Neuromodulation Surgery For Psychiatric Disorders


Article Author:
Delvise Fogwe
Hassam Zulfiqar


Article Editor:
Fassil Mesfin


Editors In Chief:
Mark Cogburn
Jessica Yeager
Laura Casey


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/25/2019 1:08:31 PM

Introduction

Despite the advances in pharmacotherapy in the treatment of some psychiatric disorders like schizophrenia, anxiety disorders, obsessive-compulsive disorder, and depression, a significant number of patients become refractory and will not respond to pharmacologic treatments[1]. Clinicians are beginning to reconsider neuromodulation surgery as a last resort for the treatment of these patients. Neurosurgical interventions aimed at treating psychiatric disorders are grouped into two categories: destructive (ablative psychosurgery) or selective stimulation (neuromodulation psychosurgery)[1]. Neuromodulation surgery involves implanting a device in the brain that modulates the neural networks within the brain. The use of surgery for the treating of psychiatric diseases is not a new concept. Historically, the concept of psychosurgery always raised general skepticism and stigma because of the way that it was erroneously used in the past despite the high rate of complications and mortalities with little improvement in patients’ lives[2][1][3]. A brief history about psychosurgery is essential to understand the reason behind the skepticism toward it.

In the 1930s, a Portuguese neurologist by the name Egas Moniz first introduced a surgical procedure called prefrontal leucotomy[3]. Moniz believed that some psychiatric problems were caused by abnormal connections to the frontal lobe and that surgically removing the white fibers connecting the frontal lobe with the rest of the brain will help mental health conditions. Moniz technique was later widely utilized in  Europe and the United States.  In the United States, prefrontal leucotomy was modified by an American neurosurgeon named Walter Freeman who developed a procedure called Transorbital Leucotomy[1][2][1]. Unlike the original lobotomy that involved an open surgery, transorbital leucotomy was a closed surgery, lasted about 10 to 20 minutes and was aimed at separating the frontal lobe from the thalamus by accessing the brain through the back of the orbits. Clinicians often used this treatment even though, at the time, there was not much data to evaluate the effectiveness of this method, and because of the lack of alternative treatment for patients who had debilitating mental health problems. Later, retrospective studies showed that while Dr. Freeman's method helped calmed some severely agitated patients, others ended up with numerous complications[1].

In the 1950s pharmacotherapy was introduced, which change the approach in treating psychiatric conditions[1]. While pharmacotherapy led to the demise of psychosurgery, physicians were laying the groundwork for the development of stereotactical microsurgery techniques. Furthermore, there was the rapid development of numerous modalities that helped in the understanding of the structure and function of the brain. These new advances, coupled with the frustrations of the significant percentage of patients not responding to pharmacotherapy and positive results in the use of neuromodulation surgery like deep brain stimulation in the treatment movement disorders like parkinsonian diseases, has lead clinicians to revisit the use of neuromodulation surgery for the treatment of psychiatric disorders. In addition to the old concerns, there is a new wave concern as to what the limits of what some of these neuromodulatory surgical procedures will be. Professionals debate whether these techniques will be used only as a last resort for the treatment of refractory psychiatric symptoms, or if they will be used for other purposes like to modify the cognition of healthy individuals[1][4].

Etiology

With new diagnostic techniques, physicians' knowledge of the brain and function has improved over the past decades, but understanding the cause of psychiatric disorders remains a challenge. Physicians believe that the cause of many mental health disorders has multifactorial etiology with genetics and environmental factors having a significant role to play. For example, while the exact cause of schizophrenia is unknown, about 80% might be due to genetic influence[3]. Early childhood events like maternal infection, malnutrition, and environmental factors like urbanization have been cited to play a role in the etiology of schizophrenia[3]. Similar reports have been used to explain the cause of obsessive-compulsive disorder, anxiety disorder, depressive disorders, among others.

Epidemiology

Psychiatric disorders are a huge problem in the United States and internationally. According to the American Psychiatric Association, about 25% of United States adults are diagnosed with a mental health disorder each year. Disability caused by psychiatric disorders are overwhelming for patients, and the financial burden on the economy is immense. For example, based on a 2002 record, the cost of treatment of schizophrenia alone was about $63 billion[5]. About 20% to 30% of patients with schizophrenia are unresponsive to the antipsychotic therapy[6]. This is a considerable number of patients who will not be able to live a healthy life. While this describes cases of schizophrenia, similar inferences can be made about other mental health disorders.

Pathophysiology

The arrival of new diagnostic techniques and the ability to integrate information from different diagnostic modalities has made it possible for clinicians to understand the brain structure and function and help localize brain pathologies. Some of these diagnostic techniques include functional magnetic resonance imaging (fMRI), positive emission tomography (PET), neurophysiologic data from electroencephalogram (EEG), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS)[7][8][9]. All these diagnostic modalities provide a more in-depth knowledge of brain activities and a stronger foundation for specific targets for neuromodulation surgery as a  treatment for some psychiatric disorders. For example, researchers cite that the pathophysiology of OCD stems from abnormal function of the cortical-striatal-thalamic circuits, the genu of the corpus callosum has been strongly implicated in the pathophysiology of depression and schizophrenia, while the medial cingulate cortex has been involved in the pathophysiology of anxiety disorders[1][10].

History and Physical

While the advent of new diagnostic techniques and the ability to integrate information from different diagnostic modalities has made it possible to understand the brain structure and function and help localize brain pathologies, there are no tests or objective biological markers indicated as criteria for diagnosing a psychiatric disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)[11].  Reliable diagnosis is based on the identification of symptoms, behaviors, personality traits among other features. While diagnostic tests can be used, in most cases it is to rule out other organic cause that may be presenting as a psychiatric problem. A careful history and physical examination are fundamental tools for diagnosing and treating of psychiatric disorders.

Essential components of a patient's history include present illness, past medical and psychiatric history, substance abuse, family and social information, and medication. This history will provide insight into patient’s current illness, predisposing factors like genetic vulnerabilities and low socioeconomic status, current life stressors, family dynamics, and support systems available to the patient. In some cases, medications that have worked for one family member may suggest that patient will benefit from it.

The physical examination usually starts with examining the general appearance of the patient and begins as the physician sets eye on the patient. The overall patient well-being and nutritional status may be assessed just through observation. For example, a patient with schizophrenia may appear disheveled or bizarre with clothing that may not be appropriate for the setting. Other important aspects that can be assessed include the patient's psychomotor activity, the patient's mood and affect, and the patient's thought process and thought content. The clinician can observe whether the patient's movements are delayed or if the patient is fidgeting and agitated. The should evaluate patient speech pattern and determine if their thoughts are goal-directed or disorganized. Finally, assessing the patient's thoughts for any delusions, hallucinations, or suicidal and homicidal thoughts, among others is essential.

Furthermore, a patient's history can help guide the clinician's physical examination as to what specific organ systems on which to focus their attention first. For example, during an assessment of subconjunctival, a patient's pale and dry appearance may be suggestive of self-neglect and inadequate dietary intake due to illnesses such as depression, schizophrenia, and anorexia nervosa. Also, assessment of skin for any cuttings marks which may be associated with borderline personality disorder, depression and even some eating disorders. Other systems specific physical exams may be based on the history of the patient that gives the physician a prompt for further assessment.

Evaluation

As mentioned above, different diagnostic methods that help evaluate brain function are among the most critical advances that have made it possible to have targeted neuromodulatory psychiatric treatment.  Some diagnostic techniques are good at giving information about the cortical structures and function. For example, the transcranial magnetic stimulation provides a noninvasive means of probing the neurophysiology of different cortical structure cortical function and dysfunction and no information about the subcortical structure and function[7][8][9]. The fMRI and PET help provide information about the subcortical structures[7][8][9].

Treatment / Management

The primary goal of treatment of psychiatric disorders is to improve the functionality of the patients in the society. In schizophrenic patients, for example, this will mean decreasing the frequency and severity of the psychotic episodes. While the stigma due to the history psychosurgery still looms, the utilization of neuromodulatory surgery to treat psychiatric disorder is backed by not only a more profound understanding of brain structure and function, but also, the development of new stereotactic microsurgical technique, and data about successful management of other neurological disorders through neuromodulation.   This fountain of knowledge has led to the development of treatment options that target a particular region of the brain and with effects of these treatments that can be reversible, unlike the earlier process like prefrontal leucotomy that involves the permanent removal of parts of the brain.

The concept of deep brain stimulation in the treatment of psychiatric disorders can be attributed to DBS success in the treatment of movement disorder like Parkinson’s disease, essential tremor, dystonia[12].  Current research has shown promising results in the use of DBS in treatment-resistant OCD, anxiety disorders, depression, and trials are underway for the utilization of this procedure in the treatment of schizophrenia[13]. DBS is a nondestructive treatment option that is reversible, less invasive, and treatment options can be modifiable based on the needs of the patients[14]. While cost wise DBS may be more expensive, recent studies show long-term benefits with cost leveling off[15]. DBS involves placing electrodes deep in the brain. Through these electrodes, a specific region of the brain is stimulated with frequencies as high as >100Hz[16]. This often results in the inhibition of the target area producing some kind of functional ablation. The mechanism by which DBS exerts its effects is not entirely understood. It is believed that DBS modulates neural activity by stimulating or inhibiting neurons and fiber pathways that will allow subsequently neurochemical release[16]. For example, the stimulation of the inferior thalamic peduncle that connects the thalamus and the orbitofrontal cortex has been proven to help alleviate the symptoms of OCD[16].

Another neuromodulation surgery that has been reported to treat chronic and treatment-resistant depression is vagal nerve stimulation. Vagal nerve stimulation was initially developed to treat treatment-resistant epilepsy but later utilized for the treatment of depression[17]. This procedure involves the implantation of a device by a neurosurgeon or vascular surgeon under the chest that stimulates the left vagal afferent nerve fibers in the neck that helps modulates brain activity. The right vagus nerve is not stimulated because of its involvement in the actions of the heart[17]. The surgical and psychiatric side effects reported are rare and involve hypomania, mania and in some cases exacerbation of depression and increase suicide risk[17].

Other neuromodulation techniques that have been used for the treatment of psychiatric disorders that do not involve the application of a surgical device are Electroconvulsive Therapy (ECT) and Trans-magnetic stimulation(TMS). ECT has been widely reported in the literature as one the most effective treatment for chronic major depression and pharmacotherapy resistant major depression[18]. TMS on the other hand, often used for diagnostic purposes to assess brain function but also been cited for the treatment of psychiatric disorder like major depressive disorder[19]. While these methods are far less invasive than the neuromodulatory surgery and have been proven to be very useful, just like DBS and other ablative surgery, they are highly underutilized due to the stigma toward them.

Enhancing Healthcare Team Outcomes

Despite the advances in pharmacotherapy for treating psychiatric disorders like schizophrenia, anxiety disorders, obsessive-compulsive disorder, and depression, many patients become refractory. A multidisciplinary team of nurses and physicians should be familiar with and educate patients and their families on the option of neuromodulation surgery as a last resort for the treatment of these patients.


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Neuromodulation Surgery For Psychiatric Disorders - Questions

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A 47-year-old male with a long history of depression is considering neuromodulation as an option for the treatment of his depression that has become refractory to pharmacotherapy. Which of the following options is contraindicated?



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Which of the following psychiatric disorders is not treated with neuromodulation?



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What is the primary goal of neuromodulation based treatment of psychiatric disorders?



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Neurosurgical techniques like prefrontal leucotomy and transorbital leucotomy were erroneously used during the early periods of the 20th century to treat psychiatric disorders and in most cases causing more harm than good and leading to stigma towards surgical approaches in treating psychiatric disorders. Which of the following is not one of the rare advances that have been made that can help reduce the stigma towards neurosurgical techniques in treating psychiatric disorders?



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The advancement of diagnostic techniques and the ability to integrate information from different diagnostic modalities like functional magnetic resonance imaging (fMRI), positive emission tomography (PET), neurophysiologic data from electroencephalogram (EEG), has made it possible for clinicians to understand the brain structure and function and help localize the origin of some neuropsychiatric disorder. This has led to the ability to have more specific targets for neuromodulation procedure. What are some regions of the brain that have been targeted for deep brain stimulation for the treatment of obsessive-compulsive disorder?



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Neuromodulation Surgery For Psychiatric Disorders - References

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