Essential Tremor: Time to Kiss an Old Theory Goodbye?

When it comes to determining exactly what causes essential tremor (ET), theories have come and gone. Thanks to today’s sophisticated brain imaging as well as laboratory analysis of brains from cadavers (dead bodies), new information on the origins of ET has begun to replace older beliefs.

The olivary hypothesis of ET

For over 40 years, one of the dominant explanations for the cause of ET was the olivary model. In the part of the brain called the brain stem, there is a pair of olivary bodies (or simply olives because of their size and shape). The brain stem itself is the “autopilot” of the body in terms of involuntary survival functions like heartbeat and blood pressure. It also houses important nerve pathways to connect to the cerebellum (little brain) and areas in the forebrain (cerebrum). Each olivary body has two core parts: the inferior olivary nucleus and the superior olivary nucleus. They have different functions:

  • Inferior olivary nucleus (ION) is the largest nucleus in the olivary bodies. It plays a role in motor (movement) learning. It contains nerve cells that function like “pacemakers” because they generate rhythmic bursts of activity.i
  • Superior olivary nucleus (SON) is connected with hearing.

The olivary model of ET began with animal research in the early 1970s. While there are several other brain components that also have pacemaker properties, the ION model gained favor – but this was due to a peculiarity of animal tremor studies. In humans, ET is called an intention tremor because intentional movement such as reaching for a glass of water can trigger tremor or make it worse. Intentional tremor is rare in animals (it has been noted in dogs with brain damage to the cerebellum). For lab studies with animals like cats and guinea pigs, they are given chemicals that produce tremors. These chemicals act on the ION, producing tremors in the animal that behave like human tremors. Then, in the 1990s, imaging studies with humans lent support to the olivary model. However, they weren’t conclusive since they also showed other abnormal brain structures (cerebellum, motor cortex and thalamus).ii

New MRI studies overturn the olivary model

Advances in magnetic resonance imaging (MRI) now allow studies that characterize the difference between normal and abnormal tissues in brain structures. New imaging studies with ET patients point to other areas of the brain (cerebellum, thalamus, motor cortex, etc.) without picking up associated changes in the ION. Post-mortem studies also bear this out. Comparison of IONs between the brains of long-standing ET patients vs. controls show no significant differences. It seems that when it comes to ET, the ION is not the culprit it was once thought to be.

New treatment for ET focuses on the thalamus

The most recent literature on ET suggests that there may not be a single dysfunctional brain center that causes ET in every patient. Rather, it appears to be a family or group of diseases. However, just as “all roads lead to Rome” (to quote an old saying), all tremor pathways that are misfiring lead to a very small area of the thalamus called the VIM that seems to relay dysfunctional rhythmic motor messages to the hands, head, voice, and other body parts that manifest ET.

For patients with ET that no longer responds to medication, there is a revolutionary noninvasive and effective treatment called MRI-guided Focused Ultrasound (MRgFUS). By beaming hundreds of ultrasound signals to the tiny VIM target, MRgFUS precisely destroys the relay center. MRgFUS is immediately effective, and no surgery is needed. Patients are ecstatic to be able to reclaim quality of life in feeding and dressing themselves, and performing countless daily tasks that severe tremors prevented.

While it may be time to kiss the olivary model goodbye, much more work needs to be done to identify the actual process of brain misfiring that causes ET in each patient. Meanwhile, MRgFUS offers new hope for a nonsurgical, non-drug intervention to control ET. For more information, contact the Sperling Neurosurgery Associates.


iLouis ED, Lenka A. The olivary hypothesis of essential tremor: time to lay this model to rest? Tremor Other Hyperkinet Mov (N Y). 2017 Jul 13;7:473.
iiIbid.

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