Impact of ambulatory pharmacist on hospital visits in older adults with epilepsy: A case-control study.

OBJECTIVE: Older adults have the highest prevalence of epilepsy of any age group. Care in this group is complex because of comorbidities, polypharmacy, and cognitive impairment. We aimed to assess the impact of an ambulatory pharmacist in decreasing hospital visits in this group. METHODS: We performed a case-control study at a tertiary care center. The study group was seen in a multi-disciplinary older adult epilepsy clinic with the services of an ambulatory pharmacist to help with medication reconciliation, assessment, and adherence. The control clinic also cared for older adults with epilepsy but lacked a pharmacist. The occurrence and factors related to hospital visits were compared three months post-clinic visit. Demographic data were reported using descriptive statistics. A multinomial regression analysis was conducted to assess how well hospital visits could be predicted by pharmacist presence and other relevant variables. RESULTS: Over 19 months, 58 and 74 patients were seen in the study and control groups, respectively. 26.6% and 18.4% of study and control group clinic visits were associated with a hospital visit, respectively (nonsignificant difference). The study group had significantly more patients with cognitive impairment (53.4% vs. 16.2%; p < 0.001), a higher burden of comorbidities as measured by Charlson comorbidity index (CCI) (mean 3.5 vs. 2.9; p = 0.02), and a greater number of patients with >1 seizure per month (17.2% vs. 6.8%) as compared to the control group. Hospital visits unrelated to epilepsy were associated with a higher CCI. Hospital visits related to epilepsy were associated with >1/month seizure frequency (>3 times risk). CONCLUSIONS: This study demonstrates the multifactorial complexity of older adults with epilepsy. While the presence of a pharmacist resulted in similar hospital visits as the control group, the study group had a much more complex patient population. More studies are required to assess the best use of a pharmacist in older adults with epilepsy outpatient care.

Understanding the Influence of Hospital Volume on Inpatient Outcomes Following Hospitalization for Status Epilepticus.

BACKGROUND: Prior studies show hospital admission volume to be associated with poor outcomes following elective procedures and inpatient medical hospitalizations. However, it is unknown whether hospital volume impacts Inpatient outcomes for status epilepticus (SE) hospitalizations. In this study, we aimed to assess the impact of hospital volume on the outcome of patients with SE and related inpatient medical complications. METHODS: The 2005 to 2013 National Inpatient Sample database was queried using International Classification of Diseases 9th Edition diagnosis code 345.3 to identify patients undergoing acute hospitalization for SE. The National Inpatient Sample hospital identifier was used as a unique facility identifier to calculate the average volume of patients with SE seen in a year. The study cohort was divided into three groups: low volume (0-7 patients with SE per year), medium volume (8-22 patients with SE per year), and high volume (> 22 patients with SE per year). Multivariate logistic regression analyses were used to assess whether medium or high hospital volume had lower rates of inpatient medical complications compared with low-volume hospitals. RESULTS: A total of 137,410 patients with SE were included in the analysis. Most patients (n = 50,939; 37%) were treated in a low-volume hospital, 31% (n = 42,724) were treated in a medium-volume facility, and 18% (n = 25,207) were treated in a high-volume hospital. Patients undergoing treatment at medium-volume hospitals (vs. low-volume hospitals) had higher odds of pulmonary complications (odds ratio [OR] 1.18 [95% confidence interval {CI} 1.12-1.25]; p < 0.001), sepsis (OR 1.24 [95% CI 1.08-1.43] p = 0.002), and length of stay (OR 1.13 [95% CI 1.0 -1.19] p < 0.001). High-volume hospitals had significantly higher odds of urinary tract infections (OR 1.21 [95% CI 1.11-1.33] p < 0.001), pulmonary complications (OR 1.19 [95% CI 1.10-1.28], p < 0.001), thrombosis (OR 2.13 [95% CI 1.44-3.14], p < 0.001), and renal complications (OR 1.21 [95% CI 1.07-1.37], p = 0.002). In addition, high-volume hospitals had lower odds of metabolic (OR 0.81 [95% CI 0.72-0.91], p < 0.001), neurological complications (OR 0.80 [95% CI 0.69-0.93], p = 0.004), and disposition to a facility (OR 0.89 [95% CI 0.82-0.96], p < 0.001) compared with lower-volume hospitals. CONCLUSIONS: Our study demonstrates certain associations between hospital volume and outcomes for SE hospitalizations. Further studies using more granular data about the type, severity, and duration of SE and types of treatment are warranted to better understand how hospital volume may impact care and prognosis of patients.

Factors Associated with Refractory Status Epilepticus Termination Following Ketamine Initiation: A Multivariable Analysis Model.

BACKGROUND: In this study, we identify factors associated with ketamine success in the treatment of refractory status epilepticus (SE). We also evaluate for adverse events including systemic and cerebral hemodynamic stability and fluid volume overload. METHODS: In this retrospective, large, single-center, observational study over a 10-year period, 879 consecutive patients receiving intravenous (IV) ketamine were reviewed, and 81 patients were identified as receiving IV ketamine for the treatment of SE. Descriptive analysis was done to determine treatment response and adverse events in patients receiving IV ketamine for SE. Multivariable logistic regression analyses were fitted to determine prediction models for seizure cessation. RESULTS: Permanent cessation of SE was achieved in 49 of 81 (60.5%) of patients for whom ketamine was part of the treatment plan. Of those, 36 (44.4%) were attributed to ketamine as the last drug used (ketamine-associated cessation [AC]). Prior history of epilepsy had an odds ratio of 3.19 (confidence interval 0.83-12.67, p = 0.09) associated with efficacious medication response. Increased latency to ketamine was associated with cessation of SE specifically in patients in the AC group (p = 0.077). Longer SE duration (p = 0.04), administration of ketamine loading dose (bolus; p = 0.03), and anoxia (p = 0.007) were negatively associated with AC. Administration of ketamine loading dose (p = 0.02) and anoxia (p = 0.009) were negatively associated with overall SE cessation. There was no significant impact of ketamine on cerebral hemodynamics, but evidence of fluid volume overload was seen (28.4% of patients). CONCLUSIONS: Our cohort is a large observational study showing a high success rate of permanent cessation of SE after the addition of ketamine. Using multivariable analysis, we demonstrate a significant association with seizure cessation in patients with prior history of epilepsy and those with prolonged latency to ketamine initiation. Furthermore, we describe the impact of fluid volume overload as an anticipated complication with ketamine use.

Rasch analysis of fatigue severity scale in patients with epilepsy.

OBJECTIVE: To utilize the Rasch model to validate and assess the psychometric properties of the Fatigue Severity Scale (FSS) in patients with epilepsy. METHODS: A total of 307 patients (age > 18 years) with a confirmed diagnosis of epilepsy were consented to participate. Exclusion criteria included patients with psychogenic nonepileptic events, cognitive disabilities, and patients who did not speak/understand English. The nine-step FSS was programmed into software administered to patients on electronic tablets, and patient responses were auto-scored. The Rasch rating scale model (RSM) was used to evaluate the unidimensionality, reliability, and targeting of the FSS. To assess unidimensionality, we examined infit and outfit mean squares. We also assessed unidimensionality of the FSS using a principal component analysis of Rasch residuals, where residuals are understood as the difference between observed and expected data values. We evaluated the internal consistency of person and item performance by examining separation reliability estimates and separation ratio. Differential Item Functioning (DIF) was calculated for gender. RESULTS: There was mixed evidence regarding the extent to which the FSS fit the Rasch model. Outfit values ranged from 0.52 to 2.72 and infit values were 0.60 to 2.18, strongly suggesting the presence of misfitting items: Item 1 ("My motivation is lower when I am fatigued") and Item 2 ("Exercise brings on my fatigue"). SIGNIFICANCE: The nine-item FSS showed fair psychometric properties in this sample of patients with epilepsy. Our study provides unique, supportive information for the use of a modified version of the FSS, omitting the first two items, in patients with epilepsy. Given the prevalence of fatigue and other neuropsychiatric comorbidities of epilepsy, having a validated fatigue scale can aid healthcare providers to identify moderate-to-severe fatigue levels in patients with epilepsy and address the plausible risk factors.

Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a myriad of neurological manifestations and its effects on the nervous system are increasingly recognized. Seizures and status epilepticus (SE) are reported in the novel coronavirus disease (COVID-19), both new onset and worsening of existing epilepsy; however, the exact prevalence is still unknown. The primary aim of this study was to correlate the presence of seizures, status epilepticus, and specific critical care EEG patterns with patient functional outcomes in those with COVID-19. METHODS: This is a retrospective, multicenter cohort of COVID-19-positive patients in Southeast Michigan who underwent electroencephalography (EEG) from March 12th through May 15th, 2020. All patients had confirmed nasopharyngeal PCR for COVID-19. EEG patterns were characterized per 2012 ACNS critical care EEG terminology. Clinical and demographic variables were collected by medical chart review. Outcomes were divided into recovered, recovered with disability, or deceased. RESULTS: Out of the total of 4100 patients hospitalized with COVID-19, 110 patients (2.68%) had EEG during their hospitalization; 64% were male, 67% were African American with mean age of 63 years (range 20-87). The majority (70%) had severe COVID-19, were intubated, or had multi-organ failure. The median length of hospitalization was 26.5 days (IQR = 15 to 44 days). During hospitalization, of the patients who had EEG, 21.8% had new-onset seizure including 7% with status epilepticus, majority (87.5%) with no prior epilepsy. Forty-nine (45%) patients died in the hospital, 46 (42%) recovered but maintained a disability and 15 (14%) recovered without a disability. The EEG findings associated with outcomes were background slowing/attenuation (recovered 60% vs recovered/disabled 96% vs died 96%, p < 0.001) and normal (recovered 27% vs recovered/disabled 0% vs died 1%, p < 0.001). However, these findings were no longer significant after adjusting for severity of COVID-19. CONCLUSION: In this large multicenter study from Southeast Michigan, one of the early COVID-19 epicenters in the US, none of the EEG findings were significantly correlated with outcomes in critically ill COVID-19 patients. Although seizures and status epilepticus could be encountered in COVID-19, the occurrence did not correlate with the patients' functional outcome.

Implementation of an older adult epilepsy clinic utilizing pharmacist services.

BACKGROUND: Antiseizure medications are commonly associated with adverse effects including behavioral and cognitive issues, drug interactions, idiosyncratic reactions, and long-term complications, which can lead to non-adherence. At the same time, there are limited reports describing multidisciplinary models of epilepsy care that include pharmacists. OBJECTIVE: To describe the pharmacist services in an epilepsy clinic for older adults and document the patient care delivered using this design. PRACTICE DESCRIPTION: A subspecialty older adult epilepsy clinic, embedded within a neurology clinic, in an urban academic medical center. PRACTICE INNOVATION: Integration of pharmacy services to document medication history, provide medication reconciliation, identify medication-related problems, and make interventions. EVALUATION METHODS: Data were retrospectively evaluated for the patients seen by the pharmacist and epilepsy team between July 2019 and January 2021. Data were summarized with descriptive statistics. RESULTS: Fifty-eight patients with a total of 94 encounters (70.7% of all specialty clinic visits) were seen collaboratively by the physician and the pharmacist. The majority of patients were African American (87.9%), aged 63.7 ± 8.2 years, and more frequently male (58.6%), and a high proportion had some baseline memory loss or diagnosis of dementia (53.4%). Medication reconciliation occurred in 94 (100%) encounters. More than half the encounters required reconciliation to the existing medication list by adding medication (55.3 % of encounters) or deleting mediations (53.2% of encounters). Presence of adverse effects was the most common medication-related problem identified (23.4%). Resolutions to the medication-related problems were also reported. CONCLUSION: The population of older adults with epilepsy is expected to increase in prevalence. Pharmacists are able to impact medication-related problems in a vulnerable, high-risk patient population. The multidisciplinary model we describe here can be used as a template to provide care in ambulatory care practices involving other neurology specialties with a high proportion of older adult patients.

Seizure occurrence and related mortality in dementia with Lewy bodies.

Dementia is a risk factor for epilepsy. While seizures have a well-established association with Alzheimer's disease (AD), their association with dementia with Lewy bodies (DLB) is not established. We utilized the National Alzheimer's Coordinating Centers' Uniform Data Set (NACC-UDS V1-3) to analyze occurrence of seizures in DLB and seizure occurrence associations with mortality. We excluded subjects with conventional seizure risk factors. Seizure occurrence was noted in 36 subjects (2.62%) out of 1376 subjects with DLB. Among 500 subjects with pathologically confirmed DLB, seizure occurrence was documented in 19 (3.8%) subjects. Half of the subjects had onset of seizures three years before or after DLB diagnosis. Two-year mortality for subjects with DLB with seizures was high at 52.8% but no increased risk was noted as compared with subjects with DLB without seizures. More prospective and long-term longitudinal studies are needed to clarify relationships between DLB, seizure occurrence, and risk of increased mortality.

Acute symptomatic seizures and status epilepticus in older adults: A narrative review focusing on management and outcomes.

A clear narrative of acute symptomatic seizures (ASyS) in older adults is lacking. Older adults (≥60 years) have the highest incidence of seizures of all age groups and necessitate a tailored approach. ASyS has a bimodal peak in infancy and old age (82.3-123.2/100,000/year after 65 years of age). ASyS can represent half of the new-onset seizures in older adults and can progress to acute symptomatic status epilepticus (ASySE) in 52-72% of the patients. Common etiologies for ASyS in older adults include acute stroke and metabolic disturbances. For ASySE, common etiologies are acute stroke and anoxic brain injury (ABI). Initial testing for ASyS should be consistent with the most common and urgent etiologies. A 20-min electroencephalogram (EEG) is less sensitive in older adults than in younger adults and might not help predict chronic epilepsy. The prolonged postictal phase is an additional challenge for acute management. Studies note that 30% of older adults with ASyS subsequently develop epilepsy. The risk of wrongly equating ASyS as the first seizure of epilepsy is higher in older adults due to the increased long-term challenges with chronic anti-seizure medication (ASM) treatment. Specific challenges to managing ASyS in older adults are related to their chronic comorbidities and polypharmacy. It is unclear if the prognosis of ASyS is dependent on the underlying etiology. Short-term mortality is 1.6 to 3.6 times higher than younger adults. ASySE has high short-term mortality, especially when it is secondary to acute stroke. An acute symptomatic etiology of ASySE had five times increased risk of short-term mortality compared to other types of etiology.

NeuroMeasures-Implementation of a Web-Based, Real-Time Quality Metric Tool to Improve Provider Practices in an Epilepsy Clinic.

Background and Objectives: The retrospective nature of most available epilepsy quality improvement (QI) tools focuses on changing health care provider (HCP) clinical habits and documentation practices rather than a focus on real-time patient interventions. Furthermore, patient-reported outcome data are often not available to determine the efficacy of these tools. Our primary objective was to demonstrate the improvement of HCPs' documentation and review of epilepsy quality measures (EQMs) during the patient visit with the implementation of a novel web application, NeuroMeasures. Our secondary objective was to improve the percentage of point-of-care counseling and interventions based on quality measures during the patient encounter based on the results of the NeuroMeasures tool. Methods: Our QI study focused on comparing a preintervention and postintervention cohort of patients with epilepsy (PWE) before the implementation of NeuroMeasures, a web-based application that takes a self-guided patient survey through self-scoring algorithms focused on the American Academy of Neurology (AAN)'s 2017 EQMs. This e-tool then provides the HCP a tool to directly review the EQMs highlighted and perform any necessary counseling or interventions at the point-of-care visit. After intervention, EQMs were gained from the review of the NeuroMeasures HCP quality measures tool and a chart review for physician documentation. Patients with language barriers and severe cognitive disabilities were excluded from the study. Results: The preintervention cohort consisted of 150 unique PWE, and the postintervention cohort included 379 unique adult PWE and 515 total encounters. Overall percentages of review/adherence of EQMs were significantly improved between the preintervention and postintervention group for counseling for women of childbearing potential (91.7%), intractable epilepsy referral to a comprehensive epilepsy center (74%), quality of life assessment (80%), improvement of quality of life measurements (41.7%), and depression and anxiety screening (85.6%), demonstrating a significant increase when compared with the preintervention group (p < 0.00001). Discussion: A web-based point-of-care EQM application demonstrated significant improvement of the HCP's ability to perform and review EQMs at the point-of-care patient visit. Furthermore, the application was successful in creating opportunities for direct intervention based on the EQMs and chances for better patient education and provider-patient communication. Further considerations would include automated survey requests and expansion into other AAN QMs.

Racial and ethnic trends in antiseizure medications trial enrolment: A systematic review using ClinicalTrials.gov.

OBJECTIVE: To describe the racial and gender distribution in antiseizure medications (ASM) clinical trials using a systemic review of clinical trial registry database. METHODS: We searched ClinicalTrials.gov database for ASM trials registered from September 1988 to January 2019. All randomized and non-randomized trials investigating ASM for epilepsy were included. Trials with intervention other than ASM or condition other than epilepsy were excluded. Data on age, race, ethnicity, and gender were extracted directly from database and from published data where available. Study location, trial identifier, year of completion, and funding sources were also collected. Meta-analysis of proportions was conducted using R software. RESULT: Two hundred and thirty studies conducted globally with 39,576 participants were included. Overall, there are 53 % male on all registered ASM studies globally. For trials conducted in the United States (61 studies/5126 participants), 52 % of the participants were male with the following weighted racial distribution (80 % White 13 % Black 3% Asian 7% Hispanic). Subgroup analysis revealed that non-pharma-sponsored studies (50 studies, 4296 participants) have a higher representation of minorities as compared to pharma-sponsored studies (180 studies, 35,280 participants), including Hispanic (9% vs 3% respectively) and Black (18 % vs 11 % respectively). Temporal trends in racial distribution were noted when the duration of 2007-2019 was split into two groups: 2007-2013 (0% Asian, 5% Hispanic, 20 % Black); 2014-2019 (4% Asian, 7% Hispanic, 8% Black). CONCLUSION: In this systematic review, participation of racial and ethnic minorities of Asian and Hispanic background was under-represented. Disparities of all minorities including Black participants was more notable over time and in studies sponsored by industry. Generalizability of ASM clinical trials to certain subgroups should be further examined.

Atypical representation of sensorimotor cortex in a patient with autism and epilepsy confirmed by direct electrocortical stimulation.

Prior studies have used functional neuroimaging to demonstrate that the organization of the autistic brain is different from that of the non-autistic brain. Similarly, patients with epilepsy have also shown cortical reorganization. We present a case study that provides direct confirmation of disorganized sensorimotor distribution in a patient with autism spectrum disorder and epilepsy. To our knowledge, this is the first time cortical mapping directly showing abnormal cortical organization in a patient with autism spectrum disorder and epilepsy has been reported in the literature.

Outcomes of status epilepticus and their predictors in the elderly-A systematic review.

Status epilepticus (SE) is associated with high mortality and morbidity. Although SE is frequently seen in elderly patients, there is a lack of a cohesive report of outcome measures and associated factors within this population. Our aim was to systematically review studies reporting outcomes of SE among elderly patients and factors influencing these outcomes. A literature search was conducted in PubMed/MEDLINE, EMBASE, CINAHL Complete, and Cochrane Library from database conception to April 22, 2018. A total of 85 studies were included in this systematic review. The included studies show that mortality is higher in elderly patients than in adult patients. Lesional etiologies, higher number of comorbidities, NCSE, RSE, longer hospital and intensive care unit stays, and infection during hospitalization are associated with poor outcome. Future studies should consider measuring functional outcomes, comparative studies between elderly and adults and AED clinical trials specific for elderly with SE.

Gabapentin or pregabalin induced myoclonus: A case series and literature review.

Gabapentin (GBP) and pregabalin (PGB) are FDA approved for adjunctive treatment of partial seizures and for treatment of post-herpetic neuralgia. Both drugs are primarily eliminated by renal excretion. However, PGB or GBP induced myoclonus has only been reported infrequently in case reports/series. It is not discussed with patients and its sudden occurrence can lead to anxiety because of "seizure-like" nature. In addition, first-contact physicians might treat it as seizures, leading to unnecessary tests and aggressive management. Medical records of patients who had myoclonus because of PGB or GBP seen by Neurology service between Jan & May 2017 in inpatient or outpatient setting at our tertiary care setting were reviewed. We identified six patients who were on either GBP or PGB or both who developed likely subcortical myoclonus in the setting of renal insufficiency and one patient who developed myoclonus independent of renal dysfunction. Our results indicate that myoclonus is commonly seen in patients in various clinical settings with or without renal insufficiency, and is independent of the severity of the renal failure. However, this is a reversible side effect of medication and it resolves either by discontinuing the medication, removing the medication with hemodialysis or by improvement of renal dysfunction. With a high index of suspicion, aggressive testing and treatment for other possible conditions like seizures (in non-epilepsy patients) or CNS infections can be avoided. In patients with renal failure and with decreased physiological renal clearance such as the elderly, GBP or PGB dose initiation and changes should be conservative.

Updates in Refractory Status Epilepticus.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.

Functional MRI Correlates of Resting-State Temporal Theta and Delta EEG Rhythms.

PURPOSE: The EEG rhythms demonstrate changes in frequency and power with spontaneous changes in behavioral state that do not have well-understood metabolic correlates within the brain. To investigate this question and compare the temporal lobe theta and delta rhythms, resting-state functional MRI was obtained with simultaneous EEG. METHODS: Simultaneous EEG-functional MRI was recorded from 14 healthy sleep-deprived subjects in awake and drowsy states. Scalp electrodes corresponding to bilateral temporal lobes were used to calculate delta and theta band power. The resulting time series was used as input in a general linear model, and the final power curves were convolved with the standard hemodynamic response function. Resulting images were thresholded at Z > 2.0. RESULTS: Positive and negative correlations for unilateral theta and delta rhythms were present bilaterally in different structures and with differing correlation signs. Theta rhythm positive correlation was present in hindbrain, peri-opercular, and frontoparietal regions and subcortical gray structures, whereas negative correlation was present in parietooccipital cortex. Delta rhythm positive correlation was present in parietooccipital cortex, and negative correlation roughly resembled positive correlations for the theta rhythm. CONCLUSIONS: Temporal lobe theta and delta rhythms are correlated with functional MRI signal in an almost mutually exclusive distribution. The different distributions indicate different corresponding networks. These normal findings supplement the understanding of theta and delta rhythm significance.

Postictal psychosis in a 3-year-old child.

A case of a 3½-year-old with clinical and correlated electroencephalographic (EEG) features of postictal psychosis is described. The clinical course and sequence of EEG changes parallel the evolution of changes well described in the adult population. Although well established and defined in the adults, postictal psychosis is rarely characterized and diagnosed in the pediatric population. The true incidence of postictal psychosis in children may be underestimated because of lack of awareness as well as biological differences in presentation of clinical symptoms. To our knowledge, this is the youngest reported case of postictal psychosis in the pediatric population.