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Incidence and characteristics of cerebral hypoxia after craniectomy in brain-injured patients: a cohort study

Alexandrine Gagnon, Mathieu Laroche, David Williamson, Marc Giroux, Jean-François Giguère, and Francis Bernard

OBJECTIVE

After craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors’ objective was to describe the incidence and characteristics of brain hypoxia after craniectomy.

METHODS

The authors included 25 consecutive patients who underwent a craniectomy after traumatic brain injury or intracerebral hemorrhage and who were monitored afterward with a brain tissue oxygen pressure monitor.

RESULTS

The frequency of hypoxic values after surgery was 14.6% despite ICP being controlled. Patients had a mean of 18 ± 23 hypoxic episodes. Endotracheal (ET) secretions (17.4%), low cerebral perfusion pressure (10.3%), and mobilizing the patient (8.6%) were the most common causes identified. Elevated ICP was rarely identified as the cause of hypoxia (4%). No cause of cerebral hypoxia could be determined 31.2% of the time. Effective treatments that were mainly used included sedation/analgesia (20.8%), ET secretion suctioning (15.4%), and increase in fraction of inspired oxygen or positive end-expiratory pressure (14.1%).

CONCLUSIONS

Cerebral hypoxia is common after craniectomy, despite ICP being controlled. ET secretion and patient mobilization are common causes that are easily treatable and often not identified by standard monitoring. These results suggest that monitoring should be pursued even if ICP is controlled. The authors’ findings might provide a hypothesis to explain the poor functional outcome in the recent randomized controlled trials on craniectomy after traumatic brain injury where in which brain tissue oxygen pressure was not measured.

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Incidence and characteristics of cerebral hypoxia after craniectomy in brain-injured patients: a cohort study

Alexandrine Gagnon, Mathieu Laroche, David Williamson, Marc Giroux, Jean-François Giguère, and Francis Bernard

OBJECTIVE

After craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors’ objective was to describe the incidence and characteristics of brain hypoxia after craniectomy.

METHODS

The authors included 25 consecutive patients who underwent a craniectomy after traumatic brain injury or intracerebral hemorrhage and who were monitored afterward with a brain tissue oxygen pressure monitor.

RESULTS

The frequency of hypoxic values after surgery was 14.6% despite ICP being controlled. Patients had a mean of 18 ± 23 hypoxic episodes. Endotracheal (ET) secretions (17.4%), low cerebral perfusion pressure (10.3%), and mobilizing the patient (8.6%) were the most common causes identified. Elevated ICP was rarely identified as the cause of hypoxia (4%). No cause of cerebral hypoxia could be determined 31.2% of the time. Effective treatments that were mainly used included sedation/analgesia (20.8%), ET secretion suctioning (15.4%), and increase in fraction of inspired oxygen or positive end-expiratory pressure (14.1%).

CONCLUSIONS

Cerebral hypoxia is common after craniectomy, despite ICP being controlled. ET secretion and patient mobilization are common causes that are easily treatable and often not identified by standard monitoring. These results suggest that monitoring should be pursued even if ICP is controlled. The authors’ findings might provide a hypothesis to explain the poor functional outcome in the recent randomized controlled trials on craniectomy after traumatic brain injury where in which brain tissue oxygen pressure was not measured.

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Comparative study of Gamma Knife surgery and percutaneous retrogasserian glycerol rhizotomy for trigeminal neuralgia in patients with multiple sclerosis

Clinical article

David Mathieu, Khaled Effendi, Jocelyn Blanchard, and Mario Séguin

Object

Among patients with multiple sclerosis (MS) there is a high incidence of trigeminal neuralgia (TN), and outcomes after treatment seem inferior to those in patients suffering from idiopathic TN. The goal of this study was to evaluate clinical outcomes in patients with MS-related TN after Gamma Knife surgery (GKS) and compare them with those obtained using percutaneous retrogasserian glycerol rhizotomy (PRGR).

Methods

The authors retrospectively reviewed the charts of 45 patients with MS-related TN. The first procedure undertaken was GKS in 27 patients and PRGR in 18 patients. Pain had been present for a median of 60 months (range 12–276 months) in patients who underwent GKS and 48 months (range 12–240 months) in patients who underwent PRGR. The following outcome measures were assessed in both groups of patients: pain relief (using the Barrow Neurological Institute [BNI] Pain Scale), procedure-related morbidity, time to pain relief and recurrence, and subsequent procedures that were performed.

Results

The median duration of follow-up was 39 months (range 13–69 months) in the GKS group and 38 months (range 2–75 months) in the PRGR group. Reasonable pain control (BNI Pain Scale Scores I–IIIb) was noted in 22 patients (81.5%) who underwent GKS and in 18 patients (100%) who underwent PRGR. For patients who underwent GKS, the median time to pain relief was 6 months; for those who underwent PRGR, pain relief was immediate. In the GKS group12 patients required subsequent procedures (3 patients for absence of response and 9 patients for pain recurrence), whereas in the PRGR group 6 patients required subsequent procedures (all for pain recurrence). As of the last follow-up, complete or reasonable pain control was finally achieved in 23 patients (85.2%) in the GKS group and in 16 patients (88.9%) in the PRGR group. The morbidity rate was 22.2% in the GKS group (all due to sensory loss and paresthesia) and 66.7% in the PRGR group (mostly hypalgesia, with 2 patients having corneal reflex loss and 1 patient suffering from meningitis).

Conclusions

Both GKS and PRGR are satisfactory strategies for treating MS-related TN. Gamma Knife surgery has a lower rate of sensory and overall morbidity than PRGR, but requires a delay before pain relief occurs. The authors propose that patients with extreme pain in need of fast relief should undergo PRGR. For other patients, both management strategies can lead to satisfactory pain relief, and the choice should be made based on patient preference and expectations.

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Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control

Clinical article

Christian Iorio-Morin, Laurence Masson-Côté, Youssef Ezahr, Jocelyn Blanchard, Annie Ebacher, and David Mathieu

Object

Optimal case management after surgical removal of brain metastasis remains controversial. Although postoperative whole-brain radiation therapy (WBRT) has been shown to prevent local recurrence and decrease deaths, this modality can substantially decrease neurocognitive function and quality of life. Stereotactic radiosurgery (SRS) can theoretically achieve the same level of local control with fewer side effects, although studies conclusively demonstrating such outcomes are lacking. To assess the effectiveness and safety profile of tumor bed SRS after resection of brain metastasis, the authors performed a retrospective analysis of 110 patients who had received such treatment at the Centre Hospitalier Universitaire de Sherbrooke. They designed the study to identify risk factors for local recurrence and placed special emphasis on factors that could potentially be addressed.

Methods

Patients who had received treatment from 2004 through 2013 were included if they had undergone surgical removal of 1 or more brain metastases and if the tumor bed was treated by SRS regardless of the extent of resection or prior WBRT. All cases were retrospectively analyzed for patient and tumor-specific factors, treatment protocol, adverse outcomes, cavity outcomes, and survival for as long as follow-up was available. Univariate and multivariate Cox regression analyses were performed to identify risk factors for local recurrence and predictors of increased survival times.

Results

Median patient age at first SRS treatment was 58 years (range 37–84 years). The most frequently diagnosed primary tumor was non–small cell lung cancer. The rate of gross-total resection was 81%. The median Karnofsky Performance Scale score was 90%. Tumor bed SRS was performed at a median of 3 weeks after surgery. Median follow-up and survival times were 10 and 11 months, respectively. Actuarial local control of the cavity at 12 months was 73%; median time to recurrence was 6 months. According to multivariate analysis, risk factors for recurrence were a longer surgery-to-SRS delay (HR 1.625, p = 0.003) and a lower maximum radiation dose delivered to the cavity (HR 0.817, p = 0.006). Factors not associated with increased recurrence were subtotal or piecemeal resections, prior WBRT, histology of the primary tumor, and larger cavity volume. No factors predictive of survival were identified. Symptomatic radiation-induced enhancement occurred in 6% of patients and leptomeningeal dissemination in 11%. Pathologically confirmed radiation-induced necrosis occurred in 1 (0.9%) patient.

Conclusions

Adjuvant tumor bed SRS after the resection of brain metastasis is a valuable alternative to adjuvant WBRT. Risk factors for local recurrence are lower maximum radiation dose and a surgery-to-SRS delay longer than 3 weeks. Outcomes were not worse for patients who had undergone prior WBRT and subtotal or piecemeal resections. Pending the results of prospective randomized controlled trials, the authors' study supports the safety and efficacy of adjuvant SRS after resection of brain metastasis. SRS should be performed as early as possible, ideally within 3 weeks of the surgery.

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Proceedings of the 2018 next-generation Gamma Knife research meeting

Veronica L. Chiang, Samuel T. Chao, Constantin Tuleasca, Matthew C. Foote, Cheng-chia Lee, David Mathieu, Hany Soliman, and Arjun Sahgal

In order to determine what areas of research are a clinical priority, a small group of young Gamma Knife investigators was invited to attend a workshop discussion at the 19th International Leksell Gamma Knife Society Meeting. Two areas of interest and the need for future radiosurgical research involving multiple institutions were identified by the young investigators working group: 1) the development of additional imaging sequences to guide the understanding, treatment, and outcome tracking of diseases such as tremor, radiation necrosis, and AVM; and 2) trials to clarify the role of hypofractionation versus single-fraction radiosurgery in the treatment of large lesions such as brain metastases, postoperative cavities, and meningiomas.

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Minimal PaO2 threshold after traumatic brain injury and clinical utility of a novel brain oxygenation ratio

Laura Dellazizzo, Simon-Pierre Demers, Emmanuel Charbonney, Virginie Williams, Karim Serri, Martin Albert, Jean-François Giguère, Mathieu Laroche, David Williamson, and Francis Bernard

OBJECTIVE

Avoiding decreases in brain tissue oxygenation (PbtO2) after traumatic brain injury (TBI) is important. How best to adjust PbtO2 remains unclear. The authors investigated the association between partial pressure of oxygen (PaO2) and PbtO2 to determine the minimal PaO2 required to maintain PbtO2 above the hypoxic threshold (> 20 mm Hg), accounting for other determinants of PbtO2 and repeated measurements in the same patient. They also explored the clinical utility of a novel concept, the brain oxygenation ratio (BOx ratio = PbtO2/PaO2) to detect overtreatment with the fraction of inspired oxygen (FiO2).

METHODS

A retrospective cohort study at an academic level 1 trauma center included 38 TBI patients who required the insertion of a monitor to measure PbtO2. Various determinants of PbtO2 were collected simultaneously whenever a routine arterial blood gas was drawn. A PbtO2/PaO2 ratio was calculated for each blood gas and plotted over time for each patient. All patients were managed according to a standardized clinical protocol. A mixed effects model was used to account for repeated measurements in the same patient.

RESULTS

A total of 1006 data points were collected. The lowest mean PaO2 observed to maintain PbtO2 above the ischemic threshold was 94 mm Hg. Only PaO2 and cerebral perfusion pressure were predictive of PbtO2 in multivariate analysis. The PbtO2/PaO2 ratio was below 0.15 in 41.7% of all measures and normal PbtO2 values present despite an abnormal ratio in 27.1% of measurements.

CONCLUSIONS

The authors’ results suggest that the minimal PaO2 target to ensure adequate cerebral oxygenation during the first few days after TBI should be higher than that suggested in the Brain Trauma Foundation guidelines. The use of a PbtO2/PaO2 ratio (BOx ratio) may be clinically useful and identifies abnormal O2 delivery mechanisms (cerebral blood flow, diffusion, and cerebral metabolic rate of oxygen) despite normal PbtO2.

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Natural history of ventriculostomy-related infection under appropriate treatment and risk factors of poor outcome: a retrospective study

Roman Mounier, Ron Birnbaum, Fabrice Cook, Paul-Henri Jost, Mathieu Martin, Bouziane Aït-Mamar, Biba Nebbad, Séverine Couffin, Françoise Tomberli, Ryad Djedid, Gilles Dhonneur, and David Lobo

OBJECTIVE

The authors aimed to describe the natural history of ventriculostomy-related infections (VRIs) under appropriate treatment and to assess risk factors for poor outcome.

METHODS

All patients older than 18 years in whom an external ventricular drain (EVD) had been implanted and who had developed a VRI requiring treatment were included in this retrospective study. D0 was defined as the first day of antibiotic administration. Clinical and biological parameters were compared each day beginning with D1 and ending with D10 to those of D0. The authors defined D0 in a control group as the day a CSF culture came back positive, without any sign of infection. The authors then searched for poor prognostic factors in the VRI group.

RESULTS

Among 567 patients requiring an EVD between January 2007 and October 2017, 39 developed a VRI. Most were monomicrobial infections, and 47 microbes were responsible (45% were gram-positive cocci). Clinical parameters differed significantly from the control group during the first 2 days and then returned to baseline. The CSF parameters differed significantly from the control group for a longer period, returning to baseline after 5 days. CSF sterilization occurred in a median time of 2 days. An intrathecal route or EVD exchange was not associated with a poor outcome. No clinical or biological parameter between D3 and D5 was linked to outcome.

CONCLUSIONS

Clinical status improved faster than CSF parameters (before and after D5, respectively). Some CSF parameters remained abnormal until D10. Body temperature and microbiological cultures normalized faster than other parameters.

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Stereotactic radiosurgery for idiopathic glossopharyngeal neuralgia: an international multicenter study

Hideyuki Kano, Dusan Urgosik, Roman Liscak, Bruce E. Pollock, Or Cohen-Inbar, Jason P. Sheehan, Mayur Sharma, Danilo Silva, Gene H. Barnett, David Mathieu, Nathaniel D. Sisterson, and L. Dade Lunsford

OBJECTIVE

The goal of this study was to evaluate the outcomes of Gamma Knife stereotactic radiosurgery (SRS) when used for patients with intractable idiopathic glossopharyngeal neuralgia.

METHODS

Six participating centers of the International Gamma Knife Research Foundation identified 22 patients who underwent SRS for intractable glossopharyngeal neuralgia between 1998 and 2015. The median patient age was 60 years (range 34–83 years). The median duration of symptoms before SRS was 46 months (range 1–240 months). Three patients had unsuccessful prior surgical procedures, including microvascular decompression (MVD) (n = 2) and balloon compression (n = 1). The radiosurgical target was the glossopharyngeal meatus. The median maximum dose was 80 Gy.

RESULTS

The median follow-up was 45 months after SRS (range 6–120 months). Twelve patients (55%) had < 4 years of follow-up. Thirteen patients (59%) had initial complete pain relief at a median of 12 days after SRS (range 1–60 days). Three patients (14%) had partial pain relief at a median of 70 days after SRS (range 60–90 days). Six patients (27%) had no pain relief. Among 16 patients with initial pain relief, 5 maintained complete pain relief without medication (Barrow Neurological Institute [BNI] pain intensity score Grade I), 1 maintained occasional pain relief without medication (BNI Grade II), 3 maintained complete pain relief with medication (BNI Grade IIIb), and 7 patients had pain recurrence at a median of 20 months after SRS (range 6–120 months). The rates of maintenance of adequate pain relief (BNI Grades I–IIIb) were 63% at 1 year, 49% at 2 years, 38% at 3 years, 38% at 5 years, and 28% at 7 years. When 7 patients without pain recurrence within 4 years of follow-up were excluded, the rates of maintenance of adequate pain relief were 38% at 5 years and 28% at 7 years. Ten patients required additional procedures (MVD, n = 4; repeat SRS, n = 5; glossopharyngeal nerve block, n = 1). Four of 5 patients who underwent repeat SRS maintained pain relief (BNI Grade I, n = 3; and BNI Grade IIIb, n = 1). No adverse effects of radiation were observed after a single SRS. Two patients developed hyperesthesia in the palatoglossal arch 5 and 8 months after repeat SRS, respectively.

CONCLUSIONS

Stereotactic radiosurgery for intractable, medically refractory glossopharyngeal neuralgia provided lasting pain reduction in 55% of patients after 1 or 2 SRS procedures. Patients who had a poor response or pain recurrence may require additional procedures such as repeat SRS, MVD, nerve blocks, or nerve section. No patient developed changes in vocal cord function or swallowing disorders after SRS in this study.

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Stereotactic radiosurgery for arteriovenous malformations of the basal ganglia and thalamus: an international multicenter study

Ching-Jen Chen, Kathryn N. Kearns, Dale Ding, Hideyuki Kano, David Mathieu, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Inga S. Grills, Gene H. Barnett, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.

METHODS

The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.

RESULTS

The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).

CONCLUSIONS

SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

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Neurofibromatosis type 2–associated meningiomas: an international multicenter study of outcomes after Gamma Knife stereotactic radiosurgery

Nasser Mohammed, Yi-Chieh Hung, Zhiyuan Xu, Tomas Chytka, Roman Liscak, Manjul Tripathi, David Arsanious, Christopher P. Cifarelli, Marco Perez Caceres, David Mathieu, Herwin Speckter, Gautam U. Mehta, Gregory P. Lekovic, and Jason P. Sheehan

OBJECTIVE

The management of neurofibromatosis type 2 (NF2)–associated meningiomas is challenging. The role of Gamma Knife radiosurgery (GKRS) in the treatment of these tumors remains to be fully defined. In this study, the authors aimed to examine the role of GKRS in the treatment of NF2-associated meningiomas and to evaluate the outcomes and complications after treatment.

METHODS

Seven international medical centers contributed data for this retrospective cohort. Tumor progression was defined as a ≥ 20% increase from the baseline value. The clinical features, treatment details, outcomes, and complications were studied. The median follow-up was 8.5 years (range 0.6–25.5 years) from the time of initial GKRS. Shared frailty Cox regression was used for analysis.

RESULTS

A total of 204 meningiomas in 39 patients treated with GKRS were analyzed. Cox regression analysis showed that increasing the maximum dose (p = 0.02; HR 12.2, 95% CI 1.287–116.7) and a lower number of meningiomas at presentation (p = 0.03; HR 0.9, 95% CI 0.821–0.990) were predictive of better tumor control in both univariable and multivariable settings. Age at onset, sex, margin dose, location, and presence of neurological deficit were not predictive of tumor progression. The cumulative 10-year progression-free survival was 94.8%. Radiation-induced adverse effects were noted in 4 patients (10%); these were transient and managed medically. No post-GKRS malignant transformation was noted in 287 person-years of follow-up.

CONCLUSIONS

GKRS achieved effective tumor control with a low and generally acceptable rate of complications in NF2-associated meningiomas. There did not appear to be an appreciable risk of post–GKRS-induced malignancy in patients with NF2-treated meningiomas.