A. F. van Rootselaar

Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

INTRODUCTION Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. METHODS Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. RESULTS In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. CONCLUSION The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor.

Normal cortical excitability in Myoclonus-Dystonia - A TMS study

OBJECTIVE The aim of the present study is to investigate cortical excitability in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial magnetic stimulation (TMS). METHODS Silent period, motor evoked potential (MEP) recruitment curve, short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short interval intracortical facilitation (SICF), with short interstimulus intervals (ISIs) ranging from 1.2 to 3.2 ms, were studied in 15 DYT 11-positive M-D patients and their matched controls. In four patients and matched controls peripheral double pulse electrical nerve stimulation was performed. RESULTS All TMS parameters of cortical excitability were normal compared to healthy controls. In the SICF protocol we observed more variable and polyphasic MEPs in M-D patients. Cross-covariance analysis of MEP area revealed a significant correlation difference at ISI 2.2 and 2.8 ms. This increased variability was not seen in other TMS protocols or with peripheral nerve stimulation. CONCLUSIONS In contrast with other types of dystonia, no changes in cortical excitability were found in DYT 11 patients. Our findings suggest that M-D is both clinically and pathophysiologically a separate entity from other dystonic disorders. Polyphasic MEPs during the SICF protocol in M-D patients could reflect central neuron membrane instability. Application of the SICF protocol in other patient groups has to prove its value in movement disorders.

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.

Oculomotor abnormalities in myoclonic tremor: a comparison with spinocerebellar ataxia type 6

In the present study, eye movements are recorded in two patient groups with an autosomal dominantly inherited cerebellar disorder, i.e. spinocerebellar ataxia type 6 (SCA6) and familial cortical myoclonic tremor with epilepsy (FCMTE). In SCA6 and FCMTE patients striking similarities with the extensive Purkinje cell changes in the cerebellar cortex were described, but the two disorders have a distinctive clinical picture. SCA6 is a late-onset cerebellar syndrome, with relatively minimal brain stem and cerebral cortex symptoms. In contrast, FCMTE is clinically characterized by cortical symptomatology with a distal cortical myoclonic tremor and infrequent epileptic attacks without cerebellar dysarthria and limb ataxia. Comparison of oculomotor function of six FCMTE patients, five SCA6 patients and 18 healthy controls demonstrated both in SCA6 patients and FCMTE patients square wave jerks, downbeat nystagmus (DBN) and a stronger reduced downward smooth pursuit gain than an upward smooth pursuit gain. Only in SCA6 patients horizontal smooth pursuit gain was reduced. Except for the downward direction mean saccadic gain in both patient groups was reduced. This is consistent with cerebellar cortical pathology in both disorders. Subsequently, both patient groups showed increase of DBN with hyperventilation. As a novel finding, only the FCMTE patients showed a significantly increased amount of express saccades in the pro-saccade paradigm.

Robust EMG-fMRI artifact reduction for motion (FARM)

OBJECTIVE Current template-based artifact reduction methods are inadequate to reduce irregular volume- and slice-artifacts induced by limb motion in combined (surface) EMG-fMRI (electromyography-functional magnetic resonance imaging) studies. In addition, artifacts are not removed adequately for EMG frequencies above 50 Hz. We present a new fMRI artifact reduction algorithm for motion (FARM) and compare it with standard artifact correction as implemented in fMRI artifact slice-template removal (FASTR). METHODS One control subject generated motion artifacts during EMG-fMRI. Low-frequency motion artifacts and volume-artifacts were removed prior to slice-artifact correction. Slice-artifacts were phase-shifted and removed with motion adaptive templates (FARM). EMG data were also corrected applying FASTR. RESULTS Time traces demonstrate that artifacts related to sudden changes in wire position are contained to shorter time periods. EMG power spectra from neck and arm muscles show that FARM has improved performance at higher frequencies. CONCLUSIONS High-pass filtering, volume-artifact removal, phase-shifting and adaptation of slice-templates to motion improve the quality of artifact-corrected EMG recorded during limb motion. SIGNIFICANCE The improved accuracy at which EMG-fMRI data can be obtained opens up new ways to directly relate self-paced movements to brain activations and to study patients suffering from movement disorders.

How to tackle tremor - systematic review of the literature and diagnostic work-up

Background: Tremor is the most prevalent movement disorder in clinical practice. It is defined as involuntary, rhythmic, oscillatory movements. The diagnostic process of patients with tremor can be laborious and challenging, and a clear, systematic overview of available diagnostic techniques is lacking. Tremor can be a symptom of many diseases, but can also represent a distinct disease entity. Objective: The objective of this review is to give a clear, systematic and step-wise overview of the diagnostic work-up of a patient with tremor. The clinical relevance and value of available laboratory tests in patients with tremor will be explored. Methods: We systematically searched through EMBASE. The retrieved articles were supplemented by articles containing relevant data or provided important background information. Studies that were included investigated the value and/or usability of diagnostic tests for tremor. Results: In most patients, history and clinical examination by an experienced movement disorders neurologist are sufficient to establish a correct diagnosis, and further ancillary examinations will not be needed. Ancillary investigation should always be guided by tremor type(s) present and other associated signs and symptoms. The main ancillary examination techniques currently are electromyography and SPECT imaging. Unfortunately, many techniques have not been studied in large prospective, diagnostic studies to be able to determine important variables like sensitivity and specificity. Conclusion: When encountering a patient with tremor, history, and careful clinical examination should guide the diagnostic process. Adherence to the diagnostic work-up provided in this review will help the diagnostic process of these patients.

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.

P937: Essential tremor and the olivocerebellar system – an fMRI study

there is an appreciable overlap between tremor-dominant PD and advanced ET with regard to basic tremor parameters like amplitude, frequency, activation pattern or phase deviation of different affected muscles. Methods: Postural hand tremor was measured using an ultrasound-based three-dimensional (3D) real time motion analysis system (CMS 70P, Zebris, Isny, Germany). Different spatiotemporal parameters of tremor like 3D amplitude, frequency and vector angles of hand tremor movement in the transversal plane through the metacarpal joints as well as the variation and dispersion of these parameters throughout two recorded sequences of 60s each were calculated. Statistical analysis used Student’s T-Test for unpaired samples. Results: A total of n=45 Patients (mean age ± SD 67±11 years) with considerable postural tremor (score ≥2 on UPDRS III item 21), diagnosed according to usual clinical criteria either with ET (n=22) or PD (only tremor type I; n=23), were included in the study. Mean tremor frequency was slightly but not significantly higher in the ET group (5.7±0.8Hz vs. 5.3±0.7Hz; p=0.084). However, both the variation of the 3D tremor amplitude over time (see Fig. 1A for examples in a single ET and PD patient) as well as the dispersion of the vector angle of the tremor beats in the metacarpal plane (Fig. 1B) were significantly higher in the PD group (p>0.05). In 20 out of 23 PD patients characteristic oscillations of the tremor amplitude could be observed (see Fig. 1A, tremor beats 150-300 in the PD example), but only in 6 out of 22 patients with ET. Conclusions: The analysis of particular spatiotemporal 3D parameters of tremor like the variation of tremor amplitude over time or the dispersion of the 3D vector angle of the tremor movement might be an additional diagnostic tool for the differentiation of patients with tremor-dominant PD from advanced ET.

P04. Intermuscular coherence and eye movement studies in two sisters with orthostatic tremor

and smooth pursuit. Peak saccade velocity (main sequence) and saccadic gain were calculated. In addition, video recordings were performed to evaluate OMA. Results: Oculomotor abnormalities ranged from a complete ophthalmoplegia to dysmetric saccades. Slowing of saccades was found in six out of the seven patients. Five out seven patients showed OMA. Interestingly, unlike her sister one of girl the monozygotic twin did not show any eye movement abnormality. Smooth pursuit was normal except for the patient with complete ophthalmoplegia. Conclusions: All observed eye movement abnormalities in the patient group with type 3 Gaucher disease are indicative for brainstem pathology. Particularly, the neural circuitry consisting of burst neurons and pause cells in the reticular formation is malfunctioning. Phenotype varied, even between monozygotic twins.

FC16.2 Brain activity in cortical and essential tremor during wrist flexion-extension movement and posture; a simultaneous EMG-fMRI study

was delivered on the tongue. Analysis was performed using peristimulus time histograms and cumulative sum plots. Results: Seventy-six SMUs were sampled from 11 subjects. Twenty-four SMUs were localized in the OOr region (activated by lip protrusion). Fifty-two SMUs were in the eccentric muscles region (activated by mouth opening). Cutaneous stimulation: 77% of SMUs from the eccentric muscles showed a clear SP without a preceding facilitatory peak. Twenty-nine percentage of SMUs from the OOr responded with a SP without a preceding excitatory peak. Intra-oral stimulation: 40% of SMUs from the eccentric muscles showed a SP not preceded by excitation. Eight percentage showed an early facilitatory peak and a following SP. Twelve percentage of the OOr SMUs showed an isolated SP and none showed a facilitatory peak. Discussion: These results show the presence of an inhibitory modulation on lower facial motor neurons by trigeminal afferents. Both stimulus modalities are effective in inducing an SP in both muscle groups, though the maximal effect was found in the eccentric muscles for cutaneous stimulation. The SP produced after cutaneous stimulation is not due to synchronization of motor unit discharge after a facilitatory discharge. The present data confirm the presence of a trigemino-facial inhibitory reflex in lower facial muscles.