Transcranial Stimulation for Essential Tremor
Transcranial Stimulation for Essential Tremor
The main purpose of this study is to see if transcranial magnetic stimulation (TMS) can be
 used to help study brain function in healthy people and in those with neurological diseases
 like essential tremor. This portion of the study is being done to establish the optimal
 methods for stimulating the brain to measure its responses.
Essential tremor (ET) is a movement disorder characterized by tremor of both hands, and often
 head and voice, affecting approximately 4.8-6.7 million individuals over the age of 40 in the
 United States alone. Hand tremor can limit basic activities of daily living like feeding,
 drinking, writing and dressing. While medications can be effective for tremor, they are often
 poorly tolerated due to their sedative or neuronal activity depressant properties. Surgical
 options such as deep brain stimulation of the ventral intermedius thalamus (Vim DBS) can be
 highly effective but its invasive nature limits its popularity. Noninvasive brain stimulation
 has demonstrated the ability to reduce tremor but precisely where to target brain stimulation
 to achieve the best results is currently unknown.

 Repetitive transcranial magnetic stimulation (rTMS) enables noninvasive, selective and
 sustained modulation of specific neural networks, and can lead to clinical benefits in
 debilitating neurologic and psychiatric disorders, including medication-resistant depression,
 paresis following stroke or traumatic brain injury, Parkinson's disease, or dementia. There
 is also recent evidence that rTMS of the cerebellum can relieve hand tremor due to essential
 tremor. TMS uses electromagnetic induction to generate controlled currents in targeted brain
 structures that can be identified and defined using MRI-based neuronavigation. TMS is safe if
 appropriate guidelines are adhered to. To date, the impact of rTMS on ET has not been
 sufficiently established, but pilot studies offer promising results.

 The investigators are testing whether MRI-guided neuronavigated cerebellar paired pulse TMS
 demonstrates abnormal physiologic measures in ET subjects compared to controls and whether
 there is reduction of tremor via cerebellar rTMS in patients with ET. The investigators plan
 to collect imaging, functional and neurophysiological assessments before and after the rTMS
 to identify the mechanistic underpinnings of rTMS-induced changes in tremor and
 cerebello-cortical inhibition.
Inclusion Criteria for ET subjects:

 1. Outpatients with essential tremor as diagnosed and confirmed by movement disorder
 specialist

 2. Women of child-bearing potential must provide a negative pregnancy test at entry into
 the study

 3. Stable doses of all medications for at least 14 days prior to study entry and for the
 duration of the study,

 4. At least a 1cm amplitude tremor as judged by the screener using a ruler

 Inclusion Criteria for Healthy Volunteers:

 1. Healthy subjects without tremor and without significant neurologic disease suggestive
 of cerebellar ataxia or other neurodegenerative diseases

 2. Ages 18-80

 Exclusion Criteria:

 1. Any unstable illness or concomitant medical condition that, in the investigator's
 opinion, precludes participation in this study, including disorders that may affect
 gait or balance (i.e., stroke, arthritis, etc).

 2. Pregnancy or lactation.

 3. Concurrent participation in another clinical study.

 4. Dementia or other psychiatric illness that prevents the patient from giving informed
 consent (Montreal Cognitive Assessment Score score less than or equal to 21).

 5. Legal incapacity or limited legal capacity.

 6. Tremor derived from any cause other than essential tremor (Parkinson's disease,
 drug-induced, anxiety-induced) in the clinical assessment at screening

 7. Currently taking lithium or amiodarone or any other drug judged to be contributing to
 tremor as judged by the investigator (may be a cause of tremor)

 8. No medication is an absolute exclusion from TMS. Medications will be reviewed by the
 responsible MD and a decision about inclusion will be made based on the following:

 -  The patient's past medical history, drug dose, history of recent medication
 changes or duration of treatment, and combination with other Central Nervous
 System active drugs.

 -  The published TMS guidelines review of medications to be considered with TMS

 9. History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG, or
 family history of treatment resistant epilepsy with the exception of a single seizure
 of benign etiology (e.g. febrile seizures) in the judgement of the investigator

 10. TMS and MRI-Specific exclusion criteria including:

 -  Known metal in the head (such as a surgical aneurysm clip) or a history of prior
 neurosurgical procedures.

 -  Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic
 means, such as cochlear implants, pacemakers, medication pumps, vagal
 stimulators, deep brain stimulators, neurostimulators, biostimulators, or
 ventriculo-peritoneal shunts.

 -  Subjects who have or might have bullet fragments or other shrapnel (veterans or
 workers exposed to metal in their work environment).

 -  Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic
 eyeliner)

 -  Subjects expressing significant claustrophobia.