Pathophysiological Mechanisms in Parkinsonian and Essential Tremor

The present project deals with the pathophysiological basis of the two most frequent tremor disorders, Parkinsonian and essential tremor. Combined EEG-EMG investigations provided evidence that there is tremor-correlated activity in the sensorimotor cortex in both Parkinson's disease and essential tremor. This suggests that the sensorimotor cortex is involved in tremor generation, and that the tremor generating mechanisms in both disorders are partly identical (Hellwig et al., Clin Neurophysiol 2000; 111: 806–809; Hellwig et al., Lancet 2001; 357: 519–523). In bilaterally activated essential tremor, tremor-correlated activities in the right and left sensorimotor cortex are not entirely independent of each other. Central oscillators in the right and left brain seem to synchronize in a dynamic way, presumably by interhemispheric coupling via the corpus callosum. This right-left synchronization is associated with increased tremor amplitudes (Hellwig et al., Clin Neurophysiol 2003; 114: 1462–1467). In unilateral Parkinsonian rest tremor, PET studies and morphometrically analyzed MRI studies showed both functional and morphological changes in the ventrolateral thalamus contralateral to the tremor side. The amount of the thalamic changes covaried with tremor amplitudes. The functional changes were located in the nucleus ventrooralis anterior and posterior, a thalamic subnucleus receiving input from the basal ganglia. The morphological changes were found in the nucleus ventralis intermedius whose afferences are derived from the cerebellum. The results support the hypothesis that both the basal ganglia and the cerebellum are involved in the generation of Parkinsonian tremor (Kassubek et al., Neurosci Lett 2001: 304: 17–20; Kassubek et al., Neurosci Lett 2002; 323: 29–32). Electromyographic recordings from the wrist extensors and flexors showed that both Parkinsonian and essential tremor are influenced by the position of the hand. This indicates that the activity of the central oscillators in both disorders can be modified by proprioceptive afferences (Lauk et al., Muscle Nerve 2001; 24: 1365–1379). The present results and the studies of other groups provide the basis for pathophysiological models of Parkinsonian and essential tremor. Electrophysiological studies in subcortical structures of the tremor generating networks, for instance, during stereotactic operations, should elucidate the pathophysiological basis of tremor disorders in more detail.