What exactly causes essential tremor (ET)? No one yet knows for sure, but it is generally thought to arise with abnormal movement signals from the part of the brain called the cerebellum. The cerebellum is like the command headquarters for bodily movements. It is responsible for coordinating voluntary movements, posture, balance, speech and more.
When it comes to regulating movement throughout the body and limbs, the cerebellum has a vast army of “output helpers” called Purkinje (purr-kin-gee) cells. They are among the largest types of neurons (nerve cells) in the brain, and they occupy an entire layer near the outer edges of the cerebellum. They play a key role in controlling movement and coordination but they themselves are partially regulated by basket cells so they don’t send runaway signals. These basket cells help keep the brakes on Purkinje cells. The two types of cells form a sort of interlocking system.
Purkinje cell bodies are nestled in the dendrites (branches) of basket cells. It is thought that basket cells help govern Purkinje cells’ movement signals to deeper cerebellar centers by “firing” inhibitory messenger molecules (neurotransmitters) to Purkinje cell receptors. In turn, this slows down the tendency to excite movement.
Empty basket cells reveal loss of Purkinje cells in ET
One of the major theories about the process of ET has to do with the deterioration of Purkinje cells. Exactly why Purkinje cells would degenerate isn’t known. However, it makes sense that if there are fewer Purkinje cells to receive the inhibitory neurotransmitters, some signals won’t be properly controlled. These abnormal signals will run their course along the tremor pathway, ending up as uncontrollable rhythmic shaking of the hands, arms, head, voice or other body parts.i
The loss of Purkinje cells can actually be seen in brain specimens from organ donors. In fact, a research collaboration involving Yale University, Columbia University, NY Presbyterian Hospital, Albany Medical College and the Veterans Administration involved cellular analysis of 127 brain cerebellums. In this study, 50 of the brains came from persons with ET while 25 were from persons with no neurodegenerative condition.ii
The research team found that in cases of ET, loss of Purkinje cells (PC) was one-and-a-half times greater than in brains with no movement disorders. Based on this, the study authors concluded, “These data provide support for PC loss in ET and are consistent with the notion that ET could represent a mild form of cerebellar degeneration with an intermediate degree of PC loss.”
The theory of diminished Purkinje cells still requires much more research, but there are enough consistencies within the literature that I see it as a leading hypothesis. While the idea of cerebellar degeneration is discouraging and leads to feelings of depression and helplessness, it’s important to recognize that even without knowing the exact cause, there are still many treatments and strategies for living well with ET.
MRgFUS to control medication-resistant tremors
At Sperling Neurosurgery Associates, we offer an FDA-approved ET treatment that does not involve drugs, surgery or radiation. It is called MRI-guided Focused Ultrasound and it is highly effective. It is a one-time outpatient procedure that results in safe and durable tremor control by ablating a motor signal “relay station” called the VIM nucleus in the thalamus. Patients are thrilled to reclaim a quality of life they thought they had lost forever, as can be seen in their own video stories.
Visit our website for more information on the treatment, and how to contact us.
iLouis E. Essential tremor: a common disorder of Purkinje neurons? Neuroscientist 2016 Apr; 22(2): 108-118. Whole article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467972/
iiLee PJ, Kerridge CA, Chatterjee D, Koeppen AH et al. A Quantitative Study of Empty Baskets in Essential Tremor and Other Motor Neurodegenerative Diseases. Feb 1;78(2):113-122.