Eric M. Massicotte
Marc R. Del Bigio and Eric M. Massicotte
Object. Hydrocephalus, a pathological dilation of the ventricles of the brain, causes damage to periventricular white matter, at least in part, through chronic ischemia. The authors tested the hypothesis that treatment with nimodipine, an L-type calcium channel-blocking agent with demonstrated efficacy in a range of cerebral ischemic disorders, would ameliorate the adverse effects of experimental hydrocephalus.
Methods. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. The rats were treated by continuous administration of nimodipine or control vehicle for 2 weeks, beginning 2 weeks after induction of hydrocephalus. During the treatment period, the animals underwent repeated tests of motor and cognitive behavior. At the end of the treatment period, the rat brains were analyzed by histopathological and biochemical means.
Nimodipine treatment prevented the declines in motor and cognitive behavior that were observed in untreated control rats. During the treatment period, ventricular enlargement, determined by magnetic resonance imaging, was equal in the two groups, although the corpus callosum was thicker in the treated rats. Myelin content in white matter and synaptophysin content in gray matter, an indicator of synapses, did not differ.
Conclusions. The protective effect of nimodipine is most likely based on improved blood flow, although prevention of calcium influx—mediated proteolytic processes in axons cannot be excluded. Adjunctive pharmacological therapy may be beneficial to patients with hydrocephalus.
Eric M. Massicotte and Marc R. Del Bigio
Object. The origin of chronic communicating hydrocephalus following subarachnoid hemorrhage (SAH) is not well understood. Fibrosis of the arachnoid villi has been suggested as the cause for obstruction of cerebrospinal fluid (CSF) flow, but this is not well supported in the literature. The goal of this study was to determine the relationship between blood, inflammation, and cellular proliferation in arachnoid villi after SAH.
Methods. Arachnoid villi from 50 adult patients were sampled at autopsy. All specimens were subjected to a variety of histochemical and immunohistochemical stains. The 23 cases of SAH consisted of patients in whom an autopsy was performed 12 hours to 34 years post-SAH. Fifteen cases were identified as moderate-to-severe SAH, with varying degrees of hydrocephalus. In comparison with 27 age-matched non-SAH controls, the authors observed blood and inflammation within the arachnoid villi during the 1st week after SAH. Greater mitotic activity was also noted among arachnoid cap cells. The patient with chronic SAH presented with ventriculomegaly 2 months post-SAH and exhibited remarkable arachnoid cap cell accumulation.
Conclusions. The authors postulate that proliferation of arachnoidal cells, triggered by the inflammatory reaction or blood clotting products, could result in obstruction of CSF flow through arachnoid villi into the venous sinuses. This does not exclude the possibility that SAH causes generalized fibrosis in the subarachnoid space.
Eric M. Massicotte, Richard Buist and Marc R. Del Bigio
It can be inferred from data published in the literature that brain compression occurs in the early stages of acute hydrocephalus and that drainage of extracellular waste products is impaired. The authors hypothesized that compression of the cortical extracellular compartment will alter water distribution and retard the diffusion of fluid in the hydrocephalic brain.
Using magnetic resonance imaging proton diffusion, blood perfusion, and T1 and T2 relaxation times were determined in adult rat brain prior to, and 1 and 8 days following induction of hydrocephalus by using kaolin injection. Five anatomical regions of interest were studied. The striatum, dorsal cortex, and lateral cortex were shown to exhibit decreased T2 and apparent diffusion coefficient (ADC) values but no change in perfusion. Examination of white matter demonstrated an initial decrease in ADC followed by a significant increase. The T2 relaxation times increased and perfusion decreased progressively from 1 to 8 days.
Acute experimental hydrocephalus causes compression of gray matter, perhaps associated with reduction in total water, which impairs diffusion of protons in the tissue. White matter compression and hypoperfusion precede the development of edema. These findings have importance for understanding the neurochemical changes that occur in hydrocephalic brains.
Eric M. Massicotte, Richard Buist and Marc R. Del Bigio
Object. It can be inferred from data published in the literature that brain compression occurs in the early stages of acute hydrocephalus and that drainage of extracellular waste products is impaired. The authors hypothesized that compression of the cortex would alter water distribution and retard the diffusion of fluid in the hydrocephalic brain.
Methods. Proton diffusion, blood perfusion, and T1 and T2 relaxation times were determined in adult rat brain by using magnetic resonance imaging prior to, and 1 and 8 days after induction of hydrocephalus by kaolin injection. Five anatomical regions of interest were studied. The striatum, dorsal cortex, and lateral cortex exhibited decreased T2 and apparent diffusion coefficient (ADC) values but no change in perfusion. Examination of white matter revealed an initial decrease in ADC followed by a significant increase. The T2 relaxation times increased and perfusion decreased progressively between 1 and 8 days after induction of hydrocephalus.
Conclusions. Acute experimental hydrocephalus causes compression of gray matter, perhaps associated with reduction in total water, which impairs diffusion of water in the tissue. White matter compression and hypoperfusion precede the development of edema. These findings have importance for understanding the neurochemical changes that occur in hydrocephalic brains.
Ramamani Mariappan, Pirjo Manninen, Eric M. Massicotte and Anuj Bhatia
A hypersensitivity reaction, either anaphylactic or anaphylactoid, is a well-known adverse effect following intravenous and oral administration of vancomycin. The authors report a case of circulatory collapse and its management after the topical application of vancomycin powder during spinal instrumentation surgery. A 52-year-old woman with breast cancer and metastasis to her spine underwent a vertebrectomy of the T-10 vertebra with instrumented reconstruction from T-8 to T-12. The patient was hemodynamically stable during most of the procedure despite a 2-L blood loss requiring administration of crystalloids, colloids, packed red blood cells, and fresh-frozen plasma. During closure of the subcutaneous layer, there was a sudden drop in blood pressure from 120/60 to 30/15 mm Hg and an increase in heart rate from 95 to 105 bpm. No skin erythema or rash was visible, and there was no bronchospasm or increase in airway pressure. The patient was treated with fluids, boluses of ephedrine, phenylephrine, and adrenaline. The operation was completed and the patient woke up neurologically intact but did require blood pressure support with a norepinephrine infusion for the next 4 hours. She was discharged from hospital in a good clinical state on the 4th postoperative day. It was speculated that the rapid absorption of vancomycin powder applied on the surgical wound caused an anaphylactoid reaction and the circulatory collapse. With an increase in the use of topical vancomycin in surgical wounds, communication and awareness among all intraoperative team members is important for rapid diagnosis of an adverse reaction and for appropriate management.
Nardin Samuel, Lindsay Tetreault, Carlo Santaguida, Anick Nater, Nizar Moayeri, Eric M. Massicotte and Michael G. Fehlings
The objective of this study was to identify clinically relevant predictors of progression-free survival and functional outcomes in patients who underwent surgery for intramedullary spinal cord tumors (ISCTs).
An institutional spinal tumor registry and billing records were reviewed to identify adult patients who underwent resection of ISCTs between 1993 and 2014. Extensive data were collected from patient charts and operative notes, including demographic information, extent of resection, tumor pathology, and functional and oncological outcomes. Survival analysis was used to determine important predictors of progression-free survival. Logistic regression analysis was used to evaluate the association between an “optimal” functional outcome on the Frankel or McCormick scale at 1-year follow-up and various clinical and surgical characteristics.
The consecutive case series consisted of 63 patients (50.79% female) who underwent resection of ISCTs. The mean age of patients was 41.92 ± 14.36 years (range 17.60–75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07–31.11, p = 0.0026) and myxopapillary ependymomas (HR 8.01, 95% CI 1.44–44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23–9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an “optimal” outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89–0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33–17.63, p = 0.017), McCormick score (OR 0.22, 95% CI 0.084–0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012–0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001–0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores.
Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status.
Ameen Al-Omair, Roger Smith, Tim-Rasmus Kiehl, Louis Lao, Eugene Yu, Eric M. Massicotte, Julia Keith, Michael G. Fehlings and Arjun Sahgal
Spine stereotactic radiosurgery (SRS) is increasingly being used to treat metastatic spinal tumors. As the experience matures, high rates of vertebral compression fracture (VCF) are being observed. What is unknown is the mechanism of action; it has been postulated but not confirmed that radiation itself is a contributing factor. This case report describes 2 patients who were treated with spine SRS who subsequently developed signal changes on MRI consistent with tumor progression and VCF; however, biopsy confirmed a diagnosis of radiation-induced necrosis in 1 patient and fibrosis in the other. Radionecrosis is a rare and serious side effect of high-dose radiation therapy and represents a diagnostic challenge, as the authors have learned from years of experience with brain SRS. These cases highlight the issues in the new era of spine SRS with respect to relying on imaging alone as a means of determining true tumor progression. In those scenarios in which it is unclear based on imaging if true tumor progression has occurred, the authors recommend biopsy to rule out radiation-induced effects within the bone prior to initiating salvage therapies.
Michael G. Fehlings, Neilank K. Jha, Stephanie M. Hewson, Eric M. Massicotte, Branko Kopjar and Sukhvinder Kalsi-Ryan
Surgical intervention for appropriately selected patients with cervical spondylotic myelopathy (CSM) has demonstrated favorable outcomes. This study evaluates the cost-effectiveness of this type of surgery in terms of cost per quality-adjusted life year (QALY) gained.
As part of a larger prospective multicenter study, the direct costs of medical treatment for 70 patients undergoing surgery for CSM at a single institution in Canada were retrospectively obtained from the hospital expenses database and physician reimbursement data. Utilities were estimated on the entire sample of 278 subjects enrolled in the multicenter study using SF-6D–derived utilities from 12- and 24-month SF-36v2 follow-up information. Costs were analyzed from the payer perspective. A 10-year horizon with 3% discounting was applied to health-utilities estimates. Sensitivity analysis was performed by varying utility gain by 20%.
The SF-6D utility gain was 0.0734 (95% CI 0.0557–0.0912, p < 0.01) at 12 months and remained unchanged at 24 months. The 10-year discounted QALY gain was 0.64. Direct costs of medical treatment were estimated at an average of CaD $21,066. The estimated cost-utility ratio was CaD $32,916 per QALY gained. The sensitivity analysis showed a range of CaD $27,326–$40,988 per QALY gained. These estimates are within the limits for medical procedures that have an acceptable cost-utility ratio.
Surgical treatment for CSM is associated with significant improvement in health utilities as measured by the SF-6D. The direct cost of medical treatment per QALY gained places this form of treatment within the category deemed by payers to be cost-effective.
Faisal S. Taleb, Abhijit Guha, Paul M. Arnold, Michael G. Fehlings and Eric M. Massicotte
Patients with neurofibromatosis Type 1 (NF-1) at the cervical spine present significant surgical challenges due to neural compression, multiplicity of tumors, and complex spinal deformities. Iatrogenic instability following resection of tumors is underappreciated in the literature. The focus of this study was to understand the indications for stabilization in this specific group of patients.
The authors performed a retrospective review of 20 cases involving NF-1 patients with symptomatic cervical spine neurofibromas who underwent surgical decompression and tumor resection, with or without instrumentation, between 1991 and 2008. They also included 2 additional cases involving patients treated before 1991. Imaging findings and data pertaining to clinical presentation, intraoperative management, and postoperative assessment were compiled to clarify the indications for stabilization. An ordinal pain scale based on patient self-assessment was used. Neurological function was evaluated using American Spinal Injury Association Impairment Scale scores.
The patient group comprised 13 men and 9 women. Their median age at presentation was 42.5 years; their median age at initial diagnosis of NF-1 was 30 years (range 8–74 years). The median duration of follow-up (since presentation) was 7 years (range 1–32 years). Progressive myelopathy was the main presenting symptom. Spinal cord compression was identified in 13 patients on presentation. Complete removal of the symptomatic tumors was performed in 11 patients. Ten patients underwent instrumented fusion during their first surgery. Six of these 10 required a second surgery—with fixation in 4 cases and without in 2. Of the 12 patients who did not receive instrumented fusion in their first surgery, 8 required a second surgery—with fixation in 5 cases and without in 3. Neurological deterioration due to progressive deformity was the indication for the second surgery in 3 of the 5 patients who required instrumented fusion only in their second surgery; the other 2 patients presented with neurological deterioration secondary to tumor progression. Four patients needed a third operation and instrumented fusion: 3 for deformity-related deficit and 1 for tumor progression. Based on the latest follow-up, 21 patients were stable clinically and radiologically, and 1 patient had died.
This specific group of patients represents a significant surgical challenge. In this retrospective analysis, emphasis is placed on early stabilization of the cervical spine to prevent late deformity as part of the comprehensive management of patients with NF-1.