OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.
- MeSH
- Adult MeSH
- Interoception * physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Mapping MeSH
- Young Adult MeSH
- Brain * physiopathology diagnostic imaging MeSH
- Nervous System Diseases * physiopathology diagnostic imaging MeSH
- Attention physiology MeSH
- Heart Rate physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. OBJECTIVES: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. METHODS: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. RESULTS: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). CONCLUSIONS: This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- alpha-Synuclein metabolism MeSH
- Lewy Body Disease * diagnostic imaging pathology MeSH
- Cognitive Dysfunction * diagnostic imaging pathology physiopathology etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Locus Coeruleus * diagnostic imaging pathology MeSH
- Magnetic Resonance Imaging * MeSH
- Neuropsychological Tests MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Cognitive impairment in Parkinson's disease (PD) is a key non-motor complication during the disease course. OBJECTIVES: A review of detailed cognitive instruments to detect mild cognitive impairment (PD-MCI) or dementia (PDD) is needed to establish optimal tests that facilitate diagnostic accuracy. METHODS: We performed a systematic literature review of tests that assess memory, language including premorbid intelligence, and visuospatial domains (for tests of attention and executive functions see accompanying review) to determine suitability to assess cognition in PD. Based on in-depth scrutiny of psychometric and other relevant clinimetric properties, tests were rated as "recommended," "recommended with caveats," "suggested," or "listed" by the International Parkinson and Movement Disorder Society (IPMDS) panel of experts according to the IPMDS Clinical Outcome Assessment Scientific Evaluation Committee guidelines. RESULTS: We included 39 tests encompassing 48 outcome measures. Seven tests (different versions or subtests of the test counted once) were recommended, including four for memory, one for visuospatial domains, one for language (including three measures), and one for estimated premorbid intelligence. Furthermore, 10 tests (12 measures) were "recommended with caveats," 11 were "suggested," and 11 (15 measures) were "listed." CONCLUSIONS: Recommended neuropsychological tests in memory, visuospatial functions, and language are proposed to guide the assessment of cognitive impairment and its progression in PD-MCI and PDD, and for use in clinical trials to stratify participants or as outcome measures. Novel measures being developed will need extensive validation research to be "recommended." © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- Language * MeSH
- Cognitive Dysfunction * diagnosis etiology MeSH
- Humans MeSH
- Neuropsychological Tests * standards MeSH
- Memory * physiology MeSH
- Parkinson Disease * complications MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
Dystonia is a movement disorder characterized by genetic and clinical heterogeneity. A recurring p.(Glu303del)-deletion in TOR1A is a well-established cause for DYT-TOR1A (DYT1), an autosomal dominant early-onset isolated dystonia. TOR1A encodes TorsinA, an AAA + ATPase located in the nuclear envelope. By whole exome analyses of a family with a novel dystonia-hemichorea-/hemiballism phenotype, we identified a TOR1AIP2 NM_001199260.2 c.1234A > G p.(Arg412Gly) variant. The variant is very rare in databases and was absent from whole exome data from >1000 dystonia patients. TOR1AIP2 encodes LULL1, a transmembrane protein that activates TorsinA, and correct interaction between TorsinA and LULL1 is essential for proper nuclear envelope architecture. The p.(Arg412Gly) variant disrupts the binding interface between TorsinA and LULL1 around p.Arg412; this same interface is also impaired in DYT1. Functional analyses via a co-purification assay revealed that interaction between TorsinA-LULL1Arg412Gly is weaker than the wild-type interaction, and that it resembles the situation in DYT1 (TorsinAΔE303-LULL1). A second family with milder dystonia, hemichorea, and stereotypic leg flexion during gait and a TOR1AIP2 p.(Gln338His) variant was identified. The clinical phenotype of both families shared proximal arm movements, and flutter in facial musculature. Expressivity of the movement disorder symptoms was variable. Several proteins in the nuclear envelope have been implicated in various forms of neurodevelopmental disorders with dystonia. Taken together, our findings suggest TOR1AIP2 as a new candidate gene implicated in a complex hereditary movement disorder with dystonia and hemichorea/hemiballism.
- MeSH
- Chorea * genetics MeSH
- Adult MeSH
- Dyskinesias * genetics MeSH
- Dystonic Disorders * genetics MeSH
- Dystonia * genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Molecular Chaperones * genetics MeSH
- Pedigree MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: To assess the effect of overall, between- and within-day subjectively rated fluctuations in motor and non-motor symptoms in people with functional motor disorder (FMD) on the health-related quality of life (HRQoL). BACKGROUND: FMD is a complex condition characterized by fluctuating motor and non-motor symptoms that may negatively impact HRQoL. METHODS: Seventy-seven patients (54 females, mean age 45.4 ± 10.4 years) with a clinically established diagnosis of FMD, including weakness, completed symptom diaries, rating the severity of motor and non-motor symptoms (i.e., pain, fatigue, mood, cognitive difficulties) on a 10-point numerical scale three times daily for seven consecutive days. HRQoL was assessed using the SF-36 questionnaire. For the analysis, fluctuation magnitude was defined in terms of the variability in self-reported symptom scores. RESULTS: The mental component of SF-36 was jointly predicted by the overall severity scores (t(74) = -3.61, P < 0.001) and overall general fluctuations (t(74) = -2.98, P = 0.004). The physical SF-36 was found to be related only to the overall symptom severity scores (t(74) = -7.09, P < 0.001), but not to the overall fluctuations. The assessment of the impact of different components showed that the mental component of SF-36 was significantly influenced by the combined effect of average fatigue (t(73) = -3.86, P < 0.001), between-day cognitive symptoms fluctuations (t(73) = -3.22, P = 0.002), and within-day mood fluctuations (t(73) = -2.48, P = 0.015). CONCLUSIONS: This study demonstrated the impact of self-reported symptom fluctuations across multiple motor and non-motor domains on mental but not physical HRQoL in FMD and highlighted the importance of assessing and managing fluctuations in clinical practice.
- MeSH
- Affect physiology MeSH
- Pain psychology physiopathology MeSH
- Adult MeSH
- Quality of Life * psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Movement Disorders psychology physiopathology MeSH
- Surveys and Questionnaires MeSH
- Severity of Illness Index MeSH
- Fatigue * psychology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
RATIONALE: Patients who experience seizures, including PNES, are usually advised to discontinue driving, or have their driving privileges revoked until a determined period of seizure-freedom is achieved. In this retrospective study, patients with PNES who requested driving privileges or reported having resumed driving were compared to those who did not on measures of depression, anxiety, PTSD, and cognitive flexibility/motor speed. METHODS: DiagnosisofPNESwasconfirmedwithvideo-EEG.Demographicand clinical dataand requests for reinstatement of driving privileges (requiring 6 or more months seizure freedom) and reports of decisions to resume driving were noted. Tests of motor speed and hand eye coordination and self-report questionnaires of depression, anxiety and PTSD administered as part of neuropsychological assessment were analyzed. RESULTS: A total of 403 patients with PNES evaluated in 2010-2020 were identified. Of those, 365 patients were eligible for inclusion, and of those, 60 applied for driving privileges or reported that they resumed driving. When the two groups were compared, the group that applied for driving privileges or decided to resume driving was significantly less depressed (p = 0.001) when tested than the group that did not. Furthermore, a significant difference was seen in measures of motor performance between those who requested to resume driving and those who did not (DKEFS T1, p = 0.006, DKEFS T2, p = 0.001, DKEFS T3, p = 0.002, DKEFS T4, p = 0.001; GPT dominant, p = 0.05, GPT non-dominant, p = 0.003). CONCLUSION: Driving a motor vehicle is a useful measure of improvement for PNES because patients with seizures are required to discontinue driving until seizure-freedom is achieved. This study revealed that lower levels of depression and better fine motor functioning were associated with reported seizure-freedom and driving resumption. Depression is commonly associated with diminished performance (slower motor response times and impaired fine motor movements) on tests of motor functioning, both of which may result in less interest in pursuing permission to resume driving. These findings suggest that mood symptoms (and associated performance on measures of motor speed and coordination) may have prognostic significance in patients diagnosed with PNES. This also suggests that timely treatment of depression in newly diagnosed patients with PNES may be indicated.
- MeSH
- Depression psychology diagnosis etiology MeSH
- Adult MeSH
- Electroencephalography MeSH
- Conversion Disorder psychology diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Neuropsychological Tests MeSH
- Stress Disorders, Post-Traumatic psychology diagnosis MeSH
- Psychomotor Performance physiology MeSH
- Psychophysiologic Disorders diagnosis psychology MeSH
- Retrospective Studies MeSH
- Automobile Driving * psychology MeSH
- Anxiety psychology etiology diagnosis MeSH
- Seizures * psychology diagnosis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The aim of this work was to study the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on the subnetwork of subcortical and cortical motor regions and on the whole brain connectivity using the functional connectivity analysis in Parkinson's disease (PD). The high-density source space EEG was acquired and analyzed in 43 PD subjects in DBS on and DBS off stimulation states (off medication) during a cognitive-motor task. Increased high gamma band (50-100 Hz) connectivity within subcortical regions and between subcortical and cortical motor regions was significantly associated with the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III improvement after DBS. Whole brain neural correlates of cognitive performance were also detected in the high gamma (50-100 Hz) band. A whole brain multifrequency connectivity profile was found to classify optimal and suboptimal responders to DBS with a positive predictive value of 0.77, negative predictive value of 0.55, specificity of 0.73, and sensitivity of 0.60. Specific connectivity patterns related to PD, motor symptoms improvement after DBS, and therapy responsiveness predictive connectivity profiles were uncovered.
- MeSH
- Electroencephalography methods MeSH
- Deep Brain Stimulation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain physiopathology diagnostic imaging MeSH
- Subthalamic Nucleus * physiopathology MeSH
- Parkinson Disease * therapy physiopathology MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Léze lícního nervu vede ve všech fázích onemocnění k celé řadě funkčních, motorických i psychických omezení. Akutní terapie má v neurologii a neurochirurgii již dlouhou dobu definované postupy na základech evidence based medicine. V navazující rehabilitační terapii jsou však postupy nekonzistentní, terapie jsou aplikovány dle empirických zkušeností, s malou oporou v evidenci. V současné době jsou již některé postupy ověřovány, ale stále buď na malém vzorku pacientů, nebo pouze v jednotlivých oblastech. Např. v oblasti elektroterapie jsou metodiky nejednotné, bez jednoznačně definovaných doporučení. K účinku relaxačních metod, masáží a manuální lymfatické drenáže neexistují rovněž žádná přesvědčivá data. Pozitivně se jeví využití zrcadlové terapie a virtuální terapie s biofeedbackem, ale i zde je potřebné sjednotit postup a doplnit evidenci.
Facial nerve lesions lead to a variety of functional, motor, and psychological limitations in all stages of the disease. Acute therapy in neurology and neurosurgery has long defined procedures based on evidence-based medicine. However, in follow-up, rehabilitation therapy procedures are inconsistent, with therapies applied according to empirical experience with little support from the evidence. Currently, some procedures are already being validated, but still either in a small sample of patients or only in individual areas. For example, in the field of electrotherapy, methodologies are inconsistent, without clearly defined recommendations. There are also no conclusive data on the effect of relaxation methods, massage, and manual lymphatic drainage. The use of mirror therapy and virtual therapy with biofeedback is positive, but here too, there appears a need for standardization of practice and the addition of evidence.
Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD.
- MeSH
- Depression epidemiology physiopathology MeSH
- Adult MeSH
- Comorbidity * MeSH
- Middle Aged MeSH
- Humans MeSH
- Nocturnal Myoclonus Syndrome epidemiology physiopathology MeSH
- Polysomnography * MeSH
- Disorders of Excessive Somnolence * epidemiology physiopathology MeSH
- Sleep Wake Disorders epidemiology physiopathology MeSH
- Surveys and Questionnaires MeSH
- Sleepiness MeSH
- Sleep Latency physiology MeSH
- Restless Legs Syndrome physiopathology epidemiology MeSH
- Fatigue physiopathology epidemiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
BACKGROUND: Cerebral palsy (CP) is the most common cause of physical disability in childhood defined as a group of permanent disorders of movement. The aim of this study was to determine the effects of 12-week aquatic exercise program on gross motor function, swimming skills, and walking ability in children with cerebral palsy. METHODS: Eighteen children (mean±SD age: 12.3±3 years) with cerebral palsy classified at levels I, II and III on the Gross Motor Function Classification System were allocated to one group, where the first 12 weeks were a control period while another 12 weeks were an experimental period. The participants underwent the same battery of tests focusing gross motor function, swimming skills, and walking ability on three occasions. RESULTS: Control period was stable with no significant changes in any of measurements. After the 12-week experimental program, a statistically significant improvement was determined in gross motor function (P=0.005), swimming skills (P=0.000), walking endurance and walking velocity (P=0.000). No significant differences (P>0.05) were observed for walking efficiency. CONCLUSIONS: The 12-week aquatic exercise program (3/week, 60 minutes), combining Halliwick method, swimming and walking activities may improve the gross motor function, swimming skills, walking endurance and velocity in ambulatory children with cerebral palsy.
