Uzma Samadani

Imipramine Treatment Improves Cognitive Outcome Associated with Enhanced Hippocampal Neurogenesis after Traumatic Brain Injury in Mice

Previous animal and human studies have demonstrated that chronic treatment with several different antidepressants can stimulate neurogenesis, neural remodeling, and synaptic plasticity in the normal hippocampus. Imipramine is a commonly used tricyclic antidepressant (TCA). We employed a controlled cortical impact (CCI) mouse model of traumatic brain injury (TBI) to assess the effect of imipramine on neurogenesis and cognitive and motor function recovery after TBI. Mice were given daily imipramine injections for either 2 or 4 weeks after injury. Bromodeoxyuridine (BrdU) was administered 3-7 days post-brain injury to label the cells that proliferated as a result of the injury. We assessed the effects of imipramine on post-traumatic motor function using a beam-walk test and an assessment of cognitive function: the novel object recognition test (NOR). Histological analyses were performed at 2 and 4 weeks after CCI. Brain-injured mice treated with imipramine showed significantly improved cognitive function compared to a saline-treated group (p<0.001). However, there was no significant difference in motor function recovery between imipramine-treated and saline-treated mice. Histological examination revealed increased preservation of proliferation of Ki-67- and BrdU-positive cells in the hippocampal dentate gyrus (DG) at 2 and 4 weeks after TBI. Immunofluorescence double-labeling with BrdU and neuron-specific markers at 4 weeks after injury showed that most progenitors became neurons in the DG and astrocytes in the hilus. Notably, treatment with imipramine increased preservation of the total number of newly-generated neurons. Our findings provide direct evidence that imipramine treatment contributes to cognitive improvement after TBI, perhaps by enhanced hippocampal neurogenesis.

Intracranial hypotension after intraoperative lumbar cerebrospinal fluid drainage.

OBJECTIVEIntraoperative lumbar cerebrospinal fluid drainage is frequently performed in a variety of neurosurgical procedures. A retrospective review is presented of the complications of lumbar cerebrospinal fluid drainage. METHODSThe records from 75 consecutive operations requiring intraoperative lumbar cerebrospinal drainage during a 1-year period at the Hospital of the University of Pennsylvania were reviewed to assess the types of complications attributable to spinal drainage and their rates of occurrence. The operations were categorized into 46 aneurysm clippings, 21 craniotomies for tumors, and 8 other cranial base procedures. RESULTSTwo patients developed transient postoperative neurological complications as a result of intracranial hypotension that resolved after epidural blood patching, with a reexploration craniotomy to drain an epidural collection performed in one patient. A third patient in the study developed a persistent deficit when intracranial hypotension led to intraoperative transtentorial herniation, which resulted in an unusual constellation of multiple brainstem infarcts that caused cranial neuropathy. CONCLUSIONComplications of intraoperative lumbar cerebrospinal fluid drainage resulting in transient (2 of 75 patients, 3%) or persistent (1 of 75 patients, 1%) neurological deficits caused by intracranial hypotension occur infrequently and may be related to preexisting conditions such as hydrocephalus.

A retrospective analysis of pedicle screws in contact with the great vessels

OBJECT Pedicle screws placed in the thoracic, lumbar, and sacral spine occasionally come in contact with the aorta, vena cava, or iliac vessels. When such screws are seen on postoperative imaging in an asymptomatic patient, the surgeon must decide whether it is riskier to revise the screw or to observe it. The authors hypothesized that the incidence of screw placement causing perioperative vessel injury is low and, further, that screws placed in contact with major vessels do not always result in vessel injury. METHODS A retrospective review of the operative records of 182 consecutive patients undergoing thoracic, lumbar, and lumbosacral pedicle screw fusion was performed to determine the frequency of intraoperative vessel injury. Postoperative imaging for 107 patients was available to determine the incidence of screws in contact with major vessels. Charts were examined to determine if any adverse sequelae had resulted from malpositioned screws. Patient outcomes were documented. RESULTS There were no intraoperative vessel injuries or deaths in 182 consecutive operations. One hundred seven patients with available postoperative films had 680 pedicle screws placed between T-3 and the sacrum during 115 operations. No patient had arterial screw penetration or deformation on postoperative imaging. Thirty-three of the 680 inserted screws were in contact with a major vessel on routine postoperative imaging. The contacted vessels included the aorta (4 cases), the iliac artery (7 cases), and the iliac veins (22 cases). Patients were followed up until death or November 2009, for a mean follow-up of 44 months (median 44 months, range 5-109 months). None of the patients with vessel contact was noted to suffer symptoms or sequelae as a result of vessel contact. Radiographic follow-up as long as 50 months after surgery revealed no detectable vessel abnormality at the contacted site. CONCLUSIONS Placing pedicle screws in contact with major vessels is a known risk of spinal surgery. The risk of repositioning a screw in contact with a major vessel but causing no symptoms must be weighed against the relative risk of leaving it in place.

Cerebral atrophy is associated with development of chronic subdural haematoma

Objective: To test that cerebral atrophy is associated with increased risk for development of chronic subdural haematoma (cSDH), this study performed volumetric analysis of computed tomography (CT) brain scans from patients who were diagnosed with cSDH on subsequent CT scans and their age-matched controls. Methods: Volumetric analysis was performed on CT scans acquired a mean of 209 days prior to cSDH diagnosis in 19 patients. Cerebral atrophy present on these scans was then compared to 76 age-matched control patients randomly selected from cSDH-free subjects. Results: There was a higher degree of atrophy in cSDH patients (n = 19, 14.3% ± 5.4%) than in age-matched control patients (n = 76, 11.9% ± 5.5%; p = 0.044). Logistical regression demonstrated that atrophy was found to be a significant predictor of cSDH at all ages (OR = 1.11, 95% CI = [1.01, 1.23], p = 0.05). For younger subjects ≤65 years of age (n = 50), atrophy was an even stronger predictor of cSDH (OR = 1.17, 95% CI = [1.02, 1.34], p = 0.026). Conclusions: Cerebral atrophy is associated with the development of cSDH and this association is greater in patients ≤65 years of age.

Attrition rates in neurosurgery residency: Analysis of 1361 consecutive residents matched from 1990 to 1999

OBJECT The objective of this study is to determine neurosurgery residency attrition rates by sex of matched applicant and by type and rank of medical school attended. METHODS The study follows a cohort of 1361 individuals who matched into a neurosurgery residency program through the SF Match Fellowship and Residency Matching Service from 1990 to 1999. The main outcome measure was achievement of board certification as documented in the American Board of Neurological Surgery Directory of Diplomats. A secondary outcome measure was documentation of practicing medicine as verified by the American Medical Association DoctorFinder and National Provider Identifier websites. Overall, 10.7% (n=146) of these individuals were women. Twenty percent (n=266) graduated from a top 10 medical school (24% of women [35/146] and 19% of men [232/1215], p=0.19). Forty-five percent (n=618) were graduates of a public medical school, 50% (n=680) of a private medical school, and 5% (n=63) of an international medical school. At the end of the study, 0.2% of subjects (n=3) were deceased and 0.3% (n=4) were lost to follow-up. RESULTS The total residency completion rate was 86.0% (n=1171) overall, with 76.0% (n=111/146) of women and 87.2% (n=1059/1215) of men completing residency. Board certification was obtained by 79.4% (n=1081) of all individuals matching into residency between 1990 and 1999. Overall, 63.0% (92/146) of women and 81.3% (989/1215) of men were board certified. Women were found to be significantly more at risk (p<0.005) of not completing residency or becoming board certified than men. Public medical school alumni had significantly higher board certification rates than private and international alumni (82.2% for public [508/618]; 77.1% for private [524/680]; 77.8% for international [49/63]; p<0.05). There was no significant difference in attrition for graduates of top 10-ranked institutions versus other institutions. There was no difference in number of years to achieve neurosurgical board certification for men versus women. CONCLUSIONS Overall, neurosurgery training attrition rates are low. Women have had greater attrition than men during and after neurosurgery residency training. International and private medical school alumni had higher attrition than public medical school alumni.

Evolving management of symptomatic chronic subdural hematoma: experience of a single institution and review of the literature.

Abstract Objective: Chronic subdural hematoma (cSDH) has an increasing incidence and results in high morbidity and mortality. We review here the 10-year experience of a single institution and the literature regarding the treatment and major associations of cSDH. Methods: We retrospectively reviewed all cSDHs surgically treated from 2000 to 2010 in the New York Harbor Health Care System to evaluate the duration from admission to treatment, type of treatment, length of stay (LOS) in critical care, LOS in the hospital, and recurrence. The literature was reviewed with regards to incidence, associations, and treatment of cSDH. Results: From 2000 to 2008, 44 patients were treated with burr holes (BHs). From 2008 to 2010, 29 patients were treated with twist-drill evacuation (subdural evacuating port system, SEPS). Four patients from each group were readmitted for reoperation (9% vs 14%; P  =  0·53). The average time to intervention for SEPS (11·2±15·3 hours) was faster than for BHs (40·3±69·1 hours) (P  =  0·02). The total hospital LOS was shorter for SEPS (9·3±6·8 days) versus BHs (13·4±10·2 days) (P  =  0·04); both were significantly longer than for a brain tumor patient undergoing craniotomy (7·0±0·5 days, n  =  94, P < 0·01). Conclusion: Despite decreasing LOSs as treatment for cSDH evolved from BHs to SEPS, the LOS for a cSDH is still longer than that of a patient undergoing craniotomy for brain tumor. We noted 11% recurrence in our series of patients, which included individuals who recurred as late as 3 years after initial diagnosis.

Inhibition of Nogo-66 Receptor 1 Enhances Recovery of Cognitive Function after Traumatic Brain Injury in Mice

Central nervous system (CNS) axons recover poorly following injury because of the expression of myelin-derived inhibitors of axonal outgrowth such as Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp), all of which bind to the Nogo-66 receptor 1 (NgR1). Herein we examine the role of NgR1 in the recovery of motor and cognitive function after traumatic brain injury (TBI) using a controlled cortical impact (CCI) model in NgR1 knockout (KO) and wild-type (WT) mice. Four weeks post-injury, scores on the Novel Object Recognition test were significantly increased in NgR1 KO mice compared with WT mice (p<0.05), but motor behavior test scores did not differ significantly between the two groups. Nissl staining showed that NgR1 KO mice had less brain injury volume 2 weeks after CCI (p<0.05). Histological analysis revealed more doublecortin (DCX+) cells (p<0.01) and more Ki-67+ cells in the contralateral dentate gyrus (DG) (p<0.05) 2 weeks after CCI in NgR1 KO mice than in WT. Furthermore, DCX+ cells still retained their longer processes in KO mice (p<0.01) 4 weeks following trauma. The number of bromodeoxyuridine (BrdU)+ cells did not differ between the two groups at 4 weeks post-trauma, but KO mice had higher numbers of cells that co-stained with NeuN, a marker of mature neurons. Increased transcription of growth-associated protein (GAP)-43 in both the injured and contralateral sides of the hippocampus (both p<0.05) was detected in NgR1 KO mice relative to WT. These data suggest that NgR1 negatively influences plasticity and cognitive recovery after TBI.

Brachial Plexus Region Tumors: A Review of Their History, Classification, Surgical Management, and Outcomes

Tumors in the region of the brachial plexus comprise less than 5% of all tumors of the upper extremity. Due to their rarity and anatomical complexity, they present a neurosurgical challenge. This article is a review of brachial plexus tumors, beginning with their historical management and classification. The distribution of tumor pathology at the University of Pennsylvania Medical Center and at other institutions is discussed. The clinical presentation and preoperative assessment of patients with brachial plexus masses segue into a section describing the indications for surgery. The relevant anatomy, surgical techniques, and intraoperative adjuncts are reviewed next. Finally, the surgical outcome for both benign nerve sheath tumors and malignant tumors of the brachial plexus region is discussed. A thorough understanding of the management of brachial plexus tumors can optimize care of patients with these lesions and minimize neurologic deficit.

Administration of human recombinant bone morphogenetic protein-2 for spine fusion may be associated with transient postoperative renal insufficiency.

Study Design. Retrospective chart review. Objective. We reviewed the peri- and postoperative outcomes of our patients who had undergone lumbar and lumbosacral fusion both with and without recombinant human bone morphogenetic protein (rhBMP) over a period of 8 years to assess the frequency of complications and new diagnoses associated with the use of rhBMP2. Summary of Background Data. Administration of rhBMP2 for augmentation of lumbar and lumbosacral spinal fusion has not previously been associated with systemic complications. Methods. A review of all patients undergoing lumbar and lumbosacral fusion over an 8-year period was performed to determine the frequency of postoperative complications and new diagnoses. Comparisons in complication frequency and new postoperative diagnoses between patients receiving rhBMP2 versus only allo- or autograft were made. Statistical methodology was applied to determine significance. Results. None of the 105 patients not receiving rhBMP2 and 3 of 24 patients receiving rhBMP2 had blood urea nitrogens and creatinines that more than doubled and reached values >30 and 1.5 mg/dL, respectively, after surgery (P = 0.006). Renal parameters returned to baseline within 45 days of surgery. Two of the 3 patients with postoperative renal insufficiency had been administered 16 mL (24 mg) of rhBMP2, whereas all other patients receiving rhBMP2 had received 8 mL (12 mg). Both of these patients also had supraventricular tachycardia, fever, and mental status changes after surgery. We recorded no significant increase in the incidence of new endocrinologic, autoimmune, neurologic, or neoplastic disorders associated with the use of rhBMP2 in our small patient population. Conclusion. A small subset of patients may develop transient renal insufficiency after rhBMP2 to augment spinal fusion. Higher doses of rhBMP2 may possibly increase the risk of developing renal insufficiency in particular patients; however, additional study is needed before all the risk factors are understood.

Helmet efficacy against concussion and traumatic brain injury: a review.

Helmets are one of the earliest and most enduring methods of personal protection in human civilization. Although primarily developed for combat purposes in ancient times, modern helmets have become highly diversified to sports, recreation, and transportation. History and the scientific literature exhibit that helmets continue to be the primary and most effective prevention method against traumatic brain injury (TBI), which presents high mortality and morbidity rates in the US. The neurosurgical and neurotrauma literature on helmets and TBI indicate that helmets provide effectual protection against moderate to severe head trauma resulting in severe disability or death. However, there is a dearth of scientific data on helmet efficacy against concussion in both civilian and military aspects. The objective of this literature review was to explore the historical evolution of helmets, consider the effectiveness of helmets in protecting against severe intracranial injuries, and examine recent evidence on helmet efficacy against concussion. It was also the goal of this report to emphasize the need for more research on helmet efficacy with improved experimental design and quantitative standardization of assessments for concussion and TBI, and to promote expanded involvement of neurosurgery in studying the quantitative diagnostics of concussion and TBI. Recent evidence summarized by this literature review suggests that helmeted patients do not have better relative clinical outcome and protection against concussion than unhelmeted patients.