New MRI Technology Shows Biochemical Brain Differences in Essential Tremor

To help you get started reading this, here are a few terms you should know:

• Thalamus – a small mass with two halves on top of the brain stem near the center of the brain. It organizes sensory and motor input, then relays it to other parts of the brain.
• VIM nucleus – the part of the thalamus that acts as a relay circuit for motor signals from the cerebellum (part of the hindbrain with a major role in movement control) to the motor cortex. The VIM nucleus is an important component of the motor control pathway from the brain to the limbs. If the origin of motor signals is dysfunctional, the output of the VIM nucleus will also be distorted or incomplete. Essential tremor (ET) may originate from an abnormality in the cerebellum, or the VIM nucleus itself may be malfunctioning.
• Metabolism – the chemical and biological processes by which cells convert nutrients and other substances into life-sustaining activities such as growth, generating energy and information transmission. Too few or too many metabolites can alter outcomes.
• MRI spectroscopy – a radiation-free sequence used in magnetic resonance imaging (MRI) to detect metabolic concentrations in the brain or other parts of the body. The biochemical information thus obtained is diagnostic because it can help tell the difference between normal and abnormal tissues.

MRI of the brain

It is well-established that MRI is an accurate, noninvasive way to identify the anatomy of the thalamus and its VIM nucleus. State-of-the-art MRI technology offers very high resolution of soft-tissue structures in the brain. This enables physicians to create a 3-dimensional atlas of the brain in order to plan neurological interventions deep in the brain. Such interventions as MRI-guided Focused Ultrasound or Deep Brain Stimulation (DBS) are use to treat conditions like Parkinson’s disease tremors, epileptic seizures, chronic pain, and even obsessive-compulsive disorder. However, since the brain has so many areas – many of them very small – so close together, any type of neurosurgical or neurological treatment that physically alters a structure comes with the risk of impairing an adjacent brain area. MRI excels at the accurate imaging essential for developing treatment strategies.

Sometimes, more information than anatomy alone is also needed. Adapting MRI so it can characterize normal vs. abnormal tissues, the brain can be better understood and treatment can be that much safer, more precisely targeted, and ultimately more effective.

MRI spectroscopy of the thalamus and ET

A 2017 paper published by Barbagallo et al.¹ describes their use of MRI spectroscopy (MRI-S) to compare thalamic metabolic differences between ET patients vs. normal individuals. Because MRI-S is sensitive to many different metabolites (substances) that generate brain activity, it can identify specific levels of each particular metabolite that is being scanned for.

Two substances that are connected with thalamus activity are called glutamate and glutamine. When these are present in high concentrations, they increase the “excitability” of the thalamus and the structures within it, such as the VIM nucleus. Barbagallo’s team conducted MRI-S scans of 16 ET patients and 14 healthy control subjects. They set the scan software to detect the spectrum of each of several metabolites. The only substances with increased concentrations were glutamate and glutamine. Furthermore, the higher the concentration, the more severe or intense the tremor.

Research evidence that the thalamus itself may be implicated in ET due to a biochemical imbalance of two key metabolites may open new possibilities for treating ET. If a normal metabolite balance can somehow be achieved, perhaps interventions into the brain for ET patients will gradually become a thing of the past. For now, however, the most successful non-drug treatments to break the tremor cycle involve changing the physical structures that give rise to tremor.

MRgFUS for ET

A new FDA-approved nonsurgical treatment called Neuravive stops the dysfunctional messages forwarded by the VIM nucleus. Neuravive is for ET patients who are currently on medication, those whose tremors no long respond to drugs, and patients who do not wish to take medication. Under MRI guidance, Neuravive aims focused “beams” of ultrasound energy through the skull to the precise part of the VIM nucleus that relays the abnormal signals. When the beams intersect, they act on the VIM nucleus to block the tremor signals. Neuravive has immediate results. It is a safe treatment that restores a patient’s use of his/her dominant hand and rekindles quality of life. NOTE: Patients must be qualified by a physician to ensure they are candidates.

If you or a loved one is struggling with ET that impairs quality of life and does not respond to medication, contact Sperling Neurosurgery Associates.

¹ Barbagallo G, Arabia G, Novellino F, Nisticò R, Salsone M et al. Increased glutamate + glutamine levels in the thalamus of patients with essential tremor: A preliminary proton MR spectroscopic study. Parkinsonism Relat Disord. 2017 Nov 28. pii: S1353-8020(17)30811-8.