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NeurosciencesUpdate
Neurologic Surgery and Clinical Neurology News
INSIDE THIS ISSUE
Surgery and ICU:
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Sports-Related Concussion:
Managing Long-Term Effects
Although repeated concussive head trauma is a
purported risk factor for later neurodegenerative
disease, the problem is far from fully elucidated.
“Some, but certainly not all, people with repeated
concussion develop neurodegenerative problems
later in life. But does the risk increase a little bit or
Autoimmune
a lot?”says Bradley F. Boeve, M.D., a consultant in
Dementia: Defining
Neurology at Mayo Clinic in Rochester, Minnesota.
a Treatable Disorder
At the severe end of the spectrum of possible
effects is chronic traumatic encephalopathy (CTE),
experienced by a minority of athletes (Figure 1).
DBS for OCD and
Other athletes might have long-term cognitive or
Tourette Syndrome
neuropsychological problems (Figure 2), but the
timing and mechanism of symptom onset and
specific risk factors that might predispose individuals with sports-related concussion (SRC) to
develop neurodegenerative disease aren’t clear.
Mayo Clinic devotes considerable clinical and
research expertise across multiple specialties to
athletes with concussive injuries, from peewee to
professional leagues. The goal is to
relieve patient symptoms, uncover
risk factors for long-term effects
of SRC and make evidence-based
recommendations for increasing the
safety of sports.
“We have an integrated system
of expertise, with a common will
and drive to improve the care of
people with concussive injuries and
their ability to function later in their
lives,”says Rodolfo Savica, M.D.,
Ph.D., a consultant in Neurology at
Mayo Clinic’s campus in Minnesota.
Figure 1. Photomicrograph of tau-immunoreactive
Patients have comprehensive
lesions (stained brown) in a former professional
U.S. football player. Image provided by Dennis W. Dickson,
evaluations from consultants
M.D., and Kevin F. Bieniek, Mayo Clinic.
in behavioral neurology, brain
Collaborating for
the Best Outcomes
Vol. 12, No. 4, 2015
rehabilitation and neuropsychology, headache
neurology, and sports medicine.“Even if we find
no definitive evidence of neurodegenerative disease, our role as clinicians is to treat the patient’s
symptoms,”says Allen W. Brown, M.D., division
chair of Brain Rehabilitation at Mayo Clinic’s
campus in Minnesota.“It’s very common for us
to see individuals who have had sports-related
concussive injuries and are experiencing many
symptoms unrelated to brain dysfunction.”
Large population at risk
It’s generally accepted that among people who
experience symptoms from concussion, approximately 70 to 80 percent are no longer experiencing them two weeks later.“But that leaves 1 in
5 people who don’t recover within seven to 10
days. That’s a huge population at risk,”says David
W. Dodick, M.D., a consultant in Neurology at
Mayo Clinic in Phoenix/Scottsdale, Arizona.“The
accepted number of sports-related concussions
is on the order of 3.5 million to 4 million in the
United States each year. I would say it’s at least
double that.”
Concussion is significantly underreported
because it can be asymptomatic, and recovery
is tricky to pinpoint.“When we say ‘recover,’ we
mean the athlete is no longer reporting symptoms and the neurological evaluation is normal,”
Dr. Dodick says.“However, residual symptoms
may be quite vague — a little irritability or
trouble sleeping — and may not be attributed to
the concussion. Moreover, an athlete can truly
have no symptoms, but the brain might actually
not have recovered yet.
“Sometimes athletes are reluctant to report,”
Dr. Dodick adds.“One professional athlete told
Bradley F. Boeve, M.D.
Rodolfo Savica, M.D., Ph.D.
me, ‘Concussion is a four-letter word in the locker
room.’ Athletes know that if they report symptoms, they will be taken out of the game, see a lot
of doctors and undergo tests, and they might lose
their positions on the team. Previous concussions may also affect the way they are viewed by
future teams. That’s true if you’re a 12-year-old
Pop Warner football player. It’s even more true if
you’re a professional athlete.”
To discern specific risk factors for long-term
effects, Mayo Clinic researchers are conducting a
longitudinal study of people with traumatic brain
injury (TBI) who later developed Alzheimer’s
disease or related conditions. The study cohort is
drawn from the Rochester Epidemiology Project,
a collection of medical data covering virtually all
residents of Olmsted County, Minnesota.
“We hypothesize that we will find no association between TBI and neurodegenerative disease
overall,” Dr. Brown says.“But we predict we are
likely to find an increased risk of developing
Alzheimer’s disease and related conditions after
TBI in subsets of the cohort with clinical features
that have been suspected of increasing this risk,
such as multiple injuries or injuries of increased
severity. If so, we hope to determine the factors
that isolate that group.”
Allen W. Brown, M.D.
David W. Dodick, M.D.
Figure 2. On the top, PET scan using
fluorodeoxyglucose (FDG) appears normal.
Below, FDG-PET scan after a long-standing
traumatic injury in the left frontal lobe,
visible in the MRI on the right.
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MAYO CLINIC | NeurosciencesUpdate
“We have many questions that need answers,”
Dr. Savica adds.“Is a concussion in a car accident
the same as one when playing a sport? Are some
sports less likely to have long-term consequences? Is some direction or vector of trauma
better than others?”
Mayo Clinic’s work with SRC is enhanced
by the center’s broad expertise in neurodegenerative disorders. Dr. Boeve notes that tau, the
primary abnormal protein in CTE, is a target of
emerging therapies for Alzheimer’s disease and
other tauopathies.
“There are tau-active drugs that are starting
clinical trials. If they prove to be safe and effective
for Alzheimer’s or related conditions, they might
be applicable to CTE,”he says.“Athletes can benefit from Mayo Clinic’s expertise in Alzheimer’s
disease and related neurodegenerative diseases,
imaging, and brain injury rehabilitation.”
Evidence to make sports safer
To further safeguard athletes’ health, Mayo Clinic
is at the forefront of efforts to promote change in
contact sports.“To truly prevent concussion, you
must understand the mechanisms of injury and
then come up with strategies that are not only
effective but pragmatic,”says Michael J. Stuart,
M.D., co-director of the Sports
Medicine Program at the Rochester campus of Mayo Clinic and
chief medical and safety officer
for USA Hockey.“Evidence-based
decision-making is critical. We’re
trying to make sports safer.”
In an evidence-based action
plan published in the March 2015
issue of Clinical Journal of Sport
Medicine, Mayo Clinic researchers and colleagues called for the
elimination of head hits and
fighting from all levels of professional and amateur ice hockey and
changes in body-checking policies.
“Concussion prevention is
multifaceted, involving behavior
modification, education, enforcing existing rules and modifying
rules,”Dr. Stuart says.
Equipment design is necessary but not sufficient. Dr. Stuart
notes that in contrast to football
helmets,“hockey helmets have
a very poor suspension system,
often with a very loose strap
that doesn’t engage the chin.
Therefore, the helmet moves
around on the head and often
comes off. We’re very interested in
improving the design and materials of the hockey
helmet.”
However, a better helmet can’t prevent all
concussions in ice hockey or football.“When an
athlete has a blow to the body, force is transmitted through the body to the head. The combined
linear and rotational acceleration and deceleration to the brain can cause concussion without
a direct blow to the head,” Dr. Stuart says.“In ice
hockey, we are addressing that with various strategies — body control and awareness, open-ice
awareness, sportsmanship and mutual respect.”
“We’re slowly starting to understand what’s
actually happening inside the brain — the cascade of molecular, chemical and electrical events
that can lead to progressive damage,”Dr. Dodick
adds.“But this field is really in its infancy in terms
of understanding the biology of concussion and
how to manage it, how to identify those at risk
for long-term consequences, and how to mitigate
or prevent the long-term effects.”
For more information
Smith AM, et al. Ice hockey summit II: Zero tolerance for head hits and fighting. Clinical Journal of
Sport Medicine. 2015;25:78.
Michael J. Stuart, M.D.
Surgery and ICU: Collaborating for the Best Outcomes
As a fully integrated practice, Mayo Clinic has
the breadth of expertise to offer the best possible
neurological care to critically ill patients. Collaboration between neurological surgeons and
neurointensivists helps provide excellent functional outcome even for patients with aneurysmal
subarachnoid hemorrhage (aSAH), historically
considered a devastating disease.
A study published in the February 2015 issue
of the Journal of Neurosurgery found that 63.3
percent of patients treated for aSAH at Mayo
Clinic’s Minnesota campus from 2001 to 2013
had excellent functional outcome — defined as
modified Rankin Scale score of 0 or 1 (no symptoms or mild symptoms, but no disability) at last
follow-up visit within one year of aSAH. The
retrospective review of 373 patients included the
severe cases referred by tertiary centers to Mayo
Clinic’s neurointensive care unit (neuro-ICU).
“We believe that our outcomes are a reflection of our multidisciplinary approach and a lack
of turf battles in our group practice,” says Alejandro A. Rabinstein, M.D., a consultant in Neurology at Mayo Clinic in Rochester, Minnesota.“Our
neurointensivists and surgeons
have a very close relationship
A
throughout a patient’s acute
course and follow-up treatment.”
Continuity of care
“The degree of expertise that a
single patient receives is unparalleled,”adds Giuseppe Lanzino,
M.D., a consultant in Neurosurgery at the Rochester campus of
Mayo Clinic.“Each one of us brings
to the table particular expertise,
and by working closely together
we ensure continuity of care.”
When a patient with aSAH is
referred to Mayo Clinic, the neuro-
intensivist and neurosurgery groups communicate
while the patient is en route.“A physician from
both groups goes to meet the patient as soon as
the patient arrives at our ICU,”Dr. Rabinstein says.
“We work together because those first few hours are
essential to the outcome of the patient.”
The neurointensivists focus on aspects of care
such as ventilation, oxygenation, stabilization of
blood pressure and treatment of brain swelling,
while the surgeons treat hydrocephalus.“There
is a multidisciplinary conversation about the best
treatment for the patient,”Dr. Rabinstein says.
“For example, if there is a question of sacrificing a certain blood vessel during treatment, the
surgeon might ask the neurointensivists if they
think the patient will tolerate that.”
At Mayo Clinic, neurological surgeons have
experience in both endovascular and surgical treatment of aneurysm (Figure).“Once the
patient is sufficiently stable, we transfer the
patient to our angiography suite and, if possible,
treat the aneurysm there,”Dr. Lanzino says.“But
if the aneurysm is not amenable to endovascular
treatment, then we fix it with surgery and a clip.”
B
C
Alejandro A. Rabinstein, M.D.
Giuseppe Lanzino, M.D.
D
Figure. A. CT scan of a patient with severe aneurysmal subarachnoid hemorrhage before
treatment. Hemorrhage, brain swelling and hydrocephalus are visible. The patient was in a
coma when she arrived. B. Arrow indicates the clip used to treat a ruptured superior cerebellar artery aneurysm. C. Ventricular drain used to treat the symptomatic hydrocephalus. D. CT
scan at the time of the patient’s discharge from Mayo Clinic Hospital, Saint Marys Campus.
At six weeks, the patient had returned to her previous function without any limitation.
MAYO CLINIC | NeurosciencesUpdate
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After treatment for aSAH, patients generally
spend at least 10 to 14 days in the neuro-ICU. At
Mayo Clinic, patients in the neuro-ICU aren’t routinely kept sedated and intubated for the duration
of acute treatment.“We try to wake up the patient as
soon as we can,”Dr. Rabinstein says.“Induced coma
generally doesn’t prevent secondary complications
such as brain swelling. Whenever possible, we want
to assess the patient through physical examination
rather than relying on brain-monitoring devices,
which are commonly invasive.”
The most notable complication experienced by
these patients is vasospasm, which puts them at risk
of stroke.“We deal with vasospasm not only with
medical treatment — typically, raising the blood
pressure while maintaining adequate fluid balance
— but also by pursuing endovascular therapy if
medical treatment fails,”Dr. Rabinstein says.
After a patient returns home, surgical and
neurointensivist groups continue to follow up.
Appointments with both groups are typically
scheduled at four to six weeks and at six months
after treatment.
“It’s important for patients to go to centers
that have expertise and all the services that they
need,”Dr. Rabinstein says.“We think we can
benefit even patients who are severely ill. When
I was in medical school, a case of subarachnoid
hemorrhage was a spectacular success if the
patient was able to walk and talk after treatment.
Now, although outcomes for aSAH have generally improved, there is still an acceptance that
some deficits are unavoidable. At Mayo Clinic,
our definition of success is essentially a patient
who is back to baseline at six weeks.”
For more information
Pegoli M, et al. Predictors of excellent functional
outcome in aneurysmal subarachnoid hemorrhage. Journal of Neurosurgery. 2015;122:414.
Autoimmune Dementia: Defining a Treatable Disorder
Eoin P. Flanagan, M.B., B.Ch.
Sean J. Pittock, M.D.
Daniel A. Drubach, M.D.
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Encephalopathies — typically characterized by
confusion, seizures, memory loss and behavioral
changes — have been well-recognized as having
an autoimmune cause. In contrast, patients with
progressive dementia without delirium have usually
been classified as having neurodegenerative disease.
Building on the pioneering work of Vanda
A. Lennon, M.D., Ph.D., a consultant in the
Mayo Clinic Neuroimmunology Research
Laboratory, neurologists at Mayo Clinic in
Rochester, Minnesota, have found that patients
whose symptoms mimic those of neurodegenerative dementias can actually have an autoimmune cause for their conditions. Although
autoimmune dementia responds to immunotherapy, the disease often goes untreated
because of misdiagnosis as a neurodegenerative or psychiatric condition.
“It can be devastating for patients to be labeled
with a neurodegenerative disease but actually
have an immune-mediated dementia, because
they’re missing out on a treatment that can
reverse their symptoms,” says Eoin P. Flanagan,
M.B., B.Ch., a consultant in Neurology at Mayo
Clinic in Rochester, Minnesota. “If treatment is
delayed, patients tend not to respond as well. It’s
important to recognize this condition because you
might miss your opportunity for treatment.”
A nose for atypical disease
Among patients at Mayo Clinic who responded
to immunotherapy for autoimmune dementia
from 2002 to 2009, 35 percent were initially
misdiagnosed with a neurodegenerative dis-
MAYO CLINIC | NeurosciencesUpdate
order. Mayo Clinic neurologists have also used
immunotherapy to successfully treat patients
who experienced a rapidly progressing dementia
and were initially diagnosed with CreutzfeldtJakob disease.
Patients with autoimmune dementia typically
present with some, but certainly not all, clinical
and laboratory features associated with limbic
encephalitis. Clinical and laboratory features of
autoimmune dementia include:
• Subacute onset
• Fluctuating course
• Tremor
• Headache
• Personal or family (first-degree relative)
history of autoimmunity
Figure 1. On the left, MRI shows abnormal T2 hyperintensity in the left mesial temporal lobe in a patient
with autoimmune dementia due to antibodies
to the leucine-rich, glioma-inactivated 1 (LGI1)
protein, a component of the voltage-gated potassium
channel complex. On the right, MRI shows abnormal
T1 hyperintensity within the basal ganglia in a patient
with autoimmune dementia and accompanying faciobrachial dystonic seizures due to LGI1 autoantibodies.
History of recent or past neoplasia
Evidence of central nervous system inflammation from cerebral spinal fluid or MRI
• Detection of neural antibody
MRI might show abnormalities in the limbic
lobes or elsewhere (Figure 1); PET imaging might
show hypometabolism (Figure 2). Cognitive
decline, particularly memory loss, is the predominant symptom. But patients can also have
hallucinations and a fluctuating course of disease.
“It’s important to look for atypical disease,” says
Daniel A. Drubach, M.D., a consultant in Neurology at Mayo Clinic’s campus in Minnesota. “For
example, when a patient is diagnosed at 45 years of
age with schizophrenia, that raises a red flag. I have
seen many patients with an autoimmune-based
dementia who were in psychiatric hospitals.”
“It comes down to the clinician having a good
nose for this diagnosis,” adds Sean J. Pittock,
M.D., a consultant in Neurology and director of
the Center for Multiple Sclerosis and Autoimmune
Neurology at Mayo Clinic’s campus in Minnesota.
“You look for the clues that tell you this isn’t just
run-of-the-mill neurodegenerative disease.”
Mayo Clinic has developed a standardized
approach to diagnostic evaluation of suspected autoimmune neurological disorders, based on three M’s:
• Maximum reversibility — also called the
“diagnostic test” — determined by comparison of objective baseline testing of main
deficits compared with post-immunotherapy
testing
• Maintenance of reversibility, using long-term
immunotherapy in chronic autoimmune
diseases
• Minimal therapeutic dosage to reduce the side
effect profile
To assist with diagnosis, Mayo Clinic is the
first center in the U.S. to offer biomarker testing
for autoimmune dementia. Serum and cerebral
spinal fluid are evaluated for neural antibodies associated with the condition. Consultative comments from Mayo Clinic neurologists
accompany test findings.
“The panel results must be interpreted in the
clinical context because there are patients with
Alzheimer’s disease who have low titers of some
of these antibodies,” Dr. Pittock says. Mayo Clinic
consultants are also available to discuss test results
over the telephone with referring neurologists.
•
•
Treatment and response
Acute treatment for autoimmune dementia
generally involves intravenous steroids once
a day for five days. “If patients improve, and
do indeed have an autoimmune dementia, it
usually occurs within the first week of treatment. A smaller minority will start to improve
Figure 2. Top image, PET scan of a 68-year-old woman with a history
of lupus and a 10-year history of cognitive difficulties. The scan shows
prominent hypometabolism with a pattern suggestive of Alzheimer’s
disease. Bottom image, PET scan of the patient after treatment with
immunosuppressants. Normalization of the scan was associated with
dramatic improvement in cognitive abilities.
within the first month,” Dr. Flanagan says. For
more-sustained improvement, patients
sometimes have immunotherapy once a
week for six to 12 weeks.
To measure cognitive change, patients
are given the Kokmen Short Test of
Mental Status or more-detailed neuropsychological testing at the beginning
and end of treatment. MRI and spinal
fluid testing are also often done before
and after treatment.
“Patients may not go back to normal,”
Dr. Drubach says. “But they may do better than those without treatment.”
At Mayo Clinic, patients benefit from
the close interaction between physicianresearchers with expertise in autoimmunity and in behavioral neurology.
Dr. Flanagan has training in both. “It’s
generally thought that dementias are
always neurodegenerative,” he says.
“But we’re at only the tip of the iceberg
in terms of discovering neural antibodies. It’s important to look out for these
atypical dementia cases because they can
respond very well to immunotherapy.”
Autoimmune
Dementia Evaluation
A comprehensive autoimmune dementia evaluation
for serum and cerebral
spinal fluid is available from
Mayo Medical Laboratories.
The evaluation provides
neurologists with neural
antibody testing for patients
with symptoms of autoimmune dementia. Mayo Clinic
neurologists provide interpretation of test results and
are available for consultation
with referring physicians.
Testing must be ordered by a
hospital laboratory.
MAYO CLINIC | NeurosciencesUpdate
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DBS for OCD and Tourette Syndrome
Kendall H. Lee, M.D., Ph.D.
Mark A. Frye, M.D.
Figure. Functional MRI
reveals areas of cortical
activation that result
from DBS for OCD (top)
and Tourette syndrome
(bottom).
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Deep brain stimulation (DBS) has been used at
Mayo Clinic to successfully treat hundreds of
patients with essential tremor, Parkinson’s disease and dystonia. Mayo Clinic neurosurgeons
are now offering DBS as a treatment option for
patients with refractory obsessive-compulsive
disorder (OCD) and Tourette syndrome. DBS
for OCD is provided through a humanitarian
device exemption granted by the Food and Drug
Administration; DBS for Tourette is available in
limited cases for clinical care.
Although the number of patients treated
so far is fairly small,“we are seeing that DBS
can be highly effective for OCD and Tourette,”
says Kendall H. Lee, M.D., Ph.D., a consultant
in Neurosurgery at Mayo Clinic in Rochester,
Minnesota.
“From a psychiatric perspective, refractory
OCD is one of the most disabling diseases in
psychiatry,”notes Mark A. Frye, M.D., chair of
Psychiatry and Psychology at Mayo Clinic’s
campus in Minnesota.“For the right patient, this
intervention can be life-restoring and life-saving.”
Refractory, severe conditions
Patients who have DBS treatment for OCD at
Mayo Clinic typically haven’t responded to two
or three types of conventional pharmacotherapy,
augmentation strategies and structured cognitive behavioral therapy (CBT).“We do a careful
assessment to make sure that the evidence base
for how we treat OCD has been utilized, because
we don’t want to use DBS if conventional treatments haven’t been tried,” Dr. Frye says.
The conditions of patients who haven’t
responded to conventional treatment can be disabling. Dr. Frye cites a young man with OCD and
a history of 10 psychiatric hospitalizations, and
secondary complicating features of depression.
“He was plagued by recurring thoughts of sanitation and disorderliness, and compulsive behavior
where he would spend hours washing his hands,
engaging in ritualistic behavior, and counting,”
Dr. Frye says.“Activities that most people might
do for several seconds a day, he would do for several hours a day.”The patient was unable to finish
college or to develop a social support network or
a significant-other relationship.
Since treatment with DBS, the young man
has returned to college and is looking for parttime work.“By all the rating scales we’re using,
his symptoms are 60 to 70 percent better,” Dr.
Frye says.“The associated functional improvement has really been dramatic.”
As for Tourette, Dr. Lee cites a young man
with a severe tic that caused his neck suddenly to
swivel powerfully. Although the patient was on
MAYO CLINIC | NeurosciencesUpdate
strong medication and, as a result, experienced
constant sleepiness, the tic remained severe,
prompting concern of possible cervical spinal
injury. After DBS, the patient’s tic significantly
abated, and he was able to reduce his medication.
The January 2012 issue of Mayo Clinic Proceedings contained a report on that patient and
two others with refractory Tourette, all of whom
had excellent outcomes after treatment with
DBS. Stimulation was generally well-tolerated,
and some degree of efficacy against tics was
noted immediately. One year after treatment, the
patients had a mean reduction of 70 percent in
the Yale Global Tic Severity Scale score.
DBS, then CBT
The procedure for performing DBS for OCD
is similar to the DBS procedure for movement
disorders. Patients are awake, with their heads
in a stereotactic frame, so they can speak with
the surgeon.“It is very helpful for us to know
the effect of stimulation intraoperatively,” Dr.
Lee says. The ventral capsule/ventral striatum is
targeted.
However, for Tourette, DBS is often done
under general anesthesia.“A lot of these patients
have such severe neck tics that it would be very
dangerous to have them awake in a stereotactic
frame,” Dr. Lee says. The target for Tourette
syndrome is the centrum-median/parafascicular
nucleus of the thalamus.
After DBS, it is important for patients to
resume CBT.“The neurosurgical intervention can
alleviate terribly disabling symptoms and the
associated complete functional disability related
to those. But more work is needed beyond the
neurosurgical procedure,” Dr. Frye says.“In fact,
we find that after surgery, patients can engage
in therapy in a much more beneficial way than
before surgery.”
The mechanism by which DBS benefits
patients isn’t fully understood.“But over the past
10 years in our Neural Engineering Laboratory,
we have discovered — using fMRI, electrochemistry and electrophysiology — that we are really
modulating neurocircuits in the brain,” Dr. Lee
says (Figure).“We have some understanding of
that process for patients with movement disorders, but we know much less about how it works
in psychiatric circuits.”
For more information
Savica R, et al. Deep brain stimulation in Tourette
syndrome: A description of 3 patients with
excellent outcome. Mayo Clinic Proceedings.
2012;87:59.
Research Highlights in
Neurology and Neurosurgery
New Diagnostic Criteria for NMOSD
Neuromyelitis optica (NMO) is an inflammatory syndrome of the central nervous system (CNS) that is distinct from
multiple sclerosis (MS) and is associated with serum aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies. Prior
NMO diagnostic criteria required optic nerve and spinal cord involvement, although more-restrictive or moreextensive CNS involvement may occur. An international consensus panel, chaired by consultants in Neurology at
Mayo Clinic in Phoenix/Scottsdale, Arizona, and Mayo Clinic in Rochester, Minnesota, has introduced new diagnostic criteria. Using systematic literature reviews and electronic surveys to facilitate consensus, the panel defined
the unifying term neuromyelitis optica spectrum disorders (NMOSDs), which is stratified further by serologic testing
(NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem,
diencephalic or cerebral presentations. More-stringent clinical criteria, with additional neuroimaging findings,
are required for NMOSD without AQP4-IgG or when serologic testing is unavailable. The international panel also
proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS. Under the new criteria, a diagnosis of optic neuritis and myelitis is no longer
required to identify NMOSD if an AQP4-IgG blood test proves positive. The criteria are expected to facilitate earlier
and more-accurate diagnosis by identifying individuals who would have been diagnosed with idiopathic transverse
myelitis, idiopathic optic neuritis or atypical MS. The criteria should also provide greater specificity for distinguishing both AQP4-IgG-seropositive and AQP4-IgG-seronegative NMOSD from MS. Early-stage diagnostic specificity
is critical because recent observational data suggest that MS therapies (interferon-b, natalizumab and fingolimod)
may aggravate NMOSDs. (Wingerchuk DM, et al. International consensus diagnostic criteria for neuromyelitis
optica spectrum disorders. Neurology. 2015;85:177.)
Molecular Classifications of Gliomas
The prediction of clinical behavior, response to therapy and outcome of infiltrative glioma is challenging. Studies of
glioma biology have led to the discovery of hundreds of molecular alterations in grade II, III and IV gliomas. Among
these molecular alternations, three are particularly noteworthy because they occur early during glioma formation,
are prevalent in glioma or are strongly associated with overall survival. Researchers at Mayo Clinic in Rochester,
Minnesota, and colleagues at the University of California, San Francisco, have classified gliomas into five principal groups on the basis of these three tumor markers: mutations in the telomerase reverse transcriptase (TERT)
promoter, mutations in isocitrate dehydrogenase (IDH), and codeletion of chromosome arms 1p and 19q. Using the
results of previous studies of tumor biology, the researchers scored tumors in 1,087 gliomas as negative or positive for each of the three markers. Using 11,590 controls, the researchers assessed associations between the top
five molecular groups and known glioma germline variants. Patients within each of the five groups (triple-positive,
TERT- and IDH-mutated, IDH-mutated only, TERT-mutated only, and triple-negative) had similar age of onset and
overall survival. However, the five groups differed from one another in age at onset, overall survival and association
with germline variants. The results imply that gliomas in the five groups are characterized by distinct mechanisms
of pathogenesis. (Eckel-Passow JE, et al. Glioma groups based on 1p/19q, IDH and TERT promoter mutations in
tumors. New England Journal of Medicine. 2015;372:2499.)
Neurosciences Research
Brain Transcriptome Profiles in ALS
Misregulated RNA processing and metabolism are recurrent themes in neurological disorders, but their involvement in amyotrophic lateral sclerosis (ALS) isn’t clearly established. Researchers at Mayo Clinic in Jacksonville,
Florida, have identified widespread transcriptome changes in individuals with ALS carrying a C9orf72 repeat
expansion (c9ALS) as well as in individuals with sporadic ALS. Utilizing next-generation RNA sequencing to analyze
post-mortem brain tissue, the researchers found major misregulated RNA-processing events in ALS, several of
which affected genes previously associated with the disease, such as ATXN2 and FUS. Several aberrant transcriptome changes were shared between people with c9ALS and people with sporadic ALS. However, overall,
the c9ALS transcriptome was affected to a greater degree than that of sporadic ALS, with little overlap. This
limited overlap may result from the presence of pathological features unique to c9ALS in the frontal cortex and
cerebellum, as well as heterogeneity among sporadic ALS cases — for example, mutation in an unknown gene.
Unexpectedly, more-robust transcriptome changes were found in the cerebellum than in the frontal cortex. The
study results indicate that distinctive factors may contribute to c9ALS and sporadic ALS, with consequences for
the development of therapies. (Prudencio M, et al. Distinct brain transcriptome profiles in C9orf72-associated and
sporadic ALS. Nature Neuroscience. 2015;18:1175.)
To read more about Mayo Clinic neurosciences research and patient care, visit www.MayoClinic.org/medicalprofs.
MAYO CLINIC | NeurosciencesUpdate
7
MAYO CLINIC
Neurosciences Update
Medical Editors:
Claudia F. Lucchinetti, M.D.
Robert J. Spinner, M.D.
Education 2015-2016 Neurology and Neurologic
Surgery Continuing Medical Education Programs
Editorial Board:
Mark K. Lyons, M.D.
James F. Meschia, M.D.
Joseph I. Sirven, M.D.
Robert E. Wharen Jr., M.D.
December
International Dementia with Lewy Bodies Conference 2015
Dec. 1-4, 2015
Marriott Harbor Beach, Fort Lauderdale, Fla.
Science Writer:
Barbara J. Toman
Mayo Clinic Neurosciences Update is written for
physicians and should be relied upon for medical
education purposes only. It does not provide a
complete overview of the topics covered and should
not replace the independent judgment of a physician
about the appropriateness or risks of a procedure for
a given patient.
Contact Us
Mayo Clinic welcomes inquiries and referrals,
and a request to a specific physician is not
required to refer a patient.
Phoenix/
Scottsdale, Arizona
866-629-6362 (toll-free)
Jacksonville, Florida
800-634-1417 (toll-free)
Rochester,
Minnesota
800-533-1564 (toll-free)
Resources
MayoClinic.org/medicalprofs
Clinical trials, CME, Grand Rounds,
scientific videos and online referrals
April
3rd Annual Southwest Laryngology Voice Rehabilitation Conference 2016
April 8-10, 2016
Taylor Auditorium, Mayo Clinic, Scottsdale, Ariz.
Neurorehabilitation Summit: Regeneration, Recovery, Reintegration 2016
April 11-12, 2016
Leighton Auditorium, Mayo Clinic, Rochester, Minn.
May
Neuro and Intensive Critical Care: Review and Hands-on Workshops 2016
May 12-14, 2016
Loews Royal Pacific Resort, Orlando, Fla.
November
Neuroradiology: Practice to Innovation Course 2016
Nov. 14-18, 2016
The Ritz-Carlton, Grand Cayman, Cayman Islands
Information and registration
Mayo Clinic in Rochester, Minnesota
Phone: 800-323-2688 (toll-free) or 507-284-2509
Email: [email protected]
Mayo Clinic in Jacksonville, Florida
Phone: 800-462-9633 (toll-free) or 904-953-0421
Email: [email protected]
Mayo Clinic in Phoenix/Scottsdale, Arizona
Phone: 480-301-4580
Email: [email protected]
Website: www.Mayo.edu/cme/neurology-and-neurologic-surgery
Expedited Patient Referrals to Mayo Clinic
Departments of Neurology and Neurologic Surgery
While Mayo Clinic welcomes appointment requests for all neurologic and neurosurgical conditions,
patients with the following conditions are offered expedited appointments:
1. Cerebral aneurysms
2. Cerebral or spinal arteriovenous malformations
3. Brain, spinal cord or peripheral nerve tumors
4. Epilepsy with indications for surgery
5. Carotid disease
MC5520-1015