Essential Tremor

Pathophysiology

The precise mechanism underlying ET remains unknown. Initial post-mortem studies of ET brain have identified groups with two different pathologic changes: cerebellar degenerative changes and brain stem Lewy bodies. The distribution of Lewy bodies differs from that in Parkinson's disease, being primarily in the locus ceruleus. These neurons are the primary source of norepinephrine in the brain, and project to Purkinje cells in the cerebellum. Based on these pathologic findings, it is possible that a dysfunction of inhibitory cerebellar output underlies both pathologic subtypes of ET.

Several theories of tremorogenesis have been proposed that implicate a central source of oscillation. More specifically, ET is thought to arise from oscillatory activity within a central network or cell group that becomes dysregulated, allowing spinal reflex loop oscillations. It has also been proposed that stretch loop circuits may become unstable and drive muscle contractions to produce tremor as in ET.

C¹⁵-labeled O₂ positron emission tomography (PET) of ET patients has suggested a possible abnormality in the olivocerebellar tracts with midbrain activation in the region of the red nucleus. PET testing in patients with ET also revealed increased cerebellar activity even while at rest. These findings are consistent with the theory that the cerebellum plays an important role in the generation of tremor.

Increased glucose metabolism in the inferior olivary nucleus of the medulla has also been demonstrated, suggesting that this structure may be the source of the rhythmic discharge causing the tremors. This is further supported by the fact that lesions in the cerebellum or thalamus may result in cessation of tremor. In another study, functional magnetic resonance imaging in 12 people with ET and 15 control subjects suggested that ET is mainly associated with an additional contralateral cerebellar pathway activation and overactivity in the cerebellum, red nucleus, and globus pallidus without significant intrinsic olivary activation.

In another study, ingestion of ethanol (EtOH), which suppresses tremor in ET patients, led to a bilateral decrease in cerebellar blood flow in both tremor patients and normal subjects, plus increased blood flow in the inferior olivary nuclei in the ET patients but not in the control subjects.

Peripheral factors may contribute to tremor as well. Beta-adrenergic blockers such as propranolol attenuate ET and physiologic tremor, possibly via peripheral beta₂ adrenoreceptors. In addition, intravenous and intra-arterial epinephrine enhance physiologic tremor via peripheral beta-adrenoreceptors, which are blocked by propranolol. However, beta-blockers may also affect central pathways.