Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: To delineate the clinical characteristics and outcomes of late-onset myelin oligodendrocyte glycoprotein antibody-associated disease (LO-MOGAD) and compare them with those of early-onset MOGAD (EO-MOGAD).

Methods: This observational cohort study included 199 adult patients with MOGAD. We reviewed the patients' demographic and clinical data and performed comparative analyses between EO-MOGAD and LO-MOGAD (onset age 18-50 and ≥50 years, respectively).

Results: Among the 199 patients, 42 had LO-MOGAD. Compared with patients with EO-MOGAD, those with LO-MOGAD patients exhibited a significantly higher incidence of optic neuritis both at the initial attack (66.67% vs 43.31%, p=0.007) and throughout all attacks (72.15% vs 52.51%, p=0.001). Over a similar disease duration, patients with LO-MOGAD exhibited significantly fewer relapsing courses (45.16% vs 70.97%), higher Expanded Disability Status Scale (EDSS) and visual functional system scores at the last visit (all p<0.05). Compared with patients with EO-MOGAD, those with LO-MOGAD had a significantly lower risk of relapse (HR 0.512, 95% CI 0.268 to 0.978, p=0.034), but higher risks of reaching EDSS ≥2 (HR 2.893, 95% CI 1.524 to 5.494, p<0.001) and visual acuity ≤0.6 (HR 3.097, 95% CI 1.073 to 8.937, p=0.022). Immunosuppressive therapies significantly reduced the annualised relapse rates of patients with LO-MOGAD, although adverse events leading to drug discontinuation and hospitalisation were observed.

Conclusions: Compared with patients with EO-MOGAD, patients with LO-MOGAD exhibited fewer relapsing courses but worse disability outcomes and should be actively treated.

Background: It remains imperative to discover the time course that cardiovascular risk factors influence neurodegeneration in males and females and decipher whether the apolipoprotein (APOE) genotype mediates this relationship. Here we perform a large-scale evaluation of the influence of cardiovascular risk and obesity on brain volume in males and females in different age groups.

Methods: 34 425 participants between the ages of 45 and 82 years were recruited from the UK Biobank database https://www.ukbiobank.ac.uk. T1-weighted structural MR images (n=34 425) were downloaded locally for all participants, and voxel-based morphometry was performed to characterise the volumetric changes of the whole brain. The influence of Framingham cardiovascular risk (general cardiovascular risk), abdominal subcutaneous adipose tissue, and visceral adipose tissue volume (obesity) on cortical grey matter volume across different decades of life was evaluated with voxel-wise analysis.

Results: In males, cardiovascular risk and obesity demonstrated the greatest influence on lower grey matter volume between 55-64 years of age. Female participants showed the greatest effect on lower grey matter volume between 65-74 years of age. Associations remained significant in APOE ε4 carriers and APOE ε4 non-carriers when evaluated separately.

Conclusions: The strongest influence of cardiovascular risk and obesity on reduced brain volume was between 55-64 years of age in males, whereas women were most susceptible to the detrimental effects of cardiovascular risk a decade later between 65-74 years of age. Here we elucidate the timing that targeting cardiovascular risk factors and obesity should be implemented in males and females to prevent neurodegeneration and Alzheimer's disease development.

Background: The Global Burden of Disease Study (GBD) produces prevalence estimates for 'idiopathic epilepsy' (ie, of unknown aetiology) and 'secondary epilepsy' (ie, with known aetiology) but does not report prevalence by underlying aetiologies for 'secondary epilepsy'.

Methods: We used nationwide, population-based register data from Denmark to identify underlying causes of epilepsy and their contribution to prevalence of 'secondary epilepsy' and compared with global prevalence data from GBD 2019. We identified all persons with a hospital-based epilepsy diagnosis and a filled prescription for antiseizure medication between 1 January 2009 and 31 December 2018. Epilepsy was categorised into 'idiopathic' or 'secondary' and 'total epilepsy' as the sum of the two epilepsy categories.

Results: On 31 December 2018, a total of 5 784 284 individuals (49.7% males) were living in Denmark including 40 336 with epilepsy (51.5% males). Perinatal conditions, traumatic brain injury, brain tumours and stroke were prominent underlying causes of 'secondary epilepsy'. The prevalence of 'total epilepsy' in Denmark was 697 (95% CI 691 to 704) per 100 000 population (264 (95% CI 260 to 269) for 'secondary epilepsy' and 433 (95% CI 428 to 438) for 'idiopathic epilepsy'). In the GBD 2019 Study, the prevalence of 'total epilepsy' in 2018 was 682 (95% uncertainty interval (UI) 586 to 784) per 100 000 population (359 (95% UI 324-397) for 'secondary epilepsy' and 324 (95% UI 249 to 404) for 'idiopathic epilepsy').

Conclusions: Prevalence estimates of 'total epilepsy', 'idiopathic epilepsy' and 'secondary epilepsy' in Denmark align with the GBD 2019 estimates. In future studies, it is suggested to explicitly include all types of epilepsy, including 'secondary epilepsy', which is currently estimated as sequelae (consequences) of underlying diseases.

Background: Pure autonomic failure (PAF) presents with progressive autonomic failure without other neurological features. Atypical presentations may lead to diagnostic uncertainty. We studied whether cutaneous phosphorylated-alpha-synuclein (p-syn) could distinguish between PAF, multiple system atrophy (MSA) and non-synucleinopathy-related autonomic failure, and examined its relationship with quantitative markers of cardiovascular autonomic failure.

Methods: All individuals underwent Composite Autonomic Symptom Score-31 autonomic questionnaires, cardiovascular autonomic testing and bilateral distal leg skin biopsies. We noted whether p-syn was present in nerves supplying autonomic adnexa, including sweat glands, blood vessels, arrector pili muscles, and subepidermal fibres, dermal fibres and nerve fascicles (maximum autonomic subscore 3, total p-syn score 6 for each sample, average calculated for both sides).

Results: 36 individuals were studied: 11 PAF, 13 MSA and 12 non-synucleinopathy-related autonomic failure. P-syn was present in 22/22 (100%) PAF biopsies, 19/26 (73%) MSA biopsies and 0/22 (0%) non-synucleinopathy biopsies. Mean total p-syn score was significantly higher in PAF compared with MSA (median 4.5 vs 1, p<0.001). Total p-syn score >3 distinguished PAF from MSA with 100% specificity and 82% sensitivity. Autonomic p-syn subscores correlated with orthostatic intolerance ratio on tilt (ρ=0.63, p=0.0004), blood pressure recovery time following Valsalva manoeuvre (r=0.44, p=0.03) and patient-reported orthostatic intolerance (ρ=0.57, p=0.006).

Conclusion: Cutaneous p-syn was abundant in PAF, a predominantly peripheral alpha-synucleinopathy. It is a promising biomarker to help distinguish between PAF, MSA and non-synucleinopathy-related autonomic failure to aid early diagnosis and recruitment to future clinical trials. P-syn deposition on autonomic nerves may impair control of total peripheral resistance giving rise to symptomatic orthostatic hypotension.

Background: Deep brain stimulation (DBS) and infusion therapies are effective treatments for the motor complications of Parkinson's disease (PD), but less established is their role in fall prevention. This systematic review and network meta-analysis (NMA) aimed to evaluate the risk of falls associated with advanced therapies in PD.

Methods: Following PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-analyses) guidelines, we searched PubMed, Medline, Embase and CINAHL up to 20 March 2024. Eligibility criteria based on PICOS (Population Intervention Control Outcome Study design) framework were used for DBS of the subthalamic nucleus (STN) or globus pallidus pars interna (GPi), or infusion therapies, compared with best medical treatment (BMT) or sham stimulation. Pairwise meta-analysis was conducted using RevMan V.5.4, and NMA using the netmeta package in R software.

Results: Fourteen studies were included. A higher number of falls were observed in the DBS group compared with BMT, although the difference was not significant. Sensitivity analysis excluding a heterogeneity-contributing study showed a significantly higher fall risk in the DBS group (Risk Ratio (RR)=2.74, 95% CI 1.60, 4.67, p=0.0002). Subgroup analyses indicated that levodopa-carbidopa intestinal gel tended towards increased fall risk, while continuous subcutaneous infusion of (fos)levodopa (CSCI) significantly decreased risk with high certainty of evidence. NMA showed CSCI as the most effective in reducing falls, while STN DBS was associated with the highest risk.

Conclusions: DBS, especially targeting the STN, may increase fall risk compared with other advanced non-DBS procedures. While LCIG might not alter fall risk, preliminary evidence suggests that CSCI positively affects fall prevention.

Prospero registration number: CRD42023420637.

Background: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear.

Method: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed.

Results: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-beta_NREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-beta_NREM: r=0.6, p=0.0301; SFI-gamma_NREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPR_NREM: r=-0.8, p=0.0053; ArI-LHPR_REM: r=-0.6, p=0.0373; SFI-LHPR_NREM: r=-0.7, p=0.0204; SFI-LHPR_REM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (β=-0.24, p<0.001).

Conclusion: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction.

Trial registration number: NCT02937727.

Background: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings.

Methods: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task).

Results: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula.

Conclusions: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements.

Trial registration number: NCT03679468.