The diagnostic value of clinical neurophysiology in hyperkinetic movement disorders: A systematic review.

INTRODUCTION: To guide the neurologist and neurophysiologist with interpretation and implementation of clinical neurophysiological examinations, we aim to provide a systematic review on evidence of electrophysiological features used to differentiate between hyperkinetic movement disorders. METHODS: A PRISMA systematic search and QUADAS quality evaluation has been performed in PubMed to identify diagnostic test accuracy studies comparing electromyography and accelerometer features. We included papers focusing on tremor, dystonia, myoclonus, chorea, tics and ataxia and their functional variant. The features were grouped as 1) basic features (e.g., amplitude, frequency), 2) the influence of tasks on basic features (e.g., entrainment, distraction), 3) advanced analyses of multiple signals, 4) and diagnostic tools combining features. RESULTS: Thirty-eight cross-sectional articles were included discussing tremor (n = 28), myoclonus (n = 5), dystonia (n = 5) and tics (n = 1). Fifteen were rated as 'high quality'. In tremor, the basic and task-related features showed great overlap between clinical tremor syndromes, apart from rubral and enhanced physiological tremor. Advanced signal analyses were best suited for essential, parkinsonian and functional tremor, and cortical, non-cortical and functional jerks. Combinations of electrodiagnostic features could identify essential, enhanced physiological and functional tremor. CONCLUSION: Studies into the diagnostic accuracy of electrophysiological examinations to differentiate between hyperkinetic movement disorders have predominantly been focused on clinical tremor syndromes. No single feature can differentiate between them all; however, a combination of analyses might improve diagnostic accuracy.

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia.

OBJECTIVE: Finding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients. METHODS: EEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4-12 Hz) and beta band (13-30 Hz) peak coherences were studied. RESULTS: Dystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3-10), TWSTRS: 22%, median 6.8 (IQR 4-9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit. CONCLUSIONS: Peak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity. SIGNIFICANCE: IMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.

Wavelet coherence analysis: A new approach to distinguish organic and functional tremor types.

OBJECTIVE: To distinguish tremor subtypes using wavelet coherence analysis (WCA). WCA enables to detect variations in coherence and phase difference between two signals over time and might be especially useful in distinguishing functional from organic tremor. METHODS: In this pilot study, polymyography recordings were studied retrospectively of 26 Parkinsonian (PT), 26 functional (FT), 26 essential (ET), and 20 enhanced physiological (EPT) tremor patients. Per patient one segment of 20 s in duration, in which tremor was present continuously in the same posture, was selected. We studied several coherence and phase related parameters, and analysed all possible muscle combinations of the flexor and extensor muscles of the upper and fore arm. The area under the receiver operating characteristic curve (AUC-ROC) was applied to compare WCA and standard coherence analysis to distinguish tremor subtypes. RESULTS: The percentage of time with significant coherence (PTSC) and the number of periods without significant coherence (NOV) proved the most discriminative parameters. FT could be discriminated from organic (PT, ET, EPT) tremor by high NOV (31.88 vs 21.58, 23.12 and 10.20 respectively) with an AUC-ROC of 0.809, while standard coherence analysis resulted in an AUC-ROC of 0.552. CONCLUSIONS: EMG-EMG WCA analysis might provide additional variables to distinguish functional from organic tremor. SIGNIFICANCE: WCA might prove to be of additional value to discriminate between tremor types.

Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus. METHODS: Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed. RESULTS: A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities. CONCLUSIONS: Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.

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.

Sympathetic regulation of cerebral blood flow in humans: a review.

Cerebral blood flow (CBF) is regulated by vasomotor, chemical, metabolic, and neurogenic mechanisms. Even though the innervation of cerebral arteries is quite extensively described and reviewed in the literature, its role in regulation of CBF in humans remains controversial. We believe that insufficient attention has so far been focused on the potential role of the innervation of the cerebral vasculature in cerebral autoregulation in humans. We have performed an extensive search and selection of available literature on electrical, chemical, and surgical manipulations of the sympathetic innervation of cerebral arteries, and the effects of circulation sympathetically active agents on CBF. Studies on (surgical) ganglion block show a role of sympathetic tone in preventing increases in CBF in humans, which are consistent with the view based on animal studies. Both direct innervation of the cerebral arteries from cervical ganglia and stimulation of adrenergic receptors by circulating sympathomimetics prevent sudden increases of CBF associated with hypertension and hypercapnia. We postulate that under normal physiological conditions neurogenic control has little influence on cerebral autoregulation as other methods of control (vasomotor, chemical, and metabolic) are dominant. In severely challenging circumstances, such as delayed cerebral ischaemia after subarachnoid haemorrhage, these methods might be overwhelmed, increasing the relative importance of neurogenic, sympathetic control of CBF. This insight might lead to future therapeutic possibilities.