Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Deep brain stimulation (DBS) has been investigated for patients with drug-resistant epilepsy who are not candidates for resective surgery. Because different types of epilepsy involve distinct brain networks, numerous DBS targets have been explored, yet a comprehensive synthesis is lacking.

Methods: To provide a comprehensive overview of this expanding literature, we conducted a systematic review of studies for DBS in epilepsy, including case series, prospective and retrospective studies. We collected data on surgical targets, individual disease characteristics, outcomes and precise electrode placements. DBS electrode coordinates were gathered into a common template space and related to clinical outcomes.

Results: We included 124 studies, corresponding to 1210 patients and 20 distinct surgical targets. While the anterior (ANT) and centromedian (CM) nuclei of the thalamus remain the most studied, we also review less commonly used targets that show promise for specific forms of epilepsy and may warrant further investigation. Substantial variability in targeting strategies and electrode placement was observed within each of the target regions. Importantly, significant relationships between stimulation location and outcomes were identified for ANT-DBS and CM-DBS. For ANT-DBS, shorter distance to the mammillothalamic tract junction was associated with greater seizure reduction on both study-level and patient-level analyses (r=-0.55, p<0.001 and r=-0.51, p<0.001, respectively). For CM-DBS, localisation effects may be dependent on the form of epilepsy, with stimulation of the parvocellular CM being associated with better outcomes in generalised epilepsy.

Conclusions: Our results emphasise the importance of accurate targeting in DBS for epilepsy. Our database and atlas of DBS targets are made publicly available, potentially serving further meta-analytical work.

Prospero registration number: CRD420250649304.

Background: Recovery following traumatic brain injury (TBI) is highly heterogeneous. Characterising longitudinal functional trajectories may enable more individualised care and inform the trial design. This study aimed to identify distinct patterns of functional recovery in the first 12 months post-injury using the Glasgow Outcome Scale - Extended (GOSE).

Methods: Patients with available GOSE data from Transforming Research and Clinical Knowledge in Traumatic Brain Injury, a prospective, multicentre study, were included. A two-stage multiple imputation procedure addressed missingness, and trajectories were modelled using polytomous variable latent class analysis (poLCA) in both complete-case and imputed datasets.

Results: Among the 2,100 participants with TBI, poLCA identified seven distinct recovery trajectories based on GOSE scores. These included (1) death (6.2%), (2) persistent GOSE 2-5 (5.7%), (3) improvement from GOSE 3-5 to GOSE 5 by 3 months with no further gains (9.0%), (4) rapid improvement from GOSE 3-5 to GOSE 7-8 sustained through follow-up (7.0%), (5) gradual improvement from GOSE 3-6 to GOSE 5-7 over 6 months (15.3%), (6) rapid early improvement from GOSE 4-7 to GOSE 6-8 by 3 months and then plateauing (21.8%) and (7) progression from GOSE 5-8 to GOSE 7-8 within 3 months, with stable outcomes thereafter (25.1%). Recovery class membership was significantly associated with the initial Glasgow Coma Scale scores, CT severity (Marshall and Rotterdam scores) and presence of psychiatric comorbidities.

Conclusions: Our findings support a shift towards trajectory-based stratification in clinical care and research. Incorporating these patterns into prognostic modelling may improve outcome prediction, personalise rehabilitation and refine eligibility criteria for interventional trials.

Background: A relevant proportion of patients experience early neurological deterioration (END) despite technically successful recanalisation for acute ischaemic stroke. We prospectively assessed the distal occlusion tracker (DOT) sign, detectable on flat-panel detector CT (FPDCT) immediately after mechanical thrombectomy (MT), to identify distal embolisation or incomplete microvascular reperfusion associated with END.

Methods: Our prospective multicentre observational study included consecutive patients with anterior circulation stroke treated with MT between January 2022 and December 2023 at two large comprehensive stroke centres. Post-procedural FPDCT was used to assess the presence of the DOT sign. The primary outcome was END. Secondary outcomes included 3 month functional outcome, 24 hour Alberta Stroke Program Early CT Score (ASPECTS) and haemorrhagic complications. Associations between the DOT sign and clinical-radiological variables, including Thrombolysis in Cerebral Infarction recanalization score (TICI), were evaluated through univariate and multivariate logistic regression.

Results: The DOT sign was present in 31% of cases and was associated with higher rates of END (25% vs 12.8%, p=0.003), lower recanalisation success (79.3% vs 91.1%, p<0.001) and greater prevalence of cortical hyperattenuation. On multivariate analysis, independent predictors of END included the DOT sign (aOR=2.07, p=0.040), cardioembolic aetiology, baseline National Institutes of Health Stroke Scale, FPDCT ASPECTS and unsuccessful reperfusion. The DOT sign led to reclassification of half of TICI 3 cases to lower grades. No significant difference in symptomatic intracranial haemorrhage was observed between groups.

Conclusions: The DOT sign is a practical post-thrombectomy imaging marker helping in the prediction of END. Integrating the DOT sign assessment may help in the stratification of tissues at risk and risk of END, adding to the selection of patients for adjunctive intra-arterial medications.

Background: Intravenous immunoglobulin (IVIg) is effective in many neuroinflammatory disorders but carries a risk of thromboembolic events (TEEs). Subcutaneous immunoglobulin (SCIg) is effective, but its thromboembolic risk profile is less well-described, particularly in patients with prominent vascular risk factors. We investigated the thromboembolic risk profile of IVIg and SCIg using a large single-centre retrospective dataset of patients with neuroinflammatory disorders.

Methods: 243 patients treated with immunoglobulin over a 15-year monitoring period were analysed. Demographic information was used to calculate QRISK3 vascular risk scores. Patients were grouped based on having received IVIg-only, SCIg-only or both IVIg and SCIg (with subgroup analysis of IVIg and SCIg treatment periods). TEE incidence rates were compared. The relationship between QRISK3 and TEE likelihood was analysed.

Results: A total of 1401 patient-years immunoglobulin treatment data were obtained. The SCIg-only cohort was older with higher QRISK3 scores. More patients on IVIg (n=14) than SCIg (n=2) experienced TEEs on treatment (1.38 vs 0.52 events per 100 patient-years), but this difference was not statistically significant. IVIg-treated patients with TEEs were younger (p=0.039) than SCIg-treated TEE patients. QRISK3 scores broadly correlated with thromboembolic risk across the cohort (p=0.027), but some younger IVIg patients with low QRISK3 scores experienced TEEs indicating that IVIg but not SCIg independently increases thromboembolic risk. QRISK3 scores >10% identified 71% and 100% of TEEs in IVIg-treated and SCIg-treated patients, respectively, but are insensitive (7%) as TEEs are rare events.

Conclusions: SCIg is at least equivalent in thromboembolic risk to IVIg and may be safer for patients with existing vascular risk factors.

Background: Brain structural changes in frontotemporal dementia (FTD) can occur decades before symptom onset. Precise characterisation of grey matter changes is necessary for developing models of biomarker progression, while better understanding the trajectory of the pathology is invaluable for prognosis and detecting treatment effects as we enter the era of clinical trials.

Methods: Cortical and subcortical grey matter volume and thickness from structural MRI were assessed in a large cohort of 892 participants including presymptomatic and symptomatic carriers of mutations within the three main genetic causes of FTD (C9 open reading-frame 72 (C9orf72), progranulin (GRN) and microtubule-associated protein tau (MAPT)) compared with mutation-negative relatives (controls). We compared the distribution of grey matter changes of each metric at different stages of the disease cross sectionally. We aimed to identify grey matter composites for each genetic group which would show the earliest changes and which separated presymptomatic carriers from controls.

Results: While C9orf72 mutation carriers showed widespread presymptomatic grey matter changes, MAPT and particularly GRN mutation carriers showed changes more proximally to symptom onset. Our composite grey matter signatures, which discriminate asymptomatic/prodromal carriers from controls with high to very high areas under the curve, involved bilateral thalami volumes, precuneus and postcentral thickness in C9orf72; left caudal middle frontal thickness, frontal pole and pars orbitalis volumes in GRN; right temporal pole volume and left insula thickness in MAPT mutation carriers.

Conclusion: We propose the use of cortical thickness and volume measurements combined from multiple regions into a composite region of interest for each FTD genetic group to identify the earliest changes and track disease progression. Our quasi-longitudinal design illustrates that these regions continue to evolve throughout the symptomatic stages. Investigating how our selected composites progress and validating these in longitudinal samples will be invaluable for future clinical trials.

Background: No disorder-specific patient-reported outcome measure (PROM) has yet been validated for functional movement disorders (FMDs), leaving a critical gap in clinical care and research.

Objective: To validate the FMD questionnaire (FMDQ) in a prospectively recruited sample through a multicentre study.

Methods: Confirmatory factorial analysis (CFA) tested the assumed structure of the questionnaire with factors reflecting severity of motor symptoms, impairment of everyday activities, impact of non-motor symptoms and impairment of social functioning. Internal consistency and floor/ceiling effects were examined. The 36-item short form health survey (SF-36), patient health questionnaire-15 (PHQ-15), the fatigue assessment scale (FAS) and a clinician-rated scale corresponding to motor symptom items of the FMDQ (FMDQ-CR) were used to test criterion and construct validity. The minimally clinically important difference (MCID) was assessed through distribution-based and anchor-based methods in a convenience sample of patients with follow-up assessments.

Results: Complete datasets from 157 patients were analysed; follow-up assessments were available from 30 patients. CFA confirmed that a four-factor model provides a better fit to the data compared with a more restrictive one-factor model. Internal consistency was appropriate for all factors/subscales. No floor or ceiling effects were detected. Criterion and content validity were supported by significant correlations with respective SF-36 subscores, PHQ-15, FAS and FMDQ-CR. Anchor-based MCID was estimated at 8 to 20 points, with the central value aligning with the distribution-based MCID of 12 points (8% of the total score range).

Conclusions: The FMDQ is a psychometrically robust PROM, making it a useful tool for clinical practice and treatment trials.

Background: Adult adrenoleukodystrophy is a rare X linked disorder with heterogeneous phenotypes, complicating prognosis and trial design. We characterised phenotype and natural history in a large single-centre nationwide cohort and contextualised findings with prior reports.

Methods: We performed a combined retrospective-prospective observational study of adults (≥18 years) with confirmed ABCD1 variants evaluated at Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan (January 2004-June 2023), with reassessments between July and December 2023. Clinical, genetic, biochemical, MRI and neurophysiological data were analysed.

Results: The cohort comprised 140 patients (64 males, 76 females) from 58 families, carrying 50 ABCD1 variants, including 11 novel mutations. Adrenomyeloneuropathy (AMN) predominated in males, with low mortality (<10%) and rare cerebral progression (7%) across 18 years, suggesting protective factors. An intermediate phenotype, adrenoleukomyeloneuropathy (ALMN), showed earlier onset, demyelinating MRI changes without cerebral symptoms at baseline and higher mortality than AMN (HR 4.75, 95% CI 1.60 to 14.11). In females, symptom prevalence increases with age, affecting 57% over 60, although only 37% required walking aids. Males had higher very long-chain fatty acid (VLCFA) levels than females, but intrasex correlations with phenotype were absent. Brainstem auditory evoked potentials (BAEPs) were consistently abnormal, whereas nerve conduction studies were abnormal in ~half of male patients (less often in females).

Conclusions: Adult adrenoleukodystrophy comprises distinct phenotypes with variable prognosis. Recognition of ALMN as an intermediate form and the low cerebral progression rate in Italian AMN refine disease classification. Sex-related VLCFA differences may influence severity, although standard assays lack sensitivity. Neurophysiological testing, particularly BAEPs, can support differential diagnosis in patients with hereditary spastic paraplegias.

Trial registration number: NCT04880356.