Cognition in children and young adults with myoclonus dystonia - A case control study

INTRODUCTION: In adult patients with myoclonus dystonia (MD), cognitive deficits regarding information processing speed and executive functioning have been demonstrated, but it is unclear whether cognition is also affected in young MD patients. The present study investigates cognition in young MD patients and the role of an SGCE mutation. METHODS: In this case control study 20 young MD patients (9 children (5.75-12.58 years) and 11 adolescents/young adults (13.5-25.42 years)) were included and compared to an age-, IQ- and gender-matched healthy control group (n = 40). Within the patient group, we compared patients with (n = 12) and without (n = 8) an SGCE mutation (SGCE+/-). All participants completed neuropsychological tests for memory, attention/processing speed, executive functioning, social cognition and language. RESULTS: Overall, patients performed in the (low) average range, comparable to healthy controls. Only on a semantic fluency test, patients scored significantly lower. SGCE + patients had lower emotion recognition scores (a social cognition test) compared to SGCE-patients. CONCLUSION: We could not demonstrate cognitive deficits as found in adult MD patients in our younger group. Patients performed on the same level as healthy controls, with only a small difference in semantic fluency. We did not find executive deficits that were manifest in adult SGCE + patients, but we did find an association of an SGCE mutation and lower scores on a social cognition test. Similar to executive functioning, social cognition is a prefrontally regulated function, but had not been tested in adult MD. Hence, social cognition may precede executive problems in adulthood, suggesting growing into deficit

Which disease features run in essential tremor families?:A systematic review

Essential tremor is a common and highly heritable movement disorder. It is largely unknown, however, to what extent family members share overlapping symptoms. Such knowledge would be useful, as it may lead to the definition of familial essential tremor phenotypes, which will aid the ongoing search for genotypes. Also, this information can be used by clinicians in patient counselling. Therefore, we conducted a systematic review to provide an overview of the evidence on which essential tremor features run in families, to assess the literature's strengths and weaknesses, and to provide recommendations for future studies. PubMed was searched resulting in 460 titles: sixteen articles ultimately proved fit for inclusion. The results are represented in line with the Axis 1 classification of tremor as published in the latest Consensus Statement. In summary, we found varying levels of positive evidence for familial aggregation of age at onset, disease progression, alcohol responsiveness, parkinsonism and dystonia. Evidence on midline tremor was conflicting. The evidence on familial clustering was negative for cerebellar signs and action tremor asymmetry. Although the level of evidence is modest, it seems that some disease features are indeed familial, while other features are not. We discuss complicating factors, such as state-vs-trait dependency of characteristics, the place of familial dystonia, and the development of diagnostic criteria for essential tremor over time. In the future, comprehensive replication studies are needed, with the addition of several characteristics that have not been investigated so far, as the next step towards discovery of essential tremor phenotypes

The auditory startle response in relation to outcome in functional movement disorders

Background: The auditory startle reflex (ASR) is enlarged in patients with functional movement disorders (FMD). Objectives: To study whether the ASR relates to symptom reduction in FMD patients, who participated in a placebo controlled double blind treatment trial with Botulinum Neurotoxin (BoNT). Methods: Response to treatment in the BoNT study was assessed using the Clinical Global Impression - Improvement scale (CGI-I). The electromyography (EMG) muscle activity of 7 muscles following 110 dB tones was measured in 14 FMD patients before and after one-year treatment and compared to 11 matched controls. The early and a late (behaviorally affected) component of the ASR and the sympathetic skin response (SSR) were assessed. Results: 10 of 14 patients (71.4%) showed symptom improvement, which was believed to be mainly caused by placebo effects. The early total response probability of the ASR at baseline tended to be larger in patients compared to controls (p = 0.08), but normalized at follow-up (p = 0.84). The late total response probability was larger in patients vs. controls at baseline (p < 0.05), a trend that still was present at follow-up (p = 0.08). The SSR was higher in patients vs. controls at baseline (p < 0.01), and normalized at follow-up (p = 0.71). Conclusions: On a group level 71.4% of the patients showed clinical symptom improvement after treatment. The early part of the ASR, most likely reflecting anxiety and hyperarousal, normalized in line with the clinical improvement. Interestingly, the augmented late component of the ASR remained enlarged suggesting persistent altered behavioral processing in functional patients despite motor improvement

Myoclonus-dystonia : distinctive motor and non-motor phenotype from other dystonia syndromes

Background: myoclonus-dystonia (M-D) due to a pathogenic variant of SGCE is an autosomal dominant inherited movement disorder. Apart from motor symptoms, psychiatric disorders are highly prevalent in patients with MD. Previous studies suggest, but never tested directly, that the type of psychiatric disorder differs between dystonia syndromes, probably related to disease specific pathology. Little is known about other non-motor symptoms (NMS) in M.D. Here, we systematically study NMS in M-D in direct comparison to other types of dystonia and healthy controls. Methods: Standardized questionnaires were used to assess type and severity of psychiatric co-morbidity, sleep problems, fatigue and quality of life. Results of M-D patients with a pathogenic variant of SGCE were compared to results of idiopathic cervical dystonia (CD) patients, dopa-responsive dystonia (DRD) patients with a pathogenic variant of GCH1 and controls. Results: We included 164 participants: 41 M-D, 51 CD, 19 DRD patients, 53 controls. Dystonia patients (M-D, CD and DRD) had an increased prevalence of psychiatric disorders compared to controls (56-74% vs. 29%). In M-D we found a significantly increased prevalence of obsessive-compulsive disorder (OCD) and psychosis compared to CD and DRD. All dystonia patients had more sleep problems (49-68% vs. 36%) and fatigue (42-73% vs. 15%) than controls. Compared to other dystonia subtypes, M-D patients reported less excessive daytime sleepiness and fatigue. Conclusion: Psychiatric comorbidity is frequent in all dystonia types, but OCD and psychosis are more common in M-D patients. Further research is necessary to elucidate underlying pathways

Shared demographics and comorbidities in different functional motor disorders

Introduction: Functional motor disorders are often delineated according to the dominant motor symptom. In a large cohort, we aimed to find if there were differences in demographics, mode of onset, pain, fatigue, depression and anxiety and levels of physical functioning, quality of life and social adjustment between patients with different dominant motor symptoms. Methods: Baseline data from the Self-Help and Education on the Internet for Functional Motor Disorders Trial was used. Patients were divided into dominant motor symptom groups based on the diagnosis of the referring neurologist. Data on the above topics were collected by means of an online questionnaire and compared between groups using parametric and nonparametric statistics. Results: In 160 patients a dominant motor symptom could be determined, 31 had tremor, 45 myoclonus, 23 dystonia, 30 paresis, 31 gait disorder. No statistical differences between groups were detected for demographics, mode of onset and severity of pain, fatigue, depression and anxiety. Physical functioning was worse in the gait disorder group (median 20, IQR 25) compared to tremor (50 (55), p = 0.002) and myoclonus (50 (52), p = 0.001). Work and social adjustment was less impaired in the myoclonus group (median 20, IQR 18) compared to gait disorder (median 30, IQR18, p < 0.001) and paresis (28, IQR 10, p = 0.001). Self-report showed large overlap in motor symptoms. Conclusion: No differences were detected between groups of functional motor symptoms, regarding demographics, mode of onset, depression, anxiety, pain and fatigue. The large overlap in symptoms contributes to the hypothesis of shared underlying mechanisms of functional motor disorders

The prognosis of functional limb weakness, a 14-year case-control study

Reliable data on the prognosis of functional motor disorder are scarce, as existing studies of the prognosis of functional motor disorder are nearly all retrospective, small and uncontrolled. In this study we used a prospectively recruited, controlled cohort design to assess misdiagnosis, mortality and symptomatic and health outcome in patients with functional limb weakness compared to neurological disease and healthy control subjects. We also carried out an exploratory analysis for baseline factors predicting outcome. One hundred and seven patients with functional limb weakness, 46 neurological and 38 healthy control subjects from our previously studied prospective cohort were traced for follow-up after an average of 14 years. Misdiagnosis was determined in a consensus meeting using information from records, patients and their GPs. Numbers and causes of death were collected via death certificates. Outcome of limb weakness, physical and psychiatric symptoms, disability/quality of life and illness perception were recorded with self-rated questionnaires. Outcome measures were compared within and between groups. Seventy-six patients (71%) with functional limb weakness, 31 (67%) neurological and 23 (61%) healthy controls were included in follow-up. Misdiagnosis was found in one patient in the functional limb weakness group (1%) and in one neurological control (2%). Eleven patients with functional limb weakness, eight neurological control subjects and one healthy control subject had died. Weakness had completely remitted in 20% of patients in the functional limb weakness group and in 18% of the neurological controls (P = 0.785) and improved in a larger proportion of functional limb weakness patients (P = 0.011). Outcomes were comparable between patient groups, and worse than the healthy control group. No baseline factors were independent predictors of outcome, although somatization disorder, general health, pain and total symptoms at baseline were univariably correlated to outcome. This study is the largest and longest follow-up study of functional limb weakness. Misdiagnosis in functional limb weakness is rare after long-term follow-up. The disorder is associated with a higher mortality rate than expected, and symptoms are persistent and disabling. It appears difficult to predict outcome based on common baseline variables. These data should help inform clinicians to provide a more realistic outlook of the outcome and emphasize the importance of active and targeted therapy

Axial jerks: a clinical spectrum ranging from propriospinal to psychogenic myoclonus

Propriospinal myoclonus (PSM) is a rare disorder with repetitive flexor, arrhythmic jerks of the trunk, hips and knees. Its generation is presumed to relay in the spinal cord. We report a case series of 35 consecutive patients with jerks of the trunk referred as possible PSM to a tertiary referral center for movement disorders. We review classical PSM features as well as psychogenic and tic characteristics. In our case series, secondary PSM was diagnosed in one patient only. 34 patients showed features suggestive of a psychogenic origin of axial jerks. Diagnosis of psychogenic axial jerks was based on clinical clues without additional investigations (n = 8), inconsistent findings at polymyography (n = 15), regular eye blinking preceding jerks (n = 2), or the presence of a Bereitschaftspotential (BP) (n = 9). In addition, several tic characteristics were noted. Almost all patients referred with possible PSM in our tertiary referral clinic had characteristics suggesting a psychogenic origin even in the presence of a classic polymyography pattern or in the absence of a BP. Clinical overlap with adult-onset tics seems to exist

The Effect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Effects:A Double-Blind Placebo-Controlled Trial

Purpose:The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D(2/3)receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND) after a six-week treatment course with escitalopram or placebo.Methods:CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo. Treatment effect was evaluated with the Clinical Global Impression scale for dystonia, jerks and psychiatric symptoms, both by physicians and patients.Results:In both patients treated with escitalopram and placebo there were no significant differences after treatment in SERT, DAT or D2/3R BPND. Comparing scans after treatment with escitalopram (n = 8) to placebo (n = 8) showed a trend (p= 0.13) towards lower extrastriatal SERT BPND in the SSRI group (median SERT occupancy of 64.6%). After treatment with escitalopram, patients who reported a positive effect on dystonia or psychiatric symptoms had significantly higher SERT occupancy compared to patients who did not experience an effect.Conclusion:Higher extrastriatal SERT occupancy after treatment with escitalopram is associated with a trend towards a positive subjective effect on dystonia and psychiatric symptoms in CD patients

Functional or not functional; that's the question Can we predict the diagnosis functional movement disorder based on associated features?

Background and purpose Functional movement disorders (FMDs) pose a diagnostic challenge for clinicians. Over the years several associated features have been shown to be suggestive for FMDs. Which features mentioned in the literature are discriminative between FMDs and non-FMDs were examined in a large cohort. In addition, a preliminary prediction model distinguishing these disorders was developed based on differentiating features. Method Medical records of all consecutive patients who visited our hyperkinetic outpatient clinic from 2012 to 2019 were retrospectively reviewed and 12 associated features in FMDs versus non-FMDs were compared. An independentttest for age of onset and Pearson chi-squared analyses for all categorical variables were performed. Multivariate logistic regression analysis was performed to develop a preliminary predictive model for FMDs. Results A total of 874 patients were eligible for inclusion, of whom 320 had an FMD and 554 a non-FMD. Differentiating features between these groups were age of onset, sex, psychiatric history, family history, more than one motor phenotype, pain, fatigue, abrupt onset, waxing and waning over long term, and fluctuations during the day. Based on these a preliminary predictive model was computed with a discriminative value of 91%. Discussion Ten associated features are shown to be not only suggestive but also discriminative between hyperkinetic FMDs and non-FMDs. Clinicians can use these features to identify patients suspected for FMDs and can subsequently alert them to test for positive symptoms at examination. Although a first preliminary model has good predictive accuracy, further validation should be performed prospectively in a multi-center study