This Local Coverage Determination (LCD) addresses use of [Magnetic Resonance
Guided Focused Ultrasound Surgery System
(MRgFUS)](https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150038S006B.pdf) for
the treatment of neurologic conditions.

_MRgFUS unilateral thalamotomy is considered medically reasonable and
necessary in patients who have essential tremor (ET) and all of the
following:_

  1. Medication refractory ET (defined as refractory to at least 2 trials of medical therapy, including at least 1 first-line agent)
  2. Moderate to severe postural or intention tremor of the dominant hand (defined by a score of 2 on the Clinical Rating Scale for Tremor (CRST))
  3. Disabling ET (defined by a score of 2 on any of the 8 items in the disability subsection of the CRST)
  4. Has failed deep brain stimulation (DBS) or is not able to tolerate the procedure due to other medical problems

_MRgFUS unilateral thalamotomy is considered medically reasonable and
necessary in patients who have Tremor-Dominant Parkinson 's disease (TDPD) and
all of the following:_

  1. Medication refractory TDPD, defined as refractory (or intolerant) to levodopa or levodopa equivalent medications (LEDD)  900 mg
  2. Parkinson's disease (PD) with tremor-dominant subtype. This should generally be reflected by administering the unified Parkinson's disease rating scale (UPDRS) in the on-medication state using the ratio of the mean score for tremor items (items 16, 20, and 21) to the mean postural instability/gait disorder score (items 13-15,29, and 30). A ratio of  1.5 indicates TDPD
  3. Severe and disabling tremor as indicated by documentation of specific activities in daily life that the patient is unable to perform or has substantial difficulty performing secondary to the tremor
  4. Has failed DBS or is not able to tolerate the procedure due to other medical problems

_Limitations (not covered):_

  1. Treatment of head or voice tremor
  2. Bilateral thalamotomy
  3. Conditions 
    1. Unstable cardiac disease
    2. Coagulopathy
    3. Risk factors for deep-vein thrombosis
    4. Severe depression (defined by a score 20 on Patient Health Questionnaire 9 (PHQ-9))
    5. Cognitive impairment (defined by a score of <24 on the Mini-Mental State Examination)
    6. Previous brain procedure (transcranial magnetic stimulation, DBS, stereotactic lesioning, or electroconvulsive therapy)
    7. A skull density ratio (the ratio of cortical to cancellous bone) <0.4011,12
    8. Magnetic resonance imaging (MRI) contraindicated

ET is a most common movement disorder affecting roughly 0.9% of individuals
over age 65 years, though it can have a large range of symptom severity
ranging from mildly symptomatic to sufficiently severe as to render an
individual unable to self-feed.1 Although there are no curative therapies,
symptoms of ET are often managed medically using a variety of available oral
or injected treatments.1,2 For patients whose tremor is not adequately
controlled medically, surgical treatment options are also available including
stereotactic thalamotomy with radiofrequency (RF) ablation and DBS.1
Radiosurgery has also been described, though there is less data available on
its efficacy.1 Both unilateral thalamotomy and DBS are acceptable surgical
interventions for medically refractory ET, though DBS is thought to have fewer
adverse events.3

MRgFUS has emerged as a potential non-invasive thalamotomy technique.

Food and Drug Administration (FDA) approval for MRgFUS treatment of ET4 was
based on its pivotal study, a prospective, double-blind, randomized, sham-
controlled trial of MRgFUS to create a unilateral thalamic ablation for the
treatment of ET, for which results were published in the peer reviewed
literature.5 In this study, investigators examined the impact of the ExAblate
MRgFUS device in 76 patients with ET. There were 56 patients assigned to the
treatment arm with ExAblate and 20 patients assigned to the sham control
group. Patients in the sham group could crossover to active treatment after 3
months, after initial effectiveness endpoints were assessed. The primary
efficacy outcome measure was the change from baseline to 3 months in the on-
medication upper limb tremor subscore of the Clinical Rating Scale for Tremor
(CRST A+B) for the treated limb. The baseline CRST A+B score was 18.4 in the
treatment group and 16.0 in the sham group. The CRST A+B score improved 47% by
3 months in the treatment group and 0.01% in the sham group with a between
group difference of 8.3 (P < 0.001). The between group difference persisted at
12 months. Following the initial 3 month outcome assessment, 19 of the 20
patients originally randomized to the sham group and 2 patients randomized to
MRgFUS, in whom the procedure was not completed crossed over to receive MRgFUS
treatment. The mean baseline CRST A+B score at crossover in this group was
16.5, but 3 months after the crossover, the mean dropped to 7.4 (P <0.001),
similar to the 3 month outcomes in the group originally allocated to
treatment.

Following the FDA approval of MRgFUS for ET, MRgFUS for unilateral thalamotomy
was approved by the FDA for the treatment of medication-refractory TDPD.6,7
Research has suggested that the pathophysiology of TDPD may be different from
the pathophysiology of PD in patients affected primarily by rigidity and
bradykinesia.8 Additionally, a unique medication strategy is often indicated
for TDPD, but for refractory patients, surgery may be considered.9

In a study patterned off of the study used in FDA approval of MRgFUS for ET,
investigators studied the impact of the ExAblate MRgFUS device in 27 patients
with TDPD.6,7 There were 20 patients assigned to the treatment arm and 7
patients assigned to the sham control group. Patients in the sham group could
crossover to active treatment after 3 months, after initial effectiveness
endpoints were assessed. The patients in the treatment arm received a
unilateral MRgFUS thalamotomy. The primary efficacy outcome measure was the
change from baseline to 3 months in the on-medication upper limb tremor
subscore of the CRST A+B for the treated limb. The baseline CRST A+B score was
17 (range of 10.5-27.5) in the treatment group and 23 (range of 14-27) in the
sham group. The CRST A+B score improved 62% by 3 months in the treatment group
and 22% in the sham group (p = 0.04). The investigators also noticed
improvements in efficacy secondary outcome measures at 3 months including the
CRST, UPDRS, and PD Questionnaire-39 in the treatment group. Following the
initial 3 month outcome assessment, 6 of the 7 patients originally randomized
to the sham group crossed over to receive MRgFUS treatment. The median
baseline CRST A+B score at crossover in these 6 was 21, but 3 months after the
sham group crossed over, the median dropped to 5.5, similar to the 3 month
outcomes in the group originally allocated to treatment. The investigators
also considered the 1 year outcome of response in on-medication CRST A+B
score. Of the 20 patients enrolled in the treatment group, 14 were unblended
for 1 year assessments, and the median CRST was 5. Among the sham patients who
crossed over, the median CRST was 6 at 1 year.

Additionally, MRgFUS is currently being studied for use in medically-
refractory dyskinesia symptoms or motor fluctuations of advanced PD as part of
a study registered at clinicaltrials.gov.10 This study does not yet have
results available, so evidence from it was not reviewed.

When making coverage determinations, Centers for Medicare and Medicaid
Services (CMS) and Medicare Administrative Contractors (MACs) generally
evaluate relevant clinical evidence to determine whether or not the evidence
is of sufficient quality to support a finding that an item or service falling
within a benefit category is reasonable and necessary for the diagnosis or
treatment of illness or injury or to improve the functioning of a malformed
body member. The critical appraisal of the evidence enables us to determine to
what degree we are confident that: 1) the specific assessment questions can be
answered conclusively; and 2) the intervention will improve health outcomes
for beneficiaries. An improved health outcome is 1 of several considerations
in determining whether an item or service is reasonable and necessary.

MRgFUS is a treatment approach that relies on high-intensity focused
ultrasound delivered with Magnetic Resonance (MR) guidance. It can be used to
ablate specific deep brain structures non-invasively. While, long term
effectiveness and safety have not been studied, the use of this technology to
non-invasively ablate structures for which surgical ablation is considered an
accepted treatment approach suggests that this technology would have a similar
therapeutic effect as surgical approaches to the ablation of these regions of
the brain. In the background of this bioplausibility, clinical trials have
been performed to study the outcomes achieved from treating of patients with
neurological conditions with MRgFUS. Efficacy of this therapeutic technique
has been specifically demonstrated when MRgFUS is used for unilateral
thalamotomy (ventralis intermedius) for ET and for TDPD. We did not find any
high quality head-to-head studies comparing MRgFUS to existing surgical
techniques, so we are unable to definitively conclude how it compares to these
treatment methods.

This appears to be an evolving area of research with at least 1 other ongoing
study for the use of this technology in neurologic disease. This A/B MAC will
continue to monitor scientific developments, and may adjust this coverage
policy in accordance.