Deep brain stimulation (DBS) is a neurosurgical procedure introduced in 1987, involving the implantation of a medical device called a neurostimulator (sometimes referred to as a 'brain pacemaker'), which sends electrical impulses, through implanted electrodes.
The system consists of a lead that is implanted into a specific deep brain target. The lead is connected to an implantable pulse generator (IPG), which is the power source of the system. The lead and the IPG are connected by an extension wire that is tunneled under the skin between both of them. This system is used to chronically stimulate the deep brain target by delivering a high-frequency current to this target.
Deep brain stimulation (DBS) has been used to treat various neurological and psychiatric disorders. Over the years, the most suitable surgical candidates and targets for some of these conditions have been characterized and the benefits of DBS well demonstrated in double-blinded randomized trials 1). 2).
Functional stereotactic neurosurgery by means of deep brain stimulation or ablation provides an effective treatment for movement disorders and affective disorders, but the outcome of surgical interventions depends on the accuracy by which the target structures are reached.
Stereotactic deep brain stimulation surgery is most commonly performed while patients are awake. This allows for intraoperative clinical assessment and electrophysiological target verification, thereby promoting favorable outcomes with few side effects. Intraoperative CT and MRI have challenged this concept of clinical treatment validation. Image-guided surgery is capable of delivering electrodes precisely to a planned, stereotactic target; however, these methods can be limited by low anatomical resolution even with sophisticated MRI modalities.
DBS in select brain regions has provided therapeutic benefits for otherwise-treatment-resistant movement and affective disorders such as Parkinson's disease, essential tremor, dystonia, chronic pain, major depression and obsessive–compulsive disorder (OCD). Despite the long history of DBS, its underlying principles and mechanisms are still not clear. DBS directly changes brain activity in a controlled manner, its effects are reversible (unlike those of lesioning techniques), and it is one of only a few neurosurgical methods that allow blinded studies.
The Food and Drug Administration (FDA) approved DBS as a treatment for essential tremor in 1997, for Parkinson's disease in 2002, dystonia in 2003, and OCD in 2009. DBS is also used in research studies to treat chronic pain, PTSD, and has been used to treat various affective disorders, including major depression; neither of these applications of DBS have yet been FDA-approved. While DBS has proven effective for some patients, potential for serious complications and side effects exists.
The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement.
Though mechanisms underlying deep brain stimulation are still unclear, commonly accepted theories include a “functional inhibition” of neuronal cell bodies and the excitation of axonal projections near the electrodes.
It is becoming clear, however, that the paradoxical dissociation “local inhibition” and “distant excitation” is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium.
Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis.
The red nucleus is a important centre for the genesis of cerebellar tremor and thus a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration 3).
Deep brain stimulation is nowadays a frequently performed surgery in patients with movement disorders, intractable epilepsy, and severe psychiatric disorders.
Its application is expanding to the treatment of other intractable neuropsychiatric disorders including depression and obsessive compulsive disorder (OCD), Gilles de la Tourette syndrome, and addiction. Latest research suggests beneficial effects of DBS in Alzheimer disease (AD).
Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted 6).
Deep brain stimulation (DBS) has shown considerable promise for relieving nociceptive and neuropathic symptoms of refractory chronic pain. Nevertheless, for some patients, standard DBS for pain remains poorly efficacious.
Sixteen patients (13 male and 3 female patients) with neuropathic pain underwent bilateral ACC DBS. The mean age at surgery was 48.7 years (range, 33-63 years). Patient-reported outcome measures were collected before and after surgery using a Visual Analog Scale, SF-36 quality of life survey, McGill Pain Questionnaire, and EQ-5D (EQ-5D and EQ-5D Health State) questionnaires.
Fifteen patients (93.3%) transitioned from externalized to fully internalized systems. Eleven patients had data to be analyzed with a mean follow-up of 13.2 months. Post-surgery, the Visual Analog Scale score dropped below 4 for 5 of the patients, with 1 patient free of pain. Highly significant improvement on the EQ-5D was observed (mean, +20.3%; range, +0%-+83%; P = .008). Moreover, statistically significant improvements were observed for the physical functioning and bodily pain domains of the SF-36 quality-of-life survey: mean, +64.7% (range, -8.9%-+276%; P = .015) and mean +39.0% (range, -33.8%-+159%; P = .050), respectively.
Affective ACC DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and restore quality of life 7).
Scelzo et al. report a retrospective case series of women, followed in two DBS centers, who became pregnant and went on to give birth to a child while suffering from disabling MD or psychiatric diseases [Parkinson's disease, dystonia, Tourette's syndrome (TS), Obsessive Compulsive Disorder (OCD)] treated by DBS. Clinical status, complications and management before, during, and after pregnancy are reported. Two illustrative cases are described in greater detail.
DBS improved motor and behavioral disorders in all patients and allowed reduction in, or even total interruption of disease-specific medication during pregnancy. With the exception of the spontaneous early abortion of one fetus in a twin pregnancy, all pregnancies were uneventful in terms of obstetric and pediatric management. DBS parameters were adjusted in five patients in order to limit clinical worsening during pregnancy. Implanted material limited breast-feeding in one patient because of local pain at submammal stimulator site and led to local discomfort related to stretching of the cable with increasing belly size in another patient whose stimulator was implanted in the abdominal wall.
Not only is it safe for young women with MD, TS and OCD who have a DBS-System implanted to become pregnant and give birth to a baby but DBS seems to be the key to becoming pregnant, having children, and thus greatly improves quality of life 8).
Ramayya et al. reviewed medical records of patients over the age of 18 who underwent DBS surgery at Pennsylvania Hospital of the University of Pennsylvania between 2009 and 2014. They identified patients who were readmitted to an inpatient medical facility within 30 days from their initial discharge.
Over the study period, 23 (6.6%) of 347 DBS procedures resulted in a readmission to the hospital within 30 days. Causes of readmission were broadly categorized into surgery-related (3.7%): intracranial lead infection (0.6%), battery-site infection (0.6%), intracranial hematoma along the electrode tract (0.6%), battery-site hematoma (0.9%), and seizures (1.2%); and nonsurgery-related (2.9%): altered mental status (1.8%), nonsurgical-site infections (0.6%), malnutrition and poor wound healing (0.3%), and a pulse generator malfunction requiring reprogramming (0.3%). Readmissions could be predicted by the presence of medical comorbidities ( P < .001), but not by age, gender, or length of stay ( P s > .15).
All-cause 30-day readmission for DBS is 6.6%. This compares favorably to previously studied neurosurgical procedures. Readmissions frequently resulted from surgery-related complications, particularly infection, seizures, and hematomas, and were significantly associated with the presence of medical comorbidities ( P < .001). 9).
Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery 10).
A 79-year-old woman with a history of coarse tremors effectively managed with deep brain stimulation presented with multiple intracranial metastases from a newly diagnosed lung cancer and was referred for whole-brain radiation therapy. She was treated with a German helmet technique to a total dose of 30 Gy in 10 fractions using 6 MV photons via opposed lateral fields with the neurostimulator turned off prior to delivery of each fraction. The patient tolerated the treatment well with no acute complications and no apparent change in the functionality of her neurostimulator device or effect on her underlying neuromuscular disorder. This represents the first reported case of the safe delivery of whole-brain radiation therapy in a patient with an implanted neurostimulator device. In cases such as this, neurosurgeons and radiation oncologists should have discussions with patients about the risks of brain injury, device malfunction or failure of the device, and plans for rigorous testing of the device before and after radiation therapy 11).
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