BACKGROUND AND OBJECTIVE: Approximately half of children with epilepsy continue to have seizures as adults thus requiring transition from pediatric to adult epilepsy care. We developed an adult-based epilepsy transition...BACKGROUND AND OBJECTIVE: Approximately half of children with epilepsy continue to have seizures as adults thus requiring transition from pediatric to adult epilepsy care. We developed an adult-based epilepsy transition program (ETP) in an academic institution in the US to meet these patients' needs. METHODS: We retrospectively analyzed our ETP, which operated from July 2022 to July 2025, examining its programmatic successes and challenges across development, implementation, and evolution. We also reviewed all patients whose initial ETP visit occurred between July 1, 2022, and January 1, 2025, collecting healthcare delivery metrics and patient-level clinical data including demographics, clinical characteristics, insurance profiles, referral sources, visit logistics, and clinical recommendations from the first ETP encounter. RESULTS: A total of 135 patients were included (median 21 years). Roughly a third of patients had drug-resistant epilepsy, almost half were on two or more antiseizure medications, and more than half had at least one neuropsychiatric comorbidity. The first ETP clinic visits had a median billable time of 90 min (range 40-150), and 41% had trainee participation. Following the initial encounter, brain MRI was ordered for 43% of patients, routine EEG for 38%, epilepsy monitoring unit evaluation for 20%, and genetic testing for 34%. Referral to specialty services were made for 16% of patients. DISCUSSION: Our study highlights challenges and successes of implementing an adult-based ETP in the US. Challenges included resource and infrastructure limitations, healthcare system structural barriers, and care coordination obstacles. Successes included clinical opportunities for care reassessment with revenue potential, patient-centered transition approach, and educational opportunities for neurology trainees.
PURPOSE: To evaluate long-term structural, cognitive, functional, and seizure outcomes among survivors of cryptogenic new-onset refractory status epilepticus (C-NORSE) according to the timing of intravenous cyclophospham...PURPOSE: To evaluate long-term structural, cognitive, functional, and seizure outcomes among survivors of cryptogenic new-onset refractory status epilepticus (C-NORSE) according to the timing of intravenous cyclophosphamide (IVCPA) initiation. METHODS: We examined seven consecutive patients with C-NORSE treated between 2012 and 2025. Of those, super-refractory status epilepticus (SRSE, n = 5) cases were stratified into SRSE-Early IVCPA (IVCPA initiated within 20 days after seizure onset) and SRSE-Late/No IVCPA (IVCPA initiated >20 days after onset or not administered); the refractory status epilepticus (RSE) group served as a reference. 4 of the 5 SRSE patients received IVCPA (3 cases were classified as early and 1 case as late). We assessed whole-brain volume change quantified on serial MRI, neurocognition by standardized tests, functional outcomes by mRS, and seizure outcomes during the acute phase, at discharge, and in the chronic phase (≥1 year) among groups. RESULTS: The median follow-up was 5 years (range, 2-11 years). Whole-brain volume loss remained <10% in the RSE and SRSE-Early IVCPA groups, whereas marked medial temporal and diffuse brain atrophy developed in the two cases in the SRSE-Late/No IVCPA group, with whole-brain volume losses of 18.2% and 16.0%. Neurocognitive trajectories improved gradually in SRSE-Early IVCPA and showed severe chronic impairment in SRSE-Late/No IVCPA. Functional outcomes were excellent in SRSE-Early IVCPA and RSE but were poorer in SRSE-Late/No IVCPA. All patients developed drug-resistant epilepsy. CONCLUSIONS: In this case series, earlier IVCPA initiation in patients with SRSE due to C-NORSE was potentially associated with less chronic brain atrophy and more favorable neurocognitive and functional trajectories. Future studies are warranted to determine whether early seizure control plus immunotherapy reduces the risk of chronic drug-resistant epilepsy and improves long-term cognition.
BACKGROUND: Comorbidities may exacerbate disease burden in people with Multiple Sclerosis (pwMS), yet their influence on disease progression and patient-reported outcomes (PROs) remains poorly understood. Understanding h...BACKGROUND: Comorbidities may exacerbate disease burden in people with Multiple Sclerosis (pwMS), yet their influence on disease progression and patient-reported outcomes (PROs) remains poorly understood. Understanding how comorbidities relate to progression and PROs can inform personalised care. OBJECTIVES: Identify comorbidity profiles in pwMS and assess their impact on MS type progression and PROs. METHODS: This observational study analysed UK MS Register data from 2011 to 2025. Hierarchical clustering was based on cardiovascular and mental health comorbidities. Logistic and linear regression examined associations between clusters, comorbidities, progression and PROs. RESULTS: Cluster analysis in 5944 pwMS identified 3 clusters: 1 (no comorbidities, n = 4278), 2 (100% cardiovascular, 5% mental health, n = 910), and 3 (98% mental health, 24% cardiovascular, n = 756). Amongst participants with relapsing-remitting MS at baseline (n = 4942), compared to cluster 1, cluster 2 showed no difference in odds (OR 1.15, 95%CI: 0.93-1.43) whilst cluster 3 greater odds (OR 1.90, 95%CI: 1.53-2.35) of progressing to secondary-progressive MS, after adjusting for age, gender, and time since diagnosis. Depression showed the strongest association with progression. Comorbidities were associated with worse PROs, with anxiety and depression linked to lower psychological and physical symptoms. CONCLUSIONS: Mental health conditions clustered with cardiovascular multimorbidity consistently associated with poorer MS progression and prognosis, emphasising the need for integrated mental health management in pwMS.
BACKGROUND: PPA-variant attribution of the clinically overt word-deafness phenotype remains incompletely characterized. Word deafness has been described across PPA phenotypes, but published reports often emphasize nonflu...BACKGROUND: PPA-variant attribution of the clinically overt word-deafness phenotype remains incompletely characterized. Word deafness has been described across PPA phenotypes, but published reports often emphasize nonfluent/agrammatic variant PPA (naPPA); group-level auditory studies have not addressed clinically recognized presentations dominated by difficulty understanding speech. We aimed to identify patients meeting prespecified criteria for this phenotype and describe their adjudicated PPA-variant diagnoses. METHODS: We retrospectively screened 109 patients with PPA from six centers (2012-2025) using a three-step algorithm: (1) symptom-driven screening (listening difficulty, frequent requests for repetition, auditory-written dissociation on the Japanese Western Aphasia Battery); (2) exclusion of severe peripheral hearing loss by pure-tone audiometry; and (3) audiological corroboration of disproportionate speech-perception impairment on speech audiometry. RESULTS: Eight patients screened positive; two were excluded for severe peripheral hearing loss, and the remaining six fulfilled criteria, all adjudicated as logopenic variant PPA (lvPPA). Listening difficulty emerged early and prompted otolaryngologic evaluation in five patients. Despite normal-to-mildly elevated pure-tone thresholds, speech audiometry showed markedly reduced discrimination scores in all cases. Auditory brainstem responses were preserved when tested; the Two-Burst Fusion Test was abnormal in one tested patient. Neuroimaging showed temporoparietal-predominant involvement compatible with lvPPA. CONCLUSIONS: Word deafness may occur across PPA phenotypes. In this symptom-driven series, all clinically recognized, audiologically corroborated cases were lvPPA, though the design does not permit prevalence estimates across variants. Clinicians should consider this phenotype across PPA variants, rather than assuming naPPA alone, when patients present with disproportionate difficulty understanding speech despite preserved pure-tone hearing.
BACKGROUND: Observational studies suggest that alterations in circulating lipid levels may be associated with multiple sclerosis (MS) susceptibility and severity. OBJECTIVES: Our study employs two-sample Mendelian random...BACKGROUND: Observational studies suggest that alterations in circulating lipid levels may be associated with multiple sclerosis (MS) susceptibility and severity. OBJECTIVES: Our study employs two-sample Mendelian randomisation (MR) to investigate whether these relationships are causal. METHODS: Genetic instruments for 249 metabolites, predominantly lipids and lipoproteins, were obtained from a combined dataset of European-ancestry individuals from the UK and Estonian Biobanks. Outcome data were obtained from the International MS Genetics Consortium GWAS studies of MS susceptibility and severity. MR analyses used the inverse variance-weighted multiplicative random-effects method in the main analysis. RESULTS: No metabolic exposures demonstrated statistically significant evidence of a causal relationship with MS susceptibility. For MS severity, two traits showed suggestive associations - triglycerides in very-low-density lipoproteins (VLDL) (β = -0.101, p = 3.9x10) and triglycerides in chylomicrons and extremely large VLDL (β = -0.104, p = 1.2x10). The MR-Egger intercept suggested horizontal pleiotropy. Sensitivity analysis with multivariable MR using Body Mass Index as a possible confounder demonstrated substantial attenuation of instrument strength. CONCLUSIONS: We found no convincing evidence that circulating lipids or lipid-related metabolites exert a causal influence on susceptibility to, or severity of, multiple sclerosis. The nominally statistically significant result is likely a result of horizontal pleiotropy.
Fatigue is one of the most disabling non-motor symptoms in Parkinson's disease (PD). Evidence suggests that it may be underpinned by altered central fatigability mechanisms and deficits in attentional control. This study...Fatigue is one of the most disabling non-motor symptoms in Parkinson's disease (PD). Evidence suggests that it may be underpinned by altered central fatigability mechanisms and deficits in attentional control. This study investigated the relationships among subjective fatigue, executive-attentional dysfunction, and central fatigability in PD. Twenty-seven PD patients and 21 age- and education-matched healthy controls underwent a multidimensional assessment including subjective fatigue (16-item Parkinson Fatigue Scale; PFS), perceived cognitive difficulties (Perceived Cognitive Difficulties Scale; PCDS), executive functioning (Frontal Assessment Battery; FAB), and sustained attention measured through a computerized reaction time task (Sustained Attention Task; SAT). Central fatigability was assessed using transcranial magnetic stimulation (TMS), measuring post-exercise depression (PED) of cortical excitability via changes in resting motor threshold (RMT), motor evoked potential (MEP) amplitude, and cortical silent period (CSP) duration before (PRE) and after (POST) a fatiguing pinching task. PD patients reported higher fatigue, more cognitive complaints, lower FAB scores, and longer SAT latencies. PED was impaired in PD, with lower PRE/POST % of change of RMT, MEP amplitude, and CSP as compared to HCs. PFS correlated with PCDS (r = 0.513), FAB (r = -0.410), SAT latency (r = 0.519), PRE/POST % of change of CSP (r = -0.497). All p < 0.01. SAT latency, PRE/POST % change of MEP, PRE/POST % of change of CSP independently predicted fatigue. These results indicate that fatigue in PD may arise from disrupted inhibitory PED mechanisms and reduced attentional efficiency, converging toward the hypothesis that GABAergic dysfunction could impair cortical adaptability to effort.