Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Beta-synuclein is an emerging blood biomarker for detecting synaptic damage in Alzheimer's disease (AD) but its role in early AD as well as in other dementias is unclear.

Methods: We measured with immunoprecipitation mass-spectrometry serum beta-synuclein levels in an exploratory cohort of 80 patients recruited at the University of Perugia (Perugia, Italy) (n=56 AD; n=24 controls) and in a validation cohort of 269 patients recruited at the University of Barcelona (Barcelona, Spain) (n=108 AD; n=53 frontotemporal lobar degeneration (FTLD); n=73 dementia with Lewy bodies and mild cognitive impairment (MCI) with Lewy bodies, together Lewy body disease (LBD); n=27 controls). We tested associations with diagnostic groups, cognitive decline and other cerebrospinal fluid (CSF) and blood markers (phosphorylated tau protein in position 181 (pTau181), neurofilament light chain protein (NfL), glial fibrillar acidic protein (GFAP)).

Results: Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all). The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96). High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=-0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006). Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001).

Conclusion: High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.

Background: Ultra-processed foods (UPFs), widely consumed globally, are increasingly recognised as a key factor in poor dietary quality and diet-related health risks. However, little is known about the role of UPF consumption in the development and progression of Parkinson's disease (PD).

Methods: We followed 121 440 participants who were free of cancer, PD and dementia at baseline, each completing at least two 24-hour dietary assessments. UPF consumption was defined according to the Nova classification. Eight prodromal features were identified through self-reported diagnoses, hospital admission records and primary care data. Prodromal PD was defined as the presence of ≥3 prodromal PD features. Incident PD cases were identified through linkages with hospital admissions, death registers and self-reported data. Information on vital status, date of death and cause of death was obtained from the UK National Health Service (NHS) and the NHS Central Register. The multivariable Cox proportional hazards models were used to estimate the HRs and 95% CIs.

Results: During a median of 10.5 years of follow-up, 1047 participants had ≥3 prodromal PD features, 640 participants developed PD and 114 participants died from PD. Comparing extreme quartiles of UPF consumption, the HRs were 1.65 (95% CI: 1.35 to 2.02) for having ≥3 versus 0 prodromal PD features, 1.32 (95% CI: 1.02 to 1.71) for developing PD and 3.11 (95% CI: 1.56 to 6.17) for PD death (p value trend <0.05 for all).

Conclusions: In this large prospective cohort study, higher UPF consumption was associated with higher risk of developing prodromal PD, incident PD and PD-specific mortality.

Background: The natural history of clinically stable patients with Chiari I malformation (CM-I)-syringomyelia is uncertain. To understand their outcomes, we examined conservatively managed CM-I-syringomyelia patients' long-term clinical and radiological courses.

Methods: We enrolled 156 mild CM-I-syringomyelia cases (Japanese Orthopaedic Association (JOA) score ≥13) managed non-surgically between 1994 and 2014 and followed them periodically until December 2024 for significant progressive myelopathy that we termed 'obvious deterioration'. Obvious deterioration was defined as a ≥2-point decline in JOA score to less than 13. Spontaneous syrinx resolution was radiologically defined as >50% reduction in syrinx length or maximal axial diameter on T1-weighted MRI.

Results: The entire cohort had over 1401 patient-years of follow-up. 55 patients exhibited clinical deterioration, yielding an annual progression rate of 3.9%. Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) (HR=1.841, 95% CI 0.999 to 3.392; p=0.049), positive Babinski sign (HR=2.252, 95% CI 1.229 to 4.125; p=0.009) and without spontaneous resolution (HR=20.308, 95% CI 4.804 to 85.849; p<0.001) independently predicted later clinical obvious deterioration. Spontaneous resolution of CM-I-syringomyelia was more frequent with cervical syringes (HR=2.12, 95% CI 1.224 to 3.674; p=0.007) and absence of OSAHS (HR=3.83, 95% CI 1.376 to 10.640; p=0.01).

Conclusion: This study showed that the natural course of myelopathy in CM-I-syringomyelia varies according to the OASHS status, Babinski sign and spontaneous syrinx resolution. Additionally, baseline characteristics, including the spinal region of the syrinx and the absence of OSAHS, correlated with spontaneous syrinx resolution.

Background: This study investigates the predictive value of baseline quantitative susceptibility mapping (QSM) metrics for assessing the risk of future symptomatic haemorrhages in patients with brainstem cavernous malformations (CMs).

Methods: From July 2020 to September 2023, a prospective multicentre cohort of 155 patients with brainstem CMs was enrolled from 12 institutions. We analysed baseline QSM metrics, including lesional mean, median, IQR and maximum susceptibility. Propensity score matching was adjusted for baseline confounders, and Cox regression models assessed haemorrhage risk. Risk stratification was performed based on thresholds determined from planned receiver operating characteristic (ROC) analyses.

Results: Postmatching cohorts (56 haemorrhage-free vs 30 haemorrhage cases) showed balanced baseline characteristics. Over a mean follow-up of 22.6 months, the baseline QSM metrics, particularly the median susceptibility (QSMmedian) (HR 58.896, 95% CI 8.544 to 405.989, p<0.001; Bonferroni-adjusted p=0.0001, k=4) and IQR of susceptibility (QSMIQR) (HR 29.754, 95% CI 6.101 to 145.119, p<0.001; Bonferroni-adjusted p=0.0001, k=4) were associated with prospective haemorrhage after adjusting for age, gender, lesion volume and prior haemorrhage. QSMmedian (area under curve (AUC)=0.759) and QSMIQR (AUC=0.740) demonstrated modest predictive performance. Risk stratification based on QSMmedian and QSMIQR demonstrated 2-year haemorrhage-free survival rates of 83.3%, 62.8% and 35.7% for the low-risk, intermediate-risk and high-risk groups, respectively. High-risk patients showed a 7.7-fold greater risk of haemorrhage compared with the low-risk group.

Conclusions: This study explored the predictive value of QSM metrics for future symptomatic haemorrhage, suggesting that QSM may serve as a complementary imaging biomarker to existing prognostic models. Further validation in larger, independent cohorts is warranted.

Background: Kappa free light chain (KFLC) index has emerged as a diagnostic biomarker for multiple sclerosis (MS). This study aims to evaluate the diagnostic accuracy of the KFLC-index in Chinese patients with MS, and its capacity to discriminate MS from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorders with aquaporin-4 antibody (AQP4+NMOSD).

Methods: 428 patients tested for KFLC-index were enrolled in the study, including 130 patients with MS, 41 with MOGAD, 25 with AQP4+NMOSD, 123 with other inflammatory or infectious neurological disorders (OIND) and 109 with non-inflammatory neurological disorders (NIND). Their oligoclonal band (OCB) results and clinical data were reviewed.

Results: KFLC-index was significantly higher in MS (20.1 (0.9-388.9)) compared with MOGAD (4.8 (0.8-56.1), p=0.003), AQP4+NMOSD (4.5 (1.5-46.4), p=0.011), OIND (2.9 (0.6-238.7), p<0.001) and NIND (1.8 (0.6-110.7), p<0.001). The optimal cut-off value for the KFLC-index to identify MS from the non-selective controls was 8.3, with an accuracy comparable to that of OCB (area under the curve 0.84 vs 0.81, p=0.249). The optimal cut-off values for differentiating MS from MOGAD and AQP4+NMOSD were 18.5 and 12.1, with performance similar to OCB (p=0.756 and 0.064). Combination of KFLC-index and OCB outperformed OCB alone in differentiating MS from non-selective controls and MOGAD (p<0.001 and p=0.044). Female (p=0.009) and higher cerebrospinal fluid leucocyte count (p<0.001) were associated with higher KFLC-index in MS.

Conclusion: KFLC-index is a valuable diagnostic tool for differentiating MS from other inflammatory demyelinating diseases.