Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks. OBJECTIVE: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial. METHODS: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose. RESULTS: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL. CONCLUSIONS: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Oral Cannabidiol for Seborrheic Dermatitis in Patients With Parkinson Disease: Randomized Clinical Trial.

BACKGROUND: Seborrheic dermatitis (SD) affects 18.6%-59% of persons with Parkinson disease (PD), and recent studies provide evidence that oral cannabidiol (CBD) therapy could reduce sebum production in addition to improving motor and psychiatric symptoms in PD. Therefore, oral CBD could be useful for improving symptoms of both commonly co-occurring conditions. OBJECTIVE: This study investigates whether oral CBD therapy is associated with a decrease in SD severity in PD. METHODS: Facial photographs were collected as a component of a randomized (1:1 CBD vs placebo), parallel, double-blind, placebo-controlled trial assessing the efficacy of a short-term 2.5 mg per kg per day oral sesame solution CBD-rich cannabis extract (formulated to 100 mg/mL CBD and 3.3 mg/mL THC) for reducing motor symptoms in PD. Participants took 1.25 mg per kg per day each morning for 4 ±1 days and then twice daily for 10 ±4 days. Reviewers analyzed the photographs independently and provided a severity ranking based on the Seborrheic Dermatitis Area and Severity Index (SEDASI) scale. Baseline demographic and disease characteristics, as well as posttreatment SEDASI averages and the presence of SD, were analyzed with 2-tailed t tests and Pearson χ2 tests. SEDASI was analyzed with longitudinal regression, and SD was analyzed with generalized estimating equations. RESULTS: A total of 27 participants received a placebo and 26 received CBD for 16 days. SD severity was low in both groups at baseline, and there was no treatment effect. The risk ratio for patients receiving CBD, post versus pre, was 0.69 (95% CI 0.41-1.18; P=.15), compared to 1.20 (95% CI 0.88-1.65; P=.26) for the patients receiving the placebo. The within-group pre-post change was not statistically significant for either group, but they differed from each other (P=.07) because there was an estimated improvement for the CBD group and an estimated worsening for the placebo group. CONCLUSIONS: This study does not provide solid evidence that oral CBD therapy reduces the presence of SD among patients with PD. While this study was sufficiently powered to detect the primary outcome (efficacy of CBD on PD motor symptoms), it was underpowered for the secondary outcomes of detecting changes in the presence and severity of SD. Multiple mechanisms exist through which CBD can exert beneficial effects on SD pathogenesis. Larger studies, including participants with increased disease severity and longer treatment periods, may better elucidate treatment effects and are needed to determine CBD's true efficacy for affecting SD severity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03582137; https://clinicaltrials.gov/ct2/show/NCT03582137.

The Role of Clinical Pharmacists in Patient-Centric Comprehensive Multiple Sclerosis Care.

BACKGROUND: Individuals with multiple sclerosis (MS) may experience a variety of visible and invisible symptoms and, as they age, comorbidities related and unrelated to their MS. This can result in a complex medication regimen that includes disease-modifying therapies, symptom management drugs, and prescriptions for other comorbid disorders. METHODS: We reviewed the existing literature to discover how to optimally integrate neurology clinical pharmacists into the MS care team and how clinical pharmacists can directly support both providers and patients through their expertise in pharmacology and medication management. RESULTS: With approaches founded on a shared decision-making process alongside neurology providers, patients, and care partners, clinical pharmacists can help meet the complex challenges of MS care in a variety of ways. Especially within MS clinics, they are well positioned to enhance current neurology practices given their extensive training in comprehensive medication management and their ability to identify nuances in medication management to promote pharmacovigilance and patient-centered care. CONCLUSIONS: Neurology clinical pharmacists bring multifaceted medication management and patient counseling and education skills to the MS care team and can support the shared decision-making process by serving as an accessible resource for patients and clinicians. By building trusted partnerships between neurology providers and clinical pharmacists, MS care teams can achieve effective and efficient patient care. Future research should compare clinical and patient-reported outcomes between patients receiving standard care and those receiving multidisciplinary, pharmacist-integrated care.

Cognitive Safety Data from a Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase IIb Study of the Effects of a Cannabidiol and Δ9-Tetrahydrocannabinol Drug on Parkinson's Disease-Related Motor Symptoms.

BACKGROUND: Cannabis is increasingly available worldwide but its impact on cognition in Parkinson's disease (PD) is unknown. OBJECTIVE: Present cognitive safety data from study of an oral high-dose cannabidiol (CBD; 100 mg) and low-dose Δ9-tetrahydocannabinol (THC; 3.3 mg) drug in PD. METHODS: Randomized, double-blind, parallel-group, placebo-controlled study of a CBD/THC drug administered for 16.3 (SD: 4.2) days, with dosage escalating to twice per day. Neuropsychological tests were administered at baseline and 1-1½ hours after final dose; scores were analyzed with longitudinal regression models (alpha = 0.05). Cognitive adverse events were collected. RESULTS: When adjusted for age and education, the CBD/THC group (n = 29) performed worse than the placebo group (n = 29) on Animal Verbal Fluency. Adverse cognitive events were reported at least twice as often by the CBD/THC than the placebo group. CONCLUSION: Data suggest this CBD/THC drug has a small detrimental effect on cognition following acute/short-term use in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Would people living with epilepsy benefit from palliative care?

Palliative care (PC) is an approach to the care of persons living with serious illness and their families that focuses on improving quality of life and reducing suffering by addressing complex medical symptoms, psychosocial needs, spiritual well-being, and advance care planning. While PC has traditionally been associated with hospice care for persons with cancer, there is now recognition that PC is relevant to many noncancer diagnoses, including neurologic illness, and at multiple points along the illness journey, not just end of life. Despite the recent growth of the field of neuropalliative care there has been scant attention paid to the relevance of PC principles in epilepsy or the potential for PC approaches to improve outcomes for persons living with epilepsy and their families. We believe this has been a significant oversight and that PC may provide a useful framework for addressing the many sources of suffering facing persons living with epilepsy, for engaging patients and families in challenging conversations, and to focus efforts to improve models of care for this population. In this manuscript we review areas of significant unmet needs where a PC approach may improve patient and family-centered outcomes, including complex symptom management, goals of care, advance care planning, psychosocial support for patient and family and spiritual well-being. When relevant we highlight areas where epilepsy patients may have unique PC needs compared to other patient populations and conclude with suggestions for future research, clinical, and educational efforts.

Continuing Burden of Refractory Epilepsy.

Epilepsy is one of the most common neurological diseases, and uncontrolled seizures remain a significant problem for one-third of patients with epilepsy on drug therapy. Ongoing seizures affect the morbidity and mortality of patients with epilepsy. Premature death is up to 3 times higher in those with epilepsy than in the general population. Quality of life is affected by refractory epilepsy with physical, social, and psychological consequences. Patients may be stigmatized by society, institutions, and their own shame surrounding seizures. Questions remain on how to treat refractory epilepsy, also called drug-resistant, pharmacoresistant, or intractable epilepsy. Cenobamate, a novel antiseizure medication, may provide additional benefit for refractory epilepsy treatment.

Safety and Tolerability of Cannabidiol in Parkinson Disease: An Open Label, Dose-Escalation Study.

Background: Cannabis is increasingly used in Parkinson disease (PD), despite little information regarding benefits and risks. Objectives: To investigate the safety and tolerability of a range of doses of cannabidiol (CBD), a nonintoxicating component of cannabis, and it's effect on common parkinsonian symptoms. Methods: In this open-label study Coloradans with PD, substantial rest tremor, not using cannabis received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL). CBD was titrated from 5 to 20-25 mg/kg/day and maintained for 10-15 days. Results: Fifteen participants enrolled, two were screen failures. All 13 participants (10 male), mean (SD) age 68.15 (6.05), with 6.1 (4.0) years of PD, reported adverse events, including diarrhea (85%), somnolence (69%), fatigue (62%), weight gain (31%), dizziness (23%), abdominal pain (23%), and headache, weight loss, nausea, anorexia, and increased appetite (each 5%). Adverse events were mostly mild; none serious. Elevated liver enzymes, mostly a cholestatic pattern, occurred in five (38.5%) participants on 20-25 mg/kg/day, only one symptomatic. Three (23%) dropped out due to intolerance. Ten (eight male) that completed the study had improvement in total and motor Movement Disorder Society Unified Parkinson Disease Rating Scale scores of 7.70 (9.39, mean decrease 17.8%, p=0.012) and 6.10 (6.64, mean decrease 24.7%, p=0.004), respectively. Nighttime sleep and emotional/behavioral dyscontrol scores also improved significantly. Conclusions: CBD, in the form of Epidiolex, may be efficacious in PD, but the relatively high dose used in this study was associated with liver enzyme elevations. Randomized controlled trials are needed to investigate various forms of cannabis in PD.

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee.

PURPOSE: Established tonic-clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE. METHODS: A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to identify original studies on the treatment of CRSE in children and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-control seizures in special circumstances. Studies were evaluated by predefined criteria and were classified by strength of evidence in stopping clinical CRSE (either as the last ASM added or compared to another ASM) according to the 2017 American Academy of Neurology process. RESULTS: No studies exist on the use of ACTH, corticosteroids, or IVIg for the treatment of CRSE. Small series and case reports exist on the use of these agents in the treatment of RSE of suspected immune etiology, severe epileptic encephalopathies, and rare epilepsy syndromes. For adults with CRSE, insufficient evidence exists on the effectiveness of brivaracetam (level U; 4 class IV studies). For children and adults with CRSE, insufficient evidence exists on the effectiveness of ketamine (level U; 25 class IV studies). For children and adults with CRSE, it is possible that lacosamide is effective at stopping RSE (level C; 2 class III, 14 class IV studies). For children with CRSE, insufficient evidence exists that LEV and VPA are equally effective (level U, 1 class III study). For adults with CRSE, insufficient evidence exists to support the effectiveness of LEV (level U; 2 class IV studies). Magnesium sulfate may be effective in the treatment of eclampsia, but there are only case reports of its use for CRSE. For children with CRSE, insufficient evidence exists to support either that MDZ and diazepam infusions are equally effective (level U; 1 class III study) or that MDZ infusion and PTB are equally effective (level U; 1 class III study). For adults with CRSE, insufficient evidence exists to support either that MDZ infusion and PRO are equally effective (level U; 1 class III study) or that low-dose and high-dose MDZ infusions are equally effective (level U; 1 class III study). For children and adults with CRSE, insufficient evidence exists to support that MDZ is effective as the last drug added (level U; 29 class IV studies). For adults with CRSE, insufficient evidence exists to support that PTB and PRO are equally effective (level U; 1 class III study). For adults and children with CRSE, insufficient evidence exists to support that PTB is effective as the last ASM added (level U; 42 class IV studies). For CRSE, insufficient evidence exists to support that PRO is effective as the last ASM used (level U; 26 class IV studies). No pediatric-only studies exist on the use of PRO for CRSE, and many guidelines do not recommend its use in children aged <16 years. Pyridoxine-dependent and pyridoxine-responsive epilepsies should be considered in children presenting between birth and age 3 years with refractory seizures and no imaging lesion or other acquired cause of seizures. For children with CRSE, insufficient evidence exists that VPA and diazepam infusion are equally effective (level U, 1 class III study). No class I to III studies have been reported in adults treated with VPA for CRSE. In comparison, for children and adults with established convulsive SE (ie, not RSE), after an initial benzodiazepine, it is likely that loading doses of LEV 60 mg/kg, VPA 40 mg/kg, and fosphenytoin 20 mg PE/kg are equally effective at stopping SE (level B, 1 class I study). CONCLUSIONS: Mostly insufficient evidence exists on the efficacy of stopping clinical CRSE using brivaracetam, lacosamide, LEV, valproate, ketamine, MDZ, PTB, and PRO either as the last ASM or compared to others of these drugs. Adrenocorticotropic hormone, IVIg, corticosteroids, magnesium sulfate, and pyridoxine have been used in special situations but have not been studied for CRSE. For the treatment of established convulsive SE (ie, not RSE), LEV, VPA, and fosphenytoin are likely equally effective, but whether this is also true for CRSE is unknown. Triple-masked, randomized controlled trials are needed to compare the effectiveness of parenteral anesthetizing and nonanesthetizing ASMs in the treatment of CRSE.

Surface Detection of THC Attributable to Vaporizer Use in the Indoor Environment.

The number of cannabis users increased up to 188 million users worldwide in 2017. Smoking and vaping are the most common consumption routes with formation of side-stream smoke/vapor and secondhand exposure to cannabinoids has been described in the literature. External contamination of hair by cannabis smoke has been studied but there are no studies on third-hand cannabis exposure due to deposition of smoke or vapor on surfaces. We tested whether cannabinoids could be detected on surfaces and objects in a room where cannabis is vaporized. Surface samples were collected using isopropanol imbued non-woven wipes from hard surfaces and objects. Each surface was swabbed three times with standardized swabbing protocol including three different patterns. Samples were analyzed using LC-ESI-MS/MS in combination with online extraction. THC was detected on 6 samples out of the 15 collected in the study room at quantifiable levels ranging 348-4882 ng/m2. Negative control samples collected from areas outside the study room were all negative. We demonstrated that surfaces exposed to side-stream cannabis vapor are positive for THC at quantifiable levels. This study represents a first step in understanding how side-stream cannabis vapor deposits in the environment and potentially results in a tertiary exposure for users and non-users.

Survey highlights the need to expand offerings of introductory pharmacy practice experiences in psychiatry and neurology: Benefits and example experiences.

INTRODUCTION: Introductory pharmacy practice experiences (IPPEs) are 1 requirement schools and colleges of pharmacy must fulfill to meet accreditation standards. The purpose of this manuscript is to report existing IPPEs in psychiatry and neurology across the United States. METHODS: Two separate electronic surveys were administered to individual College of Psychiatric and Neurologic Pharmacists members with board certification in psychiatric pharmacy with an academic affiliation and academic institutions in the 2014-15 academic year to assess the neuropsychiatric curriculum in pharmacy programs. Results focusing on IPPEs were summarized using descriptive statistics. RESULTS: Academic institutional data reveal only 37.3% offered IPPEs in psychiatry, and 6.7% offered neurology. The number of available IPPEs is low even if a program offered an available rotation. The majority of College of Psychiatric and Neurologic Pharmacists member respondents (69.9%) did not offer IPPEs in psychiatry in the 2014-15 academic year, and none offered an IPPE in neurology. More than half of individual respondents feel their institution should increase IPPEs in psychiatry and neurology in order to enhance their curriculum. DISCUSSION: To expand IPPE availability, pharmacy programs should increase early exposure of pharmacy students to patients with psychiatric and neurologic conditions. Longitudinal experiences may allow students to engage in hands-on experiences, which may impact future career aspirations and reduce stigma. Current example IPPEs at the authors' institutions are included to stimulate discussion and action among readers on how IPPEs in these practice areas may be developed. Implementation of IPPEs in psychiatry and neurology is needed for students to gain experience working with these patients.

Population Pharmacokinetic Evaluation and Missed-Dose Simulations for Eslicarbazepine Acetate Monotherapy in Patients With Partial-Onset Seizures.

Given the potential consequences of antiepileptic therapy nonadherence, missed-dose scenarios of 12- to 48-hour dose delays (4-hour intervals) for eslicarbazepine acetate monotherapy were evaluated using simulated plasma concentrations of a population pharmacokinetic model (representing 493 subjects). When 1600-mg doses were delayed 12 to <16 or 36 to <44 hours, simulations showed immediate administration of 1600 mg followed by the same dose at the scheduled time maintained plasma concentrations within the target concentration range. With 16- to 24- or 44- to 48-hour delays, administration of 2400 mg at the scheduled time followed by resumption of 1600 mg/day maintained plasma concentrations within the target concentration range. For exploratory purposes, the population pharmacokinetic model was refined to predict (n = 6 subjects) and also to allow for simulation of cerebrospinal fluid concentrations. Based on the plasma concentration simulations conducted herein, potential dosing recommendations were developed that suggest a missed ESL dose should be taken when remembered, and the usual dose regimen resumed. If it is remembered within 4 hours of the next dose, 1.5 times the usual dose should be taken immediately, the scheduled dose for that day should be skipped, and the usual regimen resumed the next day.

Curriculum in Psychiatry and Neurology for Pharmacy Programs.

Objective. To describe pharmacy curricula in psychiatry and neurology and to report on neuropsychiatric pharmacy specialists' views on optimal curriculum. Methods. Design and administer one electronic survey to accredited pharmacy programs asking them to report information on curricula in psychiatry and neurology for the 2014-2015 academic year. Design and administer a separate electronic survey to board certified pharmacists with an academic affiliation who are members of the College of Psychiatric and Neurologic Pharmacists (CPNP) asking about their teaching activities and their opinion on optimal curricula. Results. Fifty-six percent of pharmacy programs and 65% of CPNP members responded to the surveys. The program survey revealed greater than 80% of topics were taught by full-time faculty. Didactic lecturing, team-based learning, and case studies were the most common teaching methods. Programs dedicated the most didactics (3 to 5+ hours) to epilepsy, depression, schizophrenia, substance use disorders, and pain. Autism, traumatic brain injury, personality, and eating disorders were either not taught or given ≤ 1 hour of didactics in most programs. Inpatient psychiatry had the most APPE placements with a mean of 19.6, range 0-83. APPE electives in psychiatry outnumbered those in neurology 5 to 1. CPNP member survey results showed 2 out of 3 members agreed that curriculum could be improved with additional APPEs in psychiatry and neurology. Conclusion. Didactic hour distribution in psychiatry and neurology could be improved to better align with board certification in psychiatric pharmacy (BCPP) recommendations and disorder prevalence and complexity. Specialists recommend an experiential component in neurology and psychiatry to combat stigma and improve pharmacist knowledge and skills.

Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores.

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p < 0.0001), were more likely to be male (75.3% vs 57.0%; p < 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p < 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865.

Autonomic and electrocardiographic findings in Parkinson's disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P<0.05) between QTcB and PD severity in individuals that were taking QT-interval affecting drugs. A longer QT-interval at baseline was associated with more advanced PD at 5years (P<0.05), and greater disease progression over 5years (P<0.05). There was an association between diminished HRV and an orthostatic decrease in standing blood pressure at baseline in individuals with PD (P<0.05). HRV was not associated with PD severity or progression. In conclusion, we were able to detect measurable associations between the QTcB interval and PD severity, PD severity 5years later, and the change in disease over time. However, routine ECG tracings appear inadequate for the evaluation of autonomic function in PD.

Caffeine, creatine, GRIN2A and Parkinson's disease progression.

Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD.

A Framework of Care in Multiple Sclerosis, Part 2: Symptomatic Care and Beyond.

The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS.

Safety and tolerability of lacosamide monotherapy in the elderly: A subgroup analysis from lacosamide trials in diabetic neuropathic pain.

Objective: To assess the safety profile of lacosamide monotherapy in elderly (≥65 years) subjects with diabetic neuropathic pain (DNP). Methods: Of 1,863 DNP subjects in double-blind, randomized, placebo-controlled trials of lacosamide monotherapy (NCT00861445, NCT00235469, NCT00238524, NCT00135109, NCT00350103), 502 were elderly. Safety data from elderly subjects were compared with that of younger subjects (<65 years) within these DNP trials. It should be noted that lacosamide is approved for the treatment of focal (partial-onset) seizures; it is not approved/recommended for the treatment of DNP. Results: Overall, cardiovascular diseases were prevalent in the DNP population, as was the use of cardiac, blood pressure, diabetes, and cholesterol-lowering medications among both young and elderly subjects. The most frequently reported adverse events (AEs) for lacosamide monotherapy (200, 400, and 600 mg/day combined) in elderly versus younger subjects were dizziness (16.2% vs. 13.2%), nausea (10.0% vs. 9.4%), and headache (8.0% vs. 8.7%). Incidences of cardiac disorder AEs were higher in elderly versus younger subjects receiving placebo (6.2% vs. 3.9%), lacosamide 200 (4.8% vs. 3.3%), lacosamide 400 (7.0% vs. 4.1%), and lacosamide 600 mg/day (7.7% vs. 4.0%). Discontinuation rates because of any AE in the elderly versus younger subjects were similar for placebo (8.8% vs. 7.0%) and lacosamide 200 mg/day (9.6% vs. 11.9%) and higher for lacosamide 400 (25.1% vs. 10.8%) and lacosamide 600 mg/day (52.7% vs. 28.3%). Significance: Lacosamide monotherapy was well tolerated in elderly subjects with DNP, with an overall AE profile consistent with that reported in epilepsy trials.

CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances.

Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. TARGET AUDIENCE: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS). LEARNING OBJECTIVES: Apply new information about MS to a comprehensive individualized treatment plan for patients with MSIntegrate the team approach into long-term planning in order to optimize rehabilitation care of patients with MSAccreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Consortium of Multiple Sclerosis Centers (CMSC), Nurse Practitioner Alternatives (NPA), and Delaware Media Group. The CMSC is accredited by the ACCME to provide continuing medical education for physicians. The CMSC designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Practitioner Alternatives (NPA) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NPA designates this enduring material for 1.0 Continuing Nursing Education credit. Laurie Scudder, DNP, NP, has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. Disclosures: Francois Bethoux, MD, Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has received royalties from Springer Publishing and has received intellectual property rights from Biogen. Laurie Scudder, DNP, NP, has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. Scott D. Newsome, DO, MSCS (author), has served on scientific advisory boards for Biogen, Genentech, Novartis, and Genzyme, and has performed contracted research (institution received funds) for Biogen, Genentech, and Novartis. Philip J. Aliotta, MD, MSHA, CHCQM, FACS (author), has served on speakers' bureaus for Astellas Pharma, Actavis, Augmenix, and Allergan and has performed contracted research for Allergan. Jacquelyn Bainbridge, PharmD (author), has disclosed no relevant financial relationships. Susan E. Bennett, PT, DPT, EdD, NCS, MSCS (author), has served on speakers' bureaus for Acorda Therapeutics, Biogen, and Medtronic; has received consulting fees from and performed contracted research for Acorda Therapeutics; and is chair of the Clinical Events Committee at Innovative Technologies. Gary Cutter, PhD (author), has participated on Data and Safety Monitoring Committees for AMO Pharma, Apotek, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Modigenetech/Prolor, Merck, Merck/Pfizer, Opko Biologics, Neuren, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), and NICHD (OPRU Oversight Committee); has received consulting fees from and/or served on speakers' bureaus and scientific advisory boards for Cerespir, Genzyme, Genentech, Innate Therapeutics, Janssen Pharmaceuticals, Klein-Buendel Incorporated, MedImmune, Medday, Nivalis, Novartis, Opexa Therapeutics, Roche, Savara, Somahlution, Teva Pharmaceuticals, Transparency Life Sciences, and TG Therapeutics; and is President of Pythagoras, Inc., a private consulting company located in Birmingham, AL. Kaylan Fenton, CRNP, APNP, MSCN (author), has disclosed no relevant financial relationships. Fred Lublin, MD (author), has received consulting fees/fees for non-CME/CE activities from Bayer HealthCare Pharmaceuticals, Biogen, EMD Serono, Novartis, Teva Neuroscience, Actelion, Sanofi/Genzyme, Acorda, Questcor/Mallinckrodt, Roche/Genentech, MedImmune, Osmotica, Xenoport, Receptos/Celgene, Forward Pharma, Akros, TG Therapeutics, AbbVie, Toyama, Amgen, Medday, Atara Biotherapeutics, Polypharma, Pfizer, Johnson & Johnson, Revalesio, Coronado Bioscience, and Bristol-Myers Squibb; has served on speakers' bureaus for Genentech/Roche and Genzyme/Sanofi; has performed contracted research for Acorda, Biogen, Novartis, Teva Neuroscience, Genzyme, Xenoport, and Receptos; is the co-chief editor of Multiple Sclerosis and Related Disorders; and has an ownership interest in Cognition Pharmaceuticals. Dorothy Northrop, MSW, ACSW (author), has disclosed no relevant financial relationships. David Rintell, EdD (author), has received consulting fees from Novartis and has served as a patient education speaker for Teva Neuroscience. He started as a salaried employee of Sanofi Genzyme in November 2015. Dr. Rintell's work on this project was completed before he became a salaried employee of Sanofi Genzyme.Bryan D. Walker, MHS, PA-C (author), has served on scientific advisory boards for EMD Serono and Sanofi Genzyme and owns stock in Biogen. Megan Weigel, DNP, ARNP-C, MSCN (author), has received consulting fees from Mallinckrodt, Genzyme, and Genentech, and has served on speakers' bureaus for Bayer Corp, Acorda Therapeutics, Teva Neuroscience, Biogen, Mallinckrodt, Genzyme, Novartis, and Pfizer. Kathleen Zackowski, PhD, OTR, MSCS (author), has performed contracted research for Acorda Therapeutics. David E. Jones, MD (author), has received consulting fees from Biogen and Novartis, and has performed contracted research for Biogen. One anonymous peer reviewer for the IJMSC has performed contracted research (institution received funds) for Novartis, Chugai, and Biogen. Another reviewer has received consulting fees and served on speakers' bureaus for Biogen, Sanofi Genzyme, Genentech, EMD Serono, and Novartis. The third reviewer has disclosed no relevant financial relationships. Lori Saslow, MS (medical writer), has disclosed no relevant financial relationships. The staff at the IJMSC, CMSC, NPA, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Disclosures listed for authors are those applicable at the time of their work on this project and within 12 months previously. Financial relationships for some authors may have changed in the interval between the time of their work on this project and publication of the article. Funding/Support: Funding for the Framework of Care consensus conference was provided by the Consortium of Multiple Sclerosis Centers, Mallinckrodt Pharmaceuticals, and Mylan Pharmaceuticals. Method of Participation: Release Date: December 1, 2016 Valid for Credit Through: December 1, 2017 In order to receive CME/CNE credit, participants must: Review the CME/CNE information, including learning objectives and author disclosures.Study the educational content.Complete the post-test and evaluation, which are available at http://www.cmscscholar.org. Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This CME/CNE activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC, NPA, and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC, NPA, or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

Epilepsy during pregnancy: focus on management strategies.

In the US, more than one million women with epilepsy are of childbearing age and have over 20,000 babies each year. Patients with epilepsy who become pregnant are at risk of complications, including changes in seizure frequency, maternal morbidity and mortality, and congenital anomalies due to antiepileptic drug exposure. Appropriate management of epilepsy during pregnancy may involve frequent monitoring of antiepileptic drug serum concentrations, potential preconception switching of antiepileptic medications, making dose adjustments, minimizing peak drug concentration with more frequent dosing, and avoiding potentially teratogenic medications. Ideally, preconception planning will be done to minimize risks to both the mother and fetus during pregnancy. It is important to recognize benefits and risks of current and emerging therapies, especially with revised pregnancy labeling in prescription drug product information. This review will outline risks for epilepsy during pregnancy, review various recommendations from leading organizations, and provide an evidence-based approach for managing patients with epilepsy before, during, and after pregnancy.