J Affect Disord. 2010 Sep;125(1-3):323-9. Epub  2010 Mar 3.

Is successful electroconvulsive therapy related to stimulation of the vagal system?

Bär KJ, Ebert A, Boettger MK, Merz S, Kiehntopf M, Jochum T, Juckel G, Agelink MW.

Department of Psychiatry and Psychotherapy, University Hospital, Jena, Germany. Karl-Juergen.Baer@med.uni-jena.de

Is successful electroconvulsive therapy related to stimulation of the vagal system?

Bär KJ, Ebert A, Boettger MK, Merz S, Kiehntopf M, Jochum T, Juckel G, Agelink MW.

Department of Psychiatry and Psychotherapy, University Hospital, Jena, Germany. Karl-Juergen.Baer@med.uni-jena.de

Abstract

BACKGROUND: Electroconvulsive therapy (ECT) has been shown to exhibit strong beneficial effects in the treatment of major depressive disorder (MDD). While the exact underlying mechanisms are under debate, a role for the sympathetic response upon ECT has been suggested. When assessing patients with MDD for autonomic function, however, a loss of vagal function is prominent.

OBJECTIVE: Here, we aimed to assess the immediate effects of ECT on vagal activity and to test the hypothesis that surrogates of the latter correlate with therapeutic outcome.

METHODS: Twenty patients with MDD who underwent ECT treatment were assessed regarding their vagal function using electrophysiological measures and determination of pancreatic polypeptide (PP), which is known to be released upon vagal stimulation. Parameters were correlated to the improvement of disease severity upon ECT treatment.

RESULTS: Patients showed a significant increase of PP shortly after ECT which correlated with clinical improvement. Furthermore, the described association with the sympathetic phase after ECT could be verified.

CONCLUSION: ECT increases vagal activity which might be associated with the beneficial effect seen following this treatment. PP elevation after administration of ECT might be a useful parameter to estimate the degree of such vagal stimulation after treatment.

PMID: 20202688 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/20202688

Is Alternative Medicine Risky for Kids?

In keeping with my advocacy and endorsement of patient
and/or support person education I want to share this important article with you
the readers.

Warmly,

Herb

vnsdepression@gmail.com

http://www.vnstherapy-herb.blogspot.com/

  

Is Alternative Medicine Risky for Kids?

Researchers Say Parents Need to Be Aware of Potential
Side Effects of Alternative Medicine

By Denise Mann

WebMD Health News

Reviewed
by Laura J. Martin, MD

           

Dec. 23, 2010 - The growing numbers of parents who turn toward complementary and alternative medicine (CAM) to treat their children’s illnesses may often assume that “natural” means safe and harmless.

But new research in the Archives of Childhood Diseases suggests that many complementary and alternative remedies can have significant -- even fatal -- side effects.

Complementary and alternative medicine includes vitamins, herbs, and special diets.

Alissa Lim, MD, a pediatrician at the Royal Children’s Hospital in Melbourne, Australia,
and colleagues tracked and analyzed all CAM-related adverse events reported to
the Australian Paediatric Surveillance Units from January 2001 through December
2003.

There were 39 reports of such events, including four deaths that occurred among children
age from birth to 16 years. The greatest risks were seen among infants who were
put on restrictive diets and children with chronic illnesses who were treated
with complementary and alternative medicine (CAM) instead of conventional
medicine.  For example, a child with epilepsy died after being
treated with alternative therapies instead of anticonvulsants, the study
showed.

“Parents should be aware that, like any other treatments and medicines, adverse effects
can be associated with CAM use,” she tells WebMD in an email. “They should talk
with their doctor before changing prescribed medications or
restricting their child's fluid or diet.”

According to Lim, “the take-home message for families is to be aware of potential side
effects from the use of CAM [and] weigh up the benefits and risks of any
treatment they use for their children."

Second Opinion

Lawrence Rosen, MD, a pediatrician at the Whole Child Center in Oradell, N.J., and
chairman of the American Academy of Pediatrics Section on Complementary and
Integrative Medicine, says that the types of complementary and alternative
medicine used vary from country to country, as to how and when such therapies
are used.

Rosen does not think that the new findings apply to the U.S. “Most studies in the U.S.
show that the use of these therapies is done in complement to conventional
medications, not as an alternative,” he says. Restrictive diets in infants such
as those cited in the new report are rarely used here, he says.

What’s more, many of the adverse effects seen in the new report occurred when these
therapies were used in lieu of conventional, proven treatments.

“If you have a child with a chronic illness or a complex illness, do not stop conventional
therapy to use alternative without discussing it with your physician,” he says.

“Talk to your doctor about everything you give your children,” he says. “Are there going
to be adverse events? Yes. Do we need to do a better job monitoring them? Yes.”

Lim agrees that such surveillance is important to get a better handle on the risks
associated with these therapies.

Communication About CAM Is Key

John Dorsey, MD, an attending pediatrician at Beaumont Hospital in Royal Oak, Michigan,
urges parents to stay in touch with their child’s pediatrician even if they
choose to seek care from an alternative medicine provider.

“There could be hazards to what you are doing,” he says. “Collaboration is essential because
people may do this on their own and these therapies should be supervised by a
conventional doctor.”

“It is absolutely vital that parents and health care providers communicate with one
another about the use of CAM,” says Adam Rindfleisch, MD, an assistant
professor at the University of Wisconsin in Madison and director of the
Academic Integrative Medicine fellowship program there.

“Many parents don't report its use, because they feel either their provider won't be
familiar with the forms of treatment they are using, or because they fear
criticism,” he says in an email.

But “open communication and trust can go a long way in enhancing the safety of care, be
it with CAM approaches, medications, surgery, or any intervention,” he says.

More research is needed, he says. “The body of CAM research is increasing, but
very little of this has to do with CAM in children,” he says. “Every treatment
-- CAM or otherwise -- can have its dangers in some circumstances.”

“To decide how dangerous it is, we have to ask how dangerous other approaches are as
well,” he says. “Medications are not without their side effects, and there is a
reason that many parents hesitate when it comes to giving them to
children.”

Safe Supplement Use in Kids

Duffy MacKay, ND, vice president of scientific and regulatory affairs at the Council
for Responsible Nutrition, a trade association that represents the supplement
industry, urges caution in interpreting the new findings, at least as they
pertain to dietary supplement use in kids.

“Many supplements are safe when they are used as directed and under the advice of a professional
such as a pediatrician or integrative medicine provider,” he says. In terms of
avoiding overdose, “treat all home health care products and cleaning products
the same way -- lock ‘em up and keep them up high.”

http://children.webmd.com/news/20101223/is-alternative-medicine-risky-for-kids 

DEBATE:
Should patients with epilepsy who are depressed be routinely treated with
antidepressant medication (ADM) or vagus nerve stimulation (VNS)? YES for VNS.
SEE also ADM POSITION and COMMENTARY Epilepsy: Psychological Aspects

October 29, 2010 13:10

http://www.informed-scientist.org/presentation/debate-should-patients-with-epilepsy-who-are-depressed-be-routinely-treated-with-antidepressant-medication-adm-or-vagus-nerve-stimulation-vns-yes-for-vns-see-also-adm-position-and-commentary 

DEBATE:
Should patients with epilepsy who are depressed be routinely treated with
antidepressant medication or vagus nerve stimulation (VNS)? YES for
ANTIDEPRESSANTS. SEE also VNS POSITION and COMMENTARY Epilepsy: Psychological
Aspects

October 29, 2010 14:10

http://www.informed-scientist.org/presentation/debate-should-patients-with-epilepsy-who-are-depressed-be-routinely-treated-with-antidepressant-medication-or-vagus-nerve-stimulation-vns-yes-for-antidepressants-see-also-vns-position-and-commentary

COMMENTARY:
Should patients with epilepsy who are depressed be routinely treated with
antidepressant medication (ADM) or vagus nerve stimulation (VNS)? SEE also ADM
and VNS POSITION Epilepsy: Psychological Aspects

October 29, 2010 15:10

http://www.informed-scientist.org/presentation/commentary-should-patients-with-epilepsy-who-are-depressed-be-routinely-treated-with-antidepressant-medication-adm-or-vagus-nerve-stimulation-vns-see-also-adm-and-vns-position

12-13-2010 VNS Therapy Joyce's 11th Year.

http://www.youtube.com/v/K7R-jpDS4WY?

Neuro Endocrinol Lett. 2010 Nov 21;31(5). [Epub ahead of print]

The role of the vagus nerve in depression.

Ondicova K, Pecenák J, Mravec B.

Institute of Pathophysiology, Faculty of Medicine, Comenius University, Slovakia. boris.mravec@fmed.uniba.sk.

Abstract

The etiopathogenesis of depression is a highly complex process characterized by several neurobiological alterations including decreased monoamine neurotransmission in the brain, dysregulated hypothalamic-pituitary-adrenal axis activity, decreased neuronal plasticity, and chronic inflammation in the brain and peripheral tissues. Experimental and clinical studies indicate that the vagus nerve may influence these processes. The importance of the vagus nerve in the etiopathogenesis of depression is further supported by its involvement in the induction of sickness behavior, as well as by clinical studies confirming a beneficial effect of vagus nerve stimulation in depressed patients. The aim of this article is to describe current knowledge of aferent and efferent vagal pathways role in the development and progression of depression.

PMID: 21173739 [PubMed - as supplied by publisher

http://www.ncbi.nlm.nih.gov/pubmed/21173739

COST-EFFECTIVENESS OF CYBERONICS’ VNS THERAPY®SYSTEM FOR EPILEPSY REINFORCED BY 1,600-PATIENT EMORY UNIVERSITY SCHOOL OF MEDICINE STUDY

For Release Tuesday, December 21, 2010; 9:00 AM ET

 COST-EFFECTIVENESS OF CYBERONICS’ VNS THERAPY^®SYSTEM FOR EPILEPSY REINFORCED BY
1,600-PATIENT EMORY UNIVERSITY SCHOOL OF MEDICINE STUDY

 

HOUSTON, Texas, December 21, 2010 -- Cyberonics, Inc. (NASDAQ:CYBX) announced today that the VNS Therapy System, the only FDA-approved implantable medical device for the treatment of refractory epilepsy, was featured in 22 poster presentations and in the Plenary II session on neurostimulation at the annual American Epilepsy Society Meeting that took place recently in San Antonio, Texas.
Of particular significance at the meeting, Sandra Helmers, M.D., Associate
Professor of Neurology at the Emory School of Medicine, presented the results
of a study entitled, “Characteristics and Clinical and Economic Outcomes in
MEDICAID Patients Receiving Vagus Nerve Stimulation Therapy for the Treatment
of Refractory Epilepsy.”  Dr. Helmers and colleagues at Emory University
School of Medicine and The Analysis Group, an economic consultant, analyzed
data from five Medicaid state claims databases, including Florida, Iowa,
Kansas, Missouri, and New Jersey, to evaluate trends over time in
epilepsy-related health problems, healthcare utilization and healthcare costs.
The studyresults confirmed that the use of vagus nerve stimulation (VNS) therapy in
patients with refractory epilepsy is associated with:

• Lower occurrence of epilepsy-related co-morbidities.  Patients experienced fewer injuries and other health issues after being implanted with the VNS Therapy System, compared to the period before implantation.
• Lower healthcare utilization. All-cause hospitalizations and emergency room visits significantly     decreased over time after implantation with the VNS Therapy System, compared to the six months prior to implantation.
• Significant long-term cost savings.  With a reduction in healthcare utilization and co-morbidities as a result of VNS therapy, there are significant net total healthcare cost savings beginning 18 months after implantation.

These results confirm numerous prior studies demonstrating significant reductions in
both emergency room visits and inpatient admissions.  “This study again
shows the long-term clinical benefits of VNS.  Additionally, it addresses
an increasingly relevant aspect of treatment options –  cost effectiveness
over the long term,”  noted Dr. Helmers.

“This Emory University study reaffirms the safety, efficacy, cost effectiveness, and
quality-of-life benefits of the VNS Therapy System,” said Dan Moore, President
and Chief Executive Officer of Cyberonics. “Worldwide, more than 60,000
patients with epilepsy have received VNS therapy, and these patients are
consistently opting to continue treatment, which is evidenced by an initial
re-implant rate that exceeds 70 percent.  These study findings further
establish VNS therapy as a beneficial option for patients with medically
refractory epilepsy who are not candidates for resective surgery, or who have
failed resective surgery.” 

About Cyberonics, Inc. and the VNS Therapy^®System

Cyberonics, Inc. (NASDAQ:CYBX) is a medical technology company with core expertise in
neuromodulation.  The company developed and markets the VNS Therapy
System, which is FDA-approved for the treatment of refractory epilepsy and
treatment-resistant depression.  The VNS Therapy System uses a surgically
implanted medical device that delivers electrical pulsed signals to the vagus
nerve.  Cyberonics markets the VNS Therapy System in selected markets
worldwide.
Additional information on Cyberonics and VNS therapy is available at www.cyberonics.com.
Contact Information
Greg Browne, CFO
Cyberonics, Inc.
100 Cyberonics Blvd.
Houston, TX 77058
Main:  (281) 228-7262
Fax:  (281) 218-9332
ir@cyberonics.com

J Chem Neuroanat. 2010 Dec 15. [Epub ahead of print]

The chemical neuroanatomy of vagus nerve stimulation.

Ruffoli R, Giorgi FS, Pizzanelli C, Murri L, Paparelli A, Fornai F.

Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56100 Pisa, Italy.

Abstract

In this short overview a reappraisal of the anatomical connections of vagal afferents is reported. The manuscript moves from classic neuroanatomy to review details of vagus nerve anatomy which are now becoming more and more relevant for clinical outcomes (i.e. the therapeutic use of vagus nerve stimulation). In drawing such an updated odology of central vagal connections the anatomical basis subserving the neurochemical effects of vagal stimulation are addressed. In detail, apart from the thalamic projection of central vagal afferents, the monoaminergic systems appear to play a pivotal role. Stemming from the chemical neuroanatomy of monoamines such as serotonin and norepinephrine the widespread effects of vagal stimulation on cerebral cortical activity are better elucidated. This refers both to the antiepileptic effects and most recently to the beneficial effects of vagal stimulation in mood and cognitive disorders.

PMID: 21167932 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21167932

Epilepsy Behav. 2010 Dec 15. [Epub ahead of print]

Mania following vagus nerve stimulation: A case report and review of the literature.

Gerson R, Murray E, Price B, Frankel M, Douglass LM, Cunningham M.

Department of Child and Adolescent Psychiatry, New York University, New York, NY, USA.

Abstract

Vagus nerve stimulation (VNS) is an increasingly used therapy for patients with treatment-refractory epilepsy and depression. Hypomanic and manic symptoms are a rare but recognized adverse effect of VNS treatment. Here we describe a case in which VNS treatment in a patient with epilepsy and unipolar depression was associated with the rapid development of manic symptoms. The patient's manic symptoms resolved with temporary discontinuation of the VNS current, and the patient was eventually able to resume VNS treatment with good effect and without further manic symptoms. Mania is a rare but serious side effect of VNS; however, in this case and in the majority of reported cases of VNS-associated mania, symptoms resolve and VNS can be safely administered.

PMID: 21167787 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21167787

Heart Fail Rev. 2010 Dec 17. [Epub ahead of print]

Vagus nerve stimulation: from pre-clinical to clinical application: challenges and future directions.

De Ferrari GM, Schwartz PJ.

Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100, Pavia, Italy, g.deferrari@smatteo.pv.it.

Abstract

Vagus nerve stimulation was performed experimentally for the first time more than 150 years ago. In the 1980s and 1990s, vagus nerve stimulation was shown, both in the anesthetized and in the conscious animal, to exert marked antiarrhythmic effects, particularly during acute myocardial ischemia. There is a strong rationale for a beneficial effect of augmented vagal activity in the setting of chronic heart failure. Studies in experimental models of heart failure showed that chronic vagus nerve stimulation exerts beneficial effects on left ventricular function and on survival. Vagus nerve stimulation is approved in man for refractory epilepsy and depression. The first-in-man study performed in 32 patients with chronic heart failure suggests that vagus nerve stimulation was safe and well tolerated. Six months of open-label treatment was associated with significant improvements (P < 0.001) in NYHA class, quality of life, 6-min walk test, LV ejection fraction (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. Mechanisms of action may include the following: heart rate, anti-adrenergic, anti-apoptotic, and anti-inflammatory effects as well as an increase in nitric oxide. Controlled clinical trials will start soon to assess whether vagus nerve stimulation can indeed represent a new non-pharmacological approach for the treatment of symptomatic heart failure.

PMID: 21165697 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21165697

Pharmacopsychiatry. 2010 Dec 14. [Epub ahead of print]

Changes in Gustatory Perceptions of Patients with Major Depression Treated with Vagus Nerve Stimulation (VNS).

Sperling W, Biermann T, Spannenberger R, Clepce M, Padberg F, Reulbach U, Kornhuber J, Thuerauf N.

Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Erlangen, Germany.

Abstract

BACKGROUND: Olfactory and gustatory functions were investigated before and during vagus nerve stimulation (VNS) in a group of 9 patients with therapy-resistant depression, implanted with a VNS system.

METHODS: Gustation and olfaction were tested using standard sniffing tests. Subjects participated in 2 sessions with the vagal stimulator switched on and off, respectively.

RESULTS: Under conditions of stimulation of the VNS, there were statistically significant differences of the threshold of perception, with an intensification of the taste "sweet" (Z=-2.0; p=0.048) and "bitter" (Z=-2.5; p=0.011) compared to the "off-mode". A statistical trend (Z=-1.7; p=0.098) for increased intensity of the taste "salty" was observed, however, these results would supposedly disappear after correction for multiple testing presumably due to the large number of variables and the small sample size. There were no statistically relevant differences concerning olfactory perception.

CONCLUSIONS: The changes of gustatory perception under conditions of vagal nerve stimulation observed in this study show another important central nervous effect of vagal stimulation on the limbic system that might be of importance in the elucidation of mechanisms of action of VNS especially on refractory depression.

© Georg Thieme Verlag KG Stuttgart · New York.

 

PMID: 21157695 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21157695

Neurostimulation Poised to Take On Tough Seizures

Neurostimulation Poised to Take On Tough Seizures

By: DIANA MAHONEY,
Internal Medicine News Digital Network

12/15/10 

SAN ANTONIO – It’s still too soon to know whether
neurostimulation will be the therapeutic advance that treatment-refractory
epilepsy patients have been waiting for, but the possibility that it might be
has the epilepsy community buzzing.

For approximately 30% of epilepsy patients, seizures cannot
be controlled with antiepileptic drugs or surgery. New long-term safety and
efficacy data for vagus nerve simulation (VNS) and the results of recent
pivotal trials of two approaches to direct brain stimulation offer beacons of
hope to these patients, Dr. Gregory K. Bergey said in a plenary session on
neurostimulation at the annual meeting of the American Epilepsy Society.

"One of the frustrating things for those of us treating
patients with epilepsy has been the fact that, although a number of new
antiepileptic drugs have been developed over the past 10-15 years and most are
better tolerated and have better pharmacokinetic profiles than earlier drugs,
the number of patients with seizures that don’t respond to medical therapy has
not been significantly reduced," said Dr. Bergey, director of the Johns
Hopkins Epilepsy Center, Baltimore.

"So we’re stepping back and saying, ‘Is there some other
way we can treat these patients?’ That has been the impetus for looking at
neurostimulation, which has been around for well over a decade, and what we’re
seeing is exciting."

Although the 40%-50% response rates observed in direct brain
stimulation trials do not appear to be overwhelming, "this is just the
beginning," Dr. Bergey stressed in an interview. "As opposed to a
drug trial, where you go up to a certain dose and it either works or it doesn’t
work, in the case of neurostimulation we don’t know the optimal stimulus parameters,
and I think that’s what you’re going to begin to see over the next several
years," he said.

"There’s going to be a lot of investigation into
neurostimulation of the brain structures to try to figure out who are the best
candidates and what the best stimulus parameters are. It’s easy to say we’re
stimulating the brain, but do we stimulate 100 times per second, 50 times per
second, 25 times per second, and what should the stimulus intensities be?"

Vagus Nerve Stimulation. Currently, Cyberonics’ VNS
Therapy System is the only Food and Drug Administration–approved form of
neurostimulation for the treatment of epilepsy. The technology was approved in
1997 for the treatment of medically refractory partial-onset seizures in
patients 12 years or older. It consists of a stimulator that sends electric
impulses to the left vagus nerve in the neck via a lead wire that is implanted
under the skin. Studies since 1997 have indicated efficacy in generalized
seizure disorders and children as well, according to Dr. Elinor Ben-Menachem,
professor of neurology and epilepsy at the Institute for Clinical Neurosciences
and Physiology, Göteborg (Sweden) University.

To date, more than 60,000 patients worldwide have been
treated with VNS, and studies suggest that approximately 50% of patients who
undergo the procedure experience a long-term decrease in mean seizure frequency
of 50% or more. But fewer than 10% become seizure-free, Dr. Ben-Menachem said
during the neurostimulation plenary presentation.

"[VNS] has a long history now, and what we know is that
it does not cure or affect seizures immediately. We actually don’t notice a
change in seizure activity until about 18 months or 2 years after
starting."

For example, a recent long-term follow-up study of VNS
patients in the Czech Republic showed that at 1 year post implantation, 44.4%
of patients achieved more than 50% seizure reduction. The percentage of
patients who reached that level of seizure reduction then increased from 58.7%
at 2 years after implant to 64.4% at 5 years. At the 5-year mark, 15.5% of the
patients had achieved a minimum 90% seizure reduction, and 5.5% were seizure
free (Seizure
2009;18: 269-74).

The mechanism of action of VNS remains uncertain, but a
number of possibilities have been suggested, including arousal of the reticular
formation; stimulation of locus coeruleus and noradrenaline pathways; changes
in a neurotransmitter, amino acid, or neuropeptide; or indirect thalamus stimulation,
according to Dr. Ben-Menachem. "It’s also possible that there is long-term
learning through synaptic structural changes," she said. "The more I
work with this, the more I think it is a learning paradigm. It’s like learning
to play the piano. You can’t just sit down and play, you have to redo and redo
until the brain is trained."

In a recent study of 144 patients who had undergone VNS
implantation, 10 patients were seizure free for more than 1 year post
implantation, 89 patients experienced seizure improvement, and no changes were
observed in 45 patients. "Stepwise multivariate analysis showed that
unilateral interictal epileptiform discharges [IEDs], cortical dysgenesis, and
younger age at implantation were independent predictors of seizure freedom in
the long-term follow-up," they wrote (Seizure
2010;19: 264-8).

Most of the adverse events associated with VNS therapy, such
as hoarseness and cough, tend to be mild and are stimulation related, Dr.
Ben-Menachem explained. "Typically, they occur only during stimulation and
they generally diminish over time on their own, or they may be diminished or
eliminated by adjustment of the parameter settings."

Programmed Deep Brain Stimulation. The programmed deep
brain stimulation device manufactured by Medtronic, one of the two emerging
neurostimulation treatments for intractable epilepsy that is under FDA review,
demonstrated efficacy in a pivotal trial that involved stimulation in the anterior
thalamus. This site has connections with the temporal lobe, which is a common
site for the origin of partial seizures, Dr. Bergey explained.

The device, which is already approved for Parkinson’s
disease, comprises four deep brain electrodes that are implanted bilaterally
into the target structure with a pulse generator placed below the clavicle. It
delivers stimuli at scheduled intervals "to hopefully modulate and reduce
the number of seizures the patient is having," he said.

In the Medtronic-funded Stimulation of the Anterior Nucleus
of the Thalamus for Epilepsy (SANTE) study, 110 patients with medically
refractory partial seizures were implanted with the device and randomized to
intermittent bilateral stimulation (1 minute on/5 minutes off) or no-stimulation
for a 3-month blinded stage, followed by unblinded stimulation for all of the
patients (Epilepsia
2010;51:899-908). At the end of the blinded period, patients who received
stimulation experienced a median seizure reduction of 40.4%, compared with
14.5% of patients with the stimulator off, reported study coauthor Dr. Vincenta
Salanova of Indiana University, Indianapolis.

In the open-label follow-up, 56% of all the patients had
greater than 50% seizure reduction at 2 years, and there was a median 68%
reduction in seizures among the 42 patients for whom 3-year data were
available. Over the course of the study, "14 [12.7%] of the patients were
seizure free for at least 6 months," she reported in a press briefing at
the meeting.

Although the mechanism of action is not fully understood, Dr.
Salanova said that "the thalamus has connections between the limbic system
and the frontal lobe, so it’s possible that high-frequency stimulation may
prevent the propagation of seizures."

Five deaths occurred in the study population, but none were
attributed to lead implantation or stimulation, Dr. Salanova stressed. There
were no symptomatic or clinically significant hemorrhages associated with implantation,
but 4.5% of patients experienced asymptomatic intracranial hemorrhages –
detected via neuroimaging – that were not clinically significant. Additionally,
two patients experienced seizures that were linked to the stimulus, which were
resolved by lowering the voltage.

Direct stimulation of the hippocampus may also offer seizure
relief in some patients, according to Dr. Richard Wennberg of the University of
Toronto. "The hippocampus is clinically recognized as a region of high
epileptogenicity, and animal studies have demonstrated antiepileptic properties
of electrical fields applied to the region," he said in a presentation
during the neurostimulation plenary session, noting that the goal of direct
hippocampal stimulation is to prevent seizure generation and spread from the
temporal limbic region.

To date, the experimental procedure has been evaluated in
small series and has shown some efficacy, Dr. Wennberg said. For example, in a
recent study designed to assess the effect of continuous electrical stimulation
of the hippocampus bilaterally, two patients with seizures from both mesial
temporal lobes who were not candidates for surgical resection were implanted
bilaterally with two four-contact electrodes along the hippocampal axis. After
randomization to either stimulation on or off conditions for 3-month intervals,
seizure frequency decreased by 33% during stimulation, and stayed and remained
lower by 25% for the 3 months after stimulation was turned off, after which the
seizure frequency returned to baseline, the authors reported. Although seizure
frequency was reduced both during and for a period after bilateral hippocampal
stimulation, "the overall impact in this study is not as robust as has
been previously reported," the authors stated (Epilepsia
2010;51:304-7).

Responsive Neurostimulation. Another direct brain
neurostimulating technology under FDA review is the Responsive Neurostimulator System
(RNS) by NeuroPace. "The system detects and aborts [functional mapping]
induced afterdischarges in the brain to prevent seizures," explained Dr.
Lawrence J. Hirsch of Columbia University in New York. "It is designed to
respond within seconds to abnormal activity in the brain by delivering a series
of up to five stimuli to terminate the abnormal discharge."

The RNS device is implanted in a recess of the skull, and is
connected to up to two four-contact electrodes that are placed within the brain
or on the brain surface, depending on where the seizures begin. The device
collects and stores seizure information, which the patient subsequently
downloads to a laptop using a wand. Physicians can access the stored
electrocorticograms via a secure Web page through which they can adjust
detection and stimulation parameters specific to the individual patient, Dr.
Hirsch said during the neurostimulation plenary session.

In the pivotal clinical trial of the RNS system, 191 patients
with medically intractable, partial-onset seizures localized to one or two foci
received the cranial implant. During a blinded period, patients received active
or sham stimulation, followed by an open-label phase in which all the patients
received active stimulation. During the entire blinded evaluation period,
active stimulation was associated with a mean 37.9% reduction in seizure
frequency, compared with a mean 17% reduction during the sham activation, Dr.
Hirsch said.

"In the final month of the blinded period – month 4 to 5
– the respective reduction in seizure frequency was 42% and 9%." During
the last 3 months of the open-label period, "47% of the patients had a
greater than 50% seizure reduction," he said. "And at 4 years post
implant, more than 50% of the patients had at least a 50% reduction in seizure
frequency."

A subset analysis showed that neither prior surgery nor the
number of seizure foci had an effect on treatment response, Dr. Hirsch noted.
"It also showed that [RNS] is possibly more effective with medial temporal
onset."

With respect to adverse events, implant site infections were
reported in 5% of the patients, and led to explantation in 2%. The combined
rate of status epilepticus reported in all trials of the device (256 patients)
was 3.5%, and included episodes occurring between 5 months and 5 years post
implant. Intracranial hemorrhage was reported in 4% of the patients, and
included only one patient with neurological sequelae, which was chronic
headache, he said.

The chronic, intracranial EEG recordings provided by the RNS
technology have other potentially valuable uses, including seizure
prediction/warning; seizure awareness and counting as a way to assess treatment
efficacy; identification of circadian, catamenial, and other ictal and
interictal patterns; and the lateralization of bitemporal seizures, Dr. Hirsch
said.

Dr. Bergey disclosed financial relationships with Pfizer,
UCB, and Eli Lilly. Dr. Ben-Menachem disclosed financial relationships with
UCB, Eisai, Janssen, Cilag, Cyberonics, Lundbeck, and Sunovion. Dr. Wennberg
disclosed a financial relationship with Medtronic. Dr. Hirsch reported having
no financial disclosures.

Medtronic's DBS system (top left) stimulates the anterior
nucleus of the thalamus, whereas NeuroPace's RNS device (bottom left) responds
to abnormal activity in targeted areas and Cyberonics' VNS Therapy System
(right) periodically stimulates the left vagus nerve. (Photo Credit: top left:
(c) Medtronic Inc., bottom left: (c) NeuroPace Inc., right: (c) Cyberonics
Inc.)

* CORRECTION, 12/16/2010: The original version of this
article misstated the action of the Responsive Neurostimulator System (RNS) by
NeuroPace. The system detects and aborts abnormal discharges in the brain. Also,
the programmed deep brain stimulation device manufactured by Medtronic contains
one deep brain electrode on each side, not four. This version has been
updated.

http://www.internalmedicinenews.com/news/neurology/single-article/neurostimulation-poised-to-take-on-tough-seizures/17d1537114.html

Med Hypotheses. 2010 Dec 6. [Epub ahead of print]

Vagus nerve stimulation as a strategy to prevent and manage metabolic syndrome.

Das UN.

School of Biotechnology, Jawaharlal Nehru Technological University, Kakinada 533 003, India; UND Life Sciences, 13800 Fairhill Road, #321, Shaker Heights, OH 44120, USA.

Abstract

An increase in pro-inflammatory cytokines, decrease in endothelial nitric oxide (eNO) and adiponectin levels and an alteration in hypothalamic peptides and gastrointestinal hormones such as incretins and cholecystokinin that regulate satiety, hunger, and food intake occur in metabolic syndrome. Thus, metabolic syndrome is a low-grade systemic inflammatory condition and could be due to inappropriate cross-talk between the peripheral tissues and the hypothalamic centers implying that methods designed to restore these two abnormalities to normal could be of significant benefit in metabolic syndrome. Vagus nerve stimulation has been shown to suppress inflammation and acetylcholine, the principal vagal neurotransmitter, modulates the actions of several hypothalamic peptides and incretins and cholecystokinin. Based on these evidences, it is proposed that vagus nerve stimulation could be of significant benefit in the management of the metabolic syndrome.

PMID: 21144670 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21144670

Epilepsy Behav. 2010 Dec 6. [Epub ahead of print]

Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: Long-term outcomes and predictors of response.

Elliott RE, Morsi A, Kalhorn SP, Marcus J, Sellin J, Kang M, Silverberg A, Rivera E, Geller E, Carlson C, Devinsky O, Doyle WK.

Department of Neurosurgery, New York University Langone Medical Center, New York, NY, USA.

Abstract

OBJECTIVE: The goal of this study was to assess the efficacy and safety of vagus nerve stimulation in a consecutive series of adults and children with treatment-resistant epilepsy (TRE).

METHODS: In this retrospective review of a prospectively created database of 436 consecutive patients who underwent vagus nerve stimulator implantation for TRE between November 1997 and April 2008, there were 220 (50.5%) females and 216 (49.5%) males ranging in age from 1 to 76years at the time of implantation (mean: 29.0±16.5). Thirty-three patients (7.6%) in the primary implantation group had inadequate follow-up (<3months from implantation) and three patients had early device removal because of infection and were excluded from seizure control outcome analyses.

RESULTS: Duration of vagus nerve stimulation treatment varied from 10days to 11years (mean: 4.94years). Mean seizure frequency significantly improved following implantation (mean reduction: 55.8%, P<0.0001). Seizure control ≥90% was achieved in 90 patients (22.5%), ≥75% seizure control in 162 patients (40.5%), ≥50% improvement in 255 patients (63.75%), and <50% improvement in 145 patients (36.25%). Permanent injury to the vagus nerve occurred in 2.8% of patients.

CONCLUSION: Vagus nerve stimulation is a safe and effective palliative treatment option for focal and generalized TRE in adults and children. When used in conjunction with a multidisciplinary and multimodality treatment regimen including aggressive antiepileptic drug regimens and epilepsy surgery when appropriate, more than 60% of patients with TRE experienced at least a 50% reduction in seizure burden. Good results were seen in patients with non-U.S. Food and Drug Administration-approved indications. Prospective, randomized trials are needed for patients with generalized epilepsies and for younger children to potentially expand the number of patients who may benefit from this palliative treatment.

http://www.ncbi.nlm.nih.gov/pubmed/21144802

Research Nerve Stimulation Therapy May Improve Outcomes and Reduce Healthcare Costs...

From HealthNewsDigest.com

 

Research Nerve Stimulation Therapy May Improve Outcomes and Reduce Healthcare Costs for Epilepsy

By

Dec 6, 2010 - 3:37:16 PM

(HealthNewsDigest.com) - ATLANTA – The use of nerve stimulation therapy
in patients with refractory epilepsy is associated with a lower occurrence of
epilepsy-related health problems and a lower use of healthcare resources,
according to a new study from the Emory University School of Medicine.
Refractory epilepsy is the occurrence of seizures that are not controlled with
medication alone.

Findings of the study were presented Dec. 5 at the American Epilepsy Society
Meeting in San Antonio, Texas. Sandra L. Helmers, MD, MPH, the R. Edward
Faught, MD, professor of neurology at Emory School of Medicine, conducted the
retrospective study of 1,655 patients treated with vagus nerve stimulation
(VNS) therapy from 1997 to 2009.

Using data from five Medicaid state claims databases, including Florida, Iowa,
Kansas, Missouri and New Jersey, the study is the first to review the long-term
medical and economic impact of VNS therapy for treatment of refractory epilepsy
in a clinical setting.

VNS therapy is an adjunctive therapy to antiepileptic drugs in patients 12
years or older and the only FDA-approved implantable medical device for the
treatment of refractory epilepsy. An implanted stimulator sends electric
impulses to the left vagus nerve in the neck via a lead wire implanted under
the skin.

“Poorly controlled seizures are an important risk factor for mortality in
people with epilepsy and put patients at higher risk of physical injuries such
as fractures or head injuries, as well as morbidities including depression and
anxiety,” says Helmers.

“The results of this study demonstrate that with VNS therapy for patients with
refractory epilepsy there may be improved clinical outcomes for patients that
subsequently result in significant savings for the healthcare system.”

The study evaluated epilepsy-related health problems such as frequency of
fractures and head trauma related to seizures. It also reviewed patient data
for healthcare utilization including seizure-related and non-seizure-related
emergency room visits, outpatient services, neurology services, and factors
such as length of hospital stay and prescription drug claims.

Study results confirmed that use of VNS therapy in patients with refractory
epilepsy is associated with:

A lower occurrence of epilepsy-related co-morbidities. Patients experienced
fewer injuries and other health issues after being implanted with VNS therapy,
compared to the period before VNS implantation.

A lower utilization of healthcare. All-cause hospitalizations and emergency
room visits significantly decreased over time after implantation with VNS
therapy compared to the six months prior to implantation.

Significant longer term cost savings. With a reduction in healthcare
utilization and co-morbidities as a result of VNS therapy, there is a
significant net total healthcare cost savings beginning at 1.5 years after
implantation. The study found that average quarterly total healthcare costs
were reduced approximately 28 percent, from an average of $19,945 pre-VNS
implantation to $14,316 at 1.5 years after implantation.

“While there are initial costs to VNS therapy including the surgical procedure
and the cost of the device, our study finds that the cost savings of VNS are
usually seen in about 18 months,” says Helmers. “By reducing overall healthcare
utilization such as emergency room visits, VNS therapy becomes a reasonable
option for patients with medically refractory epilepsy.”

http://www.healthnewsdigest.com/news/Research_270/Nerve_Stimulation_Therapy_May_Improve_Outcomes_and_Reduce_Healthcare_Costs_for_Epilepsy.shtml

 

Epilepsy Res. 2010 Dec 1. [Epub ahead of print]

Magnetoencephalography in epilepsy patients carrying a vagus nerve stimulator.

Carrette E, De Tiège X, De Beeck MO, De Herdt V, Meurs A, Legros B, Raedt R, Deblaere K, Van Roost D, Bourguignon M, Goldman S, Boon P, Van Bogaert P, Vonck K.

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

Abstract

Due to technical constraints, magnetoencephalography (MEG) is challenging in vagus nerve stimulation (VNS) patients. This study evaluates (1) the feasibility of MEG in VNS patients and (2) the added value of MEG in their presurgical evaluation (PE). Ten VNS patients were studied by MEG using the spatiotemporal signal space separation (tSSS) method. Equivalent current dipoles (ECD) were classified "clustered"/"scattered". It was evaluated whether MEG (1) confirmed localisation of the hypothesized epileptogenic zone (HEZ), (2) improved delineation of the HEZ, or (3) identified 1 out of multiple HEZs. Finally it was evaluated whether adding MEG to the PE improved patient management by changing or supporting the hypothesis. In 7/10 patients, tSSS allowed to obtain interpretable MEG data, with interictal epileptiform discharges in 6/7. ECD clustered within 1 lobe in 4/6; confirming the localisation of the HEZ in 2/4 and improving delineation of the HEZ in 2/4. When ECD clustered within 2 lobes (1/6) or were scattered (1/6), MEG could not identify 1 out of multiple HEZs. In 2 patients, MEG changed management to invasive video-EEG monitoring (IVEM) and resective surgery (RS). In 4 patients, MEG further supported the management; IVEM in 2/4 and unsuitability for RS in 2/4. So far IVEM, performed in 2, resulted into RS. This study demonstrates the feasibility of MEG in VNS patients. MEG changed management in 20% and further supported the proposed management in 40% illustrating the clinical value of MEG in the PE of VNS patients.

PMID: 21129918 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21130042

Epilepsy Behav. 2010 Dec 1. [Epub ahead of print]

Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis.

Grujic J, Bien CG, Pollo C, Rossetti AO.

Service de Neurologie, Département de Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.

Abstract

We describe a patient with adult-onset Rasmussen's encephalitis (RE) responsive to vagus nerve stimulation. This previously healthy woman developed RE in the right hemisphere at the age of 27. Despite antiepileptic drug polytherapy, she continued to experience subcontinuous, simple-partial left-sided motor seizures and slowly progressive cognitive impairment. Resective surgery was not considered owing to the preservation of left motor skills. She was implanted with a vagus nerve stimulator at the age of 41; after 6months she experienced a greater than 50% reduction in seizure frequency, which persisted over 2years together with improvement of her neurological and cognitive status.

PMID: 21130042 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21130042

Heart Fail Rev. 2010 Dec 3. [Epub ahead of print]

Vagus nerve stimulation in experimental heart failure.

Sabbah HN, Ilsar I, Zaretsky A, Rastogi S, Wang M, Gupta RC.

Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202, USA, hsabbah1@hfhs.org.

Abstract

Chronic heart failure (HF) is associated with autonomic dysregulation characterized by a sustained increase in sympathetic drive and by withdrawal of parasympathetic activity. Sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Considerable evidence exists that supports the use of pharmacologic agents that partially inhibit sympathetic activity as effective long-term therapy for patients with HF; the classic example is the wide use of selective and non-selective beta-adrenergic receptor blockers. In contrast, modulation of parasympathetic activation as potential therapy for HF has received only limited attention over the years given its complex cardiovascular effects. In this article, we review the results of recent experimental animal studies that provide support for the possible use of electrical Vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. In addition to exploring the effects of chronic VNS on left ventricular (LV) function, the review will also address the effects of VNS on potential modifiers of the HF state that include cytokine production and nitric oxide elaboration. Finally, we will briefly review other nerve stimulation approaches which is also currently under investigation as potential therapeutic modalities for treating chronic HF.

PMID: 21128115 [PubMed - as supplied by publisher

http://www.ncbi.nlm.nih.gov/pubmed/21128115