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  • Author or Editor: Nicholas M. Barbaro x
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Dario J. Englot, Mitchel S. Berger, Nicholas M. Barbaro and Edward F. Chang

Object

Seizures are the most frequent presenting symptom in patients with low-grade gliomas (LGGs), and significantly influence quality of life if they are uncontrolled. Achieving freedom from seizures is of utmost importance in surgical planning, but the factors associated with seizure control remain incompletely understood.

Methods

The authors performed a systematic literature review of seizure outcomes after resection of LGGs causing seizures, examining 773 patients across 20 published series. Rates of seizure freedom were stratified across 7 variables: patient age, tumor location, preoperative seizure control with medication, seizure semiology, epilepsy duration, extent of resection, and the use of intraoperative electrocorticography (ECoG).

Results

Gross-total resection was most predictive of complete seizure freedom, when compared with subtotal resection (OR 3.41, 95% CI 2.36–4.93). Other predictors of seizure freedom included preoperative seizure control on antiepileptic medication (OR 2.12, 95% CI 1.33–3.38) and duration of seizures of ≤ 1 year (OR 1.85, 95% CI 1.22–2.79). Patients with simple partial seizure semiology achieved seizure freedom less often than those with complex partial, generalized, or mixed seizure types (OR 0.46, 95% CI 0.26–0.80). No significant differences in seizure outcome were observed between adults versus children, patients with temporal lobe versus extratemporal tumors, or with the use of intraoperative ECoG.

Conclusions

Seizure control is one of the most important considerations in planning surgery for low-grade brain tumors. Gross-total resection is a critical factor in achieving seizure freedom.

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Tejas Sankar and Andres M. Lozano

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Edward F. Chang, Doris D. Wang, David W. Perry, Nicholas M. Barbaro and Mitchel S. Berger

Object

Language dominance in the right hemisphere is rare. Therefore, the organization of essential language sites in the dominant right hemisphere is unclear, especially compared with cases involving the more prevalent left dominant hemisphere.

Methods

The authors reviewed the medical records of 15 patients who underwent awake craniotomy for tumor or epilepsy surgery and speech mapping of right hemisphere perisylvian language areas at the University of California, San Francisco. All patients were determined to have either complete right-sided or bilateral language dominance by preoperative Wada testing.

Results

All patients but one were left-handed. Of more than 331 total stimulation sites, 27 total sites were identified as essential for language function (14 sites for speech arrest/anarthria; 12 for anomia; and 1 for alexia). While significant interindividual variability was observed, the general pattern of language organization was similar to classic descriptions of frontal language production and posterior temporal language integration for the left hemisphere. Speech arrest sites were clustered in the ventral precentral gyrus and pars opercularis. Anomia sites were more widely distributed, but were focused in the posterior superior and middle temporal gyri as well as the inferior parietal gyrus. One alexia site was found over the superior temporal gyrus. Face sensory and motor cortical sites were also identified along the ventral sensorimotor strip. The prevalence and specificity of essential language sites were greater in unilateral right hemisphere–dominant patients, compared with those with bilateral dominance by Wada testing.

Conclusions

The authors' results suggest that the organization of language in right hemisphere dominance mirrors that of left hemisphere dominance. Awake speech mapping is a safe and reliable surgical adjunct in these rare clinical cases and should be done in the setting of right hemisphere dominance to avoid preventable postoperative aphasia.

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Lilly Tang, Mary Mantle, Paul Ferrari, Hagen Schiffbauer, Howard A. Rowley, Nicholas M. Barbaro, Mitchel S. Berger and Timothy P. L. Roberts

Object. The aim of this study was to evaluate the spatial accuracy of interictal magnetoencephalography (MEG) in localizing the primary epileptogenic focus in comparison with alternative MEG-derived estimates such as ictal onset recording or sensory mapping of the periphery where seizures manifest.

Methods. During this retrospective study of 12 patients with epilepsy who had undergone successful magnetic source (MS) imaging with the aid of a dual 37-channel biomagnetometer as well as simultaneous MEG/electroencephalography (EEG) recordings, ictal events were observed in five patients and quantitative comparisons of interictal spike and ictal seizure onset source localizations were made. In the eight patients who had presented with sensorimotor seizure, source localization of cortical sites concordant with seizure foci was determined using somatosensory functional mapping, and the results were quantitatively compared with interictal spike source localizations.

Interictal spike sources demonstrated on MEG localized to the same region as the corresponding ictal event or somatosensory source localizations. The mean distance between the ictal foci and interictal spike sources was 1.1 ± 0.3 cm. Results of functional somatosensory mapping in patients with sensorimotor seizures demonstrated that seizure sources consistently colocalized with interictal MEG spike sources, with a mean distance of 1.5 ± 0.4 cm. No systematic directional bias was observed. Interictal sources tended to be tightly clustered, and the mean ellipsoid volume, defined by one standard deviation of the source spatial coordinates, was 1 cm3.

Conclusions. Interictal spike localizations on MEG were concordant with ictal and, where relevant, functional somatosensory mapping localizations. These findings support the interpretation of interictal spikes on MEG as a useful and effective noninvasive method for localizing primary seizure foci.

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Edward F. Chang, Matthew B. Potts, G. Evren Keles, Kathleen R. Lamborn, Susan M. Chang, Nicholas M. Barbaro and Mitchel S. Berger

Object

Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control.

Methods

The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003.

Results

Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with ≥ 1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p = 0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p = 0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p < 0.001) and simple partial seizures (p = 0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2–124, p = 0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p = 0.001).

Conclusions

The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, > 90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.

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Edward F. Chang, Justin S. Smith, Susan M. Chang, Kathleen R. Lamborn, Michael D. Prados, Nicholas Butowski, Nicholas M. Barbaro, Andrew T. Parsa, Mitchel S. Berger and Michael M. Mcdermott

Object

Hemispheric low-grade gliomas (LGGs) have an unpredictable progression and overall survival (OS) profile. As a result, the objective in the present study was to design a preoperative scoring system to prognosticate long-term outcomes in patients with LGGs.

Methods

The authors conducted a retrospective review with long-term follow-up of 281 adults harboring hemispheric LGGs (World Health Organization Grade II lesions). Clinical and radiographic data were collected and analyzed to identify preoperative predictors of OS, progression-free survival (PFS), and extent of resection (EOR). These variables were used to devise a prognostic scoring system.

Results

The 5-year estimated survival probability was 0.86. Multivariate Cox proportional hazards modeling demonstrated that 4 factors were associated with lower OS: presumed eloquent location (hazard ratio [HR] 4.12, 95% confidence interval [CI] 1.71–10.42), Karnofsky Performance Scale score ≤ 80 (HR 3.53, 95% CI 1.56–8.00), patient age > 50 years (HR 1.96, 95% CI 1.47–3.77), and tumor diameter > 4 cm (HR 3.43, 95% CI 1.43–8.06). A scoring system calculated from the sum of these factors (range 0–4) demonstrated risk stratification across study groups, with the following 5-year cumulative survival estimates: Scores 0–1, OS = 0.97, PFS = 0.76; Score 2, OS = 0.81, PFS = 0.49; and Scores 3–4, OS = 0.56, PFS = 0.18 (p < 0.001 for both OS and PFS, log-rank test). This proposed scoring system demonstrated a high degree of interscorer reliability (kappa = 0.86). Four illustrative cases are described.

Conclusions

The authors propose a simple and reliable scoring system that can be used to preoperatively prognosticate the degree of lesion resectability, PFS, and OS in patients with LGGs. The application of a standardized scoring system for LGGs should improve clinical decision-making and allow physicians to reliably predict patient outcome at the time of the original imaging-based diagnosis.

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Edward F. Chang, Aaron Clark, Justin S. Smith, Mei-Yin Polley, Susan M. Chang, Nicholas M. Barbaro, Andrew T. Parsa, Michael W. McDermott and Mitchel S. Berger

Object

Low-grade gliomas (LGGs) frequently infiltrate highly functional or “eloquent” brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown.

Methods

We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not.

Results

One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6–14.1; PFS, HR 1.9, 95% CI 1.2–2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6–25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0–8.5).

Conclusions

Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

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S. Andrew Josephson, Alexander M. Papanastassiou, Mitchel S. Berger, Nicholas M. Barbaro, Michael W. McDermott, Joan F. Hilton, Bruce L. Miller and Michael D. Geschwind

Object

Obtaining brain biopsy specimens is often the diagnostic test of last resort for patients with unexplained neurological conditions, particularly those with a rapidly deteriorating neurological course. The goals of this analysis were to determine the diagnostic sensitivity of brain biopsy specimens in these types of patients and retrospectively identify features of these disorders that may have enabled an earlier diagnosis, which may prevent the need for diagnostic brain biopsy procedures in the future.

Methods

The authors reviewed the case records of all brain biopsy procedures that had been performed at a single tertiary care institution between January 1993 and April 2002 in 171 patients. Patients with HIV or nonlymphomatous brain tumors were excluded from this analysis because the utility of brain biopsy specimens for these conditions has been determined from previous studies. A subgroup analysis of this cohort was performed in the 64 patients who had comprehensive medical records and a clinical syndrome involving a progressively deteriorating neurological condition of less than 1 year in duration.

The overall sensitivity of brain biopsy procedures for diagnostic purposes in the cohort was 65% (111 of 171 patients). The two most common diagnoses in the subgroup with rapidly deteriorating neurological conditions were primary central nervous system (CNS) B-cell lymphoma in 20.3% (13 patients) and Creutzfeldt–Jakob disease in 15.6% (10 patients), followed by viral encephalitis in 14.1% (nine patients) and CNS vasculitis in 9.4% (six patients). Clinical symptoms and laboratory data were compared among the diagnostic groups.

Conclusions

These results will help guide the evaluation of patients with neurological conditions that are difficult to diagnose and will provide a foundation for further prospective studies.

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Edward F. Chang, Catherine Christie, Joseph E. Sullivan, Paul A. Garcia, Tarik Tihan, Nalin Gupta, Mitchel S. Berger and Nicholas M. Barbaro

Object

Dysembryoplastic neuroepithelial tumors (DNETs) are a subset of relatively rare glioneuronal tumors that typically present with epilepsy during childhood. The authors' aim was to identify factors that predict seizure control following excision.

Methods

The authors reviewed the cases of 50 patients who underwent resection of DNETs at the University of California, San Francisco, between 1990 and 2006. Demographic, seizure history, radiographic, and histopathological data were collected and analyzed for statistical association with postoperative seizure control.

Results

Of the 50 patients, 86% presented with intractable epilepsy. The median age at surgery was 21 years (range 4–46 years; 40% were < 18 years old at time of surgery), with a median duration of 8 years from onset of seizures (24% were adult-onset seizures). Fifty-two percent of the cases were associated with adjacent focal cortical dysplasia. Complete resection was achieved in 78% of cases. Intraoperative electrocorticography in 23 patients identified extralesional interictal activity in 16 cases, which led to extended lesionectomy or lobectomy. The remaining patients underwent lesionectomy alone. The median follow-up was 5.6 years, during which time tumor progression occurred after subtotal resection. The proportional estimates of seizure freedom (Engel Class I outcome) were 0.86 at 1 year and 0.85 at 5 years. Seizure freedom was predicted by complete or extended resection (OR 1.68, 95% CI 1.39–2.03; p < 0.0001) and extratemporal location (OR 1.20, 95% CI 1.02–1.42; p = 0.03) on multivariate analysis. Secondary analysis for intraoperative electrocorticography cases demonstrated that seizure outcome was better when extralesional spiking foci were detected (94% seizure free) compared with when they were absent (43% seizure free).

Conclusions

Excision of DNETs and, when present, adjacent dysplastic cortex was highly effective for seizure control. Excellent seizure-free outcomes and tumor control were seen with lesionectomy alone in most cases. Electrocorticography with extended resection was useful for patients with pharmacoresistant epilepsy.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010