ABSTRACT
INTRODUCTION: Aim of the present study was to assess personality and psychopathological characteristics in patients with functional movement disorders (FMDs) compared to patients with other neurological disorders (OND). METHODS: In this cross-sectional study, patients affected by clinically established FMDs and OND who attended the Neurologic Unit of the University-Hospital "Policlinico-San Marco" of Catania from the 1st of December 2021 to the 1st of June 2023 were enrolled. Personality characteristics were assessed with the Rorschach test coded according to Exner's comprehensive system and the Structured Clinical Interview for DSM-5 (SCID-II). RESULTS: Thirty-one patients with FMDs (27 women; age 40.2±15.5 years; education 11.7±3.2 years; disease duration 2.3±2.5 years) and 24 patients affected by OND (18 women; age 35.8±16.3 years; education 11.9±2.9 years; disease duration 3.4±2.8 years) were enrolled. At the Rorschach, FMDs presented a significantly higher frequency of Popular (P) and sum of all Human content codes (SumH>5) responses and avoidant coping than OND. CONCLUSION: FMDs presented "conformity behaviors", excessive interest in others than usual a maladaptive avoidant style of coping and a difficulty in verbalizing emotional distress. These psychopathological characteristics may favor the occurrence of FMDs.
Subject(s)
Movement Disorders , Personality , Humans , Female , Male , Adult , Movement Disorders/psychology , Movement Disorders/physiopathology , Cross-Sectional Studies , Middle Aged , Adaptation, PsychologicalABSTRACT
INTRODUCTION: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. METHODS: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. RESULTS: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. DISCUSSION: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. CONCLUSION: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be.
Subject(s)
Movement Disorders , Neuropsychological Tests , Parkinson Disease , Social Cognition , Humans , Parkinson Disease/complications , Parkinson Disease/physiopathology , Parkinson Disease/psychology , Parkinson Disease/diagnosis , Male , Female , Middle Aged , Movement Disorders/diagnosis , Movement Disorders/psychology , Movement Disorders/physiopathology , Aged , Theory of Mind/physiology , Attention/physiologyABSTRACT
PURPOSE OF REVIEW: This article reviews the recognition and management of cognitive syndromes in movement disorders, including those with parkinsonism, chorea, ataxia, dystonia, and tremor. RECENT FINDINGS: Cognitive and motor syndromes are often intertwined in neurologic disorders, including neurodegenerative diseases such as Parkinson disease, atypical parkinsonian syndromes, Huntington disease, and other movement disorders. Cognitive symptoms often affect attention, working memory, and executive and visuospatial functions preferentially, rather than language and memory, but heterogeneity can be seen in the various movement disorders. A distinct cognitive syndrome has been recognized in patients with cerebellar syndromes. Appropriate recognition and screening for cognitive changes in movement disorders may play a role in achieving accurate diagnoses and guiding patients and their families regarding progression and management decisions. SUMMARY: In the comprehensive care of patients with movement disorders, recognition of cognitive syndromes is important. Pharmacologic treatments for the cognitive syndromes, including mild cognitive impairment and dementia, in these movement disorders lag behind the therapeutics available for motor symptoms, and more research is needed. Patient evaluation and management require a comprehensive team approach, often linking neurologists as well as neuropsychologists, psychologists, psychiatrists, social workers, and other professionals.
Subject(s)
Cognitive Dysfunction , Movement Disorders , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/therapy , Humans , Movement Disorders/psychology , SyndromeABSTRACT
BACKGROUND AND PURPOSE: We investigated the relation between the ipsilesional corticospinal tract (CST) state and activity of daily living independence in patients with chronic intracerebral hemorrhage. METHODS: Fifty-six consecutive patients with unilateral intracerebral hemorrhage and 38 healthy control subjects were recruited for this study. The Motricity index and the modified Barthel index were used to evaluate motor function of the affected extremities and activity of daily living independence, respectively. The diffusion tensor imaging parameter values for fractional anisotropy (FA) and voxel number (VN) of the CST were determined. Ratios of the ipsilesional to the contralesional CST measures were calculated and are presented as the CST-ratio (FA value and VN). RESULTS: The FA value and VN of the ipsilesional CST and the CST-ratio in the patient group were lower than those of the control group (P<0.05). There was a strong positive correlation between the Motricity index score of the affected extremities and the modified Barthel index score (P<0.05), while the FA value and VN of the ipsilesional CST and the CST-ratio showed moderate and strong positive correlations with the Motricity index and modified Barthel index scores, respectively (P<0.05). In addition, the VN of the ipsilesional CST showed excellent utility as a classifier, whereas the FA value of the ipsilesional CST and the FA value and VN of the CST-ratio showed good classifier utility (P<0.05). CONCLUSIONS: We demonstrated that impairment of activity of daily living independency was closely related to the injury severity of the ipsilesional CST in patients with chronic intracerebral hemorrhage. In addition, the injury severity of the ipsilesional CST can be used to classify the degree of activity of daily living independency. Registration: URL: http://www.e-irb.com/index.jsp; Unique identifier: 2021-03-014.
Subject(s)
Activities of Daily Living , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/psychology , Pyramidal Tracts/diagnostic imaging , Adult , Aged , Anisotropy , Chronic Disease , Diffusion Tensor Imaging , Disability Evaluation , Female , Humans , Male , Middle Aged , Movement Disorders/pathology , Movement Disorders/psychology , Stroke/etiology , Stroke Rehabilitation , Treatment Outcome , White Matter , Young AdultABSTRACT
'Yips' in golf is a complex spectrum of anxiety and movement-disorder that affects competitive sporting performance. With unclear etiology and high prevalence documented in western literature, the perception and management of this psycho-neuromuscular problem among Japanese elite golfers is unknown. The objective of this study was to explore factors associated with yips, investigate the performance deficits and the strategies implemented to prevent yips. We surveyed approx. 1300 professional golfers on their golfing habits, anxiety and musculoskeletal problems, kinematic deficits, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis. 35% of the respondents had experienced yips in their career, their odds increasing proportionally to their golfing experience. Regardless of musculoskeletal symptoms, about 57% of all yips-golfers attributed their symptoms to psychological causes. Network analysis highlighted characteristic movement patterns, i.e. slowing, forceful or freezing of movement for putting, approach and teeing shots respectively. Golfers' self-administered strategies to relieve yips were mostly inconsequential. Within the limits of our self-reported survey, most golfers perceived yips as a psychological phenomenon despite evidence pointing to a movement-disorder. While self-administered interventions were satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early management of the problem.
Subject(s)
Anxiety Disorders/epidemiology , Dystonic Disorders/epidemiology , Golf/physiology , Movement Disorders/epidemiology , Neural Networks, Computer , Stress, Psychological/epidemiology , Adolescent , Adult , Aged , Anxiety Disorders/psychology , Dystonic Disorders/psychology , Female , Humans , Japan/epidemiology , Male , Middle Aged , Movement Disorders/psychology , Perception , Prevalence , Self Report , Stress, Psychological/psychology , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) as invariably observed in patients with Parkinson's Disease (PD). The co-chaperone DNAJB6 has previously been found to be expressed at higher levels in PD patients than in control subjects and was also found in Lewy bodies. Our previous experiments showed that knock out of DNAJB6 induced α-syn aggregation in cellular level. However, effects of overexpression of DNAJB6 against α-syn aggregation remains to be investigated. METHODS: We used a α-syn CFP/YFP HEK293 FRET cell line to investigate the effects of overexpression of DNAJB6 in cellular level. α-syn aggregation was induced by transfection α-syn preformed fibrils (PPF), then was measured FRET analysis. We proceeded to investigate if DNAJB6b can impair α-syn aggregation and toxicity in an animal model and used adeno associated vira (AAV6) designed to overexpress of human wt α-syn, GFP-DNAJB6 or GFP in rats. These vectors were injected into the SNpc of the rats, unilaterally. Rats injected with vira to express α-syn along with GFP in the SNpc where compared to rats expressing α-syn and GFP-DNAJB6. We evaluated motor functions, dopaminergic cell death, and axonal degeneration in striatum. RESULTS: We show that DNAJB6 prevent α-syn aggregation induced by α-syn PFF's, in a cell culture model. In addition, we observed α-syn overexpression caused dopaminergic cell death and that this was strongly reduced by co-expression of DNAJB6b. The lesion caused by α-syn overexpression resulted in behavior deficits, which increased over time as seen in stepping test, which was rescued by co-expression of DNAJB6b. CONCLUSION: We here demonstrate for the first time that DNAJB6 is a strong suppressor of α-syn aggregation in cells and in animals and that this results in a suppression of dopaminergic cell death and PD related motor deficits in an animal model of PD.
Subject(s)
HSP40 Heat-Shock Proteins/genetics , Molecular Chaperones/genetics , Nerve Tissue Proteins/genetics , Parkinson Disease/genetics , alpha-Synuclein/genetics , Animals , Axons/pathology , Cell Death , Disease Models, Animal , Dopaminergic Neurons/pathology , Female , Gene Expression Regulation , HEK293 Cells , HSP40 Heat-Shock Proteins/biosynthesis , Humans , Molecular Chaperones/biosynthesis , Movement Disorders/genetics , Movement Disorders/psychology , Neostriatum/pathology , Nerve Tissue Proteins/biosynthesis , Parkinson Disease/physiopathology , Psychomotor Performance , Rats , Rats, Sprague-Dawley , alpha-Synuclein/antagonists & inhibitorsABSTRACT
Functional movement disorder (FMD) presents as disabling motor symptoms that cannot be explained by organic processes. Despite the lack of lesion or known central nervous system dysfunction, distortion in sensorimotor processing in movement generation and execution is often observed. A person's capacity to judge laterality of a body part requires processing of sensorimotor information. This prospective observational study compared reaction time (RT) and accuracy (ACC) of hand laterality recognition between 30 people diagnosed with FMD and 30 age-matched healthy control participants. The association of RT and ACC with severity of FMD as measured by the Simplified Functional Movement Disorders Rating Scale (SFMDRS) was also explored. RT was on average 0.6 s slower (95% CI 0.4 - 0.8 s, p < 0.001) in patients with FMD (mean 2.2 s, standard deviation (SD) 0.5) than controls (mean 1.7 s, SD 0.3). ACC was on average 8.9% lower (95% CI -15.7 - -2.2, p = 0.01) in patients with FMD (mean 79.6%, SD 16.6) than controls (mean 88.5%, SD 8.1). When adjusted for SFMDRS using robust regression, RT was 0.3 s slower (95% CI 0.01 - 0.5, p = 0.04) in cases than in controls, but ACC was no longer different between groups. There was a moderate negative correlation between RT and ACC in FMD patients (ρ -0.58, p < 0.001 but not in controls (ρ -0.26, p = 0.17). People with FMD had significantly slower RT and lower ACC compared to the control group. These results provide new insights into underlying sensorimotor processing deficits in those with FMD.
Subject(s)
Functional Laterality/physiology , Hand/physiology , Imagination/physiology , Movement Disorders/physiopathology , Movement/physiology , Recognition, Psychology/physiology , Adult , Female , Humans , Male , Middle Aged , Movement Disorders/diagnosis , Movement Disorders/psychology , Prospective Studies , Reaction Time/physiologyABSTRACT
OBJECTIVES: The aim of this study was to determine the impact of the COVID-19 pandemic on access to rehabilitation therapies and the impact of changes in therapy access on the physical and mental well-being of children with motor impairment and their caregivers. DESIGN: Caregivers of children younger than 18 yrs with childhood-onset motor impairment (primarily cerebral palsy) completed an anonymous survey through the online platform REDCap between May 5 and July 13, 2020. RESULTS: The survey was completed by 102 participants. Before the pandemic, 92 of 102 children (90%) were receiving one or more therapies; at the time surveyed, 55 children (54%) were receiving any therapies (P < 0.001). More than 40% of the sample reported increased child stress, decreased physical activity, and/or decline in mobility/movement. Participants who reported a decrease in number of therapies at the time surveyed more frequently reported lower satisfaction with treatment delivery (P < 0.001), a decline in child's mobility (P = 0.001), and increased caregiver stress (P = 0.004). Five qualitative themes were identified from open-ended question responses related to therapies and well-being. CONCLUSIONS: Access to pediatric rehabilitation therapies was disrupted during COVID-19. Disrupted access may be related to impact on physical and mental health. With the expansion of telehealth, caregiver and child feedback should be incorporated to optimize benefit.
Subject(s)
COVID-19 , Cerebral Palsy/rehabilitation , Health Services Accessibility/statistics & numerical data , Movement Disorders/rehabilitation , Quarantine/psychology , Adolescent , Adult , Caregiver Burden/epidemiology , Caregivers/psychology , Cerebral Palsy/psychology , Child , Continuity of Patient Care/statistics & numerical data , Female , Humans , Male , Mobility Limitation , Movement Disorders/psychology , Qualitative Research , SARS-CoV-2 , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Surveys and QuestionnairesABSTRACT
The evaluation and management of patients with movement disorders has evolved considerably due to the COVID-19 pandemic, including the assessment of candidates for deep brain stimulation (DBS) therapy. Members of the Neuropsychology Focus Group from the Parkinson Study Group Functional Neurosurgical Working Group met virtually to discuss current practices and solutions, build consensus, and to inform the DBS team and community regarding the complexities of performing DBS neuropsychological evaluations during COVID-19. It is our viewpoint that the practice of neuropsychology has adapted successfully to provide tele-neuropsychological pre-DBS evaluations during the global pandemic, thus permanently changing the landscape of neuropsychological services.
Subject(s)
COVID-19 , Deep Brain Stimulation/trends , Movement Disorders/psychology , Movement Disorders/surgery , Neuropsychological Tests , Neuropsychology/trends , Neurosurgery/trends , Pandemics , Parkinson Disease/psychology , Parkinson Disease/surgery , Deep Brain Stimulation/statistics & numerical data , Humans , TelemedicineABSTRACT
OBJECTIVES: Neurocognitive disorders in Parkinson's disease (PD) are common and heterogeneous. The aim of this study was to use a data-driven method to describe different cognitive phenotypes in PD and to explore anxiety, depression, and motor disturbances across the different cognitive profiles. METHOD: Latent profile analysis was applied to the neuropsychological performances of 65 patients with idiopathic PD assessed by means of a battery of tests that encompass measures of attention, memory, executive functions, social cognition, language, and visuospatial abilities. RESULTS: A three-cluster model produced the best solution: Cluster A (21.54%) included patients with intact cognition or with a relatively slight cognitive impairment in memory and executive functioning; Cluster B (53.85%) included patients with an intermediate level of cognitive impairment; and Cluster C (24.61%) included patients with the most severe cognitive impairment, with greater deficit compared to Cluster B in executive functioning, and, notably, in tasks with a predominantly posterior cortical basis (naming and visuospatial abilities). The three subgroups did not differ in terms of age, gender, disease duration, motor symptom severity or side of onset, levodopa equivalent daily dose, level of anxiety, or depression; however, patients from Cluster C showed greater impairment than patients from Cluster A in measures of everyday functioning. CONCLUSIONS: We presented a qualitative description of three distinct cognitive phenotypes emerging from a sample of 65 PD patients. The three clusters seem to be related to daily functioning but are independent from the stage of disease, motor functioning, anxiety, and depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Subject(s)
Cognition , Parkinson Disease/psychology , Aged , Aged, 80 and over , Anxiety/etiology , Anxiety/psychology , Attention , Cluster Analysis , Cognition Disorders/etiology , Cognition Disorders/psychology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Depression/etiology , Depression/psychology , Executive Function , Female , Humans , Language , Male , Memory , Movement Disorders/etiology , Movement Disorders/psychology , Neuropsychological Tests , Parkinson Disease/complications , Phenotype , Space PerceptionABSTRACT
BACKGROUND: While the etiology remains elusive, macrophages and T cells in peripheral nerves are considered as effector cells mediating autoimmune peripheral neuropathy (APN), such as Guillain-Barre syndrome. By recognizing both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) signals, TLRs play a central role in the initiation of both innate and adaptive immune responses. In this study, we aimed to understand the involvement of TLR4 in the pathogenesis of APN and explore the potential of TLR4 as a drug target for therapeutic use. METHODS: APN was induced by a partial ligation on one of the sciatic nerves in B7.2 (L31) transgenic mice which possess a predisposed inflammatory background. APN pathology and neurological function were evaluated on the other non-injured sciatic nerve. RESULTS: TLR4 and its endogenous ligand HMGB1 were highly expressed in L31 mice, in circulating immune cells and in peripheral nerves. Enhanced TLR4 signaling was blocked with TAK 242, a selective TLR4 inhibitor, before and after disease onset. Intraperitoneal administration of TAK 242 not only inhibited monocyte, macrophage and CD8+ T cell activation, but also reduced the release of pro-inflammatory cytokines. TAK 242 protected mice from severe myelin and axonal loss, resulting in a remarkable improvement in mouse motor and sensory functions. TAK 242 was effective in alleviating the disease in both preventive and reversal paradigms. CONCLUSION: The study identified the critical contribution of TLR4-mediated macrophage activation in disease course and provided strong evidence to support TLR4 as a useful drug target for treating inflammatory autoimmune neuropathy.
Subject(s)
Autoimmune Diseases/physiopathology , Movement Disorders/physiopathology , Peripheral Nervous System Diseases/physiopathology , Sensation Disorders/physiopathology , Toll-Like Receptor 4/genetics , Animals , Autoimmune Diseases/prevention & control , Autoimmune Diseases/psychology , CD8-Positive T-Lymphocytes/drug effects , Female , HMGB1 Protein/metabolism , Macrophages/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Monocytes/drug effects , Movement Disorders/prevention & control , Movement Disorders/psychology , Peripheral Nervous System Diseases/psychology , Sciatic Nerve/injuries , Sensation Disorders/prevention & control , Sensation Disorders/psychology , Signal Transduction , Sulfonamides/pharmacology , Toll-Like Receptor 4/antagonists & inhibitorsABSTRACT
OBJECTIVE: To determine rates of psychiatric comorbidity in a clinical sample of childhood movement disorders (MDs). DESIGN: Cohort study. SETTING: Tertiary children's hospital MD clinics in Sydney, Australia and London, UK. PATIENTS: Cases were children with tic MDs (n=158) and non-tic MDs (n=102), including 66 children with dystonia. Comparison was made with emergency department controls (n=100), neurology controls with peripheral neuropathy or epilepsy (n=37), and community controls (n=10 438). INTERVENTIONS: On-line development and well-being assessment which was additionally clinically rated by experienced child psychiatrists. MAIN OUTCOME MEASURES: Diagnostic schedule and manual of mental disorders-5 criteria for psychiatric diagnoses. RESULTS: Psychiatric comorbidity in the non-tic MD cohort (39.2%) was comparable to the tic cohort (41.8%) (not significant). Psychiatric comorbidity in the non-tic MD cohort was greater than the emergency control group (18%, p<0.0001) and the community cohort (9.5%, p<0.00001), but not the neurology controls (29.7%, p=0.31). Almost half of the patients within the tic cohort with psychiatric comorbidity were receiving medical psychiatric treatment (45.5%) or psychology interventions (43.9%), compared with only 22.5% and 15.0%, respectively, of the non-tic MD cohort with psychiatric comorbidity. CONCLUSIONS: Psychiatric comorbidity is common in non-tic MDs such as dystonia. These psychiatric comorbidities appear to be under-recognised and undertreated.
Subject(s)
Depressive Disorder/diagnosis , Dystonia/psychology , Movement Disorders/psychology , Australia , Case-Control Studies , Child , Cohort Studies , Comorbidity , Depressive Disorder/psychology , Diagnostic and Statistical Manual of Mental Disorders , Emergency Service, Hospital , England , Female , Humans , Male , PsychometricsABSTRACT
Dysfunction of neuronal circuits is an important determinant of neurodegenerative diseases. Synaptic dysfunction, death, and intrinsic activity of neurons are thought to contribute to the demise of normal behavior in the disease state. However, the interplay between these major pathogenic events during disease progression is poorly understood. Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a deficiency in the ubiquitously expressed protein SMN and is characterized by motor neuron death, skeletal muscle atrophy, as well as dysfunction and loss of both central and peripheral excitatory synapses. These disease hallmarks result in an overall reduction of neuronal activity in the spinal sensory-motor circuit. Here, we show that increasing neuronal activity by chronic treatment with the FDA-approved potassium channel blocker 4-aminopyridine (4-AP) improves motor behavior in both sexes of a severe mouse model of SMA. 4-AP restores neurotransmission and number of proprioceptive synapses and neuromuscular junctions (NMJs), while having no effects on motor neuron death. In addition, 4-AP treatment with pharmacological inhibition of p53-dependent motor neuron death results in additive effects, leading to full correction of sensory-motor circuit pathology and enhanced phenotypic benefit in SMA mice. Our in vivo study reveals that 4-AP-induced increase of neuronal activity restores synaptic connectivity and function in the sensory-motor circuit to improve the SMA motor phenotype.SIGNIFICANCE STATEMENT Spinal muscular atrophy (SMA) is a neurodegenerative disease, characterized by synaptic loss, motor neuron death, and reduced neuronal activity in spinal sensory-motor circuits. However, whether these are parallel or dependent events is unclear. We show here that long-term increase of neuronal activity by the FDA-approved drug 4-aminopyridine (4-AP) rescues the number and function of central and peripheral synapses in a SMA mouse model, resulting in an improvement of the sensory-motor circuit and motor behavior. Combinatorial treatment of pharmacological inhibition of p53, which is responsible for motor neuron death and 4-AP, results in additive beneficial effects on the sensory-motor circuit in SMA. Thus, neuronal activity restores synaptic connections and improves significantly the severe SMA phenotype.
Subject(s)
Movement Disorders/drug therapy , Muscular Atrophy, Spinal/drug therapy , Psychomotor Performance/drug effects , Sensation Disorders/drug therapy , 4-Aminopyridine/therapeutic use , Animals , Cell Death/drug effects , Mice , Mice, Knockout , Motor Neurons/drug effects , Movement Disorders/etiology , Movement Disorders/psychology , Muscular Atrophy, Spinal/complications , Muscular Atrophy, Spinal/psychology , Neuromuscular Junction/drug effects , Potassium Channel Blockers/therapeutic use , Proprioception/drug effects , Sensation Disorders/etiology , Sensation Disorders/psychology , Survival of Motor Neuron 1 Protein/genetics , Synapses/drug effects , Synaptic Transmission/drug effects , Tumor Suppressor Protein p53/antagonists & inhibitorsABSTRACT
KCNN2 encodes the small conductance calcium-activated potassium channel 2 (SK2). Rodent models with spontaneous Kcnn2 mutations show abnormal gait and locomotor activity, tremor and memory deficits, but human disorders related to KCNN2 variants are largely unknown. Using exome sequencing, we identified a de novo KCNN2 frameshift deletion in a patient with learning disabilities, cerebellar ataxia and white matter abnormalities on brain MRI. This discovery prompted us to collect data from nine additional patients with de novo KCNN2 variants (one nonsense, one splice site, six missense variants and one in-frame deletion) and one family with a missense variant inherited from the affected mother. We investigated the functional impact of six selected variants on SK2 channel function using the patch-clamp technique. All variants tested but one, which was reclassified to uncertain significance, led to a loss-of-function of SK2 channels. Patients with KCNN2 variants had motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Altogether, our findings provide evidence that heterozygous variants, likely causing a haploinsufficiency of the KCNN2 gene, lead to novel autosomal dominant neurodevelopmental movement disorders mirroring phenotypes previously described in rodents.
Subject(s)
Movement Disorders/genetics , Neurodevelopmental Disorders/genetics , Small-Conductance Calcium-Activated Potassium Channels/genetics , Adolescent , Adult , Cerebellar Ataxia/genetics , Cerebellar Ataxia/psychology , Child , Child, Preschool , Electrophysiological Phenomena , Exome , Frameshift Mutation , Genetic Variation , Haploinsufficiency , Humans , Intellectual Disability/genetics , Intellectual Disability/psychology , Learning Disabilities/genetics , Learning Disabilities/psychology , Magnetic Resonance Imaging , Male , Middle Aged , Movement Disorders/psychology , Mutation, Missense/genetics , Neurodevelopmental Disorders/psychology , Patch-Clamp Techniques , White Matter/abnormalities , White Matter/diagnostic imaging , Young AdultABSTRACT
BACKGROUND AND PURPOSE: The majority of patients with advanced Parkinson's disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson's disease; the proportion of Parkinson's patients with advanced Parkinson's disease, the referral process, and the clinical features used to characterize advanced Parkinson's disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson's patients identified as advanced patients according to physician's judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. METHODS: The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson's disease status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson's disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. RESULTS: Overall, 2627 patients with Parkinson's disease from 126 sites were documented. In Hungary, 100 patients with Parkinson's disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson's disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson's disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). CONCLUSION: Physicians in Hungarian movement disorder centers assessed that half of the Parkinson's patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson's disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.
Subject(s)
Movement Disorders/psychology , Parkinson Disease/classification , Parkinson Disease/diagnosis , Quality of Life/psychology , Cross-Sectional Studies , Humans , Hungary/epidemiology , Movement Disorders/diagnosis , Movement Disorders/epidemiology , Parkinson Disease/epidemiology , Parkinson Disease/psychology , Severity of Illness Index , Surveys and QuestionnairesSubject(s)
Anxiety/psychology , COVID-19 , Conversion Disorder/psychology , Depression/psychology , Movement Disorders/psychology , Seizures/psychology , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/psychology , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Italy , Male , Middle Aged , Young AdultABSTRACT
AIM: To develop a cognitive behavioural treatment (CBT) approach that included novel attention training components to support symptom management in children with a primary diagnosis of Functional Movement Disorder (FMD). METHOD: Eighteen children (9 male and 9 female) with a mean age of 13 years (sd = 2.46, range 10-18 years) were assessed and completed CBT with novel attention training components. Treatment outcomes were measured using the Child Global Assessment Scale (CGAS) which was administered at baseline and post-treatment. RESULTS: Scores on the CGAS improved significantly post-treatment (p < 0.001) with all participants showing significant change in functioning on the basis of the Reliable Change Index (RCI), with clinically significant change across classification boundaries. INTERPRETATION: This case series provides support for the use of CBT with attention training components for the management of FMD. Larger trials are necessary to identify which individual treatment components are most effective and to better understand and quantify response to treatment. Future clinical treatment studies would benefit from the inclusion of objective measures of interoception and attentional focus.
Subject(s)
Cognitive Behavioral Therapy/methods , Movement Disorders/psychology , Movement Disorders/therapy , Psychophysiologic Disorders/psychology , Psychophysiologic Disorders/therapy , Adolescent , Child , Female , Humans , Male , Treatment OutcomeABSTRACT
Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders.
Subject(s)
Consensus , Movement Disorders/physiopathology , Psychomotor Performance/physiology , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Animals , Congresses as Topic , Europe/epidemiology , Humans , Movement Disorders/diagnosis , Movement Disorders/epidemiology , Movement Disorders/psychology , Prospective Studies , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Schizophrenia/diagnosis , Schizophrenia/epidemiologySubject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/psychology , Movement Disorders/diagnosis , Movement Disorders/psychology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/psychology , Adult , COVID-19 , Coronavirus Infections/complications , Female , Humans , Movement Disorders/complications , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2ABSTRACT
OBJECTIVE: Emotional difficulties are common in functional movement disorders (FMD), yet their contribution to the disease remains unclear. We explored the potential role of emotional difficulties as risk and maintaining factors of FMD by looking at the effect of emotions on attention. METHOD: The dot-probe task was used to investigate attentional biases induced by emotional faces in 25 patients with FMD and 25 healthy controls (HC). A pair of faces, one emotional (happy, angry, sad) and the other neutral, was displayed on a monitor to either the left or the right side of a central fixation cross. The face disappeared and a dot was flashed in place of one of the faces. Participants had to indicate the location of the dot. All participants completed the Toronto Alexithymia Scale. Psychological assessment of 23 patients also involved the Short Form Health Survey, the Hamilton Anxiety and the Hamilton Depression Rating Scales. RESULTS: A general attentional bias away from emotional faces was noted for the FMD group compared to the HC. A more fine-tuned analysis revealed an attentional bias specifically away from sad faces for the FMD. CONCLUSION: Our findings suggest a specific effect of emotions on attention in FMD that likely involves avoidance of sadness. Since this was not related to alexithymia or mood, we excluded these factors in explaining the results. Attentional bias away from sad faces correlated with general health, suggesting that avoidance of sadness might contribute to the perception of a better general health status in FMD.