouth, ictal crying, recall of ictal experiences and absence of postictal confusion. PNES can also present as syncope-like episodes with unresponsiveness and reduced muscle tone. There is no unique epileptological or brain pathology profile putting patients with epilepsy at risk of additional PNES. However, patients with epilepsy and PNES typically have lower educational achievements and higher levels of psychiatric comorbidities than patients with epilepsy alone. Psychological trauma, including sexual abuse, appears to be a less relevant aetiological factor in patients with mixed seizure disorders than those with isolated PNES, and the gender imbalance (i.e. the greater prevalence in women) is less marked in patients with PNES and additional epilepsy than those with PNES alone. PNES sometimes develop after epilepsy surgery. A diagnosis of ‘known epilepsy’ should never be accepted without (at least brief) critical review. This narrative review summarises clinical, electrophysiological and historical features that can help identify patients with epilepsy and additional PNES.

Outcomes Among Patients With Reversible Cerebral Vasoconstriction Syndrome: A Nationwide United States Analysis

Background and Purpose: Reversible cerebral vasoconstriction syndrome (RCVS) is a well-established cause of stroke, but its demographics and outcomes have not been well delineated. Methods: Analysis of the United States Nationwide Inpatient Sample database (2016–2017) to characterize the frequency of hospitalizations for RCVS, demographic features, inpatient mortality, and discharge outcomes. Results: During the 2-year study period, 2020 patients with RCVS were admitted to Nationwide Inpatient Sample hospitals, representing 0.02 cases per 100 000 national hospitalizations. The mean age at admission was 47.6 years, with 85% under 65 years of age, and 75.5% women. Concomitant neurological diagnoses during hospitalization included ischemic stroke (17.1%), intracerebral hemorrhage (11.0%), subarachnoid hemorrhage (32.7%), seizure disorders (6.7%), and reversible brain edema (13.6%). Overall, 70% of patients were discharged home, 29.7% discharged to a rehabilitation facility or nursing home and 0.3% died before discharge. Patient features independently associated with the poor outcome of discharge to another facility or death were advanced age (odds ratio [OR], 1.04 [95% CI, 1.03–1.04]), being a woman (OR, 2.45 [1.82–3.34]), intracerebral hemorrhage (OR, 2.91 [1.96–4.31]), ischemic stroke (OR, 5.72 [4.32–7.58]), seizure disorders (OR, 2.61 [1.70–4.00]), reversible brain edema (OR, 6.26 [4.41–8.89]), atrial fibrillation (OR, 2.97 [1.83–4.81]), and chronic kidney disease (OR, 3.43 [2.19–5.36]). Conclusions: Projected to the entire US population, >1000 patients with RCVS are hospitalized each year, with the majority being middle-aged women, and about 300 required at least some rehabilitation or nursing home care after discharge. RCVS-related inpatient mortality is rare.