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Raheel Ahmed, Arnold H. Menezes and James C. Torner

OBJECTIVE

Surgical excision is the mainstay treatment for resectable low-grade intramedullary spinal cord tumors (IMSCTs) in the pediatric age group. Chemotherapy and radiation treatments are generally reserved for progressive or recurrent disease. Given the indolent nature of low-grade tumors and the potential side effects of these approaches, their long-term treatment benefits are unclear. The aim of the study was to determine long-term disease outcomes and the therapeutic roles of surgery and adjuvant therapies in pediatric patients with low-grade IMSCTs over an extended follow-up period.

METHODS

Case records for all pediatric patients (< 21 years of age) with a histopathological diagnosis of low-grade IMSCT were selected over a period from January 1975 to January 2010. Outcome variables including McCormick functional grade, overall survival (OS), and progression-free survival (PFS) were analyzed with respect to demographic and treatment variables.

RESULTS

Case records of 37 patients with low-grade IMSCTs were identified, with a mean follow-up duration of 12.3 ± 1.4 years (range 0.5–37.2 years). Low-grade astrocytomas were the most prevalent histological subtype (n = 22, 59%). Gross-total resection (GTR) was achieved in 38% of patients (n = 14). Fusion surgery was required in 62% of patients with pre- or postoperative deformity (10 of 16). On presentation, functional improvement was observed in 87% and 46% of patients in McCormick Grades I and II, respectively, and in 100%, 100%, and 75% in Grades III, IV, and V, respectively. Kaplan-Meier PFS rates were 63% at 5 years, 57% at 10 years, and 44% at 20 years. OS rates were 92% at 5 years, 80% at 10 years, and 65% at 20 years. On multivariate analysis, shunt placement (hazard ratio [HR] 0.33, p = 0.01) correlated with disease progression. There was a trend toward improved 5-year PFS in patients who received adjuvant chemotherapy and radiation therapy (RT; 55%) compared with those who did not (36%). Patients who underwent subtotal resection (STR) were most likely to undergo adjuvant therapy (HR 7.86, p = 0.02).

CONCLUSIONS

This extended follow-up duration in patients with low-grade IMSCTs beyond the first decade indicates favorable long-term OS up to 65% at 20 years. GTR improved PFS and was well tolerated with sustained functional improvement in the majority of patients. Adjuvant chemotherapy and RT improved PFS in patients who underwent STR. These results emphasize the role of resection as the primary treatment approach, with adjuvant therapy reserved for patients at risk for disease progression and those with residual tumor burden.

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Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage

Preliminary observations from the Cooperative Aneurysm Study

Neal F. Kassell, James C. Torner and Harold P. Adams Jr.

✓ Antifibrinolytic therapy remains a controversial issue in the management of subarachnoid hemorrhage (SAH). The relationship of antifibrinolytic therapy with mortality, rebleeding, ischemia, hydrocephalus, and clotting abnormalities was studied in 672 patients in the International Cooperative Study on the Timing of Aneurysm Surgery. The patients with antifibrinolytic therapy had a significantly lower rebleeding rate, but higher rates of ischemic deficits and hydrocephalus. The net result was no difference in mortality in the 1st month following the initial SAH. Further clinical trials are needed to determine the overall effects of antifibrinolytic therapy.

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Kelly B. Mahaney, Michael M. Todd and James C. Torner

Object

The past 30 years have seen a shift in the timing of surgery for aneurysmal subarachnoid hemorrhage (SAH). Earlier practices of delayed surgery that were intended to avoid less favorable surgical conditions have been replaced by a trend toward early surgery to minimize the risks associated with rebleeding and vasospasm. Yet, a consensus as to the optimal timing of surgery has not been reached. The authors hypothesized that earlier surgery, performed using contemporary neurosurgical and neuroanesthesia techniques, would be associated with better outcomes when using contemporary management practices, and sought to define the optimal time interval between SAH and surgery.

Methods

Data collected as part of the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) were analyzed to investigate the relationship between timing of surgery and outcome at 3 months post-SAH. The IHAST enrolled 1001 patients in 30 neurosurgical centers between February 2000 and April 2003. All patients had a radiographically confirmed SAH, were World Federation of Neurosurgical Societies Grades I–III at the time of surgery, and underwent surgical clipping of the presumed culprit aneurysm within 14 days of the date of hemorrhage. Patients were seen at 90-day follow-up visits. The primary outcome variable was a Glasgow Outcome Scale score of 1 (good outcome). Intergroup differences in baseline, intraoperative, and postoperative variables were compared using the Fisher exact tests. Variables reported as means were compared with ANOVA. Multiple logistic regression was used for multivariate analysis, adjusting for covariates. A p value of less than 0.05 was considered to be significant.

Results

Patients who underwent surgery on Days 1 or 2 (early) or Days 7–14 (late) (Day 0 = date of SAH) fared better than patients who underwent surgery on Days 3–6 (intermediate). Specifically, the worst outcomes were observed in patients who underwent surgery on Days 3 and 4. Patients who had hydrocephalus or Fisher Grade 3 or 4 on admission head CT scans had better outcomes with early surgery than with intermediate or late surgery.

Conclusions

Early surgery, in good-grade patients within 48 hours of SAH, is associated with better outcomes than surgery performed in the 3- to 6-day posthemorrhage interval. Surgical treatment for aneurysmal SAH may be more hazardous during the 3- to 6-day interval, but this should be weighed against the risk of rebleeding.

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Carl J. Graf, George E. Perret and James C. Torner

✓ The case records of 191 patients with a cerebral arteriovenous malformation (AVM) were reviewed to determine bleeding characteristics of these lesions. Possible influences of age, sex, the location and size of the AVM, type of initial hemorrhage, and condition of the patients were analyzed. Of these 191 patients, 102 had a single hemorrhage, 32 had a recurrent hemorrhage, and 57 never bled. The follow-up period for patients with an unruptured AVM was a mean of 4.8 years and a maximum of 31 years; for those with a ruptured AVM, the mean was 2 years, and the maximum 37 years.

Size of the AVM was significantly related to the risk of first hemorrhage. The average yearly risk for first hemorrhage was between 2% and 3%. Bleeding occurred most frequently in the 11- to 35-year-old age group. The risk of rebleeding increased with advancing age. Among 93 patients followed after their AVM had ruptured, the risk of rebleeding was 6% in 1 year. After the first year, the average rebleeding rate was about 2% per year up to 20 years.

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Raheel Ahmed, Arnold H. Menezes, Olatilewa O. Awe and James C. Torner

Object

Radical resection is recommended as the first-line treatment for pediatric intramedullary spinal cord tumors (IMSCTs), but it is associated with morbidity, including risk of neurological decline and development of postoperative spinal deformity. The authors report long-term data on clinical and treatment determinants affecting disease survival and neurological outcomes.

Methods

Case records for pediatric patients (< 21 years of age at presentation) who underwent surgery for IMSCTs at the authors' institution between January 1975 and January 2010 were analyzed. The patients' demographic and clinical characteristics (including baseline neurological condition), the treatment they received, and their disease course were reviewed. Long-term disease survival and functional outcome measures were analyzed.

Results

A total of 55 patients (30 male and 25 female) were identified. The mean duration of follow-up (± SEM) was 11.4 ± 1.3 years (median 9.3 years, range 0.2–37.2 years). Astrocytomas were the most common tumor subtype (29 tumors [53%]). Gross-total resection (GTR) was achieved in 21 (38%) of the 55 patients. At the most recent follow-up, 30 patients (55%) showed neurological improvement, 17 (31%) showed neurological decline, and 8 (15%) remained neurologically stable. Patients presenting with McCormick Grade I were more likely to show functional improvement by final follow-up (p = 0.01) than patients who presented with Grades II–V. Kaplan-Meier actuarial tumor progression-free survival rates at 5, 10, and 20 years were 61%, 54%, and 44%, respectively; the overall survival rates were 85% at 5 years, 74% at 10 years, and 64% at 20 years. On multivariate analysis, GTR (p = 0.04) and tumor histological grade (p = 0.02) were predictive of long-term survival; GTR was also associated with improved 5-year progression-free survival (p = 0.01).

Conclusions

The prognosis for pediatric IMSCTs is favorable with sustained functional improvement expected in a significant proportion of patients on long-term follow-up. Long-term survival at 10 years (75%) and 20 years (64%) is associated with aggressive resection. Gross-total resection was also associated with improved 5-year progression-free survival (86%). Hence, the treatment benefits of GTR are sustained on extended follow-up.

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E. Clarke Haley Jr., Neal F. Kassell, James C. Torner and Participants

✓ Because of their action as cerebral vasodilators, dihydropyridine calcium antagonists have received intense scrutiny for their potential benefit in ameliorating the devastating consequences of delayed cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). From October, 1987, to September, 1989, 41 North American neurosurgical centers in the Cooperative Aneurysm Study accrued 906 patients with recent (Days 0 to 7) aneurysmal SAH into a prospective randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine to test whether treatment with this agent improved overall outcome. Eligible patients received 0.15 mg/kg/hr of either nicardipine or placebo by continuous infusion for up to 14 days following hemorrhage. The 449 patients randomly assigned to the nicardipine-treated group and the 457 patients assigned to the placebo-treated group were balanced with regard to prognostic factors for ischemic deficits from vasospasm and for overall outcome. Other medical and surgical interventions were used with similar frequency in both groups, except that antihypertensive agents were used less frequently in the nicardipine-treated patients (26% of the nicardipine-treated group vs. 43% of the placebo-treated group, p < 0.001), and more patients in the placebo-treated group had intentional hypervolemia, induced hypertension, and/or hemodilution administered therapeutically for symptomatic vasospasm (38% of the placebo-treated group vs. 25% of the nicardipine-treated group, p < 0.001). The incidence of symptomatic vasospasm during the treatment period was higher in the placebo-treated group (46%) than in the nicardipine-treated group (32%) (p < 0.001). Despite the reduction in symptomatic vasospasm in the nicardipine-treated group, overall outcome at 3 months was similar between the two groups. Fifty-five percent of nicardipine-treated patients were rated as having a good recovery according to the Glasgow Outcome Scale at follow-up review and 17% were dead, compared to 56% and 18%, respectively, in the placebo-treated group (not statistically significant).

These data suggest that high-dose intravenous nicardipine treatment is associated with a reduced incidence of symptomatic vasospasm in patients with recent aneurysmal SAH, but not with an improvement in overall outcome at 3 months when compared to standard management in North America. It is postulated that, while nicardipine prevents vasospasm, hypertensive/hypervolemic therapy may be effective in reversing ischemic deficits from vasospasm once they occur.

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John A. Jane, Neal F. Kassell, James C. Torner and H. Richard Winn

✓ The authors summarize the findings of previous studies relating to the natural history of aneurysms and arteriovenous malformations (AVM's). Ruptured aneurysms have their highest rate of rebleeding on Day 1, and at least 50% will rebleed during the 6 months after the first hemorrhage. Thereafter, the rate drops to at least 3% a year. This is the same rate as seen in anterior and posterior communicating artery aneurysms treated by anterior cerebral artery clipping and carotid ligation; these operations provide immediate protection but do not result in long-term diminution of the risk of rebleeding. Patients with unruptured incidental and unruptured multiple aneurysms rebleed at a rate of 1% per year, as do patients with subarachnoid hemorrhage of unknown etiology. The risk of rebleeding for AVM's is 3% a year.

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Patrick W. Hitchon, Jeffrey M. Lobosky, Thoru Yamada and James C. Torner

✓ Spinal cord blood flow (SCBF) in 10 sheep subjected to laminectomy at L6–7, T6–7, and C7–T1 was compared to that of 10 control sheep subjected to anesthesia alone. Blood flow was measured using the radioactive microsphere technique, with the PaCO2 maintained at 40 ± 2 mm Hg. Both laminectomy and control animals showed a decrease in SCBF at a rate of 7% to 16%/hr for the 3 hours following the first blood flow determination. When prelaminectomy and postlaminectomy SCBF values were compared to their counterparts in the control animals, there were no significant differences. Laminectomy does not appear to alter SCBF from control values. Spinal evoked potentials (SEP's) were elicited in the laminectomy group by direct cord stimulation at C-7 and L-7. No changes were noted in amplitude or latency of SEP's over time in either caudal or rostral conduction.

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Aditya V. Ingalhalikar, Chandan G. Reddy, Tae Hong Lim, James C. Torner and Patrick W. Hitchon

Object

The artificial disc has been proposed as an alternative to spinal fusion for degenerative disc disease. The primary aim of this biomechanical study was to compare motion and intradiscal pressure (IDP) in a ball-and-socket artificial disc–implanted cadaveric lumbar spine, at the operative and adjacent levels, using a displacement-controlled setup. A secondary comparison involved a “salvage” construct, consisting of pedicle screws (PSs) added in supplementation to the artificial disc construct.

Methods

Ten human cadaveric lumbosacral spines (L2–S1) were potted at L-2 and S-1. All measurements were initially made in the intact spine, followed by implantation of the artificial disc, and finally by the salvage PS condition. For the artificial disc condition, a Maverick ball-and-socket artificial disc was implanted at L4–5. For the PS condition, CD Horizon PSs were placed at L4–5, and the artificial disc was left in place. A displacement-controlled, custom-designed testing apparatus was used to impart motion in the sagittal and coronal planes. Motion at both the implanted level (L4–5) and immediately adjacent levels (L3–4 and L5–S1) was measured. Intradiscal pressure at the rostral adjacent level (L3–4) was also measured. The Tukey test was used for statistical analysis (p < 0.05).

Results

In flexion, no significant difference was noted between the artificial disc and the intact spine with regard to motion at the operative level, motion at adjacent levels, or IDP. In lateral bending, while the artificial disc significantly decreased operative-level motion (p < 0.05), no significant difference was noted in adjacent-level motion or IDP. With regard to extension, the artificial disc significantly increased operative level motion and decreased the rostral adjacent level (L3–4) motion and IDP (p < 0.05). Caudal adjacent-level (L5–S1) motion was not significantly different.

In flexion and lateral bending, the addition of PSs significantly decreased motion at the implanted level when compared with the intact spine and the artificial disc (p < 0.05). This decrease in motion at the index level was associated with a compensatory increase in motion at both adjacent levels in flexion only (p < 0.05), but not in lateral bending (p > 0.05). The IDP was significantly increased in lateral bending but not in flexion. With regard to extension, the significant decrease in IDP that was noted with the artificial disc persisted despite the addition of PSs (p < 0.05).

Conclusions

The artificial disc either maintains or reduces adjacent-level motion and pressure, compared with the intact spine. The addition of PSs to the artificial disc construct leads to significantly increased motion at adjacent levels in flexion and significantly increased IDP in lateral bending. At the operative level, the artificial disc is associated with hypermobility in extension, which is restored to the intact state after the addition of supplementary PSs.

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Brian J. Dlouhy, Ana W. Capuano, Karthik Madhavan, James C. Torner and Jeremy D. W. Greenlee

Object

Patients with hydrocephalus often present with both intraventricular obstructive and communicating components, and determination of the predominant component is difficult. Other investigators have observed that third ventricular floor deformation, or “bowing” of the third ventricular floor, is a good indicator of intraventricular obstructive hydrocephalus, resulting in higher success rates with endoscopic third ventriculostomy (ETV). However, additional third ventricular bowing assessment and statistical evidence demonstrating a difference in ETV outcome with third ventricular bowing is needed. The authors hypothesized that patients with preoperative bowing of the third ventricle would exhibit greater long-term success rates after ETV and that lack of bowing would result in increased failure rates after ETV.

Methods

The authors determined success and failure for 59 ETVs performed in 56 patients, and recorded patient age, time to failure, and preoperative third ventricular anatomy, as well as history of infection, intraventricular hemorrhage, and previous shunt. Third ventricular anatomy was assessed on MR imaging for bowing, which was classified as any of the following: depression of the third ventricular floor, enlargement of the supraoptic recess, anterior curvature of the lamina terminalis, dilation of the proximal aqueduct to a greater extent than the distal aqueduct, and blunting or posterior bowing of the suprapineal recess. Univariate and multivariate analyses of ETV failure and the time to failure were performed using logistic regression and the Cox proportional hazards model, respectively.

Results

After adjusting for patient age and history of infection, there was a significant association between lack of anterior third ventricular preoperative bowing (either lamina terminalis, supraoptic recess, or third ventricular floor) and ETV failure (adjusted HR 2.79, 95% CI 1.08–7.20). Of the patients with bowing, 70.5% experienced success with ETV, as did 33.3% of the patients without bowing. Among the individual structures, absence of bowing in the anterior aspect of the third ventricular floor was significantly associated with censored time to ETV failure (multivariate HR 2.59, 95% CI 1.01–6.66; final model including age and history of infection).

Conclusions

The presence of preoperative third ventricular bowing is predictive of ETV success, with nearly a 3-fold likelihood of success compared with patients treated with ETV in the absence of such bowing. Although bowing is predictive, 33% of patients without bowing were also treated successfully with ETV.