BMJ Neurology Open最新文献

Background: Functional neurological disorder (FND) is a common cause of neurological disability with symptoms spanning motor, sensory and cognitive domains. While effective treatments exist, the impact of symptom chronicity on treatment outcomes is unclear. This systematic review and meta-analysis investigated whether longer symptom duration influences treatment outcomes across FND phenotypes: functional movement disorders, functional/dissociative seizures (FDS) and mixed presentations.

Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO and grey literature were systematically searched till 29 June 2024. Studies were included if they involved adult FND participants undergoing any intervention and evaluated symptom change, function and health-related quality of life (HrQoL). Studies were excluded with <10 participants, missing symptom duration data or irrelevant outcomes. Two reviewers independently extracted data and assessed risk of bias. Meta-analyses used random effects models, subgroup analyses and univariate meta-regression to examine associations with symptom chronicity.

Results: 63 studies met inclusion criteria; 27 studies (885 participants) were meta-analysed. Longer symptom duration modestly reduced improvements in motor symptoms (-3.24 points/year, scale: 0-100) and physical HrQoL (-1.2 points/year, scale: 0-100). Global improvements (mean Clinical Global Impression-Change 2.43, 95% CI: 2.28 to 2.59, scale: 1-7) and mental HrQoL gains (mean Short Form-Mental Component Summary +5.04 points, 95% CI: 1.67 to 8.41) were observed irrespective of chronicity. FDS frequency reduced after psychotherapy in eight of nine studies, even with prolonged symptoms.

Conclusions: Symptom chronicity modestly reduced motor and physical HrQoL improvements, but did not negate meaningful gains across a range of outcomes. Early diagnosis and treatment are critical for better outcomes, but remain beneficial in chronic stages.

Background: Tumefactive demyelinating lesions (TDLs) are rare, large demyelinating lesions of the central nervous system that can mimic brain tumours in radiological appearance. They have been observed across multiple demyelinating diseases. Previous studies have suggested that antibody profiles may correlate with distinct clinical or imaging characteristics, but detailed comparisons between antibody-defined subgroups in TDLs remain limited.

Methods: We retrospectively analysed 30 patients with confirmed TDLs. Demographic, clinical, imaging and laboratory data were collected, and patients were stratified by myelin oligodendrocyte glycoprotein (MOG) and N-methyl-D-aspartic acid receptor (NMDAR) antibody results. Lesion characteristics were evaluated on brain MRI, and outcomes were assessed by modified Rankin Scale at last follow-up. Statistical comparisons were made between antibody-positive and antibody-negative subgroups.

Results: Among TDLs subgroups, MOG+ patients had elevated cerebrospinal fluid white cell counts and showed greater lesion volume reduction on follow-up MRI than MOG- patients. NMDAR+ patients showed elevated levels of systemic inflammatory markers compared with NMDAR- counterparts. Regardless of antibody status, most TDLs patients responded well to immunotherapy, with 86.7% achieving a favourable outcome.

Conclusions: TDLs represent a heterogeneous inflammatory syndrome. MOG and NMDAR antibodies influence the clinical and laboratory characteristics of TDL patients but have limited impact on prognosis.

Background: Disproportionately fewer females with Parkinson's disease (PD) undergo deep brain stimulation surgery (DBS). Some data show worse depression, anxiety, and quality of life (QOL) in females with PD. Investigations into these gender disparities, or the effect of DBS on these non-motor symptoms, remain limited.

Methods: 61 PD patients across seven UK DBS centres were recruited for the Clinical Response of Impulsive behaviours to deep brain Stimulation in PD (CRISP) prospective cohort study. Questionnaires measured primary outcomes of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and QOL (Parkinson's Disease Questionnaire-39) before and 6 months after bilateral subthalamic nucleus DBS, and secondary outcomes of predictors of postoperative changes in mood.

Results: Females were disproportionately under-referred for DBS (28% of cohort). Baseline depression and anxiety were similar between genders. While DBS significantly improved overall anxiety (p<0.001), females reported significantly more postoperative anxiety than males (median score 7 vs 1.5, Cohen's d=0.33, p=0.009). Postoperatively, only males experienced a significant reduction in moderate depression, by 29% (p=0.004) (12% in females). QOL improved significantly by similar proportions, thus significantly worse QOL in females preoperatively was sustained as 9.12% worse postoperatively (Cohen's d=0.75, p=0.02). Preoperatively, females reported significantly worse mobility, social support, and pain; postoperatively, the significant difference in mobility was sustained. Longer PD duration, worse QOL, and mobility predicted postoperative depression (R² =0.156, p=0.003), while female gender and reduced social support predicted postoperative anxiety (R²=0.23, p<0.001).

Conclusions: DBS showed clinical efficacy for non-motor PD symptoms across genders, evidencing the need to close the gender gap in DBS. Analysis by gender highlighted significant disparities and postoperative predictors that provide impetus for tailored DBS counselling.

Background: The updated International Panel's diagnostic criteria for multiple sclerosis (2024 revision of McDonald criteria) have for the first time included the optic nerve as the fifth location for dissemination in space (DIS) criterion. The new requirement consists of evidence of significant retinal asymmetry. However, this can be challenging in the acute phase in absence of optic disc swelling. Here, we have investigated the sensitivity of retinal asymmetry over time, from the acute to the chronic phase of optic neuritis.

Methods: This observational study analysed longitudinal optical coherence tomography (OCT) images of 25 patients with optic neuritis and 5 healthy controls. Spectral domain OCT scans were obtained from the macula and optic disc. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell (mGCL) and inner plexiform layers (mIPL) were measured in the acute (≤7 days), subacute (between 1 and 12 weeks) and chronic (>3 months) phase.

Results: The OCT measurements showed progressive thinning in pRNFL and mGCIPL layers as the disease progressed. In the acute phase, the sensitivity of the pRNFL was 69% (due to optic disc swelling) and for the mGCPL 27%. In the chronic phase, sensitivity levels increased up to 76% (pRNFL) and 88% (mGCIPL) due to atrophy.

Conclusions: A clear understanding of the temporal dynamics of diagnostic findings is important. For OCT, the highest diagnostic sensitivity is achieved for the mGCIPL in the chronic phase. This should be taken into account for timing the test in patients where the acquisition of optic nerve involvement is essential for DIS.

Background: Criteria-led transfer allows transfer of select stroke patients to inpatient rehabilitation without rehabilitation physician review, which may be a barrier for timely transfers.

Objective: Primary: determine the proportion of patients transferred via criteria-led transfer and waitlist time. Secondary: determine the number of unplanned 30-day acute hospital representations and readmissions from inpatient rehabilitation, and number of daily allied health contacts while waitlisted.

Method: A single-centre retrospective analysis was conducted on all patients transferred from the acute stroke unit to inpatient rehabilitation in 2023.

Results: 178 (79%) patients successfully used criteria-led transfer, 22 (9.5%) did not meet criteria and the remainder attended inpatient rehabilitation via a separate pathway. Median waitlist time (in days) was shorter for criteria led transfer patients compared with those who did not meet criteria (3 (1-5) vs 5 (3-8), p=0.005). Emergency department representation rates were lower in the criteria-led transfer cohort (30 (16.9%) vs 8 (36.3%), p=0.03) compared with those who did not meet criteria. No difference in readmission rates was seen (p=0.22). Waitlisted patients received 1 (0.5-1.5) allied health reviews daily.

Conclusions: Criteria-led transfer is associated with shorter waitlist times for transfer to rehabilitation without increased adverse events. Further research is needed to determine result generalisability.

Background: As the average age of multiple sclerosis (MS) population rises globally, unclear guidelines on disease-modifying therapy (DMT) use in older persons with MS (pwMS) contribute to increased variability in clinical practice. The factors driving DMT utilisation in this population are not well understood. We explored DMT utilisation patterns in pwMS aged 55 and older enrolled in the Swiss MS Registry (SMSR), a nationwide observational study with voluntary participation.

Methods: We conducted an exploratory analysis using data from SMSR participants who had reported DMT status in the most recent follow-up survey and at least once within the previous 3 years. Participants were categorised and compared by current and past DMT use: No DMT (no use), Stopped (prior use), Continued (same DMT), Switcher (changed DMT) and New (initiated DMT). Log-binomial regression identified factors associated with non-use, grouping participants as No DMT (No DMT, Stopped) and DMT (Continued, Switcher, New).

Results: Among 378 participants (mean age 63.2±6.7 years), 206 (54.5%) reported DMT use: 176 (46.6%) continued the same DMT, 20 (5.3%) switched and 10 (2.6%) newly initiated DMT. Among non-users, 54 (14.3%) had stopped treatment, while the rest did not use DMT during the study period. In participants with regular neurological care, longer MS duration (relative risk (RR)=1.018, 95% CI 1.008 to 1.028) and older age (RR=1.016, 95% CI: 1.001 to 1.032) were associated with higher likelihood of DMT non-use, and participants with primary (RR=1.736, 95% CI: 1.175 to 2.565) and secondary progressive MS (RR=1.423, 95% CI: 1.023 to 1.981) were more likely not to use DMTs compared with relapsing-remitting MS. No significant associations were observed in participants without regular neurological follow-up.

Conclusions: Despite unclear efficacy and safety, many older pwMS continue DMT use. Use is primarily associated with relapsing-remitting MS, while age and disease duration show only modest or no association.

Background: The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) is a standardised framework for organising healthcare data. This study uses data in the OMOP CDM format to analyse information on neurology patients.

Methods: Routinely collected data harmonised to OMOP at a large referral hospital in England were used. A study cohort was defined as patients who attended at least one neurology outpatient appointment between 01 April 2022 and 31 March 2023 (n=23 862). Data collected at all visits to the hospital made by this cohort between 01 April 2021 and 31 March 2024 were extracted. The cohort was then divided into four subcohorts according to appointment types attended: outpatient appointment(s) only (n=15 2); outpatient appointment(s) and inpatient stay(s) (n=2750); outpatient appointment(s) and emergency department attendance(s) (n=1658); outpatient appointment(s), inpatient stay(s) and emergency department attendance(s) (n=4199).

Results: We found there to be more data available for patients who had at least one inpatient stay or emergency department attendance than for those with only outpatient appointments. Notably, an average of 0 out of 100 patients in the outpatient only subcohort had a record of a condition, compared with 100 out of 100 patients in the subcohort with outpatient appointments, emergency attendances and inpatient stays.

Conclusions: Neurology outpatients have far less data recorded than inpatients or patients attending emergency departments. This disparity arises from the lack of outpatient diagnostic coding and impairs the advancement of research in this area. Using the OMOP CDM structure makes it easy to highlight these differences.

Background: Placebo effects are powerful and have been suggested to be particularly relevant in certain neurological conditions, including functional neurological disorder (FND).

Methods: A survey on attitudes towards and current practice of deceptive placebo treatments and ethical alternatives, notably positive suggestion, trust and open-label placebo was performed among health professionals and lay people with and without neurological diagnoses.

Results: 116 healthcare professionals and 631 lay people (176 FND, 332 with other neurological diagnoses, 61 with medical diagnoses, 62 healthy controls) completed the survey.71% of lay people but only 46% of healthcare professionals were in favour of deceptive placebo treatments. Among lay people, healthy individuals were most in favour (87%), and people with FND were least in favour (62%). All groups were sceptical towards open-label placebo, yet neurologists were most open to this practice.Placebo was considered more effective for functional than non-functional disorders by healthcare professionals, but not by patients. Healthcare professionals reported only rarely using placebo in clinical practice, and if so, mainly in the diagnosis or treatment of FND.

Conclusions: This is the first survey on opinions and current practice of placebo treatments in neurological practice. The results show a mixed picture, with deceptive placebos being perceived as effective and acceptable by most lay people (though strongly opposed by some, particularly by some patients with FND) and mostly considered more negatively by healthcare professionals. Ethically acceptable alternatives of harnessing the power of placebo without deception were considered with scepticism by all respondents, but least so by neurologists.

Background: Epilepsy-related ligand-receptor complex, leucine-rich glioma-inactivated 1 (LGI1)-a disintegrin and metalloproteinase 22 (ADAM22), regulates neuronal excitability and synaptic transmission and has emerged as a determinant of brain excitability. Epilepsy-related variants have been described in both LGI1 and ADAM 22 genes. A partial epilepsy, autosomal dominant lateral temporal epilepsy (ADLTE) is caused by an LGI1 heterozygous variant. A recessive developmental and epileptic encephalopathy with infantile onset is due to homozygous inactivating ADAM22 variants.

Objective: We present the case of Moroccan siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene previously unreported in the homozygous state.

Methods: We performed whole-exome sequencing and family segregation analysis to identify and confirm the genetic cause of the condition in the affected siblings.

Results: The clinical features mimic ADAM22-related developmental and epileptic encephalopathy rather than the typical LGI1-associated autosomal dominant lateral temporal epilepsy. Family segregation analysis demonstrated variable expressivity, with asymptomatic carrier parents and a cousin with focal temporal epilepsy carrying the variant in the heterozygous state.

Conclusion: This case highlights a homozygous LGI1 variant previously unreported in the homozygous state, leading to a clinical presentation more reminiscent of ADAM22-related pathology rather than the classical ADLTE, expanding our understanding of LGI1-associated conditions.

Introduction: One in six stroke survivors continue to experience arm and language disability at 3 months post-stroke. This study aims to identify which model(s) of integrated UPper limb and Language Impairment and Functional Training (UPLIFT) show promise for people 3 months to 24 months post-stroke. We hypothesise that at least one promising UPLIFT model of rehabilitation will be identified.

Methods and analysis: This is an adaptive Phase IIa master protocol umbrella design that includes four simultaneous Bayesian Optimal Phase II studies to evaluate individual UPLIFT interventions against prespecified objective performance criteria. The intervention is upper limb and language training at 2 or 4 hours/day, 5 days/week for 4 weeks, delivered either in person (severe stratum) or via telerehabilitation (mild-moderate stratum). Up to 160 adult participants will be recruited across six metropolitan/regional university or healthcare hubs spanning five Australian states. Baseline and post-intervention assessments are blinded. A promising response is defined as a composite binary outcome combining indicators of promise of efficacy, safety and feasibility. For each UPLIFT intervention, the proportion of participants with a promising response will be monitored at three equally spaced, predefined interim stopping points and one final analysis point (n=40 participants/study). An intervention will be stopped if too few promising responses are observed.

Ethics and dissemination: Ethical approval was obtained from The Royal Melbourne Human Research Ethics Committee. All participating sites obtained local governance approval. All recruited participants will provide informed consent. Trial results will be disseminated through peer-reviewed publications and presented at major stroke and rehabilitation conferences.

Trial registration number: ACTRN12622000373774.