[Clinical and neurophysiological parameters in patients with epilepsy in the long-term period after COVID-19]. / Kliniko-neirofiziologicheskie pokazateli u patsientov s epilepsiei v otdalennom periode novoi koronavirusnoi infektsii.

OBJECTIVE: Clinical and psychophysiological assessment of the dynamics of the condition of patients with epilepsy in 4-6 months after the coronavirus infection. MATERIAL AND METHODS: An open controlled prospective comparative outpatient clinical and physiological study of patients diagnosed with epilepsy after suffering from COVID-19 (after 4-6 months) of moderate severity (n=16), patients diagnosed with epilepsy who did not suffer from COVID-19 (n=7), a control group (n=11) after confirmed COVID-19 (after 4-6 months). All groups were in the age range 23 to 50 years. Clinical/neurological and somatic research included: anamnesis, neurological examination, questioning, ECG, EEG, clinical and psychometric tests. RESULTS: There was an increase in the representation of epileptiform activity in the background EEG and more pronounced activity in provoking samples compared with background recording in 26.5% of patients who had suffered COVID-19 compared with the group of patients with epilepsy who had not suffered COVID-19. The detection of rare epileptic seizures in 18.8% of cases in the group of epilepsy patients, who underwent COVID-19, indicates an increase in epileptogenesis and a decrease in therapeutic control over seizures. At the same time, 87.5% of patients in this group showed a statistically significant increase in the influence of the sympathetic nervous system on the regulation of heart rhythm and an increase in anxiety and depression. CONCLUSION: The results can complement the understanding of the neuropsychiatric status of patients with epilepsy after COVID-19, which provides prerequisites for the development of optimal recovery directions in the rehabilitation period to maintain drug remission of epilepsy and reduce the possible progression of the disease.

Telemedicine and Epilepsy Care.

Telemedicine is a method of health care delivery well suited for epilepsy care, where there is an insufficient supply of trained specialists. The telemedicine "Hub and Spoke" approach allows patients to visit their local health clinic ('Spokes') to establish appropriate care and monitoring for their seizure disorder or epilepsy, and remotely connect with epileptologists or neurologists at centralized centers of expertise ('Hubs'). The COVID-19 pandemic resulted in an expansion of telemedicine capabilities and use, with favorable patient and provider experience and outcomes, allowing for its wide scale adoption beyond COVID-19.

Cognitive deficit in post-acute COVID-19: an opportunity for EEG evaluation?

BACKGROUND AND PURPOSE: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. METHODS: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. RESULTS: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. CONCLUSIONS: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

Adaptive behaviour in children exposed to topiramate in the womb: An observational cohort study.

OBJECTIVE: Many women with epilepsy need to continue anti-seizure medications (ASMs) throughout pregnancy. The current study investigated adaptive behaviour outcomes in children exposed to topiramate in the womb. METHOD: An observational, cross-sectional study was designed, recruiting mother-child-pairs from the UK Epilepsy and Pregnancy Register (UKEPR). Health, developmental histories and Vineland Adaptive Behaviour Scale-Third Edition (VABS-III) assessments were administered via telephone by a blinded researcher, supplemented with prospectively collected pregnancy and medication information. Topiramate monotherapy exposed children were compared to VABS-III normative data as recruitment was disrupted by the COVID-19 pandemic. RESULTS: Thirty-four women with epilepsy from 135 (25%) initially agreed to participate in the study, of whom 26 women completed telephone interviews about their children (n = 28). Children ranged from 2.5 to 17 years of age at the time of assessment. Six topiramate-exposed children were born small for gestational age, and there were significant associations between birthweight, dose and VABS-III scores. Significantly lower scores were observed in topiramate-exposed children (n = 21) with a significant dose-response relationship established after adjustment for parental educational level. Daily mean dosage was 280.21 mg, with high dosages of topiramate associated with a 12-point reduction in VABS-III scores. Additionally, four topiramate-exposed children (19.05%) had diagnoses of Autism Spectrum Disorder, which was significantly higher than UK prevalence rates (1.1%). CONCLUSIONS: The findings of poorer adaptive behaviour, higher incidence of ASD and associations with birth weight are of concern and require further validation and replication using larger prospectively-recruited samples and comparator cohorts. Implications for research and clinical practice are discussed.

Canadian epilepsy priority-setting partnership: Toward a new national research agenda.

BACKGROUND: Health research agendas are often set by researchers or by industry and may not reflect the needs and priorities of end users. This priority-setting partnership (PSP) for epilepsy was undertaken to identify the most pressing unanswered questions about epilepsy and seizures from the perspective of people with epilepsy (PWE) and their care providers. METHODS: Using the methodology developed by the James Lind Alliance (JLA), evidence uncertainties were gathered via online surveys from stakeholders across Canada. Submissions were formed into summary questions and checked against existing evidence to determine if they were true uncertainties. Verified uncertainties were then ranked by patients, caregivers, and healthcare providers and a final workshop was held to reach a consensus on the top 10 priorities. RESULTS: The final top 10 list reflects the priority areas of focus for research as identified by the Canadian epilepsy community, including genetic markers for diagnosis and treatment, concerns about living with the long-term effects of epilepsy, and addressing knowledge gaps in etiology and treatment approaches. CONCLUSION: This project represents the first systematic evidence of patient- and clinician-centered research priorities for epilepsy. The results of this priority-setting exercise provide an opportunity for researchers and funding agencies to align their agendas with the values and needs of the epilepsy community in order to improve clinical outcomes and quality of life (QOL) for PWE.

Exploring seizure management in hospitals, unmet need, and the impact of the COVID-19 pandemic on seizure presentations to hospital.

PURPOSE: This study assesses investigations, referrals and admissions in patients presenting to the Emergency Department (ED) with seizures, and the effect of the COVID-19 pandemic on such management. Outcomes in patients with learning disabilities, active significant mental health concerns, and from the most socioeconomically deprived areas were compared to those of the general cohort. METHODS: Investigations, referrals and admissions were recorded for 120 patients across two cohorts; pre-pandemic (September 2019) and during the pandemic (December 2020). Retrospective review of individual patient electronic health care records was used for data collection. RESULTS: There was a decrease in patient numbers from 2019 to 2020. A greater proportion of patients presented with organic cause seizures and fewer presented with non-epileptic attacks. Frequent use of CT heads (45%) is likely to represent improper use of limited resources. There were low referral rates, both to acute neurology (28%) and to the adult epilepsy team (32%). Patients with active significant mental health concerns were significantly less likely to be referred to neurology or admitted. CONCLUSIONS: Despite a greater proportion of admissions during the Covid-19 pandemic, referrals to acute neurology and the epilepsy team remained low. Failure to refer prevents the most vulnerable seizure patients from receiving appropriate support, as seen in patients with active significant mental health concerns. Neurology staff were unaware of a significant number of patients presenting with seizures, which is of concern in an already over-stretched department. This offers an opportunity to improve care for people with epilepsy.

Psychogenic non-epileptic seizures (PNES) in the COVID-19 pandemic era: A systematic review with individual patients' analysis.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures but are not due to underlying epileptic activity and in some cases coexist alongside epilepsy. We described the clinical characteristics of patients with PNES as reported in the literature from the outbreak of the COVID-19 pandemic. We evaluated differences between patients with a diagnosis made immediately before the pandemic (pPNES) and those newly diagnosed during it (nPNES). METHODS: A systematic search with individual patient analysis of PNES cases published since the COVID-19 pandemic outbreak was performed. Differences between pPNES and nPNES were analyzed using Chi-square or Fisher exact test. RESULTS: Eleven articles were included, with 133 patients (106 pPNES and 27 nPNES). In the pPNES group, PNES frequency increased during the pandemic in 20/106 patients, whereas in 78/106, the frequency remained stable or decreased. nPNES was associated with higher risks of SARS-CoV-2 infection and epilepsy diagnosis, whereas psychiatric comorbidities were less frequent. CONCLUSIONS: During the pandemic, most patients with pPNES remained stable or improved, whereas nPNES was associated with a lower burden of psychiatric comorbidities. These intriguing findings suggest that, at least in some patients, the COVID-19 pandemic may not necessarily lead to worsening in the frequency of PNES and quality of life.

Do the neurologists recognize autoimmune epilepsy well enough? What is the effect of the pandemic on this matter?

INTRODUCTION: The concept of "autoimmune epilepsy" (AE) has been emphasized more frequently through the recent increase in recognition of various autoantibodies specific to neuronal proteins. AIMS: To evaluate the attitudes of neurologists in regard to AE, to review the differential diagnosis, treatment options, and to reveal the effect of COVID-19 on this matter. METHODS: A detailed questionnaire prepared for AE was sent to neurologists via social media and WhatsApp after the approval of the Ethics Committee. The responses of 245 respondents working in different settings were analyzed, and the group with 15 years or less experience in neurology was statistically compared to the group with more than 15 years of experience. RESULTS: Awareness and knowledge levels on AE seemed high in all groups, while 11% had never thought about AE during the differential diagnosis in real life. Before starting treatment, 20% thought that the autoantibody result should definitely support it, and 77.6% reported that they did not recognize AE well. Participants stated that satisfactory guidelines for diagnosis and treatment (88.2%) and widespread laboratory support (83.7%) were lacking. Neurologists with less experience and those working outside of training hospitals get more often consultation from an experienced clinician while diagnosing and conduct more detailed investigations at the diagnosis stage (p = 0.0025, p = 0.0001). CONCLUSION: This first survey study conducted in a large group of neurologists on the attitudes for the concept of AE suggested that postgraduate education, and diagnostic and treatment guidelines should be organized and antibody screening tests need to be better disseminated.

Evaluation of neurology consultations in a COVID-19 pandemic hospital, A retrospective study.

Background: Affinity of coronavirus disease to the central nervous system is not well known. Aim: We aimed to share the data of COVID-19 patients with neurological complaints in a pandemia hospital. Material and Method: Consultation results requested from the neurology clinic of Konya Meram State Hospital were retrospectively examined. PCR test positive patients, PCR negative patients with positive clinical, laboratory and radiological findings with COVID-19 were evaluated. Age, gender, history of neurological diseases, and neurological symptoms were recorded. Results: The reason for consultation was acute neurological symptom in 96 (84.2%) patients, counseling for treatment in chronic disease in 15 (13.2%) patients, and worsening in chronic disease in 3 (2.6%) patients. As neurological disorders, 22 (19.3%) had a history of previous stroke, 10 (8.8%) had dementia, 4 (3.5%) had epilepsy, 4 (3.5%) had Parkinson's disease, 3 (2.6%) had multiple sclerosis, 2 (1.8%) had myasthenia graves, and 1 (0.9%) had restless legs syndrome respectively. The most common reason for requesting consultation was changes in consciousness (56.1%). Of the 114 patients who requested neurology consultation, 65 (57%) were discharged, 49 (43%) were died. Conclusion: The change in consciousness was the reason in more than half of the patients who requested neurology consultation during COVID-19 follow-up. Impaired consciousness in a patient with COVID-19 may indicate a poor prognosis. If the studies planned in the near future can shed light on the cause of the unconsciousness developing in COVID-19, it will be promising in terms of treatment plans to reduce mortality.

New-onset functional seizures during the COVID-19 pandemic.

OBJECTIVE: We investigated whether the COVID-19 pandemic has influenced the characteristics of functional seizures (FS) at the onset of seizures. METHODS: This was a retrospective study of all patients with new-onset FS, who were admitted at the epilepsy monitoring unit at Shiraz University of Medical Sciences, Shiraz, Iran, during two time periods: the onset of FS and also the diagnosis of FS in 2017-2019 (pre-COVID era) and the onset of FS and also the diagnosis of FS in 2020-2021 (COVID era). RESULTS: Forty-five patients were studied (32 patients from the pre-COVID era and 13 patients from the COVID era). Patients who developed FS during the pandemic more likely had comorbid epilepsy compared with the patients who presented with FS before the pandemic [30.1% vs. 9.4%; Odds ratio (OR): 81.2]. Furthermore, those who developed FS during the pandemic more likely were employed compared with the patients who presented with FS before the pandemic (46.2% vs. 12.5%; OR: 16.2). A family history of seizures was associated with the FS timing as a trend (OR: 8.4); those who developed FS during the pandemic more likely had a family history of seizures compared with the patients who presented with FS before the pandemic (53.8% vs. 18.8%). CONCLUSION: This study showed that patients who developed FS during the COVID-19 pandemic had significant underlying differences (i.e., employment status, comorbid epilepsy, and a family history of seizures) compared with those who presented with FS before the pandemic.

A Near-Global Slowing of Background Activity and Epileptic Discharges in Children With Mild to Moderately Symptomatic COVID-19 Infection: An Electro-Neurophysiological Study.

Background. To assess the functional involvement of the central nervous system (CNS) via quantitative electroencephalography (EEG) analysis in children with mild to moderate COVID-19 infection who were otherwise previously healthy children. Methods. This prospective, case-control study was conducted between June and September 2020. Sleep EEG records of at least 40 min were planned for children who tested positive for COVID-19 using real-time PCR analysis and within 4-6 months post-recovery. All of the EEG analyses in this study were performed on an Ubuntu 20.04.2 LTS Operating System with the developed software using Python 3.7.6. The quantitative analysis of the epileptic discharges within the EEG records was performed using random forest after elimination of the artifacts with a model training accuracy of 98% for each sample data point. The frequency analysis was performed using the Welch method. Results. Among the age and sex-matched groups, the global mean frequency was significantly lower among the COVID-19 patients, with a P-value of 0.004. The spike slow-wave and sharp slow-wave indices were significantly higher in the patients when compared to the controls. The mean frequency values were significantly lower in almost all of the electrodes recording the frontal, central, and occipital areas. For the temporal and parietal areas, those significantly low mean frequencies were limited to the right hemisphere. Conclusion. A near-global involvement of background activity with decreased frequency, in addition to epileptic discharges, was recorded in mild to moderately COVID-19 infected children post-infection.

Socioeconomic disparities in epilepsy care.

PURPOSE OF REVIEW: Epilepsy is a common, chronic neurologic disease with continued disparities in care. The COVID-19 pandemic and recent social movements have drawn greater attention to social determinants of health and our progress (or lack thereof) toward delivering more equitable care. RECENT FINDINGS: Recent studies continue to document racial and economic disparities in diagnosis, treatment, and overall care of epilepsy and associated conditions. Notably, an increasing number of studies are attempting to design healthcare pathways and other interventions to improve access and equity in epilepsy care. SUMMARY: The present literature highlights the importance of identifying and addressing the particular needs of vulnerable persons with epilepsy. Practitioners and researchers should continue to develop interventions aimed at improving care for all patients and, crucially, measure the impact of their changes to ensure that any interventions are truly advancing health equity.

A Comprehensive Biological and Synthetic Perspective on 2-Deoxy-d-Glucose (2-DG), A Sweet Molecule with Therapeutic and Diagnostic Potentials.

Glucose, the primary substrate for ATP synthesis, is catabolized during glycolysis to generate ATP and precursors for the synthesis of other vital biomolecules. Opportunistic viruses and cancer cells often hijack this metabolic machinery to obtain energy and components needed for their replication and proliferation. One way to halt such energy-dependent processes is by interfering with the glycolytic pathway. 2-Deoxy-d-glucose (2-DG) is a synthetic glucose analogue that can inhibit key enzymes in the glycolytic pathway. The efficacy of 2-DG has been reported across an array of diseases and disorders, thereby demonstrating its broad therapeutic potential. Recent approval of 2-DG in India as a therapeutic approach for the management of the COVID-19 pandemic has brought renewed attention to this molecule. The purpose of this perspective is to present updated therapeutic avenues as well as a variety of chemical synthetic strategies for this medically useful sugar derivative, 2-DG.

COVID-19 vaccine take-up rate and safety in adults with epilepsy: Data from a multicenter study in China.

OBJECTIVE: This study was undertaken to investigate the COVID-19 vaccine uptake rate and possible postvaccination effects in adults with epilepsy. METHODS: We invited adults with epilepsy attending three centers in China from July 24 to August 31, 2021 to participate in this study. We also asked age- and sex-matched controls among people attending for other chronic neuropsychiatric conditions and healthy controls accompanying people with illness attending the hospitals to participate. We excluded people who, under the national guidelines, had evident contradictions to vaccination. Participants were interviewed face-to-face using questionnaires. Vaccine uptake and postvaccine adverse events among the people with epilepsy were compared with those with neuropsychiatric conditions and controls. We also compared the willingness and reasons for hesitancy among unvaccinated participants. RESULTS: We enrolled 981 people, of whom 491 had epilepsy, 217 had other neuropsychiatric conditions, and 273 were controls. Forty-two percent of those with epilepsy had had the first dose of a vaccine, compared with 93% of controls and 84% of the people with neuropsychiatric conditions (p < .0001). The majority (93.8%) of those immunized had inactivated vaccines. Among the unvaccinated people with epilepsy, 59.6% were willing to have the vaccine. Their main reasons for hesitation were potential adverse effects (53.3%) and concerns about losing seizure control (47.0%). The incidence of adverse events in the epilepsy group was similar to controls. Nineteen people with epilepsy reported an increase in seizure frequency. No episode of status epilepticus or prolonged seizures was reported. Two controls had their first-ever seizure, which was unlikely related to the vaccine. SIGNIFICANCE: The vaccine uptake rate in people with epilepsy was lower than in their same-age controls. The postvaccination effect was no higher than in controls. We found no evidence suggesting worsening seizures after vaccination. Measurement and education focused on increasing the vaccination rate in epilepsy are warranted.

Elective inpatient video-EEG monitoring during the COVID-19 pandemic.

To evaluate the safety and feasibility of admission for elective video-EEG monitoring during the SARS-CoV-2 pandemic. We performed a retrospective review of elective inpatient epilepsy monitoring unit admissions at our institution from May 3rd, 2020 to August 12th, 2020. All patients were screened by telephone for symptoms concerning infection or recent diagnosis of SARS-CoV-2 or excess medical risk prior to admission. Patients deemed eligible for admission underwent testing via a nasopharyngeal swab for SARS-CoV-2 within three days of admission, and were directed to self-quarantine between testing and admission. The community seven-day case rate for SARS-CoV-2 (new cases per 100,000 population) ranged from 2.8 to 28.9 during the study period in our region. A total of 95 patients (63 adults and 32 children) were admitted. One adult patient developed mild SARS-CoV-2 infection and one adult patient tested positive for asymptomatic SARS-CoV-2 infection. These findings illustrate that inpatient epilepsy monitoring can be safely performed in carefully selected patients when appropriate processes are in place, even in the setting of the SARS-CoV-2 pandemic. There is a risk of nosocomial spread, and the potential benefits of admission should be balanced against the risks of infection.

Further delineation of PIGB-related early infantile epileptic encephalopathy.

Pathogenic variants in phosphatidylinositol glycan anchor biosynthesis class B (PIGB) gene have been first described as the cause of early infantile epileptic encephalopathy 80 (EIEE-80) in 2019. This disorder, an inherited glycosylphosphatidylinositol deficiency, is associated with a complex neurologic phenotype, including developmental delay, early-onset epilepsy and peripheral neuropathy. We report on a 5 year-old girl born from consanguineous parents, manifesting severe global developmental delay with absent speech, mixed peripheral polyneuropathy, hypotonia, bilateral equino-varo-supinated-cavus foot, early-onset scoliosis, elevated serum alkaline phosphatase and a single episode of febrile status epilepticus. Hypomyelination was documented on brain MRI. Whole-exome sequencing (WES) disclosed the likely pathogenic biallelic PIGB NM_004855.4: c.463G > C, p.(Asp155His) missense variant. In our patient, while other characteristic clinical, neuroimaging and laboratory findings (as described in the first research paper) were present, seizures were not a major clinical issue, thus contributing to our knowledge on this ultra-rare disorder.

Importance of access to epilepsy monitoring units during the COVID-19 pandemic: Consensus statement of the International League against epilepsy and the International Federation of Clinical Neurophysiology.

Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic. Long-term video-EEG monitoring is an essential diagnostic service. Access to video-EEG monitoring of the patients in the EMUs must be given high priority. Patients should be screened for COVID-19, before admission, according to the local regulations. Local policies for COVID-19 infection control should be adhered to during the video-EEG monitoring. In cases of differential diagnosis where reduction of antiseizure medication is not required, consider home video-EEG monitoring as an alternative in selected patients.

Neuroinflammation: A Signature or a Cause of Epilepsy?

Epilepsy can be both a primary pathology and a secondary effect of many neurological conditions. Many papers show that neuroinflammation is a product of epilepsy, and that in pathological conditions characterized by neuroinflammation, there is a higher probability to develop epilepsy. However, the bidirectional mechanism of the reciprocal interaction between epilepsy and neuroinflammation remains to be fully understood. Here, we attempt to explore and discuss the relationship between epilepsy and inflammation in some paradigmatic neurological and systemic disorders associated with epilepsy. In particular, we have chosen one representative form of epilepsy for each one of its actual known etiologies. A better understanding of the mechanistic link between neuroinflammation and epilepsy would be important to improve subject-based therapies, both for prophylaxis and for the treatment of epilepsy.

Virtual epilepsy clinics - A Canadian Comprehensive Epilepsy Center experience pre-COVID and during the COVID-19 pandemic period.

OBJECTIVE: The objective of this study is to assess the role of prior experience with virtual care (through e-visits) in maintaining continuity in ambulatory epilepsy care during an unprecedented pandemic situation, comparing in person versus e-visit clinic uptake. METHODS: This is an observational study on virtual epilepsy care (through e-visits) over two years, during a pre-COVID period (14 months) continuing into the COVID-19 pandemic period (10 months). For a small initial section of patients seen during the study period a physician survey and a patient satisfaction survey were completed (n = 53). Outcomes of eVisits were analyzed using descriptive statistics. RESULTS: Median numbers of epilepsy clinic visits conducted during the COVID-19 period (27.5 new and 113 follow up) remained similar to the median uptake during the pre-COVID period (28 new and 116 follow up). Prior experience with e-visits for epilepsy yielded smooth transition into the pandemic period, with several other advantages. The majority of eVisits were successful despite technical difficulties and major components of history and management were still easily implemented. Results from patient surveys supported that a significant amount of time and money were saved, which was in keeping with our health-economic analysis. CONCLUSION: Our study is one of the first few reports of fully integrated virtual care in a comprehensive epilepsy clinic starting much before start of the COVID-19 pandemic. The results of our study support the feasibility of using virtual care to deliver specialized outpatient care in a comprehensive epilepsy center.