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ABSTRACT: With recent advances in the adjuvant treatment of malignant brain astrocytomas, it is increasingly debated whether extent of resection affects survival. In this study, the authors investigate this issue after primary and revision resection of these lesions.
The authors retrospectively reviewed the cases of 1215 patients who underwent surgery for malignant brain astrocytomas (World Health Organization [WHO] Grade III or IV) at a single institution from 1996 to 2006. Patients with deep-seated or unresectable lesions were excluded. Based on MR imaging results obtained < 48 hours after surgery, gross-total resection (GTR) was defined as no residual enhancement, near-total resection (NTR) as having thin rim enhancement of the resection cavity only, and subtotal resection (STR) as having residual nodular enhancement. The independent association of extent of resection and subsequent survival was assessed via a multivariate proportional hazards regression analysis.
Magnetic resonance imaging studies were available for review in 949 cases. The mean age and mean Karnofsky Performance Scale (KPS) score at time of surgery were 51 +/- 16 years and 80 +/- 10, respectively. Surgery consisted of primary resection in 549 patients (58%) and revision resection for tumor recurrence in 400 patients (42%). The lesion was WHO Grade IV in 700 patients (74%) and Grade III in 249 (26%); there were 167 astrocytomas and 82 mixed oligoastrocytoma. Among patients who underwent resection, GTR, NTR, and STR were achieved in 330 (35%), 388 (41%), and 231 cases (24%), respectively. Adjusting for factors associated with survival (for example, age, KPS score, Gliadel and/or temozolomide use, and subsequent resection), GTR versus NTR (p < 0.05) and NTR versus STR (p < 0.05) were independently associated with improved survival after both primary and revision resection of glioblastoma multiforme (GBM). For primary GBM resection, the median survival after GTR, NTR, and STR was 13, 11, and 8 months, respectively. After revision resection, the median survival after GTR, NTR, and STR was 11, 9, and 5 months, respectively. Adjusting for factors associated with survival for WHO Grade III astrocytoma (age, KPS score, and revision resection), GTR versus STR (p < 0.05) was associated with improved survival. Gross-total resection versus NTR was not associated with an independent survival benefit in patients with WHO Grade III astrocytomas. The median survival after primary resection of WHO Grade III (mixed oligoastrocytomas excluded) for GTR, NTR, and STR was 58, 46, and 34 months, respectively.
In the authors' experience with both primary and secondary resection of malignant brain astrocytomas, increasing extent of resection was associated with improved survival independent of age, degree of disability, WHO grade, or subsequent treatment modalities used. The maximum extent of resection should be safely attempted while minimizing the risk of surgically induced neurological injury.
Journal of Neurosurgery 10/2008; 110(1):156-62. · 2.96 Impact Factor
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ABSTRACT: Clinical depression has been shown to negatively influence the morbidity and mortality of multiple disease states. It remains unclear if clinical depression affects survival after surgical management of malignant brain astrocytoma. We set out to determine whether patients with a diagnosis of clinical depression before surgery experienced decreased survival independent of treatment modality or degree of disability.
One thousand fifty-two patients undergoing surgical management for malignant brain astrocytoma (WHO grade 3 or 4) performed at a single institution from 1995 to 2006 were retrospectively reviewed. The independent association of depression prior to surgery and subsequent survival was assessed via multivariate proportional hazards regression analysis.
Surgical management consisted of primary resection in 605 (58%) patients, secondary resection in 410 (39%), and biopsy in 37 patients (3.5%). Pathology was WHO grade IV in 829 (79%) and grade III in 223 (21%). Forty-nine patients (5%) carried the diagnosis of depression at the time of surgery. Mean age and KPS on admission was 51 +/- 16 and 80 +/- 10 years, respectively. Two hundred ninety patients (28%) received Gliadel (BCNU MGI Pharma, Inc., Bloomington, MN, USA) wafer implantation and 274 (26%) received postoperative temozolomide (concomitant in 102, delayed adjuvant in 172 patients). Subsequent resection was performed at the time of recurrence in 135 (13%) patients a mean of 10 +/- 6 months after surgery. Adjusting for all variables associated with survival in this model, age (P < .001), KPS (P < .001), WHO grade III vs IV (P < .001), primary versus secondary resection (P < .001), gross-total resection (P < .001), Gliadel wafer implantation (P = .048), postoperative temozolomide therapy (P < .001), and subsequent resection at time of recurrence (P < .001); preoperative depression was independently associated with decreased survival (relative risk [95% CI]: 1.41 [1.1-1.96], P < .05). The difference in percent survival between the depression and nondepression cohorts was most notable at 12 months (15% vs 41%) and 20 months (0% vs 21%) after surgery.
In our experience, patients who are actively depressed at the time of surgery were associated with decreased survival after surgical management of malignant astrocytoma, independent of degree of disability, tumor grade, or subsequent treatment modalities. In our opinion, the presence of an association between preoperative depression and survival warrants further investigation.
Surgical Neurology 10/2008; 71(3):299-303, discussion 303. · 1.67 Impact Factor
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ABSTRACT: Patients with malignant brain astrocytomas are at high risk for developing hyperglycemia secondary to frequent corticosteroid administration. Several clinical studies have shown that hyperglycemia is associated with poor outcome in multiple disease states. Furthermore, hyperglycemia augments in vitro astrocytoma growth, whereas hypoglycemia attenuates in vitro astrocytoma cell growth. We hypothesized that persistent hyperglycemic states in the outpatient setting may serve as a prognostic marker of decreased survival in patients with malignant brain astrocytomas.
We retrospectively reviewed 367 cases of craniotomy for malignant brain astrocytomas (World Health Organization Grade III or IV). Persistent hyperglycemia was defined as serum glucose greater than 180 mg/dL occurring three or more times between 1 and 3 months postoperatively. Isolated hyperglycemia was defined as an isolated occurrence of serum glucose greater than 180 mg/dL. The independent association of outpatient glucose levels and recorded clinical and treatment variables with overall survival was assessed via multivariate proportional-hazards regression analysis.
A total of 367 craniotomies (209 primary, 158 secondary) were performed for malignant brain astrocytomas (glioblastoma multiforme, 297; anaplastic astrocytomas, 70); 68 (19%) and 28 (8%) of the patients experienced isolated or persistent outpatient hyperglycemia, respectively. Patients experiencing persistent hyperglycemia were older (59 +/- 13 versus 51 +/- 14 yr), were diabetic more frequently (7 [25%] versus 10 [3%]), continued to receive corticosteroids more frequently (21 [75%] versus 35 [10%]); and received temozolomide less often (4 [14%] versus 116 [34%]). Adjusting for intergroup differences and variables associated with survival in this model, age (P = 0.001), Karnofsky Performance Scale score (P = 0.001), tumor grade (P = 0.001), primary versus secondary resection (P = 0.008), temozolomide (P = 0.007), subsequent resection (P = 0.07), and continued outpatient dexamethasone therapy, persistent outpatient hyperglycemia (relative risk, 1.79; 95% confidence interval, 1.05-3.05, P = 0.03) remained independently associated with decreased survival. Median survival for persistently hyperglycemic versus normal-glycemic cohorts was 5 and 11 months, respectively.
In our experience, persistent outpatient hyperglycemia was associated with decreased survival in patients undergoing surgical resection for malignant astro- cytomas and was independent of the degree of disability, tumor grade, diabetes, prolonged dexamethasone use, or subsequent treatment modalities. Increased glucose control is warranted in this patient population and may contribute to improved outcomes in the treatment of malignant brain astrocytomas.
Neurosurgery 09/2008; 63(2):286-91; discussion 291. · 2.79 Impact Factor
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ABSTRACT: Indications for duraplasty in treatment of Chiari malformation Type I (CM-I) remain unclear. In the present study, the authors evaluate their surgical experience to determine whether intraoperative ultrasonography is effective in the selection of patients with CM-I who can be adequately treated with craniectomy alone without duraplasty.
The authors reviewed the records of 256 children who underwent first-time hindbrain decompression for CM-I. Craniectomy alone (without duraplasty) was performed when intraoperative ultrasonography suggested adequate decompression of the subarachnoid spaces ventral and dorsal to the tonsils after suboccipital craniectomy alone. Duraplasty was performed if intraoperative ultrasonography demonstrated persistent dural compression of the tonsils following craniectomy. Symptom recurrence as a function of time was compared between cases of duraplasty versus suboccipital decompression alone stratified by extent of tonsillar herniation.
Duraplasty was performed in 140 patients (55%), and suboccipital decompression alone was performed in 116 patients (45%). Patients underwent follow-up for 29 +/- 15 months. Symptoms included headache in 192 patients (75%) and lower cranial nerve and brainstem dysfunction in 68 (27%). In 38 patients (15%) there was tonsillar herniation rostral to the C-1 lamina, in 195 (76%) it extended between the C-1 and C-2 lamina, and in 23 patients (9%) there was herniation caudal to the lower border of the C-2 lamina. In children with tonsillar herniation caudal to C-1, ultrasonography-guided suboccipital decompression alone was associated with a 2-fold increase in the risk of symptom recurrence compared with those who also underwent duraplasty (p = 0.01). In children with tonsillar herniation rostral to C-1, outcome was equivalent between suboccipital decompression alone and duraplasty (p = 0.41).
In the setting of moderate-to-severe tonsillar CM-I, intraoperative ultrasonography demonstrating decompression of the subarachnoid spaces ventral and dorsal to the tonsils may not effectively select patients in whom bone decompression alone is sufficient. Duraplasty may be warranted in cases of tonsillar herniation that extends below the C-1 lamina regardless of intraoperative ultrasonography findings. More objective cerebrospinal fluid flow or volumetric measures may be needed intraoperatively to guide duraplasty in patients with more pronounced tonsillar herniation.
Journal of Neurosurgery Pediatrics 08/2008; 2(1):52-7. · 1.53 Impact Factor
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ABSTRACT: Many patients with symptomatic Chiari I malformation experience symptom recurrence after surgical decompression. Improved radiographic predictors of outcome are needed to better select patients most likely to benefit from surgical intervention. We examined whether ventral or dorsal cerebrospinal fluid (CSF) flow dynamics assessed by cine phase-contrast MRI scans could predict response to posterior fossa decompression for Chiari I malformation.
Forty-four consecutive pediatric patients undergoing pre-operative cine phase-contrast MRI followed by posterior fossa decompression for Chiari I malformation were retrospectively reviewed. The association of pre-operative ventral or dorsal CSF flow abnormalities at the foramen magnum with symptom-free survival after surgical decompression was assessed via Kaplan-Meier plots and log-rank analysis.
Mean +/- SD age at time of surgery was 8 +/- 6 years. Sixteen (36%) patients demonstrated decreased CSF flow dorsal to the cervico-medullary brainstem alone. Fourteen (32%) patients demonstrated abnormal CSF flow both ventral and dorsal to the cervico-medullary brainstem. Fourteen (32%) had normal hindbrain CSF flow. Overall, 13 (30%) patients experienced some degree of symptom recurrence by last follow-up (mean of 27 +/- 16 months post-operatively). Symptom recurrence did not differ as a function of degree of tonsilar ectopia (p = 0.55). Abnormal CSF flow dorsal to the cervico-medullary brainstem was not associated with symptom recurrence after surgical decompression (p = 0.10). However, combined pre-operative ventral and dorsal CSF flow abnormality was associated with a significant reduction (2.6-fold) in the risk of post-operative symptom recurrence (p < 0.05). Only one patient (7%) with pre-operative ventral and dorsal CSF flow pathology experienced symptom recurrence 3.5 years after surgery versus 12 (40%) patients without ventral CSF flow pathology. There were otherwise no differences in baseline clinical, radiological, or operative variables between patients with abnormal versus normal ventral CSF flow.
The presence of decreased CSF flow both ventral and dorsal to the cervico-medullary brainstem was associated with improved response to hindbrain decompression for Chiari I malformation in children. Cine phase-contrast MRI may be a useful tool for surgical risk stratification and identifying patients that may be optimal surgical candidates. Combined ventral and dorsal hindbrain CSF flow pathology may better predict response to posterior fossa decompression compared to dorsal CSF flow pathology alone.
Child s Nervous System 08/2008; 24(7):833-40. · 1.54 Impact Factor
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ABSTRACT: Chiari I malformation is complicated by syringomyelia in many cases. Hindbrain decompression remains first-line surgical treatment; however, the incidence, time course, and predictors of syrinx resolution remain unclear. We set out to determine predictors of syrinx improvement after hindbrain decompression for Chiari I- associated syringomyelia.
Forty-nine consecutive pediatric patients undergoing posterior fossa decompression for Chiari I-associated syringomyelia were followed with serial magnetic resonance imaging evaluations postoperatively. Clinical, radiological, and operative variables were assessed as predictors of syrinx improvement as a function of time using Kaplan-Meier plots and log-rank analysis.
Mean patient age was 11 +/- 5 years. Syringomyelia was symptomatic in 39 (80%) and asymptomatic in 10 (20%) cases. Twenty-one (54%) patients experienced symptom resolution (median, 4 mo postoperatively). Twenty-seven (55%) patients experienced radiographic improvement in syringomyelia (median, 14 mo postoperatively). After hindbrain decompression, motor symptoms were associated with a 2.35 increased hazard ratio for symptom improvement (P = 0.031) versus all other symptoms. Among patients with sensory deficits, dysesthesia was associated with a 3.12 increased hazard ratio for symptom improvement (P = 0.032) versus symptoms of paresthesia or anesthesia.
In our experience, just more than one-half of patients with Chiari- associated syringomyelia demonstrated clinical and radiographic improvement after hindbrain decompression. Median time to radiographic improvement lagged behind clinical improvement by 10 months. Motor symptoms were more likely to improve with hindbrain decompression. Paresthesia or anesthesia symptoms were less likely to improve with hindbrain decompression. These findings may help guide surgical decision making and aid in patient education.
Neurosurgery 07/2008; 62(6):1307-13; discussion 1313. · 2.79 Impact Factor
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ABSTRACT: Chiari malformation Type I (CM-I) is often associated with scoliosis. It remains unclear which subgroups of patients are most likely to experience progression of spinal deformity after cervicomedullary decompression. The authors' goal was to determine the time frame of curvature progression and assess which patient subgroups are at greatest risk for progression of spinal deformity after surgery.
The authors retrospectively reviewed the records of all pediatric patients with significant scoliosis in whom suboccipital decompression was performed to treat for CM-I during a 10-year period at a single academic institution. Clinical, radiological, and operative variables were assessed as independent factors for failure (worsening of scoliosis) by using a univariate regression analysis.
Twenty-one children (mean age 9 +/- 3 years; 4 male) underwent hindbrain decompression for CM-I-associated scoliosis and were followed for a mean of 39 months. All patients harbored a syrinx. Eight patients (38%) experienced improvement in scoliosis curvature, whereas 10 (48%) suffered a progression. Thoracolumbar junction scoliosis (p = 0.04) and failure of the syrinx to improve (p = 0.05) were associated with 5- and 4-fold respective increases in the likelihood of deformity progression. Each increasing degree of preoperative Cobb angle was associated with an 11% increase in the likelihood of scoliotic curve progression (p < 0.05).
Over one third of patients with CM-I-associated scoliosis will improve after cervicomedullary decompression alone. Cervicomedullary decompression is a good first-line option, particularly in children with concordant posterior fossa symptoms. Patients presenting with more severe scoliosis (increasing Cobb angle) or scoliosis that crosses the thoracolumbar junction may benefit from earlier orthopedic involvement and should be monitored regularly for curvature progression after cervicomedullary decompression. In cases in which there is a failure of the syrinx to show improvement after suboccipital decompression, the patients are also more likely to develop curvature progression.
Journal of Neurosurgery Pediatrics 06/2008; 1(6):456-60. · 1.53 Impact Factor
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ABSTRACT: In 1987, Miyajima et al. first characterized an autosomal recessive, adult-onset neurodegenerative disorder resembling Parkinson's disease associated with near-absent circulating serum ceruloplasmin levels. Coined "familial apoceruloplasmin deficiency", they described a patient with a presenting triad of diabetes mellitus, retinal degeneration, and neurodegeneration with blepharospasm. Neuropathological evaluation revealed abundant iron deposition in selected neurons of the basal ganglia and substantia nigra with associated neuronal dropout and spongioform degeneration without evidence of reactive gliosis. Subsequently, mutations in the ceruloplasmin gene have been determined to result in the excessive iron accumulation seen in the pancreas, retina, and brain. Elevated serum ferritin suggests a systemic iron overload syndrome, yet affected patients had low transferrin saturation and a mild anemia. This new disease, "aceruloplasminemia", reveals a role for ceruloplasmin as an essential ferroxidase critical for iron homeostasis. This multicopper oxidase promotes efficient iron efflux such that individuals lacking ceruloplasmin develop a presumed oxidative injury secondary to iron accumulation and significant neuronal damage. Aceruloplasminemic mice provide a valuable model to further study the mechanisms by which ceruloplasmin regulates iron trafficking and the role of iron in oxidative injury. Despite the dependence of ceruloplasmin on copper for its function, aceruloplasminemia represents an iron storage disease and not a defect in copper metabolism. However, recent evidence in Saccharomyces cerevisiae indicates that Fet3, the yeast homologue of ceruloplasmin, functions as an essential cuprous oxidase. Further investigation into the mechanisms by which ceruloplasmin regulates iron and copper homeostasis will provide valuable insight into the pathogenesis of metallo-mediated diseases and elucidate mechanisms for transition metal (copper, iron) neuropathology.
Annals of the New York Academy of Sciences 04/2004; 1012:299-305. · 3.15 Impact Factor
