Matthew J. McGirt

Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas

OBJECTIVEIt remains unknown whether the extent of surgical resection affects survival or disease progression in patients with supratentorial low-grade gliomas. METHODSWe conducted a retrospective cohort study (n = 170) between 1996 and 2007 at a single institution to determine whether increasing extent of surgical resection was associated with improved progression-free survival (PFS) and overall survival (OS). Surgical resection of gliomas defined as gross total resection (GTR) (complete resection of the preoperative fluid-attenuated inversion recovery signal abnormality), near total resection (NTR) (<3-mm thin residual fluid-attenuated inversion recovery signal abnormality around the rim of the resection cavity only), or subtotal resection (STR) (residual nodular fluid-attenuated inversion recovery signal abnormality) based on magnetic resonance imaging performed less than 48 hours after surgery. Our main outcome measures were OS, PFS, and malignant degeneration-free survival (conversion to high-grade glioma). RESULTSOne hundred thirty-two primary and 38 revision resections were performed for low-grade astrocytomas (n = 93) or oligodendrogliomas (n = 77). GTR, NTR, and STR were achieved in 65 (38%), 39 (23%), and 66 (39%) cases, respectively. GTR versus STR was independently associated with increased OS (hazard ratio, 0.36; 95% confidence interval, 0.16–0.84; P = 0.017) and PFS (HR, 0.56; 95% confidence interval, 0.32–0.98; P = 0.043) and a trend of increased malignant degeneration-free survival (hazard ratio, 0.46; 95% confidence interval, 0.20–1.03; P = 0.060). NTR versus STR was not independently associated with improved OS, PFS, or malignant degeneration-free survival. Five-year OS after GTR, NTR, and STR was 95, 80, 70%, respectively, and 10-year OS was 76, 57, and 49%, respectively. After GTR, NTR, and STR, median time to tumor progression was 7.0, 4.0, and 3.5 years, respectively. Median time to malignant degeneration after GTR, NTR, and STR was 12.5, 5.8, and 7 years, respectively. CONCLUSIONGTR was associated with a delay in tumor progression and malignant degeneration as well as improved OS independent of age, degree of disability, histological subtype, or revision versus primary resection. GTR should be safely attempted when not limited by eloquent cortex.

Simvastatin Reduces Vasospasm After Aneurysmal Subarachnoid Hemorrhage: Results of a Pilot Randomized Clinical Trial

Background and Purpose— Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH. Methods— Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; n=19) or placebo (n=20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis. Serum markers of brain injury were recorded daily. The primary end point of vasospasm was defined as clinical impression (delayed ischemic deficit not associated with rebleed, infection, or hydrocephalus) in the presence of ≥1 confirmatory radiographic test (angiography or transcranial Doppler demonstrating mean VMCA >160 m/sec). Results— There were no significant differences in laboratory-defined transaminitis or myositis between groups. No patients developed clinical symptoms of myopathy or hepatitis. Plasma von Willebrand factor and S100&bgr; were decreased 3 to 10 days after SAH (P<0.05) in patients receiving simvastatin versus placebo. Highest mean middle cerebral artery transcranial Doppler velocities were significantly lower in the simvastatin-treated group (103±41 versus 149±47; P<0.01). In addition, vasospasm was significantly reduced (P<0.05) in the simvastatin-treated group (5 of 19) compared with those who received placebo (12 of 20). Conclusion— The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.

Simvastatin Increases Endothelial Nitric Oxide Synthase and Ameliorates Cerebral Vasospasm Resulting From Subarachnoid Hemorrhage

Background and Purpose— Endothelial nitric oxide synthase (eNOS) activity is decreased after subarachnoid hemorrhage (SAH). Simvastatin increases eNOS activity. We hypothesized that simvastatin would increase eNOS protein and ameliorate SAH-induced cerebral vasospasm. Methods— Mice were treated with subcutaneous simvastatin or vehicle for 14 days and then subjected to endovascular perforation of the right anterior cerebral artery or sham surgery. Three days later, neurological deficits were scored (5 to 27; 27=normal), and middle cerebral artery diameter and eNOS protein were measured. The study was repeated, but simvastatin treatment was started after SAH or sham surgery. Results— In SAH mice, simvastatin pretreatment increased middle cerebral artery diameter (SAH-simvastatin=74±22 &mgr;m, SAH-vehicle=52±18 &mgr;m, P =0.03; sham-simvastatin=102±8 &mgr;m, sham-vehicle=105±6 &mgr;m). Pretreatment reduced neurological deficits (SAH-simvastatin=25±2, SAH-vehicle=20±2, P =0.005; sham-simvastatin and sham-vehicle=27±0). Simvastatin pretreatment also increased eNOS protein. Simvastatin posttreatment caused a modest increase in middle cerebral artery diameter in SAH mice (SAH-simvastatin=56±12 &mgr;m, SAH-vehicle=45±4 &mgr;m, P =0.03; sham-simvastatin=92±13 &mgr;m, sham-vehicle=99±10 &mgr;m) and reduced neurological deficits (SAH-simvastatin=21±1, SAH-vehicle=19±2, P =0.009). Simvastatin posttreatment did not significantly increase eNOS protein. Conclusions— Simvastatin treatment before or after SAH attenuated cerebral vasospasm and neurological deficits in mice. The mechanism may be attributable in part to eNOS upregulation.

Association of surgically acquired motor and language deficits on overall survival after resection of glioblastoma multiforme

OBJECTIVEBalancing the benefits of extensive tumor resection with the consequence of potential postoperative deficits remains a challenge in malignant astrocytoma surgery. Although studies have suggested that increasing extent of resection may benefit survival, the effect of new postoperative deficits on survival remains unclear. We set out to determine whether new-onset postoperative motor or speech deficits were associated with survival in our institutional experience with glioblastoma multiforme (GBM). METHODSWe retrospectively reviewed records of all patients (age range, 18–70 years; Karnofsky Performance Scale score, 80–100) who had undergone GBM resection between 1996 and 2006 at a single institution. Survival was compared between patients who had experienced surgically acquired motor or language deficits versus those who did not experience these deficits. RESULTSThree hundred six consecutive patients (age, 54 ± 11 years; median Karnofsky Performance Scale score, 80) underwent primary GBM resection. Nineteen patients (6%) developed surgically acquired motor deficits and 15 (5%) developed surgically acquired language deficits. Median survival was decreased in patients who acquired language deficits (9.6 months; P < 0.05) or motor deficits (9.0 months; P < 0.05) versus patients without surgically acquired deficits (12.8 months). Two-year survival was 8% and 0% for patients with surgically acquired motor or language deficits, respectively, versus 23% for patients without new-onset deficits. CONCLUSIONIn our experience, the development of new perioperative motor or language deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. Although it is well known that surgically induced neurological deficits affect quality of life, our results suggest that these surgical morbidities may also affect survival. Care should be taken to avoid surgically induced deficits in the management of GBM.

Diagnosis, treatment, and analysis of long-term outcomes in idiopathic normal-pressure hydrocephalus.

OBJECTIVE The response to shunt surgery for idiopathic normal-pressure hydrocephalus (INPH) is variable because INPH is difficult to distinguish from other conditions causing the same symptoms. To date, no clinical picture or diagnostic test can distinguish INPH or predict response to cerebrospinal fluid (CSF) shunt surgery. We reviewed our 10-year experience with INPH to characterize long-term outcome and to identify independent predictors of outcome after shunt surgery. METHODS Patients were classified as having INPH only if they had: 1) ventriculomegaly, 2) two or more INPH clinical features, 3) no risk factor for secondary normal-pressure hydrocephalus, 4) A- or B-waves on CSF pressure monitoring, and 5) clinical improvement during a 3-day CSF drainage trial via a spinal catheter. Independent predictors of outcome were assessed via a multivariate proportional hazards regression analysis. RESULTS One hundred thirty-two patients underwent 179 shunt surgeries. Forty-four (33%), 79 (60%), and 99 (75%) patients demonstrated objective improvement 3, 6, and 24 months after shunt surgery, respectively. Gait improved first in 88 (93%) patients. Dementia and urinary incontinence were twofold less likely to improve. Radiological evidence of corpus callosum distension, gait impairment as the primary symptom, and shorter duration of INPH symptoms predicted improvement. Duration of symptoms and gait as the primary symptom were independent predictors by multivariate analysis. CONCLUSION INPH can be diagnosed accurately with CSF pressure monitoring and CSF drainage via a spinal catheter. CSF shunting is safe and effective for INPH with a long-term shunt response rate of 75%. Independent predictors of improvement are the presence of gait impairment as the dominant symptom and shorter duration of symptoms.

Vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: an evidenced-based review of the literature.

BACKGROUND Vertebroplasty (VP) and kyphoplasty (KP) are routinely used to treat vertebral body compression fractures (VCFs) resulting from osteoporosis or vertebral body tumors in order to provide rapid pain relief. However, it remains debated whether VP or KP results in superior outcomes versus medical management alone in patients experiencing VCFs. PURPOSE To determine the level of evidence supporting VP or KP for the treatment of VCFs. STUDY DESIGN Systematic review of the literature. PATIENT SAMPLE Patients with osteoporotic or tumor-associated VCFs. OUTCOME MEASURES Self-reported and functional measures. METHODS We reviewed all articles published between 1980 and 2008 reporting outcomes after VP or KP for osteoporotic or tumor-associated VCFs and rated the level of evidence and grades of recommendation (per North American Spine Society [NASS] guidelines) supporting the use of VP or KP for the treatment of VCFs. RESULTS Seventy-four VP studies for osteoporotic VCF (1 level I, 3 level II, 70 level IV), 35 KP studies for osteoporotic VCF (2 level II, 33 level IV), and 18 VP/KP for tumor VCFs (all level IV) were reviewed. There is good evidence (level I) that VP results in superior pain control within the first 2 weeks of intervention compared with optimal medical management for osteoporotic VCFs. There is fair evidence (level II-III) that VP results in less analgesia use, less disability, and greater improvement in general health when compared with optimal medical management within the first 3 months after intervention. There is fair evidence (level II-III) that by 2 years after intervention, VP provides a similar degree of pain control and physical function as optimal medical management. There is fair evidence (level II-III) that KP results in greater improvement in daily activity, physical function, and pain relief when compared with optimal medical management for osteoporotic VCFs by 6 months after intervention. There is poor-quality evidence that VP or KP results in greater pain relief for tumor-associated VCFs. CONCLUSIONS Although evidence suggests that physical disability, general health, and pain relief are better with VP and KP than those with medical management within the first 3 months after intervention, high-quality randomized trials with 2-year follow-up are needed to confirm this. Furthermore, the reported incidence of symptomatic procedure-related morbidity for both VP and KP is very low.

Risk Factors for Pediatric Ventriculoperitoneal Shunt Infection and Predictors of Infectious Pathogens

Identification of risk factors for shunt infection and predictors of infectious pathogens may improve current methods to prevent and treat shunt infections. We reviewed data on 820 consecutive ventriculoperitoneal (VP) shunt placement procedures in 442 pediatric patients at our institution during 1992-1998. Ninety-two shunts (11%) developed infection a median of 19 days (interquartile range, 11-35 days) after insertion. Premature birth (relative risk [RR], 4.81; 95% confidence interval [CI], 2.19-10.87), previous shunt infection (RR, 3.83; 95% CI, 2.40-6.13), and intraoperative use of the neuroendoscope (RR, 1.58; 95% CI, 1.01-2.50) were independent risk factors for shunt infection. The bacterial organisms early after shunt surgery (<14 days) were the same as those late after shunt surgery (>14 days). As determined by an analysis of the 92 infected shunts, hospital stay of >3 days at the time of shunt insertion (odds ratio [OR], 5.27; 95% CI, 1.15-25.3) and prior Staphylococcus aureus shunt infection (OR, 5.91; 95% CI, 1.35-25.9) independently increased the odds that S. aureus was the causal pathogen.

Cerebrospinal Fluid Shunt Survival and Etiology of Failures: A Seven-Year Institutional Experience

Background: Innovations in shunt technology and neuroendoscopy have been increasingly applied to shunt management. However, the relative life span of shunts and the etiology of shunt failure have not been characterized recently. Methods: We reviewed the records of all shunting procedures at our institution between January 1992 and December 1998. Independent predictors of shunt failure were analyzed via multivariate Cox regression analysis in 836 shunting procedures. Independent predictors of the etiology of failure (infection, proximal obstruction, distal malfunction) were analyzed via multivariate logistic regression analysis in the 383 shunts which failed. Results: A total of 353 pediatric patients underwent 308 shunt placements and 528 revisions. The risk (hazard ratio; HR) of shunt failure decreased as a function of time in both primary placements and revised shunts. In failed shunts, the odds of infection decreased 4-fold per year of shunt function, while the odds of distal malfunction increased 1.45-fold per year. Increasing number of shunt revisions (HR 1.31, p < 0.05), decreasing patient age in years (HR 1.04, p < 0.001), gestational age <40 weeks (HR 2.15, p < 0.001) but not the etiology of hydrocephalus were associated with an increased risk of shunt failure. Revisions versus primary placements, Dandy-Walker cysts and gestational age <40 weeks were independently associated with proximal, distal and infectious causes of failure, respectively. Conclusions: The long-term shunt revision rates observed here are similar to those reported over the past 2 decades. Shunt life span remains poorer in shunt revisions and in younger patients. Patient characteristics may suggest a specific risk and mechanism of failure, aiding in the long-term management of shunted hydrocephalus.

Recurrent disc herniation and long-term back pain after primary lumbar discectomy: review of outcomes reported for limited versus aggressive disc removal.

OBJECTIVEIt remains unknown whether aggressive disc removal with curettage or limited removal of disc fragment alone with little disc invasion provides a better outcome for the treatment of lumbar disc herniation with radiculopathy. We reviewed the literature to determine whether outcomes reported after limited discectomy (LD) differed from those reported after aggressive discectomy (AD) with regard to long-term back pain or recurrent disc herniation. METHODSA systematic MEDLINE search was performed to identify all studies published between 1980 and 2007 reporting outcomes after AD or LD for a herniated lumbar disc with radiculopathy. The incidence of short- and long-term recurrent back or leg pain and recurrent disc herniation was assessed from each reported LD or AD cohort and the cumulative incidence compared. RESULTSFifty-four studies (60 discectomy cohorts) met the inclusion criteria, reporting the outcomes of 13 359 patients after lumbar discectomy (LD, 6135 patients; AD, 7224 patients). The reported incidence of short-term recurrent back or leg pain was similar after LD (mean, 14.5%; range, 7–16%) and AD (mean, 14.1%; range, 6–43%) (P < 0.01). However, more than 2 years after surgery, the reported incidence of recurrent back or leg pain was 2.5-fold less after LD (mean, 11.6%; range, 7–16%) compared with AD (mean, 27.8%; range, 19–37%) (P < 0.0001). The reported incidence of recurrent disc herniation after LD (mean, 7%; range, 2–18%) was greater than that reported after AD (mean, 3.5%; range, 0–9.5%) (P < 0.0001). CONCLUSIONReview of the literature demonstrates a greater reported incidence of long-term recurrent back and leg pain after AD but a greater reported incidence of recurrent disc herniation after LD. Prospective, randomized trials are needed to firmly assess this possible difference.

Correlation of serum brain natriuretic peptide with hyponatremia and delayed ischemic neurological deficits after subarachnoid hemorrhage.

OBJECTIVE:Serum brain natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wasting), and may exacerbate delayed ischemic neurological deficits. We examined the temporal relationship between serum BNP elevation, hyponatremia, and the onset of delayed ischemic neurological deficits and determined whether serum BNP levels correlated with the 2-week outcome after SAH. METHODS:Serum BNP and sodium were measured prospectively every 12 hours for 14 days in 40 consecutive patients admitted with SAH. All patients remained euvolemic, underwent transcranial Doppler assessment every 48 hours, and underwent angiography at the onset of delayed neurological deficits. New-onset neurological deficits were attributed to vasospasm only in the absence of other causes and when supported by transcranial Doppler or cerebral angiography. RESULTS:Sixteen patients (40%) experienced symptomatic cerebral vasospasm after SAH. A more than threefold increase in admission serum BNP was associated with the onset of hyponatremia (P <0.05). Mean BNP levels were similar between vasospasm and nonvasospasm patients fewer than 3 days after SAH (126 ± 39 pg/ml versus 154 ± 40 pg/ml; P = 0.61) but were elevated in the vasospasm cohort 4 to 6 days after SAH (285 ± 67 pg/ml versus 116 ± 30 pg/ml; P < 0.01), 7 to 9 days after SAH (278 ± 72 pg/ml versus 166 ± 45 pg/ml; P < 0.01), and 9 to 12 days after SAH (297 ± 83 pg/ml versus 106 ± 30 pg/ml; P < 0.01). BNP level remained independently associated with vasospasm adjusting for Fisher grade and Hunt and Hess grade (odds ratio, 1.28; 95% confidence interval, 1.1–1.6). In patients in whom vasospasm developed, mean serum BNP increased 5.4-fold within 24 hours after vasospasm onset and 11.2-fold the first 3 days after vasospasm onset. Patients with increasing BNP levels from admission demonstrated no change (0 ± 3) in Glasgow Coma Scale score 2 weeks after SAH versus a 3.0 ± 2 (P < 0.05) improvement in Glasgow Coma Scale score in patients without increasing serum BNP levels. CONCLUSION:Increasing serum BNP levels independently were associated with hyponatremia, significantly increased the first 24 hours after onset of delayed ischemic neurological deficits, and predicted the 2-week Glasgow Coma Scale score.