eMedicine Specialties > Neurosurgery > Functional

Neuromodulation Surgery for Psychiatric Disorders

Author: Brian H Kopell, MD, Assistant Professor, Director of Restorative Neuroscience Program, Department of Neurosurgery, Medical College of Wisconsin
Coauthor(s): Jerry L Halverson, MD, Assistant Professor, Department of Psychiatry, University of Wisconsin School of Medicine and Public Health; Director of Treatment Resistant Depression Program, Department of Psychiatry, University of Wisconsin Medical School; Clinical Assistant Professor of Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical College of Wisconsin
Contributor Information and Disclosures

Updated: May 14, 2008

Introduction

History of the Procedure

The legacy of lobotomy

Nowhere was the desire to "do something" stronger than in the field of psychiatry at the dawn of the 20th century. Indeed, no drugs or medical procedures were available that specifically treated the symptoms of mental illness. "Therapeutic nihilism" was the philosophy of treatment among psychiatrists at this time, as patients were allowed by default to languish according to the natural history of their disease.

Beginning in the 1930s, a wave of "somatic" therapies, such as injections of Metrazol (camphor), insulin-induced hypoglycemic comas, and electroconvulsive therapy, began to revolutionize psychiatric practice. All of these were designed to trigger convulsions and states of unconsciousness in the patient; these shock therapies were dangerous, difficult to manage, and frightening for the patient. Yet these unfortunate aspects were tolerated because of these somatic treatments’ ability to manifestly alter the clinical course of a patient’s mental disease.1

Emerging simultaneously with the development of these somatic treatments was the seminal work by Portuguese neurologist Egas Moniz on the development of frontal leucotomy, the severing of frontal white matter tracts to treat psychiatric disorders. Not long after, Walter Freeman, an American neurologist and psychiatrist, seized upon Moniz’s discovery and brought the procedure to the United States in 1936. John Fulton, the prominent Yale neurophysiologist, was in solid support of the medical community proceeding with the operations but predicated this support on the concept ofcarefully designed clinical trials in elite academic institutions.2 The era of frontal lobotomy had begun.

With the publication of Freeman and Watts’ Psychosurgery in 1942, the fervor for the "success" of the lobotomy spread from the professional to the lay communities as Fulton’s advice was largely ignored. Psychosurgery’s fragile connection to the laboratory and the scientific community began to grow weaker and weaker. Gone were the days of "surgery of last resort," as Freeman wished to operate on a "better grade" of patient that included the recently institutionalized as well as the nonhospitalized. This led to Freeman’s development of the transorbital lobotomy, a ghastly procedure in which an ice pick is inserted through skin and bone to sever tracts in the frontal lobe. The awarding of the Nobel Prize in medicine to Moniz in 1949 echoed Freeman’s accelerated efforts.

Yet, even as these operations enjoyed their heyday, a backlash had begun; the luster on this "miracle" cure began to tarnish. The indiscriminate use of crude surgical interventions, coupled with a paucity of valid tools to assess psychiatric outcomes, often led to tragic consequences such as radical personality changes and cognitive decline. By the mid 1950s, over 20,000 frontal lobotomies had been performed in the United States alone.3 The damage associated with such indiscriminate use of this procedure was twofold. Firstly, although some patients benefited, many patients suffered. Secondly, the effort to surgically treat psychiatric disorders was permanently sullied. Indeed, many countries throughout the world outlawed the practice altogether .

Problem

The emergence of the patient with treatment-resistant disease

In the mid-20th century, the only effective medical treatment of movement disorders such as Parkinson disease and essential tremor was stereotactic surgical procedures that lesioned various areas of the thalamus, subthalamus, and basal ganglia. By the end of the 1950s, Arvid Carlsson introduced levodopa to the world, and the surgical intervention for Parkinson disease had radically declined by the 1970s. 

Nevertheless, within 10 years, a new class of Parkinson disease patient, the medically refractory patient, became evident. This group was deemed medically refractory because of the diminishing effects of levodopa and the emergence of side effects such as dyskinesias. Surgery once again became, and still remains, a pillar of treatment for these patients.

Psychiatric disease faces a similar situation. One of the chief causes of the demise of lobotomy was the introduction of chlorpromazine (Thorazine) in 1954. However, the emergence of the psychiatric patient with treatment-refractory disease evolved more quickly than the Parkinson disease counterpart, largely because of the heterogeneous nature of psychiatric disease and the limited types of pharmacotherapy available. Clinicians once again turned to surgical intervention. 

With the advent of stereotaxis, surgery for psychiatric disease evolved from the open lobotomy into minimally invasive lesioning such as cingulotomy (stereotactic ablation of the anterior cingulate cortex; see Image 1), capsulotomy (surgical ablation of the anterior limb of the internal capsule; see Image 2), subcaudate tractotomy (surgical ablation of the area known as the substantia innominate, a region ventral to head of the caudate; see Image 3), and limbic leucotomy (essentially a combined subcaudate tractotomy and cingulotomy).4   Nevertheless, because of the legacy of lobotomy and the permanence of the procedure, these procedures never came into widespread use and were not subject to scientific rigor and strict experimental protocol.

The evolution of neuromodulation offers new promise for these patients with treatment-resistant psychiatric disease. Neuromodulation can be defined as the therapeutic alteration of activity in the central, peripheral, or autonomic nervous systems (electrically or pharmacologically), often by means of implanted devices. In the field of movement disorders, neuromodulation in the form of deep brain stimulation (DBS) has become the criterion-standard treatment of advanced Parkinson disease, tremor, and dystonia. 

The chief hallmark of neuromodulation is the inherent adjustability and reversibility of the process, which is a clear advance beyond older techniques such as lobotomy and electroconvulsive therapy. Once implanted, these devices can be programmed to minimize side effects and maximize benefits and ultimately can be entirely removed without substantially altering the nervous system. This rapidly growing field, combined with new insights gained in the pathophysiology of psychiatric disease from functional imaging, has allowed clinicians to revisit this once-taboo medical practice. This article focuses on various new, more-focused, and reversible neuromodulation procedures being investigated for the treatment of treatment-refractory obsessive-compulsive disorder (OCD) and major depressive disorder (MDD), the 2 difficult-to-treat, dire psychiatric diseases.

Frequency

OCD is one of the most debilitating and refractory psychiatric disorders. OCD affects up to 2-3% of the US population (an estimated 2.2 million people) and almost 50 million people worldwide.5 Up to 40% of patients with OCD are partial responders or nonresponders.6 Few patients with OCD experience a complete remission of symptomatology. 

MDD is the leading cause of disability in the United States for patients aged 15-44 years.7 In any given 1-year period, 9.5%of the population, or about 20.9 million American adults, suffer from a depressive illness.8 Up to 30% of these patients are refractory to treatment.9

Pathophysiology

Prior to the advent of functional imaging techniques such as functional MRI (fMRI), PET, and magnetoencephalography (MEG), insight into the neural structures underlying psychiatric phenomena was based on the same processes that led to lobotomy and the stereotactic lesioning procedures: careful observation of patient behavior after discrete lesions in specific brain areas. Several classifications of psychiatric surgery have developed over the past century. In 1937, James Papez introduced a circuitry that included the hippocampus, the fornix, the mammillary bodies, the mammillothalamic tract, the anterior thalamic, the subgenual cingulate (Brodmann area 25 or Cg25), the parahippocampal gyrus, and the entorhinal cortex.4  

This circuit, known as the Papez circuit, has been an important heuristic model for psychiatric research and practice (see Image 4).

In 1954, Paul McLean described a neural circuit that included cortical and subcortical structures. Known as the limbic system, this has been perhaps the most influential neuroanatomic model of psychiatric phenomena in the 20th and 21st centuries. The limbic system consists of the regions involved in the Papez circuit and adds the amygdala, the hypothalamus, the nucleus accumbens, and the orbitofrontal cortex.4

In general, insight into the pathophysiology of psychiatric disease is much less defined than the pathophysiology of movement disorders. Chief among these reasons is the lack of animal models of depression and OCD, as compared with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson disease. Animal models of psychiatric disease are currently being developed but are not nearly as mature as their movement disorder counterparts. The result is that much of the insight into the anatomy of psychiatric disease is derived from the observation of behavior after brain lesions in humans.

A boon to this effort, however, is the application of functional imaging techniques such as fMRI, PET, and MEG to the understanding of the neural circuitry underlying psychiatric disease. However, there are currently limitations to their interpretation and perhaps contradictory findings. This may be due to the heterogeneous nature of psychiatric illness itself (eg, MDD). According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), to have MDD, a patient must show at least 5 of 9 different symptoms within a 2-week period. At the very least, there are 15,120 permutations according to this scheme. It is likely that biologically distinct subtypes may have different patterns of activity on functional imaging. A similar situation exists for the clinical subtypes of OCD.10

The advent of functional imaging, nevertheless, has allowed clinicians to reorganize the above understanding of the neuroanatomy of psychiatric disease into the following related systems:

Frontal lobe

Despite the prejudice it cast on the practice of surgery for psychiatric disease, lobotomy emphasized the inherent role the frontal lobe has in the genesis of psychiatric symptoms and behaviors. The evolution of this insight has been the basis of the evolution of lobotomy to stereotactic lesions and now to the use of deep brain stimulation (DBS) for psychiatric disease. The following anatomic areas within the frontal lobe have to be considered:
  • Orbitofrontal cortex (Brodmann areas 10, 11, 12, 47; see Image 5) 
    • This area processes tasks related to reward and punishment and extinction behavior in response to aversive stimuli.
    • This area’s role in psychiatric disease is perseverative cognitions and emotional response.
    • The anatomic connections in this area include the following:
      • It receives projections from every sensory modality (unique among any neocortical region).
      • Its influence over the autonomic nervous system is second only to the Cg25.
      • This area has extensive reciprocal connections to the dorsolateral prefrontal cortex and cingulate.
    • Functional imaging data
      • Increased metabolic activity in depression11
      • Increased metabolic activity in OCD that normalizes with successful treatment12
  • Dorsolateral prefrontal cortex (Brodmann area 9, lateral 10, 46; see Image 6)
    • This area processes tasks related to working memory, spatial memory and executive function, and mediation of external environment on limbic responses.
    • This area’s role in psychiatric disease involves the patient’s insight into symptoms, the ability to suppress negative feelings and painful stimuli, and the psychomotor retardation of severe depression.
    • Anatomic connections include extensive reciprocal connections to OFC and the cingulate.
    • Functional imaging data include decreased metabolism in negative mood states and untreated depressed patients and increased metabolism with successful treatment.11,13
  • Cingulate (Brodmann areas 24, 32, and 25; see Image 7)
    • This area processes tasks related to attention and influence over visceromotor and vegetative functions.
    • This area’s role in psychiatric disease is related to disruptions in hedonic tone and motivation.
    • This area’s anatomic features include the following:
      • Extensive connections to autonomic circuitry
      • Extensive reciprocal connections to the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC)
    • Functional imaging data include the following:
      • Increased metabolism in OCD12
      • Increased metabolism in Cg25 in MDD14
      • Decreased metabolism in Cg25 in the successfully treated state of MDD14
      • Increased metabolism that predicts response to cingulotomy15
These frontal lobe regions can be organized into 2 functionally related compartments: the dorsal compartment (DLPFC/ lateral orbitofrontal cortex [LOFC]; see Image 8) and a ventral compartment (medial orbitofrontal cortex [MOFC]/cingulate; see Image 9).

Thalamocortical loop

Evidence shows that neuronal ensemble oscillation and resonance between the thalamus and the cortex is "deeply related to the emergence of brain functions."16 The thalamocortical (TC) loop is thought to be the basic building block of behaviors that span from motor activity to psychiatric phenomena. Each TC loop consists of a specific region of cerebral cortex and its reciprocal excitatory connections with a specific target within the thalamus. Derangement in these loops can result in neurologic disorders.

In the case of motor disorders such as Parkinson disease, the TC loop in question involves the cortical regions of the motor cortex, the premotor cortex, and the supplementary motor area and the ventral lateral thalamic motor nucleus (VL). With regard to psychiatric disease, the following 2 TC loops are important: an associative loop that consists of the dorsal frontal lobe compartment and its reciprocal projections to the ventral anterior (VA) and the parvocellular dorsomedial thalamic nuclei (DMpc) and a limbic loop that consists of the ventral frontal lobe compartment and its reciprocal projections to the magnocellular portion of the dorsomedial thalamus (DMmc; see Images 10 and 11).

C ortico-striato-thalamocortical loop

In 1986, Alexander and Delong described a series of 5 loops of information, from cortex to basal ganglia and back to cortex.17 Each loop activity courses through the basal ganglia in parallel direct and indirect pathways. These heuristic schemes provided the basis for modern movement disorder surgery. In the case of movement disorders, the motor loop is of importance. For psychiatric disease, the dorsolateral, orbitofrontal, and anterior cingulate loops are important. Each loop has a direct and indirect component (see Image 12).

One of the features of these basal ganglia loops is that information is segregated according to the anatomic areas of their components. The primary cortical association of the associative loop is the dorsal compartment. Most of the information in the dorsal compartment flows through central striatal regions, such as the head of the caudate and portions of the NA core. The primary cortical association of the limbic loop is the ventral compartment. Most of the information in the ventral compartment flows through ventromedial striatal regions, such as the NA core and the NA shell. Like other cortico-striato-pallido-thalamocortical (CSPTC) loops, information travels through parallel indirect and direct pathways, with the output structures being the globus pallidus pars interna (GPi) and substantia nigra pars reticularis (SNr).

Hypothalamic-pituitary axis

The third anatomic circuitry that must be discussed is the interface of these thalamocortical and basal ganglia loops with the hypothalamic-pituitary axis. Via direct and indirect connections, the associative and limbic loops have access to autonomic machinery via the amygdala, the NA shell, the hypothalamus, and the serotonergic midbrain. The autonomic circuitry is especially important to the so-called vegetative aspects of psychiatric disease, such as wake/sleep cycles, feeding aberrances, and anxiety manifestations (see Image 13).

Currently, 6 targets for neuromodulation surgery have been published: the Cg25, the anterior internal capsule (AIC), the nucleus accumbens (NA), the ventral striatum (VS), the inferior thalamic peduncle (ITP), and the left vagus nerve. Each of these regions can be seen as nodes in the aforementioned circuitry. Putative modulation at these nodes is the basis of the current efforts investigating neuromodulation surgery for refractory psychiatric disease. The highlighted areas of Images 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 show how neuromodulation at each target may influence the aforementioned circuitry.

Increasingly, psychiatric changes are believed to not be attributed to a "center" of mood or behavior but, rather, are secondary to an imbalance in communication of multiple neuronal loops. However, the efficacy of DBS is typically attributed to a small generated electrical field that encompasses a very limited amount of cerebral tissue. Perhaps the stimulation generated at a certain target propagates downstream into the rest of the circuitry, gaining an amplified effect.

Alternatively, the limitations so far encountered with the proposed therapies are possibly due not only to difficulties in patient selection but also to the restricted effect generated by the focal electrical field on the overall circuitry. Future analysis may reveal that the best results come not from a single stereotactic target but, instead, from a combination of neuromodulatory strategies that affect discrete circuits.

Most of the currently accepted somatic treatments for MDD and OCD are thought to primarily work through the manipulation of discrete neurotransmitter systems. MDD has been primarily managed clinically through the use of medications that manipulate serotonergic, noradrenergic, and dopaminergic systems, based largely on drug response and monoamine depletion data. OCD has been managed primarily with manipulation of the serotonergic system, based largely on drug response data.

The neurotransmitter theories are not necessarily at odds with the "circuit theory" outlined above; they very well could be describing 2 parts of the same system. The neurotransmitter aberrancies addressed by medications may be the "micro" changes expressed by abnormalities in the "macro" circuits. One may be able to manage the aberrant circuits from the "bottom up," based on treatment of neurotransmitter deficiencies pharmacologically. Conversely, one may also be able to manage the aberrant neurotransmitter levels by correctingabnormalities in the "mood circuits."

Presentation

What is obsessive-compulsive disorder?

Obsessive-compulsive disorder (OCD) is defined by the National Institute of Mental Health as an anxiety disorder characterized by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions).

Repetitive behaviors such as handwashing, counting, checking, or cleaning are often performed with the hope of preventing obsessive thoughts or making them go away.

Performing these so-called "rituals," however, provides only temporary relief, and not performing them markedly increases anxiety.

What is major depressive disorder?

Major depressive disorder (MDD) is defined by the National Institute of Mental health as manifesting a combination of symptoms that interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Such a disabling episode of depression may occur only once but more commonly occurs several times in a lifetime. Symptoms may include the following:

  • Persistent sad, anxious, or "empty" mood
  • Feelings of hopelessness or pessimism
  • Feelings of guilt, worthlessness, or helplessness
  • Loss of interest or pleasure in hobbies and activities that were once enjoyed, including sex
  • Decreased energy, fatigue, or being "slowed down"
  • Difficulty concentrating, remembering, or making decisions
  • Insomnia, early-morning awakening, or oversleeping
  • Appetite loss and/or weight loss or overeating and weight gain
  • Thoughts of death or suicide; suicide attempts
  • Restlessness or irritability
  • Persistent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain

What is treatment resistance?

“Treatment-resistant” OCD or depression has no universally agreed upon definition. “Treatment resistance” can mean many things other than a difficult-to-treat biological illness, such as incorrect diagnosis (including comorbid psychiatric disorders, personality disorders, and substance abuse disorders), inadequate or incomplete antidepressant trials, and medication nonadherence. 

True treatment resistance is usually defined, however, as the subset of these refractory patients in whom contributory factors to treatment failure have been ruled out. These truly refractory patients are the patients who should be considered for these procedures. The incidence of patients with truly treatment-refractory disease is a controversial topic but is felt to be about 10-15%. 

Treatment-resistance obsessive-compulsive disorder  

No definitive agreement exists on what constitutes treatment-resistant OCD. The definition most commonly used is an unsatisfactory response to 2 adequate trials of serotonin reuptake inhibitors,18  although most would suggest a trial of cognitive behavioral therapy (CBT) prior to defining someone as treatment resistant. Determination of "failure" or an “unsatisfactory response” is made when the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score is reduced by less than 25% or when improvement is greater than 25% but the patient still experiences significant OCD-caused impairment (meaning that the obsessions or compulsions continue to cause impairment in functioning, even in their improved state). Approximately 10% of the OCD population may be candidates for neuromodulation surgery based on these criteria of treatment resistance.19
 
Treatment-resistant depression

Treatment-resistant depression also has no agreed upon definition. Attempts have been made to define degrees of treatment refractoriness.20 Thase and O’Reardon defined treatment refractory depression as treatment nonresponse (ie, persistence of significant depressive symptoms) despite at least 2 treatment trials with drugs from different pharmacologic classes, each used in an adequate dose for an adequate time period.20,21

The FDA went beyond this most commonly used definition when its approved vagus nerve stimulation (VNS) for treatment-resistant depression raised the number of failed adequate trials to 4 but did not define the types or quality of trials needed. These trials may include medications, therapies, and other treatments such as electroconvulsive therapy (ECT). Approximately 10-15% of the major depressive disease (MDD) population may be candidates for neuromodulation surgery based on these criteria of treatment resistance.22

Indications

Patient selection is perhaps the most crucial issue facing the renewed interest in neuromodulation for psychiatric disease. Careful patient selection is the key to not recapitulating the mistakes of the lobotomy era. An emphasis is placed on a multidisciplinary approach in which a team led by psychiatrists who are expert in the treatment of refractory obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) carefully reviews all patients prior to surgical intervention.

Recent publications have given the following guidelines for forming such a team: an ethics committee, a patient assessment committee, strict adherence to accepted criteria for treatment-refractory MDD/OCD, limitation of such efforts to tertiary-care academic centers, limitation of patient selection to those patients with decision-making capacity, and the avoidance of procedures whose purpose involves law enforcement, political, or social ends.23

Relevant Anatomy

See Pathophysiology

Contraindications

The primary contraindications for deep brain stimulation (DBS) or VNS implantation for psychiatric disease are similar to those for movement disorders or refractory epilepsy: current antiplatelet or anticoagulation therapy or unstable medical comorbidity. At this time, age per se is not an absolute contraindication, but pediatric patients are excluded.

Also, because DBS relies heavily on MRI images for electrode targeting, the presence of an implanted cardiac pacemaker also presumably contraindicates this surgery. Specific psychiatric contraindications for DBS or VNS implantations may include the following general disorders:

  • Psychotic disorders  
    • The efficacy and safety of DBS or VNS in psychotic disorders, including major depressive disorder (MDD) with psychotic features, has not been established.
    • This may be problematic for several reasons, including the difficulty of obtaining informed consent for surgery in a psychotic patient as well as the obvious concerns about implanting a permanent indwelling device in a psychotic patient.
  • Substance use disorders  
    • Severe and active substance use disorders can obscure the diagnostic certainty needed in these disorders. Further, in the face of active substance use, establishing the adequacy of failed medical trials is impossible.
    • Like most interventions, neither DBS nor VNS has been systematically studied in patients with severe and active substance use.
  • Personality disorders  
    • Neither of these interventions has been studied systematically in populations with severe and active personality disorders.
    • Some patients with cluster B personality disorders (borderline, histrionic) have been excluded from recent neuromodulation trials.
    • This can be a particular diagnostic challenge, as patients with severe depression can manifest personality traits that resolve with treatment of the depression.
    • As with most treatments, the presence of a personality disorder lowers the expected benefit and may shift the risk-benefit analysis in surgical treatments, such as those treatments with relatively high risk compared with standard treatments.
  • Axis I comorbidity  
    • DBS and VNS have not been systematically studied in patients who have comorbid mood and anxiety disorders.
    • Attempts have been made in some of the trials to exclude patients with axis I comorbidity.
  • VNS-specific disorders  
    • Although bipolar depression is generally believed to be within the indications for VNS, as several patients with bipolar disorder were included in the VNS pivotal trial, no large trials of VNS for bipolar disorder have been published.
    • VNS may be more likely to cause mood instability in those with bipolar disorder and with inadequate levels of mood stabilization medication.
    • VNS has not been systematically studied for use in anxiety disorders, including OCD.
  • DBS-specific disorders: DBS has not been studied in patients with bipolar disorder, and there is a concern about DBS causing an unbalanced switch to mania.

More on Neuromodulation Surgery for Psychiatric Disorders

Overview: Neuromodulation Surgery for Psychiatric Disorders
Treatment: Neuromodulation Surgery for Psychiatric Disorders
Follow-up: Neuromodulation Surgery for Psychiatric Disorders
Multimedia: Neuromodulation Surgery for Psychiatric Disorders
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

neuromodulation surgery for psychiatric disorders, neuromodulation, psychiatric surgery, deep brain stimulation, DBS, vagus nerve stimulation, VNS, dorsolateral prefrontal cortex, DLPFC, cingulate gyrus, Brodmann area 25, subgenual cingulate, Cg25, ventral striatum, VS, anterior internal capsule, AIC, nucleus accumbens, NA, psychiatric disorders

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Contributor Information and Disclosures

Author

Brian H Kopell, MD, Assistant Professor, Director of Restorative Neuroscience Program, Department of Neurosurgery, Medical College of Wisconsin
Brian H Kopell, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, American Society of Stereotactical and Functional Neurosurgery, Congress of Neurological Surgeons, Movement Disorders Society, and North American Neuromodulation Society
Disclosure: Prism Clinical Imaging None Consulting

Coauthor(s)

Jerry L Halverson, MD, Assistant Professor, Department of Psychiatry, University of Wisconsin School of Medicine and Public Health; Director of Treatment Resistant Depression Program, Department of Psychiatry, University of Wisconsin Medical School; Clinical Assistant Professor of Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical College of Wisconsin
Jerry L Halverson, MD is a member of the following medical societies: Academy of Psychosomatic Medicine, American Medical Association, and American Psychiatric Association
Disclosure: Forest Pharmaceuticals Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; BMS Honoraria Speaking and teaching; Northstar Grant/research funds None; Cyberonics Grant/research funds None; GSK Grant/research funds Other

Medical Editor

Michael G Nosko, MD, PhD, Chief, Division of Neurosurgery, Director of Neurovascular Surgery, Medical Director of Neuroscience Unit, Associate Professor, Department of Surgery, University of Medicine and Dentistry of New Jersey
Michael G Nosko, MD, PhD is a member of the following medical societies: Academy of Medicine of New Jersey, Alpha Omega Alpha, American Association of Neurological Surgeons, American College of Surgeons, American Heart Association, American Medical Association, New York Academy of Sciences, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Allen R Wyler, MD, Former Medical Director, Northstar Neuroscience, Inc
Allen R Wyler, MD is a member of the following medical societies: American Academy of Neurological and Orthopaedic Surgeons, American Association of Neurological Surgeons, and Society of Neurological Surgeons
Disclosure: Nothing to disclose.

CME Editor

Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy
Paolo Zamboni, MD is a member of the following medical societies: American Venous Forum and New York Academy of Sciences
Disclosure: Nothing to disclose.

Chief Editor

Allen R Wyler, MD, Former Medical Director, Northstar Neuroscience, Inc
Allen R Wyler, MD is a member of the following medical societies: American Academy of Neurological and Orthopaedic Surgeons, American Association of Neurological Surgeons, and Society of Neurological Surgeons
Disclosure: Nothing to disclose.

 
 
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