1. Complications of Deep Brain Stimulation: Risks of Placement vs Neurostimulator Device Issues Shahid M. Nimjee, MD, PhD Isaac O. Karikari, MD Tiffany R. Hodges, MD Dennis A. Turner, MD, MA

2. Background Deep brain stimulation (DBS) is effective treatment for tremor and Parkinson's disease in controlled trials, yet requires the implant of both electrode leads into specific brain regions (ie, hemorrhage, stroke), and a control unit and battery. Complications can arise from the brain placement of the leads, systemic risks associated with a major surgical procedure, as well as infection, wound or electrode migration issues associated with the neurostimulator device.

3. Study Retrospective review of DBS implants at a single institution and evaluation of complications, infections, dehiscence, revisions, morbidity and mortality

4. Demographics 162 patients/301 DBS lead implantations 107 (66%) were male and 55 (34%) were female The mean age was 63 ± 13 years.

5. Indications for Surgery Akinetic-rigid Parkinson’s disease in 92 patients (56%) Essential tremor in 42 (26%) Tremor-dominant Parkinson’s disease in 11 (7%) Dystonia in 9 patients (6%) Average time to surgery from diagnosis was 13.4 ± 11.7 years.

6. Co-morbidities Number (%) Hypertension Coronary artery disease Hyperlipidemia GERD Osteoarthritis Depression Anxiety Diabetes Prostate cancer Atrial Fibrillation Renal stones COPD CHF Asthma OSA Tobacco abuse PUD Osteoporosis Alcohol abuse PVD Bipolar disorder 45 (28%) 19 (11%) 11 (7.4%) 18 (11%) 24 (15%) 9 (5.6%) 8 (4.9%) 7 (4.3%) 6 (3.7%) 5 (3.1%) 4 (2.5%) 2 (1.2%) 1 (0.6%)

7. Battery Placement All but 17 (11.7%) patients underwent battery implantation at the time of electrode placement 13 (76.4%) are male and 4 (23.5%) are female No correlation between gender and delayed battery placement (p=0.42) Age of the patients ranged from 38 – 72 years Reason for not implanting the battery with electrode placement included: – fatigue in 11 (64.7%) patients – confusion and cardiac changes in 2 (11.7%) patients – respiratory changes and preference for a different battery in 1 (5.8%) patient.

8. Battery Replacement 109 battery replacements in 75 patients Batteries lasted approximately (2.88 ± 1.76 years) years before needing replacement – 2 patients who required 4 battery changes, one had Parkinson’s-induced tremor and the other had essential tremor – Average duration each battery lasted was 1.78 ± 0.34 years and 1.52 ± 0.54 years respectively – One patient had 5 and another had 6 battery changes. Both patients underwent DBS to treat dystonia. Their batteries lasted on average 1.20 ± 0.18 and 0.79 ± 0.19 years.

9. Hemorrhage 4 (2.5%) patients demonstrated asymptomatic intracranial hemorrhages post-operatively on the routine CT scans 2 patients (1.2%) showed evidence of intraventricular hemorrhage and 2 (1.2%) patients were noted to have intraparenchymal hemorrhages No patient had any focal neurological deficits or other symptoms secondary to the hemorrhage noted on the routine CT scan. There was no relationship between age or sex and bleed (p=1.0).

10. Infection 8 (4.9%) bacterial infections in the series – 4 female and 4 male – 6 were greater than 65 years of age, although this was not statistically significant (p=0.28). Average time of infection after surgery was 4.3 ± 3.6 months Species identified in culture included: – methicillin-sensitive staphylococcus (3) – Coagulase-negative staphylococcus (3) – enterobacter (1) – co-infection with coagulase-negative staphylococcus and pseudomonas (1) 3 of the 4 patients with coagulase-negative staphylococcus infections underwent removal of the hardware with treatment of infection with antibiotics before replacing hardware, including the patient with co-infection with pseudomonas 4 th patient underwent simple irrigation and debridement with antibiotic treatment. Antibiotic therapy included vancomycin for the single species and in the case of combined coagulase-negative staphylococcus and pseudomonas infection, vancomycin, ceftazidime, cefepime and ciprofloxacin were used. Lone patient with an enterobacter infection had their hardware removed and was treated with keflex. All three patients with methicillin-sensitive staphylococcus aureus underwent surgery. – Two patients had their hardware removed and one underwent irrigation and debridement – All three patients received antibiotics. One received nafcillin, the second received vancomycin and the third patient received clindamycin None of the 8 patients died of their infections Mean time in the hospital secondary to infection was 4.1 days (range 1 – 8 days) All except one patient eventually had their hardware replaced uneventfully; this one patient has decided not to have DBS performed again.

11. Dehiscence 3 patients (1.9%) had dehiscence without any culture evidence of infection – 2 were at the burr hole sites and 1 was a lead that had eroded through the skin All 3 patients underwent irrigation and revision without any additional complications There was no removal of hardware No patient received antibiotics subsequent to revision With respect to medical co-morbidities as it relates to dehiscence, one of the patients had hypertension and hyperlipidemia, the second had asthma and the third had no medical issues.

12. Lead Revision 3.0% lead revisions – 3 (1.3%) were secondary to tip migration post-operatively – 2 (0.67%) were the results of displacing the leads after tunneling, following verification of placement with intra- operating fluoroscopic testing – 2 were secondary to lead fracture from patients bumping their head – 1 (0.33%) involved re-positioning leads due to poor location (DBS placement performed initially at an outside institution).

13. Intraoperative Morbidity 1 patient’s (0.62%) procedure was aborted secondary to air embolism; the patient had lead implantation uneventfully at a later date. There were no postoperative deep venous thrombosis episodes noted, and no pulmonary embolism; all patients were followed in detail at 2 and 4 weeks and postoperative complications were noted routinely, even if the patient had episodes of care outside of our hospital system. All patients had intra-operative sequential compression devices and rapid postoperative mobilization; over 90% were discharged on the first post-operative morning, so postoperative lovenox or heparin was not administered (in contrast to Bauman et al 2009).

14. Mortality 1 (0.62%) death post-operatively Patient suffered a myocardial infarction which began during the awake lead implantation procedure, being performed for severe essential tremor – remote history of coronary artery disease and had stopped taking aspirin for 7 days and plavix for 3 weeks in preparation for the DBS procedure – placement of multiple previous coronary stents and had been on long-term plavix to prevent myocardial infarction recurrence.

15. Conclusions Highest risks of primary DBS implants are those related to the implants (infection, dehiscence and lead revision) rather than the brain placement These risks are similar in scope to similar neuroprosthetic devices proposed for treatment of movement disorders, including cortical brain stimulation and spinal cord stimulation In contrast to DBS, these suggested alternative sites for neuromodulation have much less demonstrated efficacy despite similar overall risks Our DBS complication data compare favorably to events noted in recent multi-center trials of DBS and retrospective series