The cerebellum is assumed to play a major role in the pathophysiology of essential tremor (ET). As intention tremor is considered one of the classical features of cerebellar disease, we have assessed a large group of patients with ET for the semiology of the tremor and have performed objective quantitative analysis of a grasping movement in patients with ET, cerebellar disease and a normal control group. We found 25% of the patients to have a moderate or severe kinetic tremor with clear-cut features of a classical intention tremor. Another 33% of the patients had a mild intentional component of their kinetic tremor. Patients with intention tremor (ET(IT)) did not differ from those with predominant postural tremor (ET(PT)) with respect to alcohol sensitivity of the tremor and the frequency of a family history. ET(IT) patients were older and more often showed head and trunk involvement. The onset of this intention tremor has been assessed retrospectively. It was found to begin at a randomly distributed time interval after the onset of the postural tremor, but older patients had a shorter time to development of intention tremor. Quantitative accelerometry of postural tremor showed similar tremor frequencies in both patient groups, but ET(IT) patients had a slightly larger tremor amplitude. Quantitative analysis of a grasping movement using an infrared-camera system was performed in two subgroups of the patients with ET(PT) and ET(IT) and control groups with cerebellar disease or normal subjects. The intention tremor could be quantified objectively as an increased amplitude of curvature during the deceleration and target phase of the movement. The amplitude measurements of intention tremor were clearly abnormal and of comparable magnitude for ET(PT) and cerebellar disease. Additionally, the patients with ET(IT) had a significantly slowed grasping movement during the deceleration and target period. Hypermetria was significantly increased for the patients with ET(IT) and cerebellar disease. We conclude that intention tremor is a feature of ET. ET(IT) patients have abnormalities of their upper limb function compatible with cerebellar disease. This suggests that patients with more advanced ET show abnormalities of cerebellar functions.

Gait disturbances of patients with essential tremor (ET) have been described anecdotally, but have never been investigated quantitatively. Recent studies provided evidence for a cerebellar-like hand tremor in some patients with ET. Therefore, we designed a study to assess cerebellar-like abnormalities of leg function. Twenty-five patients with ET, eight patients with cerebellar diseases (CD) and 21 age-matched healthy subjects were studied for their normal and tandem gait using a three-dimensional gait analysis system. During normal walking, CD and ET patients showed only slight abnormalities. However, ET patients exhibited abnormalities in tandem gait with an increased number of mis-steps and a broad-based, ataxic and dysmetric gait which was indistinguishable from the findings in CD. When ET patients were separated into groups of those with or without intention tremor of the hands, the gait disorder was found to be much more pronounced in the intention tremor group. Patients with this gait disorder were more severely disturbed in their activities of daily living, and suffer from an advanced stage of ET. The present results quantitatively describe a gait disturbance in advanced ET which affects tandem gait, but leaves normal gait almost unaffected. This is strong evidence for a cerebellar-like disturbance in ET.

Background: Although gait disturbance is one of the most pronounced and disabling symptoms in cerebellar disease (CD), quantitative studies on this topic are rare. Objectives: To characterise the typical clinical features of cerebellar gait and to analyse ataxia quantitatively. Methods: Twelve patients with various cerebellar disorders were compared with 12 age matched controls. Gait was analysed on a motor driven treadmill using a three dimensional system. A tandem gait paradigm was used to quantify gait ataxia. Results: For normal locomotion, a significantly reduced step frequency with a prolonged stance and double limb support duration was found in patients with CD. All gait measurements were highly variable in CD. Most importantly, balance related gait variables such as step width and foot rotation angles were increased in CD, indicating the need for stability during locomotion. The tandem gait paradigm showed typical features of cerebellar ataxia such as dysmetria, hypometria, hypermetria, and inappropriate timing of foot placement. Conclusions: Typical features of gait in CD are reduced cadence with increased balance related variables and an almost normal range of motion (with increased variability) in the joints of the lower extremity. The tandem gait paradigm accentuates all the features of gait ataxia and is the most sensitive clinical test.

Deep brain stimulation of the thalamus (thalamic DBS) is an established therapy for medically intractable essential tremor and tremor caused by multiple sclerosis. In both disorders, motor disability results from complex interaction between kinetic tremor and accompanying ataxia with voluntary movements. In clinical studies, the efficacy of thalamic DBS has been thoroughly assessed. However, the optimal anatomical target structure for neurostimulation is still debated and has never been analysed in conjunction with objective measurements of the different aspects of motor impairment. In 10 essential tremor and 11 multiple sclerosis patients, we analysed the effect of thalamic DBS through each contact of the quadripolar electrode on the contralateral tremor rating scale, accelerometry and kinematic measures of reach-to-grasp-movements. These measures were correlated with the anatomical position of the stimulating electrode in stereotactic space and in relation to nuclear boundaries derived from intraoperative microrecording. We found a significant impact of the stereotactic z-coordinate of stimulation contacts on the TRS, accelerometry total power and spatial deviation in the deceleration and target period of reach-to-grasp-movements. Most effective contacts clustered within the subthalamic area (STA) covering the posterior Zona incerta and prelemniscal radiation. Stimulation within this region led to a mean reduction of the lateralized tremor rating scale by 15.8 points which was significantly superior to stimulation within the thalamus (P < 0.05, student's t-test). STA stimulation resulted in reduction of the accelerometry total power by 99%, whereas stimulation at the ventral thalamic border (68%) or within the thalamus proper (2.5%) was significantly less effective (P < 0.01). Concomitantly, STA stimulation led to a significantly higher increase of tremor frequency and decrease in EMG synchronization compared to stimulation within the thalamus proper (P < 0.001). In reach-to-grasp movements, STA stimulation reduced the spatial variability of the movement path in the deceleration period by 28.9% and in the target period by 58.4%, whereas stimulation within the thalamus was again significantly less effective (P < 0.05), with a reduction in the deceleration period between 6.5 and 21.8% and in the target period between 1.2 and 11.3%. An analysis of the nuclear boundaries from intraoperative microrecording confirmed the anatomical impression that most effective electrodes were located within the STA. Our data demonstrate a profound effect of deep brain stimulation of the thalamic region on tremor and ataxia in essential tremor and tremor caused by multiple sclerosis. The better efficacy of stimulation within the STA compared to thalamus proper favours the concept of a modulation of cerebello-thalamic projections underlying the improvement of these symptoms.

Experimental and clinical data indicate that the cerebellum is involved in the pathophysiology of advanced stages of essential tremor (ET). The aim of this study was to determine whether a dysfunction also affects cerebellar structures involved in eye movement control. Eye movements of 14 patients with ET and 11 age-matched control subjects were recorded using the scleral search-coil technique. Vestibular function was assessed by electro-oculography. Eight ET patients had clinical evidence of intention tremor (ET(IT)); six had a predominantly postural tremor (ET(PT)) without intention tremor. ET patients showed two major deficits that may indicate cerebellar dysfunction: (i) an impaired smooth pursuit initiation; and (ii) pathological suppression of the vestibulo-ocular reflex (VOR) time constant by head tilts ('otolith dumping'). In the step ramp smooth pursuit paradigm, the initial eye acceleration in the first 60 ms of pursuit generation was significantly reduced in ET patients, particularly in ET(IT) patients, by approximately 44% (mean 23.4 degrees/s(2)) compared with that of control subjects (mean 41.3 degrees/s(2)). Subsequent steady-state pursuit velocity and sinusoidal pursuit gain (e.g. 0.4 Hz: 0.90 versus 0.78) were also significantly decreased in ET patients, whereas pursuit latency was unaffected. The intention tremor score correlated with the pursuit deficit, e.g. ET(IT) patients were significantly more affected than ET(PT) patients. Gain and time constant (tau) of horizontal VOR were normal, but suppression of the VOR time constant by head tilt ('otolith dumping') was pathological in 41% of ET patients, particularly in ET(IT) patients. Saccades and gaze-holding function were not impaired. The deficit of pursuit initiation, its correlation with the intensity of intention tremor, and the pathological VOR dumping provide additional evidence of a cerebellar dysfunction in the advanced stage of ET, when intention tremor becomes part of the clinical symptoms, and point to a common pathomechanism. The oculomotor deficits may indicate an impairment of the caudal vermis in ET.