Older adults with multiple sclerosis (MS) face unique issues related to the combined effects of MS and age-related changes, which often present with overlapping symptoms that complicate assessment and treatment decisions. In this review, based on the Consortium of MS Centers’ Aging and MS Consensus Statement committee meeting in 2024, we address the contributions of aging in MS by focusing on direct, biological aging effects on MS pathology and comorbid age-related changes in physical and cognitive function. Features of biological aging include cellular senescence and immune dysregulation, which may drive disease progression in MS through a variety of proinflammatory mediators that may maintain low levels of chronic inflammation in the immune and central nervous system compartments and offset regulatory processes, ultimately impairing remyelination and increasing neurodegeneration. Measuring biological aging in MS may help identify individuals at risk of worse MS outcomes and support gerotherapeutic treatments that target aging mechanisms. Compounding any direct effects of aging on MS pathology, aging-related impairments in neuromuscular function and cognition can worsen functional outcomes in people with MS. Characteristics of cognitive impairments in MS affecting attention and processing speed occur early in the disease course and are distinct from other age-associated neurodegenerative disorders, such as Alzheimer disease, that commonly affect language and executive function domains. As MS clinicians care for growing numbers of older adults with MS, a more comprehensive understanding of the interplay between aging and MS-related changes can improve the timing and modality of treatments to optimize MS neurogeriatric care.

Worldwide, the average age of people with multiple sclerosis (MS) has increased significantly over the past several decades. Findings from natural history studies reveal that the risk of new relapse and MRI activity diminishes with age. Available since 1993, the use of disease-modifying therapies (DMTs) for MS has expanded dramatically, with many patients using the drugs indefinitely. The participants of most phase 3 clinical trials that have resulted in regulatory approval of MS DMTs have been 55 years or younger at the onset of participation, so there remains a dearth of data as to the benefits and risks of DMT use in older people with MS. Risks associated with DMT use may increase as people age, especially vascular and malignancy comorbidities. Although some people with MS older than 55 years have discontinued DMT, some are reluctant to even consider a trial off DMT. Findings from many observational DMT discontinuation studies and 2 discontinuation randomized controlled trials have confirmed that the greatest risk of recurrent MS disease activity is in younger patients who discontinue DMT. For clinically stable people older than 60 years, the greatest enhanced risk faced by those who discontinue DMT is that of 1 to 2 brain MRI-detected lesions of unclear long-term clinical significance. Thus, although it may be reasonable to consider a personal DMT discontinuation or de-escalation trial, patients, their families, and MS clinicians would benefit from a substantial increase in clinical studies relevant to the risks and benefits of DMT use and nonuse in those older than 55 years.

As age increases, the prevalence of comorbidities increases in the general population. In turn, this often leads to an increase in the number of medications administered. This phenomenon creates additional challenges in the management of neurodegenerative disorders such as multiple sclerosis (MS). Higher comorbidity burden is associated with longer diagnostic delays and greater disability at diagnosis. A higher burden of comorbidities in people with MS is associated with higher disability levels and accelerated disability progression. Responses to rehabilitation therapy may also be altered in terms of timing and sustainability of response. Conversely, a diagnosis of MS negatively affects the management and outcomes of some comorbidities, and treatment of certain comorbidities can worsen MS symptoms. Thus, comorbid conditions in people with MS have important implications with respect to MS-specific care and general health care throughout the life course of the disease. Comorbidities must be considered when developing plans of care. Similarly, polypharmacy is common in non-MS populations, even more so in MS populations, and can adversely affect quality of life and worsen underlying disability. In 2023, the Consortium of Multiple Sclerosis Centers needs assessment identified comorbidity and polypharmacy as a core topic relevant to the care of aging adults with MS, and an in-person meeting of experts in 2024 discussed the existing literature. This narrative review discusses how comorbid disease and polypharmacy affect people with MS, strategies to mitigate these negative risks, as well as areas where evidence is lacking and further study is needed to inform optimal treatment strategies for older adults with MS.

Cannabis use is increasing and is of particular interest to patients with cancer. There is no prospective data regarding its impact on perioperative outcomes. We asked how chronic usage of cannabis compounds (cannabinoids) impacted postoperative pain, opiate use, and complications after abdominal surgery for the treatment of cancer. This was a single center prospective observational cohort study conducted from 9/2021–3/2024 of patients 21+ years old, undergoing abdominal surgery for the treatment of cancer, and either chronic cannabinoid users (≥1x/week for last 3 months) or non-users (for the last year). Plasma cannabinoids were measured preoperatively on the day of surgery. Of 223 patients screened, 64 subjects completed enrollment (24 chronic cannabinoid users, 40 non-users). Most were male (67

BackgroundCannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks.ObjectiveThe aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Delta-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial.MethodsPersons 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.ResultsParticipants 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.ConclusionsThe 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. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

ABSTRACT 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.

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicine begins to play a larger role in determining targeted treatments for specific types of epilepsy, a complete understanding of various medications is needed. Additionally, access to several of these medications can be limited in the United States and are especially limited globally. All these factors can make proper selection of ASM challenging and difficult for clinicians. This review highlights important aspects of older and newer medications, developments in precision medicine for epilepsy, increasing understanding of effective treatments for status epileptics, and a global perspective on ASM availability.

BackgroundSeborrheic 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. ObjectiveThis study investigates whether oral CBD therapy is associated with a decrease in SD severity in PD. MethodsFacial 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. ResultsA 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. ConclusionsThis 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 RegistrationClinicalTrials.gov NCT03582137; https://clinicaltrials.gov/ct2/show/NCT03582137

Cannabis is increasingly available worldwide but its impact on cognition in Parkinson's disease (PD) is unknown.

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.

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.

•Palliative care improves quality of life for persons living with serious illness.•Palliative care provides a framework for supporting people with epilepsy.•Palliative care supports both patients and family caregivers.•Research is needed to meet the unique palliative care needs of epilepsy.

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.

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.

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.