We reviewed our deep brain stimulation patient database to describe hardware complications which resulted from implantable pulse generator mobility, a phenomenon referred to as twiddler’s syndrome. A prospectively collected database of adverse events for all patients operated on at the University of Florida was queried searching for hardware malfunctions. Of 362 total leads implanted in 226 patients since 2002, there were 17 hardware malfunctions. Three of them were due to twiddler’s syndrome, representing 1.3% of patients (3 of 226 patients) and 1.4% of leads (5 of 362 leads). The subjects had characteristic presentations including re-emergence of symptoms, pain along the path of the hardware, abnormal impedances/current drain and radiographic signs of twisting/fracture. In all cases securing the implantable pulse generator within the chest pocket resolved the issue. Twiddler’s syndrome in the population of movement disorder patients treated with deep brain stimulation is an uncommon but important adverse event. It possesses a characteristic presentation and with appropriate diagnostic evaluation it is treatable and future occurrences are preventable.

Objective: To report the results of ventralis intermedius nucleus/ventralis oralis posterior nucleus (VIM) plus ventralis oralis anterior (VOA)/ventralis oralis posterior (VOP) thalamic deep brain stimulation (DBS) for the treatment of posttraumatic and multiple sclerosis tremor. Objective: The treatment of posttraumatic tremor and multiple sclerosis tremor, by either medication or surgery, has proven difficult. Lesions and DBS have had mixed and somewhat disappointing results. Previously, we reported the use of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border) as effective for the treatment of posttraumatic tremor in a single patient. In this study, we report the results of this technique on four patients. Methods: Four patients with either posttraumatic tremor (n = 3) or multiple sclerosis tremor (n = 1) underwent placement of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border). Patients underwent preoperative testing and testing at a minimum of 6 months after implantation in four conditions: On VIM DBS/On VOA/VOP DBS; On VIM DBS/Off VOA VOP DBS (5 h DBS washout); Off VIM DBS/Off VOA/VOP DBS (12 h overnight washout); and Off VIM DBS/On VOA/ VOP DBS (5 h DBS washout). Results: Each of the patients showed improvements in all four conditions when compared with the baseline. All of the improvements were maintained with chronic DBS, without tremor rebound. An analysis was performed to determine whether each condition was associated with symptom reduction (percentage change). The percentage reduction was significant for each condition and measure, despite the small number of participants. For the total tremor rating scale score, the Off VIM/Off VOA/VOP condition yielded less symptom reduction than the On VIM condition or the On VOA/VOP condition. The On VIM and On VOA/VOP conditions did not differ significantly from each other in terms of contralateral upper extremity symptoms or total clinical score. Activation of both the VIM and VOA/VOP electrodes was associated with the greatest symptom reduction. Conclusion: Tremors, such as those examined in this study, that are refractory to medications and have a poor response to VIM DBS monotherapy, may respond favorably to VIM plus VOA/VOP DBS. Two electrodes may be better than one for the treatment of certain disorders; however, more study will be required to confirm this hypothesis.

BACKGROUND Testosterone deficiency has been reported in patients with Parkinson disease (PD), Alzheimer disease, and Huntington disease. It is not known whether testosterone therapy (TT) in men with borderline hypogonadism and neurodegenerative diseases will be of substantial benefit. Previously, we reported that testosterone deficiency is more common in patients with PD compared with age-matched control subjects, and we also reported in 2 small open-label studies that some nonmotor symptoms responded favorably to TT. OBJECTIVE To define the effects of TT on nonmotor and motor symptoms in men with PD and probable testosterone deficiency. DESIGN Double-masked, placebo-controlled, parallel-group, single-center trial. PATIENTS Two experimental groups: patients with PD who were receiving either TT or placebo. INTERVENTIONS Participants received either the study drug by intramuscular injection (200 mg/mL of testosterone enanthate every 2 weeks for 8 weeks) or placebo (isotonic sodium chloride solution injections). In patients in each group, the testosterone serum concentration was obtained at each study visit. During 2 study visits, testosterone levels were blindly evaluated and the intramuscular testosterone dose was increased by 200 mg/mL if the free testosterone value failed to double from the baseline value. MAIN OUTCOME MEASURES The primary outcome variable was the St Louis Testosterone Deficiency Questionnaire, and secondary outcome measures included measures of mood, cognition, fatigue, motor function, and frequency of adverse events. At the end of the double-blind phase, all patients were offered open-label TT and were followed up after 3 and 6 months. RESULTS Fifteen patients in the placebo group (mean age, 69.9 years), receiving a mean total levodopa equivalent dose of 924 mg/d, had a baseline free testosterone level of 47.91 pg/mL, compared with 15 patients in the TT group (mean age, 66.7 years), receiving an average total levodopa equivalent dose of 734 mg/d, who had a baseline free testosterone level of 63.49 pg/mL. Testosterone was generally well tolerated. More subjects in the TT group experienced lower extremity edema (40% vs 20%). In 2 patients, 1 in each group, prostate-specific antigen levels were elevated from baseline. The improvement in the TT group compared with the placebo group (1.7 vs 1.1) on the St Louis Testosterone Deficiency Scale was not statistically significant. In addition, there were no significant differences in motor and nonmotor features of PD between the 2 groups, although a few subscales showed improvements (Hopkins Verbal Learning Test, P<.04; and Backward Visual Span subtrial, P<.03). However, long-term open-label TT resulted in delayed but sustained improvement in subjects in the TT group who continued to receive treatment (n = 6) compared with subjects in the placebo group who elected not to receive TT (n = 3). CONCLUSIONS Testosterone therapy was generally well tolerated in elderly men with PD and probable testosterone deficiency. While there was no significant difference in the motor and nonmotor scales between the TT and placebo groups at the end of 8 weeks compared with baseline, this may be due to several study limitations, including small sample size, a strong placebo effect with intramuscular therapy, and short follow-up that did not allow measurement of delayed effects of TT in some subjects. Until more definitive studies are reported, practitioners should be particularly cautious in treatment of low testosterone concentrations in men with PD and borderline testosterone deficiency, and careful consideration should be given to the risks vs the benefits of TT.

It may be that these two types of symptoms are able to be dissociated based on pathology or pathophysiology. Studies have typically associated orbitofrontal-basal ganglia connections in the presence of depression in PD, whereas anterior cingulatebasal ganglia connections are suggested in the presence of apathy. It is possible that PD subjects with apathy in the absence of depression have more pathological involvement of the anterior cingulate than the orbitofrontal area, but this remains for future investigation.