Taking a better history for behavioral issues pre- and post-deep brain stimulation: issues missed by standardized scales.

OBJECTIVES: To screen for potentially underreported behavioral changes in patients with idiopathic Parkinson's disease (PD) pre- and post-deep brain stimulation (DBS), a retrospective data base review was performed. METHODS: In total, 113 patients who underwent unilateral or bilateral DBS at the University of Florida in either subthalamic nucleus or globus pallidus internus for PD were screened for behavioral issues by asking about the presence or absence of seven neuropsychiatric symptoms (panic, fear, paranoia, anger, suicidal flashes, crying, and laughing). RESULTS: There was a high prevalence of fear (16.3%), panic (14.0%), and anger (11.6%) at baseline in this cohort. In the first six months following DBS implantation, anger (32.6%), fear (26.7%), and uncontrollable crying (26.7%) were the most frequent symptoms reported. Those symptoms also were present following six months of DBS surgery (30.2%, 29.1%, and 19.8%, respectively). New uncontrollable crying occurred more in the acute postoperative stage (less than or equal to six months) (p = 0.033), while new anger occurred more in the chronic postoperative stage (greater than six months) (p = 0.017). The frequency of uncontrollable laughing significantly increased with bilateral DBS (p = 0.033). CONCLUSIONS: Many of the neuropsychiatric issues were identified at preoperative baseline and their overall occurrence was more than expected. There was a potential for worsening of these issues post-DBS. There were subtle differences in time course, and in unilateral vs. bilateral implantations. Clinicians should be aware of these potential behavioral issues that may emerge following DBS therapy, and should consider including screening questions in preoperative and postoperative interviews. Standardized scales may miss the presence or absence of these clinically relevant issues.

Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial.

OBJECTIVE: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

Tracing the origin of L-2-hydroxyglutaric aciduria in a family.

We describe late diagnosis of an adult with L-2-hydroxyglutaric aciduria (MIM 236792) on the basis of characteristic metabolite data and mutation analysis in the L2HGDH gene. The patient lacked MRI abnormalities which have been purported to be constant or typical findings in this disease. We further report the genetic status of his parents and his one living sibling. Our observations underline the clinical heterogeneity of the syndrome of L-2-hydroxyglutaric aciduria. This report emphasizes the diagnostic benefit of the assessment of urinary organic acids not only in children, but also in adult patients with unexplained neurological symptoms. The patient was determined to be compound heterozygous for two novel missense mutations in exon 4 of the gene (c.418G>C, c.446T>G), resulting in amino acid exchanges from alanine to proline (p.Ala140Pro) and leucine to arginine (p.Leu149Arg), respectively. The mother of our patient was heterozygous for Ala140Pro, and the father heterozygous for Leu149Arg only. Mutation analysis of a healthy 49-year-old third son of the non-consanguineous parents revealed a normal exon 4.

Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study.

Polysomnographic studies of Parkinson's disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapine's efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study. Sixteen PD patients experiencing VH were recruited. Eight patients were randomized to quetiapine and eight patients to placebo. Patients underwent pre- and post-treatment polysomnography. The Clinical Global Impression Scale (CGIS), Brief Psychiatric Rating Scale (BPRS), and Unified Parkinson Disease Rating Scale (UPDRS) motor subscale were obtained. There were no differences in baseline characteristics between the treatment arms except that the placebo group had more sleep in stage REM (74.7 min vs. 40.1 min; p < .001). Data were imputed for all patients who prematurely discontinued (four quetiapine and one placebo) in an intention-to-treat analysis. The average quetiapine dose was 58.3 mg/day. While there was no significant difference in the change in REM duration pre- vs. post-treatment in either arm, patients randomized to quetiapine improved on the CGIS (p = .03) and the hallucination item of the BPRS (p = .02). No difference was noted in the UPDRS motor scores. Despite the small sample, this is the first double-blind trial to show quetiapine's efficacy over placebo in controlling VH in the PD population. However, normalization of sleep architecture was not supported as the mechanism.

Tardive parkinsonism in a bipolar patient: post-mortem examination supports a physiological rather than pathological dysfunction.

We describe a case of tardive parkinsonism in the setting of bipolar syndrome, and we offer pathological confirmation that idiopathic Parkinson disease was not the underlying etiology. A 74-year-old Hispanic woman with a history of bipolar disease was noted to have oro-buccal-lingual chorea and parkinsonian symptoms such as resting tremor, rigidity, bradykinesia, and gait disorder persisting several months after neuroleptic discontinuation. She had minor improvement in ambulation with levodopa treatment, and she significantly improved in ambulation only during her manic states. Examination of the subject's post-mortem brain revealed no explicit evidence of degeneration in substantia nigra or other brainstem centers, and no nigral or cortical Lewy bodies were present. Glial cytoplasmic inclusions (characteristic of multiple systems atrophy) and globose neurofibrillary tangles (seen in progressive supranuclear palsy) were not seen either. This patient's presentation was most consistent with neuroleptic-induced parkinsonism and tardive dyskinesia; the etiology was likely related to previous neuroleptic exposure.

Clinical cases where lesion therapy was chosen over deep brain stimulation.

Deep brain stimulation (DBS) surgery has become the gold standard for treatment of select refractory cases of Parkinson disease and essential tremor. Despite the usefulness of DBS surgery in many cases, there remain situations where lesion therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable alternative to DBS. We reviewed the University of Florida Institutional Review Board-approved database for movement disorders surgery and identified 286 DBS leads placed in 189 patients as well as 4 additional patients who had lesion therapy. In these 4 cases we reviewed the clinical presentations that resulted in a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy represents a viable alternative and has several important advantages, including a decreased need for access to specialists and clinical follow-up, improved affordability, and a lower infection risk.

Testosterone therapy in men with Parkinson disease: results of the TEST-PD Study.

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.

Deep Brain Stimulation in a Case of Mitochondrial Disease.

BACKGROUND: DBS has proven to be an effective therapy for Parkinson's disease, essential tremor, and primary dystonia. Mixed results have been reported in case series for other hyperkinetic disorders, and sparse data are available regarding secondary movement disorders. We report on the clinical effects of bilateral globus pallidus internus (GPi) DBS, a progressive mitochondrial cytopathy. METHODS: A single patient with myoclonus and dystonia syndrome secondary to a mitochondrial cytopathy with history of perinatal hypoxia was identified from our University of Florida DBS database. Demographics, clinical, surgical, and DBS data were documented. RESULTS: At 6 months post-DBS, we observed a 32% (361 to 527) improvement on quality of life (36-item Medical Outcome Study Short-Form Health Survey; SF-36). Objective clinical scales revealed a 33% (143 to 96) improvement in the Unified Myoclonus Rating Scale (UMRS) total score. The UMRS action myoclonus subsection revealed a 29% (69 to 46) improvement. No significant changes were observed in the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS). After 1-year follow-up, a worsening of 59% (527 to 215) was observed in the SF-36 scale, of 19% (28.5 to 35) in the BFMDRS, and of 23% (96 to 124) in the UMRS. However, the frequency and intensity of action myoclonus scores remained lower when compared to baseline scores. CONCLUSIONS: Although we observed a loss of benefit in the long term for most quality-of-life and clinical outcomes, the DBS effects on action myoclonus seemed to remain stable. Longer follow-up studies are necessary to confirm our short-term and unblinded findings.

Rationale for current therapies in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that affects an estimated 1 million people in the US and tens of millions worldwide. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. This review will describe the rationale and strategies for current medical therapies in PD, with special emphasis on the use of antipsychotic agents. Levodopa remains the most efficacious medication for the management of PD. Long-term use of levodopa, however, is associated with the development of motor fluctuations including dyskinesia. Trials with dopamine agonists have demonstrated a delay in the onset of dyskinesia with the use of this therapy. There is also active, ongoing investigation to determine whether a neuroprotective effect may be present with agonist therapy. Anticholinergics have been successfully used to treat tremor as well as sialorrhoea and urinary urgency. Catechol-O-methyltransferase inhibitors increase 'on time', decrease 'off time,' and improve motor scores. Continuous stimulation of dopamine receptors may decrease the fluctations observed with pulsatile delivery of anti-Parkinsonian medications, but this will require more study. Monoamine oxidase-B inhibitors, specifically selegiline, may provide symptomatic improvement; the question as to whether a neuroprotective benefit is present remains unanswered. Amantadine has demonstrated both symptomatic benefit and dyskinesia benefit in some patients. Selective dopamine blockers such as clozaril and quetiapine, have been shown to be effective in the treatment of psychosis. This class of medications is particularly useful as an adjunctive to levodopa and dopamine agonists. Doses of dopaminergic drugs can be escalated to treat Parkinsonian symptoms, whereas selective dopamine blockers can be added to block psychosis. Old management strategies required a reduction in dopaminergic therapy and therefore worsened Parkinsonian symptoms. Even though there have been great advances in the medical options for symptomatic management of PD, there are still many unmet needs for this patient population.

An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting.

BACKGROUND: To examine our eight year clinic-based experience in a Parkinson's disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). METHODS: The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. RESULTS: There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45-87 years (mean 68.3±10.15), disease duration of 17-240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = -0.36, p<0.01) and H&Y score (r = -0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). CONCLUSIONS: This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting.

GPi and STN deep brain stimulation can suppress dyskinesia in Parkinson's disease.

OBJECTIVES: To compare subthalamic nucleus (STN) to globus pallidus internus (GPi) deep brain stimulation (DBS) for control of motor fluctuations and for potential dyskinesia-suppressing qualities. METHODS: We conducted a retrospective database review of all patients who underwent GPi or STN DBS for idiopathic Parkinson's disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the unified Parkinson's disease rating scale (UPDRS) part IV (items 32-34), despite lack of reduction in dopaminergic medication dosage. We analyzed the data using methods appropriate for a case-control study. RESULTS: A total of 133 patients were evaluated. At the last evaluation Dyskinesia scores and motor fluctuations significantly improved in both the GPi (p < 0.0001) and STN groups (p < 0.0001). The GPi group was more likely than the STN group to experience dDS (odds ratio = 1.95, 95% CI = 0.556, 3.21). However, the association between DBS target and dDS was not statistically significant (Pearson chi-square = 2.286, p = 0.131). CONCLUSIONS: The overall clinical outcome of STN and GPi DBS for control of dyskinesia and motor fluctuations was similar. STN and GPi DBS both had some direct dyskinesia suppression effects.

Delayed clinical improvement after deep brain stimulation-related subdural hematoma. Report of 4 cases.

OBJECT: The purpose of this paper is to present 4 cases that illustrate the management and outcome of subdural hematoma (SDH) following deep brain stimulation (DBS) lead implantation. METHODS: The authors identified 4 cases of SDH following DBS lead implantation from a pool of 500 consecutive lead implantations (incidence 0.08%) performed at the University of Florida. Cases were characterized by chart review, serial Unified Parkinson's Disease Rating Scale evaluations, and changes on serial postoperative imaging studies. RESULTS: Two of the 4 patients with DBS-related SDH were clinically symptomatic. In the other 2 cases the SDH was incidentally discovered on routine postoperative lead localization imaging studies. None of the patients required craniotomy for evacuation of the SDH in the acute phase. Three of the 4 cases were managed with bur hole drainage in the chronic phase, and one was successfully managed nonoperatively. In all 4 cases, thresholds for stimulationinduced side effects were lower during initial postoperative programming than during intraoperative macrostimulation. Expected clinical improvement from DBS was achieved without lead revision in all 4 cases, but only after a significant delay. CONCLUSIONS: Subdural hematoma is a rare and potentially avoidable complication of DBS that does not typically mandate acute hematoma evacuation or hardware revision and does not preclude an excellent outcome from DBS therapy. The clinical picture and apparent lead position tend to improve with time, and it may be wise to delay repositioning of an ineffective DBS lead following a hemorrhage until the DBS lead and surrounding brain tissue have settled into their final position and the insulted brain has had sufficient time to recover.

Steady or not following thalamic deep brain stimulation for essential tremor.

Deep brain stimulation (DBS) has become an important option for medication-refractory essential tremor (ET), but may contribute to worsened gait and falling. This study evaluates impaired gait in a cohort of patients treated with DBS with a retrospective review of ET patients before and after DBS implantation. Factors examined included: age, duration of symptoms, pre-morbid gait difficulties/falls, Fahn-Tolosa-Marin tremorrating scale (TRS) scores at baseline, 6 months post-unilateral DBS implantation, and 6 or 12 months post-bilateral implantation. All implantations targeted the nucleus ventralis intermediate (Vim). Thirty-eight patients (25 males, 13 females) were included. Twenty-five patients (65.8%) underwent unilateral DBS implantation and 13 (34.2%) bilateral. The mean age at surgery was 67.1 years ± 11.4 (range 34-81). The mean disease duration was 31 years ± 18.3 (range 6-67). Fifty-eight percent of patients had worsened gait post-operatively. Seventy percent of patients with unilateral Vim DBS experienced gait worsening while 55% of bilateral DBS patients experienced gait worsening. Patients with worsened gait post-DBS had higher baseline pre-operative TRS scores than those without worsened gait (43.1 points ± 8.4 vs. 33.1 points ± 10.1, p = 0.002) (odds ratio 2.5, p = 0.02). Gait/balance may worsen following DBS for medication refractory ET. Higher baseline TRS score may factor into these issues, although a larger prospective study will be required with a control population. The larger percentage of difficulties observed in unilateral versus bilateral cases likely reflected the bias not to proceed to second-sided surgery if gait/balance problems were encountered.

Prevalence of hypersexual behavior in Parkinson's disease patients: Not restricted to males and dopamine agonist use.

This study investigates the prevalence and demographic characteristics of hypersexuality in Parkinson's disease (PD). Impulse control disorders in PD patients have been associated with dopamine agonist therapy. Moreover, hypersexuality and pathological gambling have been associated with males, while females may be inherently thought to be more likely to participate in compulsive shopping and binge-eating behaviors. In this study, a screening mail-in survey was sent to all PD patients at a single Movement Disorders Center. One hundred forty one of 400 (35.3%) research packets were returned completed. Fifteen of 141 patients met initial screening criteria for hypersexual behavior. After detailed interview, only 6/141 (4.3%) of PD patients met criteria for pathologic hypersexual behavior. These behaviors included: compulsive masturbation, prostitution, and paraphilias. Patients with a younger age of PD onset were more likely to exhibit hypersexual behavior. Unlike previous report, no significant association was found between hypersexuality and gender or dopamine agonist use. Rather, this study suggests that physicians should be vigilant for hypersexual behavior in all PD patients, regardless of gender and PD medication regimen. Ultimately, given the innate sensitivity of the topic and survey limitations, it is very likely that hypersexual behavior in our cohort, as it is in the general PD population, has been under-reported.

Laterality, region, and type of motor dysfunction correlate with cognitive impairment in Parkinson's disease.

We studied the relationship between two screening cognitive measures and off motor Unified Parkinson's Disease Rating Scale (UPDRS) scores in 108 Parkinson's disease patients. Multiple regressions were conducted to examine the UPDRS subscores' unique contributions to cognitive function. When including bradykinesia, rigidity, and postural/gait instability subscores, only bradykinesia predicted Mini Mental Status Examination (MMSE), normalized beta = -0.57, t(104) = -3.31, P < 0.01, and Dementia Rating Scale-2 (DRS-2), normalized beta = -0.45, t(104) = -2.55, P < 0.05. Tremor was not included in the regression analyses because it did not correlate with cognitive function. When including axial and appendicular subscores, only the axial subscore predicted MMSE, normalized beta = -0.39, t(105) = -3.19, P < 0.01, and DRS-2 scores, normalized beta = -0.40, t(106) = -3.28, P < 0.01. When including left-sided and right-sided subscores, only the right-sided symptoms predicted DRS-2 scores, normalized beta = -0.28, t(105) = -2.45, P < 0.05, and showed a trend toward predicting MMSE scores, normalized beta = -0.22, t(105) = -1.95, P = 0.054. We therefore found that right-sided symptoms (for laterality), axial symptoms (for region), and bradykinesia (for type of symptoms) were the best predictors of cognitive function.

Dual electrode thalamic deep brain stimulation for the treatment of posttraumatic and multiple sclerosis tremor.

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.

Aphasia and thalamotomy: important issues.

Patients may present with classical symptoms suggesting aphasia following thalamotomy (repetition, comprehension, fluency and naming abnormalities). They may also present with 'freezing of speech', and this symptom should not be considered as a speech disorder or a symptom of Parkinson's disease progression, without careful testing to rule out language deficits, particularly dysfluency. There are important issues related to all language complications of thalamotomy, including (1) the time course of problems following surgery, (2) the impact of preexistingspeech problems, (3) the importance of the size and location of lesions, (4) the potential circuits important in the pathogenesis of a thalamic language disturbance and (5) whether laterality makes a difference (left- versus right-sided thalamic lesions). As more centers switch from thalamotomy to deep brain stimulation, the issues regarding aphasia will need to be addressed.