Connecting the dots - A systematic review on coherence analysis in dystonia.

BACKGROUND: Increased 4-12 Hz oscillatory activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop is reported in dystonia. Coherence analysis is a measure of linear coupling between two signals, revealing oscillatory activity drives that are common across motor units. By performing coherence analysis, activity of the CBGTC-loop can be measured with modalities like local field potentials (LFPs), electromyography (EMG), and electro-encephalography (EEG). The aim of this study is to perform a systematic review on the use of coherence analysis for clinical assessment and treatment of dystonia. METHODS: A systematic review was performed on a search in Embase and PubMed on June 28th, 2023. All studies incorporating coherence analysis and an adult dystonia cohort were included. Three authors evaluated the eligibility of the articles. Quality was assessed using the QUADAS-2 checklist. RESULTS: A total of 41 articles were included, with data of 395 adult dystonia patients. In the selected records, six different types of coherence were investigated: corticocortical, corticopallidal, corticomuscular, pallidopallidal, pallidomuscular, and intermuscular coherence. Various types of 4-12 coherence were found to be increased in all dystonia subtypes. CONCLUSION: There is increased 4-12 Hz coherence found between the cortex, basal ganglia, and affected muscles in all dystonia subtypes. However, the relationship between 4-12 Hz coherence and the dystonic clinical state has not been established. DBS treatment leads to a reduction of 4-12 Hz coherence. In combination with the results of this review, the 4-12 Hz frequency band can be used as a promising phenomenon for the development of a biomarker.

Management of rare movement disorders in Europe: outcome of surveys of the European Reference Network for Rare Neurological Diseases.

BACKGROUND AND PURPOSE: The diagnosis of rare movement disorders is difficult and specific management programmes are not well defined. Thus, in order to capture and assess care needs, the European Reference Network for Rare Neurological Diseases has performed an explorative care need survey across all European Union (EU) countries. METHODS: This is a multicentre, cross-sectional study. A survey about the management of different rare movement disorders (group 1, dystonia, paroxysmal dyskinesia and neurodegeneration with brain iron accumulation; group 2, ataxias and hereditary spastic paraparesis; group 3, atypical parkinsonism; group 4, choreas) was sent to an expert in each group of disorders from each EU country. RESULTS: Some EU countries claimed for an increase of teaching courses. Genetic testing was not readily available in a significant number of countries. Regarding management, patients' accessibility to tertiary hospitals, to experts and to multidisciplinary teams was unequal between countries and groups of diseases. The availability of therapeutic options, such as botulinum toxin or more invasive treatments like deep brain stimulation, was limited in some countries. CONCLUSIONS: The management of these conditions in EU countries is unequal. The survey provides evidence that a European care-focused network that is able to address the unmet rare neurological disease care needs and inequalities is highly warranted.

Quality and reporting of guidelines on the diagnosis and management of dystonia.

BACKGROUND AND PURPOSE: The quality of clinical practice guidelines on dystonia has not yet been assessed. Our aim was to appraise the methodological quality of guidelines worldwide and to analyze the consistency of their recommendations. METHODS: We searched for clinical practice guidelines on dystonia diagnosis/treatment in the National Guideline Clearinghouse, PubMed, National Institute for Health and Care Excellence, Guidelines International Network and Web of Science databases. We also searched for guidelines on homepages of international neurological societies. We asked for guidelines from every Management Committee member of the BM1101 Action of the Cooperation between Science and Technology European framework and every member of the International Parkinson and Movement Disorders Society with special interest in dystonia. RESULTS: Fifteen guidelines were evaluated. Among guidelines on treatment, only one from the American Academy of Neurology could be considered as high quality. Among guidelines on diagnosis and therapy, the guideline from the European Federation of Neurological Societies was recommended by the appraisers. Clinical applicability and reports of editorial independence were the greatest shortcomings. The rigor of development was poor and stakeholder involvement was also incomplete in most guidelines. Discrepancies among recommendations may result from the weight given to consensus statements and expert opinions due to the lack of evidence, as well as inaccuracy of disease classification. CONCLUSIONS: The quality of appraised guidelines was low. It is necessary to improve the quality of guidelines on dystonia, and the applied terminology of dystonia also needs to be standardized.

The relationship between the dopaminergic system and depressive symptoms in cervical dystonia.

PURPOSE: Cervical dystonia (CD) is associated with tremor/jerks (50%) and psychiatric complaints (17-70%). The dopaminergic system has been implicated in the pathophysiology of CD in animal and imaging studies. Dopamine may be related to the motor as well as non-motor symptoms of CD. CD is associated with reduced striatal dopamine D2/3 (D2/3) receptor and increased dopamine transporter (DAT) binding. There are differences in the dopamine system between CD patients with and without jerks/tremor and psychiatric symptoms. METHODS: Patients with CD and healthy controls underwent neurological and psychiatric examinations. Striatal DAT and D2/3 receptor binding were assessed using [123I]FP-CIT and [123I]IBZM SPECT, respectively. The ratio of specific striatal to non-specific binding (binding potential; BPND) was the outcome measure. RESULTS: Twenty-seven patients with CD and 15 matched controls were included. Nineteen percent of patients fulfilled the criteria for a depression. Striatal DAT BPND was significantly lower in depressed versus non-depressed CD patients. Higher DAT BPND correlated significantly with higher scores on the Unified Myoclonus Rating Scale (UMRS). The striatal D2/3 receptor BPND in CD patients showed a trend towards lower binding compared to controls. The D2/3 BPND was significantly lower in depressed versus non-depressed CD patients. A significant correlation between DAT and D2/3R BPND was found in both in patients and controls. CONCLUSIONS: Alterations of striatal DAT and D2/3 receptor binding in CD patients are related mainly to depression. DAT BPND correlates significantly with scores on the UMRS, suggesting a role for dopamine in the pathophysiology of tremor/jerks in CD.

Clinical characterization of dystonia in adult patients with Huntington's disease.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant, neurodegenerative movement disorder, typically characterized by chorea. Dystonia is also recognized as part of the HD motor phenotype, although little work detailing its prevalence, distribution, severity and impact on functional capacity has been published to date. METHODS: Patients (>18 years of age) were recruited from the Cardiff (UK) HD clinic, each undergoing a standardized videotaped clinical examination and series of functional assessment questionnaires (Unified Huntington's Disease Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale and modified version of the Toronto Western Spasmodic Torticollis Rating Scale). The presence and severity of dystonia were scored by four independent neurologists using the Burke-Fahn-Marsden Dystonia Rating Scale and Unified Huntington's Disease Rating Scale. Statistical analysis included Fisher's exact test, Wilcoxon test, anova and calculation of correlation coefficients where appropriate. RESULTS: Forty-eight patients [91% (48/53)] demonstrated evidence of dystonia, with the highest prevalence in the left upper limb (n = 44, 83%), right upper limb most severely affected and eyes least affected. Statistically significant positive correlations (P < 0.05) were observed between dystonia severity and increasing HD disease stage and motor disease duration. Deterioration in functional capacity also correlated with increasing dystonia severity. No significant relationship was observed with age at motor symptom onset or CAG repeat length. CONCLUSIONS: We report a high prevalence of dystonia in adult patients with HD, with worsening dystonia severity with increasing HD disease stage and motor disease duration. The recognition and management of dystonic symptoms in routine clinical practice will aid overall symptomatic treatment and functional improvement.

Cerebellar Atrophy in Cortical Myoclonic Tremor and Not in Hereditary Essential Tremor-a Voxel-Based Morphometry Study.

Essential tremor (ET) presumably has a cerebellar origin. Imaging studies showed various cerebellar and also cortical structural changes. A number of pathology studies indicated cerebellar Purkinje cell pathology. ET is a heterogeneous disorder, possibly indicating different underlying disease mechanisms. Familial cortical myoclonic tremor with epilepsy (FCMTE), with evident Purkinje cell degeneration, can be an ET mimic. Here, we investigate whole brain and, more specifically, cerebellar morphological changes in hereditary ET, FCMTE, and healthy controls. Anatomical magnetic resonance images were preprocessed using voxel-based morphometry. Study 1 included voxel-wise comparisons of 36 familial, propranolol-sensitive ET patients, with subgroup analysis on age at onset and head tremor, and 30 healthy controls. Study 2 included voxel-wise comparisons in another nine ET patients, eight FCMTE patients, and nine healthy controls. Study 3 compared total cerebellar volume between 45 ET patients, 8 FCTME patients, and 39 controls. In our large sample of selected hereditary ET patients and ET subgroups, no local atrophy was observed compared to healthy controls or FCMTE. In ET patients with head tremor, a volume increase in cortical motor regions was observed. In FCMTE, a decrease in total cerebellar volume and in local cerebellar gray matter was observed compared to healthy controls and ET patients. The current study did not find local atrophy, specifically not in the cerebellum in hereditary ET, contrary to FCMTE. Volume increase of cortical motor areas in ET patients with head tremor might suggest cortical plasticity changes due to continuous involuntary head movements.

Management of dystonia in Europe: a survey of the European network for the study of the dystonia syndromes.

BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.

Electroencephalographic Findings in Posthypoxic Myoclonus.

The physical examination findings of early posthypoxic myoclonus (PHM) are associated with poor prognosis. Recent findings indicate that patients with multifocal PHM, assumed to have a cortical origin, have a comparable outcome to resuscitated patients without PHM. Generalized PHM, assumed to have a subcortical myoclonus origin, is still associated with a bad clinical outcome. It is not known whether the electroencephalographic (EEG) findings differ between the multifocal and generalized myoclonus groups nor is the clinical significance clearly defined. Forty-three patients with PHM were retrospectively derived from an EEG database. Patients were categorized as having multifocal (i), generalized (ii), or undetermined (iii) PHM. Outcome was expressed in cerebral performance category scores. The EEG background was categorized into isoelectric (I), low voltage (II), burst suppression (III), status epilepticus (SE; IV), diffuse slowing (V), and mild encephalopathic or normal (VI). 17 patients had generalized PHM and 23 had multifocal PHM (3 undetermined). The EEG showed more SE in generalized compared to multifocal PHM (64% vs 13%, P< .001). Diffuse slowing was more often present in multifocal PHM (52% vs 17%, P < .05). Early-onset myoclonus occurred significantly more often in generalized PHM, and early generalized PHM was invariantly associated with poor outcome. In conclusion, patients with generalized PHM showed more SE. These EEG findings might be either subcortical corollaries or primarily cortical phenomena. Our retrospective results conflict with currently used clinical criteria for myoclonus classification, and we suggest that more refined difference may be needed for accurate assessment of PHM. To better understand PHM, prospective research with standardized clinical assessment and quantitative EEG analysis is needed.

Neurometabolic disorders are treatable causes of dystonia.

A broad range of rare inherited metabolic disorders can present with dystonia. For clinicians, it is important to recognize dystonic features, but it can be complicated by the mixed and complex clinical picture seen in many neurometabolic patients. Careful phenotyping is the first step towards the diagnosis of the underlying condition and subsequent targeted treatment, further supported by imaging, biochemical diagnostics and the availability of modern diagnostic techniques such as next generation sequencing. As several neurometabolic disorders are treatable causes of dystonia, these should have priority in the diagnostic process. In the symptomatic treatment of dystonia, several therapeutic options are available. Awareness for the occurrence and optimal treatment of dystonia and other movement disorders in neurometabolic conditions is important because these symptoms can have a substantial impact on the quality of life and daily functioning; this effect is not only exerted by the dystonia itself, but also by the frequently associated non-motor features. In this paper, the highlights and key concepts of neurometabolic forms of dystonia are discussed, with a focus on phenomenology, the diagnostic approach, the most important neurometabolic aetiologies, co-occurring non-motor features and therapeutic options.

[Severe treatment-resistant tardive dystonia: is deep brain stimulation a treatment option]. / Ernstige, therapieresistente tardieve dyskinesie: is diepe hersenstimulatie een behandeloptie?

BACKGROUND: Severe tardive dyskinesia or dystonia (TD) are side-effects of dopamine-blocking agents, most of which are antipsychotics. A small subgroup of patients develop a severe debilitating treatment-resistant form of TD. AIM: To assess the effects and side-effects of deep brain stimulation (DBS) in this subgroup of TD patients. METHOD: We searched PubMed and Embase using the search terms 'tardive' and 'deep brain stimulation'. We found 19 articles containing data referring to 52 patients. Using the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS), the Abnormal Involuntary Movement Scale (AIMS) and the Extrapyramidal Symptoms Rating Scale (ESRS) we calculated the average improvement in the patients' condition. RESULTS: On all the scales the improvement was statistically significant (p < 0.00001), the average improvement being 67% to 78%. In only 4% of the patients was there a deterioration in the psychiatric disorder. CONCLUSION: DBS seems to be an effective treatment for treatment-resistant TD and the side-effects seem to be limited. However, the evidence is limited because our conclusion is based on case-reports and on small-scale trials without randomisation or blinding.

Treatment of task-specific dystonia in sports: A systematic review.

Introduction: Task specific dystonia is a movement disorder only affecting a highly practiced skill and is found in a broad set of expert movements including in sports. Despite affecting many sports, there is no comprehensive review of treatment options, which is in contrast to better studied forms of task specific dystonia in musicians and writers. For this reason, studies involving an intervention to treat task specific dystonia in sports were systematically reviewed, with special attention for the quality of outcome measures. Methods: The PICO systematic search strategy was employed on task-specific dystonia, and all synonyms. Inclusion criteria were peer reviewed published studies pertaining to sports, studies with a measurement and/or intervention in TSD, all in English. We excluded abstracts, expert opinions, narrative review articles, unpublished studies, dissertations and studies exclusively relating to choking. We included case reports, case studies and case-control studies. Results: In April 2022 Pubmed, Embase, Web of Science, and Psychinfo were searched. Of the 7000 articles identified, 31 were included that described psychological and invasive and/or pharmacological interventions. There was a lack of formal standardized outcome measures in studies resulting in low quality evidence for the effectiveness of treatment options. A descriptive synthesis showed emotional regulation was effective, but was exclusively tried in golfers. Interventions like botulinum toxin or pharmacology had a similar effectiveness compared to studies in musicians dystonia, however there was almost no formal evidence for these treatments. Conclusion: The quality of studies was low with a lack of standardized outcome measures. Future studies with larger cohorts and quantitative outcome measures are needed to improve understanding of treatments for task specific dystonia in athletes.

Personality in speed skaters with skater's cramp: A preliminary cross-sectional study.

OBJECTIVE: Skater's cramp is a debilitating disorder in expert speedskaters and recent evidence from muscle and movement studies nominate it is a task-specific dystonia (TSD). Building on these studies we investigated clinical features and personality in skater's cramp, hypothesizing that similar to other TSDs, trait emotionality would be higher in affected skaters. METHODS: In a cross-sectional study we employed the HEXACO inventory to examine the personality of a cohort of skaters with skater's cramp (n = 26) compared to age, sex, and experience-matched controls (n = 28). Affected skaters were selected based on relevant clinical features important to the diagnosis of TSD. RESULTS: Sentimentality (a sub-factor of emotionality) was higher in affected skaters, but only in the male population. Extraversion was lower in skaters with skater's cramp. Clinical findings resembled other forms of TSD. DISCUSSION: Higher sentimentality is in line with previous studies in TSD. Lower Extraversion in affected skaters was an unexpected finding that may be a new feature of skater's cramp and TSD. Due to our small sample size and cross-sectional design, these findings are preliminary, but offer tentative evidence of personality differences in skater's cramp in line with TSD.

Inter-muscular coherence in speed skaters with skater's cramp.

INTRODUCTION: Skater's cramp is a career-ending movement disorder in expert speed skaters noted to be a likely task-specific dystonia. In other movement disorders, including task-specific dystonia, studies have found evidence of central dysregulation expressed as higher inter-muscular coherence. We looked at whether inter-muscular coherence was higher in affected skaters as a possible indicator that it is centrally driven, and by extension further evidence it is a task-specific dystonia. METHODS: In 14 affected and 14 control skaters we calculated inter-muscular coherence in the theta-band in a stationary task where tonic muscle activation was measured at 10%, 20% and 50% of maximum voluntary contraction. Additionally, we calculated wavelet coherence while skating at key moments in the stroke cycle. RESULTS: Coherence did not differ in the stationary activation task. While skating, coherence was higher in the impacted leg of affected skaters compared to their non-impacted leg, p = .05, η2 = 0.031, and amplitude of electromyography correlated with coherence in the impacted leg, p = .009, R2adjusted = 0.41. A sub-group of severely affected skaters (n = 6) had higher coherence in the impacted leg compared to the left and right leg of controls, p = .02, Cohen's d = 1.59 and p = .01, Cohen's d = 1.63 respectively. Results were less clear across the entire affected cohort probably due to a diverse case-mix. CONCLUSION: Our results of higher coherence in certain severe cases of skater's cramp is preliminary evidence of a central dysregulation, making the likelihood it is a task-specific dystonia higher.

Measuring saccades in patients with Niemann-Pick type C: A comparison between video-oculography and a novel eye tracking test based on continuous psychophysics.

Introduction: Vertical supranuclear gaze palsy is a key feature of Niemann-Pick type C (NP-C) and is commonly quantified using video-oculography (VOG). VOG requires sitting still for long times and performing specific tasks, thus it can be challenging or impossible for patients severely affected by movement disorders or cognitive impairment. To overcome this limitation, we measure saccades of NP-C patients using a fast eye tracking test based on continuous psychophysics and compare it to VOG. Methods: Saccades of six NP-C patients and six age-matched controls were assessed using VOG and Standardized Oculomotor and Neuro-ophthalmic Disorders Assessment (SONDA). In SONDA, participants continuously track a semi-randomly moving dot on a computer screen while their gaze is being tracked. For both assessments, saccades were quantified using four conventional measures: amplitude, gain, latency, and peak velocity. Furthermore, SONDA's continuous measures were quantified with several novel spatio-temporal properties. Results: In the NP-C patients, both methods revealed reduced amplitude, gain, peak velocity, and increased latency of vertical saccades compared to horizontal saccades and compared to healthy controls. Effect sizes obtained with SONDA were overall larger than those for VOG. SONDA's spatio-temporal properties showed similar trends. Conclusion: SONDA reveals a deterioration of vertical saccades in NP-C patients that is consistent with VOG. SONDA's measures based on continuous psychophysics are consistent with traditional saccadic parameters and can potentially provide complementary information. SONDA shows larger effect sizes than VOG, suggesting that it provides robust and clinically relevant outcomes with a more intuitive task and shorter testing time.

Intermuscular coherence as a biomarker of subthalamic nucleus deep brain stimulation efficacy in Parkinson's disease.

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD. METHODS: EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated. RESULTS: Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01). CONCLUSIONS: Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement. SIGNIFICANCE: We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS.

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia.

INTRODUCTION: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia. METHODS: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed. RESULTS: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1; p.(Leu100del) in family 2; p.(Gly50Asp) in family 3; and p.(Glu208*) in family 4). Two subjects presented with action tremor around age 10-12 years and developed tremor-dominant parkinsonism with prominent neuropsychiatric features later in their 20s. Two subjects presented with a progressive myoclonus-ataxia dominant phenotype. One subject presented with spasticity, choreo-dystonia, myoclonus, and speech problems. One subject presented with speech problems, ataxia, and tremor. Western blotting analyses in patient-derived fibroblasts showed a markedly decreased expression of the full-length WARS2 protein in both subjects carrying p.(Trp13Gly) and an exon-2 deletion in compound heterozygosity. CONCLUSIONS: This study expands the spectrum of the disease to later onset phenotypes of early-onset tremor-dominant parkinsonism and progressive myoclonus-ataxia phenotypes.

Structural, functional and molecular imaging of the brain in primary focal dystonia--a review.

Primary focal dystonias form a group of neurological disorders characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures. The estimated incidence is 12-25 per 100,000. The pathophysiology is largely unclear but genetic and environmental influences are suspected. Over the last decade neuroimaging techniques have been applied in patients with focal dystonia. Using structural, functional and molecular imaging techniques, abnormalities have been detected mainly in the sensorimotor cortex, basal ganglia and cerebellum. The shared anatomical localisations in different forms of focal dystonia support the hypothesis of a common causative mechanism. The primary defect in focal dystonia is hypothesised in the motor circuit connecting the cortex, basal ganglia, and cerebellum. Imaging techniques have clearly enhanced current knowledge on the pathophysiology of primary focal dystonia and will continue to do so in the future.

Severity of dystonia is correlated with putaminal gray matter changes in myoclonus-dystonia.

BACKGROUND: Myoclonus-dystonia (M-D) is an autosomal dominantly inherited movement disorder characterized by myoclonic jerks and dystonic postures or movements. Morphometric studies have been performed in other, mainly heterogenous, types of dystonia producing conflicting results. However, all these studies agree on abnormalities in sensorimotor structures, mainly in the basal ganglia. We aimed to study gray matter (GM) volumes in sensorimotor brain structures with magnetic resonance imaging (MRI) in a genetically homogeneous form of dystonia, M-D. METHODS: Twenty-five clinically affected DYT11 mutation carriers (MC) and 25 matched control subjects were studied using T1-weighted 3D anatomical images of the entire brain, obtained with a 3.0 Tesla MRI. MC were clinically scored using the Burke Fahn Marsden dsytonia rating scale (BFMDRS) and the unified myoclonus rating scale (UMRS). GM volumes in sensorimotor cortices and basal ganglia of patients and controls were compared, and multiple regression analyses were used to correlate the GM volumes of patients with the clinical rating scales BFMDRS and UMRS. RESULTS: No significant differences were found between groups, but dystonia severity in MC was strongly correlated with increased GM volume in bilateral putamina. CONCLUSIONS: This study provides further evidence for the involvement of putamina as important motor structures in the pathophysiology of (myoclonus-) dystonia. Changes in these structures are associated with the severity of dystonia.

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.