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Friday, November 26, 2010

Revision of Vagal Nerve Stimulator Electrodes Through a Posterior Cervical Triangle Approach: Technical Note.

Neurosurgery. 2010 Dec;67 Operative Neurosurgery, 2:ons457-ons460.

Revision of Vagal Nerve Stimulator Electrodes Through a Posterior Cervical Triangle Approach: Technical Note.

1Division of Pediatric Neurosurgery, The Children's Hospital, University of Colorado, Aurora, Colorado 2Department of Neurosurgery, Allegheny General Hospital, Drexel University School of Medicine, Pittsburgh, Pennsylvania.


BACK GROUND:: We describe an approach to vagal nerve stimulator (VNS) lead replacement through the posterior cervical triangle. Scar around the structures of the carotid sheath is avoided and new leads are placed on a pristine section of the vagus nerve proximal to the original site.

CLINICAL PRESENTATION:: Skin incision from the implantation surgery is incorporated and extended to allow access to the posterior border of the sternocleidomastoid muscle (SCM). Dissection proceeds along the posterior border of the SCM. The SCM and jugular vein are retracted anterior to expose a fresh segment of the vagal nerve immediately superficial to the carotid artery and proximal to the original electrode site. Once the nerve is adequately exposed, electrode placement proceeds in the standard fashion. Dysfunctional electrodes are left in place, and the lead wire is cut as near the electrodes as can be easily accessed. Three patients have undergone lead revision with this approach. Lead placement was successful and free from complications in all cases.

CONCLUSION:: The posterior cervical triangle approach provides a virgin dissection plane for VNS revision.

PMID: 21099572 [PubMed - as supplied by publisher

Operative and Technical Complications of Vagus Nerve Stimulator Implantation.

Neurosurgery. 2010 Dec;67 Operative Neurosurgery, 2:ons489-ons494.

Operative and Technical Complications of Vagus Nerve Stimulator Implantation.

1Department of Neurosurgery, Medical University of Luebeck, Luebeck, Germany 2Department of Neuropediatrics, Medical University of Luebeck, Luebeck, Germany 3Department of Phoniatrics and Pediatric Audiology, Medical University of Luebeck, Luebeck, Germany 4Department of Neurosurgery, Clemenshospital GmbH Münster, Münster, Germany.


BACKGROUND: The treatment of refractory epilepsy by vagus nerve stimulation (VNS) is a well-established therapy option for patients not suitable for epilepsy surgery and therapy refractory depressions.

OBJECTIVE: To analyze surgical and technical complications after implantation of left-sided VNS in patients with therapy-refractory epilepsy and depression.

METHODS: One hundred five patients receiving a VNS or VNS-related operations (n = 118) from 1999 to 2008 were investigated retrospectively.

RESULTS: At the time of operation, 84 patients were younger than 18 years, with a mean age of 10.5 years. Twenty (19%) patients had technical problems or complications. In 6 (5.7%) patients these problems were caused by the operation. The device was removed in 8 cases. The range of surgically and technically induced complications included electrode fractures, early and late onset of deep wound infections, transient vocal cord palsy, cardiac arrhythmia under test stimulation, electrode malfunction, and posttraumatic dysfunction of the stimulator.

CONCLUSION: VNS therapy is combined with a wide spread of possible complications. Technical problems are to be expected, including electrode fracture, dislocation, and generator malfunction. The major complication in younger patients is the electrode fracture, which might be induced by growth during adolescence. Surgically induced complications of VNS implantation are comparably low. Cardiac symptoms and recurrent nerve palsy need to be taken into consideration.

PMID: 21099577 [PubMed - as supplied by publisher

Wednesday, November 24, 2010




HE van der Aa, MD, Ph.D., Department of neurosurgery, Medisch Spectrum Twente, Haaksbergerstraat 55, 7513 ER Enschede, Netherlands

JJM Vangeneugden, MD, Ph.D., Department of neurosurgery, AZ ST Maarten, Duffel, Belgium

HPJ Buschman, Ph.D., Twente Institute for Neuromodulation, Medisch Spectrum Twente, Netherlands

BACKGROUND: Vagal nerve stimulation (VNS) for the management of intractable seizure disorders and chronic depression is increasingly being used. Concern was raised about the possibility of revision or removal of the VNS-Therapy helical stimulating electrode in case of a technical failure or once treatment is considered no longer desired or proven ineffective. Because the electrodes are wrapped around the nerve, there is the potential for nerve injury during their removal. We report our experience with removal and revision of the VNS-Therapy electrodes.

METHODS: We performed removal and/or revision of VNS-electrodes in 4 patients who received long-term VNS-therapy for drug-resistant epilepsy.

RESULTS: All patients (2 males and 2 females), were adults at the onset of VNS-Therapy. The mean duration of electrode implantation was 2.8 years (range 0.5-4.0 years).

In all patients, the old electrodes were removed completely from the nerve. One patient had the system removed because of severe VNS-therapy related side-effects combined with insufficient clinical benefit. Two patients had the system removed because of the need for MRI of the head, of whom one underwent subsequent radiosurgery. In the fourth patient a new electrode was placed as a result of lead failure. No adverse events occurred intraoperatively or postoperatively.

CONCLUSIONS: Vagal nerve stimulation remains a viable option for improving seizure control in difficult to treat patients with epilepsy or improving mood in patients with chronic refractory depression. Device removal or revision as a result of insufficient clinical response and/or surgical complications such as hardware failure can be performed with success by an experienced surgeon.

Saturday, November 20, 2010

Efficacy and tolerability of long-term treatment with vagus nerve stimulation in adolescents and adults with refractory epilepsy and learning disabilities.

Seizure. 2010 Oct 27. [Epub ahead of print]

Efficacy and tolerability of long-term treatment with vagus nerve stimulation in adolescents and adults with refractory epilepsy and learning disabilities.

National Centre for Epilepsy, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.


The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 50 patients with epilepsy and learning disabilities. Mean observation time was 4.6 years. At follow-up, none of the patients was seizure-free, 25% had more than 50% seizure reduction, and 46% had some seizure reduction, but less than 50%. The discontinuation rate was 18%. Our results indicate that, like antiepileptic drugs, VNS does not have such a good seizure-reducing effect in patients with epilepsy and learning disabilities compared with the general epilepsy population.

Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
PMID: 21035358 [PubMed - as supplied by publisher

Tuesday, November 16, 2010



The toll of epilepsy has been
overlooked—and the research underfunded—for too long. A call to action.

The statistics are stark and sobering— and for the uninitiated (which is to
say most of us), startling. Epilepsy in America is as common as breast cancer,
and takes as many lives. A mysterious and widely misunderstood affliction,
epilepsy is a disorder in which the brain produces sudden bursts of electrical
energy that can interfere with a person's consciousness, movements or
sensations. Up to 50,000 Americans die each year from seizures and related
causes, including drownings and other accidents; one in 10 people will suffer a
seizure in their lifetimes. By some estimates, the mortality rate for people
with epilepsy is two to three times higher—and the risk of sudden death is 24
times greater—than that of the general population. There are 200,000 new cases
each year, and a total of more than 3 million Americans are affected by it—more
than multiple sclerosis, cerebral palsy, muscular dystrophy and Parkinson's
disease combined. Between 1 and 3 percent of the population will develop some
form of epilepsy before age 75. (Article continued below...)

There is also a rise expected in the incidence of epilepsy among the veterans
of the wars in Afghanistan and Iraq who have sustained traumatic head injuries.
Yet public and private funding for research lag far behind other neurological
afflictions, at $35 a patient (compared, for instance, with $129 for Alzheimer's
and $280 for multiple sclerosis). It is time to remedy that gap, and to raise
epilepsy to the front ranks of public and medical concern.

There is cause for hope. Science is unraveling more and more of the mysteries
of the brain, and perhaps the source of the cataclysmic electrical storms of
epilepsy will yield its secrets. Such, at least, is the aim of Sen. Edward M.
Kennedy, who is considering a major bill to support enhanced research that will
fund more work toward a cure, and of a resolute band of advocates that includes
the man who sits nearest the Oval Office in the West Wing. White House senior
adviser David Axelrod and his wife, Susan, are the parents of Lauren, a
27-year-old who began suffering seizures when she was 7 months old. Mrs.
Axelrod, who contributes a piece in the following pages, is a founding board
member and president of CURE—Citizens United for Research in Epilepsy. The
group's mission is clear from the acronym: to learn everything we can about
epilepsy in search of a cure.

Epilepsy is an ancient brain disorder, and different cultures at different
times have veered between considering it a disease or thinking of it as a sign
of demonic possession. Around 400 B.C., Hippocrates defined it as a physical,
not a spirit, affliction, writing of what was then called "the Sacred Disease":
"It appears to me to be nowise more divine nor more sacred than other diseases,
but has a natural cause like other affections." Julius Caesar suffered from it;
Jesus cured people with epilepsy in Gospel accounts of his ministry. The word
itself is derived from the Latin epilepsia, which means "to take hold of." In
1604, Shakespeare has Othello suffer a kind of seizure as Iago works him into a
frenzy of jealousy: "My lord is fall'n into an epilepsy," Iago tells Cassius.
Seizures played a role in convicting suspected witches through the ages. Well
into the 20th century, some states had sterilization laws that applied to people
with epilepsy, and several more forbade those with epilepsy from marrying. In
1956, Roscoe L. Barrow and Howard D. Fabing published "Epilepsy and the Law: A
Proposal for Legal Reform in the Light of Medical Progress," a book that helped
lead to the repeal of many sterilization and antimarriage laws.

Though the most overt examples of discrimination and demonization have faded
with time, epilepsy still receives too little attention, either from the medical
community or the public at large. Why? One reason is that advances in drug
treatments have created the popular impression that epilepsy is now an
essentially manageable condition. (Which, for two thirds of patients, it is. But
that still leaves a third for whom it is not.) It is thought to be rarely fatal,
controllable by medication. There is a terrible irony here: because most people
with epilepsy are not in a constant state of seizure—they are, rather, in
perpetual but quiet danger—their condition can appear less serious than it truly
is. It is all too human, but all too true, that a problem, including the problem
of a serious medical affliction, stays out of mind when it is out of sight.

Because so many of those who must endure it do so valiantly, and with grace
and grit, it is more difficult for those not directly affected by it to grasp
that epilepsy can kill. Put harshly, we need more of a cancerlike sensibility
around epilepsy. We cannot usually see our friends' cancer, but we do not
hesitate to invest the search for a cure for different cancers with the utmost
cultural and political importance. We must now do the same with epilepsy. "We
want complete freedom from seizures," says Susan Axelrod. "We want future
families to be spared what so many other families, for so many years, have
endured. Lives should not be defined by diseases." No, they should not—which is
why all of us must focus on understanding epilepsy. And then we must defeat

Saturday, November 13, 2010

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve:

Epilepsy Res. 2010 Nov 9. [Epub ahead of print]

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: Pilot trial at Ghent University Hospital.

Reference Centre for Refractory Epilepsy, Department of Neurology, Ghent University Hospital, De Pintelaan 185, K12IA, Gent 9000, Belgium.


PURPOSE: Vagus nerve stimulation (VNS) is an established treatment for refractory epilepsy. The ADNS-300 is a new system for VNS that includes a rechargeable stimulus generator and an electrode for combined stimulation and recording. In this feasibility study, three patients were implanted with ADNS-300 for therapeutic VNS. In addition, compound action potentials (CAPs) were recorded to evaluate activation of the vagus nerve in response to VNS.

METHODS: Three patients were implanted with a cuff-electrode around the left vagus nerve, that was connected to a rechargeable pulse generator under the left clavicula. Two weeks after surgery, therapeutic VNS (0.25-1.25mA, 500μs, 30s on, 10min off and 30Hz) was initiated and stimulus-induced CAPs were recorded.

RESULTS: The ADNS-300 system was successfully implanted in all three patients and patients were appropriately stimulated during six months of follow-up. A reduction in seizure frequency was demonstrated in two patients (43% and 40% in patients 1 and 3, respectively), while in patient 2 seizure frequency remained unchanged. CAPs could be recorded in patients 1 and 2, proving stimulation-induced activation of the vagus nerve.

CONCLUSION: This feasibility study demonstrates that the ADNS-300 system can be used for combined therapeutic stimulation (in 3/3 patients) and recording of CAPs in response to VNS (in 2/3 patients) up to three weeks after surgery. Implantation in a larger number of patients will lead to a better understanding of the electrophysiology of the vagus nerve, which in turn could result in more adequate and individualized VNS parameter choice.

Copyright © 2010 Elsevier B.V. All rights reserved.
PMID: 21071177 [PubMed - as supplied by publisher

Saturday, November 6, 2010

Why the FDA can’t protect the public

BMJ 2010; 341:c4753 doi: 10.1136/bmj.c4753 (Published 2 November
Cite this as: BMJ 2010; 341:c4753
Why the FDA can’t protect the public
1.      Jeanne Lenzer, medical investigative journalist1,
2.      Shannon Brownlee, instructor, Dartmouth Institute for
Health Policy and Clinical Practice
+ Author Affiliations
1.      1New York
2.      2Washington,
device makers often fail to properly conduct safety studies and the US Food and
Drug Administration provides scant oversight. Jeanne Lenzer and Shannon Brownlee look
at some of the problems with post approval surveillance of novel devices
In 1997, the US Food and Drug
Administration’s neurological devices panel met to consider approval of a vagus
nerve stimulator (VNS). The manufacturer, Cyberonics, said it could prevent or
reduce seizures in patients with partial onset epilepsy who did not respond to
drug treatment. The device consists of a generator the size of a matchbox that
is implanted under the skin below the patient’s clavicle. Lead wires from the
generator are tunnelled up to the patient’s neck and wrapped around the left
vagus nerve at the carotid sheath, where it delivers electrical impulses to the
nerve lasting about 30 seconds every 3-5 minutes.
Representatives from Cyberonics offered no
definitive explanation during the FDA meeting of how the device stopped or
reduced seizures, but they had three studies, E03, E04, and E05, to show its
safety and efficacy.
Two of the
studies, E03 and E05, involved 313 patients with treatment resistant partial
seizures randomised to high or low dose stimulation. The low stimulation arm
was intended to avoid the problem of an unblinded placebo arm because all
patients would be implanted and told they were receiving stimulation. The
studies did not include a medical treatment arm for comparison, leaving
unanswered the question of whether either treatment arm was superior to
existing care.
reported that 25% of patients in the high stimulation arms of the trials
achieved the primary end point: a 50% reduction in seizure frequency from baseline.
However, 20% of patients in the high stimulation arm had more seizures.1
about safety
The safety of the device hinged on the
cause of death among 17 patients of the 1000 implanted with the device
worldwide. The device had been approved in Europe and Australia before approval
in the US. The most common cause of death among young epileptics is sudden
unexpected death from epilepsy (SUDEP), a poorly understood complication that
is thought to be related to cardiac or respiratory arrest that sometimes occurs
shortly after a seizure. SUDEP is reported most often among younger patients
and those with poorly controlled seizures.
2 3 The company told FDA panellists that
the deaths were from SUDEP or other causes unrelated to its product.
1 However, one panellist, Steven
Piantadosi, professor of oncology and biostatistics and a clinical trial
methodologist at Johns Hopkins, expressed concerns, saying, “I’m still a little
worried about the death rates that we are seeing.”
In the
data provided by Cyberonics, patients implanted with the device had a SUDEP
rate of 7.3/1000. Dr Piantadosi asked, “Should we be concerned by that?”
response to Dr Piantadosi’s questions, Ann Costello, an FDA reviewer, cited one
epidemiological study that showed an even higher SUDEP rate, 9.3/1000, among
treatment resistant patients about to have brain surgery to treat their severe
seizures.4 W Allen
Hauser, a member of Cyberonics’ scientific advisory board, also responded to Dr
Piantadosi’s concerns, saying, “I don’t think that the sudden death is an issue
specific to the device. It’s a specific issue in terms of people with bad
of approval
Dr Piantadosi continued to express concern
about the SUDEP rate, but the advisory panel nonetheless voted unanimously to
approve the vagus nerve stimulator for patients with treatment resistant
partial seizures. The FDA made the approval conditional: Cyberonics would have
to conduct a post-approval study to examine the safety of the device and it
would have to report promptly all serious adverse reactions to the agency.
the 13 years since the device was approved in the US, more than 900 deaths have
been reported to the FDA, and it is still not clear what impact, if any, the
device has had on patient mortality. Although Cyberonics conducted
post-approval studies, none of the studies submitted to the FDA included
mortality data. The FDA did not specifically require Cyberonics to submit
mortality data as part of the follow up study, merely to “characterize
morbidity and mortality.” According to a spokesman for Cyberonics, the company
did collect mortality data from the Social Security Death Index, but they have
not published the results and they declined to show the data to the BMJ. The FDA told the BMJ that it has not
requested further studies concerning mortality.
with post-approval surveillance
The FDA’s failure to request and rigorously
monitor mortality data related to the VNS is but one example of the gap in
post-approval surveillance of medical devices. Most devices and drugs on the
market are supported by studies that are underpowered to detect rare but
potentially life threatening events that can kill tens of thousands of people
if the drug or device is widely used.
6 The impracticality of conducting
large scale clinical trials before approval for every drug and device places a
burden on post-approval surveillance.
burden is especially important for devices because they are less likely than
drugs to be supported by clinical studies before use. Less than one third of
devices approved under FDA’s premarket approval process had been evaluated in a
randomised study, according to a review of 78 high risk cardiovascular devices
approved by the FDA from 2000 to 2007.7 Just 5% were supported by two or
more blinded, randomised studies. Most of the outcomes measured, according to
the FDA study, were surrogate markers.
monitor safety of devices, the FDA relies on reports of harms associated with
devices once they have been approved. According to the agency, the most
“comprehensive source of information about the safety and effectiveness” of
devices as they are used in everyday circumstances is its Manufacturer and User
Facility Device Experience (MAUDE) database.8 However, the data contained in the
database does not constitute a comprehensive record of the numbers of adverse
events or exposures, and thus can only pick up “signals” of possible safety
problems that could be used to trigger more definitive investigation (box). Of
course, these signals can be picked up only if someone is monitoring the data.
An FDA taskforce on device regulation concluded in August, however, that
“challenges” in “current data sources . . . make it difficult to . . .
effectively obtain complete information about the risks and benefits of
regulated products.”9
The problem with MAUDE
reports of adverse events associated with medical devices doubled from 2003 to
8 the MAUDE
database remains an imperfect tool.
6 10 Several factors can contribute to
under-reporting, including the voluntary nature of the reports; fear of
litigation by surgeons and others in a position to report the event; and
failure by patients and healthcare providers to connect new medical problems
with a device.
11 Even
when device related adverse events do make it into FDA’s databases, 39% are
reported late.
8 A review
by the BMJ of
deaths among vagus nerve stimulator patients listed in the FDA’s database shows
that some deaths weren’t reported until several years after the patient died.
Perhaps the most serious flaw in the MAUDE database is
the fact that manufacturers—not the FDA or any other independent body—can decide
whether the device is connected with a negative outcome. Manufacturers are not
required to report deaths or serious adverse events if they decide that the
events were unrelated to the device.12
FDA’s ability to detect potentially unsafe devices is further hampered by the
fact that many post-approval studies required as a condition of the device’s
approval are not conducted or conducted so poorly as to be meaningless. In
2005, the FDA evaluated the quality of post-approval studies. Susan Gardner,
director of the Office of Surveillance and Biometrics at the Centers for Device
and Radiological Health, which oversees approval and safety of devices, told an
FDA advisory panel that 45 of the 127 premarket approvals granted between 1998
and 2000 had orders requiring post-approval surveillance or studies. But more
than one fifth of the studies, she said, couldn’t be evaluated for quality
because there was no record at the FDA showing they had ever even been
conducted.13 FDA has
since automated its records but many companies continue to submit data deemed
“inadequate” by the agency, while other studies remain unreported.
So what does the MAUDE database tell us
about the vagus nerve stimulator? Most MAUDE death reports, which are mainly
written by manufacturers, contain descriptions so brief that no definitive
cause of death can be inferred. Despite the paucity of information available
(narratives are often just a sentence or two in length), the device is often
exonerated. For example, one death associated with the VNS was reported to be
from SUDEP on the basis of a “visual autopsy.” Marcia Angell, a pathologist and
former editor in chief of the New
England Journal of Medicine,
says that without an actual autopsy it
is impossible to determine whether it was SUDEP or some other factor, including
potentially the device itself, that caused the patient’s death, and even then
causality could remain uncertain.
narrative descriptions, however, are clear enough that further investigation of
the device would seem warranted. For example, on 4 December 2008, a patient
with a vagus nerve stimulator was admitted to hospital after an abrupt increase
in seizures and was found to have “severe asystolia” coincident with vagus
nerve stimulation. The device was disabled and the asystole ceased. The
database has more than a dozen reports in which the device’s activity seems to
be associated with asystole.
database also contains reports of what could conceivably be downstream effects
of asystole and bradycardia, such as increased “seizures,” new onset drop
attacks, and fainting—which in turn could be responsible for some instances in
which patients were reported to have died in a fall, by drowning, or in a road
case that ostensibly should have prompted further investigation by the FDA, was
that of 48 year old Dennis Fegan. According to medical records obtained by the BMJ with Mr Fegan’s
permission, he woke up in pain at 2 am on 2 July 2006, only to pass out. After
regaining consciousness, Mr Fegan, who had a 14 year history of partial complex
seizures, passed out several more times. He thought he was having an unusually bad
run of seizures. When an ambulance crew arrived, they witnessed Fegan having a
seizure and administered intravenous diazepam. Once he was at the hospital and
connected to a cardiac monitor, an apparent cause of his seizures emerged; at 3
minute intervals, his heart stopped for 30 seconds—synchronous with the firing
of his vagus nerve stimulator. As soon as the device was disabled, the asystole
ceased. His neurologist, a consulting cardiologist, and the treating emergency
physician concluded that the device was the likely cause of his asystole.
study bias, and failure to report
The FDA cautions that the MAUDE database
“is not intended to be used either to evaluate rates of adverse events or to
compare adverse event occurrence rates across devices.”
14 Its purpose is to allow FDA
analysts and others to pick up “signals” of harm that can trigger further
investigation. Any investigation would need to evaluate the numerator (number
of adverse events) and the denominator (number of exposures), but this
information is routinely absent.
the case of the vagus nerve stimulator the denominator depends not only on the
number of patients implanted with the device but also on how many devices are
still functioning. Cyberonics reports that by 10 March 2010, they had received
registrations for 57 284 patients worldwide implanted with the device, yet it
acknowledges that it is impossible to know how many patients have had their
devices deactivated because it has no way to collect these data. The
combination of possible under-reporting of adverse events (the numerator) and
possible over-reporting of the number of active devices (the denominator) could
mean that the rate of deaths among device users is higher than is apparent. The
more than 900 deaths among relatively young people (most of those with implants
are 15 to 44 years old) 3 did not trigger a request for
further investigation.
what of the post-approval study, known as XE05, ordered by the FDA as a
condition of approval? A spokeswoman for the FDA cited XE05 as part of the
evidence that “supported the long term safety and effectiveness of the device.”
Cyberonics confirmed that only 50 patients were enrolled in the open label
study and deaths were not recorded. When asked how such a small study that
didn’t include mortality data could show the device’s “long term safety,”
Cyberonics replied that “the purpose of that study wasn’t to look at SUDEP or
mortality rates” but to evaluate other long term safety issues.
FDA gave the BMJ
references to five additional post-approval studies as evidence of the device’s
safety. Yet the five studies do not establish that the device wasn’t responsible
for deaths because none of them included mortality data. The largest study
consisted of 4743 patients in the company’s outcome registry. The other studies
evaluated subsets of registry patients. Cyberonics acknowledged that “mortality
was not an endpoint collected as part of the Epilepsy Patient Outcomes
2005, the FDA approved the vagus nerve stimulator for the treatment of
depression, despite the unanimous recommendation against approval by its own
scientists. The FDA experts were concerned, in part, about the device’s safety.
Nicholas Stine, who was then a research associate at Public Citizen, a public
interest group, wrote to the agency, urging that the device should not be
approved for treating depression. He and his coauthor, Peter Lurie, now adviser
to FDA’s assistant commissioner for policy, said that “numerous reports” of
worsening depression, suicides, and sudden deaths during clinical trials of vagus
nerve stimulation “had not been adequately investigated,” and that the
manufacturer “had not demonstrated long term safety of the device.”16 However, Cyberonics told the BMJ: “The FDA concluded
that Cyberonics provided ‘reasonable assurance of safety and effectiveness’ of
VNS therapy for the treatment of depression based on valid scientific evidence.
There is no evidence linking VNS therapy to worsening depression, suicides, or
sudden deaths.”
company has also suggested that the stimulator might have a role in treating
obesity, stroke, traumatic brain injury, and other conditions, and has
previously taken out patents for these potential therapies.17
The gaps in post-approval monitoring of the
vagus nerve stimulator are emblematic of the FDA’s surveillance of all devices.
Many of the problems have relatively easy fixes. Although the MAUDE database is
flawed, it can still serve its purpose if qualitative signals are detected and
trigger better analysis and quantification of a potential safety issue.
Manufacturers could be required to regularly submit denominator data, which
could be facilitated by requiring companies to provide a website link that
patients or their surgeons could use to report whether the device is disabled
or removed. An independent review panel could be appointed to decide whether
adverse outcomes could be excluded from reporting. And, as the FDA has
suggested, mechanisms to limit widespread uptake of new devices could be put in
place so that fewer patients are harmed if it ultimately turns out that newly
approved devices are flawed.
Cite this as: BMJ 2010;341:c4753
·       Competing interests:
JL and SB have completed the Unified Competing Interest form at
(available on request from JL and declare: no support from any organisation for
the submitted work; no financial relationships with any organisations that
might have an interest in the submitted work in the previous three years; no
other relationships or activities that could appear to have influenced the
submitted work.
·       Provenance and peer
review: Commissioned and peer reviewed.
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