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Stephen T. Magill, Seunggu J. Han, Jing Li and Mitchel S. Berger

OBJECTIVE

Brain tumors involving the primary motor cortex are often deemed unresectable due to the potential neurological consequences that result from injury to this region. Nevertheless, we have challenged this dogma for many years and used asleep, as well as awake, intraoperative stimulation mapping to maximize extent of resection. It remains unclear whether these tumors can be resected with acceptable morbidity, whether performing the surgery with the patient awake or asleep impacts extent of resection, and how stimulation mapping influences outcomes.

METHODS

A retrospective chart review was performed on the senior author’s cohort to identify patients treated between 1998 and 2016 who underwent resection of tumors that were located within the primary motor cortex. Clinical notes, operative reports, and radiographic images were reviewed to identify intraoperative stimulation mapping findings and functional outcomes following tumor resection. Extent of resection was quantified volumetrically. Characteristics of patients were analyzed to identify factors associated with postoperative motor deficits.

RESULTS

Forty-nine patients underwent 53 resections of tumors located primarily within the motor cortex. Stimulation mapping was performed in all cases. Positive cortical sites for motor response were identified in 91% of cases, and subcortical sites in 74%. Awake craniotomy was performed in 65% of cases, while 35% were done under general anesthesia. The mean extent of resection was 91%. There was no statistically significant difference in extent of resection in cases done awake compared with those done under general anesthesia. New or worsened postoperative motor deficits occurred in 32 patients (60%), and 20 patients (38%) had a permanent deficit. Of the permanent deficits, 14 were mild, 4 were moderate, and 2 were severe (3.8% of cases). Decreased intraoperative motor response and diffusion restriction on postoperative MRI were associated with permanent deficit. Awake motor mapping surgery was associated with increased diffusion signal on postoperative MRI.

CONCLUSIONS

Resection of tumors from the primary motor cortex is associated with an increased risk of motor deficit, but most of these deficits are transient or mild and have little functional impact. Excellent extent of resection can be achieved with intraoperative stimulation mapping, suggesting that these tumors are indeed amenable to resection and should not be labeled unresectable. Injury to small perforating or en passage blood vessels was the most common cause of infarction that led to moderate or severe deficits. Awake motor mapping was not superior to mapping done under general anesthesia with regard to long-term functional outcome.

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Andrew C. Zacest, Stephen T. Magill, Valerie C. Anderson and Kim J. Burchiel

Object

Ilioinguinal neuralgia is one cause of chronic groin pain following inguinal hernia repair, and it affects ~ 10% of patients. Selective ilioinguinal neurectomy is one proposed treatment option for carefully selected patients. The goal of this study was to determine the long-term outcome of patients who underwent selective ilioinguinal neurectomy for chronic post-hernia pain.

Methods

The authors retrospectively reviewed the clinical assessment, surgical treatment, and long-term outcome in 26 patients with ilioinguinal neuralgia who underwent selective ilioinguinal neurectomy performed by the senior author (K.J.B.) at Oregon Health & Science University between 1998 and 2008. Data were collected from patient charts and a follow-up telephone questionnaire.

Results

Twenty-six patients (14 men and 12 women) had a clinical diagnosis of ilioinguinal neuralgia based on a history of radiating neuropathic groin, medial thigh, and genitalia pain. One patient had bilateral disease (therefore there were 27 surgical cases). A selective nerve block was performed in 21 (81%) of 26 patients and was positive in 20 (77%) of the 26. In all but 2 patients, pain onset followed abdominal surgery (for hernia repair in 18 patients), and was immediate in 16 (67%) of 24 patients. The mean patient age was 48.7 years, and the mean duration of pain prior to neurosurgical consultation was 3.9 years. Surgery was performed after induction of local or general anesthesia in 17 and 10 cases, respectively. The ilioinguinal nerve was identified in 25 cases, and the genitofemoral nerve in 2, either entrapped in mesh, scar, or with obvious neuroma (22 of 27 cases). The identified nerve was doubly ligated, cut, and buried in muscle at its most proximal point. At the 2-week follow-up evaluations, 14 (74%) of 19 patients noted definite pain improvement.

Nineteen (73%) of the 26 patients were contacted by telephone and agreed to participate in completing long-term follow-up questionnaires. The mean follow-up duration was 34.78 months. Return of pain was reported by 13 (68%) of 19 patients. Using a verbal numerical rating scale (0–10), pain was completely relieved in 27.8%, better in 38.9%, no better in 16.7%, and worse in 16.7% of patients.

Conclusions

Ilioinguinal neurectomy is an effective and appropriate treatment for selected patients with iatrogenic ilioinguinal neuralgia following abdominal surgery. Although a high proportion of patients reported some long-term recurrence of pain, complete or partial pain relief was achieved in 66.7% of the patients observed.

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Darryl Lau, Stephen T. Magill and Manish K. Aghi

Object

Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma.

Methods

A systematic search was performed with the phrase “(name of particular agent) and glioblastoma” as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies.

Results

A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10–15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%–20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%–20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied.

Conclusions

Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials.

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Stephen T. Magill, Marcel Brus-Ramer, Philip R. Weinstein, Cynthia T. Chin and Line Jacques

Neurogenic thoracic outlet syndrome (nTOS) is caused by compression of the brachial plexus as it traverses from the thoracic outlet to the axilla. Diagnosing nTOS can be difficult because of overlap with other complex pain and entrapment syndromes. An nTOS diagnosis is made based on patient history, physical exam, electrodiagnostic studies, and, more recently, interpretation of MR neurograms with tractography. Advances in high-resolution MRI and tractography can confirm an nTOS diagnosis and identify the location of nerve compression, allowing tailored surgical decompression. In this report, the authors review the current diagnostic criteria, present an update on advances in MRI, and provide case examples demonstrating how MR neurography (MRN) can aid in diagnosing nTOS. The authors conclude that improved high-resolution MRN and tractography are valuable tools for identifying the source of nerve compression in patients with nTOS and can augment current diagnostic modalities for this syndrome.

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Dario J. Englot, Stephen T. Magill, Seunggu J. Han, Edward F. Chang, Mitchel S. Berger and Michael W. McDermott

OBJECT

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

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Stephen T. Magill, Jacob S. Young, Ricky Chae, Manish K. Aghi, Philip V. Theodosopoulos and Michael W. McDermott

OBJECTIVE

Prior studies have investigated preoperative risk factors for meningioma; however, no association has been shown between meningioma tumor size and tumor grade. The objective of this study was to investigate the relationship between tumor size and grade in a large single-center study of patients undergoing meningioma resection.

METHODS

A retrospective chart review of patients undergoing meningioma resection at the University of California, San Francisco, between 1985 and 2015 was performed. Patients with incomplete information, spinal meningiomas, multiple meningiomas, or WHO grade III meningiomas were excluded. The largest tumor dimension was used as a surrogate for tumor size. Univariate and multivariate logistic regression models were used to investigate the relationship between tumor grade and tumor size. A recursive partitioning analysis was performed to identify groups at higher risk for atypical (WHO grade II) meningioma.

RESULTS

Of the 1113 patients identified, 905 (81%) had a WHO grade I tumor and in 208 (19%) the tumors were WHO grade II. The median largest tumor dimension was 3.6 cm (range 0.2–13 cm). Tumors were distributed as follows: skull base (n = 573, 51%), convexity/falx/parasagittal (n = 431, 39%), and other (n = 109, 10%). On univariate regression, larger tumor size (p < 0.001), convexity/falx/parasagittal location (p < 0.001), and male sex (p < 0.001) were significant predictors of WHO grade II pathology. After controlling for interactions, multivariate regression found male sex (OR 1.74, 95% CI 1.25–2.43), size 3–6 cm (OR 1.69, 95% CI 1.08–2.66), size > 6 cm (OR 3.01, 95% CI 1.53–5.94), and convexity/falx/parasagittal location (OR 1.83, 95% CI 1.19–2.82) to be significantly associated with WHO grade II. Recursive partitioning analysis identified male patients with tumors > 3 cm as a high-risk group (32%) for WHO grade II meningioma.

CONCLUSIONS

Larger tumor size is associated with a greater likelihood of a meningioma being WHO grade II, independent of tumor location and male sex, which are known risk factors.

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Jonathan P. Miller, Stephen T. Magill, Feridun Acar and Kim J. Burchiel

Object

Microvascular decompression (MVD) is an effective treatment for trigeminal neuralgia (TN). However, many patients do not experience complete pain relief, and relapse can occur even after an initial excellent result. This study was designed to identify characteristics associated with improved long-term outcome after MVD.

Methods

One hundred seventy-nine consecutive patients who had undergone MVD for TN at the authors' institution were contacted, and 95 were enrolled in the study. Patients provided information about preoperative pain characteristics including preponderance of shock-like (Type 1 TN) or constant (Type 2 TN) pain, preoperative duration, trigger points, anticonvulsant therapy response, memorable onset, and pain-free intervals. Three groups were defined based on outcome: 1) excellent, pain relief without medication; 2) good, mild or intermittent pain controlled with low-dose medication; and 3) poor, severe persistent pain or need for additional surgical treatment.

Results

Type of TN pain (Type 1 TN vs Type 2 TN) was the only significant predictor of outcome after MVD. Results were excellent, good, and poor for Type 1 TN versus Type 2 TN patients in 60 versus 25%, 24 versus 39%, and 16 versus 36%, respectively. Among patients with each TN type, there was a significant trend toward better outcome with greater proportional contribution of Type 1 TN (lancinating) symptoms (p < 0.05).

Conclusions

Pain relief after MVD is strongly correlated with the lancinating pain component, and therefore type of TN pain is the best predictor of long-term outcome after MVD. Application of this information should be helpful in the selection of TN patients likely to benefit from MVD.

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Seunggu J. Han, Stephen T. Magill, Phiroz E. Tarapore, Jonathan C. Horton and Michael W. McDermott

Tuberculum sellae meningiomas frequently produce visual loss by direct compression from tumor, constriction of the optic nerve (ON) under the falciform ligament, and/or ON ischemia. The authors hypothesized that changes in visual function after tumor removal may be related to changes in blood supply to the ON that might be seen in the pial circulation at surgery. Indocyanine green (ICG) angiography was used to attempt to document these changes at surgery. The first patient in whom the technique was used had a left-sided, 1.4-cm, tuberculum meningioma. Time-lapse comparison of images was done postsurgery, and the comparison of video images revealed both faster initial filling and earlier complete filling of the ON pial circulation, suggesting improved pial blood flow after surgical decompression. In follow-up the patient had significant improvements in both visual acuity and visual fields function. Intraoperative ICG angiography of the ON can demonstrate measurable changes in pial vascular flow that may be predictive of postoperative visual outcome. The predictive value of this technique during neurosurgical procedures around the optic apparatus warrants further investigation in a larger cohort.

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Andrew C. Zacest, Stephen T. Magill, Jonathan Miller and Kim J. Burchiel

Object

Trigeminal neuralgia (TN) is a neuropathic pain syndrome that is often associated with neurovascular compression of the trigeminal nerve and may be effectively treated with microvascular decompression (MVD). The authors used high-resolution MR imaging with 3D reconstruction in patients with constant facial pain (Type 2 TN) to determine the presence/absence of neurovascular compression and thus a potential MVD benefit. They retrospectively contacted patients to evaluate outcome.

Methods

All patients who reported spontaneous onset of constant facial pain (Type 2 TN), which occurred at least 50% of the time, who had undergone high-resolution 3-T MR imaging with 3D reconstruction were retrospectively selected for this study. Clinical history, facial pain questionnaire data, physical examination findings, and results from 3-T 3D MR imaging reconstruction were recorded for all patients. Intraoperative findings and clinical pain outcome were recorded for all patients who underwent MVD.

Results

Data obtained in 27 patients were assessed. On the basis of history and 3D MR imaging reconstruction findings, 13 patients were selected for MVD (Group A) and 14 underwent conservative treatment (Group B). Typical or suspected artery- or vein-induced neurovascular compression was predicted preoperatively in 100% of Group A patients and in 0% of Group B patients. At the time of MVD, definitive neurovascular compression was confirmed in 11 (84.6%) of 13 Group A patients. Following MVD, facial pain was completely relieved in 3 (23%), improved in 7 (53.8%), and no better in 3 (23%) of 13 Group A patients. A history of episodic (Type 1 TN) pain at any time was reported in 100 and 50% of Group A and Group B patients, respectively. A Type 1 TN pain component was reportedly improved/relieved in all Group A patients, but the Type 2 TN pain component was improved in only 7 (53.8%) of 13 patients. The mean postoperative follow-up duration was 13 months.

Conclusions

High-resolution 3D MR imaging reconstruction in patients with constant facial pain (Type 2 TN) can help determine the presence/absence of neurovascular compression. Surgical selection based on both clinical and radiological criteria has the potential to improve surgical outcome in patients with Type 2 TN who may potentially benefit from MVD. However, even in such selected patients, pain relief is likely to be incomplete.

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Editorial

Constant facial pain in the trigeminal distribution. Does it respond to microvascular decompression?

Roberto C. Heros