Since the discovery of localized activation of the motor cortex in the late 19th century, electrical manipulation of the brain has frequently been the focus of scientific investigations. Following the revelation of the electrical properties of the motor cortex, subsequent mapping of cortical function was completed. This was followed in the 1950s, by the identification of deep structures of the brain via intraoperative stimulation. Theories of treating neurologic disorders with chronic stimulation began to emerge over the proceeding decade. By the 1970s, documentation of the management of pain, movement disorders, and epilepsy through the application of chronic stimulation was made evident. Eventually, in the 1990s, by combining the technologies of the implantable pacemaker with chronically implanted deep electrodes, the discovery of deep brain stimulation (DBS) was made possible.[1]
The DBS apparatus consists of electrodes implanted adjacent to specific deep brain structures, which are then connected to a pacemaker-like machine (pulse generator) that is implanted on the chest wall, via a subcutaneous wire. Stimulation parameters are then relayed by a computer to the pulse generator, appropriating proper amplitudes, frequencies, and pulse width. Common structures targeted by DBS include the subthalamic nucleus (STN), globus pallidus interna (GPi), and the ventral intermediate nucleus of the thalamus (VIM).[2]
The precise mechanism of the resultant therapeutic effects of deep brain stimulation remains unclear. However, theories are aplenty. As implied by the recounting of the surplus of possible applications, stimulation of the deep brain structures influences a variety of circuits involved in neuronal functioning. Therapeutic effects are incumbent upon physiologic properties of cells, surface areas of stimulated structures, the amplitude and temporal properties of the stimulation, and lastly, the characteristics of the underlying pathophysiology of different disease states. Imaging and physiologic studies corroborate the hypothesis that the ultimate effect of deep brain stimulation is the increase of the firing of the targeted neurons.[1]
DBS is approved by the United States Food and Drug Administration (FDA) for the treatment of essential tremor, dystonia, Parkinson disease, and treatment-refractory obsessive-compulsive disease (OCD).[2]
Since the nascent stages of its discovery, DBS technology has increasingly gained application and use. Initial implementation of DBS was for the treatment of essential tremor (ET) and the tremor of Parkinson disease (PD).[3][4] Studies indicate that stimulation of the “ventral intermediate nucleus of the thalamus, via DBS, results in the average tremor reduction of over 80%.”[5][6][7] Stimulation of the globus pallidus internus has demonstrated a reduction of major motor manifestations of PD, including, but not limited, to dopaminergic induced dyskinesias.[8] Stimulation of the GPi is believed to reduce parkinsonian akinesia and rigidity by normalizing the firing frequency of the dysfunctional GPi.[9] Improvement of gait, tremor, and bradykinesia has been shown via stimulation of the subthalamic nucleus.[10][11] Stimulation of the parafascicular and sensory relay nuclei of the thalamus have demonstrated analgesic properties.[12][13]
In 1999, the first psychiatric indication for DBS was published.[2] Since that initial publication, many studies focusing on DBS for treatment-resistant psychiatric illnesses have been performed. More recently, DBS has been found to have beneficial effects in Tourette Syndrome, via stimulation of the centromedian-parafascicular complex of the thalamus, along with the GPi and the anterior limb of the internal capsule. Perhaps most notably is the application of DBS for obsessive-compulsive disorder (OCD) and treatment-refractory depression.[14] DBS of the subgenual cingulate white matter has demonstrated efficacy in the improvement of mood in those afflicted with treatment-resistant depression, whereas DBS of the bilateral anterior limbs of the internal capsules has shown a reduction of OCD related symptoms.[15] Evidence demonstrating the resolution of OCD symptomatology by targeting either the ventral capsule/ventral striatum or the STN led to the FDA approval of DBS for treatment-refractory OCD, in 2009.[2] The first documented application of DBS for treatment-resistant depression (TRD) was in 2009. Hypothesized targets for the treatment of TRD are the subgenual anterior cingulate cortex, ventral capsule/ventral striatum, nucleus accumbens, and the medial forebrain bundle.[2] Future psychiatric indications that are currently being studied include addiction, autism, anorexia nervosa, anxiety disorders, and schizophrenia.
DBS has fairly minimal absolute contraindications. DBS is contraindicated in patients who cannot properly operate the neurostimulator. Once implanted, patients with deep brain stimulators should not undergo full-body magnetic resonance imaging scans (MRIs), transcranial magnetic stimulation, and diathermy.[16]
Proper DBS equipment includes a lead with electrodes, a wire, a pulse generator, along with the corresponding tools for brain surgery and chest wall implantation.[2]
The procedure requires specific personnel. Quintessential to the surgery is an experienced neurosurgeon, along with his associated staff. As DBS is currently indicated for mostly neurologic disorders, it is more likely that the referring physician will be a neurologist. However, for indications such as treatment-refractory OCD, a psychiatrist will often fill the role of the referring physician sometimes in discussion with a neurologist. Moreover, the referring physician, along with the neurosurgeon, will discuss the case and identify the structures of pertinence to be stimulated by the implanted device.[2]
Prior to the procedure, the patient will need to be medically cleared to undergo surgery, to ensure that DBS is a safe and appropriate option. Once cleared, the patient will undergo brain-imaging studies to visualize locations for implantation of the electrodes.[16]
Once underway, the surgical team will fit the patient with a special frame to immobilize head movement during the surgery. This frame is called a stereotactic head frame. Surgery is commonly performed under general anesthesia, but local anesthesia is also a viable alternative. Intriguingly, the brain itself does not require anesthetic itself, as it lacks pain receptors. The surgeon then implants a thin wire lead to the structures that were identified pre-surgery. Tiny electrodes at the end of the wire will contact the aforementioned structures. The lead is then connected to a wire which runs just superficially to the skin, which ultimately connects to a pulse generator within the chest wall. Both the neurosurgeon and neurologist will closely monitor brain function throughout the procedure to ensure appropriate electrode placement.
The subsequent chest wall surgery involves the placement of the pulse generator just under the skin near the clavicle. Unlike the preceding procedure, the chest wall surgery requires general anesthesia. The pulse generator is then connected to a special remote control.[2]
Of equal ambiguity is the side effect profile of deep brain stimulation. Whereas the surgical complications implicated with deep brain stimulation, such as hemorrhage, surgical revision of hardware, and infection, are more apparent and objective, the assessment of psychiatric and neurologic manifestations of adverse effects tend to be more discreet and protean, from patient to patient. This vagueness is multifactorial in origin. Firstly, patients may simply not relay these complaints to their respective physicians. Reciprocally, the physician, in turn, may not ask the appropriate questions in order to elucidate ongoing adverse side effects. It is plausible that even if side effects are reported, they may not be documented if they do not meet some arbitrary threshold level of severity. Moreover, it is sometimes hard to differentiate between pre-existing symptoms and comorbidities from the precipitating side effects of DBS. Furthermore, certain side effects tend to manifest over time and occur with latency. An example of this insidious onset is axial symptoms in Parkinson disease. Lastly, as science further evolves and behavioral derivatives of neurocircuitry are mapped out, it is possible that what was once celebrated as therapeutic gains from DBS treatment, will now be regarded as red flags. For example, whereas the spontaneous onset of initiative in STN-stimulated Parkinson disease patients was once applauded as progress, it is now, unfortunately, considered to be the pathological manifestation of disturbed impulse control.[17] However, current scientific literature demonstrates that deep brain stimulation is relatively safe overall and is associated with only minimal and perhaps negligible side effect profile. Nonetheless, the following includes a list of reported side effects: mild gait or speech disturbances, affective liability, worsened depression, seizure, difficulty concentrating, confusion, and headache.
Deep brain stimulation has the potential for robust application, and has specifically been heralded as offering "a new life for people with Parkinson disease."[16] DBS has already been awarded FDA approval for essential tremor, dystonia, Parkinson disease, and treatment-refractory obsessive-compulsive disease. Ongoing studies are investigating the possible off-label use in addiction, autism, anorexia nervosa, anxiety disorders, and schizophrenia.
The literature is abundant, with studies demonstrating the benefits of interprofessional collaboration. Patient outcomes such as decreasing morbidity and mortality rates, optimizing medication dosages, and reducing preventable adverse drug events have been shown to improve via interprofessional collaboration.[18][Level 4] Not only does this benefit the patient, but it also benefits the health care workers, by increasing job satisfaction and reducing extra work.[18] Successful DBS requires integrative, collaborative communication, and care. An interprofessional DBS team should include an experienced surgeon (with expertise in functional neurosurgery), a movement disorder neurologist, psychiatrist, neuropsychologist, and neuropsychologist. The nurse plays an integral role in assisting the patient gain maximum benefit from the surgical intervention. All healthcare workers must be engaged and in sync for the patient to achieve optimal results.
"This research was supported (in whole or part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities."
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