Essential Tremor: A Kodak Moment in the Brain?

Almost 200 years ago, photography made its entrance onto the stage of technology. Credit for the first known photographic image of a person goes to a Frenchman, Louis Daguerre, who captured a man getting a shoe shine in an 1838 Paris street scene.

If only it were possible to capture an image of essential tremor (ET) in the brain—but it’s not that simple. While certain areas of the brain (cerebellum, thalamus, motor cortex) are the “usual suspects” that form the tremor network, no one knows the precise abnormalities that cause ET to begin or where they are located.

Searching for ET brain abnormalities

When searching for brain abnormalities that might be clues to the source of ET, here are currently two main ways to analyze the brain:

  • Neuroimaging, which means taking pictures (scans) of the brain by means of magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET). Today’s neuroimaging includes both structural imaging (a “snapshot” of brain anatomy) and functional imaging (a “movie” of brain activity).
  • Neuropathology, which means taking the physical brain apart for study after a person has died. This allows analysis of the brain tissue based on slices mounted on slides that can be magnified and examined under powerful microscopes.

The research involved with understanding how ET operates in the brain is like putting together a jigsaw puzzle, take advantage of both neuroimaging and neuropathology. The goal is to create a “functional anatomy.” This means identifying physical brain features that differ from non-tremor brains, and finding out how they operate when they are active.

Complications and challenges

One thing that complicates the process is the fact that the tremor network includes multiple areas of the brain. Another factor is the age of tremor onset; although tremors can begin at any age, ET appears most linked with aging—that is, persons over 40. After midlife, aging brains begin to have small structural changes. According to Klaming & Annese, “One of the main challenges of neuroimaging in essential tremor is differentiating disease-specific markers from the spectrum of structural changes that occur due to aging.”i This makes it impossible to diagnose ET based on any type of brain scan. There is simply no definitive “Kodak moment” or imaging scan. Instead, as anyone with ET knows,

…the diagnosis of ET is based solely on behavioral symptoms. Relevant factors to establish a diagnosis and distinguish ET from other movement disorders include the age of onset, the evolution of clinical signs with time, which factors aggravate the symptoms, past or chronic exposure to toxic substances (heavy metals in particular), and family history.

If neuroimaging can’t detect or diagnose ET, what about neuropathology? What have studies with brains from dead people (postmortem brain dissection) shown us? Unfortunately, nothing of real merit. Unlike other neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s) that have some characteristic structural changes, nothing has yet been identified with cases of ET. Here, too, the involvement of other brain areas confounds the search for abnormalities, since there is not yet an established dissection protocol for brains affected by ET’s abnormal signals.

However, some research with postmortem brains has demonstrated that about 2/3 of cases have a diminished number of Purkinje cells. On the one hand, this is a promising clue, but on the other, it tells us nothing about the remaining 1/3 of cases. As puzzling as it may be, ET appears to not be a single condition, but rather a family of disorders. If this is true, it may well account for very inconsistent responses to medications – what works for one person does not for another, and some people with ET gain no help at all from taking drugs.

Keeping hope alive

With ongoing improvements in neuroimaging, there is reason to be optimistic that future developments will bring scanning technologies powerful enough to pinpoint specific malfunctioning brain areas that contribute to ET. In turn, this can lead to creating therapies tailored for each individual.

While we wait for that day, Sperling Neurosurgery Associates offers Neuravive, a safe and effective outpatient alternative to Deep Brain Stimulation that uses noninvasive waves of focused ultrasound (FUS) to interrupt the tremor pathway. This outpatient treatment requires that candidates be examined and qualified using neuroimaging, which also enables planning the delivery of the ultrasound to the tiny target in the brain. Unlike medication, which is unpredictable and comes with side effects, Neuravive provides consistent success. While it’s not yet possible to take a photo of the ET process in the brain, it is possible to use powerful MRI to obtain the Kodak moment showing where to aim the treatment.

For more information on MRI-guided Focused Ultrasound to control ET, visit our website.

iKlaming R, Annese J. Functional Anatomy of Essential Tremor: Lessons from Neuroimaging. Am J Neurorad. 2014 Aug; 35(8):1450-57.

iiIbid.

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