Neuro News Roundup : Brain Awareness Week

In recent months, the NeurologyLive® team has been covering the news on the latest updates in the clinical care of individuals with neuromuscular disorders, multiple sclerosis, movement disorders, sleep disorders, and more.

For Brain Awareness Week — March 13, 2023, to March 19, 2023 —the team has culminated some of the biggest pieces of news to offer updates on new developments in literature in neurology to spread awareness on the prevention and treatment of neurological conditions.

Click here for more coverage of the latest news from NeurologyLive®.

Latest Literature

Narcolepsy Causes Significant Impact on Social Relationship Health in Adolescents, Study Shows

In an exploratory study recently published in the Journal of Clinical Sleep Medicine, findings revealed an overarching theme that adolescents and their parents experience difficulty in trying to balance narcolepsy symptom management with meaningful social engagement.¹ In the study, symptoms of daytime fatigue and cataplexy were the most significant and commonly discussed among adolescents and their parents as having an impact on social relationships.

Notably, adolescents reported feeling frustrated by their sleep disorder impacting their social lives such as constantly needing to plan ahead with their sleep schedule. Additionally, both adolescents and their parents expressed the need for medical providers to better understand their changing priorities, validate social limitations, and offer more information around the social implications of condition and treatment.

Adolescents between the ages of 12 and 17 years old with narcolepsy and their parents completed a semistructured interview individually between July 2021 and December 2021. Participants were included if they had a confirmed diagnosis of narcolepsy type 1 (n = 12, 85.7%) or type 2 (n = 2, 14.3%) using polysomnography/Multiple Sleep Latency Test or other testing and were fluent in English. Data records were extracted, based on their narcolepsy medication plan and Epworth Sleepiness Scale score 3 months before the interview date, from Boston Children’s Hospital. Of note, 3 patients had a medical record from outside the hospital. Interview transcripts were analyzed using a multistage thematic analysis.

Health-Related Quality of Life Improvements Seen in Myasthenia Gravis With Efgartigimod

Recently reported ancillary data from the phase 3 ADAPT study (NCT03669588) showed that treatment with efgartigimod (Vyvgart; Argenx) had a significant impact on health-related quality of life (HRQoL) in patients with myasthenia gravis, with positive effects seen as early as the first week of treatment in both cycles.²

Of the 167 patients enrolled, 129 (77.2%) were anti-acetylcholine receptor (AChR) antibody positive. Participants were randomly assigned 1:1 to either efgartigimod or placebo for a 28-week treatment period, consisting of up to 3, 8-week treatment cycles (TCs). Between TCs was an intertreatment cycle (ITC) of at least 5 weeks, the duration of which was based on each patient’s loss of treatment effect response, indicated by predefined change in Myasthenia Gravis Activities of Daily Living (MG-ADL).

Published in the Journal of Neurology, the analysis included data from the first 2 TCs. Lead investigator Francesco Sacca, assistant professor of neurology, University Federico II Naples, and colleagues included patients with an MG-ADL score of at least 5 points, and were on at least 1 stable dose of gMG treatment prior to screening and throughout the study. HRQoL measures used included the Myasthenia Gravis-Quality of Life 15-item revised (MG-QoL15r), an MG-specific measure, the EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L), and visual analog scale (VAS), a more generic measure used across disease states.

P-Tau217 Continues to Show Benefit as Predictor of Cognitive Decline in Preclinical Alzheimer Disease

A recently published prospective population-based prognostic study evaluating combinations of different plasma biomarkers showed that phosphorylated tau 217 (P-tau217) was the best marker to predict cognitive decline in patients with preclinical Alzheimer disease (AD).³ Investigators concluded that plasma P-tau217 may be used as a complement to cerebrospinal fluid (CSF) or PET for participation selection in clinical trials of novel disease-modifying therapies.

Investigators evaluated data from 2 prospective longitudinal cohort studies: the Swedish BioFINDER-1 and the Wisconsin Registry for Alzheimer Prevention (WRAP). A total of 171 amyloid-ß-positive, cognitively unimpaired participants were included in the main analyses, with biomarkers such as P-tau181, P-tau217, P-tau231, glial fibrillary filament protein, and neurofilament light measured in plasma. Additional CSF biomarkers in the BioFINDER-1 cohort and PiB PET uptake in the WRAP cohort were also evaluated.

The Mini-Mental State Examination (MMSE) and modified Preclinical Alzheimer Cognitive Composite (mPACC) over a median of 6 years made up the primary outcome of the study, with conversion to AD dementia as a secondary end point. Models were adjusted for age, sex, years of education, apolipoprotein ε4 allele status, and baseline cognition. In the BioFINDER-1 cohort, after adjustment, plasma P-tau217 was found to be the strongest biomarker to predict cognitive decline in both the mPACC (R² = 0.41 vs 0.23 for the covariates-only model; P <.001) and the MMSE (R² = 0.34 vs 0.04 for the covariates-only model; P <.001), yielding significantly improved model fits. Additionally, P-Tau217 was the strongest CSF biomarker to predict cognitive decline for both tests (mPACC: R² = 0.37; P <.001; MMSE: R² = 0.24; P <.001).

Cognitive and Functional Differences Identified in Parkinson Disease Prior to Diagnosis

Using prospective cohort studies of community-dwelling elders followed up to 20 years, findings published in Neurology identified specific cognitive and functional declines in patients who developed incident Parkinson disease (PD).⁴ There were important sex differences as well, as men with incident PD had a steeper decline in executive function compared with women, but only women with incident PD exhibited detectably faster prediagnostic decline in global cognition.

The analysis included 9595 women from the Study of Osteoporotic Fractures (SOF) and 5795 men from the Osteoporotic Fractures in Men Study (MrOS). SOF enrolled women aged 65 and over between 1986 and 1988 from 4 sites in the US while MrOS enrolled men aged 65 and older from 2000 to 2002 from 6 sites in the US. Participants underwent 8 evaluations over 20 years of follow-up in SOF, and 12 evaluations over 17 years in MrOS.

A modified version of the Mini-Mental Status Exam (mMMSE) that scores patients 0-26 based on responses, as well as the Trails B, were used to assess cognition in SOF. For MrOS participants, a modified MMSE (3MS) assessed cognition, with scores ranging from 0 (worst cognition) to 100 (best cognition). Trails B was also administered at these time points. In both studies, eligible participants completed an interviewer administered questionnaire on 3 instrumental activities of daily living, and 2 measures of physical function.

Mixed Long-, Short-Term Benefits in Cognitively Impaired MS Seen Through Cognitive Rehabilitation, Mindfulness-Based Therapy

Findings from a randomized controlled trial of patients with multiple sclerosis (MS) presenting with cognitive complaints showed that use of both cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) alleviates cognitive issues in a short-term period; however these benefits did not persist long-term. In the long term, CRT demonstrated benefits on personalized cognitive goals and MBCT on processing speed.⁵

The REMIND-MS study randomly assigned adults with MS, aged 18 to 65 years, to either CRT (n = 37), MBCT (n = 36), or enhanced treatment as usual (ETAU), with measurements performed at baseline, post-treatment, and 6-month follow-up. CRT and MBCT consisted of 9 weekly group-based sessions of 2.5 hrs, except for 1 MBCT session that lasted 5 hrs. Participants received homework assignments during CRT and guided mindfulness meditation exercises during MBC, which both took 30-45 min, 6 days a week. ETAU consisted of 1 individual appointment with an MS specialist nurse that focused on psycho-education.

Investigators used the level of patient-reported cognitive complaints measured with the previously validated Cognitive Failures Questionnaire (CFQ) as the primary outcome. Patient-reported cognitive complaints in terms of executive functioning were measured with the patient- and informant-version of the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A). Secondary outcomes included personalized cognitive goals using Goal Attainment Scaling (GAS) and objective cognitive function using the Minimal Assessment of Cognitive Function in MS (MACFIMS).

REFERENCES
1. Zhou ES, Revette A, Heckler GK, Worhach J, Maski K, Owens JA. Building a deeper understanding of social relationship health in adolescents with narcolepsy disorder. J Clin Sleep Med. 2023;19(3):491-498. doi:10.5664/jcsm.10372
2. Sacca F, Barnett C, Vu T, et al. Efgartigimod improved health-related quality of life in generalized myasthenia gravis: results from a randomized, double-blind, placebo-controlled, phase 3 study (ADAPT). Journal of Neurol. Published online January 4, 2023. doi:10.1007/s00415-022-11517.
3. Mattsson-Carlgren N, Salvado G, Ashton NJ, et al. Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers. JAMA Neurol. Published online February 6, 2023. doi:10.1001/jamaneurol.2022.5272.
4. Bock MA, Vittinghoff E, Bahorik AL, Leng Y, Fink H, Yaffe K. Cognitive and functional trajectories in older adults with prediagnostic Parkinson disease. Neurology. Published online December 29, 2022. doi:10.1212/WNL.000000000000206762
5. Nauta IM, Bertens D, Fasotti L, et al. Cognitive rehabilitation and mindfulness reduce cognitive complaints in multiple sclerosis (REMIND-MS): a randomized controlled trial. Mult Scler & Relat Disord. 2023;71:104529. doi:10.1016/j.msard.2023.104529