Classic models of language organization posited that separate motor and sensory language foci existed in the inferior frontal gyrus (Broca's area) and superior temporal gyrus (Wernicke's area), respectively, and that connections between these sites (arcuate fasciculus) allowed for auditory-motor interaction. These theories have predominated for more than a century, but advances in neuroimaging and stimulation mapping have provided a more detailed description of the functional neuroanatomy of language. New insights have shaped modern network-based models of speech processing composed of parallel and interconnected streams involving both cortical and subcortical areas. Recent models emphasize processing in “dorsal” and “ventral” pathways, mediating phonological and semantic processing, respectively. Phonological processing occurs along a dorsal pathway, from the posterosuperior temporal to the inferior frontal cortices. On the other hand, semantic information is carried in a ventral pathway that runs from the temporal pole to the basal occipitotemporal cortex, with anterior connections. Functional MRI has poor positive predictive value in determining critical language sites and should only be used as an adjunct for preoperative planning. Cortical and subcortical mapping should be used to define functional resection boundaries in eloquent areas and remains the clinical gold standard. In tracing the historical advancements in our understanding of speech processing, the authors hope to not only provide practicing neurosurgeons with additional information that will aid in surgical planning and prevent postoperative morbidity, but also underscore the fact that neurosurgeons are in a unique position to further advance our understanding of the anatomy and functional organization of language.
Edward F. Chang, Kunal P. Raygor, and Mitchel S. Berger
Alfredo Quinones-Hinojosa, Edward F. Chang, and Michael W. McDermott
Meningiomas arising from the falcotentorial junction are rare. As a result, their clinical presentation and surgical management are not well described. During the past 3 years, the authors have treated six patients with falcotentorial meningiomas.
Most patients presented with symptoms related to raised intracranial pressure, including headaches, papilledema, and visual and gait disturbances. Magnetic resonance imaging revealed a smooth, oval, or round mass, which was typically homogeneously enhancing. Angiography was useful in evaluating arterial supply for embolization, when possible, and determining the status of venous collateral supply and sinus patency. The authors detail the surgical technique used in all six patients. Postoperatively, patients experienced transient cortical blindness, which in all cases spontaneously resolved during the course of several days to weeks. They provide a comprehensive description of the presentation and surgical management of falcotentorial meningiomas.
An excellent outcome can be expected when surgery is predicated on detailed preoperative neuroimaging and knowledge of the nuances of the surgical technique.
Dario J. Englot, Edward F. Chang, and Kurtis I. Auguste
Vagus nerve stimulation (VNS) was approved by the US FDA in 1997 as an adjunctive treatment for medically refractory epilepsy. It is considered for use in patients who are poor candidates for resection or those in whom resection has failed. However, disagreement regarding the utility of VNS in epilepsy continues because of the variability in benefit reported across clinical studies. Moreover, although VNS was approved only for adults and adolescents with partial epilepsy, its efficacy in children and in patients with generalized epilepsy remains unclear. The authors performed the first meta-analysis of VNS efficacy in epilepsy, identifying 74 clinical studies with 3321 patients suffering from intractable epilepsy. These studies included 3 blinded, randomized controlled trials (Class I evidence); 2 nonblinded, randomized controlled trials (Class II evidence); 10 prospective studies (Class III evidence); and numerous retrospective studies. After VNS, seizure frequency was reduced by an average of 45%, with a 36% reduction in seizures at 3–12 months after surgery and a 51% reduction after > 1 year of therapy. At the last follow-up, seizures were reduced by 50% or more in approximately 50% of the patients, and VNS predicted a ≥ 50% reduction in seizures with a main effects OR of 1.83 (95% CI 1.80–1.86). Patients with generalized epilepsy and children benefited significantly from VNS despite their exclusion from initial approval of the device. Furthermore, posttraumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome. In conclusion, VNS is an effective and relatively safe adjunctive therapy in patients with medically refractory epilepsy not amenable to resection. However, it is important to recognize that complete seizure freedom is rarely achieved using VNS and that a quarter of patients do not receive any benefit from therapy.
Jonathan D. Breshears, Annette M. Molinaro, and Edward F. Chang
The human ventral sensorimotor cortex (vSMC) is involved in facial expression, mastication, and swallowing, as well as the dynamic and highly coordinated movements of human speech production. However, vSMC organization remains poorly understood, and previously published population-driven maps of its somatotopy do not accurately reflect the variability across individuals in a quantitative, probabilistic fashion. The goal of this study was to describe the responses to electrical stimulation of the vSMC, generate probabilistic maps of function in the vSMC, and quantify the variability across individuals.
Photographic, video, and stereotactic MRI data of intraoperative electrical stimulation of the vSMC were collected for 33 patients undergoing awake craniotomy. Stimulation sites were converted to a 2D coordinate system based on anatomical landmarks. Motor, sensory, and speech stimulation responses were reviewed and classified. Probabilistic maps of stimulation responses were generated, and spatial variance was quantified.
In 33 patients, the authors identified 194 motor, 212 sensory, 61 speech-arrest, and 27 mixed responses. Responses were complex, stereotyped, and mostly nonphysiological movements, involving hand, orofacial, and laryngeal musculature. Within individuals, the presence of oral movement representations varied; however, the dorsal-ventral order was always preserved. The most robust motor responses were jaw (probability 0.85), tongue (0.64), lips (0.58), and throat (0.52). Vocalizations were seen in 6 patients (0.18), more dorsally near lip and dorsal throat areas. Sensory responses were spatially dispersed; however, patients' subjective reports were highly precise in localization within the mouth. The most robust responses included tongue (0.82) and lips (0.42). The probability of speech arrest was 0.85, highest 15–20 mm anterior to the central sulcus and just dorsal to the sylvian fissure, in the anterior precentral gyrus or pars opercularis.
The authors report probabilistic maps of function in the human vSMC based on intraoperative cortical electrical stimulation. These results define the expected range of mapping outcomes in the vSMC of a single individual and shed light on the functional organization of the vSMC supporting speech motor control and nonspeech functions.
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.
Dario J. Englot, Stephen T. Magill, Seunggu J. Han, Edward F. Chang, Mitchel S. Berger, and Michael W. McDermott
Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life.
The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses.
The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30–2.34); an absence of headache (OR 1.77, 95% CI 1.04–3.25); peritumoral edema (OR 7.48, 95% CI 6.13–9.47); and non–skull base location (OR 1.77, 95% CI 1.04–3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants.
Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does not support routine use of prophylactic anticonvulsants in patients without seizures. Limitations associated with systematic review and meta-analysis should be considered when interpreting these results.
Edward F. Chang, Rodney A. Gabriel, Matthew B. Potts, Mitchel S. Berger, and Michael T. Lawton
Resection of cavernous malformations (CMs) located in functionally eloquent areas of the supratentorial compartment is controversial. Hemorrhage from untreated lesions can result in devastating neurological injury, but surgery has potentially serious risks. We hypothesized that an organized system of approaches can guide operative planning and lead to acceptable neurological outcomes in surgical patients.
The authors reviewed the presentation, surgery, and outcomes of 79 consecutive patients who underwent microresection of supratentorial CMs in eloquent and deep brain regions (basal ganglia [in 27 patients], sensorimotor cortex [in 23], language cortex [in 3], thalamus [in 6], visual cortex [in 10], and corpus callosum [in 10]). A total of 13 different microsurgical approaches were organized into 4 groups: superficial, lateral transsylvian, medial interhemispheric, and posterior approaches.
The majority of patients (93.7%) were symptomatic. Hemorrhage with resulting focal neurological deficit was the most common presentation in 53 patients (67%). Complete resection, as determined by postoperative MR imaging, was achieved in 76 patients (96.2%). Overall, the functional neurological status of patients improved after microsurgical dissection at the time of discharge from the hospital and at follow-up. At 6 months, 64 patients (81.0%) were improved relative to their preoperative condition and 14 patients (17.7%) were unchanged. Good outcomes (modified Rankin Scale score ≤ 2, living independently) were achieved in 77 patients (97.4%). Multivariate analysis of demographic and surgical factors revealed that preoperative functional status was the only predictor of postoperative modified Rankin Scale score (OR 4.6, p = 0.001). Six patients (7.6%) had transient worsening of neurological examination after surgery, and 1 patient (1.3%) was permanently worse. There was no surgical mortality.
The authors present a system of 13 microsurgical approaches to 6 location targets with 4 general trajectories to facilitate safe access to supratentorial CMs in eloquent brain regions. Favorable neurological outcomes following microsurgical resection justify an aggressive surgical attitude toward these lesions.
Edward F. Chang, Doris D. Wang, David W. Perry, Nicholas M. Barbaro, and Mitchel S. Berger
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.
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.
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.
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.
Dario J. Englot, Mitchel S. Berger, Nicholas M. Barbaro, and Edward F. Chang
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.
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).
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.
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.
Dario J. Englot, Seunggu J. Han, Michael T. Lawton, and Edward F. Chang
Seizures are the most common presenting symptom of supratentorial cerebral cavernous malformations (CCMs) and progress to medically refractory epilepsy in 40% of patients. Predictors of seizure freedom in the resection of CCMs are incompletely understood.
The authors systematically reviewed the published literature on seizure freedom following the resection of supratentorial CCMs in patients presenting with seizures. Seizure outcomes were stratified across 12 potential prognostic variables. A total of 1226 patients with supratentorial CCMs causing seizures were identified across 31 predominantly retrospective studies; 361 patients had medically refractory epilepsy.
Seventy-five percent of the patients were seizure free after microsurgical lesion removal, whereas 25% continued to have seizures. All patients had had preoperative seizures and > 6 months of postoperative follow-up. Modifiable predictors of postoperative seizure freedom included gross-total resection (OR 36.6, 95% CI 8.5–157.5) and surgery within 1 year of symptom onset (OR 1.83, 95% CI 1.30–2.58). Additional prognostic indicators of a favorable outcome were a CCM size < 1.5 cm (OR 15.4, 95% CI 5.2–45.4), the absence of multiple CCMs (OR 2.02, 95% CI 1.13–3.60), medically controlled seizures (OR 2.38, 95% CI 1.29–4.39), and the lack of secondarily generalized seizures (OR 3.33, 95% CI 2.09–5.30). Other factors, including extended resection of the hemosiderin ring, were not significantly predictive.
In the surgical treatment of supratentorial CCMs, gross-total resection and early operative intervention may improve seizure outcome. While surgery should not be considered the first-line treatment for CCM-related epilepsy, it is important to understand the variables associated with seizure freedom in CCM resection given the considerable morbidity and diminished quality of life associated with epilepsy.