Tomáš Sieger

Background: Functional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye‐tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink, and pupil responses in FMD and healthy controls performing an interleaved pro‐/anti‐saccade task, and to investigate the relationships between oculomotor measures and motor and non‐motor symptom severity. Methods: We conducted video‐based eye‐tracking in 104 patients with clinically definite FMD and 115 age‐ and sex‐matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain‐related, dissociative, and non‐motor somatic symptoms. Clinician‐rated motor severity and centrally acting medication were recorded in FMD patients. Results: Compared to controls, FMD patients showed increased anti‐saccade error rates ( p < 0.001), anticipatory saccades ( p ≤ 0.003), altered blink distribution ( p < 0.001), and reduced pupil dilation velocity ( p < 0.001). However, reduced pupil dilation velocity was not significant in the subsample of unmedicated patients. Higher anti‐saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non‐motor somatic symptom burden, and motor severity (all p < 0.05). Conclusions: We hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia, which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD.

Background: Fibromyalgia is characterized by widespread pain, fatigue, sleep and cognitive symptoms. It overlaps clinically with functional motor disorder ( FMD ), yet its prevalence and impact in FMD remain uncertain. Objective: To determine the prevalence of fibromyalgia in FMD using the current criteria and evaluate its effects on motor symptoms and health‐related quality of life ( HRQoL ). Methods: A total of 138 consecutive FMD patients completed the Fibromyalgia Survey Questionnaire, subjective motor ratings and HRQoL measures. Motor impairment was assessed using the Simplified FMD Rating Scale, and physical/psychiatric comorbidities and medication use were recorded. Results: Fibromyalgia was present in 44.9% of patients (95% CI : 36.5–53.6%). Those with fibromyalgia had more severe motor symptoms, lower HRQoL and greater medication use. Higher fibromyalgia severity, S‐ FMDRS , and psychiatric comorbidity were independent predictors of lower HRQoL . Conclusions: Fibromyalgia is common in FMD and associated with worse clinical outcomes, supporting systematic screening and integrated management.

Background: Functional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye-tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink and pupil responses in FMD and healthy controls performing an interleaved pro-/anti-saccade task, and to investigate the relationships between oculomotor measures and motor and non-motor symptom severity. Methods: We conducted video-based eye-tracking in 104 patients with clinically definite FMD and 115 age- and sex-matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain-related, dissociative, non-motor somatic symptoms. Clinician-rated motor severity and centrally acting medication was recorded in FMD patients. Results: Compared to controls, FMD patients showed increased anti-saccade error rates (p < 0.001), anticipatory saccades (p ≤ 0.003), altered blink distribution (p < 0.001), and reduced pupil dilation velocity (p < 0.001). However, reduced pupil dilation velocity was not significant in subsample of unmedicated patients. Higher anti-saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non-motor somatic symptom burden, and motor severity (all p < 0.05). Conclusions: We hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD. WHAT IS ALREADY KNOWN ON THIS TOPIC: FMD is increasingly interpreted through predictive coding models suggesting abnormalities in predictions about motor and sensory states driven by abnormally focused attention. Yet the underlying neurobiology remains poorly defined. Empirical studies directly probing basic predictive processes in FMD are scarce, and implicit cognitive–motor interactions, particularly those involving motor learning and adaptation, have been insufficiently explored. WHAT THIS STUDY ADDS: Only two previous studies have used eye-tracking in FMD, focusing mainly on diagnostic saccadic markers. Using time-series analyses of saccadic, blink, and pupillary data, we show abnormalities in inhibitory control, predictive processing, and implicit learning. Due to strong homology between human and primate neurophysiology and neuroimaging findings in oculomotor control, the findings can be linked to dysfunction within cortico–basal ganglia circuits. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Oculomotor abnormalities correlated with motor and non-motor symptom severity, indicating mechanistic relevance. The findings provide empirical support for predictive coding accounts and point to involvement of subcortical structures including projections from the frontal cortex to the basal ganglia. This highlights the value of studying cortico–basal ganglia circuits with implications for treatment and of developing oculomotor measures as potential biomarkers in FMD.

Background: Fibromyalgia is a chronic pain disorder, affecting 2-3% of the population, characterised by widespread pain, fatigue, sleep and cognitive symptoms. Despite symptom overlap between functional motor disorder (FMD) and fibromyalgia, the prevalence of fibromyalgia in FMD and its impact on health-related quality of life (HRQoL) remain unclear. Objectives: To assess the prevalence of fibromyalgia in FMD using the 2016 American College of Rheumatology diagnostic criteria and to evaluate its impact on HRQoL. Methods: A total of 139 consecutive patients with clinically established FMD (115 females, mean age 44.6 (SD 11.3) years) completed Fibromyalgia Survey Questionnaire, subjective motor symptoms and HRQoL assessments. Motor symptoms were objectively rated using the Simplified FMD Rating Scale (S-FMDRS). Major physical illnesses, neurological, and psychiatric comorbidities, and the use of centrally acting and nociceptive pain medication was recorded. Results: Fibromyalgia was present in 44.6% of FMD patients (95%CI: 36.2–53.3%). Those with fibromyalgia had higher S-FMDRS scores ( p < 0.01), lower HRQoL ( p < 0.001), more frequent use of centrally acting and nociceptive pain medication ( p < 0.01). Fibromyalgia severity was positively correlated with both subjective motor symptom severity ( p < 0.01) and S-FMDRS ( p < 0.05). Higher fibromyalgia severity ( p < 0.001), S-FMDRS ( p < 0.001), and psychiatric comorbidity ( p < 0.001) were independent predictors of lower HRQoL. Conclusions: In this study, fibromyalgia was common in FMD and associated with more severe motor symptoms, greater medication use and reduced quality of life, highlighting the importance of recognising and managing fibromyalgia in FMD.

Background: Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort.Methods: One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL.Results: Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups.Conclusions: We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of ‘functional’ symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March—October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.

Individuals with Wilson disease had widespread cerebral atrophy and diffuse iron accumulation in the deep gray matter nuclei at MRI whereby reduced putaminal volume was most associated with neurolo... Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy a...

The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes.