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 PARTICIPANTSOf 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 MEASURESThe 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. RESULTSOf 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

abbreviatioNs AD = Alzheimer's disease; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; CSF = cerebrospinal fluid; GDS = Global Deterioration Scale; HVLP = high-volume lumbar puncture; NPH = normal pressure hydrocephalus. obJective Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer's disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided. methods The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups. results From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer's pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer's pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136). coNclusioNs A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer's pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evi...

Object The goal of this study was to review all cases of pediatric spinal arachnoid cysts (SACs) surgically treated at the authors' institution between 1992 and 2008 and to compare these cases to the published literature for the general population. Methods The charts of all pediatric patients with SACs were reviewed for demographics, medical history, presenting symptoms, imaging findings, operative procedure(s), complications, and outcomes. Following a complete literature review, the pediatric data were compared with data from the general population and unique findings associated with pediatric patients were identified. Results Thirty-one pediatric patients (median age 6.9 years) underwent operative intervention for SACs between 1992 and 2008 (median duration of follow-up 4.2 years). There were 17 female patients (55%) and 14 male patients (45%). Twenty-one patients (68%) presented with symptoms of radiculopathy or myelopathy. The most common presenting symptoms were pain (42%), lower-extremity weakness (39%), gait instability (32%), spasticity (19%), sensory loss (10%), and bladder dysfunction (7%). In 3 patients (10%) SACs were incidental findings. Intradural SACs were more common (18 patients, 58%) than extradural SACs (11 patients, 36%). One patient (3%) had extradural and intradural components. One patient (3%) had a purely intramedullary cyst, and 1 patient (3%) had both an intradural and intramedullary component. Of the 18 intradural SACs, 9 (50%) were located ventral to the spinal cord and 9 (50%) were dorsally situated. One dorsal intradural SAC had an intramedullary component. All extradural SACs were located dorsal to the spinal cord. Intradural SACs were primarily concentrated in the cervical and thoracic regions (67%), whereas extradural cysts were more evenly distributed between the thoracic, lumbar, and sacral regions. Of the 18 patients with intradural SACs, 13 (72%) had significant previous CNS abnormalities, compared with 3 (27%) of 11 patients with extradural SACs. There were 2 operative complications. One patient had a CSF leak treated with a lumbar drain, and the second patient had a pseudomeningocele. No patients had neurological deterioration as a result of surgical intervention. Twenty-one patients (68%) had complete remission of symptoms, 6 (19%) had improvement, 3 (10%) were stable, and 1 (3%) has worsening of symptoms with recurrence that ultimately required cystoperitoneal shunting, despite multiple failed attempts at fenestration. Conclusions Spinal arachnoid cysts are rare lesions in the pediatric population. Affected patients present with back pain, weakness, and/or gait instability. In children, SACs predominantly develop in the thoracic region and are more likely to occur intradurally, compared with SACs in the general population. Overall outcomes following surgical fenestration or excision of SACs are excellent, with complete remission or improvement of symptoms achieved in 87% of cases.

Exenatide is the first drug in the incretin mimetic class and is indicated for treatment of type 2 diabetes mellitus. Although structurally similar to the native glucagon-like peptide, this synthetic form has a much longer duration of action. Randomized trials have shown exenatide to be efficacious in improving glycemic control when combined with either metformin or a sulfonylurea. The dose is initially 5 mcg subcutaneously twice daily and may be titrated to 10 mcg subcutaneously twice daily to achieve better diabetes management. Nausea, vomiting, and diarrhea were the most common adverse events reported with exenatide therapy. Exenatide is not associated with hypoglycemia, which may provide advantages over adding insulin to a sulfonylurea or metformin.

N eurosurgeoNs have traditionally used a sublabial or transseptal incision with an operating microscope to access the sphenoid sinus and sella turcica for the resection of pituitary tumors. 9 Over the past decade, however, the endoscopic endonasal transsphenoidal approach has become an increasingly popular method of removing pituitary tumors and other lesions of the sella. 2,3,7,12,20 Among the arguments proposed for the use of endoscopy for transsphenoidal surgery are that it provides a superior view of the sella and its surrounding structures by allowing panoramic visualization, and it offers improved lighting. Angled endoscopes allow visualization into recesses within the sphenoid sinus and sella that is not offered by the operating microscope. The enhanced visualization during endoscopic procedures theoretically can improve the extent of resection of very large pituitary tumors, in particular those extending laterally or superiorly beyond the direct vision of the operating microscope. On Object. The object of this study was to compare surgical outcomes and complications in a contemporaneous series of patients undergoing either microscopic or endoscopic transsphenoidal surgery for nonfunctioning pituitary macroadenomas without imaging evidence of cavernous sinus invasion.Methods. This is a retrospective analysis of a prospectively collected database from a single institution. Data were collected from patients whose surgery had occurred in the period from June 2010 to January 2013. Patients who underwent microscopic or endoscopic surgery for Knosp Grade 0, 1, or 2 nonfunctioning pituitary macroadenomas were included in the study. Patients who had clinically secreting or Knosp Grade 3 or 4 tumors and patients who were undergoing revision surgery were excluded from analysis. Eligible patient records were analyzed for outcomes and complications. Statistical analyses were performed on tumor volume, intraoperative factors, postoperative complications, and degree of resection on 1-year postoperative MRI. The results were used to compare the outcomes after microscopic and endoscopic approaches.Results. Forty-three patients underwent microscopic transsphenoidal surgery, and 56 underwent endoscopic transsphenoidal surgery. There were no statistical differences in the intraoperative extent of resection or endocrinological complications. There were significantly more intraoperative CSF leaks in the endoscopic group (58% vs 16%); however, there was no difference in the incidence of postoperative CSF rhinorrhea (12% microscopic vs 7% endoscopic). Length of hospitalization was significantly shorter in patients undergoing an endoscopic approach (3.0 days vs 2.4 days). Two-month follow-up imaging was available in 95% of patients, and 75% of patients had 1-year follow-up imaging. At 2 months postprocedure, there was no evidence of residual tumor in 79% (31 of 39) and 85% (47 of 55) of patients in the microscopic and endoscopic groups, respectively. At 1 year postprocedure, 83% (25 of 30) of patients in the microscopic group h...