Alp Ozpinar

Systematic Review of the Benefits and Risks of Metformin in Treating Obesity in Children Aged 18 Years and Younger

IMPORTANCE Childhood obesity is an important public health problem with increasing prevalence. Because treatment often has limited success, new approaches must be identified. OBJECTIVE To evaluate the effectiveness and safety of metformin for treating obesity in children aged 18 years and younger without a diagnosis of diabetes mellitus. EVIDENCE REVIEW We included randomized clinical trials identified through searches of MEDLINE, the Cochrane Library, and ClinicalTrials.gov. Our primary outcome measure was change in body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). We assessed study quality, pooled data using a random-effects model, and performed subgroup and sensitivity analyses. FINDINGS Fourteen randomized clinical trials were eligible. For BMI, moderate-strength evidence indicated a reduction of -1.38 (95% CI, -1.93 to -0.82) from baseline compared with control at 6 months. A similar, if less dramatic, effect was observed in studies less than 6 months, but the pooled estimate from studies of 1 year of treatment was not statistically significant. Subgroup analyses indicated smaller, but significant, effects for those with baseline BMI below 35, those of Hispanic ethnicity, those with acanthosis nigricans, those who had tried and failed diet and exercise programs, and in studies with more girls or higher mean age (adolescents). Moderate-strength evidence indicated that with metformin, 26% reported a gastrointestinal event compared with 13% in control groups (relative risk, 2.05; 95% CI, 1.19-3.54), although there was no difference in discontinuations due to adverse events. No serious adverse events were reported. CONCLUSIONS AND RELEVANCE Metformin provides a statistically significant, but very modest reduction in BMI when combined with lifestyle interventions over the short term. A large trial is needed to determine the benefits to subgroups or impacts of confounders. In the context of other options for treating childhood obesity, metformin has not been shown to be clinically superior.

Deep brain stimulation for psychiatric disorders: where we are now.

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Trigeminal neuralgia without neurovascular compression presents earlier than trigeminal neuralgia with neurovascular compression.

OBJECT Trigeminal neuralgia (TN) occurs and recurs in the absence of neurovascular compression (NVC). To characterize what may be distinct patient populations, the authors examined age at onset in patients with TN with and without NVC. METHODS A retrospective review of patients undergoing posterior fossa surgery for Type I TN at Oregon Health & Science University from 2009 to 2013 was undertaken. Charts were reviewed, and imaging and operative data were collected for patients with and without NVC. Mean, median, and the empirical cumulative distribution of onset age were determined. Statistical analysis was performed using Student t-test, Wilcoxon and Kolmogorov-Smirnoff tests, and Kaplan-Meier analysis. Multivariate analysis was performed using a Cox proportional hazards model. RESULTS The charts of 219 patients with TN were reviewed. There were 156 patients who underwent posterior fossa exploration and microvascular decompression or internal neurolysis: 129 patients with NVC and 27 without NVC. Mean age at symptoms onset for patients with and without NVC was 51.1 and 42.6 years, respectively. This difference (8.4 years) was significant (t-test: p = 0.007), with sufficient power to detect an effect size of 8.2 years. Median age between groups with and without NVC was 53.25 and 41.2 years, respectively (p = 0.003). Histogram analysis revealed a bimodal age at onset in patients without NVC, and cumulative distribution of age at onset revealed an earlier presentation of symptoms (p = 0.003) in patients without NVC. Chi-square analysis revealed a trend toward female predominance in patients without NVC, which was not significant (p = 0.08). Multivariate analysis revealed that age at onset was related to NVC but not sex, symptom side or distribution, or patient response to medical treatment. CONCLUSIONS NVC is neither sufficient nor necessary for the development of TN. Patients with TN without NVC may represent a distinct population of younger, predominantly female patients. Further research into the pathophysiology underlying this debilitating disease is needed.

Volume-Outcome Relationships in Neurosurgery

For a variety of neurosurgical conditions, increasing surgeon and hospital volumes correlate with improved outcomes, such as mortality, complication rates, length of stay, hospital charges, and discharge disposition. Neurosurgeons can improve patient outcomes at the population level by changing practice and referral patterns to regionalize care for select conditions at high-volume specialty treatment centers. Individual practitioners should be aware of where they fall on the volume spectrum and understand the implications of their practice and referral habits on their patients.

A Review of Minimally Invasive Procedures for the Treatment of Adult Spinal Deformity.

Study Design. Literature review. Objective. To review the literature evaluating the role of minimally invasive (MIS) techniques in the operative treatment of adult spinal deformity (ASD). Summary of Background Data. MIS techniques have become important tools in the armamentarium of spinal deformity surgeons as a means of achieving coronal and sagittal plane correction, while minimizing the complications of open deformity surgery. The literature suggests that MIS techniques are associated with certain limitations, and to date, determining which patients are candidates for MIS deformity correction is largely based on surgeon experience. Methods. A systematic literature review was performed using the PubMed-National Library of Medicine/National Institute of Health databases. All studies describing the use of MIS techniques in ASD surgery were included for review. Results. A total of 39 articles were included in the review. All studies were specifically designed to demonstrate radiographic and clinical outcomes of MIS techniques. Thirty articles were specific to MIS techniques as they relate to ASD surgery, whereas six articles were designed to describe details of various MIS techniques, and three articles were related to general principles of corrective surgery for ASD. Conclusion. The literature has demonstrated that MIS techniques are effective in achieving radiographic correction after surgery for ASD, while reducing complications compared with traditional open surgery. However, MIS techniques have limitations and may not be as effective as open surgery for severe and/or fixed sagittal and coronal plane deformity. Therefore, selecting patients for stand-alone MIS versus circumferential (cMIS) versus hybrid MIS (hybMIS) is critically important. The MIS spinal deformity surgery algorithm was designed to address this topic. Further studies are required to better elucidate the role and limitations of MIS techniques in patient undergoing corrective surgery for ASD. Level of Evidence: N/A

Basilar Invagination: Case Report and Literature Review.

BACKGROUND Basilar invagination is a rare clinical condition characterized by upward protrusion of the odontoid process into the intracranial space, leading to bulbomedullary compression. It is often encountered in adults with rheumatoid arthritis. Transoral microscopic or endonasal endoscopic decompression may be pursued, with or without posterior fixation. We present a case of basilar invagination with C1-C2 autofusion and discuss an algorithm for choice of anterior versus posterior approaches. CASE DESCRIPTION A 47-year-old woman with rheumatoid arthritis presented with severe occipital and cervical pain, dysphagia, hoarseness, and arm paresthesias. Findings on magnetic resonance imaging revealed moderate cranial settling with the odontoid indenting the ventral medulla but no posterior compression. Computed tomography demonstrated bony fusion at C1-C2 without lateral sag. Given autofusion of C1-C2 in proper occipitocervical alignment and the absence of posterior compression, the patient underwent endoscopic endonasal odontoidectomy without further posterior fusion, with satisfactory resolution of symptoms. CONCLUSION Endoscopic endonasal odontoidectomy offers a safe and effective method for anterior decompression of basilar invagination. Preoperative assessment for existing posterior fusion, absence of posterior compression, and preservation of the anterior C1 ring during operative decompression help stratify the need for lone anterior approach versus a combined anterior and posterior treatment.

Preoperative Lateralization Modalities for Cushing Disease: Is Dynamic Magnetic Resonance Imaging or Cavernous Sinus Sampling More Predictive of Intraoperative Findings?

Objective To analyze whether cavernous sinus sampling (CSS) and dynamic magnetic resonance imaging (dMRI) are consistent with intraoperative findings in Cushing disease (CD) patients. Design Retrospective outcomes study. Setting Oregon Health & Science University; 2006 and 2013. Participants A total of 37 CD patients with preoperative dMRI and CSS to confirm central adrenocorticotropic hormone (ACTH) hypersecretion. Patients were 78% female; mean age was 41 years (at diagnosis), and all had a minimum of 6 months of follow-up. Main Outcome Measures Correlations among patient characteristics, dMRI measurements, CSS results, and intraoperative findings. Results All CSS indicated presence of CD. Eight of 37 patients had no identifiable tumor on dMRI. Three of 37 patients had no tumor at surgery. dMRI tumor size was inversely correlated with age (rs = - 0.4; p = 0.01) and directly correlated to intraoperative lateralization (rs = 0.3; p < 0.05). Preoperative dMRI was directly correlated to intraoperative lateralization (rs = 0.5; p < 0.002). CSS lateralization showed no correlation with intraoperative findings (rs = 0.145; p = 0.40) or lateralization observed on preoperative dMRI (rs = 0.17; p = 0.29). Postoperative remission rate was 68%. Conclusion dMRI localization was most consistent with intraoperative findings; CSS results were less reliable. Results suggest that small ACTH-secreting tumors continue to pose a challenge to reliable preoperative localization.

Assessment of sedated pediatric brain with 3D-FLAIR sequence at 3T MRI.

BACKGROUND AND PURPOSE In sedated pediatric brains, 2D-FLAIR causes increased signal intensity of the cerebrospinal fluid (CSF) leading to false-positive diagnoses. Our aim is to determine whether increased CSF signal intensity is observed on 3D-FLAIR images. METHODS In this institutional review board-approved study, a 2-year retrospective analysis of our MRI database was conducted which revealed 48 sedated pediatric patients with normal cranial MRI findings and 3D-FLAIR sequence. One adult volunteer was imaged before and after O2 inhalation with 2D and 3D-FLAIR sequences. The hyperintensity in the subarachnoid spaces and basal cisterns were quantified as follows: 0: artifact free; 1: homogeneous minimal CSF signal; 2: abnormal CSF signal. Inter-observer agreement was assessed with kappa agreement analysis. RESULTS Grade 0 and grade 1 signals were observed at inferior to Liliequist membrane (LLQ) in 48/48 and 0/48 cases; prepontine cistern 47/48 and 1/48; superior to LLQ 26/48 and 22/48; 4th ventricle 16/48 and 32/48; 3rd ventricle 34/48 and 14/48; lateral ventricle 3/48 and 45/48; subarachnoid space 36/48 and 12/48, respectively. No patients showed grade 2 signal. Inter-observer agreement was 0.81-1. In the volunteer, after O2 inhalation, grade 2 signal intensity was evident on 2D-FLAIR however; 3D-FLAIR did not show any signal increase. CONCLUSIONS In sedated pediatric brains, 3D-FLAIR suppresses CSF signal, and enables reliable assessment free from CSF artifacts.

Case comparison and literature review of glioblastoma: A tale of two tumors

Background: Diagnosis of glioblastoma multiforme (GBM) includes a heterogeneous group of tumors. We describe two cases with histopathologically and molecularly similar tumors, but very different outcomes. We attempt to illustrate the need for improved prognostic markers for GBM. Case Description: Two patients with similar molecular profiles were retrospectively identified. The following markers were assessed: O6-methylguanine DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53, and 1p/19q status. Each patient was assigned a Karnofsky performance score at presentation. Case 1 (62-year-old male) was a right temporal lobe glioblastoma with a molecular profile of amplified EGFR, normal PTEN, no IDH1/2 mutation, 28.7% MGMT promoter methylation, 5-20% Ki-67, 1p deletion, and 19q intact. The patient underwent resection followed by radiation therapy and 2 years of chemotherapy, and was asymptomatic and tumor free 5 years post diagnosis. Tumor eventually recurred and the patient expired 72 months after initial diagnosis. Case 2 (63-year-old male) was a right frontal white matter mass consistent with glioblastoma with a molecular profile of amplified EGFR, absent PTEN, no IDH1/2 mutation, 9.9% MGMT promoter methylation, 5-10% Ki-67, and 1p/19q status inconclusive. A radical subtotal resection was performed; however, 2 weeks later symptoms had returned. Subsequent imaging revealed a tumor larger than at diagnosis. The patient expired 3 months after initial diagnosis. Conclusion: The need for formulating more robust means to classify GBM tumor subtypes is paramount. Standard histopathologic and molecular analyses are costly and did not provide either of these patients with a realistic appraisal of their prognosis. Individualized whole genome testing similar to that being reported for medulloblastoma and other tumors may be preferable to the array of tests as currently utilized.

Stereotactic radiosurgery for intradural spine tumors using cone-beam CT image guidance

OBJECTIVE Cone-beam CT (CBCT) image guidance technology has been widely adopted for spine radiosurgery delivery. There is relatively little experience with spine radiosurgery for intradural tumors using CBCT image guidance. This study prospectively evaluated a series of intradural spine tumors treated with radiosurgery. Patient setup accuracy for spine radiosurgery delivery using CBCT image guidance for intradural spine tumors was determined. METHODS Eighty-two patients with intradural tumors were treated and prospectively evaluated. The positioning deviations of the spine radiosurgery treatments in patients were recorded. Radiosurgery was delivered using a linear accelerator with a beam modulator and CBCT image guidance combined with a robotic couch that allows positioning correction in 3 translational and 3 rotational directions. To measure patient movement, 3 quality assurance CBCTs were performed and recorded in 30 patients: before, halfway, and after the radiosurgery treatment. The positioning data and fused images of planning CT and CBCT from the treatments were analyzed to determine intrafraction patient movements. From each of 3 CBCTs, 3 translational and 3 rotational coordinates were obtained. RESULTS The radiosurgery procedure was successfully completed for all patients. Lesion locations included cervical (22), thoracic (17), lumbar (38), and sacral (5). Tumor histologies included schwannoma (27), neurofibromas (18), meningioma (16), hemangioblastoma (8), and ependymoma (5). The mean prescription dose was 17 Gy (range 12-27 Gy) delivered in 1-3 fractions. At the halfway point of the radiation, the translational variations and standard deviations were 0.4 ± 0.5, 0.5 ± 0.8, and 0.4 ± 0.5 mm in the lateral (x), longitudinal (y), and anteroposterior (z) directions, respectively. Similarly, the variations immediately after treatment were 0.5 ± 0.4, 0.5 ± 0.6, and 0.6 ± 0.5 mm along x, y, and z directions, respectively. The mean rotational angles were 0.3° ± 0.4°, 0.3° ± 0.4°, and 0.3° ± 0.4° along yaw, roll, and pitch, respectively, at the halfway point and 0.5° ± 0.5°, 0.4° ± 0.5°, and 0.2° ± 0.3° immediately after treatment. CONCLUSIONS Radiosurgery offers an alternative treatment option for intradural spine tumors in patients who may not be optimal candidates for open surgery. CBCT image guidance for patient setup for spine radiosurgery is accurate and successful in patients with intradural tumors.