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INSIDE
ADVANCES AT MASS GENERAL
SPRING 2015
Thoracic Aortic Endografts
T
horacic endovascular
aortic aneurysm repair,
or TEVAR, has been
implemented for a range
of aortic pathologies, including
traumatic tear, degenerative
aneurysm of the aorta, and
acute and chronic dissection
of the thoracic aorta.1 TEVAR
has been used more often than
open surgery since its first
introduction in the late 1990s,
as it is less invasive, and several
studies have demonstrated early
safety and utility advantages.
However, there are limited data
to address concerns about the
long-term durability of the
technique.
Richard P. Cambria, MD, chief
of Vascular and Endovascular
Surgery at the Massachusetts
General Hospital Fireman
Vascular Center and co-director
of the Thoracic Aortic Center,
and his team have conducted
trials on various TEVAR devices
for several different aortic
diseases, evaluating long-term
outcomes as well as short-term
mortality and other safety and
efficacy outcomes.
TEVAR FOR
DESCENDING THORACIC
AORTIC ANEURYSMS:
A FIVE-YEAR VIEW
In 2014, Dr. Cambria led a
team that published the results
of a five-year international
Antegrade
thrombosis
of the false
lumen
>
3
A NOVEL
TECHNOLOGY FOR
BURN SCARRING
Fractional
photothermolysis is
shown to ameliorate
burn symptoms.
Left subclavian
revascularization
is optional
Proximal
entry tear
5
Stent
graft
Proximal seal
zone is usually
to the left
common carotid
artery
Perfused
false lumen
True lumen
expands
Site of TEVAR Implementation
Anatomic principles of acute type B dissection must be considered in
stent graft repair. TEVAR devices are fitted at the proximal seal zone,
where the endograft affixes to aortic tissue. That seal zone is usually
found in the mid and distal aortic arch.
Source: Richard P. Cambria, MD
study that compared TEVAR
with open surgical repair for
descending thoracic aortic
aneurysms and large ulcers.
The results were published in
the Journal of Vascular Surgery.2
The five-year mortality rate was
similar, at 37%, for both patients
treated with TEVAR and those
treated with open surgery.
However, aneurysm-related
mortality was significantly lower
ILLUSTRATION BY BRYAN CHRISTIE
(5.9%) with TEVAR than with
open surgical repair (12%). No
ruptures of treated aneurysms
were reported in either group.
Severe morbidity was also
significantly lower in the TEVAR
group, at 21% compared with
39% for open surgical repair.
And secondary intervention
rates were similar for both
groups. This study confirmed
that using
(continued on page 2)
INNOVATION IN
TOTAL ANKLE
ARTHROPLASTY
A new generation of
devices may prompt
wider adoption of a
complex surgery.
6
PARKINSON’S
AND CIRCADIAN
DISRUPTION
Circadian rhythm
disruption may
contribute to symptoms
of neurodegenerative
disease.
Outcomes for
Traditional Surgical
Treatment vs.
Endovascular
Repair
Kaplan-Meier estimate of freedom
from severe morbid events for
both endovascular treatment
group and open surgical control
group. Vertical lines represent
95% confidence intervals. TEVAR
patients have fewer major
complications.
TEVAR to treat
anatomically suitable descending
thoracic aortic aneurysms and ulcers is
a safe and effective alternative to open
surgical repair.
(continued from page 1)
EVALUATING A CONFORMABLE
TEVAR DEVICE FOR ACUTE
COMPLICATED TYPE B
DISSECTION
In acute complicated type B dissection,
treatment with TEVAR may address
rupture or malperfusion, as well as
prevent the dissection from becoming
a more complex aneurysm over time.
Dr. Cambria and his team recently
completed a multicenter trial, with the
results soon to be published,3 of the use
of a conformable TEVAR device in acute
complicated type B dissection where all
Cambria, Richard P, Robert S Crawford, Jae-Sung
Cho, Joseph Bavaria, et al. “A Multicenter Clinical
Trial of Endovascular Stent Graft Repair of Acute
Catastrophes of the Descending Thoracic Aorta.”
Journal of Vascular Surgery, vol. 50, no. 6 (December
2009): 1255-64.
FREEDOM FROM SEVERE MORBIDITY
100
80
60
40
20
Endovascular
Log-rank P < .001
Surgical
0
0
1
Matsumura, Jon S, Germano Melissano, Richard P
Cambria, Michael D Dake, et al. “Five-Year Results
of Thoracic Endovascular Aortic Repair With the
Zenith TX2.” Journal of Vascular Surgery, vol. 60, no.
1 (July 2014): 1-10.
Cambria, Richard P, Mark F Conrad, Alan H
Matsumoto, Mark Fillinger, et al. “Conformable
Stent Graft for the Treatment of Acute, Complicated
Type B Dissection: Multicenter Clinical Trial.”
Journal of Vascular Surgery, (2015, in press).
3
2
Advances at Mass General | Spring 2015
3
4
5
YEARS
From Matsumura, Jon S., Germano Melissano, Richard P. Cambria, Michael D. Dake, et al. “Five-Year Results of
Thoracic Endovascular Aortic Repair With the Zenith TX2.” Journal of Vascular Surgery, vol. 60, no. 1 (July 2014):
1-10.
patients had rupture, malperfusion
or both. The device was engineered
specifically for some of the anatomical
and clinical features referable to acute
dissection. In the 50 patients treated
in the trial, the study authors achieved
a 30-day all-cause mortality of 8%.
Historically, this category of patients
has had a 30-day mortality of 30%,
says Dr. Cambria, and the objective
performance criteria is a 30-day
mortality of 10%. The one-year survival
rate from the study was 88%; the twoyear survival rate was 85%. That trial was
the basis for the September 2013 FDA
approval of the conformable TEVAR
device to treat type B dissection, the first
such approval.
Dr. Cambria explains that the device
has been engineered to make it more
conformable at the proximal seal zone.
The use of TEVAR devices for aortic
1
2
2
Contributor
Richard P. Cambria, MD
Chief of Vascular and
Endovascular Surgery
Fireman Vascular Center
Co-Director, Thoracic Aortic Center
Massachusetts General Hospital
Robert R. Linton, MD, Professor of
Vascular and Endovascular Surgery,
Harvard Medical School
[email protected]
dissection has typically been limited
by the anatomy and aortic fragility
at the proximal seal zone, where the
thoracic endograft affixes to normal
aortic tissue. In type B dissection, that
seal zone is usually found in the mid
and distal aortic arch.
GENERATING MORE LONG-TERM
OUTCOME DATA FOR TYPE B
DISSECTION
Currently, there is FDA approval for
two TEVAR devices, soon to be three.
In conjunction with the Society for
Vascular Surgery, Dr. Cambria is the
chair of a national study committee that,
with the FDA, is conducting a five-year
study of clinical results with TEVAR in
the treatment of acute and chronic type
B dissections. The study will enroll 200
patients with acute type B dissection
and 200 patients with chronic type B
dissection, all treated with TEVAR, and
follow them for five years.
The study will assess 30-day
mortality as well as long-term
efficacy, including the percentage
requiring secondary procedures or
additional interventions. The goal
is to quantify the success of TEVAR
technology in preventing the primary
late complication of dissection—the
formation of an aneurysm requiring
complex open surgery. ■
Ablative CO2 Fractional
Photothermolysis for Burn Scars
H
ypertrophic scarring after
burn injury presents a clinical
challenge. In addition to
persistent cosmetic concerns,
such scarring can also cause pain,
tightness, restricted motion and severe
itch. Although the field has seen few
advances in the treatment of such
scars in the past decade, recent studies
have indicated that pulsed dye laser
and fractional CO2 laser treatment
lead to improvements in abnormal
pigmentation, pruritus, pain and
tightness.1 A fractional CO2 laser that
has been in use at Massachusetts
General Hospital since 2011 has
shown great promise as a therapy that
improves appearance of burn scars
and can help address other symptoms.
Burn surgeons at Mass General’s
Sumner M. Redstone Burn Center, led
by plastic surgeon Jeremy Goverman,
MD, FACS, and colleagues, undertook a
study to evaluate the effects of ablative
CO2 fractional photothermolysis on
burn scars. The results, which have yet
to be published, showed significant
improvements in patient symptoms,
enhanced cosmetic appearance of the
burn scars and a high level of posttreatment patient satisfaction.
MECHANISMS OF ACTION
IN LASER TREATMENT OF
HYPERTROPHIC SCARS
The fractional CO2 laser used by
Mass General burn surgeons creates
small holes in the scar tissue using
a finely focused beam of light. This
technique, which can penetrate to the
base of the scar, selectively ablates
only thin columns of tissue, called
microthermal zones, limiting damage to
the surrounding tissue.
There are several mechanisms through
which CO2 fractional photothermolysis is
hypothesized to act. First, the laser creates
organized columns of microthermal
injury, which break down the collagen in
those columns, stimulating the process
of collagen remodeling and promoting
the formation of more elastic tissue. The
microscopic holes could also release
dermal tension, which is responsible
for the tightness and raised nature of
hypertrophic scars. Finally, the small
columns surrounded (continued on page 4)
Superficial and Deep Fractional Resurfacing
Two laser handpieces are used for treatment: the superficial fractional handpiece and the deep Fx handpiece. The superficial handpiece helps
to smooth surface abnormalities by ablating a thin layer of skin (left). The deep Fx handpiece is used to perform fractional photothermolysis
(FP) by creating columns of thermal damage (referred to as microthermal zones) in the epidermis and dermis surrounded by islands of
normal tissue (right). The tissue injury created with FP stimulates the process of collagen remodeling and deposition and promotes elastic
tissue formation.
SUPERFICIAL ABLATIVE
FRACTIONAL RESURFACING
DEEP ABLATIVE
FRACTIONAL RESURFACING
(CO2 & 2.94 Erb:YAG) 10-70 microns
600-1000 microns
Source: Jeremy Goverman, MD
3
massgeneral.org/advances
Before vs. After Fractional Photothermolysis
An image of Dr. Goverman’s patient before and after treatment with CO2 fractional photothermolysis. Nearly all patients in the
study reported overall satisfaction with the result, showing a 50% reduction in pain, tightness and pruritus.
A
B
Source: Jeremy Goverman, MD
by normal tissue
might create microscopic healing
zones, where the heat from the ablation
induces a metabolic cascade that
recruits stem cells from the bloodstream
to aid in repair at the scar site.
(continued from page 3)
ASSESSING EFFICACY OF LASER
TREATMENT
Although preliminary data seen with
ablative fractional CO2 laser treatment
of hypertrophic burn scars2 has been
positive, there is a need for more
robust evidence to validate its use.
Dr. Goverman and his team sought to
quantify and assess patient-reported
outcomes among those treated with
fractional CO2 laser at Mass General’s
Sumner M. Redstone Burn Center.
Assessing the effects of a treatment on
burn scars can present methodological
challenges, as it requires objective
measurements of changes on scar
tissue, which is highly heterogeneous.
The research team instead measured
success in patient-reported outcomes.
The results showed that 96.7% of
the 387 patients reported overall
satisfaction with laser therapy, citing
a 50% reduction in neuropathic pain,
tightness/contracture and pruritus.
4
Advances at Mass General | Spring 2015
FURTHER RESEARCH ON
FRACTIONAL CO2 LASER
TREATMENT
Given the promising results of their
initial analysis, Dr. Goverman and his
colleagues are now pursuing studies
that aim to elucidate the treatment’s
underlying mechanisms of action.
One chief area of investigation will be
the changes in gene expression that
result from laser treatment, which can
be observed in samples of scar tissue
removed for other purposes that are
subsequently laser treated. The scar
tissue data will then be compared with
existing research showing the laser’s
effects on gene expression in normal
skin to determine any differences.
The team is also developing a study
to quantify the specific parameters of
1 Hultman, C Scott, Jonathan S Friedstat, Renee
E Edkins, Bruce A Cairns, and Anthony A
Meyer. “Laser Resurfacing and Remodeling of
Hypertrophic Burn Scars: The Results of a Large,
Prospective, Before-After Cohort Study, With LongTerm Follow-up.” Annals of Surgery, vol. 260, no. 3
(September 2014): 519-29.
2
nderson, R Rox, Matthias B Donelan, Chad Hivnor,
A
Eric Greeson, E. Victor Ross, Peter R Shumaker, et
al. “Laser Treatment of Traumatic Scars With an
Emphasis on Ablative Fractional Laser Resurfacing:
Consensus Report.” JAMA Dermatology, vol. 150, no.
2 (February 2014): 187-93.
treatment for the fractional CO2 laser
that confer the most beneficial effect—
what doses of laser and treatment
settings produce the best outcomes,
what pattern of hole spacing and
depth is most efficacious, how long
after injury should the lasering be
performed and what is the best time
interval between laser treatments.
Another potential application of the
fractional CO2 laser is for more effective
drug delivery into the scarred tissue. It
is already common practice for topical
steroids to accompany treatment, with
the laser facilitating deeper delivery
via holes in the tissue. But it is also
possible for other medications or stem
cells to be delivered to the site with the
laser. Future studies are still needed
to ascertain which medications may
improve the healing process. ■
Contributor
Jeremy Goverman, MD, FACS
Division of Burns
Massachusetts General Hospital
Assistant Professor of Surgery
Harvard Medical School
[email protected]
Developments in Total
Ankle Replacement
F
or impediments in ankle
function, arthrodesis has long
been favored over arthroplasty.
Restoring full function through
prosthetic replacement has historically
been complicated by the difficulty
in dislocating the ankle for surgical
intervention as well as the many
joints and complex biomechanics that
characterize the region. Fusion has seen
much wider practice, with its union rate
of roughly 90%, after which significant
pain relief is generally reported.
Arthrodesis of the ankle, however, can
disturb the gait pattern and lead to stress
of nearby joints.1 Tertiary care orthopedic
foot and ankle specialists are pursuing
innovations in total ankle arthroplasty
(TAA) that are likely to promote its wider
adoption. Christopher DiGiovanni, MD,
chief of the Foot and Ankle Service and
director of the Foot and Ankle Fellowship
Program at Massachusetts General
Hospital, has been at the forefront of the
study, design and implementation of a
new generation of ankle replacement
devices and protocols. While ankle
replacement has not compared favorably
to innovations in other load bearing and
major joints, which enjoy a survivorship
of 90% to 95% over 15 to 20 years, recent
studies indicate that ankle replacements
under more recent guidelines show a
postoperative survivorship of 80% to 95%
over 5 to 10 years.
ITERATIVE IMPROVEMENTS IN
PROSTHETIC DESIGN
First- and second-generation ankle
prosthetic designs presented constraint
issues and limited function, causing them
to be either too restrictive or too unstable,
leading to implant loosening, dislocation,
chronic pain and occasional catastrophic
failure. Many also required removal of a
significant amount of bone in the distal
tibia and talus before implant insertion,
which often caused premature collapse
in soft bone, progressive bone loss and
difficult revision situations.
Third- and fourth-generation
models have corrected many of
these shortcomings, benefiting from
recent advances in implant technique
and design as well as a far improved
understanding of ankle biomechanics
and the impact that concomitant
ipsilateral foot pathology can have
on ankle implant longevity. The
results, says Dr. DiGiovanni, are more
reproducible gait cycle, better implant
function, greater postsurgical activity
and, most important, fewer significant
complications or need for revision
surgery.
Among these models is one designed
and patented by Dr. DiGiovanni, the first
FDA-approved third-generation design to
enable insertion through either a medial
or lateral approach, a strategy that has
proved influential with later designs. New
models are now typically put in as pressfit designs and have greater geometrical
biocompatibility. They come with a
greater degree of freedom that prevents
undue stress transfer without being
unstable, require less bony resection for
insertion so that revision is easier, and
offer options for significant modularity
to provide for a better fit. Many are
coated with tiny beads that allow for
the surrounding bone to grow into the
prosthesis, forming a lasting bond that
allows for bony remodeling over time.
instrumentation for making the bony cuts
and ensuring anatomic alignment during
surgery is critical, says Dr. DiGiovanni, as
these implants are smaller than those of
hip, knee and shoulder replacement, yet
by virtue of location must do more work.
Slight inaccuracies in this area can have
large consequences on implant durability,
such as subtle foot malalignment,
instability or stiffness.2 (continued on page 6)
Ankle Replacement
Imaging
This X-ray shows a total ankle replacement in
the process of insertion. The prosthetic joint
here is the Eclipse, designed by Christopher
DiGiovanni, MD. The image also captures
instrumentation for insertion, including a
cutting jig designed to remove arthritic bone
from either the medial or lateral side in
preparation for implant insertion.
This X-ray shows a patient with bilateral
ankle arthritis, with subsequent surgeries. On
the left is an arthrodesis of the ankle, fusing
it in place. On the right, the patient has an
implanted ankle prosthetic, which allows for
near-normal movement.
INSTRUMENTATION,
PATIENT EXPECTATIONS
AND FURTHER STUDY
The instrumentation used during the
surgery is another area upon which
Dr. DiGiovanni and other surgeons
have worked to improve. Precise
Source: Christopher DiGiovanni, MD
5
massgeneral.org/advances
2
3
itterman, Scott A, Todd A Fellars, and
R
Christopher W DiGiovanni. “Current Thoughts
on Ankle Arthritis.” Rhode Island Medical Journal,
vol. 96, no. 3 (2013): 30-33.
S
leep disturbances and circadian
rhythm dysfunction are
common features of Parkinson’s,
Alzheimer’s and Huntington’s
diseases. These symptoms adversely
affect quality of life. Yet the
mechanisms of sleep and circadian
disruption in neurodegenerative
diseases are not well understood.
Aleksandar Videnovic, MD, a
neurologist at Massachusetts
General Hospital and director of the
new Program in Sleep, Circadian
Biology and Neurodegeneration, is
investigating the pathophysiology of
Parkinson’s patients demonstrate significantly reduced serum melatonin secretion as
compared with controls (A), with conspicuously lower amplitude of melatonin rhythmicity
in PD patients expressing excessive daytime sleepiness (EDS), (B). Circadian time is
measured as time since awakening.
200
Contributor
Christopher DiGiovanni, MD
Chief, Foot and Ankle Center
Massachusetts General Hospital
[email protected]
6
Advances at Mass General | Spring 2015
A
PD patients
Controls
reisberg, Justin, Sigyard T Hansen Jr, and
G
Christopher W DiGiovanni. “Alignment and
Technique in Total Ankle Arthroplasty.” Operative
Techniques in Orthopaedics, vol. 14, no. 1 (2004):
21-30.
acaulay, Alec A, Scott M VanValkenburg, and
M
Christopher W DiGiovanni. “Sport and Activity
Restrictions Following Total Ankle Replacement: A
Survey of Orthopaedic Foot and Ankle Specialists.”
Foot and Ankle Surgery, accepted February 2015.
such sleep-wake disturbances.
Patients with Parkinson’s disease
(PD) in particular exhibit diurnal
fluctuations of motor and nonmotor
symptoms, in conjunction with sleep
dysfunction, which suggests a role of
the circadian system in the modulation
of these symptoms. Impaired circadian
function in PD is suspected to underlie
not only the dysregulation of the sleepwake cycle but also autonomic, cognitive, psychiatric and motor symptoms
of the disease. Investigations into the
mechanisms of circadian dysfunction
may help researchers understand the
Melatonin and Parkinson’s Disease
150
100
50
0
3
6
9
12
15
Circadian Time, h
18
21
24
70
30
B
PD patients without EDS
60
Melatonin Level pg/mL
1
Circadian Dysfunction in
Parkinson’s Disease
Melatonin Level pg/mL
Given the growing
patient demand for TAA, clinicianscientists now appreciate a parallel
need for setting proper functional
expectations presurgery. Dr. DiGiovanni
and the team at Mass General recently
conducted a cross-sectional survey
of fellowship-trained orthopedic foot
and ankle specialists across the United
States, published in Foot and Ankle
Surgery in January 2015, which was
designed to analyze the athletic and
routine activity of daily living restrictions
physicians place on patients following
ankle replacement surgery.3 Physicians
rated approximately 50 sport and
other activity choices, from which the
researchers derived a set of consensus
recommendations that include guidance
on low-impact aerobic exercises, sports
and other activities for these patients.
The rapid development of TAA also
calls for the study of long-term effects.
In conjunction with the Biomechanics
Laboratory at Mass General, Dr.
DiGiovanni is currently applying for
several biomechanics grants to study
the kinematic effects of ankle arthritis
and TAA on surrounding joint function
and, more important, the effects that foot
malalignments—such as flatfoot or higharch deformity—instability and stiffness
might have on TAA kinematics. ■
(continued from page 5)
PD patients with EDS
50
40
30
20
10
0
3
6
Source: Aleksandar Videnovic, MD
9
12
15
Circadian Time, h
18
21
24
30
Circadian Dysfunction and Parkinson’s Disease
The circadian system is managed by a collection of brain cells known as the suprachiasmatic nucleus, which is influenced by exogenic
factors such as light, food and physical activity. Many characteristic symptoms of Parkinson’s manifest as defects in the circadian
system. Patients are often sleepy during the daytime, and characteristic motor symptoms fluctuate throughout the day.
Heightened cortisol
secretion during the day
LIGHT
PARKINSON’S
DISEASE
MEALS
Melatonin secretion
is blunted
Motor symptoms
fluctuate during the
24-hour period
SUPRACHIASMATIC
NUCLEUS
Reversal of circadian heart
rate and blood pressure
during day and night
EXERCISE
Sleep/wake cycles
are disrupted
Source: Aleksandar Videnovic, MD
progress of neurodegeneration in PD
and possibly uncover novel approaches
to treatment.
DISRUPTION OF
CIRCADIAN RHYTHMS IN
PARKINSON’S DISEASE
In a study published in JAMA
Neurology1 in April 2014, funded by
a National Institute of Neurological
Disorders and Stroke Mentored
Patient-Oriented Research Career
Development Award (K23 NS072283),
Dr. Videnovic and his colleagues
studied the alteration of circadian
system in Parkinson’s disease.2 Serum
melatonin secretion over a 24-hour
period provides a reliable marker of
endogenous circadian rhythmicity,
so Dr. Videnovic and his colleagues
monitored serum melatonin levels
at 30-minute intervals in patients
with Parkinson’s disease, taking 50
samples from each subject. Melatonin
secretion proved to be severely
blunted in patients with Parkinson’s
disease compared with controls, with
Parkinson’s patients who expressed
excessive daytime sleepiness showing
a markedly lower amplitude of
melatonin rhythm. These findings
were consistent with an assumption
that circadian regulation is associated
with PD and raise intriguing questions
about the mechanisms underlying the
blunted rhythm.
Dr. Videnovic’s work doesn’t show
whether this impairment of circadian
rhythmicity is a cause or consequence
of Parkinson’s disease, but his team will
investigate causation in future research.
Instead, research is now focusing on
what happens to the function of the
circadian system as the disease progresses. Upcoming investigations will
test interventions, such as bright light
therapy and timed applications of melatonin, that target circadian function,
attempting to improve the sleep-wake
cycle disturbances and explore whether
such interventions have any effect on the
underlying neurological disease process.
REM SLEEP BEHAVIOR DISORDER
(RBD): AN EARLY INDICATOR
OF NEURODEGENERATION
REM sleep behavior disorder (RBD)
is a sleep disorder, increasingly linked
to an ongoing synuclein-related
neurodegeneration. Symptoms of RBD
include abnormal vocalizations and
movement behaviors during sleep.
RBD is thought to be a prodromal
stage of PD, preceding the expression
of cardinal motor symptoms. Patients
with PD can also exhibit freezing of gait
(FOG), a symptom that emerges from
neuroanatomical changes in the brain
stem that include the pedunculopontine
nucleus and locus coeruleus. These same
anatomical regions have been implicated
in RBD.
Dr. Videnovic and his colleagues
looked at another aspect of this
connection in a study funded by the
Michael J. Fox Foundation for Parkinson’s
Research. The study, published in
Neurology3 in September 2013, looked
at several groups
(continued on page 8)
7
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of patients: one
group with PD and FOG, a group with
PD that did not have FOG, and another
group with RBD and no diagnosis of PD
(as well as matched controls). The team
saw a marked difference in tonic muscle
activity during REM sleep between the
PD patients with and without FOG.
Patients with PD and FOG and the group
with RBD, however, had similar tonic
muscle activity patterns during REM
sleep. These latter groups also showed
similar amounts of tonic EMG activity
during REM sleep.
Dr. Videnovic and his team raise the
possibility that the commonalities in
sleep dysfunction between the RBD
(continued from page 7)
1
idenovic, Aleksandar, Charleston Noble, Kathryn
V
J Reid, Jie Peng, Fred W Turek, Angelica Marconi,
Alfred W Rademaker, et al. “Circadian Melatonin
Rhythm and Excessive Daytime Sleepiness in
Parkinson’s Disease.” JAMA Neurology, vol. 71, no.
4 (April 2014): 463-9.
2
idenovic, Aleksandar, Alpar S Lazar, Roger A
V
Barker and Sebastiaan Overeem. “The Clocks That
Time Us: Circadian Rhythms in Neurodegenerative
Disorders.” Nature Reviews Neurology, vol. 10,
no. 12 (December 2014): 683-693.
3
idenovic, Aleksandar, Clare Marlin, Laila
V
Alibiglou, Peggy J Planetta, David E Vaillancourt,
and Colum D MacKinnon. “Increased REM Sleep
Without Atonia in Parkinson Disease Patients
With Freezing of Gait.” Neurology, vol. 81, no. 12
(September 2013): 1030-5.
and PD with FOG groups might reflect
an overlap in the circuits that control
muscle activity during REM sleep and
FOG. Their data led them to hypothesize
that the presence of excessive tonic EMG
activity during REM sleep may predict
development of PD with FOG, and that
the pathophysiologic mechanisms that
mediate FOG in PD share a common
set of neurodegenerative changes that
underlie the tonic muscle activity during
REM sleep that is found in RBD.
While this is an initial, cross-sectional
study, Dr. Videnovic and his colleagues at
the Program in Sleep, Circadian Biology
and Neurodegeneration hope to recruit
more patients with RBD for a longitudinal
study that will look more closely at the
connections between RBD and FOG,
in the hope of identifying additional
markers in sleep patterns and via brain
imaging that predict the development of
FOG in Parkinson’s disease. ■
Contributor
Aleksandar Videnovic, MD
Neurologist
Director, Program on Sleep, Circadian
Biology and Neurodegeneration
Massachusetts General Hospital
[email protected]
Massachusetts General Hospital
101 Merrimac Street, Suite 200
Boston, MA 02114
massgeneral.org/advances
[email protected]
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