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Felix Umansky, Yigal Shoshan, Guy Rosenthal, Shifra Fraifeld and Sergey Spektor

✓ The long-term or delayed side effects of irradiation on neural tissue are now known to include the induction of new central nervous system neoplasms. However, during the first half of the 20th century, human neural tissue was generally considered relatively resistant to the carcinogenic and other ill effects of ionizing radiation. As a result, exposure to relatively high doses of x-rays from diagnostic examinations and therapeutic treatment was common.

In the present article the authors review the literature relating to radiation-induced meningiomas (RIMs). Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. The incidence and natural history of RIMs following exposure to high- and low-dose radiation is presented, including latency, multiplicity, histopathological features, and recurrence rates. The authors review the typical presentation of patients with RIMs and discuss unique aspects of the surgical management of these tumors compared with sporadic meningioma, based on their clinical experience in treating these lesions.

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Omer Doron, Tal Or, Limor Battino, Guy Rosenthal and Ofer Barnea

OBJECTIVE

Augmenting brain perfusion or reducing intracranial pressure (ICP) dose is the end target of many therapies in the neuro-critical care unit. Many present therapies rely on aggressive systemic interventions that may lead to untoward effects. Previous studies have used a cardiac-gated intracranial balloon pump (ICBP) to model hydrocephalus or to flatten the ICP waveform. The authors sought to sought to optimize ICBP activation parameters to improve cerebral physiological parameters in a swine model of raised ICP.

METHODS

The authors developed a cardiac-gated ICBP in which the volume, timing, and duty cycle (time relative to a single cardiac cycle) of balloon inflation could be altered. They studied the ICBP in a swine model of elevated ICP attained by continuous intracranial fluid infusion with continuous monitoring of systemic and cerebral physiological parameters, and defined two specific protocols of ICBP activation.

RESULTS

Eleven swine were studied, 3 of which were studied to define the optimal timing, volume, and duty cycle of balloon inflation. Eight swine were studied with two defined protocols at baseline and with ICP gradually raised to a mean of 30.5 mm Hg. ICBP activation caused a consistent modification of the ICP waveform. Two ICBP activation protocols were used. Balloon activation protocol A led to a consistent elevation in cerebral blood flow (8%–25% above baseline, p < 0.00001). Protocol B resulted in a modest reduction of ICP over time (8%–11%, p < 0.0001) at all ICP levels. Neither protocol significantly affected systemic physiological parameters.

CONCLUSIONS

The preliminary results indicate that optimized protocols of ICBP activation may have beneficial effects on cerebral physiological parameters, with minimal effect on systemic parameters. Further studies are warranted to explore whether ICBP protocols may be of clinical benefit in patients with brain injuries with increased ICP.

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Guy Rosenthal, Alex Furmanov, Eyal Itshayek, Yigal Shoshan and Vineeta Singh

Object

Development of a noninvasive monitor to assess cerebral oxygenation has long been a goal in neurocritical care. The authors evaluated the feasibility and utility of a noninvasive cerebral oxygenation monitor, the CerOx 3110, which uses near-infrared spectroscopy and ultrasound to measure regional cerebral tissue oxygenation in patients with severe traumatic brain injury (TBI), and compared measurements obtained using this device to those obtained using invasive cerebral monitoring.

Methods

Patients with severe TBI admitted to the intensive care unit at Hadassah-Hebrew University Hospital requiring intracranial pressure (ICP) monitoring and advanced neuromonitoring were included in this study. The authors assessed 18 patients with severe TBI using the CerOx monitor and invasive advanced cerebral monitors.

Results

The mean age of the patients was 45.3 ± 23.7 years and the median Glasgow Coma Scale score on admission was 5 (interquartile range 3–7). Eight patients underwent unilateral decompressive hemicraniectomy and 1 patient underwent craniotomy. Sixteen patients underwent insertion of a jugular bulb venous catheter, and 18 patients underwent insertion of a Licox brain tissue oxygen monitor. The authors found a strong correlation (r = 0.60, p < 0.001) between the jugular bulb venous saturation from the venous blood gas and the CerOx measure of regional cerebral tissue saturation on the side ipsilateral to the catheter. A multivariate analysis revealed that among the physiological parameters of mean arterial blood pressure, ICP, brain tissue oxygen tension, and CerOx measurements on the ipsilateral and contralateral sides, only ipsilateral CerOx measurements were significantly correlated to jugular bulb venous saturation (p < 0.001).

Conclusions

Measuring regional cerebral tissue oxygenation with the CerOx monitor in a noninvasive manner is feasible in patients with severe TBI in the neurointensive care unit. The correlation between the CerOx measurements and the jugular bulb venous measurements of oxygen saturation indicate that the CerOx may be able to provide an estimation of cerebral oxygenation status in a noninvasive manner.

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Omer Doron, Ofer Barnea, Nino Stocchetti, Tal Or, Erez Nossek and Guy Rosenthal

OBJECTIVE

Previous studies have demonstrated the importance of intracranial elastance; however, methodological difficulties have limited widespread clinical use. Measuring elastance may offer potential benefit in helping to identify patients at risk for untoward intracranial pressure (ICP) elevation from small rises in intracranial volume. The authors sought to develop an easily used method that accounts for the changing ICP that occurs over a cardiac cycle and to assess this method in a large-animal model over a broad range of ICPs.

METHODS

The authors used their previously described cardiac-gated intracranial balloon pump and swine model of cerebral edema. In the present experiment they measured elastance at 4 points along the cardiac cycle—early systole, peak systole, mid-diastole, and end diastole—by using rapid balloon inflation to 1 ml over an ICP range of 10–30 mm Hg.

RESULTS

The authors studied 7 swine with increasing cerebral edema. Intracranial elastance rose progressively with increasing ICP. Peak-systolic and end-diastolic elastance demonstrated the most consistent rise in elastance as ICP increased. Cardiac-gated elastance measurements had markedly lower variance within swine compared with non–cardiac-gated measures. The slope of the ICP–elastance curve differed between swine. At ICP between 20 and 25 mm Hg, elastance varied between 8.7 and 15.8 mm Hg/ml, indicating that ICP alone cannot accurately predict intracranial elastance.

CONCLUSIONS

Measuring intracranial elastance in a cardiac-gated manner is feasible and may offer an improved precision of measure. The authors’ preliminary data suggest that because elastance values may vary at similar ICP levels, ICP alone may not necessarily best reflect the state of intracranial volume reserve capacity. Paired ICP–elastance measurements may offer benefit as an adjunct “early warning monitor” alerting to the risk of untoward ICP elevation in brain-injured patients that is induced by small increases in intracranial volume.

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Amit Keret, Odeya Bennett-Back, Guy Rosenthal, Tal Gilboa, Moatasim Shweiki, Yigal Shoshan and Mony Benifla

OBJECTIVE

Posttraumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). The true incidence of PTE in children is still uncertain, because most research has been based primarily on adults. This study aimed to determine the true incidence of PTE in a pediatric population with mild TBI (MTBI) and to identify risk factors for the development of epileptic events.

METHODS

Data were collected from electronic medical records of children 0–17 years of age, who were admitted to a single medical center between 2007 and 2009 with a diagnosis of MTBI. This prospective research consisted of a telephone survey between 2015 and 2016 of children or their caregivers, querying for information about epileptic episodes and current seizure and neurological status. The primary outcome measure was the incidence of epilepsy following TBI, which was defined as ≥ 2 unprovoked seizure episodes. Posttraumatic seizure (PTS) was defined as a single, nonrecurrent convulsive episode that occurred > 24 hours following injury. Seizures within 24 hours of the injury were defined as immediate PTS.

RESULTS

Of 290 children eligible for this study, 191 of them or their caregivers were reached by telephone survey and were included in the analysis. Most injuries (80.6%) were due to falls. Six children had immediate PTS. All children underwent CT imaging; of them, 72.8% demonstrated fractures and 10.5% did not demonstrate acute findings. The mean follow-up was 7.4 years. Seven children (3.7%) experienced PTS; of them, 6 (85.7%) developed epilepsy and 3 (42.9%) developed intractable epilepsy. The overall incidence of epilepsy and intractable epilepsy in this cohort was 3.1% and 1.6%, respectively. None of the children who had immediate PTS developed epilepsy. Children who developed epilepsy spent an average of 2 extra days in the hospital at the time of the injury. The mean time between trauma and onset of seizures was 3.1 years. Immediate PTS was not correlated with PTE.

CONCLUSIONS

In this analysis of data from medical records and long-term follow-up, MTBI was found to confer increased risk for the development of PTE and intractable PTE, of 4.5 and 8 times higher, respectively. As has been established in adults, these findings confirm that MTBI increases the risk for PTE in the pediatric population.

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Gregory W. J. Hawryluk, Nicolas Phan, Adam R. Ferguson, Diane Morabito, Nikita Derugin, Campbell L. Stewart, M. Margaret Knudson, Geoffrey Manley and Guy Rosenthal

OBJECTIVE

The optimal site for placement of tissue oxygen probes following traumatic brain injury (TBI) remains unresolved. The authors used a previously described swine model of focal TBI and studied brain tissue oxygen tension (PbtO2) at the sites of contusion, proximal and distal to contusion, and in the contralateral hemisphere to determine the effect of probe location on PbtO2 and to assess the effects of physiological interventions on PbtO2 at these different sites.

METHODS

A controlled cortical impact device was used to generate a focal lesion in the right frontal lobe in 12 anesthetized swine. PbtO2 was measured using Licox brain tissue oxygen probes placed at the site of contusion, in pericontusional tissue (proximal probe), in the right parietal region (distal probe), and in the contralateral hemisphere. PbtO2 was measured during normoxia, hyperoxia, hypoventilation, and hyperventilation.

RESULTS

Physiological interventions led to expected changes, including a large increase in partial pressure of oxygen in arterial blood with hyperoxia, increased intracranial pressure (ICP) with hypoventilation, and decreased ICP with hyperventilation. Importantly, PbtO2 decreased substantially with proximity to the focal injury (contusion and proximal probes), and this difference was maintained at different levels of fraction of inspired oxygen and partial pressure of carbon dioxide in arterial blood. In the distal and contralateral probes, hypoventilation and hyperventilation were associated with expected increased and decreased PbtO2 values, respectively. However, in the contusion and proximal probes, these effects were diminished, consistent with loss of cerebrovascular CO2 reactivity at and near the injury site. Similarly, hyperoxia led to the expected rise in PbtO2 only in the distal and contralateral probes, with little or no effect in the proximal and contusion probes, respectively.

CONCLUSIONS

PbtO2 measurements are strongly influenced by the distance from the site of focal injury. Physiological alterations, including hyperoxia, hyperventilation, and hypoventilation substantially affect PbtO2 values distal to the site of injury but have little effect in and around the site of contusion. Clinical interpretations of brain tissue oxygen measurements should take into account the spatial relation of probe position to the site of injury. The decision of where to place a brain tissue oxygen probe in TBI patients should also take these factors into consideration.

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Guy Rosenthal, J. Claude Hemphill III, Marco Sorani, Christine Martin, Diane Morabito, Michele Meeker, Vincent Wang and Geoffrey T. Manley

Object

Previous studies have demonstrated that periods of low brain tissue oxygen tension (PbtO2) are associated with poor outcome after head trauma but have primarily focused on cerebral and hemodynamic factors as causes of low PbtO2. The purpose of this study was to investigate the influence of lung function on PbtO2 with an oxygen challenge (increase in fraction of inspired oxygen [FiO2] concentration to 1.0).

Methods

This prospective observational cohort study was performed in the neurointensive care unit of the Level 1 trauma center at San Francisco General Hospital. Thirty-seven patients with severe traumatic brain injury (TBI) undergoing brain tissue oxygen monitoring as part of regular care underwent an oxygen challenge, consisting of an increase in FiO2 concentration from baseline to 1.0 for 20 minutes. Partial pressure of arterial oxygen (PaO2), PbtO2, and the ratio of PaO2 to FiO2 (the PF ratio) were determined before and after oxygen challenge.

Results

Patients with higher PF ratios achieved greater PbtO2 during oxygen challenge than those with a low PF ratio because they achieved a higher PaO2 after an oxygen challenge. Lung function, specifically the PF ratio, is a major determinant of the maximal PbtO2 attained during an oxygen challenge.

Conclusions

Given that patients with TBI are at risk for pulmonary complications such as pneumonia, severe atelectasis, and adult respiratory distress syndrome, lung function must be considered when interpreting brain tissue oxygenation.

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Guy Rosenthal, Diane Morabito, Mitchell Cohen, Annina Roeytenberg, Nikita Derugin, S. Scott Panter, M. Margaret Knudson and Geoffrey Manley

Object

Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study.

Methods

Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration.

Results

Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine.

Conclusions

The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

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Guy Rosenthal, Rene O. Sanchez-Mejia, Nicolas Phan, J. Claude Hemphill III, Christine Martin and Geoffrey T. Manley

Object

Cerebral autoregulation may be altered after traumatic brain injury (TBI). Recent evidence suggests that patients' autoregulatory status following severe TBI may influence cerebral perfusion pressure management. The authors evaluated the utility of incorporating a recently upgraded parenchymal thermal diffusion probe for the measurement of cerebral blood flow (CBF) in the neurointensive care unit for assessing cerebral autoregulation and vasoreactivity at bedside.

Methods

The authors evaluated 20 patients with severe TBI admitted to San Francisco General Hospital who underwent advanced neuromonitoring. Patients had a parenchymal thermal diffusion probe placed for continuous bedside monitoring of local CBF (locCBF) in addition to the standard intracranial pressure and brain tissue oxygen tension (PbtO2) monitoring. The CBF probes were placed in the white matter using a separate cranial bolt. A pressure challenge, whereby mean arterial pressure (MAP) was increased by about 10 mm Hg, was performed in all patients to assess autoregulation. Cerebral CO2 vasoreactivity was assessed with a hyperventilation challenge. Local cerebral vascular resistance (locCVR) was calculated by dividing cerebral perfusion pressure by locCBF. Local cerebral vascular resistance normalized to baseline (locCVRnormalized) was also calculated for the MAP and hyperventilation challenges.

Results

In all cases, bedside measurement of locCBF using a cranial bolt in patients with severe TBI resulted in correct placement in the white matter with a low rate of complications. Mean locCBF decreased substantially with hyperventilation challenge (−7 ± 8 ml/100 g/min, p = 0.0002) and increased slightly with MAP challenge (1 ± 7 ml/100 g/min, p = 0.17). Measurements of locCBF following MAP and hyperventilation challenges can be used to calculate locCVR. In 83% of cases, locCVR increased during a hyperventilation challenge (mean change +3.5 ± 3.8 mm Hg/ml/100 g/min, p = 0.0002), indicating preserved cerebral CO2 vasoreactivity. In contrast, we observed a more variable response of locCVR to MAP challenge, with increased locCVR in only 53% of cases during a MAP challenge (mean change −0.17 ± 3.9 mm Hg/ml/100 g/min, p = 0.64) indicating that in many cases autoregulation was impaired following severe TBI.

Conclusions

Use of the Hemedex thermal diffusion probe appears to be a safe and feasible method that enables continuous monitoring of CBF at the bedside. Cerebral autoregulation and CO2 vasoreactivity can be assessed in patients with severe TBI using the CBF probe by calculating locCVR in response to MAP and hyperventilation challenges. Determining whether CVR increases or decreases with a MAP challenge (locCVRnormalized) may be a simple provocative test to determine patients' autoregulatory status following severe TBI and helping to optimize CPP management.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010