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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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Eun Young Han, He Wang, Dershan Luo, Jing Li and Xin Wang

OBJECTIVE

For patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues.

METHODS

Ten patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42–49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21–30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases.

RESULTS

Plans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans.

CONCLUSIONS

All 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

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Derek G. Southwell, Harjus S. Birk, Seunggu J. Han, Jing Li, Jeffrey W. Sall and Mitchel S. Berger

OBJECTIVE

Maximal safe resection is a primary objective in the management of gliomas. Despite this objective, surgeons and referring physicians may, on the basis of radiological studies alone, assume a glioma to be unresectable. Because imaging studies, including functional MRI, may not localize brain functions (such as language) with high fidelity, this simplistic approach may exclude some patients from what could be a safe resection. Intraoperative direct electrical stimulation (DES) allows for the accurate localization of functional areas, thereby enabling maximal resection of tumors, including those that may appear inoperable based solely on radiological studies. In this paper the authors describe the extent of resection (EOR) and functional outcomes following resections of tumors deemed inoperable by referring physicians and neurosurgeons.

METHODS

The authors retrospectively examined the cases of 58 adult patients who underwent glioma resection within 6 months of undergoing a brain biopsy of the same lesion at an outside hospital. All patients exhibited unifocal supratentorial disease and preoperative Karnofsky Performance Scale scores ≥ 70. The EOR and 6-month functional outcomes for this population were characterized.

RESULTS

Intraoperative DES mapping was performed on 96.6% (56 of 58) of patients. Nearly half of the patients (46.6%, 27 of 58) underwent an awake surgical procedure with DES. Overall, the mean EOR was 87.6% ± 13.6% (range 39.0%–100%). Gross-total resection (resection of more than 99% of the preoperative tumor volume) was achieved in 29.3% (17 of 58) of patients. Subtotal resection (95%–99% resection) and partial resection (PR; < 95% resection) were achieved in 12.1% (7 of 58) and 58.6% (34 of 58) of patients, respectively. Of the cases that involved PR, the mean EOR was 79.4% ± 12.2%. Six months after surgery, no patient was found to have a new postoperative neurological deficit. The majority of patients (89.7%, 52 of 58) were free of neurological deficits both pre- and postoperatively. The remainder of patients exhibited either residual but stable deficits (5.2%, 3 of 58) or complete correction of preoperative deficits (5.2%, 3 of 58).

CONCLUSIONS

The use of DES enabled maximal safe resections of gliomas deemed inoperable by referring neurosurgeons. With rare exceptions, tumor resectability cannot be determined solely by radiological studies.

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I-Chang Su, Chi-Cheng Yang, Wei-Han Wang, Jing-Er Lee, Yong-Kwang Tu and Kuo-Chuan Wang

The authors present a rare case of an infarction complication 15 days following acute intraventricular bleeding due to moyamoya disease. Before the infarction occurred, perfusion CT imaging disclosed early but reversible ischemic injury on the day of hemorrhage. Dehydration and hypotension are both possibly contributing factors of progressive injury from reversible ischemia due to infarction. Although the patient underwent successful bypass surgery, 1 month after the ictus the neurobehavior evaluation still showed marked executive dysfunction. The authors address that, in hemorrhagic-type moyamoya disease, early perfusion CT scanning is not only a powerful tool to identify the high-risk group of patients who could experience subacute infarction, but also alarms neurosurgeons to eliminate any predisposing factors when it shows reversible ischemic injuries.

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Owoicho Adogwa, Aladine A. Elsamadicy, Jing L. Han, Joseph Cheng, Isaac Karikari and Carlos A. Bagley

OBJECTIVE

With the recent passage of the Patient Protection and Affordable Care Act, there has been a dramatic shift toward critical analyses of quality and longitudinal assessment of subjective and objective outcomes after lumbar spine surgery. Accordingly, the emergence and routine use of real-world institutional registries have been vital to the longitudinal assessment of quality. However, prospectively obtaining longitudinal outcomes for patients at 24 months after spine surgery remains a challenge. The aim of this study was to assess if 12-month measures of treatment effectiveness accurately predict long-term outcomes (24 months).

METHODS

A nationwide, multiinstitutional, prospective spine outcomes registry was used for this study. Enrollment criteria included available demographic, surgical, and clinical outcomes data. All patients had prospectively collected outcomes measures and a minimum 2-year follow-up. Patient-reported outcomes instruments (Oswestry Disability Index [ODI], SF-36, and visual analog scale [VAS]-back pain/leg pain) were completed before surgery and then at 3, 6, 12, and 24 months after surgery. The Health Transition Index of the SF-36 was used to determine the 1- and 2-year minimum clinically important difference (MCID), and logistic regression modeling was performed to determine if achieving MCID at 1 year adequately predicted improvement and achievement of MCID at 24 months.

RESULTS

The study group included 969 patients: 300 patients underwent anterior lumbar interbody fusion (ALIF), 606 patients underwent transforaminal lumbar interbody fusion (TLIF), and 63 patients underwent lateral interbody fusion (LLIF). There was a significant correlation between the 12- and 24-month ODI (r = 0.82; p < 0.0001), SF-36 Physical Component Summary score (r = 0.89; p < 0.0001), VAS-back pain (r = 0.90; p < 0.0001), and VAS-leg pain (r = 0.85; p < 0.0001). For the ALIF cohort, patients achieving MCID thresholds for ODI at 12 months were 13-fold (p < 0.0001) more likely to achieve MCID at 24 months. Similarly, for the TLIF and LLIF cohorts, patients achieving MCID thresholds for ODI at 12 months were 13-fold and 14-fold (p < 0.0001) more likely to achieve MCID at 24 months. Outcome measures obtained at 12 months postoperatively are highly predictive of 24-month outcomes, independent of the surgical procedure.

CONCLUSIONS

In a multiinstitutional prospective study, patient-centered measures of surgical effectiveness obtained at 12 months adequately predict long-term (24-month) outcomes after lumbar spine surgery. Patients achieving MCID at 1 year were more likely to report meaningful and durable improvement at 24 months, suggesting that the 12-month time point is sufficient to identify effective versus ineffective patient care.

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Jian-Hua Zhong, Hua-Jun Zhou, Tao Tang, Han-Jin Cui, A-Li Yang, Qi-Mei Zhang, Jing-Hua Zhou, Qiang Zhang, Xun Gong, Zhao-Hui Zhang and Zhi-Gang Mei

OBJECTIVE

Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH.

METHODS

ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats’ brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively.

RESULTS

Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH.

CONCLUSIONS

Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.

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Junxiang Wen, Yingchao Han, Song Guo, Mingjie Yang, Lijun Li, Guixin Sun, Jun Wang, Fangqiong Hu, Jing Liang, Li Wei, Qi Zhou, Weibin Zhang and Jun Tan

The authors studied restoration of respiratory function in rabbits, using the recurrent laryngeal nerve to restore function after the phrenic nerve had been severed. The results of this animal study are encouraging and suggest that a similar technique could possibly be used to help patients with severe cervical spinal cord injuries.