MECHANISMS OF TREMOR 119
process in ET; Daniels et al., 2006), heterogeneous and degenerative anatomopathological changes
are reported in ET. Indeed, cerebellar changes and brainstem Lewy bodies distinguished 10 ET
cases from 12 controls (Louis et al., 2006). A further study on 33 ET and 21 control brains con-
ﬁrmed the presence in ET brains of pathological changes in the cerebellum (75.8%)—probably as a
consequence of an overactivity within cerebellar nuclei—with decreased numbers of Purkinje cells,
presence of Lewy bodies in the brainstem (24.2%), degeneration of the dentate nucleus in two cases
of ET without Lewy bodies, Purkinje cell heterotopias, and dendrite swellings (Louis et al., 2007).
The reduction in Purkinje cell number in the brains of patients with ET has been demonstrated
even in the absence of Lewy bodies, supporting the view that the cerebellum is anatomically, as well
as functionally, abnormal in these cases of ET (Axelrad et al., 2008).
It is established that the cerebellum plays a role in the event-based timing of synchronized re-
petitive movements. Farkas et al. (2006) found a severe deﬁcit of event-based rhythm generation on
both sides, supporting the presumed bilateral cerebellar dysfunction in ET. Moreover, impairment
of motor imagery (the process of mental representation of movements) was recently demonstrated.
However, whether this is related to a genuine cerebellar or motor cortical dysfunction is still unclear
(Lo et al., 2007).
In the subgroup of ET patients with predominant kinetic tremor, a relative expansion of gray
matter areas involved in higher-order visuospatial processing is detectable by MRI voxel-based
morphometry. Hypothetically, this is related to a long-term adaptive reorganization in the central
nervous system, compensating the higher demands on the visuospatial control of skilled movements
in case of trembling (Daniels et al., 2006).
7.7 REST TREMOR AND PARKINSON’S DISEASE
In a study on coherence in 22 subjects affected by Parkinson’s disease (PD), no consistent pattern
across patients was found, suggesting that tremor in PD is generated by multiple oscillatory circuits,
which tend to operate on similar frequencies (Ben-Pazi et al., 2001; Raethjen et al., 2000). PD
tremor is coupled within, but not between, limbs. The anatomy of basal ganglia loop (see Chapter
2) may explain the presence of several generators.
Three main neuronal mechanisms have been hypothesized:
corticosubthalamopallidothalamic loop generating tremor
pacemaker consisting of the external pallidum and the subthalamic nucleus
an abnormal synchronization within the whole striatopallidothalamic pathway leading to
a loss of segregation (Deuschl et al., 2000).