Prescribing Complexities: A Patient Story Related to Seizure History and the Changing Therapeutic Landscape of Alzheimer's Disease.

The therapeutic landscape of Alzheimer's disease (AD) is rapidly changing. Disease-modifying medications for AD that target amyloid-beta (Aß) deposits in the brain have been approved by the Food and Drug Administration (FDA) in recent years. However, there remain many questions about which patients are most appropriate for these medications. One group in particular with unique considerations includes older adults with a prior history of seizures. AD and seizures represent an important, bidirectional relationship. This case report presents a patient story that highlights the importance of discussions around seizure history in consideration of anti-amyloid medications and the importance of risk-benefit assessments when considering anti-amyloid therapeutics for patients with AD.

Therapeutic approaches targeting seizure networks.

Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50 % of patients continue to experience refractory seizures within a year of surgery. Over the past 2 decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.

Metformin alleviates reactive gliosis and neurodegeneration, improving cognitive deficit in a rat model of temporal lobe epilepsy.

Cognitive impairment is a prevalent co-morbidity associated with epilepsy. Emerging studies indicate that neuroinflammation could be a possible link between epilepsy and its comorbidities, including cognitive impairment. In this context, the roles of glial activation, proinflammatory mediators, and neuronal death have been well studied and correlated with epilepsy-associated cognitive impairment in animal studies. While recent reports have demonstrated the anti-epileptogenic and anti-convulsant actions of metformin, its effect on epilepsy associated cognitive deficit remains unknown. Therefore, the current study investigated the effect of metformin treatment on neuroinflammation, neurodegeneration, and cognitive deficits after inducing status epilepticus (SE) with lithium-pilocarpine in rats. Metformin treatment improved the hippocampal-dependent spatial and recognition memory in Morris water maze and Novel object recognition tasks, respectively. Further, metformin treatment attenuated microglial and astroglial activation, accompanied by reduced IL-1ß, COX-2 and NF-Ä¸ß gene expression. Additionally, metformin conferred neuroprotection by inhibiting the neuronal death as assessed by Nissl staining and transmission electron microscopy. These findings suggest that metformin holds promise as a therapeutic intervention for cognitive impairment associated with epilepsy, possibly through its modulation of glial activation and neuronal survival. Further research is needed to elucidate the precise mechanisms and to assess the long-term effect of metformin in epilepsy-associated cognitive impairment.

A Review of Hyperventilation Activation in Diagnosis and Management of Childhood Absence Epilepsy.

Childhood absence epilepsy is one of the most prevalent pediatric epilepsy syndromes, but diagnostic delay is common and consequential. Childhood absence epilepsy is diagnosed by history and physical examination including hyperventilation with electroencephalography (EEG) used to confirm the diagnosis. Hyperventilation produces generalized spike-wave discharges on EEG in >90% of patients with childhood absence epilepsy and provokes clinical absence seizures consisting of brief loss of consciousness typically within 90 seconds. Child neurologists report a high volume of referrals for children with "staring spells" that strain already limited health care resources. Resources are further strained by the use of EEG for monitoring antiseizure medication effectiveness with unclear benefit. In this review, we examine the safety and efficacy of hyperventilation activation as a tool for the diagnosis and management of childhood absence seizures.

Repeated seizure-induced brainstem neuroinflammation contributes to post-ictal ventilatory control dysfunction.

Patients with epilepsy face heightened risk of post-ictal cardiorespiratory suppression and sudden unexpected death in epilepsy (SUDEP). Studies have shown that neuroinflammation, mediated by the activation of microglia and astrocytes, may be a cause or consequence of seizure disorders. Kcnj16 (Kir5.1) knockout rats (SS kcnj16-/- ) are susceptible to repeated audiogenic seizures and recapitulate features of human SUDEP, including post-ictal ventilatory suppression, which worsens with repeated seizures and seizure-induced mortality. In this study, we tested the hypothesis that repeated seizures cause neuroinflammation within key brainstem regions that contribute to the control of breathing. Audiogenic seizures were elicited once/day for up to 10 days in groups of adult male SS kcnj16-/- rats, from which frozen brainstem biopsies of the pre-Bötzinger complex/nucleus ambiguus (preBötC/NA), Bötzinger complex (BötC), and raphe magnus (RMg) regions were subjected to a cytokine array. Several cytokines/chemokines, including IL-1α and IL-1ß, were increased selectively in preBötC/NA after 3 or 5 days of seizures with fewer changes in other regions tested. In additional groups of male SS kcnj16-/- rats that underwent repeated seizures, we quantified microglial (IBA-1+) cell counts and morphology, specifically within the preBötC/NA region, and showed increased microglial cell counts, area, and volume consistent with microglial activation. To further test the role of inflammation in physiological responses to seizures and seizure-related mortality, additional groups of SS kcnj16-/- rats were treated with anakinra (IL-1R antagonist), ketoprofen (non-selective COX inhibitor), or saline for 3 days before and up to 10 days of seizures (1/day), and breathing was measured before, during, and after each seizure. Remarkably, IL-1R antagonism mitigated changes in post-ictal ventilatory suppression on days 7-10 but failed to prevent seizure-related mortality, whereas ketoprofen treatment exacerbated post-ictal ventilatory suppression compared to other treatment groups but prevented seizure-related mortality. These data demonstrate neuroinflammation and microglial activation within the key brainstem region of respiratory control following repeated seizures, which may functionally but differentially contribute to the pathophysiological consequences of repeated seizures.

Assessment of the diagnostic utility of the electroencephalogram in pediatric emergencies.

INTRODUCTION: We analyze the diagnostic utility of urgent EEG (electroencephalogram) performed in children under 16 years of age in our center. MATERIAL AND METHODS: Descriptive, retrospective, observational study of consecutive patients from 0 to 16 years of age, who underwent an urgent EEG for any reason, from January to December 2022. RESULTS: Of the 388 patients, 70 were children: 37 (52.85%) women, and 33 (47.14%) men. Average age: 6.27 ±â€¯4.809. Of the 70 patients, 6 (8.57%) had previous epilepsy. Reasons for consultation: 17 febrile seizures, 10 first focal seizures, 10 first TCG seizures, 6 paroxysmal episodes, 6 absences, 3 myoclonus of extremities, 3 syncope, 2 SE, 2 visual alterations, 2 low level of consciousness, 2 cyanosis, 2 suspected meningitis or encephalitis, 1 choking, 1 atypical headache, 1 chorea, 1 presyncope, 1 language delay. Of the 70 patients, 47 had a normal EEG (67.14%). Of the 47 patients with a normal EEG, 10 were diagnosed with epilepsy, and 3 of them began receiving antiepileptic treatment upon discharge. None of the patients with suspected syncope or paroxysmal disorder (17 patients, 24.28%) had EEG abnormalities. Of the 17 patients with atypical febrile seizures, 3 had EEG abnormalities. CONCLUSIONS: A third of the EEG records performed in the Emergency Department showed alterations, probably due to the time taken. Almost half of the patients with suspected epilepsy or EE showed EEG abnormalities, which confirmed the diagnosis in these cases and encouraged the clinician to start drug treatment. No case with a high suspicion of epilepsy was dismissed due to the normality of the EEG recording in our series. No patient diagnosed with syncope or paroxysmal disorder had EEG abnormalities. Nearly a quarter of patients with atypical febrile seizures showed EEG abnormalities. We barely register cases of status epilepticus, probably due to the degree of complexity of our center.

A Rare Case of Immune Thrombocytopenia With Intracranial Hemorrhage Secondary to Cavernous Malformation.

Immune thrombocytopenia (ITP) is an autoimmune disease resulting in a fall in platelet count, causing ecchymoses and bleeding manifestations. The most prevalent acquired bleeding disorder in children is ITP. Intracranial hemorrhage (ICH) is a rare but most devastating complication of ITP which can cause neurological sequelae. We report the case of a four-year-old male child who presented with a history of seizures, headache, multiple ecchymoses, and bruising. Blood counts and bone marrow examination were suggestive of ITP. Magnetic resonance imaging (MRI) of the brain showed ICH with multiple cerebral cavernous malformations. ICH as the first presentation of ITP is extremely rare. ICH in a case of ITP secondary to arteriovenous malformation has been scarcely reported, establishing the rarity of the currently presented case. Morbidity and mortality of ICH occurring as a consequence of ITP can be reduced by recognizing the symptoms, diagnosing promptly, and treating aggressively.

Intraoperative mapping of epileptogenic foci and tumor infiltration in neuro-oncology patients with epilepsy.

Background: Epileptogenesis and glioma growth have a bidirectional relationship. We hypothesized people with gliomas can benefit from the removal of epileptic tissue and that tumor-related epileptic activity may signify tumor infiltration in peritumoral regions. We investigated whether intraoperative electrocorticography (ioECoG) could improve seizure outcomes in oncological glioma surgery, and vice versa, what epileptic activity (EA) tells about tumor infiltration. Methods: We prospectively included patients who underwent (awake) ioECoG-assisted diffuse-glioma resection through the oncological trajectory. The IoECoG-tailoring strategy relied on ictal and interictal EA (spikes and sharp waves). Brain tissue, where EA was recorded, was assigned for histopathological examination separate from the rest of the tumor. Weibull regression was performed to assess how residual EA and extent of resection (EOR) related to the time-to-seizure recurrence, and we investigated which type of EA predicted tumor infiltration. Results: Fifty-two patients were included. Residual spikes after resection were associated with seizure recurrence in patients with isocitrate dehydrogenase (IDH) mutant astrocytoma or oligodendroglioma (HR = 7.6[1.4-40.0], P-value = .01), independent from the EOR. This was not observed in IDH-wildtype tumors. All tissue samples resected based on interictal spikes were infiltrated by tumor, even if the MRI did not show abnormalities. Conclusions: Complete resection of epileptogenic foci in ioECoG may promote seizure control in IDH-mutant gliomas. The cohort size of IDH-wildtype tumors was too limited to draw definitive conclusions. Interictal spikes may indicate tumor infiltration even when this area appears normal on MRI. Integrating electrophysiology guidance into oncological tumor surgery could contribute to improved seizure outcomes and precise guidance for radical tumor resection.

An emerging role of STriatal-enriched protein tyrosine phosphatase in hyperexcitability-associated brain disorders.

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase that is associated with numerous neurological and neuropsychiatric disorders. STEP dephosphorylates and inactivates various kinases and phosphatases critical for neuronal function and health including Fyn, Pyk2, ERK1/2, p38, and PTPα. Importantly, STEP dephosphorylates NMDA and AMPA receptors, two major glutamate receptors that mediate fast excitatory synaptic transmission. This STEP-mediated dephosphorylation leads to their internalization and inhibits both Hebbian synaptic potentiation and homeostatic synaptic scaling. Hence, STEP has been widely accepted to weaken excitatory synaptic strength. However, emerging evidence implicates a novel role of STEP in neuronal hyperexcitability and seizure disorders. Genetic deletion and pharmacological blockade of STEP reduces seizure susceptibility in acute seizure mouse models and audiogenic seizures in a mouse model of Fragile X syndrome. Pharmacologic inhibition of STEP also decreases hippocampal activity and neuronal intrinsic excitability. Here, we will highlight the divergent roles of STEP in excitatory synaptic transmission and neuronal intrinsic excitability, present the potential underlying mechanisms, and discuss their impact on STEP-associated neurologic and neuropsychiatric disorders.

Posterior reversible encephalopathy syndrome (PRES) in classic Hodgkin's lymphoma, complicated by anthracycline-induced cardiomyopathy.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin's lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge.

Personality disorders in individuals with functional seizures: a systematic review.

Functional seizures (FS) are classified as conversion disorders in the DSM-5 and dissociative disorders in the ICD-11, showing a multifactorial psychopathology with various psychiatric comorbidities, such as depression and anxiety. Several studies have found a correlation between FS and personality disorders, mainly those in cluster B. Within this cluster, borderline personality disorder (BPD) or borderline personality traits are the most prevalent in FS. Emotion dysregulation is a hallmark of BPD and is commonly reported in individuals with FS. Cluster C personality disorders, such as avoidant or obsessive-compulsive disorders, have also been reported in FS. In this review, we aim to evaluate the relationship between FS and personality disorders. Assessing personality disorders in the context of FS is relevant for determining the most appropriate intervention. Cognitive-behavioral therapy (CBT) is considered the first-line approach to treating FS. Among various CBT strategies, dialectical behavior therapy, which specifically targets emotion dysregulation, may be helpful for individuals with BPD. Future research should assess the advantages of systematically evaluating personality disorders in FS to address specific treatment planning and evaluate its effectiveness on seizure recurrence, psychological comorbidities, and quality of life. Systematic review registration: https://www.crd.york.ac.uk/PROSPEROFILES/509286_STRATEGY_20240203.pdf, identifier CRD42024509286.

Psychogenic non-epileptic (functional) seizures in adults with intellectual disability and epilepsy: A matched case-control study.

OBJECTIVE: To describe the characteristics of psychogenic non-epileptic (functional) seizures (PNES) in adults with epilepsy and intellectual disability (ID) and to establish differences and risk factors regarding psychosocial functioning between individuals with and without PNES. METHODS: Adults with ID and epilepsy living in epilepsy care facilities in The Netherlands were screened for PNES by a neurologist. A control group consisting of people with epilepsy and ID, without PNES, was matched according to age, sex, and level of ID. Objective data were retrieved retrospectively from clinical notes of the resident. Standardized questionnaires and tests, adjusted for people with ID, were obtained from participants and their nursing staff. Differences were analyzed using paired t tests, Wilcoxon signed-rank tests, or McNemar's tests, appropriate for matched case-control studies. Conditional logistic regression identified PNES risk factors. RESULTS: Five hundred forty individuals were screened, of which 42 had PNES (point prevalence 7.8%). In total, 35 cases and 35 controls gave consent. Proxy reports indicated that PNES impacted daily life in 79% by adjusting the individual's schedule, and caused minor injuries in one-third. Those with PNES were mainly female (69%); had a mild (46%) or moderate (37%) level of ID; showed more symptoms of depression (p = .024), anxiety (p = .030), self-injurious behavior (p = .015); and experienced more negative life events (p < .001). Clinically relevant predictors of PNES were the number of negative life events (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.12-2.53) and self-injurious behaviors (OR 5.27, 95% CI .97-28.81). SIGNIFICANCE: Previously, PNES in individuals with ID and epilepsy were described mainly as a reinforced behavioral pattern, due to limited associations with psychiatric disorders. Our results demonstrate that this population does show individual psychosocial vulnerabilities when measured with instruments adjusted for this population, as indicated by proxy reports from daily caregivers. Viewing PNES as an involuntary response, especially for stress-prone individuals with ID, could reduce stigma and improve treatment.

Evaluating the serum levels of zinc, copper, magnesium, and 25-hydroxy vitamin D in children with idiopathic drug-resistant epilepsy; a cross-sectional study.

BACKGROUND: Drug-resistant epilepsy is defined as failure of seizure control in spite of using 2 or 3 proper antiepileptic drugs in appropriate time. Mineral elements play important roles in neuronal function; it is believed that mineral deficiency may lead to complications through seizure management. In the present study, serum levels of zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), and 25-hydroxy vitamin D (Vit D) in drug-resistant-epilepsy (DRE) patients were evaluated and compared with the controlled patients. METHODS: In this cross-sectional study, epileptic patients were included and categorized into two groups of DRE and well-controlled patients. Patients' serum samples were analysed to evaluate Zn, Cu, Mg, Ca, and Vit D levels. The primary objective was comparison of serum levels of different trace elements between the groups. RESULTS: Sixty-four epileptic children including 33 DRE and 31 well-controlled children entered the study. The DRE children showed a significantly earlier onset of disease compared to the other group (p = 0.014). Comparing the frequency of developmental delay between the groups, the results showed this complication was significantly more frequent in the DRE group (p < 0.001). Concerning serum elements, the results showed a significantly higher concentration of Zn in the well-controlled group than the DRE group (p = 0.007). On the other hand, no significant differences were observed between the groups regarding the means of Vit D, Ca, Cu, and Mg levels (p > 0.05). CONCLUSION: The results of the present study delineated that drug-resistant epilepsy patients had earlier onset of disease and were at higher risk of neurodevelopmental delay compared with well-controlled-epilepsy patients. A significant lower serum levels of Zn were also observed in drug-resistant-epilepsy patients. This finding may suggest the role of zinc supplementation in help to better control of drug-resistant seizures, as well as, the importance of serum zinc monitoring in epileptic patients.

A data augmentation procedure to improve detection of spike ripples in brain voltage recordings.

Epilepsy is a major neurological disorder characterized by recurrent, spontaneous seizures. For patients with drug-resistant epilepsy, treatments include neurostimulation or surgical removal of the epileptogenic zone (EZ), the brain region responsible for seizure generation. Precise targeting of the EZ requires reliable biomarkers. Spike ripples - high-frequency oscillations that co-occur with large amplitude epileptic discharges - have gained prominence as a candidate biomarker. However, spike ripple detection remains a challenge. The gold-standard approach requires an expert manually visualize and interpret brain voltage recordings, which limits reproducibility and high-throughput analysis. Addressing these limitations requires more objective, efficient, and automated methods for spike ripple detection, including approaches that utilize deep neural networks. Despite advancements, dataset heterogeneity and scarcity severely limit machine learning performance. Our study explores long-short term memory (LSTM) neural network architectures for spike ripple detection, leveraging data augmentation to improve classifier performance. We highlight the potential of combining training on augmented and in vivo data for enhanced spike ripple detection and ultimately improving diagnostic accuracy in epilepsy treatment.

GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.

Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait. Patients with GEFS+ may develop typical febrile seizures (FS), while generalized tonic-clonic seizures (GTCSs) with fever commonly occur between 3 months and 6 years of age, which is generally followed by febrile seizure plus (FS+), with or without absence seizures, focal seizures, or GTCSs. GEFS+ exhibits significant genetic heterogeneity, with polymerase chain reaction, exon sequencing, and single nucleotide polymorphism analyses all showing that the occurrence of GEFS+ is mainly related to mutations in the gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2) gene. The most common mutations in GABRG2 are separated in large autosomal dominant families, but their pathogenesis remains unclear. The predominant types of GABRG2 mutations include missense (c.983A → T, c.245G → A, p.Met199Val), nonsense (R136*, Q390*, W429*), frameshift (c.1329delC, p.Val462fs*33, p.Pro59fs*12), point (P83S), and splice site (IVS6+2T → G) mutations. All of these mutations types can reduce the function of ion channels on the cell membrane; however, the degree and mechanism underlying these dysfunctions are different and could be linked to the main mechanism of epilepsy. The γ2 subunit plays a special role in receptor trafficking and is closely related to its structural specificity. This review focused on investigating the relationship between GEFS+ and GABRG2 mutation types in recent years, discussing novel aspects deemed to be great significance for clinically accurate diagnosis, anti-epileptic treatment strategies, and new drug development.

Neuronal rhythmicity and cortical arousal in a mouse model of absence epilepsy.

OBJECTIVES: Absence seizures impair psychosocial function, yet their detailed neuronal basis remains unknown. Recent work in a rat model suggests that cortical arousal state changes prior to seizures and that single neurons show diverse firing patterns during seizures. Our aim was to extend these investigations to a mouse model with studies of neuronal activity and arousal state to facilitate future fundamental investigations of absence epilepsy. METHODS: We performed in vivo extracellular single unit recordings on awake head-fixed C3H/HeJ mice. Mice were implanted with tripolar electrodes for cortical electroencephalogram (EEG). Extracellular single unit recordings were obtained with glass micropipettes in the somatosensory barrel cortex, while animals ambulated freely on a running wheel. Signals were digitized and analyzed during seizures and baseline. RESULTS: Neuronal activity was recorded from 36 cortical neurons in 19 mice while EEG showed characteristic 7-8 Hz spike-wave discharges. Different single neurons showed distinct firing patterns during seizures, but the overall mean population neuronal firing rate during seizures was no different from pre-seizure baseline. However, the rhythmicity of neuronal firing during seizures was significantly increased (p < 0.001). In addition, beginning 10s prior to seizure initiation, we observed a progressive decrease in cortical high frequency (>40 Hz) EEG and an increase in lower frequency (1-39 Hz) activity suggesting decreased arousal state. SIGNIFICANCE: We found that the awake head-fixed C3H/HeJ mouse model demonstrated rhythmic neuronal firing during seizures, and a decreased cortical arousal state prior to seizure onset. Unlike the rat model we did not observe an overall decrease in neuronal firing during seizures. Similarities and differences across species strengthen the ability to investigate fundamental key mechanisms. Future work in the mouse model will identify the molecular basis of neurons with different firing patterns, their role in seizure initiation and behavioral deficits, with ultimate translation to human absence epilepsy.

Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.

Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Emergency department utilization among adults with epilepsy: A multi-state cross-sectional analysis, 2010-2019.

OBJECTIVE: We described patterns and trends in ED use among adults with epilepsy in the United States. METHODS: Utilizing inpatient and ED discharge data from seven states, we conducted a cross-sectional analysis to identify adult ED visits diagnosed with epilepsy or seizures from 2010 to 2019. Using ED visit counts and estimates of state-level epilepsy prevalence, we calculated ED visit rates overall and by payer, condition, and year. RESULTS: Our data captured 304,935 ED visits with epilepsy as a primary or secondary diagnosis in 2019. Across the seven states, visit rates ranged between 366 and 726 per 1000 and were higher than rates for adults without epilepsy in all states but one. ED visit rates were highest among Medicare and Medicaid beneficiaries (vs commercial or self-pay). Adults with epilepsy were more likely to be admitted as inpatients. Visits for nervous system disorders were 6.3-8.2 times higher among people with epilepsy, and visits for mental health conditions were 1.2-2.6 times higher. Increases in ED visit rates from 2010 to 2019 among people with epilepsy exceeded increases among adults without by 6.0-27.3 percentage points. CONCLUSION: Adults with epilepsy visit the ED frequently and visit rates have been increasing over time. These results underscore the importance of identifying factors contributing to ED use and designing tailored interventions to improve ambulatory care quality.

Relationship between anti-seizure medication and behaviors that challenge in older persons with intellectual disability and epilepsy: a review.

INTRODUCTION: There is increased focus on the negative impact of the overprescribing of medication, specifically psychotropic medication, including anti-seizure medications (ASM), in people with Intellectual Disability (ID). This is particularly important for the older adult population, where multi-morbidity and polypharmacy are more common. ASMs are associated with psychiatric and behavioral adverse effects. Furthermore, there is growing awareness of the anticholinergic burden for older adults with epilepsy and ID and the relationship with behaviors that challenge (BtC). AREAS COVERED: This review defines the older adult population and outlines the relationship between epilepsy and ID. BtC is outlined in the context of the population and the relationship with ASMs. The evidence base to guide prescribing and de-prescribing for newer ASMs is also presented, including pragmatic data. EXPERT OPINION: Polypharmacy, particularly psychotropics, are a mortality risk factor for older adults with epilepsy and ID. Therefore, any BtC requires a holistic assessment with a multi-disciplinary approach. This includes specific consideration of all prescribed medicines in the context of polypharmacy. There should be routine reviews, at least annually, for those aged 40 years and over particularly focused on anticholinergic burden and/or polypharmacy.