Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Estimators of biological age, such as epigenetic clocks, are promising biomarkers for neurological disorders where the risk significantly increases with age, such as Parkinson's disease (PD). The purpose of this study was to prospectively investigate whether epigenetic age acceleration can predict PD risk, age at PD onset and time to phenoconversion.

Methods: We conducted a prospective, nested case-control study within the Nurses' Health Study, including participants who provided two blood samples before being diagnosed with PD. DNA methylation profiles were obtained from 75 individuals who developed PD, 79 individuals who developed prodromal features suggestive of PD and 154 age-matched controls. We estimated epigenetic age acceleration using six different epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE and the cortical epigenetic clock) and assessed their associations with PD risk, age at PD onset and time to PD onset.

Results: Epigenetic age acceleration was not consistently associated with a higher PD risk, using estimates of biological ageing neither in the first sample (collected a median of 19 years before PD onset) nor in the second sample (collected a median of 8 years before PD onset). These results remained similar in multivariable models adjusted for smoking status, physical activity, body mass index, caffeine intake, alcohol intake and Mediterranean diet score. Furthermore, epigenetic age acceleration was not associated with earlier age at PD onset or time to PD phenoconversion.

Conclusions: In our study, epigenetic clock-based biomarkers do not reliably predict PD risk, age at PD onset or time to PD phenoconversion.

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: 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: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening disease with frequent autonomic manifestations. Autonomic testing is not widely accessible, which might cause underdiagnosis of autonomic dysfunction and delay in treatment. This retrospective study evaluates ambulatory 24-hour blood pressure measurement (ABPM) as a screening tool for neurogenic orthostatic hypotension (nOH), postprandial hypotension and worsening of orthostatic tolerance postexercise by comparison with gold standard testing. Furthermore, it investigates circadian BP rhythm in ATTRv over time.

Methods: 93 patients and 12 asymptomatic TTR variant carriers had ABPM including autonomic diary and quantitative autonomic function testing (AFT; 30% females, mean age 57.6 years). A subset of individuals underwent a modified exercise and liquid meal test. 47 individuals had follow-up ABPM.

Results: Sensitivity/specificity of ABPM in detecting nOH and postprandial hypotension were 73%/98% and 86%/81%, respectively. ABPM captured worsening of orthostatic tolerance postexercise (p=0.007). 71/105 (68%) individuals showed an abnormal dipping profile (51 reduced dippers, 20 non- or reverse dippers), and 4/71 were carriers (all reduced dippers). All non- or reverse dippers presented with pathologic AFT. 7/8 (88%) carriers and 20/26 (77%) patients with normal ABPM had abnormal AFT. At follow-up, 21% showed progressive circadian rhythm abnormalities.

Conclusions: ABPM with an autonomic diary is a widely accessible screening tool to detect nOH, postprandial hypotension, and impaired circadian rhythm. However, it does not allow for a quantitative parasympathetic/sympathetic assessment confirming subtle autonomic dysfunction, which is why a formal AFT is still required. Pathologic BP profiles are common in ATTRv, including in certain carriers, and can show progression over time.

Lecanemab is an anti-amyloid monoclonal antibody, recently approved in the UK as a treatment for mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease (AD) in adults who are apolipoprotein E ε4 gene (APOE4) heterozygotes or non-carriers.A group of UK neurologists, old age psychiatrists and geriatricians with expertise in AD convened to agree appropriate use recommendations for lecanemab in UK clinical practice. The primary focus of these recommendations is safety.Eligibility criteria for lecanemab in the UK include (a) a clinical diagnosis of MCI or mild dementia due to AD, (b) the presence of amyloid-β pathology, confirmed using approved methods (ie, an amyloid positron emission tomography scan or cerebrospinal fluid assay) and (c) APOE4 heterozygous or non-carrier status. Eligibility screening should be conducted in secondary care and those identified as being potentially eligible for lecanemab should be referred to a specialist centre for confirmation of the likely pathological diagnosis, APOE4 counselling and testing and a multidisciplinary consensus decision regarding treatment eligibility. Lecanemab is administered as an intravenous infusion every 2 weeks, and those eligible for treatment should have brain magnetic resonance imaging (MRI) scans prior to the 1st, 5th, 7th and 14th infusions. Specific guidance is provided for safety monitoring and management of potential adverse reactions, including amyloid-related imaging abnormalities and infusion-related reactions.The introduction of lecanemab into UK clinical practice provides an important opportunity to improve services for all people living with dementia, not just those eligible for lecanemab treatment.

Background: Patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) encephalitis are typically elderly men that often carry human leucocyte antigen (HLA)-DRB1*07:01 (≈90%). Herein, we aimed to investigate whether patients with atypical demographic profiles or not carrying DRB1*07:01 have distinct clinical manifestations and outcome.

Methods: Retrospective chart review of LGI1-Ab patients diagnosed at the French Reference Centre and three other European centres.

Results: Among 238 patients included, median age at onset was 66 years (IQR: 60-73), 65% were male, 89% carried DRB1*07:01 and 10% DRB1*04:02, another known secondary HLA association. We identified three age groups (young, typical, old) based on percentiles of age distribution. Young (≤51 years) patients were less commonly male (35%, p=0.004), while faciobrachial dystonic seizures (FBDS; 65%, p=0.047) and hyponatraemia (64%, p=0.046) were more frequent in old (≥79 years) patients. Old patients experienced poor outcome (modified Rankin Scale [mRS] >2 at last follow-up) more frequently (64%, p<0.001). There were no significant differences between males and females. DRB1*07:01 non-carriers were younger (p=0.005) and less frequently male (47%, p=0.044), while non-carriers of both DRB1*07:01 and DRB1*04:02 experienced poor outcome more commonly (64%, p=0.005). Older age (adjusted OR: 1.08, 95% CI [1.02 to 1.14], p=0.008), higher mRS at nadir (4.22 [2.46-7.24], p<0.001) and DRB1*07:01 non-carrier status (8.39 [1.88-37.44], p=0.005) were independently associated with poor outcome. Moreover, older age (1.08 [1.04-1.11], p<0.001), FBDS (2.20 [1.17-4.13], p=0.014) and hyponatraemia (2.30 [1.22-4.34], p=0.010) were associated with severe encephalitis (mRS >3 at nadir).

Conclusions: Age appears to be the main driver of clinical presentation, severity and outcome in LGI1-Ab encephalitis. Remarkably, DRB1*07:01 non-carriers are younger, more commonly female and experience poorer prognosis, reflecting a distinct pathophysiology.