Seizure control, stress, and access to care during the COVID-19 pandemic in New York City: The patient perspective.

OBJECTIVE: Our epilepsy population recently experienced the acute effects of the COVID-19 pandemic in New York City. Herein, we aimed to determine patient-perceived seizure control during the surge, specific variables associated with worsened seizures, the prevalence of specific barriers to care, and patient-perceived efficacy of epilepsy care delivered via telephone and live video visits during the pandemic. METHODS: We performed a cross-sectional questionnaire study of adult epilepsy patients who had a scheduled appointment at a single urban Comprehensive Epilepsy Center (Montefiore Medical Center) between March 1, 2020 and May 31, 2020 during the peak of the COVID-19 pandemic in the Bronx. Subjects able to answer the questionnaire themselves in English or Spanish were eligible to complete a one-time survey via telephone or secure online platform (REDCap). RESULTS: Of 1212 subjects screened, 675 were eligible, and 177 adequately completed the questionnaire. During the COVID-19 pandemic, 75.1% of patients reported no change in seizure control, whereas 17.5% reported that their seizure control had worsened, and 7.3% reported improvement. Subjects who reported worsened seizure control had more frequent seizures at baseline, were more likely to identify stress and headaches/migraines as their typical seizure precipitants, and were significantly more likely to report increased stress related to the pandemic. Subjects with confirmed or suspected COVID-19 did not report worsened seizure control. Nearly 17% of subjects reported poorer epilepsy care, and 9.6% had difficulty obtaining their antiseizure medications; these subjects were significantly more likely to report worse seizure control. SIGNIFICANCE: Of the nearly 20% of subjects who reported worsened seizure control during the COVID-19 pandemic, stress and barriers to care appear to have posed the greatest challenge. This unprecedented pandemic exacerbated existing and created new barriers to epilepsy care, which must be addressed.

Psychogenic nonepileptic seizures during the COVID-19 pandemic in New York City - A distinct response from the epilepsy experience.

Although psychogenic nonepileptic seizures (PNES) are a common neurologic condition, there remains a paucity of literature on the COVID-19 pandemic's effect on these patients. Using a cross-sectional questionnaire study, our group examined the experience of patients with PNES at a single Comprehensive Epilepsy Center in New York City, the epicenter of the initial COVID-19 outbreak in the United States. Among our cohort of 18 subjects with PNES, 22.2% reported an improvement in seizure control during the peak of the COVID-19 pandemic in New York City. Compared to the cohort of subjects with epilepsy without PNES, subjects with PNES were significantly more likely to report an improvement (p = 0.033). Our findings signal that sleep and stress may be relevant variables in both conditions that should be further investigated and potentially intervened upon. Larger dedicated studies of patients with PNES are needed to understand the impact of the pandemic's widespread societal effects on these patients.

Clinical characterization of the pre-ictal state in the pediatric population: A caretaker's perspective.

The unpredictability of seizures causes distress to patients with epilepsy and their caretakers. To date, no studies have explored seizure prediction specifically in the pediatric population. If the period of time preceding a seizure can be reliably identified, either by child or caretaker, there may be a role for pre-emptive interventions. The aim of this study was to investigate caretaker seizure prediction. A questionnaire was distributed to caretakers of patients with epilepsy. The patients were 0-21years old and experienced ≥1 seizure within the past year. We excluded patients with non-epileptic seizures or daily seizures. One hundred and fifty of 240 questionnaires met criteria. Of these, 32 (21.6%) caretakers indicated a positive report of seizure prediction. Age of seizure onset was earlier in the positive predictive group (3.3±3.3years) than in the non-predictor group (5.3±4.8years) (p=0.01). The most common pre-ictal symptoms reported were being tired, hazy look, and sleepiness. A total of 76.6% of caretakers reported at least one seizure precipitant. The prevalence of positive caretaker seizure prediction in this study is similar to that of seizure self-prediction in adult studies. These findings will be used to design prospective online or electronic diary studies to further investigate the caretaker's, as well as children's, perspectives on seizure prediction. We anticipate that this investigation may lead to novel treatments during times of high seizure risk.

Termination of seizure clusters is related to the duration of focal seizures.

OBJECTIVE: Clustered seizures are characterized by shorter than usual interseizure intervals and pose increased morbidity risk. This study examines the characteristics of seizures that cluster, with special attention to the final seizure in a cluster. METHODS: This is a retrospective analysis of long-term inpatient monitoring data from the EPILEPSIAE project. Patients underwent presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the occurrence of at least two consecutive seizures with interseizure intervals of <4 h. Other definitions of seizure clustering were examined in a sensitivity analysis. Seizures were classified into three contextually defined groups: isolated seizures (not meeting clustering criteria), terminal seizure (last seizure in a cluster), and intracluster seizures (any other seizures within a cluster). Seizure characteristics were compared among the three groups in terms of duration, type (focal seizures remaining restricted to one hemisphere vs. evolving bilaterally), seizure origin, and localization concordance among pairs of consecutive seizures. RESULTS: Among 92 subjects, 77 (83%) had at least one seizure cluster. The intracluster seizures were significantly shorter than the last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster resembled the isolated seizures in terms of duration. Although focal only (unilateral), seizures were shorter than seizures that evolved bilaterally and there was no correlation between the seizure type and the seizure position in relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more likely to cluster compared with other localizations (p = 0.009). Seizure pairs that are part of a cluster were more likely to have a concordant origin than were isolated seizures. Results were similar for the 2 h definition of clustering, but not for the 8 h definition of clustering. SIGNIFICANCE: We demonstrated that intracluster seizures are short relative to isolated seizures and terminal seizures. Frontal and temporal lobe seizures are more likely to cluster.

Visual hallucinosis during hypoperfusion of the right occipito-temporal cortex.

OBJECTIVES: Positive visual phenomena, although reported in lesions of visual cortex, are often overlooked in patients with acute neurological conditions. Yet, their occurrence without structural abnormalities or other underlying neurological disorders represents a unique observation. This report aims to raise awareness of these phenomena, their implications for understanding visual consciousness and to propose a practical, structured algorithm for the clinical assessment of visual hallucinations related to neurological conditions. METHODS: We describe the clinical presentation and imaging findings in two patients with isolated visual hallucinosis secondary to transitory hypoperfusion. RESULTS: One patient presented with subocclusion of the right posterior cerebral artery and the other with multifocal arterial abnormalities suggestive of reversible cerebral vasoconstriction syndrome (RCVS). Both presented isolated visual hallucinations and hypoperfusion of the right mesial occipito-temporal cortex. Hallucinated images exhibited peculiarities of certain attributes that were recognized only through guided perceptual analysis performed during their occurrence. DISCUSSION: Dysfunctions in the visual and attentional networks due to the uneven impact of hypoperfusion on the regions of the mesial occipito-temporal cortex likely contributed to the occurrence of visual hallucinations. The initial impaired awareness of certain image attributes obscured an altered, non-realistic rendering of the hallucinated images. Enhancement of awareness through clinical guidance indicates improved attentional deployment, modulation of visual information processing and hallucination-background integration. These features of the hallucinatory phenomena highlight the critical role of semiological analysis during their occurrence and question the validity of post hoc inquiries.

Outcome of Hospitalized Parkinson's Disease Patients with and without COVID-19.

Background: The Parkinson's disease (PD) patient population, with an already reduced life expectancy, is rendered particularly vulnerable by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Objectives: We determined the risk factors that increase the risk of death in patients with Parkinson's disease who are infected by SARS-CoV-2. Methods: Patients with a diagnosis of PD admitted to Montefiore Hospital (Bronx, New York) and tested for SARS-CoV-2 were identified. Retrospective review of electronic medical records confirmed the diagnosis; patients were classified by severity of PD. PD severity, demographic, socioeconomic factors, and co-morbidities were correlated with mortality rates in patients with SARS-CoV-2. Results: We identified 162 patients meeting criteria; chart review confirmed a diagnosis of PD in 70 patients. Of the 70 patients, 53 were positive for SARS-CoV-2 and 17 were negative. PD patients with SARS-CoV-2 infection had a higher mortality rate (35.8%) compared to PD patients without the infection (5.9%, P = 0.028). PD patients older than 70 years of age, those with advanced Parkinson's disease, those with reductions in their medications, and non-Hispanics (largely comprised of Black/African- Americans) had a statistically significant higher mortality rate, if infected. Conclusions: PD did not increase mortality rates from SARS-CoV-2 infection when age was controlled. However, certain unalterable factors (advanced disease and age greater than 70 years) and alterable ones (reductions in PD medications) placed PD patients at increased risk for mortality. Also several socioeconomic factors contributed to mortality, for example, non-Hispanic patients with SARS-CoV-2 infection fared worse, likely driven by poorer outcomes in the Black/African-American cohort.

Disparities in Access to Neurologic Telemedicine During the COVID-19 Pandemic: A Bronx Tale.

OBJECTIVE: To determine whether there is a disparity in access to telemedical care that may be a function of socioeconomic status, language, or other demographic factors during the peak of the coronavirus disease 2019 (COVID-19) pandemic at a highly affected urban center (Montefiore Medical Center) in Bronx, NY. METHODS: We retrospectively investigated potential patient characteristics that might be associated with an increased likelihood of receiving a telephone visit as opposed to a televideo visit for patients followed in the pediatric neurology, adult epilepsy, and general neurology practices at Montefiore Medical Center during the 30-day period starting April 2, 2020, at the peak of the COVID-19 pandemic in New York. RESULTS: We found that patients who had telephone encounters, as opposed to televideo encounters, were overall older, less likely to have commercial insurance, and more likely to have Medicaid. Among pediatric patients, a preferred language other than English was also associated with a higher proportion of telephone encounters. New patients in both the adult and pediatric groups were more likely to have televideo visits. CONCLUSIONS: Our findings identify demographic factors, including age, insurance type, and language preference, which may play a role in access to televideo encounters among neurology patients in an urban center during the COVID-19 pandemic. We suggest several potential practice, institution, and community-based interventions, which might further expand access to televideo care for neurology patients.

Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality. METHODS: A total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death. RESULTS: A total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04-1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age- and severity-matched controls. CONCLUSIONS: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Individualizing the definition of seizure clusters based on temporal clustering analysis.

OBJECTIVE: Seizure clusters are often encountered in people with poorly controlled epilepsy. Detection of seizure clusters is currently based on simple clinical rules, such as two seizures separated by four or fewer hours or multiple seizures in 24 h. Current definitions fail to distinguish between statistically significant clusters and those that may result from natural variation in the person's seizures. Ability to systematically define when a seizure cluster is significant for the individual carries major implications for treatment. However, there is no uniform consensus on how to define seizure clusters. This study proposes a principled statistical approach to defining seizure clusters that addresses these issues. METHODS: A total of 533,968 clinical seizures from 1,748 people with epilepsy in the Seizure Tracker™ seizure diary database were used for algorithm development. We propose an algorithm for automated individualized seizure cluster identification combining cumulative sum change-point analysis with bootstrapping and aberration detection, which provides a new approach to personalized seizure cluster identification at user-specified levels of clinical significance. We develop a standalone user interface to make the proposed algorithm accessible for real-time seizure cluster identification (ClusterCalc™). Clinical impact of systematizing cluster identification is demonstrated by comparing empirically-defined clusters to those identified by routine seizure cluster definitions. We also demonstrate use of the Hurst exponent as a standardized measure of seizure clustering for comparison of seizure clustering burden within or across patients. RESULTS: Seizure clustering was present in 26.7 % (95 % CI, 24.5-28.7 %) of people with epilepsy. Empirical tables were provided for standardizing inter- and intra-patient comparisons of seizure cluster tendency. Using the proposed algorithm, we found that 37.7-59.4 % of seizures identified as clusters based on routine definitions had high probability of occurring by chance. Several clusters identified by the algorithm were missed by conventional definitions. The utility of the ClusterCalc algorithm for individualized seizure cluster detection is demonstrated. SIGNIFICANCE: This study proposes a principled statistical approach to individualized seizure cluster identification and demonstrates potential for real-time clinical usage through ClusterCalc. Using this approach accounts for individual variations in baseline seizure frequency and evaluates statistical significance. This new definition has the potential to improve individualized epilepsy treatment by systematizing identification of unrecognized seizure clusters and preventing unnecessary intervention for random events previously considered clusters.

Are we responding effectively to bone mineral density loss and fracture risks in people with epilepsy?

OBJECTIVE: A 2007 study performed at Montefiore Medical Center (Bronx, NY) identified high prevalence of reduced bone density in an urban population of patients with epilepsy and suggested that bone mineralization screenings should be regularly performed for these patients. We conducted a long-term follow-up study to determine whether bone mineral density (BMD) loss, osteoporosis, and fractures have been successfully treated or prevented. METHODS: In the current study, patients from the 2007 study who had two dual-energy absorptiometry (DXA) scans performed at least 5 years apart were analyzed. The World Health Organization (WHO) criteria to diagnose patients with osteopenia or osteoporosis were used, and each patient's probability of developing fractures was calculated with the Fracture Risk Assessment Tool (FRAX). RESULTS: The median time between the first and second DXA scans for the 81 patients analyzed was 9.4 years (range 5-14.7). The median age at the first DXA scan was 41 years (range 22-77). Based on WHO criteria, 79.0% of patients did not have worsening of bone density, while 21.0% had new osteopenia or osteoporosis; many patients were prescribed treatment for bone loss. Older age, increased duration of anti-epileptic drug (AED) usage, and low body mass index (BMI) were risk factors for abnormal BMDs. Based on the first DXA scan, the FRAX calculator estimated that none of the patients in this study had a 10-year risk of more than 20% for developing major osteoporotic fracture (hip, spine, wrist, or humeral fracture). However, in this population, 11 patients (13.6%) sustained a major osteoporotic fracture after their first DXA scan. SIGNIFICANCE: Despite being routinely screened and frequently treated for bone mineral density loss and fracture prevention, many patients with epilepsy suffered new major osteoporotic fractures. This observation is especially important as persons with epilepsy are at high risk for falls and traumas.

EEG findings in acutely ill patients investigated for SARS-CoV-2/COVID-19: A small case series preliminary report.

OBJECTIVE: Acute encephalopathy may occur in COVID-19-infected patients. We investigated whether medically indicated EEGs performed in acutely ill patients under investigation (PUIs) for COVID-19 report epileptiform abnormalities and whether these are more prevalent in COVID-19 positive than negative patients. METHODS: In this retrospective case series, adult COVID-19 inpatient PUIs underwent EEGs for acute encephalopathy and/or seizure-like events. PUIs had 8-channel headband EEGs (Ceribell; 20 COVID-19 positive, 6 COVID-19 negative); 2 more COVID-19 patients had routine EEGs. Overall, 26 Ceribell EEGs, 4 routine and 7 continuous EEG studies were reviewed. EEGs were interpreted by board-certified clinical neurophysiologists (n = 16). EEG findings were correlated with demographic data, clinical presentation and history, and medication usage. Fisher's exact test was used. RESULTS: We included 28 COVID-19 PUIs (30-83 years old), of whom 22 tested positive (63.6% males) and 6 tested negative (33.3% male). The most common indications for EEG, among COVID-19-positive vs COVID-19-negative patients, respectively, were new onset encephalopathy (68.2% vs 33.3%) and seizure-like events (14/22, 63.6%; 2/6, 33.3%), even among patients without prior history of seizures (11/17, 64.7%; 2/6, 33.3%). Sporadic epileptiform discharges (EDs) were present in 40.9% of COVID-19-positive and 16.7% of COVID-19-negative patients; frontal sharp waves were reported in 8/9 (88.9%) of COVID-19-positive patients with EDs and in 1/1 of COVID-19-negative patient with EDs. No electrographic seizures were captured, but 19/22 COVID-19-positive and 6/6 COVID-19-negative patients were given antiseizure medications and/or sedatives before the EEG. SIGNIFICANCE: This is the first preliminary report of EDs in the EEG of acutely ill COVID-19-positive patients with encephalopathy or suspected clinical seizures. EDs are relatively common in this cohort and typically appear as frontal sharp waves. Further studies are needed to confirm these findings and evaluate the potential direct or indirect effects of COVID-19 on activating epileptic activity.

Characteristics of large patient-reported outcomes: Where can one million seizures get us?

Objective: To analyze data from Seizure Tracker, a large electronic seizure diary, including comparison of seizure characteristics among different etiologies, temporal patterns in seizure fluctuations, and specific triggers. Methods: Zero-inflated negative binomial mixed-effects models were used to evaluate temporal patterns of seizure events (during the day or week), as well as group differences in monthly seizure frequency between children and adults and between etiologies. The association of long seizures with seizure triggers was evaluated using a mixed-effects logistic model with subject as the random effect. Incidence rate ratios (IRRs) and odds ratios were reported for analyses involving zero-inflated negative binomial and logistic mixed-effects models, respectively. Results: A total of 1,037,909 seizures were logged by 10,186 subjects (56.7% children) from December 2007 to January 2016. Children had more frequent seizures than adults did (median monthly seizure frequency 3.5 vs. 2.7, IRR 1.26; p < 0.001). Seizures demonstrated a circadian pattern (higher frequency between 07:00 a.m. and 10:00 a.m. and lower overnight), and seizures were reported differentially across the week (seizure rates higher Monday through Friday than Saturday or Sunday). Longer seizures (>5 or >30 min) had a higher proportion of the following triggers when compared with shorter seizures: "Overtired or irregular sleep," "Bright or flashing lights," and "Emotional stress" (p < 0.004). Significance: This study explored a large cohort of patients with self-reported seizures; strengths and limitations of large seizure diary databases are discussed. The findings in this study are consistent with those of prior work in smaller validated cohorts, suggesting that patient-recorded databases are a valuable resource for epilepsy research, capable of both replication of results and generation of novel hypotheses.

Gray Matter Changes in Demyelinating Disease: Correlations with Clinical Scores.

BACKGROUND AND PURPOSE: Recent MR studies have shown that, in multiple sclerosis, selective regional, but not global gray matter atrophy occurs in multiple sclerosis. Our aim was to identify specific areas of gray matter volume changes and explore the relationship between atrophy and clinical motor outcomes. METHODS: Nine patients with relapsing remitting MS and 9 matched healthy controls were recruited. The Multiple Sclerosis Functional Composite was administered. For MR acquisitions, a GE- Genesis- Signa, 1.5T MR system, was used. A voxel-based morphometry (VBM), subcortical structures segmentation (FIRST) and volumetric (SIENAx) FSL tools were used in the study. RESULTS: Group comparison showed atrophy for several gray matter regions. The most important volume reductions were found for subcortical deep gray matter areas. Correlations with clinical scores were checked and specific gray matter areas showed significant volume reductions associated with motor scores (9-hole peg time and 25-feet walk time) and EDSS (Expanded Disability Status Scale). CONCLUSION: We performed a voxelwise analysis of gray matter changes in MS and found a more prominent atrophy for the subcortical structures than for cortical gray matter. Using an additional analysis (FIRST and SIENAx segmentation/volumetry) we were able to confirm the VBM results and to quantify the degree of atrophy in specific structures. Specific gray matter regions which volume reductions correlate with 25-feet walk, 9-hole peg times and EDSS suggest that 25-feet walk time is the best predictor of disease progression in terms of gray matter reduction.