Sandra M. A. van der Salm

The eye of the beholder: inter-rater agreement among experts on psychogenic jerky movement disorders

Objective The current criteria for conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders rely on the assumption that neurological disorders can be distinguished from conversion disorders through clinical assessment. This study aims to assess inter-rater agreement among clinicians with experience in the diagnosis of various hyperkinetic jerky movements, including psychogenic jerks. Methods 60 patients with psychogenic jerks, myoclonus or tics were rated by international experts using a standardised survey resembling daily clinical practice. The survey included the following diagnostic steps: a short video offering a visual impression of the patients and their jerky movements, medical history, neurological examination (on video), additional investigations and the findings of a standardised psychiatric interview. The diagnosis and diagnostic certainty were scored after each step. Results After all clinical information was given, moderate inter-rater agreement was reached (κ=0.56±0.1) with absolute agreement (100%) of experts on the diagnosis in 12 (20%) patients and reasonable agreement (>75%) in 43 (72%) patients. Psychiatric evaluation did not contribute to inter-rater agreement or diagnostic certainty. Conclusions Our findings illustrate the fact that experienced movement disorder specialists moderately agree on the clinical diagnosis of jerky movements. Clinical assessment, especially by a team of clinicians in challenging individual cases, might improve diagnostic agreement.

The bereitschaftspotential in jerky movement disorders

Objective To assess the diagnostic value of the bereitschaftspotential (BP) in jerky movement disorders. Methods A cross-sectional case series of 48 patients with psychogenic jerks, Gilles de la Tourette syndrome (GTS) or myoclonus was investigated. We measured the BP prior to the spontaneous jerk and voluntary wrist extension. In addition, the various jerky movements were imitated by 25 healthy subjects. Results For patients with psychogenic jerks, we observed significantly more BPs; however, the BP was not identified prior to self-paced wrist extensions in 59% of cases. In contrast, none of the patients with the clinical diagnosis of myoclonus had a BP prior to their jerks but did have a BP prior to intentional wrist extension. In GTS, we demonstrated a BP in a minority of cases preceding motor tics and with a shorter duration in comparison with patients with psychogenic jerks. In healthy control subjects, a BP was found preceding all movements in all cases. The absence of a BP prior to intended wrist extension had a sensitivity of 0.59, specificity of 0.98 and positive likelihood ratio of 25 for the diagnosis of psychogenic jerks. Conclusions We demonstrate that the BP can aid in the differentiation of jerky movements. Patients with psychogenic jerks significantly more often have a BP prior to their jerks and with a significantly earlier onset compared with GTS patients. A novel finding of our study is the absence of a BP prior to intentional movements for patients with psychogenic jerks. Validation in a prospective cohort is needed.

Decreased cortical inhibition and yet cerebellar pathology in 'familial cortical myoclonic tremor with epilepsy'.

Cortical hyperexcitability is a feature of “familial cortical myoclonic tremor with epilepsy” (FCMTE). However, neuropathological investigations in a single FCMTE patient showed isolated cerebellar pathology. Pathological investigations in a second FCMTE patient, reported here, confirmed cerebellar Purkinje cell degeneration and a normal sensorimotor cortex. Subsequently, we sought to explore the nature of cerebellar and motor system pathophysiology in FCMTE. Eye movement recordings and transcranial magnetic stimulation performed in six related FCMTE patients showed impaired saccades and smooth pursuit and downbeat nystagmus upon hyperventilation, as in patients with spinocerebellar ataxia type 6. In FCMTE patients short‐interval intracortical inhibition (SICI) was significantly reduced. Resting motor threshold, recruitment curve, silent period, and intracortical facilitation were normal. The neuropathological and ocular motor abnormalities indicate cerebellar involvement in FCMTE patients. Decreased SICI is compatible with intracortical GABAA‐ergic dysfunction. Cerebellar and intracortical functional changes could result from a common mechanism such as a channelopathy. Alternatively, decreased cortical inhibition may be caused by dysfunction of the cerebello‐thalamo‐cortical loop as a result of primary cerebellar pathology.

Cognition and psychopathology in myoclonus-dystonia

Objective (1) To study the neuropsychological and psychopathological profile in myoclonus-dystonia (M-D) patients with and without a mutation in the DYT11 gene. (2) To explore whether cognitive and psychiatric impairments are related to severity and duration of motor symptoms. Herewith, this study may help to clarify whether neuropsychological and psychiatric symptoms are associated with the DYT11 mutation or are secondary to the burden of motor impairments that originated in early childhood. Methods Extensive batteries of neuropsychological tests and psychiatric questionnaires were administered to DYT11 gene mutation-carrying (MC) M-D patients (n=31), non-mutation-carrying (NMC) M-D patients (n=20) and a healthy control group (n=36). Results MC M-D patients demonstrated mild impairments in executive functions. On the contrary, with the exception of one type of verbal fluency, no evident cognitive impairments were found in NMC M-D patients. Further, increased rates of anxiety disorders were found only in MC M-D patients, whereas increased rates of depressive symptoms were observed in both M-D groups. Correlation analyses yielded modest associations between severity of myoclonus and executive functions. No relationships were found between neuropsychological test performance and scores on the psychiatric assessments. Conclusions The findings of this study suggest that anxiety disorders and executive dysfunctions may be part of the phenotype of M-D patients with a DYT11 mutation, whereas depressive symptoms and semantic fluency impairments may be secondary to suffering from a chronic movement disorder, regardless of DYT11 gene mutation.

Propriospinal myoclonus: clinical reappraisal and review of literature

Objective: Propriospinal myoclonus (PSM) is a rare disorder with repetitive, usually flexor arrhythmic brief jerks of the trunk, hips, and knees in a fixed pattern. It has a presumed generation in the spinal cord and diagnosis depends on characteristic features at polymyography. Recently, a historical paradigm shift took place as PSM has been reported to be a functional (or psychogenic) movement disorder (FMD) in most patients. This review aims to characterize the clinical features, etiology, electrophysiologic features, and treatment outcomes of PSM. Methods: Re-evaluation of all published PSM cases and systematic scoring of clinical and electrophysiologic characteristics in all published cases since 1991. Results: Of the 179 identified patients with PSM (55% male), the mean age at onset was 43 years (range 6–88 years). FMD was diagnosed in 104 (58%) cases. In 12 cases (26% of reported secondary cases, 7% of total cases), a structural spinal cord lesion was found. Clonazepam and botulinum toxin may be effective in reducing jerks. Conclusions: FMD is more frequent than previously assumed. Structural lesions reported to underlie PSM are scarce. Based on our clinical experience and the reviewed literature, we recommend polymyography to assess recruitment variability combined with a Bereitschaftspotential recording in all cases.

Neuropsychological profile of psychogenic jerky movement disorders: Importance of evaluating non-credible cognitive performance and psychopathology

Background Psychogenic movement disorders are disorders of movements that cannot be explained by a known neurological disorder and are assumed to be associated with psychiatric symptoms such as depression and anxiety. Objective To examine the neuropsychological profile of patients with psychogenic movement disorders. Methods We examined cognitive functioning using neuropsychological tests in 26 patients with clinically established psychogenic jerky movement disorders (PMD). We included 16 patients with Gilles de la Tourette syndrome (GTS) who served as a patient control group, in addition to 22 healthy control subjects. Non-credible test performance was detected using a Symptom Validity Test (SVT). Psychopathology was also assessed. Results Apart from a worse performance on a verbal memory task, no evidence of neuropsychological impairments was found in our PMD sample. Interestingly however, patients with PMD reported more cognitive complaints in daily life and performed worse on the SVT than the two other groups. Patients with GTS did not report, or show, cognitive impairments. In patients with PMD, we found associations between verbal learning, SVT performance and severity of depression and anxiety complaints. Conclusions We conclude that some patients with PMD show non-credible cognitive symptoms. In contrast, no evident cognitive impairments were present in patients with PMD or GTS. Our study underlines the importance of assessment of non-credible response in patients with PMD. Additionally, non-credible response might aid in the differentiation of PMD from other movement disorders.

RELN rare variants in myoclonus-dystonia

Myoclonus‐dystonia (M‐D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M‐D cases are caused by mutations in the epsilon‐sarcoglycan gene. In remaining M‐D patients, no genetic factor has been established, indicating genetic heterogeneity.

Which patients with epilepsy are at risk for psychogenic nonepileptic seizures (PNES)? A multicenter case-control study

OBJECTIVE We sought to examine the clinical and electrographic differences between patients with combined epileptic (ES) and psychogenic nonepileptic seizures (PNES) and age- and gender-matched patients with ES-only and PNES-only. METHODS Data from 138 patients (105 women [77%]), including 46 with PNES/ES (39±12years), 46 with PNES-only (39±11years), and 46 with ES-only (39±11years), were compared using logistic regression analysis after adjusting for clustering effect. RESULTS In the cohort with PNES/ES, ES antedated PNES in 28 patients (70%) and occurred simultaneously in 11 (27.5%), while PNES were the initial presentation in only 1 case (2.5%); disease duration was undetermined in 6. Compared with those with ES-only, patients with PNES/ES had higher depression and anxiety scores, shorter-duration electrographic seizures, less ES absence/staring semiology (all p≤0.01), and more ES arising in the right hemisphere, both in isolation and in combination with contralateral brain regions (61% vs. 41%; p=0.024, adjusted for anxiety and depression) and tended to have less ES arising in the left temporal lobe (13% vs. 28%; p=0.054). Compared with those with PNES-only, patients with PNES/ES tended to show fewer right-hemibody PNES events (7% vs. 23%; p=0.054) and more myoclonic semiology (10% vs. 2%; p=0.073). CONCLUSIONS Right-hemispheric electrographic seizures may be more common among patients with ES who develop comorbid PNES, in agreement with prior neurobiological studies on functional neurological disorders.

A new familial syndrome with dystonia and lower limb action myoclonus

Myoclonus‐dystonia (M‐D) is genetic and clinically heterogeneous. Identification and description of rare M‐D syndromes may contribute to gene identification.

Clinical decision-making in functional and hyperkinetic movement disorders

Objective: Functional or psychogenic movement disorders (FMD) present a diagnostic challenge. To diagnose FMD, clinicians must have experience with signs typical of FMD and distinguishing features from other hyperkinetic disorders. The aim of this study was to clarify the decision-making process of expert clinicians while diagnosing FMD, myoclonus, and tics. Methods: Thirty-nine movement disorders experts rated 60 patients using a standardized web-based survey resembling clinical practice. It provided 5 steps of incremental information: (1) visual first impression of the patient, (2) medical history, (3) neurologic examination on video, (4) the Bereitschaftspotential (BP), and (5) psychiatric evaluation. After full evaluation of each case, experts were asked which diagnostic step was decisive. In addition, interim switches in diagnosis after each informational step were calculated. Results: After full evaluation, the experts annotated the first impression of the patients as decisive in 18.5% of cases. Medical history was considered decisive in 33.3% of cases. Neurologic examination was considered decisive in 39.7%, the BP in 8%, and the psychiatric interview in 0.5% of cases. Most diagnostic switches occurred after addition of the medical history (34.5%). Addition of the neurologic examination led to 13.8% of diagnostic switches. The BP results led to diagnostic switches in 7.2% of cases. Psychiatric evaluation resulted in the lowest number of diagnostic switches (2.7% of cases). Conclusions: Experts predominantly rely on clinical assessment to diagnose FMD. Importantly, ancillary tests do not determine the final diagnosis of this expert panel. In general, the experts infrequently changed their differential diagnosis.