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Vincent Y. Wang, Edward F. Chang and Nicholas M. Barbaro

Focal cortical dysplasia (FCD) is found in approximately one-half of patients with medically refractory epilepsy. These lesions may involve only mild disorganization of the cortex, but they may also contain abnormal neuronal elements such as balloon cells. Advances in neuroimaging have allowed better identification of these lesions, and thus more patients have become surgical candidates. Molecular biology techniques have been used to explore the genetics and pathophysiological characteristics of FCD. Data from surgical series have shown that surgery often results in significant reduction or cessation of seizures, especially if the entire lesion is resected.

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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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Kunal P. Raygor, Doris D. Wang, Mariann M. Ward, Nicholas M. Barbaro and Edward F. Chang

OBJECTIVE

Microvascular decompression (MVD) and stereotactic radiosurgery (SRS) are common surgical treatments for trigeminal neuralgia (TN). Many patients who receive SRS have pain recurrence; the ideal second intervention is unknown. The authors directly compared pain outcomes after MVD and repeat SRS in a population of patients in whom SRS failed as their first-line procedure for TN, and they identified predictors of pain control.

METHODS

The authors reviewed a prospectively collected database of patients undergoing surgery for TN between 1997 and 2014 at the University of California, San Francisco (UCSF). Standardized data collection focused on preoperative clinical characteristics, surgical characteristics, and postoperative outcomes. Patients with typical type 1, idiopathic TN with ≥ 1 year of follow-up were included.

RESULTS

In total, 168 patients underwent SRS as their first procedure. Of these patients, 90 had residual or recurrent pain. Thirty of these patients underwent a second procedure at UCSF and had ≥ 1 year of follow-up; 15 underwent first-time MVD and 15 underwent repeat SRS. Patients undergoing MVD were younger than those receiving repeat SRS and were more likely to receive ≥ 80 Gy during the initial SRS. The average follow-up was 44.9 ± 33.6 months for MVD and 48.3 ± 45.3 months for SRS. All patients achieved complete pain freedom without medication at some point during their follow-up. At last follow-up, 80% of MVD-treated patients and 33.3% of SRS-treated patients had a favorable outcome, defined as Barrow Neurological Institute Pain Intensity scores of I–IIIa (p < 0.05). Percentages of patients with favorable outcome at 1 and 5 years were 86% and 75% for the MVD cohort and 73% and 27% for the SRS cohort, respectively (p < 0.05). Multivariate Cox proportional hazards analysis demonstrated that performing MVD was statistically significantly associated with favorable outcome (HR 0.12, 95% CI 0.02–0.60, p < 0.01). There were no statistically significant predictors of favorable outcome in the MVD cohort; however, the presence of sensory changes after repeat SRS was associated with pain relief (p < 0.01).

CONCLUSIONS

Patients who received MVD after failed SRS had a longer duration of favorable outcome compared to those who received repeat SRS; however, both modalities are safe and effective. The presence of post-SRS sensory changes was predictive of a favorable pain outcome in the SRS cohort.

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Edward F. Chang, Srikantan S. Nagarajan, Mary Mantle, Nicholas M. Barbaro and Heidi E. Kirsch

Object

Routine scalp electroencephalography (EEG) cannot always distinguish whether generalized epileptiform discharges are the result of primary bilateral synchrony or secondary bilateral synchrony (SBS) from a focal origin; this is an important distinction because the latter may be amenable to resection. Whole-head magnetoencephalography (MEG) has superior spatial resolution compared with traditional EEG, and can potentially elucidate seizure foci in challenging epilepsy cases in which patients are undergoing evaluation for surgery.

Methods

Sixteen patients with medically intractable epilepsy in whom SBS was suspected were referred for magnetic source (MS) imaging. All patients had bilateral, synchronous, widespread, and most often generalized spike-wave discharges on scalp EEG studies, plus some other clinical (for example, seizure semiology) or MR imaging feature (for example, focal lesion) suggesting focal onset and hence possible surgical candidacy. The MS imaging modality is the combination of whole-head MEG and parametric reconstruction of corresponding electrical brain sources. An MEG and simultaneous EEG studies were recorded with a 275-channel whole-head system. Single-equivalent current dipoles were estimated from the MEG data, and dipole locations and orientations were superimposed on patients' MR images.

Results

The MS imaging studies revealed focal dipole clusters in 12 (75%) of the 16 patients, of which a single dipole cluster was identified in 7 patients (44%). Patient age, seizure type, duration of disease, video-EEG telemetry, and MR imaging results were analyzed to determine factors predictive of having clusters revealed on MS imaging. Of these factors, only focal MR imaging anatomical abnormalities were associated with dipole clusters (chi-square test, p = 0.03). Selective resections (including the dipole cluster) in 7 (87%) of 8 patients resulted in seizure-free or rare seizure outcomes (Engel Classes I and II).

Conclusions

Magnetic source imaging may provide noninvasive anatomical and neurophysiological confirmation of localization in patients in whom there is a suspicion of SBS (based on clinical or MR imaging data), especially in those with an anatomical lesion. Identification of a focal seizure origin has significant implications for both resective and nonresective treatment of intractable epilepsy.

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Doris D. Wang, Abby E. Deans, A. James Barkovich, Tarik Tihan, Nicholas M. Barbaro, Paul A. Garcia and Edward F. Chang

Object

Focal cortical dysplasia (FCD) represents a spectrum of developmental cortical abnormalities and is one of the most common causes of intractable epilepsy in children and young adults. Outcomes after surgery for FCD are highly variable, and prognosticators of seizure freedom are unclear. In a subset of FCDs, a transmantle sign is observed on imaging that focally spans the entire cerebral mantle from the ventricle to the cortical surface. The aim of this study was to characterize seizure control outcomes and prognostic significance of the transmantle sign in FCD epilepsy.

Methods

Fourteen patients with the transmantle sign underwent epilepsy surgery for medically refractory epilepsy. Thirteen patients underwent resective surgery and 1 underwent multiple subpial transections with vagus nerve stimulator placement. Patient demographics, MRI, electroencephalography, intraoperative electrocorticography (ECoG), and pathology were reviewed. The results of this series were compared with those of 114 previously reported patients with FCD without the transmantle sign.

Results

All patients were found to have childhood seizure onset and concordant MRI and ECoG findings. The primary MRI findings associated with transmantle sign included gray-white junction blurring, appearance of cortical thickening, T2 or FLAIR abnormality, and bottom-of-the-sulcus dysplasia. The transmantle sign was usually a focal finding, typically confined to 1 or several gyri with well-circumscribed epileptic tissue. Correlation of the transmantle sign with FCD histopathological subtypes was highly variable. Patients who underwent complete resection of MRI and ECoG abnormalities (12 of 13 patients) became seizure free. When compared with 114 FCD patients without the transmantle sign, patients with the transmantle sign showed significantly improved seizure-free outcomes after complete resections (p = 0.04).

Conclusions

The presence of the transmantle sign in patients with medically refractory partial epilepsy is associated with highly favorable seizure control outcomes after surgical treatment.

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Nathan C. Rowland, Dario J. Englot, Tene A. Cage, Michael E. Sughrue, Nicholas M. Barbaro and Edward F. Chang

Object

Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature.

Methods

A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol.

Results

Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery.

Conclusions

Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors—diagnostic imaging and resection—provide modalities through which improvements in the impact of FCD can be effected.

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Doris D. Wang, Kunal P. Raygor, Tene A. Cage, Mariann M. Ward, Sarah Westcott, Nicholas M. Barbaro and Edward F. Chang

OBJECTIVE

Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD), stereotactic radiosurgery (SRS), and radiofrequency ablation (RFA). Although the efficacy of each procedure has been described, few studies have directly compared these treatment modalities on pain control for TN. Using a large prospective longitudinal database, the authors aimed to 1) directly compare long-term pain control rates for first-time surgical treatments for idiopathic TN, and 2) identify predictors of pain control.

METHODS

The authors reviewed a prospectively collected database for all patients who underwent treatment for TN between 1997 and 2014 at the University of California, San Francisco. Standardized collection of data on preoperative clinical characteristics, surgical procedure, and postoperative outcomes was performed. Data analyses were limited to those patients who received a first-time procedure for treatment of idiopathic TN with > 1 year of follow-up.

RESULTS

Of 764 surgical procedures performed at the University of California, San Francisco, for TN (364 SRS, 316 MVD, and 84 RFA), 340 patients underwent first-time treatment for idiopathic TN (164 MVD, 168 SRS, and 8 RFA) and had > 1 year of follow-up. The analysis was restricted to patients who underwent MVD or SRS. Patients who received MVD were younger than those who underwent SRS (median age 63 vs 72 years, respectively; p < 0.001). The mean follow-up was 59 ± 35 months for MVD and 59 ± 45 months for SRS. Approximately 38% of patients who underwent MVD or SRS had > 5 years of follow-up (60 of 164 and 64 of 168 patients, respectively). Immediate or short-term (< 3 months) postoperative pain-free rates (Barrow Neurological Institute Pain Intensity score of I) were 96% for MVD and 75% for SRS. Percentages of patients with Barrow Neurological Institute Pain Intensity score of I at 1, 5, and 10 years after MVD were 83%, 61%, and 44%, and the corresponding percentages after SRS were 71%, 47%, and 27%, respectively. The median time to pain recurrence was 94 months (25th–75th quartiles: 57–131 months) for MVD and 53 months (25th–75th quartiles: 37–69 months) for SRS (p = 0.006). A subset of patients who had MVD also underwent partial sensory rhizotomy, usually in the setting of insignificant vascular compression. Compared with MVD alone, those who underwent MVD plus partial sensory rhizotomy had shorter pain-free intervals (median 45 months vs no median reached; p = 0.022). Multivariable regression demonstrated that shorter preoperative symptom duration (HR 1.005, 95% CI 1.001–1.008; p = 0.006) was associated with favorable outcome for MVD and that post-SRS sensory changes (HR 0.392, 95% CI 0.213–0.723; p = 0.003) were associated with favorable outcome for SRS.

CONCLUSIONS

In this longitudinal study, patients who received MVD had longer pain-free intervals compared with those who underwent SRS. For patients who received SRS, postoperative sensory change was predictive of favorable outcome. However, surgical decision making depends upon many factors. This information can help physicians counsel patients with idiopathic TN on treatment selection.

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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.