Major depressive disorder is a worldwide disease with debilitating effects on a patient's life. Common treatments include pharmacotherapy, psychotherapy, and electroconvulsive therapy. Many patients do not respond to these treatments; this has led to the investigation of alternative therapeutic modalities. Deep brain stimulation (DBS) is one of these modalities. It was first used with success for treating movement disorders and has since been extended to the treatment of psychiatric disorders. Although DBS is still an emerging treatment, promising efficacy and safety have been demonstrated in preliminary trials in patients with treatment-resistant depression (TRD). Further, neuroimaging has played a pivotal role in identifying some DBS targets and remains an important tool for evaluating the mechanism of action of this novel intervention. Preclinical animal studies have broadened knowledge about the possible mechanisms of action of DBS for TRD, Given that DBS involves neurosurgery in patients with severe psychiatric impairment, ethical questions concerning capacity to consent arise; these issues must continue to be carefully considered.

Deep brain stimulation in the treatment of depression.

Introduction
The Neurostimulation Appropriateness Consensus Committee (NACC) was formed by the International Neuromodulation Society (INS) in 2012 to evaluate the evidence to reduce the risk of complications and improve the efficacy of neurostimulation. The first series of papers, published in 2014, focused on the general principles of appropriate practice in the surgical implantation of neurostimulation devices. The NACC was reconvened in 2014 to address specific patient care issues, including bleeding and coagulation.

Methods
The INS strives to improve patient care in an evidence-based fashion. The NACC members were appointed or recruited by the INS leadership for diverse expertise, including international clinical expertise in many areas of neurostimulation, evidence evaluation, and publication. The group developed best practices based on peer-reviewed evidence and, in the absence of specific evidence, on expert opinion. Recommendations were based on international evidence in accordance with guideline creation.

Conclusions
The NACC has recommended specific measures to reduce the risk of bleeding and neurological injury secondary to impairment of coagulation in the setting of implantable neurostimulation devices in the spine, brain, and periphery.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Bleeding and Coagulation Management in Neurostimulation Devices.

Poly(ADP-ribose) polymerases (PARPs or ARTDs), originally described as DNA repair factors, have metabolic regulatory roles. PARP1, PARP2, PARP7, PARP10, and PARP14 regulate central and peripheral carbohydrate and lipid metabolism and often channel pathological disruptive metabolic signals. PARP1 and PARP2 are crucial for adipocyte differentiation, including the commitment toward white, brown, or beige adipose tissue lineages, as well as the regulation of lipid accumulation. Through regulating adipocyte function and organismal energy balance, PARPs play a role in obesity and the consequences of obesity. These findings can be translated into humans, as evidenced by studies on identical twins and SNPs affecting PARP activity.

http://genesdev.cshlp.org/content/34/5-6/321.full.pdf

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

/pdf/intraoperative-electrocorticography-for-physiological-4k8pkjpjx4.pdf

Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases

OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS 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.

/pdf/intraoperative-mri-for-optimizing-electrode-placement-for-11u0fsgkn7.pdf

Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease

Object Deep brain stimulation (DBS) is an established neurosurgical technique used to treat a variety of neurological disorders, including Parkinson disease, essential tremor, dystonia, epilepsy, depression, and obsessive-compulsive disorder. This study reports on the use of intraoperative MR imaging during DBS surgery to evaluate acute hemorrhage, intracranial air, brain shift, and accuracy of lead placement. Methods During a 46-month period, 143 patients underwent 152 DBS surgeries including 289 lead placements utilizing intraoperative 1.5-T MR imaging. Imaging was supervised by an MR imaging physicist to maintain the specific absorption rate below the required level of 0.1 W/kg and always included T1 magnetization-prepared rapid gradient echo and T2* gradient echo sequences with selected use of T2 fluid attenuated inversion recovery (FLAIR) and T2 fast spin echo (FSE). Retrospective review of the intraoperative MR imaging examinations was performed to quantify the amount of hemorrhage and the amount of...

Intraoperative magnetic resonance imaging findings during deep brain stimulation surgery.

Background: More than 80% of patients with advanced cancer develop weight loss. Because preclinical data suggest poly (ADP-ribose) polymerase (PARP) inhibitors can treat this weight loss, this study was undertaken to explore the PARP inhibitor veliparib for this indication. Objective: The current study was undertaken to analyze prospectively gathered data on weight in cancer patients on PARP inhibitors. Design/Setting: The current study relied on a previously published, prospectively conducted phase 1 single institution trial that combined veliparib and topotecan (NCT01012817) as antineoplastic therapy for advanced cancer patients. Serial weight data and, when available and clinically relevant, computerized tomography scans were also examined. Measurements: The primary endpoint was 10% or greater weight gain from trial enrollment. Results: Nearly all 60 patients lost weight over time. Only one patient manifested a 10% or greater gain in weight. However, review of computerized tomography L3 images...

/pdf/does-the-poly-adp-ribose-polymerase-inhibitor-veliparib-41bcm5zp4q.pdf

Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients.

Lung cancer in non-smoking women is a distinct entity, but few studies have examined these patients’ healthcare-related experiences. Women with lung cancer and with no smoking history underwent a face-to-face semi-structured, audio-recorded interview that was analyzed with a qualitative inductive approach. Twenty-three patients were interviewed, and three themes emerged. The first theme centered on a delay in cancer diagnosis. One patient described, “The whole initial diagnostic process just fills me with rage… I didn’t actually get my Tarceva® until the last week in April.” Second, the diagnosis of lung cancer seemed especially challenging in view of patients’ non-smoking history and otherwise good health; these factors seem to have contributed to the diagnostic delay. One patient explained, “Well, I was just so adamant that I didn’t like smoking… maybe if I had been a smoker, they [the healthcare providers] would’ve been more resourceful.” Finally, the stigma of a smoking-induced malignancy was clearly articulated, “Yeah. Because it’s a stigma, and I had read that, too -- people go, ‘Well, it’s your own damn fault because you were a smoker.’” Non-smoking women with lung cancer appear to endure a long trajectory from symptoms to cancer diagnosis to the initiation of cancer therapy. An awareness and acknowledgement of this long trajectory might help healthcare providers render more compassionate cancer care to these patients.

Olivia Huston

Papers

Intraoperative magnetic resonance imaging findings during deep brain stimulation surgery.

Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients.

A qualitative study of healthcare-related experiences of non-smoking women with lung cancer.