BMJ Neurology Open最新文献

Background: Disrupted sense of agency (SoA)-the sense of being the agent of one's own actions-has been demonstrated in patients with functional neurological disorder (FND), and a key area of the corresponding neuronal network is the right temporoparietal junction (rTPJ). Several functional MRI (fMRI) studies have found hypoactivation as well as hyperactivation of the rTPJ in FND. In a proof-of-concept study, we tested whether repetitive transcranial magnetic stimulation (rTMS) over the rTPJ could restore this aberrant activity.

Methods: In a randomised, crossover, single-blinded, sham-controlled study design, theta-burst stimulation (tb-rTMS) was applied over the rTPJ in 23 patients with FND and 19 healthy controls (HC), with each participant undergoing three stimulatory visits (inhibitory continuous TBS (cTBS), excitatory intermittent TBS (iTBS) and sham). During fMRI, participants played a visuomotor task artificially reducing their SoA (manipulated agency, MA), repeated after each neurostimulation. We compared brain activity and behavioural SoA as primary outcomes before and after tb-rTMS and investigated the feasibility of tb-rTMS over the rTPJ in FND as secondary outcome.

Results: At baseline, patients showed decreased accuracy in detecting reduced agency compared with controls (p<0.001), paralleled by lower brain activation in the rTPJ during MA (p=0.037, volume of interest). A region of interest analysis on the rTPJ showed no effect of the sham condition in FND or HC (p=0.917; p=0.375) but revealed a significant effect of stimulation protocol (cTBS/iTBS, p=0.037) in patients with FND, with the excitatory protocol increasing the blood-oxygen-level-dependent (BOLD) signal, whereas this effect was not found in HC. In neither group, a behavioural effect of tb-rTMS was observed.

Conclusion: Aberrant processing of agency in FND was confirmed at baseline, reflected in behavioural outcome and reduced activity in the rTPJ. Tb-rTMS over this key region elicited neuronal changes in patients, paving ways for future studies exploring TMS as neurobiologically informed intervention to restore SoA in FND. We critically discuss methodological intricacies and outline further steps in this research line.

Background: Sialidosis is a rare disorder caused by mutations in the NEU1 gene located on chromosome 6p21.3, constituting a group of autosomal recessive diseases. Enzyme activity analysis, electron microscopy examination and genetic testing are reliable methods for diagnosis. Despite previous reports on the disease, its rarity means that its clinical manifestations and prognosis still warrant attention due to the limited amount of information available.

Methods: We report a case of a 40-year-old woman who was admitted to our hospital for worsening dysarthria of 16 years duration and facial and limb twitching that had been present for 2 years. Genetic testing was undertaken.

Results: Genetic testing confirmed type I sialidosis, the first reported instance of this disease in the Hainan Free Trade Port in China. The patient did not have the typical cherry-red spot in the fundus. Despite aggressive treatment, she died of status epilepticus 2 months later. This result indicates that the disease has a poor prognosis.

Discussion: Cherry-red spots in the fundus are characteristic features of type I sialidosis and it has been referred to as the cherry-red spot myoclonus syndrome. We hypothesise that environmental factors may also play a significant role. Overemphasis on the presence of cherry-red spots may mislead clinicians and delay diagnosis. Furthermore, patients presenting with isolated myoclonus should undergo visual evoked potential and somatosensory evoked potential tests, as well as genetic testing to confirm or rule out sialidosis.

Background: Mitochondrial diseases are common inherited metabolic disorders. Due to improved case ascertainment and diagnosis methods, the detection of new diagnoses of mitochondrial disease can be expected to increase. In December 2009, the prevalence of mitochondrial DNA (mtDNA)-related mitochondrial disease was 4.6/100 000 (95% CI, 2.7 to 7.2) in the adult population of Southwest Finland. We investigated the number of new diagnoses and the incidence of mitochondrial disease in Southwest Finland between December 2009 and December 2022.

Methods: We collected data on all adult patients from Southwest Finland diagnosed with mitochondrial disease on 31 December 2009 and 31 December 2022. Most patients had been diagnosed at the Turku University Hospital (TUH) neurology outpatient clinic. Patients were also identified by searching the TUH electronic patient database for relevant International Classification of Diseases, Tenth Revision codes and conducted mtDNA analyses.

Results: 42 new patients were diagnosed giving a mean annual rate of 3.2 new diagnoses. In 2022, the minimum prevalence estimate of adult mtDNA-related mitochondrial disease was 9.2/100 000 (95% CI, 6.5 to 12.7). The prevalence of adult mtDNA disease associated with m.3243A>G was 4.2/100 000 (95% CI, 2.5 to 6.7), and that with large-scale mtDNA deletions was 1.3/100 000 (95% CI, 0.4 to 2.9). During the 13-year period, the annual incidence of adult mtDNA disease was 0.6/100 000 and that of adult m.3243A>G-related disease 0.3/100 000.

Conclusion: Our results suggest that improved means of diagnostics and dedicated effort increase the detection of mitochondrial disease.

Background: Acute ischaemic stroke (AIS) is a leading cause of disability and mortality worldwide. Determining subgroups and outcomes of AIS may lead to better treatment. We aimed to investigate the relationship between inflammatory markers and subgroups of AIS with further follow-up of patients in terms of functional outcome score.

Methods: In this prospective cohort study, we examined white cell count (WCC), neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR) and qualitative C reactive protein (CRP), in the first 24 hours of patients' admission. Patients were assigned to AIS subgroups as defined by the TOAST criteria. Then patients' disability score was followed up after 3 and 6 months, using the modified Rankin Scale.

Results: We included 217 patients with AIS. The mean age of participants was 72.07 years, and we included 92 women (42.4%). For the AIS subgroup, 83 (38.25%) patients had large artery atherosclerosis (LAA), 41 (18.89%) had cardioembolism and 62 (28.57) had small vessel obstruction. Neutrophil count and NLR showed a statistically significant difference in the subgroups of AIS and were highest in the 'other' subgroup of AIS (p<0.05). Lymphocyte count, ESR and qualitative CRP showed no statistically significant difference between subgroups (p>0.05). WCC, neutrophil count and NLR showed a positive correlation with functional outcomes (p<0.05), other markers did not correlate with outcomes (pp>0.05).

Conclusion: We can conclude that neutrophil count and NLR are available inflammatory biomarkers for predicting outcomes and these two biomarkers are associated with AIS subgroups. However, ESR, qualitative CRP and lymphocyte count do not appear to be correlated with outcomes or subgroup of AIS.

Background: A central feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM), which is an acute worsening of symptoms after a physical, emotional and/or mental exertion. Dynamic measures of PEM have historically included scaled questionnaires, which have not been validated in ME/CFS. To enhance our understanding of PEM and how best to measure it, we conducted semistructured qualitative interviews (QIs) at the same intervals as visual analogue scale (VAS) measures after a cardiopulmonary exercise test (CPET).

Methods: Ten ME/CFS and nine healthy volunteers participated in a CPET. For each volunteer, PEM symptom VAS (12 symptoms) and semistructured QIs were administered at six timepoints over 72 hours before and after a single CPET. QI data were used to plot the severity of PEM at each time point and identify the self-described most bothersome symptom for each ME/CFS volunteer. Performance of QI and VAS data was compared with each other using Spearman correlations.

Results: Each ME/CFS volunteer had a unique PEM experience, with differences noted in the onset, severity, trajectory over time and most bothersome symptom. No healthy volunteers experienced PEM. QI and VAS fatigue data corresponded well an hour prior to exercise (pre-CPET, r=0.7) but poorly at peak PEM (r=0.28) and with the change from pre-CPET to peak (r=0.20). When the most bothersome symptom identified from QIs was used, these correlations improved (r=0.0.77, 0.42. and 0.54, respectively) and reduced the observed VAS scale ceiling effects.

Conclusion: In this exploratory study, QIs were able to capture changes in PEM severity and symptom quality over time, even when VAS scales failed to do so. Measurement of PEM can be improved by using a quantitative-qualitative mixed model approach.

Background: The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications.

Methods: In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.

Results: 74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile.

Conclusions: COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.