Essential Tremor: Not Just a Single Disease?

Essential tremor (ET) is the most common movement disorder, affecting an estimated 10 million people in the U.S. It recognizes no geographic boundaries. From the island of Manhattan to remote islands in the South Seas, abnormal hand, arm, head and voice tremors affect their sufferers’ quality of life.

It used to be thought that ET was a problem arose in the same brain area for every person: the cerebellum. However, that view is morphing into a more complex hypothesis about the origins and manifestations tremors. In fact, ET may turn out to be a group of conditions instead of a single disease.

 

ET: a family or group of diseases

The predominant new view is that ET is likely “a cluster of separable clinical-pathological entities, that is, a family of diseases – ‘the essential tremors’.” A number of research findings support this view:

1. Although hand, arm and head tremors are the most common symptoms, there is variance such as degree of tremor, area most affected, pattern of spread, etc.
2. Other motor disturbances such as irregular gait and unusual eye motion affect many patients.
3. Some ET progression appears correlated with cognitive, emotional and psychological impairments, at greater frequency than in a normal population.
4. Non-motor symptoms such as loss of sense of smell or hearing have also been reported among ET patients with an incidence greater than among controls.
5. The age of onset appears correlated with certain symptoms, e.g. older onset patients are more at risk for Alzheimer’s disease.

These clues point to a group of diseases rather than a single disease.

 

Brain research suggests 2 ET types

New analysis of brain specimens from deceased ET patients confirms what the clues suggest. It was formerly thought that all ET cases were associated with brain degeneration in the cerebellum (caused by a reduction in number or an increase in deformities of a type of cell called Purkinje cells). This is termed the cerebellar type of ET. However, pathology has revealed a second “type” of cases originating in a different region called the locus ceruleus. There, aggregated proteins called Lewy bodies develop within nerve cells and interfere with their function, so it is termed the Lewy body type of ET. There is considerable understanding of how the loss of Purkinje cells cascades into what eventually shows up as the cerebellar type of tremors. On the other hand, it is not clear how the Lewy body type results in ET – but at least it’s known that the locus ceruleus has a maintenance function with the Purkinje cells.

Then there’s the question of whether all ET types are triggered by the same thing. Genetics plays a key role, but not in all cases. While patterns of inheritance exist in ET families, specific genes have not been identified, and may even vary from one family to another. But not all cases of ET are genetic; new evidence points to certain toxins in the environment that may trigger brain malfunction.

 

Implications for treatment

No one yet knows for sure whether ET is one disease with numerous variations, or whether it’s a group of diseases. It should also be pointed out that some features of ET-related brain degeneration observed can also be found in other neurodegenerative disorders that are completely separate from ET.

If ET is a group of diseases, will therapies tailored to each type prove effective? So far, treatment results are uneven. About half of ET patients find pharmaceutical drugs helpful, but since ET is progressive, trying higher doses or different drugs becomes the new normal. For those whose tremor is not relieved by medication, intervention into the brain to physically destroy the very small area responsible for tremor may be effective.

The Sperling Medical Group offers MR-guided Focused Ultrasound (MRgFUS), a completely noninvasive alternative to neurosurgery and deep brain stimulation. Contact us to learn if you are qualified.

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ⁱLouis, ED. The Essential Tremors: a family of neurodegenerative disorders? Arch Neurol. 2009 Oct;66(10):1202-08.