The pathogenesis of essential tremor (ET) is still under debate. Several lines of evidence indicate that ET is associated with cerebellar dysfunction. The aim of the present study was to find corroborating evidence for this claim by investigating balance and speech impairments in patients with ET. In addition, the effect of deep brain stimulation (DBS) on balance and speech function was studied. A group of 25 ET patients including 18 with postural and/or simple kinetic tremor (ETpt) and seven ET patients with additional clinical signs of cerebellar dysfunction (ETc) was compared to 25 healthy controls. In addition, 12 ET patients with thalamic DBS participated in the study. Balance control was assessed during gait and stance including tandem gait performed on a treadmill as well as static and dynamic posturography. Motor speech control was analyzed through syllable repetition tasks. Signs of balance impairment were found in early stages and advanced stages of ET. During locomotion, ET patients exhibited an increased number of missteps and shortened stride length with tandem gait. ETc patients and, to a lesser extent, ETpt patients had increased postural instability in dynamic posturography conditions that are sensitive to vestibular or vestibulocerebellar dysfunction. ETc but not ETpt patients exhibited significantly increased syllable durations. DBS had no discernable effect on speech performance or balance control. We conclude that the deficits in balance as well as the subclinical signs of dysarthria in a subset of patients confirm and extend previous findings that ET is associated with an impairment of the cerebellum.

Several lines of evidence point to an involvement of the olivo-cerebellar system in the pathogenesis of essential tremor (ET), with clinical signs of cerebellar dysfunction being present in some subjects in the advanced stage. Besides motor coordination, the cerebellum is critically involved in motor learning. Evidence of motor learning deficits would strengthen the hypothesis of olivo-cerebellar involvement in ET. Conditioning of the eyeblink reflex is a well-established paradigm to assess motor learning. Twenty-three ET subjects (13 males, 10 females; mean age 44.3 +/- 22.3 years, mean disease duration 17.4 +/- 17.3 years) and 23 age-matched healthy controls were studied on two consecutive days using a standard delay eyeblink conditioning protocol. Six ET subjects exhibited accompanying clinical signs of cerebellar dysfunction. Care was taken to examine subjects without medication affecting central nervous functioning. Seven ET subjects and three controls on low-dose beta-blocker treatments, which had no effect on eyeblink conditioning in animal studies, were allowed into the study. The ability to acquire conditioned eyeblink responses was significantly reduced in ET subjects compared with controls. Impairment of eyeblink conditioning was not due to low-dose beta-blocker medication. Additionally, acquisition of conditioned eyeblink response was reduced in ET subjects regardless of the presence of cerebellar signs in clinical examination. There were no differences in timing or extinction of conditioned responses between groups and conditioning deficits did not correlate with the degree of tremor or ataxia as rated by clinical scores. The findings of disordered eyeblink conditioning support the hypothesis that ET is caused by a functional disturbance of olivo-cerebellar circuits which may cause cerebellar dysfunction. In particular, results point to an involvement of the olivo-cerebellar system in early stages of ET.

This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.