The implications of frailty in older adults with epilepsy.

Older adults constitute a large proportion of people with epilepsy (PWE) due to the changing demographics worldwide and epilepsy's natural history. Aging-related pathophysiological changes lower the tolerance and increase our vulnerability to stressors, which manifests as frailty. Frailty is closely associated with adverse health outcomes. This narrative review examines the interplay between frailty and epilepsy, especially in older adults, emphasizing its clinical implications, including its role in managing PWE. Mechanistically, frailty develops through complex interactions among molecular and cellular damage, including genomic instability, mitochondrial dysfunction, and hormonal changes. These contribute to systemic muscle mass, bone density, and organ function decline. The concept of frailty has evolved from a primarily physical syndrome to include social, psychological, and cognitive dimensions. The "phenotypic frailty" model, which focuses on physical performance, and the "deficit accumulation" model, which quantifies health deficits, provide frameworks for understanding and assessing frailty. PWE are potentially more prone to developing frailty due to a higher prevalence of risk factors predisposing to frailty. These include, but are not limited to, polypharmacy, higher comorbidity, low exercise level, social isolation, low vitamin D, and osteoporosis. We lack commercial biomarkers to measure frailty but can diagnose it using self- or healthcare provider-administered frailty scales. Recent attempts to develop a PWE-specific frailty scale are promising. Unlike chronological age, frailty is reversible, so its management using multidisciplinary care teams should be strongly considered. Frailty can affect antiseizure medication (ASM) tolerance secondary to its impact on pharmacokinetics and pharmacodynamics. While frailty's effect on seizure control efficacy of ASM is poorly understood, its undoubted association with overall poor outcomes, including epilepsy surgery, behooves us to consider its presence and implication while treating older PWE. Incorporation of frailty measures in future research is essential to improve our understanding of frailty's role in PWE health. PLAIN LANGUAGE SUMMARY: Frailty is the declining state of the human body. People with epilepsy are more prone to it. It should be factored into their management.

Role of comorbidities in epilepsy surgery outcomes of older adults.

We lack knowledge about prognostic factors of resective epilepsy surgery (RES) in older adults (≥60 years), especially the role of comorbidities, which are a major consideration in managing the care of people with epilepsy (PWE). We analyzed a single-center cohort of 94 older adults (median age = 63.5 years, 52% females) who underwent RES between 2000 and 2021 with at least 6 months of postsurgical follow-up. Three fourths of the study cohort had lesional magnetic resonance imaging and underwent temporal lobectomy. Fifty-four (57%) PWE remained seizure-free during a median follow-up of 3.5 years. Cox proportional hazard multivariable analysis showed that aura (hazard ratio [HR] = .52, 95% confidence interval [CI] = .27-1.00), single ictal electroencephalographic pattern (HR = .33, 95% CI = .17-.660), and Elixhauser Comorbidity Index (HR = 1.05, 95% CI = 1.00-1.10) were independently associated with seizure recurrence at last follow-up. A sensitivity analysis using the Charlson Combined Score (HR = 1.38, 95% CI = 1.03-1.84, p = .027) confirmed the association of comorbidities with worse seizure outcome. Our findings provide a framework for a better informed discussion about RES prognosis in older adults. More extensive, multicenter cohort studies are needed to validate our findings and reduce hesitancy in pursuing RES in suitable older adults.

Late-onset epilepsy clinic: From clinical diagnostics to biomarkers.

The unique patho-clinical entity of late-onset epilepsy (LOE), distinguished by its distinct natural history, from its onset to the prognosis it portends, necessitates specialized care. We lack a universally accepted definition, but LOE is typically identified as epilepsy onset after the age of 60 or 65. Unlike epilepsy in younger individuals, LOE is almost by default focal in origin, secondary to acquired etiologies, and presents unique diagnostic and management challenges due to its atypical semiology, higher comorbidity burden, frailty, and increased risks of subsequent stroke and dementia. LOE clinics have been established to address these challenges, providing a multidisciplinary approach to optimize outcomes in patients with new-onset seizures beyond the fifth decade of life. LOE clinics are essential for comprehensive care, offering not only seizure management but also monitoring and addressing associated comorbidities. The care model involves collaboration among neurologists, primary care providers, cardiologists, mental health professionals, and social workers to manage LOE patients' complex needs effectively. The prevalence of cognitive dysfunction in LOE patients underscores the need for regular cognitive assessments and interventions. Biomarker research, particularly involving amyloid beta, offers promising avenues for early diagnosis and a better understanding of the interplay between LOE and Alzheimer's disease. Establishing LOE clinics in major referral centers can enhance provider expertise, improve patient outcomes, and facilitate research to advance diagnostic and therapeutic strategies. In conclusion, LOE clinics play a critical role in addressing the multifaceted needs of older adults with epilepsy, tailored to local resources and challenges, thus enhancing epilepsy care in an aging global population.

Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

Bilateral Acute Hippocampal Ischemia in Two Patients Abusing Cocaine: What is the Outcome?

Hippocampal ischemia is a rare complication of cocaine abuse that has been thought to arise from vasospasm, anoxic injury, and/or catecholaminergic excitotoxicity. We present two cases of patients abusing cocaine, who presented with an acute onset anterograde amnesia due to bilateral hippocampal ischemia, and had different outcomes. Case 1 is a 49-year-old male with a history of IV heroin abuse who presented after being found down for an unknown period of time. He awoke with no memory of events leading up to hospitalization and was unable to retain new information. Urine toxicology was positive for cocaine and opiates. Traditional vascular risk factors included obesity, hypertension, and hyperlipidemia. His recovery was complicated by continued drug use and one episode of cardiac arrest. Despite cognitive rehabilitation, only minimal improvements in his anterograde memory were observed during his annual follow-up. Case 2 is a 23-year-old male with a history of attention deficit disorder treated with dexmethylphenidate and a history of consistent marijuana and cocaine abuse, who presented with nausea, vomiting, chest pain, shortness of breath, and acute-onset short-term memory loss. Urine toxicology was negative for cocaine and opiates and positive for marijuana. He had no known vascular risk factors. With cognitive rehabilitation and discontinuation of illicit drug use, he demonstrated a significant improvement in his memory function over the course of six months. Brain MRI in both patients showed symmetric bilateral hippocampal diffusion restriction without post-contrast enhancement with corresponding hyperintensities on fluid-attenuated inversion recovery sequences. In both patients, cerebrospinal fluid (CSF) studies were unremarkable for inflammation or infection, and electroencephalograms were normal in awake and drowsy states. Bilateral hippocampal ischemia should be considered as a potential cause of acute onset anterograde amnesia in patients with a history of cocaine abuse. Other substances such as heroin and dexmethylphenidate may potentially increase susceptibility for hippocampal ischemia in patients using cocaine. Discontinuation of illicit drug abuse can influence the degree of recovery from acute bilateral hippocampal ischemia.

SARS-CoV-2 infection and seizures: the perfect storm.

Seizures have been increasingly identified as a neurologic manifestation of coronavirus disease 2019 (COVID-19) infection. They may be symptomatic due to systemic infections, as a result of direct central nervous system (CNS) invasion, or occur in response to inflammatory reactions to the virus. It is possible that proinflammatory molecules released in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to hyperexcitability and epileptogenesis, similar to infections caused by other neurotrophic viruses. Cerebral spinal fluid (CSF) in patients with COVID-19 and seizures is negative for SARS-CoV-2 (PCR) in the majority of patients, but has been found to be positive for proinflammatory molecules like IL-6, IL-8, and anti-neuronal autoantibodies. Electroencephalogram (EEG) in COVID-19 patients are nonspecific. However, in the encephalopathic and critically ill subpopulation, EEG is essential in detecting nonconvulsive seizures and status epilepticus which is associated with increased overall mortality in COVID-19 patients. Thus, as encephalopathy is often the only CNS symptom evidenced in patients with nonconvulsive seizures, more judicious use of continuous EEG in encephalopathic COVID-19 patients should be considered. This would facilitate earlier detection and treatment of seizures in this population, which would ultimately improve outcomes. Further research into the onset and potential for development of seizures and epilepsy in patients with COVID-19 is needed.

A Case of MuSK Myasthenia Gravis Presenting With Persistent Respiratory Insufficiency.

ABSTRACT: Muscle-specific kinase (MuSK) antibody is seen in 4%-10% of patients with myasthenia gravis (MG), with 40% of these patients reporting bulbar weakness as the initial symptom. We present the case of a 40-year-old woman with MuSK MG whose only presenting symptom was progressive respiratory insufficiency necessitating BiPAP use 16-24 hours daily. She was unresponsive to treatment for cardiac and pulmonary causes and thus referred to neurology. Initial workup directed toward autoimmune and genetic myopathies was unrevealing. MuSK antibodies were positive (60.7 nmol/L, nl 0.00-0.02). Electrodiagnostic studies were unremarkable other than single fiber electromyography which was consistent with a defect in neuromuscular transmission. Treatment with prednisone, plasma exchange, and rituximab led to improvement to reliance on BiPAP only at night. However, her most treatment refractory and quality of life limiting symptom continues to be respiratory insufficiency. Further investigation to better characterize differential response to treatment in this subset of patients with MuSK MG may be needed.