Essential tremor (ET), the most common movement disorder, does a great job of keeping its causes shrouded in mystery. About half of cases seem to run in families, but no genes have yet been identified. No one yet knows what triggers it, whether it could be prevented, and whether it’s truly a degenerative disorder. However, regarding the third mystery, there is relatively new evidence from autopsies and imaging studies that ET is, in fact, degenerative. It now appears that course of ET involves cumulative damage to a particular cell type called Purkinje cells.
Purkinje cells in the cerebellum
There is general agreement that ET originates in the part of the brain called the cerebellum, or “little brain.” The cerebellum is located at the back of the brain, and a little below it. To get a general idea, place your hand on the back of your neck and slowly move it upward until you feel where your skull starts to curve outward. Now cup your palm over that curve, and picture the back of your brain within it. That’s the area of the cerebellum.
The cerebellum plays a gigantic role in movement. That’s because the cerebellum is like an old-fashioned switchboard operator fielding incoming calls, then plugging a specific “live” wire into the proper connection so “electrified” messages get to the right person for appropriate action.
The body’s sensory systems, the spinal cord, and other regions of the brain send “incoming calls” to the cerebellum. The cerebellum coordinates these messages then connects them via pathways in the brain that are like outbound extensions. In doing so, the cerebellum regulates movement, integrating balance, position, posture and even speech.
The cerebellum has specialized neurons (nerve cells) called Purkinje (purr-kin-gee) cells. They are named after the person who discovered them in 1837, Czech physiologist Jan Evangelista Purkinje. They are among the largest types of neurons the brain, occupying an entire layer near the outer edges of the cerebellum. As output “helpers” they play a key role in regulating movement messages.
Purkinje cells produce GABA
How they do this is by manufacturing and releasing a molecule called GABA (gamma-aminobutyric acid). This is a neurotransmitter (biochemical messenger) that helps cells know what to do. GABA is called an inhibitor because controls motor messages by slowing down high energy neuronal activity. For example, if you were on a safari and a rhinoceros is charging, your brain goes into fear mode –an “explosion” of nerve impulses needed for the fight-or-flight response to danger. At the same time, the Purkinje cells release GABA to put the brakes on so fear mode doesn’t become a runaway chain reaction of terror, which would be paralyzing. As GABA calms things down, other parts of your brain calculate your best strategy, and carry it out with appropriate motor activity to implement the safety strategy.
What does this have to do with ET?
So, now we come back to our starting point. Is ET a degenerative condition? Author Elan Louis, MD (Yale U. Movement Disorders) is a leading authority on ET. In his 2016 article, “Essential Tremor: A Common Disorder of Purkinje Neurons?” he does a terrific job of reviewing the most recent evidence that points at dysfunction and degeneration of Purkinje cells as the source of uncontrollable tremors of the hands, arms, head, voice and other body parts.i While we still don’t know what triggers the deterioration of these cells, at least we can point to this process as the most likely root of “the shakes.”
The damage to Purkinje cells can be seen in autopsy brain specimens from ET cases, especially when compared to the same areas in donor brains without ET. The progression of ET is in line with what we would expect if the sources of GABA were no longer functioning properly, or not at all. Louis summarizes what other researchers have observed as ET progresses:
- Tremor becomes more severe and disabling
- Tremor may become more varied as both intentional and resting tremors develop
- More body parts may develop tremors
- Some features of ET can arise or worsen (gait difficulties, eye movement abnormalities)
- Possible cognitive and psychological problems can emerge.
The Purkinje cell theory of pathology requires more research, but it is a leading hypothesis. While the thought of “degeneration” is discouraging, it’s important to recognize that even without knowing the exact cause, there are still many hope-inspiring treatments and coping strategies for living well with ET.
MRgFUS to control medication-resistant tremors
At Sperling Neurosurgery Associates, we offer an FDA-approved noninvasive ET treatment that does not involve drugs, surgery or radiation. It is called MRI-guided Focused Ultrasound. It is a one-time outpatient procedure that results in safe and durable tremor control by ablating (destroying) dysfunctional tremor signals at the VIM nucleus in the thalamus. Patients are thrilled to reclaim a quality of life they thought they had lost forever.
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