C.H. Lücking

Tremor-correlated cortical activity in essential tremor

BACKGROUND In patients with parkinsonian resting tremor, tremor-correlated activity in the contralateral sensorimotor cortex has been studied by both magnetoencephalography (MEG) and electroencephalography (EEG). In essential tremor, MEG failed to detect cortical involvement. The objective of this study was to investigate whether EEG recording can reveal tremor-correlated cortical activity in patients with essential tremor or enhanced physiological tremor. METHODS Seven patients with essential tremor and three patients with enhanced physiological tremor participated in the study. Unilateral postural tremor was activated by wrist extension on the right or on the left side. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles, and a high-resolution EEG were recorded simultaneously. Coherences between the time series of the rectified tremor EMG and the EEG were estimated. FINDINGS In five of nine arms with essential tremor, we found highly significant coherences at the tremor frequency between the tremor EMG and the EEG. Isocoherence maps illustrating the topography of significant coherences over the scalp showed that the maximum coherences were located over the contralateral sensorimotor cortex. In the patients with enhanced physiological tremor, we were unable to detect consistent significant corticomuscular coherences at the tremor frequency. INTERPRETATION Using simultaneous EEG-EMG recordings, we showed that significant corticomuscular coherences at the tremor frequency can be found in essential tremor. This finding contrasts with a recent study based on MEG recordings. The results suggest that the sensorimotor cortex is involved in the generation of essential tremor, in a similar way to that previously shown in parkinsonian resting tremor.

Subacute combined degeneration : clinical, electrophysiological, and magnetic resonance imaging findings

OBJECTIVE Vitamin B12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients. METHODS Clinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients before and after treatment. RESULTS The most prominent clinical and electrophysiological findings in all patients were dysfunctions of the posterior column. Corresponding hyperintense lesions in the posterior column of the spinal cord were found in two patients by T2 weighted MRI. Damage to the central motor pathway was identified in four patients. Demyelinating neuropathy was present in one patient and axonal neuropathy in four. All patients showed improvement of their symptoms after treatment with cobalamin. Abnormalities of the spinal cord on MRI disappeared early in recovery. Motor evoked potentials and median somatosensory evoked potentials typically normalised after treatment, whereas tibial somatosensory evoked potentials remained abnormal in most patients. CONCLUSIONS Clinical, electrophysiological, and MRI findings associated with SCD in vitamin B12 deficiency are diverse. Thus vitamin B12 deficiency should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.

Pathological tremors: Deterministic chaos or nonlinear stochastic oscillators?

Pathological tremors exhibit a nonlinear oscillation that is not strictly periodic. We investigate whether the deviation from periodicity is due to nonlinear deterministic chaotic dynamics or due to nonlinear stochastic dynamics. To do so, we apply various methods from linear and nonlinear time series analysis to tremor time series. The results of the different methods suggest that the considered types of pathological tremors represent nonlinear stochastic second order processes. Finally, we evaluate whether two earlier proposed features capturing nonlinear effects in the time series allow for a discrimination between two pathological forms of tremor for a much larger sample of time series than previously investigated.

Tremor-correlated cortical activity detected by electroencephalography.

OBJECTIVE In this study we investigated whether cortical activity related to Parkinsonian resting tremor can be detected by electroencephalography (EEG). METHODS Seven patients with idiopathic Parkinsons disease suffering from unilateral tremor participated in the study. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles as well as a high resolution EEG were recorded simultaneously. Coherencies between EEG and EMG were calculated. RESULTS In all patients, we found highly significant coherencies at the tremor frequency or its first harmonic between the tremor EMG and contralateral EEG channels. There were no significant coherencies between the tremor EMG and ipsilateral EEG channels. Isocoherency maps illustrating the topography of the coherencies over the scalp showed that the maximum coherencies were situated over the cortical motor areas. In one case, a high coherency was also found over the parietal cortex. CONCLUSIONS The results show for the first time that tremor-correlated cortical activity can be detected by electroencephalography. The findings underline that motor areas of the cerebral cortex are involved in the neuronal network generating resting tremor in Parkinsons disease.

CROSS-SPECTRAL ANALYSIS OF TREMOR TIME SERIES

We discuss cross-spectral analysis and report applications for the investigation of human tremors. For the physiological tremor in healthy subjects, the analysis enables to determine the resonant contribution to the oscillation and allows to test for a contribution of reflexes to this tremor. Comparing the analysis of the relation between the tremor of both hands in normal subjects and subjects with a rare abnormal organization of certain neural pathways proves the involvement of central structures in enhanced physiological tremor. The relation between the left and the right side of the body in pathological tremor shows a specific difference between orthostatic and all other forms of tremor. An investigation of EEG and tremor in patients suffering from Parkinsons disease reveals the tremor-correlated cortical activity. Finally, the general issue of interpreting the results of methods designed for the analysis of bivariate processes when applied to multivariate processes is considered. We discuss and apply partial cross-spectral analysis in the frame of graphical models as an extention of bivariate cross-spectral analysis for the multivariate case.

Essential tremor and cerebellar dysfunction: abnormal ballistic movements

Background: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. Objective: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. Methods: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ETPT; n = 17), and essential tremor with an additional intention tremor component (ETIT; n = 15). Results: The main findings were a delayed second agonist burst (AG2) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ETIT group, which had additional prolongation of the first agonist burst (AG1) and a delayed antagonist burst (ANT). Conclusions: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ETIT group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ETPT and ETIT may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.

Side-to-side correlation of muscle activity in physiological and pathological human tremors

OBJECTIVE Many tremors occur always or often bilaterally. The question arises whether this could be explained by a common source or commonly transmitting pathways or by bilaterally represented, independent structures with the same oscillatory properties. A similar tremor frequency does not provide sufficient information to clarify this question. METHODS We analyze coherencies between surface electromyographies (EMG) to investigate if bilateral physiologic (PT), essential (ET), Parkinsonian (PD) and orthostatic (OT) tremors originate from a common source for both sides of the body. We show that commonly used techniques to test whether coherencies are significant could lead to false positive results for tremor EMGs. A new estimation procedure is proposed to test EMG tremor time series on their linear independence. We apply this test to bilateral tremors. RESULTS All measured EMG-pairs in OT (n = 7) were highly coherent between both sides with reproducible coherency values of up to 0.99. All other investigated tremors, i.e. PT and enhanced physiological tremors (EPT, n = 117), ET (n = 76) and PD resting and postural tremors (n = 70) do not show a significant side-to-side correlation. CONCLUSIONS This finding shows that the pathophysiologies of OT and other pathological tremors are definitely different. Either they have different origins or different kinds of transmitting pathways. The proposed method might also be used to investigate other electrophysiological data and is a helpful, easy to use investigation for a daily clinical routine.

Central mechanisms in human enhanced physiological tremor

The sites of the central nervous structures involved in enhanced physiological tremor (EPT) are still unclear. The syndrome of persistent mirror movements (PMM) is characterized by abnormal bilateral corticospinal projections. If a supraspinal mechanism is involved in EPT, the activity of EPT should be coherent between both sides in subjects with this abnormality. We investigated three PMM subjects and three normal controls. Focal transcranial magnetic stimulation (TMS) resulted in contralateral hand muscle responses in the controls. The PMM subjects, in contrast, had bilateral responses. Similarly, long-latency reflexes (LLR) in PMM could be recorded bilaterally, while the control subjects showed responses only on the stimulated side. EPT was evoked by intravenous salbutamol. EMG time series were recorded bilaterally from the wrist extensor muscles and cross spectra were calculated. If there was a significant right-left-coherence, phase analysis was performed. No control subject showed a significant right-left-coherence of tremor activity. In contrast, a significant coherence was found in PMM between 8 and 12 Hz. When the mechanical tremor frequency of one hand was reduced by loading, coherences and phase spectra of the EMGs remained unchanged. By comparing the results from TMS, LLR and cross spectral analysis we come to the conclusion, that the 8 to 12 Hz component of EPT is transmitted transcortically, most likely originating from two separate generators for both sides.

Tremor analysis in two normal cohorts

OBJECTIVE Quantitative tremor analyses using almost identical methods were compared between two independent large normal cohorts, to separate robust measures that may readily be used diagnostically from more critical ones needing lab-specific normalization. METHODS Hand accelerometry and surface EMG from forearm flexors and extensors were recorded with (500 and 1000 g) and without weight loading under postural conditions in 117 and 67 normal volunteers in two different specialty centers for movement disorders in Germany. RESULTS Tremor amplitude (total power) and frequency fell within a similar range but differed significantly. A significant reduction of tremor frequency under 1000 g weight load (>1 Hz), and a lack of rhythmic EMG activity at the tremor frequency in around 85-90% of the recordings were robust findings in both centers. CONCLUSIONS The differences in frequency and total power indicate that these measures critically depend on the details of the recording conditions being slightly different between the two centers. Thus each lab needs to establish its own normative data. We estimate that at least 25 normal subjects have to be recorded to obtain normal values. The reduction of tremor frequency under load and lacking tremor-related EMG activity were well reproducible allowing a differentiation of physiological from low amplitude pathological tremor. SIGNIFICANCE This study provides a framework for more standardized tremor analyses in clinical neurophysiology.

Reciprocal inhibition of forearm flexor muscles in spasmodic torticollis

Reciprocal inhibition between forearm extensor and flexor muscles was tested by means of an H-reflex technique in patients with spasmodic torticollis and normal controls. In both, patients and controls three different phases of reciprocal inhibition could be demonstrated with maximal inhibition at conditioning test intervals of 0 ms, 15 ms and 100 ms, respectively. However, the quantitative amount of this inhibition was different for the patients and the controls. Significantly less inhibition was found for the second and the third phase of reciprocal inhibition in the patient group. Discriminant analysis showed a clear separation between normal subjects and patients if the amount of reciprocal inhibition of the second and third phase were taken into account. We were not able to detect any side differences neither for the patients nor for the controls. The findings demonstrate a functional disturbance of motor control mechanisms of a clinically unaffected extremity in spasmodic torticollis. This is believed to reflect a bilateral disturbance most likely within the basal ganglia or their outflow. Therefore, our data support the idea, that spasmodic torticollis is associated with or even due to a generalized rather than a focal disturbance of motor control mechanisms.