Seizure clusters, treatment patterns, and healthcare resource utilization in patients with epilepsy: A Wisconsin-based claims analysis.

BACKGROUND: Seizure clusters are underresearched and associated with adverse outcomes in patients with epilepsy. This study was a noninterventional, retrospective claims-based analysis using the Wisconsin Health Information Organization (WHIO) All-Payer Claims Database to characterize the epilepsy population in Wisconsin, with a focus on prevalence, treatment patterns, and healthcare resource utilization (HCRU) in patients with seizure clusters prior to the introduction of nasal spray rescue medications. This timeframe allows characterization of a historical baseline for future comparisons with newer treatments. METHODS: Four cohorts were defined: (1) all-epilepsy (all patients with epilepsy); and subcohorts of: (2) patients receiving a monotherapy antiseizure medication (ASM); (3) patients receiving ASM polytherapy; and (4) patients treated for seizure clusters (ie, those taking rescue medications and ≥ 1 ASM). Primary outcomes were HCRU over a 12-month follow-up period, which were descriptively analyzed. RESULTS: Between 2017 and 2019, 16,384 patients were included in the all-epilepsy cohort; 11,688 (71.3 %) were on monotherapy, 3,849 (23.5 %) were on polytherapy, and 526 (3.2 %) were treated for seizure clusters. Twelve-month retentions to the ASM treatments were 46.7 % (7,895/16,904) in the all-epilepsy cohort, and 40.0 % (4,679/11,688) and 40.1 % (1,544/3,849) in the monotherapy and polytherapy subcohorts, respectively. Rescue medication prescriptions were obtained 1,029 times by the 526 patients in the treated seizure cluster subcohort, with infrequent refill rates (mean 1.6-1.9 times/year). A higher proportion of patients in the treated seizure cluster subcohort had epilepsy-related outpatient visits (89.7 %), other visits (71.3 %), and hospitalizations (25.3 %) than patients in the monotherapy (72.2 %, 50.2 %, 19.3 %, respectively) and polytherapy (83.3 %, 63.3 %, 22.8 %, respectively) subcohorts. Mean (standard deviation) all-cause ($114,717 [$231,667]) and epilepsy-related ($76,134 [$204,930]) costs over 12 months were higher in the treated seizure cluster subcohort than the monotherapy ($89,324 [$220,181] and $30,745 [$145,977], respectively) and polytherapy ($101,506 [$152,931] and $49,383 [$96,285], respectively) subcohorts. CONCLUSIONS: Patients treated for seizure clusters incurred higher all-cause and epilepsy-related costs and epilepsy-related HCRU than other subcohorts and had infrequent rescue medication refills. The findings of this analysis highlight the need for appropriate treatment for those patients with epilepsy experiencing seizure clusters. The effect of newer rescue medications to alter these findings will be explored in a follow-up study. Regardless, specialist providers with expertise in treating refractory epilepsy and seizure cluster patients may help to reduce the burden of seizure clusters.

Population-Level Disease Prevalence Rates Correlate With COVID-19 Mortality.

INTRODUCTION: Initial reports identified preexisting conditions associated with COVID-19 mortality risk. The Centers for Disease Control and Prevention (CDC) 500 Cities Project provides prevalence rate estimates at the census tract level for these conditions. The frequency of these individual condition prevalence rates may associate with the census tracts with greater risk of COVID-19 deaths. OBJECTIVE/RESEARCH QUESTION: Can the census tract-level outcome of Milwaukee County COVID-19 death rates correlate with the census tract-level COVID-19 individual mortality risk condition prevalence rates? METHODS: This study used the 296 Milwaukee County, Wisconsin census tracts' COVID-19 death rates per 100,000 lives to perform a linear regression with individual COVID-19 mortality risk condition prevalence rates, obtained from the CDC's 500 Cities Project, and a multiple regression with 7 condition prevalence rates. The Milwaukee County Medical Examiner provided census tract identified deaths from COVID-19 from March 2020 through May 2020. Crude death rates for these 3 months per 100,000 population were analyzed in a multiple linear regression versus prevalence rates for these conditions in each census tract. RESULTS: There were 295 assessable COVID-19-related deaths in Milwaukee County in early 2020. The model of crude death rates showed statistical significance with the condition prevalence rates in Milwaukee County. A regression analysis of each condition's prevalence rate showed no association with crude death rates. CONCLUSIONS: This study supports a correlation between high COVID-19 mortality rate census tracts and prevalence rate estimates of conditions associated with high individual COVID-19 mortality rates. The study is limited by the small COVID-19 death sample and the use of a single location. The ability to focus COVID-19 health promotion may save future lives if mitigation strategies are applied extensively in these neighborhoods.

Neighborhood Condition Prevalence Rates Correlate With COVID-19 Mortality in Milwaukee County, Wisconsin.

Purpose: We sought to determine if census tract-level (ie, neighborhood) COVID-19 death rates in Milwaukee County correlated with the census tract-level condition prevalence rates (CPRs) for individual COVID-19 mortality risk. Methods: This study used Milwaukee County-reported COVID-19 death rates per 100,000 lives for the 296 census tracts within the county to perform a linear regression with individual COVID-19 mortality risk CPR, mean age, racial composition of census tract (by percentage of non-White residents), and poverty (by percentage within census tract), followed by multiple regression with all 7 CPRs as well as the 7 CPRs combined with the additional demographic variables. CPR estimates were accessed from the Centers for Disease Control and Prevention 500 Cities Project. Demographics were accessed from the U.S. Census. The Milwaukee County Medical Examiner's office identified 898 deaths from COVID-19 in Milwaukee County from March 2020 to June 2021. Results: Among the variables included, crude death rate demonstrated a statistically significant association with the 7 COVID-19 mortality risk CPRs (as analyzed collectively), census tract mean age, and several of the CPRs individually. The addition of census tract age, race, and poverty in multiple regression did not improve the association of the 7 CPRs with crude death rate. Conclusions: Results from this population-level study indicated that census tracts with high COVID-19 mortality correlated with high-risk condition prevalence estimates within those census tracts, illustrating how health data collection and analysis at a census tract level could be helpful when planning pandemic-mitigating public health efforts.

Patient Barriers for Weight Management Among African American Women.

PURPOSE: The primary aim of this study was to assess the perceptions of local African American women who are overweight or obese using semi-structured focus groups to identify barriers to weight management and factors that support strategy success. The secondary aim of this study was to determine recommendations for patient-centered weight management interventions established specifically for African American women in the Milwaukee-area community. METHODS: Three semi-structured focus groups to explore barriers to weight management were performed among women patients. Participants (N=41) were recruited via email, postal mail, and phone as available from an academic medical center in Milwaukee, Wisconsin. Focus group discussions were transcribed verbatim, reviewed by the study team, and coded based on recurring themes within and across interviews. Responses were analyzed by frequency of occurrence using qualitative computer software. RESULTS: Five primary barriers to weight management were identified from focus groups: food choices, lifestyle changes, social support, locus of control, and health education. Based on participant reports, improvements to present practice and health literacy for patients may be merited. There was expressed interest by patients for being involved in future research and development of patient-centered interventions. CONCLUSIONS: This study provides support for the use of a community-based participatory research approach in determining appropriate considerations for weight management interventions suitable for this patient population. Future research should include stakeholders not included in this study, such as community organization leaders, and primary care physicians to develop a refined intervention targeting the primary barriers to weight management.

Physician Use of Electronic Health Records in Obesity Management.

OBJECTIVE: To assess Wisconsin physician knowledge, attitudes, and practices in obesity management. METHODS: The Wisconsin Medical Society distributed an e-mail survey to 12,372 members with questions on obesity causes, barriers to documentation, and training in obesity management. RESULTS: A total of 590 surveys (4.7%) were completed. Physicians had an accurate fund of knowledge. Reasons given for failure to document obesity were lack of reimbursement, lack of effective treatment, and discomfort in discussing obesity. Only 14% of responding physicians were optimistic about their patients achieving sustained weight loss and only 7% believed they have been successful at treating obesity. Training was infrequent in obesity management. CONCLUSIONS: Survey respondents indicated that additional training and effective tools would help treat obesity. Strategies should be developed that improve physician effectiveness in obesity management.

Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the guideline development subcommittee of the american academy of neurology.

OBJECTIVE: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. METHODS: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. RESULTS: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%-59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%-64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ~7% from 1 to 5 years postim-plantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0-11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. RECOMMENDATIONS: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. Neurology® 2013;81:1-7.

Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology.

OBJECTIVE: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. METHODS: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. RESULTS: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%-59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%-64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥ 50% seizure frequency reduction rates of ≈ 7% from 1 to 5 years postimplantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0-11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. RECOMMENDATIONS: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation.

Tiagabine in clinical practice: effects on seizure control and behavior.

OBJECTIVE: Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice. METHODS: Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB. RESULTS: Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%). CONCLUSIONS: Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug.

Alternative therapeutic options for medical management of epilepsy in apes.

Phenobarbital has been the primary antiepileptic drug used in primates, but the dosage required for seizure control is frequently associated with significant side effects. Newer antiepileptic drugs and adjunctive therapies currently being used in human medicine provide additional options for treatment of nonhuman primates. This report describes different drug regimes used for control of epileptic seizures in apes at the Milwaukee County Zoo (Milwaukee, Wisconsin, U.S.A.), including the addition of acetazolamide to phenobarbital, levetiracetam, carbamazepine, and the use of extended cycle oral contraceptives to assist seizure control in female apes with catamenial epilepsy.

Unexpected right hemisphere language representation identified by the intracarotid amobarbital procedure in right-handed epilepsy surgery candidates.

The intracarotid amobarbital procedure (IAP) is used for language lateralization in the presurgical evaluation for intractable epilepsy. Some epilepsy surgical centers forgo IAP for right temporal lobectomies in right-handed patients with no personal/family history of left-handedness, implying that right hemisphere language representation does not occur in these patients. To test this hypothesis, a retrospective analysis was performed on 156 consecutive epilepsy surgery candidates who underwent IAP. Of the 156 candidates, 122 were right-handed, and 55 of the 122 demonstrated right hemisphere seizure focus. Right hemisphere language representation was found in 22 of 55 patients, with two demonstrating significant right hemisphere language despite a right hemisphere seizure focus and no family history of left-handedness. Only 1 of 156 patients undergoing IAP experienced permanent neurological complications. Although relatively uncommon, right hemisphere language representation may occur more frequently than complications from cerebral angiography and, therefore, presurgical IAP is recommended for all epilepsy surgery candidates regardless of handedness to minimize the risk of severe language decline.

Predictors of naming decline after dominant temporal lobectomy: age at onset of epilepsy and age of word acquisition.

This study examined factors affecting object naming decline in patients who have undergone anterior temporal lobectomy (ATL) and the correlation between age of word acquisition and loss of specific object names postoperatively. The Boston Naming Test (BNT) was used to assess changes in object-naming performance in patients who underwent ATL. Correlation analyses were performed by group (dominant or nondominant ATL) on individual items from the BNT to determine if age of acquisition of object names had an effect on postoperative word loss. The influence of age at onset of seizures on naming decline was examined in the dominant ATL group. Only patients who had undergone dominant ATL experienced significant clinical and statistical declines after surgery. Among the patients who underwent dominant ATL, those with late age at onset of seizures declined significantly more than those with early-onset seizures. When individual object names were examined, age of acquisition of words predicted whether words were lost or gained after surgery.

Human sexuality, sex hormones, and epilepsy.

The function of the hypothalamic-pituitary axis (HPA), including the production of luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone, and prolactin, and the concentrations and metabolism of its end products, such as estrogen, testosterone, and dehydroepiandrosterone, appear to be modified in many people with epilepsy. Effects of the disorder itself and effects of antiepileptic drugs (AEDs) both appear to contribute to these hormonal alterations, which may be associated with sexual dysfunction. Focal epileptic discharges from the temporal lobe may affect HPA function, as is suggested by the normalization of androgen levels seen in men with temporal lobe epilepsy who become seizure-free after surgery. Hepatic enzyme-inducing AEDs such as carbamazepine and phenytoin may be most clearly linked to altered metabolism of sex steroid hormones, but valproic acid, an enzyme inhibitor, has also been implicated in the causation of reproductive endocrine abnormalities. Polycystic ovaries and polycystic ovarian syndrome (PCOS) are widely believed to be common in women with epilepsy, but the actual prevalence and the pathogenesis of PCOS in this population are disputed. Hormonal changes and sexual dysfunction need to be addressed in any comprehensive approach to epilepsy management, as well as any comprehensive epilepsy research program. Avoidance of enzyme-inducing AEDs and achievement of freedom from seizures as the goal of treatment are strongly recommended.

Reproductive and sexual dysfunction in men with epilepsy.

Disturbances of reproductive and sexual health are common in people with epilepsy. Their etiology is not well understood but appears to be multifactorial, and both epilepsy itself and drugs used to treat it are implicated. Physiologically, sex steroid hormone levels, the hypothalamic-pituitary axis, and testicular function can be affected in men with epilepsy. Psychosocial complications associated with epilepsy can also affect reproductive health and sexuality. Clinicians need to investigate such problems carefully, both because of their multifactorial nature and because patients and physicians alike may often fail to recognize or be reluctant to acknowledge them; in particular, patients whose epilepsy had its onset before puberty may lack subjective awareness of impairments of sexual response and function. Treatments for reproductive and sexual dysfunction in men with epilepsy have been inadequately studied. Modalities such as medications for erectile dysfunction and surgery may be useful. Therapy with exogenous testosterone and an aromatase inhibitor may be helpful for men with epilepsy and sexual dysfunction due to testosterone deficiency.

Vagus nerve stimulation therapy: 5-year or greater outcome at a university-based epilepsy center.

OBJECTIVE: This retrospective study documented long-term outcome of patients receiving vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. METHODS: Medical charts of 28 patients implanted for 5 years or longer were reviewed for changes in seizure frequency after 1 year of VNS therapy and at follow up, which ranged from 5 to 7 years. Numbers of antiepileptic drugs (AEDs) taken by the patients were also computed at 1 year and follow up. One patient had died and one had discontinued VNS therapy; data were available for 26 patients. RESULTS: The median percent change in seizure frequency from baseline increased from -28% (P = 0.0053, Wilcoxon signed-rank test) at 12 months to -72% (P < 0.0001) at follow up. Some patients whose seizure frequency was not reduced during the initial 12 months of VNS therapy did experience reductions in seizure frequency during the follow-up period. CONCLUSION: In this retrospective study, the effectiveness of VNS therapy increased over time. Physicians should be aware that response to VNS therapy may be delayed for some patients.

Lamotrigine for patients with juvenile myoclonic epilepsy following prior treatment with valproate: results of an open-label study.

This open-label study was designed to evaluate lamotrigine monotherapy as a possible alternative in patients with juvenile myoclonic epilepsy who previously failed treatment with valproate. Patients (n=63) were transitioned from valproate to lamotrigine during an 8-week escalation phase followed by 24 weeks of lamotrigine monotherapy. On Week 24 of the treatment phase, investigators judged that 50 and 67% of patients completing the study had shown mild, moderate, or marked improvement in adverse events and global clinical status, respectively, and 76% of patients rated lamotrigine as somewhat better (13%) or much better (63%) than valproate. The majority of patients completing the study experienced no deterioration of seizure control when switching from valproate to lamotrigine. These results support additional research on lamotrigine in juvenile myoclonic epilepsy.

A retrospective analysis of the effects of magnet-activated stimulation in conjunction with vagus nerve stimulation therapy.

Vagus nerve stimulation (VNS) therapy offers two methods to help control seizures, automatic stimulation delivered at programmed intervals and on-demand stimulation initiated with a magnet. This study retrospectively analyzes magnet use during the E03 and E04 clinical trials of VNS therapy. Magnet activation that aborted, decreased, terminated, or diminished a seizure was classified as an improvement; for purposes of evaluation, the patient was considered to have received a benefit. When patients in the E03 trial used magnets to activate stimulation, patients with active magnets were more likely to report seizure improvement than patients with inactive magnets (P=0.0479, Fisher's test). In the E04 trial, 22% of patients using the magnet reported seizure termination and 31% reported seizure diminution. Unrelated to seizure reduction with programmed VNS therapy, approximately half of the patients who used the magnet in this study received some benefit. Additional studies can provide a better understanding of this unique mode of delivering antiseizure therapy.

Lateralising value of ictal features in partial seizures: effect on postsurgical outcome.

We reviewed the videotapes of 49 consecutive patients with a history of medically refractory temporal lobe epilepsy for the presence and laterality of unilateral hand posturing (UHP), unilateral hand automatism (UHA), non-forced head turning (HT), and post-ictal dysphasia (PID). All of these patients underwent temporal resections with follow-up for more than 2 years after the surgery. We examined the correlation of consistency, frequency, and laterality of each of these signs on the postsurgical outcomes. The distribution of these signs was not significantly different between patients with Engel class 1 versus Engel class 2-4. The consistency and laterality of these signs do not correlate with postsurgical outcomes.

Observations on the use of vagus nerve stimulation earlier in the course of pharmacoresistant epilepsy: patients with seizures for six years or less.

BACKGROUND: This study retrospectively compared the effectiveness of vagus nerve stimulation (VNS) therapy among a constant cohort of patients in the patient outcome registry, which systematically monitors outcomes of patients receiving VNS therapy. Patients in the study had pharmacoresistant seizures for 6 years or less (early treatment group) or more than 6 years (late treatment group) before initiation of VNS therapy, and results are provided after both 3 and 12 months. REVIEW SUMMARY: Of 405 patients, 51 were in the early and 354 in the late treatment groups. Median age at onset of seizures was 7 years in the early and 4.5 years in the late treatment group. Seizure reduction of 100% was reported in 7.8% (early) and 3.7% (late) patients at 3 months and 11.8% (early) and 4.5% (late) at 12 months (P = 0.033). Reductions in seizure frequency greater than or equal to 90% for early and late treatment groups were similar: 11.8% (early) and 11.0% (late) at 3 months and 23.5% (early) and 17.0% (late) at 12 months. CONCLUSIONS: Patients treated earlier with VNS therapy were twice as likely to report no seizures as patients who had seizures for more than 6 years before they received VNS therapy. The effectiveness of VNS therapy should be assessed among other patients with pharmacoresistant seizures and lesser cumulative seizure loads.