BMJ Neurology Open最新文献

Background: The pathophysiological mechanism underlying functional tremor (FT) has not been elucidated. Transcranial magnetic stimulation (TMS) is a non-invasive tool to explore cortical excitability in various neurological and neuropsychiatric disorders. The aim of this study is to evaluate the changes in cortical excitability in FT and to assess the relationship between cortical excitability and tremor severity.

Methods: This study recruited 39 patients with FT and 40 healthy controls (HCs). The clinical characteristics of the patients with FT were assessed using the Simplified Functional Movement Disorders Rating Scale (SFMDRS), Clinical Global Impression Severity Scale, and Symptom Check List-90. Intracortical excitability was assessed, including short/long-interval intracortical inhibition (SICI/LICI) and intracortical facilitation (ICF), in all participants using paired-pulse TMS.

Results: Compared with HCs, patients with FT exhibited reduced SICI-2 ms and SICI-4 ms and enhanced ICF-10 ms. Interhemispheric comparisons showed unbalanced excitability with reduced SICI-2 ms, increased ICF-8 ms and increased ICF-10 ms in the more affected side, which were not observed in HCs. The correlation analysis showed that SFMDRS scores were positively correlated with the Hamilton Anxiety Rating Scale and SICI-2 ms.

Conclusions: The findings indicate altered cortical excitability in patients with FT. Reduced intracortical inhibition was correlated with tremor severity, suggesting impaired inhibitory pathways in patients with FT.

Trial registration number: ChiCTR2200066389; Chinese Clinical Trial Registry.

Background: Long COVID-19 is associated with a diverse range of debilitating neuropathic and autonomic symptoms that may indicate small fibre neuropathy (SFN). We aimed to assess the utility of multimodal non-invasive electrodiagnostic techniques in evaluating symptomatic individuals.

Methods: People with confirmed long COVID-19 who scored >10 points on the Small Fibre Neuropathy Screening List (SFNSL) questionnaire underwent routine neurophysiological testing and a non-invasive SFN protocol of (a) sympathetic skin responses, (b) cutaneous silent period, (c) quantitative thermal thresholds and (d) electrochemical skin conductance. Clinical and demographic information was collected on all individuals who underwent comprehensive physical and psychometric evaluation, including a 6-min walk test, National Aeronautics and Space Administration (NASA) Lean Test, Composite Autonomic Symptom Score-31 (COMPASS-31), European Quality of Life 5-Dimension 5-Level Questionnaire (ED-5D-5L), Modified Fatigue Impact Scale (MFIS) score and Patient Health (depression) Questionnaire (PHQ-9).

Results: We assessed nine individuals, of whom three (33%) had neurophysiological evidence of SFN. Median age was 47.8 (range 26.3-67.6) years, duration from COVID-19 infection 23.0 (range 8.5-35.7) months and median SFNSL 34/84. All individuals scored highly in disability measures.

Conclusions: Long COVID-19 is associated with functional disability and reduced quality of life. SFN should be considered in all individuals with a suggestive clinical phenotype of neuropathic and autonomic symptoms.

Background: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder caused by prion proteins, with microglial activation being a key immunopathological feature. This case report demonstrates the application of ¹⁸F-DPA-714 positron emission tomography (PET)/MRI, a second-generation translocator protein ligand, to visualise microglial activation in vivo in a patient with sporadic CJD (sCJD).

Case presentation: A 57-year-old woman presented with progressive rapid cognitive decline and behavioural change. MRI revealed restricted diffusion within the patchy cortical ribbon of bilateral frontal, parietal, occipital lobes and right caput nuclei caudate. Lumbar puncture revealed positive 14-3-3 protein and robustly positive real-time quaking-induced conversion assay, fulfilling the diagnostic criteria for definite sCJD. ¹⁸F-DPA-714 PET/MRI showed extensive tracer uptake in bilateral cortical regions, caudate nuclei and the thalamus, indicating widespread microglial activation. The extent of abnormality on PET exceeded that seen on initial MRI, suggesting higher sensitivity for early pathological changes.

Conclusions: This is the first reported case of sCJD evaluated with ¹⁸F-DPA-714 PET/MRI. The findings suggest that ¹⁸F-DPA-714 PET/MRI may provide complementary sensitivity beyond structural MRI, potentially improving early diagnostic confidence in sCJD.

Background: Patients with anti-leucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis (AIE) frequently present with faciobrachial dystonic seizures (FBDS), which are often under-detected due to their subtle motor features and lack of consistent EEG correlates. Conventional in-hospital monitoring and patient-reported seizure diaries are limited, particularly during nocturnal periods. In this pilot feasibility study, we evaluated the use of a wearable device (Empatica E4) to objectively monitor FBDS-related motor and autonomic activity in seven patients with anti-LGI1 AIE and four control subjects.

Methods: Wearable recordings included accelerometry (ACC), electrodermal activity (EDA), photoplethysmography (PPG) and skin temperature. A support vector machine-based algorithm was developed to identify disorder-related events using ACC and EDA features. Analyses were restricted to sleep periods to minimise confounding from voluntary movements.

Results: Pretreatment recordings from two patients (P1 and P2) showed significantly elevated motor event frequency, ACC magnitude and EDA activity compared to controls. Post-treatment recordings demonstrated marked reductions in these metrics, consistent with patient-reported clinical improvement. Other patients showed variable results depending on treatment timing and signal quality.

Conclusion: Our pilot study demonstrates the feasibility of using wearable technology for objective, real-world monitoring and assessment of patient status in anti-LGI1 AIE. Nocturnal monitoring offers a low-noise baseline for detecting seizure-related activity and may support earlier diagnosis, more accurate evaluation of treatment response and reduced reliance on resource-intensive inpatient evaluations. Future studies should expand monitoring to daytime periods and validate findings against conventional modalities such as video-EEG and electromyography polygraphy.

Introduction: Alpha-synucleinopathies (ASs), including Parkinson's disease, multiple system atrophy and dementia with Lewy bodies, are characterised by autonomic dysfunction that may predispose to cardiovascular events and sudden death. Heart rate variability (HRV) is a non-invasive marker of autonomic regulation, yet its modulation across sleep stages in ASs remains unclear.

Methods: We retrospectively analysed 25 patients with ASs and 35 age-matched controls who underwent overnight polysomnography between 2020 and 2023. 5 min ECG segments from wakefulness, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were used to compute time- and frequency-domain HRV indices. Statistical comparisons and multivariate models were adjusted for sex and REM sleep behaviour disorder.

Results: HRV indices, particularly percentage of successive RR intervals that differ by more than 50 milliseconds (pNN50) and root mean square of successive differences, were significantly reduced in ASs compared with controls. The most pronounced difference occurred during NREM sleep (pNN50, p=0.008), where controls exhibited normal parasympathetic elevation that was absent in ASs.

Conclusion: Patients with ASs demonstrate blunted nocturnal parasympathetic activity, most evident during NREM sleep. Sleep-stage-specific HRV analysis provides sensitive insights into cardiac autonomic dysfunction and may serve as a potential biomarker of disease severity and cardiovascular risk in synucleinopathies.

Background: Parkinson's disease (PD) is a chronic, progressive, disabling neurodegenerative disorder. Deep brain stimulation (DBS) surgery is a highly effective and beneficial therapy for advanced PD, but its substantial cost limits accessibility. This study aimed to evaluate the cost-utility and budget impact of rechargeable and non-rechargeable DBS compared with standard pharmacotherapy alone in patients with advanced PD.

Methods: We conducted a cost-utility analysis using a Markov model with a 6-month cycle length and a 20-year time horizon. Costs were valued in 2025 Thai Baht, and both costs and outcomes were discounted at 3% per year. The model consisted of six health states based on the Modified Hoehn & Yahr scale. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included total costs, life-years, QALYs and a 5-year budget impact from the government perspective. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty.

Results: Medication alone produced 5.80 QALYs, compared with 7.38 QALYs for both rechargeable and non-rechargeable DBS, yielding 1.57 incremental QALYs. Rechargeable DBS resulted in an incremental cost of THB506 720 (US$15 678), corresponding to an ICER of THB321 940 (US$9958) per QALY. While non-rechargeable DBS resulted in an incremental cost of THB639 454 (US$19 785), corresponding to an ICER of THB406 272 (US$12 567) per QALY. Probabilistic analysis produced similar values (ICERs of THB293 354-THB350 761 per QALY). All ICERs exceeded Thailand's willingness-to-pay threshold of THB160 000 (US$4950) per QALY. The projected 5-year budget impact was THB60.9-THB69.0 million (US$1.9-US$2.1 million) per year.

Conclusions: DBS for patients with advanced PD is not currently cost-effective within Thailand's national healthcare system. Supported by the actionable evidence in this study, strategic pricing and policy changes will enable equitable access to therapy.

Background: Levodopa equivalent dopaminergic dose (LEDD) reduction after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease varies widely. Identifying predictors may guide patient selection and programming. Our objectives were to identify predictors of LEDD reduction and to test whether motor improvement mediates this association.

Methods: Data from 144 patients treated by STN-DBS were analysed. Predictors of LEDD reduction were selected using the Boruta algorithm, a machine-learning method comparing variable importance to randomised features and then tested in a structural equation model for direct and motor-mediated effects.

Results: Mean LEDD reduction was 41.7% (±38.2%) and motor improvement was 48.6% (±26.7%) at 1 year. Among the four predictors identified by Boruta, lower baseline LEDD (β=0.39, p=0.001), greater axial impairment (β=-0.25, p=0.003) and higher total volume of tissue activated (β=-0.17, p=0.031) were directly associated with lower LEDD reduction, independent of motor improvement. Sensorimotor STN overlap was not directly linked to LEDD reduction but was positively associated with motor improvement (β=0.34, p=0.001), which showed a trend-level effect on LEDD reduction (β=0.16, p=0.065). The total effect of sensorimotor STN overlap on LEDD reduction was not significant.

Discussion: Dopaminergic dose reduction after STN-DBS is constrained by preoperative axial symptoms and stimulation spread, independently of motor improvement, while sensorimotor STN overlap improves motor symptoms but not dose reduction. Integrating motor phenotype with anatomical guidance may enhance medication management post DBS.

Sjögren's disease (SjD) is a chronic autoimmune connective tissue disorder primarily affecting the salivary and lacrimal glands. Extra-glandular involvement may occur, sometimes preceding the diagnosis of SjD or in the absence of sicca symptoms, contributing to diagnostic delay. Central nervous system (CNS) manifestations have been reported in SjD, though establishing a causal relationship is challenging given possible overlapping neuroinflammatory and autoimmune aetiologies. We report two patients who presented with acute encephalitis and new-onset refractory status epilepticus (NORSE), in whom features supportive of primary SjD were subsequently identified. Both patients underwent extensive evaluation that excluded infectious causes, other systemic autoimmune connective tissue diseases and known autoantibody-mediated forms of autoimmune encephalitis. These cases highlight the importance of considering systemic autoimmune diseases in the evaluation of unexplained encephalitis and NORSE, and support the early use of immunotherapy when an immune-mediated pathology is suspected.

Background: Dysphagia is common in amyotrophic lateral sclerosis (ALS), contributing to malnutrition and accelerated disease progression. Although early nutritional intervention is recommended, the optimal timing for percutaneous endoscopic gastrostomy (PEG) placement remains uncertain. This study aimed to develop and validate simple prediction models, accessible via an online calculator, to identify ALS patients likely to require PEG within 6 months.

Methods: We conducted a retrospective cohort study including ALS patients followed at three Italian reference centres between February 2018 and October 2023. Predictors of PEG placement within 6 months were identified using univariate and multivariable binary logistic regression models. Prediction models were developed following Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines and underwent both internal and external validation.

Results: In the development cohort (n=263; median age 63.8 years), 138 patients (52.5%) underwent PEG within 6 months. Three models were developed: the Anamnestic Prediction Model, based on age, onset site and non-invasive ventilation (NIV), showed fair predictive performance. The Anamnestic and Functional Prediction Model, incorporating age, bulbar subscore of Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-r) and forced vital capacity (%), demonstrated strong predictive performance (Brier score: 0.1230), excellent discrimination (concordance index (c-index) 0.91) and good calibration (Hosmer-Lemeshow p=0.59). The Anamnestic and Nutritional Prediction Model, including age, onset site, NIV, body mass index and weight loss, showed good predictive performance (Brier score: 0.1719), discrimination (c-index 0.81) and calibration (Hosmer-Lemeshow p=0.48). These findings were confirmed in an external validation cohort of 116 ALS patients.

Conclusions: The prediction models provide accurate, easily implementable tools to predict PEG need within 6 months, enabling timely nutritional interventions that may improve outcomes and care quality in ALS.

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder impairing cerebral glucose transport, leading to variable neurological symptoms in which adult care remains underexplored. This study aims to characterise adult phenotypes, identify unmet needs and inform a person-centred care model.

Methods: 32 adults with genetically confirmed GLUT1DS were retrospectively evaluated at two centres in Milan, Italy. Clinical history, diagnostic data, treatment and follow-up information were systematically collected. 19 patients underwent extended assessments including cognitive, neuropsychiatric, sleep, adaptive functioning and quality of life evaluations. Nine also participated in psychological interviews.

Results: The cohort included 68.8% female (median age: 32 years). Median age at symptom onset was 2 years, with a diagnostic delay of 18 years. 62% of individuals received a diagnosis in adulthood, with 31% diagnosed only after their child was identified. Except for two cases, all exhibited in their clinical history typical GLUT1DS symptoms that were either unrecognised or too mild to prompt medical attention. Psychosocial health issues were identified in 42% of cases, with emotional disturbances affecting 53% and social life impairments in 42%; physical health concerns in 32%.

Conclusions: Diagnostic delay in adults with GLUT1DS is more likely due to limited clinical awareness than to atypical presentations. The most effective model of care for individuals with GLUT1DS might be multidisciplinary involving paediatric and adult neurologists, rehabilitation professionals, clinical psychologists, clinical nutritionists and dietitians to support motor, cognitive and emotional functioning, thereby promoting autonomy, improving quality of life and addressing challenges associated with ketogenic diet adherence.