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Objective: Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging treatment for medication-refractory essential tremor (ET). The objective of this study was to evaluate long-term (up to 5 years) safety and efficacy of unilateral MRgFUS in the treatment of ET., Methods: The authors performed a systematic search through 4 databases to find relevant clinical studies. Binary outcomes were analyzed and reported as odds ratios and 95% confidence intervals, while continuous outcomes were analyzed and reported as standardized mean differences (SMDs) and 95% confidence intervals. Furthermore, a univariable meta-regression was performed to evaluate the association between various covariates and the outcomes including the mean difference in the Clinical Rating Scale for Tremor (CRST) score and hand tremor scores. Sensitivity analysis was performed to address any heterogeneity., Results: A total of 43 studies comprising 1818 patients with ET who underwent MRgFUS were identified. Of the 1539 patients with data on sex, 1095 (71.2%) were male. The mean follow-up duration ranged from 3 months to 8.4 years among the studies. The mean total CRST score significantly decreased at 3, 6, and 12 months post-MRgFUS (SMD -4.5, p = 0.0069; SMD -4.9, p = 0.0045; and SMD -2.95, p = 0.0039, respectively). The mean hand tremor scores significantly mitigated at 3, 6, 12, 24, and 36 months post-MRgFUS (SMD -3.99, p = 0.05; SMD -4.5, p = 0.05; SMD -1.99, p < 0.0001; SMD - 2.07, p = 0.0002; and SMD -2.1, p < 0.0001, respectively). Furthermore, the mean Quality of Life in Essential Tremor Questionnaire scores were improved at 3 months (SMD -2.8, p = 0.0025), 6 months (SMD -4.1, p = 0.04), 12 months (SMD -1.57, p = 0.0004), 2 years (SMD -1.64, p = 0.0003), and 3 years (SMD -1.14, p = 0.08). Our meta-regression findings showed that sex (p = 0.03), unlike age, handedness, symptom duration, and peak energy levels at 3 months, was associated with a significantly higher mean difference in tremor severity., Conclusions: This meta-analysis provides strong evidence supporting the efficacy and safety of unilateral MRgFUS for the treatment of ET in terms of tremor severity and quality of life with acceptable adverse events.

Objective: Foramen ovale electrodes (FOEs) are a minimally invasive method to localize mesial temporal seizures in cases in which noninvasive methods are inconclusive. The objective of this study was to identify factors predicting the ability of FOEs to yield a diagnosis in order to determine optimal candidates for this procedure., Methods: All cases of diagnostic investigations performed with FOEs at the authors' institution between 2005 and 2017 were reviewed. FOE investigation was defined as diagnostic if it led to a treatment decision. Demographic and clinical variables for diagnostic and nondiagnostic investigations were compared using a Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables., Results: Ninety-three patients underwent investigations performed with FOEs during the study period and were included in the study. FOE investigation was diagnostic in 75.3% of cases. Of patients who underwent anterior temporal lobectomy following diagnostic FOE evaluation, 75.9% were Engel class I at last follow-up (average 40.1 months). When the diagnostic and nondiagnostic FOE groups were compared, patients who had diagnostic investigations were more likely to be male (57.1% male vs 26.1% in the nondiagnostic group, p = 0.015). They were also more likely to have temporal lesions on preoperative MRI (p = 0.018)., Conclusions: FOEs are a useful, minimally invasive diagnostic modality resulting in a treatment decision in 75% of cases. Male patients and patients with temporal lesions on MRI may be most likely to benefit from FOE investigation.

Disorders of learning and memory have a large social and economic impact in today's society. Unfortunately, existing medical treatments have shown limited clinical efficacy or potential for modification of the disease course. Deep brain stimulation is a successful treatment for movement disorders and has shown promise in a variety of other diseases including psychiatric disorders. The authors review the potential of neuromodulation for the treatment of disorders of learning and memory. They briefly discuss learning circuitry and its involvement in Alzheimer disease and traumatic brain injury. They then review the literature supporting various targets for neuromodulation to improve memory in animals and humans. Multiple targets including entorhinal cortex, fornix, nucleus basalis of Meynert, basal ganglia, and pedunculopontine nucleus have shown a promising potential for improving dysfunctional memory by mechanisms such as altering firing patterns in neuronal networks underlying memory and increasing synaptic plasticity and neurogenesis. Significant work remains to be done to translate these findings into durable clinical therapies.

Unlabelled: OBJECT.: Recent findings have suggested a correlation between obsessive-compulsive disorder (OCD) symptom dimensions and clinical outcome after limbic system surgery for treatment-refractory patients. Based on previous evidence that the hoarding dimension is associated with worse outcome in conventional treatments, and may have a neural substrate distinct from OCD, the authors examined a large sample of patients undergoing limbic surgery (40 with capsulotomy, 37 with cingulotomy) and investigated if symptom dimensions, in particular hoarding, could influence treatment outcome., Methods: Data from 77 patients from 3 different research centers at São Paulo (n = 17), Boston (n = 37), and Stockholm (n = 23) were analyzed. Dimensional Yale-Brown Obsessive Compulsive Scale (Y-BOCS; São Paulo) or Y-BOCS Symptom Checklist scores (Boston and Stockholm) were used to code the presence of 4 well-established symptom dimensions: forbidden thoughts, contamination/cleaning, symmetry/order, and hoarding. Reductions in YBOCS scores determined clinical outcome., Results: Mean Y-BOCS scores decreased 34.2% after surgery (95% CI 27.2%-41.3%), with a mean follow-up of 68.1 months. Patients with hoarding symptoms had a worse response to treatment (mean Y-BOCS decrease of 22.7% ± 25.9% vs 41.6% ± 32.2%, respectively; p = 0.006), with no significant effect of surgical modality (capsulotomy vs cingulotomy). Patients with forbidden thoughts apparently also had a worse response to treatment, but this effect was dependent upon the co-occurrence of the hoarding dimension. Only the negative influence of the hoarding dimension remained when an ANOVA model was performed, which also controlled for preoperative symptom severity., Conclusions: The presence of hoarding symptoms prior to surgery was associated with worse clinical outcome after the interventions. Patients with OCD under consideration for ablative surgery should be carefully screened for hoarding symptoms or comorbid hoarding disorder. For these patients, the potentially reduced benefits of surgery need to be carefully considered against potential risks.

Object: Dural closure with synthetic grafts has been suggested to contribute to the incidence of infection and CSF leak. The objective of this study was to assess the contribution of choice of dural closure material, as well as other factors, to the incidence of infection and CSF leak., Methods: A retrospective, consecutive cohort study of adult patients undergoing elective craniotomy was established between April 2010 and March 2011 at a single center. Exclusion criteria consisted of trauma, bur hole placement alone, and temporary CSF fluid diversion., Results: Three hundred ninety-nine patients were included (mean follow-up 396.6 days). Nonautologous (synthetic) dural substitute was more likely to be used (n = 106) in cases of reoperation (p = 0.001). Seventeen patients developed a surgical site infection and 12 patients developed a CSF leak. Multivariate logistic regression modeling identified estimated blood loss (OR 1.002, 95% CI 1.001-1.003; p < 0.001) and cigarette smoking (OR 2.198, 95% CI 1.109-4.238; p = 0.019) as significant predictors of infection. Synthetic dural graft was not a predictor of infection in multivariate analysis. Infratentorial surgery (OR 4.348, 95% CI 1.234-16.722; p = 0.024) and more than 8 days of postoperative corticosteroid treatment (OR 3.886, 95% CI 1.052-16.607; p = 0.048) were significant predictors for the development of CSF leak. Synthetic dural graft was associated with a lower likelihood of CSF leak (OR 0.072, 95% CI 0.003-0.552; p = 0.036)., Conclusions: The use of synthetic dural closure material is not associated with surgical site infection and is associated with a reduced incidence of CSF leak. Modifiable risk factors exist for craniotomy complications that warrant vigilance and further study.

Object: Cingulotomy and limbic leucotomy are lesioning surgeries with demonstrated benefit for medically intractable psychiatric illnesses. They represent significant refinements of the prefrontal lobotomy used from the 1930s through the 1950s. However, the associations between anatomical characterization of these lesions and outcome data are not well understood. To elucidate these procedures and associations, the authors sought to define and compare the neuroanatomy of cingulotomy and limbic leucotomy and to test a method that uses neuroanatomical data and voxel-based lesion-symptom mapping (VLSM) to reveal potential refinements to modern psychiatric neurosurgical procedures., Methods: T1-weighted MR images of patients who had undergone cingulotomy and limbic leucotomy were segmented and registered onto the Montreal Neurological Institute T1-weighted template brain MNI152. Using an atlas-based approach, the authors calculated, by case, the percentage of each anatomical structure affected by the lesion. Because of the infrequency of modern lesion procedures and the requirement for higher-resolution clinical imaging, the sample size was small. The pilot study correlated cingulotomy and limbic leucotomy lesion characteristics with clinical outcomes for patients with obsessive-compulsive disorder. For this study, preoperative and postoperative Yale-Brown Obsessive Compulsive Scale scores for 11 cingulotomy patients and 8 limbic leucotomy patients were obtained, and lesion masks were defined and compared anatomically by using an atlas-based method. Statistically significant voxels were additionally calculated by using VLSM techniques that correlated lesion characteristics with postoperative scores., Results: Mean lesion volumes were 13.3 ml for cingulotomy and 11.8 ml for limbic leucotomy. As expected, cingulotomy was isolated to the anterior cingulum. The subcaudate tractotomy portion of limbic leucotomy additionally affected Brodmann area 25, the medial orbitofrontal cortex, and the nucleus accumbens. Initial results indicated that the dorsolateral regions of the cingulotomy lesion and the posteroventral regions of the subcaudate tractotomy lesion were associated with improved postoperative Yale-Brown Obsessive Compulsive Scale scores., Conclusions: Cingulotomy and limbic leucotomy are lesioning surgeries that target pathological circuits implicated in psychiatric disease. Lesion analysis and VLSM contextualize outcome data and have the potential to be useful for improving lesioning neurosurgical procedures.

Object: Pallidal deep brain stimulation (DBS) is a treatment option for those with early-onset dystonia. However, there are limited data on long-term outcome and treatment complications. The authors report on the short- and long-term effects of pallidal DBS in a cohort of patients with early-onset dystonia., Methods: Fourteen consecutive pediatric patients with early-onset dystonia were systematically evaluated and treated. The duration of follow-up ranged from 16 to 84 months., Results: There were no immediate postoperative complications. At last follow-up, 12 of the 14 patients displayed a significant decline in the Burke-Fahn-Marsden Dystonia Rating Scale motor subscale score, with an average decrease of 62% ± 8.4%. The most common hardware complication was lead fracture (14.3%)., Conclusions: These data provide further evidence that DBS is a safe and effective treatment for those with earlyonset dystonia.

Object: Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system lesions, including dorsal anterior cingulotomy. The authors present their results describing the efficacy and durability of limbic system surgery for OCD, characterizing a large cohort of patients treated at a single institution with a mean follow-up of more than 5 years., Methods: The authors identified 64 consecutive patients undergoing cingulotomy for refractory OCD at the Massachusetts General Hospital between 1989 and 2009. Changes in OCD and major depressive disorder symptom severity were assessed at both the initial and most recent postoperative follow-up by using the Yale-Brown Obsessive Compulsive Scale and the Beck Depression Inventory, respectively. Full and partial OCD symptom responses were defined as Yale-Brown Obsessive Compulsive Scale score reductions of ≥ 35% and 25%-34%, respectively., Results: Regarding OCD symptom improvement, at the first postoperative follow-up (mean 10.7 months), 35% of patients demonstrated a full response and 7% were partial responders. Thirty patients had a subsequent procedure (repeat cingulotomy or subcaudate tractotomy). By the most recent follow-up (mean 63.8 months), rates climbed to 47% and 22% for full and partial responses, respectively. Of the 24 patients with at least a partial response at initial follow-up, 20 (83%) retained at least a partial response at final follow-up. Comorbid major depressive disorder severity decreased by 17% at the most recent follow-up., Conclusions: Limbic system surgery based on initial cingulotomy offers a durable and effective treatment option for appropriately selected patients with severe OCD who have not responded to conventional pharmacotherapy or psychotherapy.

Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders.

Obsessive-compulsive disorder (OCD) is a psychiatric illness that can lead to chronic functional impairment. Some patients with severe, chronic OCD have been treated with ablative neurosurgical techniques over the past 4 decades. More recently, deep brain stimulation (DBS) has been investigated as a therapy for refractory OCD, and the procedure was granted a limited humanitarian device exemption by the FDA in 2009. In this article, the authors review the development of DBS for OCD, describe the current understanding of the pathophysiological mechanisms of the disorder and how the underlying neural circuits might be modulated by DBS, and discuss the clinical studies that provide evidence for the use of this evolving therapy. The authors conclude with suggestions for how a combined basic science and translational research approach could drive the understanding of the neural mechanisms underlying OCD as well as the clinical effectiveness of DBS in the setting of recalcitrant disease.

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Object: The surgical treatment of Parkinson disease (PD) has undergone a dramatic shift, from stereotactic ablative procedures toward deep brain stimulaion (DBS). The authors studied this process by investigating practice patterns, mortality and morbidity rates, and hospital charges as reflected in the records of a representative sample of US hospitals between 1996 and 2000., Methods: The authors conducted a retrospective cohort study by using the Nationwide Inpatient Sample database; 1761 operations at 71 hospitals were studied. Projected to the US population, there were 1650 inpatient procedures performed for PD per year (pallidotomies, thalamotomies, and DBS), with no significant change in the annual number of procedures during the study period. The in-hospital mortality rate was 0.2%, discharge other than to home was 8.1%, and the rate of neurological complications was 1.8%, with no significant differences between procedures. In multivariate analyses, hospitals with larger annual caseloads had lower mortality rates (p = 0.002) and better outcomes at hospital discharge (p = 0.007). Placement of deep brain stimulators comprised 0% of operations in 1996 and 88% in 2000. Factors predicting placement of these devices in analyses adjusted for year of surgery included younger age, Caucasian race, private insurance, residence in higher-income areas, hospital teaching status, and smaller annual hospital caseload. In multivariate analysis, total hospital charges were 2.2 times higher for DBS (median dollar 36,000 compared with dollar 12,000, p < 0.001), whereas charges were lower at higher-volume hospitals (p < 0.001)., Conclusions: Surgical treatment of PD in the US changed significantly between 1996 and 2000. Larger-volume hospitals had superior short-term outcomes and lower charges. Future studies should address long-term functional end points, cost/benefit comparisons, and inequities in access to care.

Object: Although the pathophysiology of spinal dural arteriovenous fistulas (AVFs) has recently been elucidated, the optimal treatment strategy for these lesions has yet to be defined. Current management techniques include endovascular embolization or microsurgical obliteration., Methods: The authors reviewed the records and angiograms of all patients with spinal dural AVFs treated at Massachusetts General Hospital over a 6-year period (1992-1998). During this period, it was intended initially to treat all patients with embolization and to reserve surgery for those in whom endovascular treatment failed or in cases in which pretreatment evaluation suggested that endovascular therapy would be ineffective or unsafe. A total of 26 patients with spinal dural AVFs were treated: there were 22 men and 4 women with a mean age of 65 years (range 39-79 years). Lesions were located in the following areas: five in foramen magnum/cervical, 13 in thoracic, five in lumbar, and three in sacral. Twenty-three (88%) of 26 patients underwent embolization and three (12%) of 23 patients underwent surgery as the primary mode of treatment. Of the 23 patients in whom embolization was performed or attempted, nine (39%) ultimately required surgery. All patients were stabilized or improved following definitive treatment, as assessed by the Aminoff-Logue scores. There was one death secondary to a myocardial infarction., Conclusions: These data demonstrate that endovascular therapy can be successful as an initial treatment for the majority of patients; however, there is a 39% failure rate, which is not observed following surgical therapy. Once a definitive therapy has been achieved using either technique virtually all patients are either stabilized or improved.