Truly “Rational” Polytherapy: Maximizing Efficacy and Minimizing Drug Interactions, Drug Load, and Adverse Effects

While several newer AEDs have study data that support monotherapy usage, most possess FDA indications for adjunctive treatment of partial onset seizures, leading to their initial (and often persistent) clinical use as adjunctive polytherapy for patients with refractory epilepsy. This review considers a practical approach to the appropriate role for polytherapy in epilepsy, presents the evidence for AED polytherapy, reviews the mythic but practically reasonable concept of “rational polytherapy,” and concludes with practical strategies for avoiding and employing polytherapy in clinical practice. The appropriate indications for AED polytherapy include transitional polytherapy during titration of a new adjunctive AED toward monotherapy or long-term maintenance AED polytherapy in medically refractory epilepsy

Monitoring Antiepileptic Drugs: A Level-Headed Approach

Despite advances in epilepsy therapeutics, some physicians feel uncomfortable with newer antiepileptic drugs (AEDs) due to difficulty in promptly obtaining blood levels to guide medication adjustment, and even when levels for newer AEDs are obtained, many practitioners feel they are not very useful. Lacking confidence in AEDs whose levels that cannot readily or expeditiously be measured, many clinicians share uncertainty about proper use of the newer AEDs and monitoring AED administration. Similarly, some epilepsy patients inflate the importance of AED blood level monitoring, feeling that blood levels falling within traditionally therapeutic ranges are a fail-safe for seizure control, regardless of their compliance or personal behavior aggravating seizure burden, such as poor sleep or use of illicit substances. This review examines the elusive concept of therapeutic AED blood levels and potential uses and abuses of blood level monitoring, reinforcing appropriate uses for blood levels to ensure compliance and adjust for altered AED pharmacokinetics in the context of aging and disease states, pregnancy, or drug interactions

Concerns with AED conversion: comparison of patient and physician perspectives.

When discussing AED conversion in the clinic, both the patient and physician perspectives on the goals and risks of this change are important to consider. To identify patient-reported and clinician-perceived concerns, a panel of epilepsy specialists was questioned about the topics discussed with patients and the clinician's perspective of patient concerns. Findings of a literature review of articles that report patient-expressed concerns regarding their epilepsy and treatment were also reviewed. Results showed that the specialist panel appropriately identified patient-reported concerns of driving ability, medication cost, seizure control, and medication side effects. Additionally, patient-reported concerns of independence, employment issues, social stigma, medication dependence, and undesirable cognitive effects are important to address when considering and initiating AED conversion

Antiepileptic Drug Monotherapy: The Initial Approach in Epilepsy Management

Antiepileptic drug (AED) monotherapy is the preferred initial management approach in epilepsy care, since most patients may be successfully managed with the first or second monotherapy utilized. This article reviews the rationale and evidence supporting preferential use of monotherapy when possible and guidelines for initiating and successfully employing AED monotherapy. Suggested approaches to consider when patients fail monotherapy include substituting a new AED monotherapy, initiating chronic maintenance AED polytherapy, or pursuit of non-pharmacologic treatments such as epilepsy surgery or vagus nerve stimulation. Reducing AED polytherapy to monotherapy frequently reduces the burden of adverse effects and may also improve seizure control. AED monotherapy remains the optimal approach for managing most patients with epilepsy

Useful Field of View Impairment in Partial Epilepsy

Patients with epilepsy are at elevated risk for automobile crashes.Most collisions in drivers with epilepsy are not seizure-related, but may insteadresult from cognitive effects of epilepsy and antiepileptic drugs (AEDs) upondriving performance. The Useful Field of View (UFOV) score has demonstratedgood sensitivity and specificity for predicting automobile crashes. The goal in thispilot study was to assess impairments in the UFOV in subjects with partialepilepsy. Participants included 20 subjects with partial epilepsy. Neurologicallynormal control subjects of comparable age also participated. UFOV was assessedin all participants using the Visual Attention Analyzer, Model 3000 (VisualResources, Inc.). UFOV Task scores were added to calculate a UFOV Total scorefor each subject. UFOV scores were higher on all UFOV tasks in subjects withpartial epilepsy compared to neurologically normal individuals of similar age (p\u3c0.05, Wilcoxon Rank Sum Test), suggesting a greater crash risk in individualswith partial epilepsy, even in the absence of an epileptic seizure. Causes ofimpaired UFOV scores include processing speed reduction, divided and selectiveattention impairments, and mild postoperative visual field deficits. Our ongoingstudies in drivers with epilepsy are aimed at further differentiating potentialeffects of seizures, antiepileptic drugs, and surgical lesions upon cognitiveabilities that are critical to safe automobile driving

Phenoconversion from probable rapid eye movement sleep behavior disorder to mild cognitive impairment to dementia in a population-based sample

© 2017 The Authors Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies

Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea

ObjectiveExcessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA) and has been linked to adverse outcomes, albeit inconsistently. Furthermore, whether the prognostic impact of EDS differs as a function of sex is unclear. We aimed to assess the associations between EDS and chronic diseases and mortality in men and women with OSA.MethodsNewly-diagnosed adult OSA patients who underwent sleep evaluation at Mayo Clinic between November 2009 and April 2017 and completed the Epworth Sleepiness Scale (ESS) for assessment of perceived sleepiness (N = 14,823) were included. Multivariable-adjusted regression models were used to investigate the relationships between sleepiness, with ESS modeled as a binary (ESS > 10) and as a continuous variable, and chronic diseases and all-cause mortality.ResultsIn cross-sectional analysis, ESS > 10 was independently associated with lower risk of hypertension in male OSA patients (odds ratio [OR], 95% confidence interval [CI]: 0.76, 0.69–0.83) and with higher risk of diabetes mellitus in both OSA men (OR, 1.17, 95% CI 1.05–1.31) and women (OR 1.26, 95% CI 1.10–1.45). Sex-specific curvilinear relations between ESS score and depression and cancer were noted. After a median 6.2 (4.5–8.1) years of follow-up, the hazard ratio for all-cause death in OSA women with ESS > 10 compared to those with ESS ≤ 10 was 1.24 (95% CI 1.05–1.47), after adjusting for demographics, sleep characteristics and comorbidities at baseline. In men, sleepiness was not associated with mortality.ConclusionThe implications of EDS for morbidity and mortality risk in OSA are sex-dependent, with hypersomnolence being independently associated with greater vulnerability to premature death only in female patients. Efforts to mitigate mortality risk and restore daytime vigilance in women with OSA should be prioritized