Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Chimeric antigen receptor (CAR) T-cell therapy has revolutionised the treatment of haematological malignancies and has demonstrated efficacy in early trials for solid tumours, neurological and rheumatological autoimmune diseases. However, CAR-T is complicated in some patients by neurotoxicity syndromes including immune-effector cell-associated neurotoxicity syndrome, and the more recently described movement and neurocognitive treatment-emergent adverse events, and tumour inflammation-associated neurotoxicity. These neurotoxic syndromes remain poorly understood and are associated with significant morbidity and mortality. A multidisciplinary approach, including neurologists, haematologists and oncologists, is critical for the diagnosis and management of CAR-T neurotoxicity. This approach will be of increasing importance as the use of CAR-T expands, its applications increase and as novel neurotoxic syndromes emerge.

Background: At least 60% of stroke, 40% of dementia and 35% of late-life depression (LLD) are attributable to modifiable risk factors, with great overlap due to shared pathophysiology. This study aims to systematically identify overlapping risk factors for these diseases and calculate their relative impact on a composite outcome.

Methods: A systematic literature review was performed in PubMed, Embase and PsycInfo, between January 2000 and September 2023. We included meta-analyses reporting effect sizes of modifiable risk factors on the incidence of stroke, dementia and/or LLD. The most relevant meta-analyses were selected, and disability-adjusted life year (DALY) weighted beta (β)-coefficients were calculated for a composite outcome. The β-coefficients were normalised to assess relative impact.

Results: Our search yielded 182 meta-analyses meeting the inclusion criteria, of which 59 were selected to calculate DALY-weighted risk factors for a composite outcome. Identified risk factors included alcohol (normalised β-coefficient highest category: -34), blood pressure (130), body mass index (70), fasting plasma glucose (94), total cholesterol (22), leisure time cognitive activity (-91), depressive symptoms (57), diet (51), hearing loss (60), kidney function (101), pain (42), physical activity (-56), purpose in life (-50), sleep (76), smoking (91), social engagement (53) and stress (55).

Conclusions: This study identified overlapping modifiable risk factors and calculated the relative impact of these factors on the risk of a composite outcome of stroke, dementia and LLD. These findings could guide preventative strategies and serve as an empirical foundation for future development of tools that can empower people to reduce their risk of these diseases.

Prospero registration number: CRD42023476939.

Background: Information on fetal risks with maternal seizures during pregnancy is scarce. This study investigates seizure control during pregnancy and fetal risks associated with maternal seizures in different stages of pregnancy among pregnant women with epilepsy (PWWE).

Methods: The nested case-control study enrolled PWWE between 2009 and 2023 in China. Information was obtained on maternal seizures, antiseizure medication (ASM), folic acid supplementation and pregnancy outcomes. The primary outcome was composite including major congenital malformations (MCMs), neurodevelopmental delay, low birth weight (LBW) and fetal death. Univariate and multivariate logistic regression analyses were conducted to adjust for ASM effects and other confounders.

Results: Among 1110 pregnancies from 934 PWWE included, 56.6% experienced seizures. Seizure deterioration during pregnancy compared with prepregnancy was observed in 25.9% of pregnancies, while 20.9% experienced worsening seizures from the first to second or third trimesters. Seizures (adjusted OR (aOR) 1.472, 95% CI 1.024 to 2.137), particularly status epilepticus (aOR 2.906, 95% CI 1.364 to 5.93), generalised tonic-clonic seizures (aOR 1.581, 95% CI 1.066 to 2.354) and seizure deterioration (aOR 1.829, 95% CI 1.233 to 2.69) were associated with composite adverse outcomes. Specifically, seizures occurring (aOR 2.324, 95% CI 1.320 to 4.084) or deteriorating (aOR 2.396, 95% CI 1.471 to 3.866) during second and third trimesters were associated with the risk of LBW. No significant association was found between seizures and MCMs.

Conclusions: While nearly half of PWWE remain seizure-free during pregnancy, those who do experience seizures face increased risks of adverse offspring outcomes. For PWWE, every effort should be made to optimise seizure control in order to minimise risks to both mother and child.

Trial registration number: ChiCTR2100046318.

Background: The link between low-density lipoprotein cholesterol (LDL-C) levels and dementia risk is poorly understood, with conflicting evidence on the role of LDL-C and the impact of statin therapy on cognitive outcomes. Thus, we aimed to examine the association between low-density LDL-C levels and the risk of dementia and assess the influence of statin therapy.

Methods: We retrospectively analysed data from 11 university hospitals participating in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Participants with a prior diagnosis of dementia or those with <180 days of observation before cohort inclusion, and those included in both cohorts were excluded. The primary outcome was all-cause dementia, with the secondary outcome being Alzheimer's disease-related dementia (ADRD). The study utilised 1:1 propensity score matching to compare individuals with LDL-C levels below 70 mg/dL (1.8 mmol/L) against those with levels above 130 mg/dL (3.4 mmol/L), resulting in a primary analysis cohort of 108 980 matched patients. Secondary analyses further examined LDL-C thresholds below 55 mg/dL (1.4 mmol/L) and the influence of statin use.

Results: The LDL-C levels below 70 mg/dL (1.8 mmol/L) were associated with a 26% reduction in the risk of all-cause dementia and a 28% reduction in the risk of ADRD, compared with levels above 130 mg/dL (3.4 mmol/L). For LDL-C levels below 55 mg/dL (1.4 mmol/L), there was an 18% risk reduction for both outcomes. Among those with LDL-C <70 mg/dL (<1.8 mmol/L), statin use was associated with a 13% reduction in all-cause dementia risk and a 12% decrease in ADRD risk compared with non-users.

Conclusion: Low LDL-C levels (<70 mg/dL (<1.8 mmol/L)) are significantly associated with a reduced risk of dementia, including ADRD, with statin therapy providing additional protective effects. These findings support the necessity of targeted lipid management as a preventive strategy against dementia, indicating the importance of personalised treatment approaches.

Background: Biomarkers for predicting myelin oligodendrocyte glycoprotein antibody (Ab)-associated disease (MOGAD) clinical course are still missing. Binding capacity to a mutant MOG protein variant (MOG-P42S; non-P42) was shown to correlate with an increased relapse risk in adult patients.The objective of our study was to assess the frequency of binding to the non-P42 MOG variant in a cohort of paediatric MOGAD and to investigate its association with specific clinical profiles and disease course.

Methods: We included children with MOG-Ab seropositive samples collected after their first demyelinating episode from five different centres. We performed live cell-based assays with native full-length MOG (MOG-FL) and mutant MOG-P42S and correlated the results with clinical data.

Results: Of the 81 MOG-FL identified patients serum, 40 bound the non-P42 MOG. Non-P42 patients exhibited an earlier median age of onset (p=0.002). Phenotype distribution was different between groups (p=0.001), with non-P42 patients predominantly exhibiting acute disseminated encephalomyelitis phenotype. Notably, the non-P42 group was associated with a higher relapse rate (relative rate: 2.6 (95% CI 1.1 to 6.2), p=0.03), adjusted for clinical phenotype.

Conclusion: Non-P42 is a promising biomarker for predicting relapse in paediatric MOGAD patients.

Background and objectives: Quantitative and operator-independent biomarkers of disease progression are urgently needed in amyotrophic lateral sclerosis (ALS) research. We assess the potential of skeletal muscle MRI as a sensitive and reliable outcome measure for future ALS clinical trials.

Methods: In this longitudinal cohort study, muscle MRI of head-neck, upper and lower limb regions, alongside clinical and functional assessments, were acquired at three time points over the individual maximum observation period (iMOP) of 1 year in 20 patients with ALS and 16 healthy controls. Quantitative MRI parameters cross-sectional area (CSA), volume (VOL), fat fraction, functional rest muscle area and water T2 (T_2m) were correlated with changes in clinical disease severity (functional rating scales and myometry).

Results: Among 20 patients with ALS, 17 completed follow-up. Progressive muscle atrophy (CSA, VOL) was observed at hand (rs=0.66), head-neck (partial η²=0.47) and lower-limb level (thighs: η²=0.56, calves: η²=0.54) over iMOP. MRI changes correlated with leg muscle strength (knee extension: r=0.77; plantar flexion: r=0.78), hand grip strength (r=0.71) and functional rating scales (r=0.68).

Interpretation: Our findings demonstrate the effectiveness of muscle MRI as a sensitive neuroimaging biomarker of disease progression in ALS, highlighting its potential application in clinical trials.

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system characterised by inflammatory lesions and neurodegeneration. Diagnosis often occurs in women of childbearing age, and therefore pregnancy is frequently encountered in women with MS. However, the effect of pregnancy on the MS brain is not well understood, including the impact on inflammatory lesion activity and rate of brain atrophy. Determining the effect of pregnancy on the MS brain is complex due to several confounding factors, including dynamic changes in brain volumes in healthy physiological (non-MS) states and the impact of withdrawing disease-modifying therapies for pregnancy on inflammatory lesion activity. This review first provides an in-depth overview of the profound structural neuroplasticity that occurs during pregnancy in healthy women without neurological disease and its association with maternal caregiving behaviours and maternal-infant attachment measures. These findings are integrated with results of MRI studies in pregnant women with MS to provide a perspective on the multifold influences on brain volume changes in this context. This review also explores the increase in inflammatory lesions observed on postpartum MRI in women with MS, which likely accrue in the postpartum phase mirroring clinical relapse dynamics. Key knowledge gaps are identified, and future research pathways are proposed to improve our understanding of how pregnancy impacts the brain in both healthy and MS states.

Background: We aimed to investigate the prodromal phase of multiple sclerosis (MS) by investigating annual sickness absence rates before MS onset.

Methods: A retrospective cohort study was conducted using Sweden's linked clinical and health administrative data. We identified MS cases via a validated algorithm using International Classification of Diseases (ICD) diagnostic codes for MS ('administrative cohort') or registration in the Swedish MS registry ('clinical cohort'). MS onset was defined as the first MS/demyelinating disease ICD code (administrative cohort) or, for the clinical cohort, MS symptom onset date, if earlier. Cases were matched with up to five controls from the general population with no MS/demyelinating disease history. Yearly sickness absence rates up to 18 years pre-MS onset were compared using negative binomial regression with generalised estimating equations.

Results: The administrative/clinical cohorts comprised 8618/6361 MS cases and 43 072/31 776 controls. Sickness absence rate ratios were significantly elevated from 6 years before MS onset in the administrative cohort and 2 years before in the clinical cohort. The adjusted rate ratios peaked in the year pre-MS onset, reaching 2.59 (95% CI 2.40 to 2.79) in the administrative cohort and 1.19 (95% CI 1.06 to 1.34) in the clinical cohort. We also observed age-related and sex-related differences primarily in the year before MS onset, with males and older individuals exhibiting higher rate ratios.

Conclusions: We observed a significant increase in sickness absence spells in individuals on the path to developing MS. Investigating sick leave patterns may provide a unique and broad perspective on the health trajectories of chronic conditions like MS.