Neuropathology of Parkinson's disease after focused ultrasound thalamotomy.

Focused ultrasound (FUS) thalamotomy is an emerging treatment for tremor-dominant Parkinson's disease (PD). We report the first postmortem neuropathologic study of FUS thalamotomy in a 68-year-old man with tremor-dominant PD, which was performed seven months before he died. Although the peak voxel temperature at the target was <54 °C, his tremor improved on intraoperative and postoperative assessments. Additionally, postoperative MRI demonstrated a thalamic lesion. Lewy body-related pathology consistent with PD was detected. There was also a 5-mm lesion in the ventral lateral thalamus characterized by demyelination and neuropil loss, with many lipid-laden macrophages, but no lymphocytic infiltrates and relatively preserved neurons and axons. Additional pathological assessments after FUS thalamotomy are needed to determine if the observed brain changes are typical of this procedure.

Focused ultrasound and other lesioning in the treatment of tremor.

There has been a long history of lesioning procedures to treat tremor associated with both essential tremor (ET) and Parkinson's disease (PD). These include radiofrequency (RF) thalamotomy, gamma knife radiosurgical (GKRS) thalamotomy, and magnetic resonance-guided focused ultrasound (MRgFUS). In this review, we summarize the clinical studies of lesioning procedures for tremor focusing on these ablative therapies for ET and tremor-predominant PD (TDPD). We then consider clinical treatment variables that influence decision-making regarding ablative therapies versus consideration of deep brain stimulation (DBS) and conclude with ongoing and future studies. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.

Cholinergic nucleus 4 atrophy and gait impairment in Parkinson's disease.

BACKGROUND: There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson's Disease (PD), especially reduced gait speed. OBJECTIVES: The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients. METHODS: We investigated 66 PD patients who underwent a pre-surgical evaluation for a neurosurgical procedure to treat motor symptoms of PD. As part of this evaluation patients had a brain MRI and formal gait assessments. By applying probabilistic maps of the cholinergic basal forebrain to voxel-based morphometry of brain MRI, we calculated gray matter density (GMD) for cholinergic nucleus 4 (Ch4), cholinergic nucleus 1, 2, and 3 (Ch123), and the entire cortex. RESULTS: Reduced Ch4 GMD was associated with reduced Fast Walking Speed in the "on" medication state (FWSON, p = 0.004). Bilateral cortical GMD was also associated with FWSON (p = 0.009), but Ch123 GMD was not (p = 0.1). Bilateral cortical GMD was not associated with FWSON after adjusting for Ch4 GMD (p = 0.44). While Ch4 GMD was not associated with improvement in Timed Up and Go (TUG) or Cognitive TUG in the "on" medication state, reduced Ch4 GMD was associated with greater percent worsening based on dual tasks (p = 0.021). CONCLUSIONS: Reduced Ch4 GMD is associated with slower gait speed in PD and greater percent worsening in TUG during dual tasks in patients with PD. These findings have implications for planning of future clinical trials investigating cholinergic therapies to improve gait impairment in PD.

Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease.

BACKGROUND: The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. METHODS: We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. RESULTS: Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months. CONCLUSIONS: Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Comparison of Parkinson's Disease Patients' Characteristics by Indication for Deep Brain Stimulation: Men Are More Likely to Have DBS for Tremor.

Background: We investigated whether the characteristics of Parkinson's disease (PD) patients differ based on the primary indication for deep brain stimulation (DBS). Methods: We reviewed data for 149 consecutive PD patients who underwent DBS at the University of Virginia. Patients were categorized based on primary surgical indication, and clinical characteristics were compared between groups. Results: Twenty-nine (93.5%) of 31 PD patients who underwent DBS for medication refractory tremor were men, and 66 (62.3%) of 106 PD patients who underwent DBS for motor fluctuations were men (p = 0.001). Other primary indications for DBS were tremor and fluctuations (n = 5), medication intolerance (n = 5), and dystonia (n = 2). Discussion: Patients who underwent DBS for medication refractory tremor were predominantly men, while patients who had DBS for motor fluctuations approximated the gender distribution of PD. Possible explanations are that men with PD are more likely to develop medication refractory tremor or undergo surgery for medication refractory tremor in PD compared to women.

Focused Ultrasound and Other Lesioning Therapies in Movement Disorders.

PURPOSE OF REVIEW: Lesioning therapies have been some of the earliest, most effective surgical treatments in movement disorders. This review summarizes recent studies, emerging modalities, and trends in lesioning procedures for movement disorders. RECENT FINDINGS: Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is the newest incisionless technology for lesioning procedures in movement disorders. It has recent FDA approval for thalamotomy in essential tremor and tremor-dominant Parkinson disease. There are current studies exploring subthalamotomy and pallidotomy in PD. Gamma knife is another incisionless modality that has been studied for decades and remains an effective treatment, albeit with less recent studies and more risks for adverse events, in movement disorders. Radiofrequency lesioning remains an efficacious treatment, particularly for unilateral pallidotomy in PD, but has fallen out of favor compared with other modalities, particularly MRgFUS. Lesioning therapies in movement disorders have shown efficacy in treating a variety of movement disorders. Enthusiasm for their use has waned with the advent of deep brain stimulation. The recent development of MRgFUS has recentered attention on lesioning therapy and its potential. Patient preference and access to care will remain determinants in the use of lesioning therapy as more data are being collected on the long-term benefit and safety.

Focused ultrasound thalamotomy in Parkinson disease: Nonmotor outcomes and quality of life.

OBJECTIVE: To examine nonmotor outcomes and correlates of quality of life (QoL) 3 and 12 months after unilateral focused ultrasound thalamotomy in tremor-dominant Parkinson disease (TDPD). METHODS: Twenty-seven patients with TDPD in a double-blind, sham-controlled, randomized clinical trial underwent comprehensive neuropsychological evaluations. These included assessment of mood, behavior, and QoL at baseline, 3 months, 3 months post crossover in the sham group, and 12 months after active treatment. We used Mann-Whitney U tests to assess differences between the active (n = 20) and sham (n = 7) groups at 3 months and Friedman tests to assess within-group changes after active treatment. We assessed correlations between disease variables and postoperative QoL using Kendall tau-b tests. RESULTS: There were no differences in cognition, mood, or behavior between the active and sham groups at 3-month blinded assessment. After active treatment, there were no differences in mood or behavior. Only declines in Stroop Color Naming and phonemic fluency were observed. Patients experienced postoperative improvements in QoL and activities of daily living (ADL). Mood and behavioral symptoms, aspects of cognitive functioning, ADL, and overall motor symptom severity, but not tremor severity specifically, were associated with QoL. CONCLUSIONS: In TDPD, unilateral focused ultrasound thalamotomy appears safe from a cognitive, mood, and behavioral perspective. QoL and ADL significantly improved following surgery. Nonmotor symptoms and ADL were more closely associated with QoL than tremor severity. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with TDPD, unilateral focused ultrasound thalamotomy did not adversely change cognition, mood, or behavior at 3 months.

Thalamic Deep Brain Stimulation Salvages Failed Focused Ultrasound Thalamotomy for Essential Tremor: A Case Report.

BACKGROUND: A recent randomized controlled trial investigating unilateral MRI-guided focused ultrasound (FUS) for essential tremor demonstrated efficacy. The long-term durability of this thalamotomy, however, is unknown. Furthermore, the feasibility of stimulating a previously lesioned target such as the thalamic nucleus ventralis intermedius (Vim) is poorly understood. We report a case of tremor recurrence, following an initially successful FUS thalamotomy, in which Vim-DBS was subsequently utilized to regain tremor control. METHODS: An 81-year-old right-handed female with medically refractory essential tremor (a Clinical Rating Scale for Tremor [CRST] value of 73) underwent left-sided FUS thalamotomy with initial abolition of right-upper extremity tremor. By the 6-month follow-up, there was complete recurrence of tremor (a CRST value of 76). The patient subsequently underwent left-sided Vim-DBS. RESULTS: Vim-DBS provided clinical improvement with a CRST value of 42 at the 3-month follow-up; the patient continues to do clinically well at the 6-month follow-up. This result mirrors previous reported cases of stimulation following radiofrequency and gamma-knife lesioning. Our literature review highlights several reasons for the waning of clinical benefit seen with lesional procedures. CONCLUSION: This case demonstrates that thalamic DBS can salvage a failed FUS thalamotomy and also the feasibility of stimulating a previously lesioned target.

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease: A Randomized Clinical Trial.

Importance: Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown. Objective: To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD. Design, Setting, and Participants: Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8, 2015. The most common reasons for disqualification were withdrawal (8 persons [31%]), and not being medication refractory (8 persons [31%]). Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome. Interventions: Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding. Main Outcomes and Measures: The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson's Disease Rating Scale (UPDRS) scores and quality of life measures. Results: Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range [IQR], 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79%) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, -11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P = .04). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, -5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events [20%]), finger paresthesia (1 event [5%]), and ataxia (1 event [5%]). Conclusions and Relevance: Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response. Trial Registration: ClinicalTrials.gov identifier NCT01772693.

Characteristics, correlates, and assessment of psychosis in Parkinson disease without dementia.

INTRODUCTION: Considering that psychosis in Parkinson disease (PD) is associated with worse outcomes, including dementia, we aimed to study the characteristics, correlates, and assessment of PD psychosis in those without dementia. METHODS: 101 PD subjects without dementia (Montreal Cognitive Assessment ≥21/30) were recruited to participate in a study of neuropsychiatric symptoms in PD. This study included a baseline standard neurological exam and common PD symptom assessments. Using the Scale for the Assessment of Positive Symptoms (SAPS) and separate assessment of visual illusions and sense of presence, NINDS-NIMH criteria for PD psychosis were applied. RESULTS: Of the 33 (32.7%) PD subjects who met diagnostic criteria for psychosis in PD, visual illusions were most common (72.7%), followed by visual hallucinations (39.4%). Adjusted for presence of REM sleep behavior disorder (RBD) (p = 0.097), use of dopamine agonists (OR = 3.7, p = 0.012) and greater autonomic symptom burden (OR = 1.1 (per 1-unit change in score on SCOPA-AUT), p = 0.012) were associated with greater risk of psychosis. Use of dopamine agonists (OR = 5.0, p = 0.007), higher MDS-UPDRS Part II score (OR = 1.1, p = 0.010), and presence of RBD (OR = 4.8, p = 0.012) were independent predictors of visual hallucinations and visual illusions. MDS-UPDRS item 1.2 score ≥1 had highly correlated with the SAPS score (r = 0.65, p < 0.0001), but was 42% sensitive and 96% specific for identifying psychosis. CONCLUSION: This study confirms the association between dopamine agonists and psychosis in PD patients without dementia. The association of RBD, autonomic symptoms, and MDS-UPDRS Part II scores with psychosis underscore its link to brainstem dysfunction and greater PD motor symptom severity.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

Characterization of Movement Disorder Phenomenology in Genetically Proven, Familial Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.

BACKGROUND: Mutations in granulin (PGRN) and tau (MAPT), and hexanucleotide repeat expansions near the C9orf72 genes are the most prevalent genetic causes of frontotemporal lobar degeneration. Although behavior, language and movement presentations are common, the relationship between genetic subgroup and movement disorder phenomenology is unclear. OBJECTIVE: We conducted a systematic review and meta-analysis of the literature characterizing the spectrum and prevalence of movement disorders in genetic frontotemporal lobar degeneration. METHODS: Electronic databases were searched using terms related to frontotemporal lobar degeneration and movement disorders. Articles were included when cases had a proven genetic cause. Study-specific prevalence estimates for clinical features were transformed using Freeman-Tukey arcsine transformation, allowing for pooled estimates of prevalence to be generated using random-effects models. RESULTS: The mean age at onset was earlier in those with MAPT mutations compared to PGRN (p<0.001) and C9orf72 (p = 0.024). 66.5% of subjects had an initial non-movement presentation that was most likely a behavioral syndrome (35.7%). At any point during the disease, parkinsonism was the most common movement syndrome reported in 79.8% followed by progressive supranuclear palsy (PSPS) and corticobasal (CBS) syndromes in 12.2% and 10.7%, respectively. The prevalence of movement disorder as initial presentation was higher in MAPT subjects (35.8%) compared to PGRN subjects (10.1). In those with a non-movement presentation, language disorder was more common in PGRN subjects (18.7%) compared to MAPT subjects (5.4%). SUMMARY: This represents the first systematic review and meta-analysis of the occurrence of movement disorder phenomenology in genetic frontotemporal lobar degeneration. Standardized prospective collection of clinical information in conjunction with genetic characterization will be crucial for accurate clinico-genetic correlation.

Surgery for Dystonia and Tremor.

Surgical procedures for dystonia and tremor have evolved over the past few decades, and our understanding of risk, benefit, and predictive factors has increased substantially in that time. Deep brain stimulation (DBS) is the most utilized surgical treatment for dystonia and tremor, though lesioning remains an effective option in appropriate patients. Dystonic syndromes that have shown a substantial reduction in severity secondary to DBS are isolated dystonia, including generalized, cervical, and segmental, as well as acquired dystonia such as tardive dystonia. Essential tremor is quite amenable to DBS, though the response of other forms of postural and kinetic tremor is not nearly as robust or consistent based on available evidence. Regarding targeting, DBS lead placement in the globus pallidus internus has shown marked efficacy in dystonia reduction. The subthalamic nucleus is an emerging target, and increasing evidence suggests that this may be a viable target in dystonia as well. The ventralis intermedius nucleus of the thalamus is the preferred target for essential tremor, though targeting the subthalamic zone/caudal zona incerta has shown promise and may emerge as another option in essential tremor and possibly other tremor disorders. In the carefully selected patient, DBS and lesioning procedures are relatively safe and effective for the management of dystonia and tremor.

Enterovirus causes rapidly progressive dementia in a 28-year-old immunosuppressed woman.

Enterovirus in the nervous system can present with protean manifestations, including polio-like paralysis, movement disorders, and seizures. This is a report of a single case of a rapidly progressive dementing illness in a young woman with common variable immunodeficiency (CVID). Over the course of several months, she developed profound aphasia, apraxia, and cerebellar signs. She underwent brain biopsy which was suggestive of toxoplasmosis; despite an adequate course of treatment, she continued to decline and ultimately died. Autopsy and PCR testing revealed diffuse coxsackie B3 infiltration in the meninges and brain parenchyma. To our knowledge, this is the first description of enterovirus causing a dementing illness in a young immunosuppressed adult. We highlight the need for a broad differential diagnosis, especially for immunocompromised individuals, who may present in an atypical fashion.

Deep Brain Stimulation in the Setting of Cochlear Implants: Case Report and Literature Review.

BACKGROUND/AIMS: As technology continues to advance for our aging population, an increasing number of deep brain stimulation (DBS) candidates will have preexisting implanted electrical devices. In this article, we discuss safe and successful DBS in a patient with Parkinson's disease (PD) and bilateral cochlear implants. METHODS: A 70-year-old male with PD and bilateral cochlear implants underwent successful microelectrode-guided DBS implantation into bilateral subthalamic nuclei (STN). The patient's cochlear implant magnets were removed and replaced in the outpatient clinic for preoperative MRI and stereotactic targeting. The cochlear implants were turned off intraoperatively for STN microelectrode recordings. RESULTS: Precise, MRI-guided stereotactic DBS implantation was possible. Intraoperative high-fidelity microelectrode recordings confirmed STN neurons with the cochlear implants turned off. These recordings were not possible with active cochlear implant devices. Our literature review describes the other approaches/techniques that have been used to manage DBS surgery in the setting of cochlear implants. CONCLUSIONS: Despite the risk of electrical interference between implanted medical devices, DBS and cochlear implants may be safe and compatible in the same patient if necessary precautions are taken.

Functional assessment and quality of life in essential tremor with bilateral or unilateral DBS and focused ultrasound thalamotomy.

BACKGROUND: Thalamic deep brain stimulation (DBS) has largely replaced radiofrequency thalamotomy as the treatment of choice for disabling, medication-refractory essential tremor. Recently, the development of transcranial, high-intensity focused ultrasound has renewed interest in thalamic lesioning. The purpose of this study is to compare functional outcomes and quality of life in essential tremor patients treated with either bilateral Vim DBS or unilateral procedures (focused ultrasound or DBS). We hypothesized that all three would effectively treat the dominant hand and positively impact functional outcomes and quality of life as measured with the Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire. METHODS: This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n = 57), unilateral Vim DBS (n = 13), or unilateral focused ultrasound Vim thalamotomy (n = 15). Tremor was rated for all patients before and after treatment, using the Clinical Rating Scale for Tremor and Quality of Life in Essential Tremor Questionnaire. RESULTS: Patients undergoing bilateral DBS treatment had more baseline tremor and worse quality of life scores. Patients had significant improvements in tremor symptoms and quality of life with all three treatments. Both DBS procedures improved axial tremor. No difference was seen in the degree of improvement in upper extremity tremor score, disability, or overall quality of life between bilateral and either unilateral procedure. CONCLUSIONS: Bilateral thalamic DBS improves overall tremor more than unilateral DBS or focused ultrasound treatment; however, unilateral treatments are equally effective in treating contralateral hand tremor. Despite the greater overall tremor reduction with bilateral DBS, there is no difference in disability or quality of life comparing bilateral versus unilateral treatments.