The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.
Nicholas C. Bambakidis, Nicholas Theodore, Peter Nakaji, Adrian Harvey, Volker K. H. Sonntag, Mark C. Preul and Robert H. Miller
Andreas Raabe, Peter Nakaji, Jürgen Beck, Louis J. Kim, Frank P. K. Hsu, Jonathan D. Kamerman, Volker Seifert and Robert F. Spetzler
Object. The authors prospectively compared a new technique of surgical microscope-based indocyanine green (ICG) videoangiography with intraoperative or postoperative digital subtraction (DS) angiography.
Method. The technique was performed during 187 surgical procedures in which 124 aneurysms in 114 patients were clipped. Using a newly developed setup, the ICG technique has been integrated into an operating microscope (Carl Zeiss Co., Oberkochen, Germany). A microscope-integrated light source containing infrared excitation light illuminates the operating field. The dye is injected intravenously into the patient, and intravascular fluorescence from within the blood vessels is imaged using a video camera attached to the microscope. The patency of parent, branching, and perforating arteries and documentation of clip occlusion of the aneurysm as shown by ICG videoangiography were compared with intraoperative or postoperative findings on DS angiography.
The results of ICG videoangiography corresponded with intra- or postoperative DS angiography in 90% of cases. The ICG technique missed mild but hemodynamically irrelevant stenosis that was evident on DS angiography in 7.3% of cases. The ICG technique missed angiographically relevant findings in three cases (one hemodynamically relevant stenosis and two residual aneurysm necks [2.7% of cases]). In two cases the missed findings were clinically and surgically inconsequential; in the third case, a 4-mm residual neck may require a second procedure. Indocyanine green videoangiography provided significant information for the surgeon in 9% of cases, most of which led to clip correction.
Conclusions. Microscope-based ICG videoangiography is simple and provides real-time information about the patency of vessels of all sizes and about the aneurysm sac. This technique may be useful during routine aneurysm surgery as an independent form of angiography or as an adjunct to intra- or postoperative DS angiography.
Implications of his work for the understanding of cerebrovascular pathology and stroke
Sam Safavi-Abbasi, Cassius Reis, Melanie C. Talley, Nicholas Theodore, Peter Nakaji, Robert F. Spetzler and Mark C. Preul
✓ The history of apoplexy and descriptions of stroke symptoms date back to ancient times. It was not until the mid-nineteenth century, however, that the contributions of Rudolf Ludwig Karl Virchow, including his descriptions of the phenomena he called “embolism” and “thrombosis” as well as the origins of ischemia, changed the understanding of stroke. He suggested three main factors that conduce to venous thrombosis, which are now known as the Virchow triad. He also showed that portions of what he called a “thrombus” could detach and form an “embolus.” Thus, Virchow coined these terms to describe the pathogenesis of the disorder. It was also not until 1863 that Virchow recognized and differentiated almost all of the common types of intracranial malformations: telangiectatic venous malformations, arterial malformations, arteriovenous malformations, cystic angiomas (possibly what are now called hemangioblastomas), and transitional types of these lesions. This article is a review of the contributions of Rudolf Virchow to the current understanding of cerebrovascular pathology, and a summary of the life of this extraordinary personality in his many roles as physician, pathologist, anthropologist, ethnologist, and politician.
Pankaj A. Gore, Peter Nakaji, Vivek Deshmukh and Harold L. Rekate
✓ Simultaneous endoscopic and microsurgical (synchronous) approaches represent a new paradigm in the treatment of complex ventricular lesions. This technique is well suited for lesions that involve multiple ventricular or cisternal compartments, have a nonlinear axis, or adhere to critical anatomical or neurovascular structures. Two distinct operative corridors, one endoscopic and the other microsurgical, are used during synchronous approaches to address such lesions, increasing the likelihood of a safe and complete resection.
The authors present the cases of two children and an adult treated via synchronous approaches. All patients had multi-compartmental lesions involving the ventricles and/or cisterns. One patient presented with a suprasellar Rathke cyst with a significant third ventricular component, one with a hypothalamic hamartoma having a substantial cisternal component, and the remaining patient with a choroid plexus papilloma in the left lateral ventricle that extended from midbody to the temporal horn.
In the cases of the Rathke cyst and the hamartoma, debulking in the third ventricle and controlled detachment of the lesion from the hypothalamus were undertaken using endoscopy, and simultaneous resection of the suprasellar component was performed through a subfrontal craniotomy. In the case of the choroid plexus papilloma, selective cautery of the choroidal feeding vessels and detachment from the temporal tela choroidea were performed using endoscopy, and the tumor from the ventricular body to the atrium was resected via a craniotomy. In each case the resection concluded with the intersection of endoscopic and microsurgical fields. All three patients had good outcomes.
Endoscopic and microsurgical approaches can be used concurrently to treat multicompartment ventricular and/or cisternal lesions with good results. The probable advantages of this method are more complete resection and improved safety.
Andrew S. Little, John F. Kerrigan, Cameron G. McDougall, Joseph M. Zabramski, Felipe C. Albuquerque, Peter Nakaji and Robert F. Spetzler
Nonconvulsive status epilepticus (NCSE) is an underrecognized and poorly understood complication of aneurysmal subarachnoid hemorrhage (SAH). The authors evaluated the risk factors, electroencephalographic (EEG) characteristics, hospital course, and clinical outcomes associated with NCSE in a population with SAH treated at a single institution.
The hospitalization and outcome data were reviewed in 11 patients who had received a diagnosis of NCSE and SAH. The study included individuals from a cohort of 389 consecutive patients with SAH who were treated between March 2003 and June 2005, and who were analyzed retrospectively. The patients' medical history, neurological grade, events of hospitalization, EEG morphological patterns, and disposition were analyzed.
Advanced age, female sex, need for ventriculostomy, poor neurological grade (Hunt and Hess Grade III, IV, or V), thick cisternal blood clots, and structural lesions (intracerebral hemorrhage and stroke) were common in the population with NCSE. Patients with normal results on angiograms, good neurological grade (Hunt and Hess Grade I or II), and minimal SAH (Fisher Grade 1 or 2) were at lower risk. The most common ictal patterns were intermittent, and consisted of generalized periodic epileptiform discharges. Medical complications were also frequent, and the outcome of these patients was poor despite aggressive treatment regimens.
Nonconvulsive status epilepticus is a devastating complication of SAH with a high rate of associated morbidity. Based on these findings it appears that the patients at highest risk for NCSE can be identified, and this should provide a basis for further studies designed to determine the clinical significance of various EEG patterns and to develop preventative strategies.
L. Fernando Gonzalez, Dixie L. Patterson, Gregory P. Lekovic, Peter Nakaji and Robert F. Spetzler
The radial artery is a common conduit used for high-flow bypasses. Until now the radial artery has been harvested using a long incision in the forearm that follows the course of the artery. The authors present an endoscopic technique that has been used during coronary bypass surgery but is not yet widespread in the neurosurgical arena.
From October 2006 to October 2007, the authors used the radial artery as a graft in 6 patients during the treatment of complex cerebral aneurysms. The artery was harvested via an endoscopic technique.
The radial artery was exposed distally at the wrist. Using the VasoView vessel harvesting system, the endoscope was inserted into the arm. The radial artery was dissected from its surrounding tissues endoscopically. With direct current energy via the HemoPro device, the side branches were coagulated and cut. The artery was transected at the wrist, then retrieved through a counterincision at the proximal forearm.
There were no neurological or bleeding complications in the hand or forearm.
Endoscopic harvesting of the radial artery is feasible, faster, and produces a more aesthetically pleasing result than standard open harvesting. The learning curve associated with the endoscope can be overcome by practice on cadavers and by collaboration with a cardiac surgical team.
Pankaj A. Gore, Harvinder Maan, Steve Chang, Alan M. Pitt, Robert F. Spetzler and Peter Nakaji
Postsurgical pneumocephalus is an unavoidable sequela of craniotomy. Sufficiently large volumes of intracranial air can cause headaches, lethargy, and neurological deficits. Supplemental O2 to increase the rate of absorption of intracranial air is a common but unsubstantiated neurosurgical practice. To the authors' knowledge, this is the first prospective study to examine the efficacy of this therapy and its effect on the rate of pneumocephalus absorption.
Thirteen patients with postoperative pneumocephalus that was estimated to be ≥ 30 ml were alternately assigned to breathe 100% O2 using a nonrebreather mask (treatment group) or to breathe room air (control group) for 24 hours. Head computed tomography (CT) scans without contrast enhancement were obtained at the beginning and end of treatment or control therapy. A neuroradiologist blinded to the type of treatment used software to calculate the 3D volume of the pneumocephalus from the CT scans. The percentage of pneumocephalus absorption was calculated for each study participant.
There was no statistically significant difference between the treatment and control groups regarding the mean initial pneumocephalus volume or time interval between CT scans. There was a significant difference (p = 0.009) between the mean rate of pneumocephalus volume reduction in the treatment (65%) and control groups (31%) per 24 hours. No patient suffered adverse effects related to treatment.
Administration of postsurgical supplemental O2 through a nonrebreather mask significantly increases the absorption rate of postcraniotomy pneumocephalus as compared with breathing room air.
Report of 3 cases
Eric M. Horn, Peter Nakaji, Stephen W. Coons and Curtis A. Dickman
Spinal meningeal melanocytomas are rare lesions that are histologically benign and can behave aggressively, with local infiltration. The authors present their experience with intramedullary spinal cord melanocytomas consisting of 3 cases, which represents the second largest series in the literature. A retrospective chart review was performed following identification of all spinal melanocytomas treated at the author's institution, based on information obtained from a neuropathology database. The charts were reviewed for patient demographics, surgical procedure, clinical outcome, and long-term tumor progression. Three patients were identified in whom spinal melanocytoma had been diagnosed between 1989 and 2006. The patients' ages were 37, 37, and 48 years, and the location of their tumor was C1–3, T9–10, and T-12, respectively. All 3 had complete resection with no adjuvant radiotherapy during follow-up periods of 16, 38, and 185 months, respectively. One patient demonstrated a recurrence 29 months after resection and the other 2 patients have demonstrated asymptomatic recurrences on imaging studies obtained at 16 and 38 months following resection.
With these cases added to the available literature, the evidence strongly suggests that complete resection is the treatment of choice for spinal melanocytomas. Even with complete resection, recurrences are common and close follow-up is needed for the long term in these patients. Radiation therapy should be reserved for those cases in which complete resection is not possible or in which there is recurrence.
Nicholas C. Bambakidis, Eric M. Horn, Peter Nakaji, Nicholas Theodore, Elizabeth Bless, Tammy Dellovade, Chiyuan Ma, Xukui Wang, Mark C. Preul, Stephen W. Coons, Robert F. Spetzler and Volker K. H. Sonntag
Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration.
The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted.
Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means ± SDs, 46.9 ± 12.9 vs 20.9 ± 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups.
An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.