Ketan R. Bulsara

Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons

In contrast to peripheral nerves, damaged axons in the mammalian brain and spinal cord rarely regenerate. Peripheral nerve injury stimulates neuronal expression of many genes that are not generally induced by CNS lesions, but it is not known which of these genes are required for regeneration. Here we show that co-expressing two major growth cone proteins, GAP-43 and CAP-23, can elicit long axon extension by adult dorsal root ganglion (DRG) neurons in vitro. Moreover, this expression triggers a 60-fold increase in regeneration of DRG axons in adult mice after spinal cord injury in vivo. Replacing key growth cone components, therefore, could be an effective way to stimulate regeneration of CNS axons.

Perioperative complications in transforaminal lumbar interbody fusion versus anterior-posterior reconstruction for lumbar disc degeneration and instability.

Objectives Multiple different approaches are used to treat lumbar degenerative disc disease and spinal instability. Both anterior–posterior (AP) reconstructive surgery and transforaminal lumbar interbody fusion (TLIF) provide a circumferential fusion and are considered reasonable surgical options. The purpose of this study was to quantitatively assess clinical parameters such as surgical blood loss, duration of the procedure, length of hospitalization, and complications for TLIF and AP reconstructive surgery for lumbar fusion. Methods A retrospective analysis was completed on 167 consecutive cases performed between January 2002 and March 2004. TLIF surgical procedure was performed on 124 patients, including 73 minimally invasive and 51 open cases. AP surgery was performed on 43 patients. Patients were treated for painful degenerative disc disease, facet arthropathy, degenerative instability, and spinal stenosis. Results The mean operative time for AP reconstruction was 455 minutes, for minimally invasive TLIF 255 minutes, and open TLIF 222 minutes. The mean blood loss for AP fusion surgery was 550 mL, for minimally invasive TLIF 231 mL, and open TLIF 424 mL. The mean hospitalization time for AP reconstruction was 7.2 days, for minimally invasive TLIF 3.1 days, and open TLIF 4.1 days. The total rate of complications was 76.7% for AP reconstruction, including 62.8% major and 13.9% minor complications. The minimally invasive TLIF patients group had the total 30.1% rate of complications, 21.9% of which were minor and 8.2% major complications. There were no major complications in the open TLIF patients group, with 35.3% minor complications. Conclusions AP lumbar interbody fusion surgery is associated with a more than two times higher complication rate, significantly increased blood loss, and longer operative and hospitalization times than both percutaneous and open TLIF for lumbar disc degeneration and instability.

Laminectomy versus Percutaneous Electrode Placement for Spinal Cord Stimulation

OBJECTIVE The purpose of this study was to compare the long-term effectiveness of spinal cord stimulation using laminectomy-style electrodes versus that using percutaneously implanted electrodes. METHODS Forty-one patients underwent an initial trial period of spinal cord stimulation with temporary electrodes at Duke Medical Center between December 1992 and January 1998. A permanent system was implanted if trial stimulation reduced the patients pain by more than 50%. Median long-term follow-up after permanent electrode placement was 34 months (range, 6-66 mo). Severity of pain was determined postoperatively by a disinterested third party using a visual analog scale and a modified outcome scale. RESULTS Twenty-seven (66%) of the 41 patients participating in the trial had permanent electrodes placed. Visual analog scores decreased an average of 4.6 among patients in whom electrodes were placed via laminectomy in the thoracic region (two-tailed t test, P < 0.0001). Patients who underwent percutaneous placement of thoracic electrodes had an average decrease of 3.1 in their visual analog scores (two-tailed t test, P < 0.001). Electrodes placed through laminectomy furnished significantly greater long-term pain relief than did those placed percutaneously, as measured by a four-tier outcome grading scale (P = 0.02). CONCLUSION Spinal cord stimulation is an effective treatment for chronic pain in the lower back and lower extremities that is refractory to conservative therapy. Electrodes placed via laminectomy in the thoracic region appear to be associated with significantly better long-term effectiveness than are electrodes placed percutaneously.

Vessel wall magnetic resonance imaging identifies the site of rupture in patients with multiple intracranial aneurysms: proof of principle.

BACKGROUND High-resolution magnetic resonance vessel wall imaging (MR-VWI) is increasingly used to study steno-occlusive cerebrovascular disease, but has not yet been applied to patients with aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE To study the ability of high-resolution MR-VWI to determine the site of rupture in patients with aneurysmal SAH. METHODS Medical records of patients admitted with aneurysmal SAH between December 2011 and May 2012 were reviewed. MR-VWI was routinely performed for patients treated in the IMRIS Neurovascular Suite immediately before definitive treatment of the ruptured aneurysm. RESULTS We report for the first time high-resolution MR-VWI in 5 patients with aneurysmal SAH. Three patients harbored multiple intracranial aneurysms. The ruptured aneurysms demonstrated thick vessel wall enhancement in all cases. None of the associated unruptured aneurysms demonstrated this MR imaging finding. CONCLUSION High-resolution MR-VWI identified the site of rupture in patients with aneurysmal SAH, including those patients harboring multiple intracranial aneurysms. It may represent a useful tool in the investigation of aneurysmal SAH.

Correlation of cerebrospinal fluid flow dynamics and headache in Chiari I malformation.

OBJECTIVE:The management of patients with a Chiari I malformation who present with headaches alone remains unclear. We studied the cerebrospinal fluid (CSF) flow dynamics of Chiari I malformation patients presenting with headaches alone so as to identify headache types that are associated with CSF flow obstruction versus those that may be unrelated to Chiari I malformations. METHODS:Preoperative cine phase-contrast magnetic resonance imaging of the craniocervical junction was prospectively performed in 33 patients presenting with headaches alone and a Chiari I malformation (tonsillar ectopia >5 mm below the foramen magnum). Headaches were classified as frontal, occipital, or generalized. CSF flow dynamics were then prospectively compared with presenting symptomatology. A subgroup of 17 patients underwent surgical decompression of the Chiari I malformations. RESULTS:Patients with frontal or generalized headaches were 10-fold less likely to demonstrate obstructed CSF flow (odds ratio, 0.10; 95% confidence interval, 0.02–0.52) and 8-fold less likely to have tonsillar descent greater than 7 mm (odds ratio, 0.12; 95% confidence interval, 0.03–0.62) compared with patients with occipital headaches. Adjusting for degree of tonsillar herniation in multivariate analysis, frontal and generalized headaches remained independently associated with nonobstructed CSF flow pathological findings, whereas occipital headaches remained associated with obstructed CSF flow independent of tonsil location (odds ratio, 5.84; 95% confidence interval, 1.01–34.28). In the surgical group, all patients with obstructed CSF flow did well compared with the group with normal flow, regardless of headache location. CONCLUSION:Regardless of the degree of tonsillar ectopia, occipital headaches were strongly associated with hindbrain CSF flow abnormalities, whereas frontal and generalized headaches were not. Normal magnetic resonance imaging-cine CSF flow in the setting of a Chiari I malformation and frontal headaches alone suggests that frontal headaches are not pathologically or causatively associated with the Chiari I malformation in the vast majority of patients. Frontal headaches with obstructed flow may respond to surgery.

Unruptured Cerebral Aneurysms Do Not Shrink When They Rupture: Multicenter Collaborative Aneurysm Study Group

BACKGROUND:The International Study of Intracranial Aneurysms found that for patients with no previous history of subarachnoid hemorrhage, small (< 7 mm) anterior circulation and posterior circulation aneurysms had a 0% and 2.5% risk of subarachnoid hemorrhage over 5 years, respectively. OBJECTIVE:To determine whether cerebral aneurysms shrink with rupture. METHODS:The clinical databases of 7 sites were screened for patients with imaging of cerebral aneurysms before and after rupture. Inclusion criteria included documented subarachnoid hemorrhage by imaging or lumbar puncture and intracranial imaging before and after cerebral aneurysm rupture. The patients were evaluated for aneurysm maximal height, maximal width, neck diameter, and other measurement parameters. Only a change of ≥ 2 mm was considered a true change. RESULTS:Data on 13 patients who met inclusion criteria were collected. The median age was 60, and 11 of the 13 patients (84.6%) were female. Only 5 patients had posterior circulation aneurysms. None of the aneurysms had a significant decrease in size. One aneurysm decreased by 1.8 mm in maximum size after rupture (7.7%). Six aneurysms had an increase in maximum size of at least 2 mm after rupture (46.2%) with a mean increase of 3.5 mm (± 0.5 mm). CONCLUSION:Unruptured aneurysms do not shrink when they rupture. The large percentage of ruptured small aneurysms in previous studies were likely small before they ruptured.

Utility of computerized isocentric fluoroscopy for minimally invasive spinal surgical techniques.

Objective: The purpose of this study was to prospectively evaluate the clinical utility and accuracy of intraoperative three-dimensional fluoroscopy as an adjunct for the placement of a complex spinal instrumentation. Methods: The Siemens Iso-C three-dimensional fluoroscopy unit in the combination with the Stealth Treon computer volumetric navigational system was used. A total of 279 spinal instrumentation screws or transpedicular cannulations were performed in 69 patients. Accuracy, operative time, and amount of fluoroscopy utilization time were assessed for transforaminal lumbar interbody fusion (TLIF) and kyphoplasty cases. Results: Only 4 percutaneous transpedicular lumbar screws out of 265 total (1.5%) were malpositioned. Average operative time for TLIF cases was 185 minutes (range 114-311 minutes) for one-level and 292.6 minutes (range 173-390 minutes) for two-level procedures. Biplanar fluoroscopy utilization time was 93 seconds (range 27-280 seconds) for one-level procedures and 216 seconds (range 80-388 seconds) for two-level procedures. Average surgery duration for kyphoplasty was 60 minutes (range 36-79 minutes) for one-level procedures and 68.5 minutes (range 65-75 minutes) for two-level cases. Biplanar fluoroscopy utilization time was 41.3 seconds per case (range 25-62 seconds). Conclusions: Use of intraoperative three-dimensional fluoroscopy for image guidance in minimally invasive complex spinal instrumentation procedures is feasible and safe. This technique provides excellent visualization of three-dimensional relationships. This potentially results in improved accuracy of screw positioning and the ability to detect misplaced screws prior to wound closure. This technique also potentially results in a significant reduction in radiation exposure for both the patient and the staff.

De Novo Cerebral Arteriovenous Malformation: Case Report

OBJECTIVE AND IMPORTANCE Arteriovenous malformations (AVMs) are generally thought to have a congenital cause. This is the first report of an angiographically proven de novo cerebral AVM in an adult patient without previous vascular abnormality. CLINICAL PRESENTATION A 26-year-old African-American woman developed multiple cranial nerve deficits and ataxia over the course of a few days after a streptococcal throat infection. T2-weighted magnetic resonance imaging scans revealed a hyperintense signal in the midbrain with extension into the diencephalon. A cerebral angiogram performed at that time to exclude vasculitis revealed normal cerebral vasculature. The patient was treated with corticosteroids, and symptoms resolved. Subsequently, at the age of 32, this patient presented with a severe headache and emesis, but with no focal neurological deficit. INTERVENTION The patient’s cranial computed tomographic and magnetic resonance imaging scans revealed a right posterior temporal intraparenchymal hemorrhage, and cerebral angiography revealed a new 3- by 2-cm AVM. The patient underwent microsurgical resection of the AVM and associated hematoma. Postoperative angiography revealed no evidence of residual AVM. CONCLUSION This study details the case of a woman who developed a de novo cerebral AVM during a 6-year period. This report challenges the conventional belief that all AVMs have a congenital cause.

A new millenium for spinal cord regeneration: growth-associated genes.

Introduction. Neurons surviving spinal cord injury undergo extensive reorganization that may result in the formation of functional synaptic contacts. Many neurons, however, fail to activate the necessary mechanisms for successful regeneration. In this review, we discuss the implications of growth cone genes that we have correlated with successful spinal cord axonal regeneration. Method. Factors that inhibit regeneration, and activation of genes that promote it are discussed. Results/Discussion. The early progress n understanding mechanisms that seem to promote or inhibit regeneration in the central nervous system may have significant clinical utility in the future.

MRI-guided stereotactic biopsy in the diagnosis of glioma: comparison of biopsy and surgical resection specimen

BACKGROUND Although there has been a dramatic increase in the accessibility and utilization of high-resolution MRI techniques for the evaluation of brain tumors, there is currently only a single report comparing stereotactic brain biopsy specimen to subsequent resection specimen exclusively in the management of gliomas. METHODS The diagnoses in 43 cases of astrocytic brain tumors were derived using MRI-guided stereotactic biopsy followed by open resection of the lesion. The histologic diagnoses yielded by biopsy were compared with subsequent histologic diagnosis after open tumor resection. All biopsies and histologic diagnoses were made by the same surgeon and pathologist, respectively. RESULTS In 23 patients undergoing resection <60 days after biopsy, the biopsy diagnosis was consistent with resection diagnosis in 18 cases (79%) and led to the correct treatment in 22 cases (96%). Recurrent glioblastoma multiforme (GBM) was undergraded as anaplastic astrocytoma in 4 patients. GBM was misdiagnosed as radiation necrosis in 1 patient. MR-nonenhancing lesions [10/10 (100%)] yielded histology that correlated with subsequent craniotomy, while only 8/13 (61%) MR-enhancing lesions yielded histology that was consistent with that at craniotomy (p < 0.05). In 20 patients undergoing resection because of radiologic tumor progression (mean 7 months after biopsy), 6/6 (100%) biopsy diagnoses of a specific glioma grade correlated with resection diagnosis, while only 6/14 (43%) biopsy diagnoses of radiation effect correlated with resection diagnosis (p < 0.01). CONCLUSION MRI-guided stereotactic brain biopsy specimen accurately represents the grade of the larger glioma mass sufficiently to guide subsequent therapy. Enhancement on MR may be a negative prognostic indicator of biopsy accuracy.