Neurosciences Update - MC5520-0921
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Neurosciences Update
Neurosciences News From Mayo Clinic Vol. 18, No. 4, 2021
SEPTEMBER 2021 Novel Endovascular Therapy for
In this issue CSF-Venous Fistulas
3 Burr Hole Approach Offers Minimally Mayo Clinic has reported the first case a quarter of people with a CSF leak, it’s
Invasive Option for Resecting Brain series of transvenous embolization of due to a fistula. That is a major subgroup,
Lesions paraspinal veins to treat cerebral spinal and we expect it to grow as our diagnos-
fluid (CSF)-venous fistulas. The innovative tic techniques advance,” says Jeremy K.
therapy resulted in clinical and radio- Cutsforth-Gregory, M.D., a neurologist who
4 NF2 Clinic: Proactive, Coordinated, graphic improvement and no permanent leads the CSF dynamics clinic at Mayo
Multidisciplinary Care complications in all participants in the Clinic’s campus in Rochester.
small case series.
The most effective treatment for a
6 Robot-Assisted Spinal Surgery Shows “It’s a significant advance in the treatment CSF-venous fistula has been surgical
Promising Initial Results of CSF-venous fistulas,” says Waleed Brin- intervention that includes laminectomy,
jikji, M.D., a neurointerventionalist at Mayo facetectomy and ligation of the nerve
Clinic in Rochester, Minnesota. “We are root and associated veins. Although
able to fix these fistulas and send patients the procedure can ease the severe
home the same day, without worrying headaches associated with intracranial
about the complications that can occur hypotension, it requires a hospital stay
with spinal surgery.” and lengthy recovery.
CSF-venous fistulas, first described in “Spinal surgery is significantly more
2014, are increasingly recognized as a invasive than the endovascular inter-
cause of spontaneous intracranial hypo- vention that we developed,” says Luis E.
tension. “We are finding that, in at least Savastano, M.D., Ph.D., a cerebrovascular
Figure 1. Preoperative MRI of a participant in Mayo Clinic’s case Figure 2. On the left, digital subtraction myelogram shows a large Figure 3. Postoperative MRI shows resolution of the brain
series shows signs of brain sag with flattening of the pons, reduced CSF-venous fistula at right T4 with filling of the right T4 paraspinal sag and meningeal enhancement.
mamillopontine distance and effacement of the suprasellar cistern, vein (red arrow). On the right, the patient underwent successful
as well as thick pachymeningeal enhancement. embolization of the vein (white arrow).
neurosurgeon at Mayo Clinic’s campus in in four patients and improved but did not
Rochester. “In addition to long recovery resolve in one patient.
times, many patients also experience new “Patient satisfaction has been very high, and
numbness and pain at the surgical site we are very rigorous in obtaining com-
that lingers for months.” plete clinical and imaging follow-up on all
patients,” Dr. Brinjikji says.
Existing minimally invasive treatment
options, such as epidural blood patch and Pain localized to the site of the emboliza-
fibrin glue injection, have been effective in tion was a common minor complication,
only a tiny minority of patients with fistulas. but no patient required narcotics. And the
“Embolization seemed like a feasible pain subsided in a matter of weeks for all
alternative, as long as we could navigate patients. No patient experienced permanent
Waleed Brinjikji, M.D. through the paraspinal venous system and neurological complications. The researchers
get our catheter to the exact right point,” note that further studies are needed to
Dr. Brinjikji says. confirm the technique and to validate the
treatment’s durability.
Dr. Brinjikji had acquired a medical text-
book from the 1970s on spinal phlebog- An essential component of this procedure is
raphy, a common diagnostic tool before state-of-the-art imaging for the diagnosis of
MRI. “We realized that if physicians could CSF-venous fistulas.
get into the paraspinal veins back then, we
— with all the advances in catheterization “Identifying the fistula is a major challenge,”
— should be able to get into them and Dr. Cutsforth-Gregory says. “DSM allows us
block them off using our newer and safer to locate fistulas that might otherwise be
embolic agents,” he says. overlooked. It’s practice changing.” Cur-
rently, eight DSMs a week are routinely per-
DSM TO LOCALIZE FISTULAS formed at the Rochester campus of Mayo
As described in the May 2021 issue of Amer- Clinic, making it one of the highest-volume
ican Journal of Neuroradiology, the Mayo CSF-leak practices in the world.
Clinic case series included five patients with
Jeremy K. Cutsforth-Gregory, M.D. CSF hypotension secondary to CSF-venous The development of innovative treatments
fistulas. The patients’ fistulas were localized is facilitated by Mayo Clinic’s multidisci-
using lateral decubitus digital subtraction plinary approach. “This new endovascular
myelography (DSM). On MRI, all patients treatment modality is the result of team-
had evidence of CSF hypovolemia, including work by highly skilled headache neurolo-
brain sag and pachymeningeal enhance- gists, interventional neuroradiologists and
ment (Figure 1, see page 1) with no extradu- endovascular neurosurgeons, as well as a
ral fluid collection on total spine MRI. radiology team at the forefront of medical
imaging,” Dr. Savastano says.
The endovascular procedures — performed
in August 2020 — involved catheterization “Historically, endovascular approaches
of the azygous vein, followed by selective have been used to fix only vascular prob-
catheterization and embolization of the lems,” he adds. “This treatment represents
paraspinal vein (Figure 2, see page 1). a paradigm shift. We are now using
endovascular procedures to fix problems
All patients had improved clinical and radio- outside the vessels themselves.”
logic findings (Figure 3, see page 1) after
Luis E. Savastano, M.D., Ph.D. the procedure. Four patients had complete FOR MORE INFORMATION
resolution of headaches, and one had a 50% Brinjikji W, et al. A novel endovascular
reduction in headache symptoms. Brain therapy for CSF hypotension secondary to
sag resolved in four patients and improved CSF-venous fistulas. American Journal of
but did not resolve in one patient. Similarly, Neuroradiology. 2021;42:882.
pachymeningeal enhancement resolved
2
Figure. On the left, preoperative MRI shows a large cerebellar metastatic tumor. The center photograph shows the burr hole, measuring less than 14 millimeters, through which the large cerebellar tumor
was resected. On the right, postoperative MRI shows complete resection of the large tumor. The patient went home on the day following the procedure.
Burr Hole Approach Offers Minimally
Invasive Option for Resecting Brain Lesions
Mayo Clinic has successfully performed greater magnification and oblique visualiza-
a series of intra-axial tumor resections tion angles.
using a burr hole approach with exoscopic
visualization. The procedures, described in “Our goal in this surgical series, as with
a study published in the March 2021 issue all our patients, was to achieve maximal,
of Journal of Neurological Surgery, provide safe resection,” Dr. Chaichana says. “The
proof of concept for this minimally invasive exoscope, as opposed to the endoscope,
approach (Figure). hovers over the surgical field, not within
the cavity. It provides a wider focus of view,
“This approach represents the extreme greater magnification and oblique visual-
boundary of keyhole surgery. We have ization angles that would be nonergonomic
been able to resect select tumors through compared with the surgical microscope.” Kaisorn L. Chaichana, M.D.
a 14-millimeter burr hole, similar to what is
used for a needle biopsy,” says Kaisorn L. The burr hole approach is suitable for
Chaichana, M.D., a neurosurgeon at Mayo resecting superficial lesions. All tumors
Clinic in Jacksonville, Florida. “Patients in the patients treated in the Mayo Clinic
generally go home the following day and series were in close proximity to the cortical
recover much faster.” surface, with the most superficial part of the
lesions located above the sulcal boundary in
Fourteen (93%) of the 15 patients in the the coronal plane.
Mayo Clinic study had gross total resection.
The tumor remaining in one patient was Patients with lesions presumed to be close
minimal and subsequently resected. None to eloquent areas had functional MRI and
of the 15 patients experienced complica- diffusion tensor imaging before surgery.
tions after the burr hole procedure, and a If access to the lesion required cortical or
majority went home the next day. subcortical violation of eloquent areas, the
burr hole approach wasn’t used.
“The incision is very small — about
three-fourths of an inch — and blood loss Among the patients studied, eight had
is much lower than with conventional metastatic brain tumors, four had low-grade
surgery,” Dr. Chaichana says. glioma and three had high-grade glioma.
Lesion diameter was typically limited to
Exoscopic visualization is the key to this 4 centimeters. Dr. Chaichana notes that
approach. Compared with the endoscope, the burr hole procedure is also suitable for
the exoscope provides a wider focus of view, evacuating hematomas.
3
“A minimally invasive approach means FOR MORE INFORMATION
patients heal faster, so they can start radia- Marenco-Hillembrand L, et al. Bur hole-
tion and chemotherapy sooner, if needed,” based resections of intrinsic brain tumors
Dr. Chaichana says. “We believe the burr with exoscopic visualization. Journal of Neu-
hole approach can be used for selective rological Surgery. Part A, Central European
lesions without compromising the extent of Neurosurgery. 2021;82:105.
resection or neurological outcomes.”
NF2 Clinic: Proactive, Coordinated,
Multidisciplinary Care
Mayo Clinic has launched the multidisci- of multiple tumors. Although nearly all
plinary Neurofibromatosis Type 2 Clinic patients have bilateral vestibular schwan-
to provide comprehensive management nomas, the number and type of additional
of this uncommon genetic condition. The tumors differ.
initiative brings together providers in 12
specialties for the diagnosis and treatment “The phenotype is extremely variable,” Dr.
of teenagers and adults with neurofibroma- Carlson says. “A patient might be 70 years
tosis 2 (NF2). old and have no features of the disease
except two small vestibular schwanno-
“Our mission is to offer highly coordinated mas. But some people have a diagnosis
care that addresses the multifaceted in their teenage years or even earlier
Matthew L. Carlson, M.D. aspects of the disease,” says Matthew L. and experience very severe disease. An
Carlson, M.D., an otolaryngologist at Mayo individual may have more than 50 tumors
Clinic in Rochester, Minnesota, and director spread throughout the brain, skull base,
of the NF2 Clinic. “We are committed to spine and peripheral nerves.”
being not just reactive but proactive, to
anticipate the future needs of patients and Besides affecting the vestibulocochlear
their families.” nerves, schwannomas can develop in
other cranial nerves as well as in the spine
Patients referred to the NF2 Clinic typically and peripheral nerves. Cranial and spinal
complete imaging tests and multispecialty meningiomas are common; spinal ependy-
examinations and start treatment within a momas also can develop. The tumors can
few days. Genetic testing is included. lead to debilitating symptoms including
hearing loss, imbalance, facial nerve paral-
“We use many new methods of genetic ysis, swallowing and speech difficulty, limb
testing on blood samples — and also often weakness, and ocular problems.
on available tumor tissue — to establish
genetic variation,” says Dusica Babovic-Vuk- “NF2 affects people in many different ways,
sanovic, M.D., a medical geneticist at the depending on where the tumors grow,” Dr.
Dusica Babovic-Vuksanovic, M.D. Rochester campus of Mayo Clinic. Carlson says. “Many patients develop hear-
ing loss to the point of being completely
As a major tertiary center, Mayo Clinic uses deaf, vision loss to the point of blindness
cutting-edge imaging to monitor tumors and motor difficulties to the point of losing
associated with NF2. A range of systemic the ability to walk.”
and targeted treatment options are avail-
able. Select patients might also be eligible To address these needs, the NF2 Clinic
for clinical trials. “Our goal is to be a com- brings together specialists in:
prehensive clinic that provides efficient, • N eurology
streamlined care,” Dr. Carlson says. • N eurosurgery
• N euroradiology
The Neurofibromatosis Clinic at Mayo • N eurotology
Clinic in Phoenix, Arizona, provides mul- • Audiology
tidisciplinary care for children and adults • R adiation oncology
with neurofibromatosis type 1 and NF2. • M edical oncology
• P ediatrics
MANAGING VARIABLE AND COMPLEX • O phthalmology, including neuro-ophthal-
PHENOTYPES mology and oculoplastic surgery
John (Jack) I. Lane, M.D. NF2 is characterized by the development • M edical genetics
4
Figure. Overlays of MRI demonstrate the growth of bilateral vestibular schwannomas over an 18-month period in a patient with neurofi-
bromatosis type 2. The current tumor volume is shown in green, and the earlier tumor volume in red.
• Physical medicine and rehabilitation, On Wednesday morning, the specialists
including physical therapy and occupa- gather to discuss patients’ care. “There
tional therapy are two or three providers for each of the
• Psychiatry 12 stakeholder specialties — so about 25
Specialists in peripheral nerve disorders, to 30 providers during every conference,”
speech pathology, and plastic and recon- Dr. Carlson says. “We start by describing a
structive surgery also are part of the treat- patient’s overall picture. Then we talk very
ment team as needed. specifically about the patient’s tumor types
and growth.”
COORDINATED APPOINTMENTS
Before arriving at Mayo’s NF2 Clinic, patients Volumetric measurements of tumors —
complete an online survey about their symp- obtained by segmenting and analyzing
toms — both physical and emotional — and patients’ MRIs in a 3D laboratory — are Michael J. Link, M.D.
their quality of life. Clinic visits typically start assessed. “What might not be readily evi-
on a Monday morning, with comprehensive dent by visual examination of the MRI can
imaging of the cranial nerves and intracranial be detected with volumetric analysis,” says
space, skull base, spine, and other parts of John (Jack) I. Lane, M.D., a neuroradiologist
the body as needed. at the Rochester campus of Mayo Clinic.
Later Monday or on Tuesday, patients have Unlike most tumors, which are generally
comprehensive neurological and audiological spherical or elliptical, NF2 tumors have
evaluations. “The audiology visit might involve highly irregular shapes. “As a result, a 2- or
just a hearing test, or evaluation or program- 3-millimeter change on a linear scan can
ming for a cochlear implant or an auditory result in a 50% to 80% change in total
brainstem implant,” Dr. Carlson says. tumor size, which would be an indication
that treatment is needed,” says Michael J.
Patients might also see a medical geneticist. Link, M.D., a neurosurgeon at Mayo Clinic’s
About half of people with NF2 have a family campus in Rochester, Minnesota.
history of the disease, and half present with
a new mutation. As an autosomal dominant The specialists also evaluate overlays of a
genetic disorder, NF2 has about a 50% patient’s current scans and scans taken two
chance of being passed on to children. years earlier (Figure). “We can drop the previ-
ous image right on top of the current image,
“Our genetic counseling can also include and then use a slide bar to pan between
referral to Obstetrics and Gynecology for them,” Dr. Lane says. “Often that analysis
specialized in vitro fertilization,” Dr. Babo- can be even more sensitive than volumetric
vic-Vuksanovic says. “If a patient already has changes in assessing tumor growth.”
a child at risk of NF2, we provide screening
and surveillance starting at age 12 because Based on these detailed evaluations, the
tumors associated with NF2 can occur at an group agrees on treatment recommenda-
early age.” tions. Patients whose tumors aren’t causing
5
problems might have no active treatment. participates with centers across the United
If only one tumor is growing, patients might States and around the world in clinical
have localized surgical or radiosurgery treat- trials of NF2 medications.
ment. Individuals with multiple, progressing
tumors typically have chemotherapy, guided “We are looking for ways to apply systemic
by a neuro-oncologist, medical oncologist or therapy to prevent the development of
pediatric oncologist. tumors,” Dr. Babovic-Vuksanovic says. “It
is very important to find alternatives to
“Sometimes, treatments are done concur- surgical therapy after tumors develop.”
rently,” Dr. Carlson says. “Patients who have
multiple tumors, including a large and active The emotional health of patients and
tumor, might need surgery or radiation their families is addressed throughout the
therapy on top of systemic therapy.” process of care. “The secondary sequelae of
NF2 are often overlooked,” Dr. Carlson says.
If surgery is recommended, Mayo Clinic “Depression and anxiety are common.
neurosurgeons and neurotologists have
experience with minimally invasive tech- We think it’s important to approach the
niques. The options for radiation therapy patient holistically and to support the family
include stereotactic radiosurgery — Mayo by bringing in a social worker or suggesting
Clinic has performed Gamma Knife radio- family counseling when needed.”
surgery for 30 years — as well as intensi-
ty-modulated therapy and proton therapy. Follow-up visits to the NF2 Clinic are sched-
uled annually or more frequently as needed.
“The multidisciplinary approach is key Mayo Clinic is committed to providing
because the best next steps for patients lifelong care.
can vary so much. Everyone on our team
has a particular area of expertise,” Dr. Link “The magnified care needed by people
says. Reconstructive surgery also might be with NF2 requires the involvement of
needed to restore facial nerve function and multiple stakeholders,” Dr. Carlson says.
eye closure. “The cross-talk between specialties is
seamless. In our model of care, every
Treatment can start as early as the following provider from each contributing specialty
day, even if that need wasn’t anticipated shares a singular goal of achieving the
before the patient’s arrival. “Certain NF2 best outcome for each patient.”
care providers have appointment slots set
aside. Patients who need radiosurgery, for FOR MORE INFORMATION
example, can have it the next day in many Neurofibromatosis Type 2 Clinic. Mayo Clinic.
cases,” Dr. Carlson says. https://www.mayoclinic.org/depart-
ments-centers/neurofibromato-
Patients seen at the NF2 Clinic might sis-type-2-clinic/overview/ovc-20481871.
qualify for clinical trials. Mayo Clinic
Robot-Assisted Spinal Surgery Shows
Promising Initial Results
Mayo Clinic has performed more than 200 postoperative revisions, according to a
robot-assisted spinal surgeries (Figure, see study published in the May 2021 issue
page 7), with positive early outcomes and of Mayo Clinic Proceedings. Two of the
declining procedural times. 402 screws required revision intraoper-
atively, and no complications related to
“Robotics has given us options to treat screw placement were encountered in
patients more safely and effectively,” any of the patients studied.
says Mohamad Bydon, M.D., a neuro-
surgeon at Mayo Clinic in Rochester, “The robotic platform significantly
Minnesota. enhances the accuracy of screw place-
ment. It removes any human error that
Among 402 screws placed in 77 pa- might be associated with fluoroscopi-
Mohamad Bydon, M.D.
tients who had robot-assisted spinal cally guided screw placement or even
surgery at Mayo Clinic, none required with stereotactic navigation,” says Selby
6
Figure. Selby G. Chen, M.D., a neurosurgeon at Mayo Clinic in Jacksonville, Florida, performs robot-assisted spinal surgery.
G. Chen, M.D., a neurosurgeon at Mayo “As a result of the minimally invasive ap-
Clinic in Jacksonville, Florida. proach, patients have less pain and a lower
need for pain medication,” Dr. Bydon says.
With the accrual of surgical experience, The procedure can be performed with the
operative time declined significantly during patient awake or under anesthesia. Among
the study period of Sept. 4, 2018, to Oct. patients in the Mayo Clinic study, the me-
16, 2019. During that period the number of dian length of hospitalization following the
procedures performed per week increased. minimally invasive surgery was two days.
“Although there is a learning curve with As an early adopter of robot-assisted tech-
this technology, it is surmountable,” says nology, Mayo Clinic is able to look ahead to
Matthew T. Neal, M.D., a neurosurgeon future applications. “We hope that as the
Selby G. Chen, M.D.
at Mayo Clinic in Phoenix/Scottsdale, technology advances, we will be able to
Arizona. “It is advantageous to develop apply it to the cervical spine as well as spi-
comfort and familiarity with the tech- nal decompression, disk preparation, the
nology at an early stage because we insertion of interbody cages and deformity
anticipate the robot will have increasing correction,” Dr. Chen says.
capabilities moving forward.”
Robot-assisted spinal surgery exemplifies
The majority of robot-assisted spinal Mayo Clinic’s patient-centered approach.
surgeries performed at Mayo Clinic “The accuracy and efficiency of the robot is
are lumbar fusions and thoracolumbar part of our strategy to help reduce patients’
fusions. Patients have preoperative and pain and enhance their recovery after
sometimes intraoperative CT imaging, spinal surgery, which are of the utmost
which navigational software uses to help importance to us,” Dr. Neal says.
create a surgical plan. During surgery
the software guides a robotic arm into FOR MORE INFORMATION
position to ensure that the preoperative Bydon M, et al. Initiation of a robotic
plan is accurately translated to trajectory program in spinal surgery: Experience at
guidance in the surgical field. a three-site medical center. Mayo Clinic
Matthew T. Neal, M.D.
Proceedings. 2021;96:1193.
7
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