RAD 1601: EDGE Radiosurgery for Intractable Essential Tremor and Tremor-Dominant Parkinson's Disease

Per the National Institute of Neurological Disorders and Stroke, tremor is an involuntary,
rhythmic muscle contraction leading to shaking movements in one or more parts of the body. It
is a common movement disorder that most often affects the upper extremities but can also
occur in the head, vocal cords, torso, and lower extremities. Tremor may be intermittent or
constant. It can be present at rest, during action, or mixed between rest and action.

Tremor can occur at any age but it is most common among middle-aged and older adults; once it
occurs, it often progresses over time. This disorder shows no gender predilection. Although
tremor is not life threatening, it can be severely disabling, making it difficult or even
impossible to perform work and daily life tasks.

Deep parts of the brain that control movements appear to be involved in tremor development.
However, most types of tremor have no actual known cause. There are some forms that appear to
be inherited and run in families. There are more than 20 types of tremor. Tremor can occur on
its own (such as essential tremor (ET) or be associated with other neurological disorders,
such as Parkinson's disease (PD).

Tremor is a common symptom of Parkinson's disease. The classification of patients with
Parkinson's disease into tremor-dominant and non-tremor subtypes is well established. The
pathophysiology of tremor in patients with tremor-dominant Parkinson's disease (TDPD) may be
distinct from other their other symptoms, such as bradykinesia, rigidity, and gait and
balance symptoms. Importantly, tremor in PD responds less well or can even be highly
resistant to dopaminergic treatment than bradykinesia and rigidity. Therefore other treatment
strategies may need to be considered.

Essential Tremor (ET) is a common neurologic condition characterized by a tremor that can
occur either with posture or action. In the US, there are reported to be as many as 10
million people with essential tremor. A significant subset of patients experience persistent
disability and disruption on activities of daily living from tremor and require intervention.

Treatment approach depends on the penetrance of disability into a patient's life, but
typically begins with pharmacologic intervention. Patients with disabling tremor refractory
to primary and secondary pharmacologic interventions are evaluated for surgical treatment
with deep brain stimulation (DBS) or thalamotomy. However, a sizeable subset of these
patients are unfavorable candidates for surgery due to medical or neurological
co-morbidities. Additionally, a significant subset of patients simply does not wish to
undergo the awake craniotomy required for DBS lead placement for tremor. Stereotactic
radiosurgery (SRS) thalamotomy is an alternative for those patients. SRS thalamotomy targets
the ventral intermediate (VIM) nucleus of the thalamus based on predetermined stereotactic
coordinates.

Almost all prior SRS thalamotomy studies performed have used the Leksell Gamma Knife
treatment unit and demonstrate that about 80% of properly selected patients respond. The
efficacy of Gamma Knife radiosurgery for tremor has been studied prospectively and has been
modeled based upon prognostic factors in larger retrospective studies. These studies provide
benchmarks for measuring the safety and efficacy of frameless Virtual Cone radiosurgery in
this trial. In order for possible frameless Virtual Cone radiosurgery to be a standard of
care in the treatment of tremor, additional clinical data is required. This pilot trial of
Virtual Cone radiosurgery will assess the safety and efficacy of this treatment. A target of
twenty patients will be treated to confirm the feasibility of the protocol procedures,
efficacy, and safety of the treatment. Secondary endpoints will include quality of life and
patient satisfaction. The investigators hypothesize that the recent improvements in LINAC
delivery, image guidance, and patient position monitoring will allow a safe frameless
procedure that has a high patient satisfaction and low toxicity.

Inclusion Criteria:

- Patients with medical refractory essential tremor or tremor-dominant Parkinson's
disease that are not candidates for deep brain stimulation (DBS), either by
medical/surgical co-morbidities or by choice.

- Patients must have an ECOG status of 0, 1, or 2.

- Patients must be at least 18 years of age.

- All patients must be given written informed consent.

Exclusion Criteria:

- Patients who have had prior radiosurgery or therapeutic brain radiation therapy.

- Patients with medical contra-indications to MRI imaging (e.g. pacemaker).