✓Discovery that the Schwann cell is the primary cell type responsible for both the neurofibroma as well as the schwannoma has proven to represent a crucial milestone in understanding the pathogenesis of peripheral nerve tumor development. This information and related findings have served as a nidus for research aimed at more fully characterizing this family of conditions. Recent discoveries in the laboratory have clarified an understanding of the molecular mechanisms underlying the pathogenesis of benign peripheral nerve tumors. Similarly, the mechanisms whereby idiopathic and syndromic (NF1- and NF2-associated) nerve sheath tumors progress to malignancy are being elucidated. This detailed understanding of the molecular pathogenesis of peripheral nerve tumors provides the information necessary to create a new generation of therapies tailored specifically to the prevention, cessation, or reversal of pathological conditions at the fundamental level of dysfunction. The authors review the data that have helped to elucidate the molecular pathogenesis of this category of conditions, explore the current progress toward exploitation of these findings, and discuss potential therapeutic avenues for future research.
Experimental therapeutic approaches to peripheral nerve tumors
Jonathan Riley, Alejandro Spiotta, and Nicholas Boulis
Difficulties with the neurological assessment of humans following a chimpanzee attack
Amer Khalil, Alejandro M. Spiotta, and Gene H. Barnett
Chimpanzee attacks can be vicious, mutilating, and disabling if not fatal. Stereotypically, the hands and face are targeted, and in male victims, genitalia are mutilated. The authors present a case highlighting the difficulties with early neurological assessment following such an attack. This 55-year-old woman was attacked by a 14-year-old chimpanzee. She suffered mutilation of both hands, severe midface bony, soft-tissue, and eye injuries, and scalp degloving. An emergency tracheotomy was performed at the scene, with an unclear duration of hypoxia. The patient was unresponsive without spontaneous movements, papillary or corneal reflexes, cough, or gag. Attempts to lighten sedation were not tolerated. Brain CTs were normal. Intracranial pressure monitoring was deemed infeasible. Brain MR imaging suggested diffuse axonal injury consistent with severe shaking trauma. Diffusion tensor imaging indicated intact corticospinal tracts, confirmed by somatosensory evoked potentials. Magnetic resonance imaging suggested left optic nerve transaction, and right retinal detachment was diagnosed. Electroencephalography showed severe diffuse encephalopathy. Auditory evoked potentials showed absent auditory pathway responses except for a right delayed wave V. Visual evoked potentials indicated absent visual function. At 1 month after the attack, sedation and analgesia weaning revealed lower-extremity movement to command, but no upper-limb response. Cervical spine and brachial plexus MR imaging showed brachial plexus edema. Two months after the attack, the patient regained strength in all her extremities and verbally communicated using a Passy-Muir tracheostomy valve. Chimpanzee attacks on humans can cause extensive, life-threatening injuries. The neurological assessment of such patients is challenging, complicated by limb and craniofacial disfigurement and the need for heavy sedation. Initial assessment of nervous system integrity may rely on costly imaging and electrophysiological studies.
“Y-stent retriever”: a new rescue technique for refractory large-vessel occlusions?
Roberto Crosa, Alejandro M. Spiotta, Matías Negrotto, Alejandra Jaume, and Walter Casagrande
Long-awaited positive trial data have shown the efficacy of endovascular treatment in patients with ischemic stroke who arrive at the hospital within the first 6 hours with large-vessel occlusion of the anterior circulation. With the introduction of stent retrievers (SRs) for mechanical thrombectomy, efficient and safe large-artery recanalization treatment can be achieved. However, sometimes there are patients who do not attain complete flow restoration following attempts with traditional maneuvers. The authors present the case of a 57-year-old man with acute ischemic stroke due to an M1 embolus that extended into both M2 trunks. This patient was successfully treated with an innovative technique in which a Solitaire SR (Covidien) and a Catch SR (Balt) were used in a “Y” configuration, for which the authors coined the term “Y-stent retriever.”
The shipboard Beirut terrorist bombing experience: a historical account and recommendations for preparedness in events of mass neurological injuries
Zachary S. Hubbard, Fraser Henderson Jr., Rocco A. Armonda, Alejandro M. Spiotta, Robert Rosenbaum, and Fraser Henderson Sr.
On a Sunday morning at 06:22 on October 23, 1983, in Beirut, Lebanon, a semitrailer filled with TNT sped through the guarded barrier into the ground floor of the Civilian Aviation Authority and exploded, killing and wounding US Marines from the 1st Battalion 8th Regiment (2nd Division), as well as the battalion surgeon and deployed corpsmen. The truck bomb explosion, estimated to be the equivalent of 21,000 lbs of TNT, and regarded as the largest nonnuclear explosion since World War II, caused what was then the most lethal single-day death toll for the US Marine Corps since the Battle of Iwo Jima in World War II. Considerable neurological injury resulted from the bombing. Of the 112 survivors, 37 had head injuries, 2 had spinal cord injuries, and 9 had peripheral nerve injuries. Concussion, scalp laceration, and skull fracture were the most common cranial injuries.
Within minutes of the explosion, the Commander Task Force 61/62 Mass Casualty Plan was implemented by personnel aboard the USS Iwo Jima. The wounded were triaged according to standard protocol at the time. Senator Humphreys, chairman of the Preparedness Committee and a corpsman in the Korean War, commented that he had never seen such a well-executed evolution. This was the result of meticulous preparation that included training not only of the medical personnel but also of volunteers from the ship’s company, frequent drilling with other shipboard units, coordination of resources throughout the ship, the presence of a meticulous senior enlisted man who carefully registered each of the wounded, the presence of trained security forces, and a drilled and functioning communication system.
Viewed through the lens of a neurosurgeon, the 1983 bombings and mass casualty event impart important lessons in preparedness. Medical personnel should be trained specifically to handle the kinds of injuries anticipated and should rehearse the mass casualty event on a regular basis using mock-up patients. Neurosurgery staff should participate in training and planning for events alongside other clinicians. Training of nurses, corpsmen, and also nonmedical personnel is essential. In a large-scale evolution, nonmedical personnel may monitor vital signs, work as scribes or stretcher bearers, and run messages. It is incumbent upon medical providers and neurosurgeons in particular to be aware of the potential for mass casualty events and to make necessary preparations.
Phanor L. Perot Jr.: South Carolina’s father of academic neurosurgery
Fraser Henderson Jr., Fraser Henderson Sr., Zachary Hubbard, David L. Semenoff, Alejandro M. Spiotta, and Sunil J. Patel
Phanor Leonidas Perot Jr., MD, PhD (1928–2011), was a gifted educator and pioneer of academic neurosurgery in South Carolina. As neurosurgical resident and then as a junior faculty member at the Montreal Neurological Institute, he advanced understandings of both epilepsy and spinal cord injury under Wilder Penfield, William Cone, and Theodore Rasmussen. In 1968, he moved to Charleston to lead neurosurgery. From his time spent with master physicians such as Isidor Ravdin and Wilder Penfield, Perot himself became “the ultimate teacher." His research spanned the fields of epilepsy to torticollis to spinal trauma, focusing the most on the basic pathophysiology of spinal cord damage elucidated through somatosensory evoked potentials. His research was distinguished by generous grant funding. By the time he stepped down as chairman in 1997, the division of neurosurgery had become a department and he had served as president of the American Academy of Neurological Surgery and the Society of Neurological Surgeons. Perot taught prolifically at the bedside, and considered the residency program at the Medical University of South Carolina his greatest achievement. Although Dr. Perot never fully retired, he also enjoyed active hobbies of fly-fishing, traveling, and hunting, until his death on February 2, 2011. He influenced many and earned his role in history as the father of academic neurosurgery in South Carolina.
Brain oxygen tension and outcome in patients with aneurysmal subarachnoid hemorrhage
Rohan Ramakrishna, Michael Stiefel, Joshua Udoetuk, Alejandro Spiotta, Joshua M. Levine, W. Andrew Kofke, Eric Zager, Wei Yang, and Peter Le Roux
Brain oxygen tension and outcome in patients with aneurysmal subarachnoid hemorrhage
Rohan Ramakrishna, Michael Stiefel, Joshua Udoteuk, Alejandro Spiotta, Joshua M. Levine, W. Andrew Kofke, Eric Zager, Wei Yang, and Peter LeRoux
Poor outcome is common after aneurysmal subarachnoid hemorrhage (SAH). Clinical studies suggest that cerebral hypoxia after traumatic brain injury is associated with poor outcome. In this study we examined the relationship between brain oxygen tension (PbtO2) and death after aneurysmal SAH.
Forty-six patients, including 34 women and 12 men (Glasgow Coma Scale Score ≤ 8 and median age 58.5 years) who underwent PbtO2 monitoring were studied prospectively during a 2-year period in a neurosurgical intensive care unit at a University Level I Trauma Center. Brain oxygen tension, intracranial pressure (ICP), mean arterial pressure, cerebral perfusion pressure (CPP), and brain temperature were continuously monitored, and treatment was directed toward ICP, CPP, and PbtO2 targets. The relationship between PbtO2 and 1-month survival was examined.
Data were available from 5424 hours of PbtO2 monitoring. For the entire cohort the mean ICP, CPP, and PbtO2 were 13.85 ± 2.40, 84.05 ± 3.41, and 30.79 ± 1.91 mm Hg, respectively. Twenty-five patients died (54%). The mean daily PbtO2 was higher in survivors than nonsurvivors (33.94 ± 2.74 vs 28.14 ± 2.59 mm Hg; p = 0.05). In addition, survivors had significantly shorter episodes of compromised PbtO2 (defined as 15–25 mm Hg) than nonsurvivors (125.85 ± 15.44 vs 271.14 ± 55.23 minutes; p < 0.01). Intracranial pressure was similar in survivors and nonsurvivors. In contrast, the average CPP was significantly lower in nonsurvivors than survivors (76.96 ± 5.50 vs 92.49 ± 2.75 mm Hg; p = 0.01). When PbtO2 was stratified according to CPP level, survivors had higher PbtO2 levels. Following logistic regression, the number of episodes of compromised PbtO2 (odds ratio 1.1, 95% confidence interval 1.003–1.2) and number of episodes of cerebral hypoxia (< 15 mm Hg; odds ratio 1.3, 95% confidence interval 1.0–1.7) were more frequent in those who died.
Patient deaths after SAH may be associated with a lower mean PbtO2 and longer periods of compromised cerebral oxygenation than in survivors. This knowledge may be used to help direct therapy.
Brain tissue oxygen–directed management and outcome in patients with severe traumatic brain injury
Alejandro M. Spiotta, Michael F. Stiefel, Vicente H. Gracias, Alicia M. Garuffe, W. Andrew Kofke, Eileen Maloney-Wilensky, Andrea B. Troxel, Joshua M. Levine, and Peter D. Le Roux
The object of this study was to determine whether brain tissue oxygen (PbtO2)–based therapy or intracranial pressure (ICP)/cerebral perfusion pressure (CPP)–based therapy is associated with improved patient outcome after severe traumatic brain injury (TBI).
Seventy patients with severe TBI (postresuscitation GCS score ≤ 8), admitted to a neurosurgical intensive care unit at a university-based Level I trauma center and tertiary care hospital and managed with an ICP and PbtO2 monitor (mean age 40 ± 19 years [SD]) were compared with 53 historical controls who received only an ICP monitor (mean age 43 ± 18 years). Therapy for both patient groups was aimed to maintain ICP < 20 mm Hg and CPP > 60 mm Hg. Patients with PbtO2 monitors also had therapy to maintain PbtO2 > 20 mm Hg.
Data were obtained from 12,148 hours of continuous ICP monitoring and 6,816 hours of continuous PbtO2 monitoring. The mean daily ICP and CPP and the frequency of elevated ICP (> 20 mm Hg) or suboptimal CPP (< 60 mm Hg) episodes were similar in each group. The mortality rate was significantly lower in patients who received PbtO2-directed care (25.7%) than in those who received conventional ICP and CPP–based therapy (45.3%, p < 0.05). Overall, 40% of patients receiving ICP/CPP–guided management and 64.3% of those receiving PbtO2–guided management had a favorable short-term outcome (p = 0.01). Among patients who received PbtO2-directed therapy, mortality was associated with lower mean daily PbtO2 (p < 0.05), longer durations of compromised brain oxygen (PbtO2 < 20 mm Hg, p = 0.013) and brain hypoxia (PbtO2 < 15 mm Hg, p = 0.001), more episodes and a longer cumulative duration of compromised PbtO2 (p < 0.001), and less successful treatment of compromised PbtO2 (p = 0.03).
These results suggest that PbtO2-based therapy, particularly when compromised PbtO2 can be corrected, may be associated with reduced patient mortality and improved patient outcome after severe TBI.
Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring
Michael F. Stiefel, Alejandro Spiotta, Vincent H. Gracias, Alicia M. Garuffe, Oscar Guillamondegui, Eileen Maloney-Wilensky, Stephanie Bloom, M. Sean Grady, and Peter D. LeRoux
Object. An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome.
Methods. Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 ± 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 ± 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05).
Conclusions. The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.
Conventional neurocritical care and cerebral oxygenation after traumatic brain injury
Michael F. Stiefel, Joshua D. Udoetuk, Alejandro M. Spiotta, Vicente H. Gracias, Aaron Goldberg, Eileen Maloney-Wilensky, Stephanie Bloom, and Peter D. Le Roux
Control of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is the foundation of traumatic brain injury (TBI) management. In this study, the authors examined whether conventional ICP- and CPP-guided neurocritical care ensures adequate brain tissue O2 in the first 6 hours after resuscitation.
Resuscitated patients with severe TBI (Glasgow Coma Scale score ≤ 8 and Injury Severity Scale score ≥ 16) who were admitted to a Level I trauma center and who underwent brain tissue O2 monitoring within 6 hours of injury were evaluated as part of a prospective observational database. Therapy was directed to maintain an ICP of 25 mm Hg or less and a CPP of 60 mm Hg or higher.
Data from a group of 25 patients that included 19 men and six women (mean age 39 ± 20 years) were examined. After resuscitation, ICP was 25 mm Hg or less in 84% and CPP was 60 mm Hg or greater in 88% of the patients. Brain O2 probes were allowed to stabilize; the initial brain tissue O2 level was 25 mm Hg or less in 68% of the patients, 20 mm Hg or less in 56%, and 10 mm Hg or less in 36%. Nearly one third (29%) of patients with ICP readings of 25 mm Hg or less and 27% with CPP levels of 60 mm Hg or greater had severe cerebral hypoxia (brain tissue O2 ≤10 mm Hg). Nineteen patients had both optimal ICP (≤25 mm Hg) and CPP (> 60 mm Hg); brain tissue O2 was 20 mm Hg or less in 47% and 10 mm Hg or less in 21% of these patients. The mortality rate was higher in patients with reduced brain tissue O2.
Brain resuscitation based on current neurocritical care standards (that is, control of ICP and CPP) does not prevent cerebral hypoxia in some patients. This finding may help explain why secondary neuronal injury occurs in some patients with adequate CPP and suggests that the definition of adequate brain resuscitation after TBI may need to be reconsidered.