Natural course of Myoclonus-Dystonia in adulthood: stable motor signs but increased psychiatry

Myoclonus‐dystonia (M‐D) is a rare hyperkinetic movement disorder characterized by upper body–predominant myoclonus and dystonia.1 A large proportion of cases are caused by autosomal‐dominant inherited mutations in the SGCE gene. In addition to the motor manifestations, psychiatric disorders are frequently reported.2 Several studies have suggested that they may form a primary component of the M‐D phenotype.3, 4 This study represents the first long‐term follow‐up study of both motor and psychiatric symptomatology in adults with M‐D (SGCE mutation), providing further insights into the natural history of M‐D and enabling more prognostic information

Long-term experience with intraoperative microrecording during DBS neurosurgery in STN and GPi

Intraoperative microelectrode recording (MER) for targeting during deep brain stimulation (DBS) procedures has been evaluated over a period of 4 years, in 57 consecutive patients with Parkinson's disease, who received DBS in the subthalamic nucleus (STN-DBS), and 28 consecutive patients with either dystonia (23) or Parkinson's disease (five), in whom the internal segment of the globus pallidus (GPi-DBS) was targeted. The procedure for DBS was a one-stage bilateral stereotactic approach using a combined electrode for both MER and macrostimulation. Up to five micro/macro-electrodes were used in an array with a central, lateral, medial, anterior, and posterior position. Final target location was based on intraoperative test stimulation. For the STN, the central trajectory was chosen for implantation in 50% of the cases and for the globus pallidus internus (GPi) in 57% of the cases. Furthermore, in 64% of the cases, the channel selected for the permanent electrode corresponded with the trajectory having the longest segment of STN MER activity. For the GPi, this was the case in 61%. The mean and standard deviation of the deepest contact point with respect to the magnetic resonance imaging (MRI)-based target for the STN was 2.1 +/- 1.5 mm and for the GPi was -0.5 +/- 1.2 mm. MER facilitates the selection of the final electrode location in STN-DBS and GPi-DBS, and based on the observed MER activity, a pre-selection could be made as to which channel would be the best candidate for macro-test stimulation and at which depth should be stimulated. The choice of the final location is based on intraoperative test stimulation, and it is demonstrated that regularly it is not the central channel that is chosen for implantation. On average, the target as defined by MER activity intensity was in accordance with the MRI-based targets both for the STN and GPi. However, the position of the best MER activity did not necessarily correlate with the locus that produced the most beneficial clinical response on macroelectrode testing intraoperativel

Psychiatric disorders, myoclonus dystonia and SGCE:An international study

OBJECTIVE: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder, typically alcohol-responsive upper body myoclonus and dystonia. The majority of autosomal dominant familial cases are caused by epsilon-sarcoglycan gene (SGCE) mutations. Previous publications have observed increased rates of psychiatric disorders amongst SGCE mutation-positive populations. We analyzed the psychiatric data from four international centers, forming the largest cohort to date, to further determine the extent and type of psychiatric disorders in M-D.METHODS: Psychiatric data from SGCE mutation-positive M-D cohorts, collected by movement disorder specialists in the Netherlands, United Kingdom, United States, and Germany, were analyzed. These data were collected using standardized, systematic questionnaires allowing classification of symptoms according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Based on motor findings and SGCE mutation analysis, participants were classified into one of three groups: manifesting carriers, nonmanifesting carriers and noncarriers.RESULTS: Data from 307 participants were evaluated (140 males, 167 females, mean age at examination: 42.5 years). Two-thirds of motor affected mutation carriers (n = 132) had ≥1 psychiatric diagnosis, specific, and social phobias being most common followed by alcohol dependence and obsessive-compulsive disorder (OCD). Compared to familial controls, affected mutation carriers had significantly elevated overall rates of psychiatric disorders (P &lt; 0.001). The most significant differences were observed with alcohol dependence (P &lt; 0.001), OCD (P &lt; 0.001), social and specific phobias (P &lt; 0.001).INTERPRETATION: M-D due to SGCE mutations is associated with specific psychiatric disorders, most commonly OCD, anxiety-related disorders, and alcohol dependence. These suggest either a potential pleiotropic function for SGCE within the central nervous system or a secondary effect of the motor disorder.</p

Diagnosis and management of functional neurological symptoms: The Dutch experience

Functional neurological symptoms (FNS) were considered as a psychiatric disorder at the beginning of the 20th century (conversion disorder). Psychiatrists performed diagnosis and treatment throughout most of the past century in the Netherlands, but in the latest decades patients were usually firstly referred to neurologists. The aim of this study was to investigate the opinions of today's neurologists, psychiatrists and rehabilitation physicians in the Netherlands, regarding pathogenesis, diagnosis and treatment of FNS. An electronic questionnaire was sent to all neurologists registered with the Dutch Society for Neurology and to the members of the Department for Consultation-liaison and General Hospital Psychiatry. 343 of 780 neurologists, 64 of 197 psychiatrists and 47 of 750 rehabilitation physicians completed the questionnaire. 60% of neurologists and 67% of psychiatrists considered disordered brain functioning together with psychogenic factors responsible for FNS. 29% of neurologists and 88% of psychiatrists felt a psychiatrist was needed for diagnosis. 55% of neurologists and 88% of psychiatrists preferred combined treatment consisting of explaining FNS to patients, psychotherapy and physiotherapy provided by a therapist trained in FNS. 15% of neurologists preferred only physiotherapy. Most neurologists and psychiatrists did not consider FNS as a mere psychiatric disorder, but counted disordered brain functioning together with psychogenic factors responsible for FNS. Subsequently, according to the majority of neurologists and psychiatrists FNS should not be solely diagnosed and treated by psychiatrists. These results can help to formulate treatment strategie

Myoclonus-dystonia and spinocerebellar ataxia type 14 presenting with similar phenotypes: Trunk tremor, myoclonus, and dystonia

We describe three genetically confirmed myoclonus dystonia (M-D) patients and one spinocerebellar ataxia type 14 (SCA14) patient, presenting with a combination of trunk tremor, multifocal myoclonus and axial dystonia as predominant clinical features. We suggest that in patients with this M-D phenotype, without a mutation in the DYT11 gene, SCA14 should be considered. (C) 2009 Elsevier Ltd. All rights reserved

Local field potentials and oscillatory activity of the internal globus pallidus in myoclonus-dystonia

The pathophysiology of myoclonus-dystonia (MD), an autosomal dominantly inherited movement disorder characterized by myoclonic jerks and dystonic contractions, is largely unknown. In the present study, local field potential (LFP) activities in the globus pallidus internus (GPi) from two genetically proven M-D patients are investigated. Coherence analysis between GPi UP activity and electromyographic muscle activity (EMG) and synchronization of GPi neuronal activity using event-related spectral perturbation (ERSP) in a go-no-go paradigm were studied. Significant increased coherence in the 3 to 15 Hz frequency band was detected between GPi LFP activity and several muscles, with the LFP leading the muscles. The ERSP analysis revealed synchronization in the 3 to 15 Hz frequency band within the GPi before the imperative cue of the go-no-go task and desynchronization in the same band after the Cue. The LFP recordings of the GPi in M-D show that the low-frequency band previously described in dystonia is also involved in the dystonia plus syndrome M-D. The 3 to 15 Hz synchronization in the go-no-go paradigm has not been described previously and may point to the existence of (myoclonus-)dystonia specific oscillatory activity in the GPi. (C) 2007 Movement Disorder Society

Functional Magnetic Resonance Imaging Evidence of Incomplete Maternal Imprinting in Myoclonus-Dystonia

Background: Myoclonus-dystonia is an autosomal dominantly inherited movement disorder, clinically characterized by myoclonic jerks and dystonic postures or movements. A previous functional magnetic resonance imaging study showed altered cortical activation patterns in clinically affected SGCE mutation carriers when compared with controls consistent with defective sensorimotor integration. Genetically, the disorder is characterized by the maternal imprinting mechanism; ie, patients who inherit the mutation from their fathers will develop symptoms. However, several clinically manifest patients with myoclonus-dystonia who inherited the mutation from their mother have been described. Objective: To compare cerebral activation patterns of paternally inherited SGCE mutation carriers are with maternally inherited mutation carriers and a control group. Design: Case-control study using functional magnetic resonance imaging. Participants: Eight paternally inherited SGCE mutation carriers, 8 asymptomatic or slightly affected (4 of 8) symptomatic maternally inherited mutation carriers, and 11 control subjects. Interventions: Participants were studied using a 3-T functional magnetic resonance imaging scanner with a finger tapping task. Results: When paternal and maternal gene mutation carriers were compared, hyperresponsiveness was seen in the contralateral secondary somatosensory cortex. When maternal mutation carriers and control subjects were compared, hyperresponsiveness of the ipsilateral cerebellum and supplementary motor area were found. Using a nonparametric analysis to study only the 4 clinically asymptomatic patients, no significant differences were found between groups. Contrast estimates were plotted for the known affected sensorimotor brain areas, showing intermediate activation in maternally inherited mutation carriers, even when this was performed for only the 4 clinically unaffected mutation carriers. Conclusions: The results suggest biased gene expression based on parent of origin rather than a strictly dichotomous maternal imprinting mechanism, consistent with clinical observations