Essential Tremor: Implications in Heterogeneous Motor Phenomenology

Essential tremor may present with co-occurrence of other neurological disorders in the same individual or in multiple individuals in the same family; this may result in clinical and research implications that will help improve the understanding of disease etiology and pathogenesis, according to study results published in Neurology Clinical Practice.

One of the most common movement disorders, essential tremor, may also affect patients diagnosed with other neurological disorders. Evidence suggests that the co-occurrence of essential tremor with Parkinson disease and/or dystonia may not be due to chance.

To better understand the relationship between these 3 disorders, a team of investigators observed people with essential tremor and their relatives, and presented the implications of their findings.

Study investigators included a total of 4 families with essential tremor in which heterogenous motor phenomenology was present in the analysis. They enrolled patients with essential tremor and their families in the Family Study of Essential Tremor, and conducted phenotyping of neurological disorders upon neurological examination by a senior movement disorders neurologist.

Of the 4 families, 14 people were affected: 8 patients had essential tremor only, 3 patients had essential tremor and Parkinson disease, 1 patient had Parkinson disease only, and 2 patients had essential tremor with dystonia.

In the first family, 3 individuals had essential tremor only and 1 individual had both essential tremor and Parkinson disease. The second family, 2 individuals had essential tremor only, 1 individual had Parkinson disease only, and 1 patient had essential tremor and dystonia. In the third family, 1 individual had essential tremor only and 1 individual had essential tremor and Parkinson disease. Lastly, the fourth family had 2 individuals with essential tremor, 1 individual with essential tremor and Parkinson disease, and 1 individual with essential tremor and dystonia.

Findings highlighted the challenges for studies to find candidate genes for essential tremor, as there may be common genetic etiologies that give rise to various movement disorders. For example, dystonia-24 (DYT24), caused by a mutation in the anoctamin 3 gene, can result in a variety of movement disorders such as tremor, dystonia, and myoclonus. 

Results also suggested mechanistic or pathophysiological commonalities, such as mutual involvement of the cerebellum or deposition of Lewy bodies in these disorders. Because cerebellar and basal ganglia circuits with the cerebral cortex may be interconnected at several subcortical levels, it is thought that the cerebellum may play a role not only in the pathophysiology of essential tremor, but also in dystonia.

“[W]e believe the concept of the ‘mixed motor disorder’ should on multiple levels enter into and inform the clinical dialogue and clinical decision making of providers,” the study authors concluded. “In assigning diagnoses, clinicians are influenced or swayed by family history information; in doing so, they should be prepared to accept the possibility of a significant mix of motor disorders within the same family rather than feeling constrained to assign a homogeneous diagnosis to every family member. This will serve to lessen the likelihood of diagnostic misclassification (ie, assigning the incorrect diagnosis to a patient) and reduce the possibility of treating patients for the wrong condition.”

Reference

Louis ED, Hernandez NC, Ottman R, Clark LN. Essential tremor families with heterogenous motor phenomenology: “mixed motor disorder.” Neurol Clin Pract. Published online April 22, 2021. doi:10.1212/CPJ.0000000000001100