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Francisco A. Ponce, Robert F. Spetzler, Patrick P. Han, Scott D. Wait, Brendan D. Killory, Peter Nakaji, and Joseph M. Zabramski

Object

The aim of this study was to clarify the surgical indications, risks, and long-term clinical outcomes associated with the use of deep hypothermic circulatory arrest for the surgical treatment of intracranial aneurysms.

Methods

The authors retrospectively reviewed 105 deep hypothermic circulatory arrest procedures performed in 103 patients (64 females and 39 males, with a mean age of 44.8 years) to treat 104 separate aneurysms. Patients' clinical histories, radiographs, and operative reports were evaluated. There were 97 posterior circulation aneurysms: at the basilar apex in 60 patients, midbasilar artery in 21, vertebrobasilar junction in 11, superior cerebellar artery in 4, and posterior cerebral artery in 1. Seven patients harbored anterior circulation aneurysms. Two additional patients harbored nonaneurysmal lesions.

Results

Perioperatively, 14 patients (14%) died. Five patients (5%) were lost to late follow-up. At a mean long-term follow-up of 9.7 years, 65 patients (63%) had the same or a better status after surgical intervention, 10 (10%) were worse, and 9 (9%) had died. There were 19 cases (18%) of permanent or severe complications. The combined rate of permanent treatment-related morbidity and mortality was 32%. The mean late follow-up Glasgow Outcome Scale score was 4, and the annual hemorrhage rate after microsurgical clipping during cardiac standstill was 0.5%/year. Ninety-two percent of patients required no further treatment of their aneurysm at the long-term follow-up.

Conclusions

Cardiac standstill remains an important treatment option for a small subset of complex and giant posterior circulation aneurysms. Compared with the natural history of the disease, the risk associated with this procedure is acceptable.

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Scott D. Wait, Adib A. Abla, Brendan D. Killory, Peter Nakaji, and Harold L. Rekate

Object

Hypothalamic hamartomas (HHs) are devastating lesions causing refractory epilepsy, rage attacks, social ineptitude, and precocious puberty. Microsurgical and/or endoscopic resection offers an excellent risk/benefit profile for cure or improvement of epilepsy.

Methods

The authors reviewed a prospective database maintained during the first 7 years of the Barrow Hypothalamic Hamartoma program. They describe and illustrate their surgical methods, and they review data from several previous publications regarding surgical outcome.

Results

To date, the authors have performed surgery in 165 patients for symptomatic HHs. Patients underwent an endoscopic, transcallosal, or skull base approach, or multiple approaches. Twenty-six patients (15.8%) required more than 1 treatment for their HH.

Conclusions

Microsurgical and endoscopic resection of symptomatic HHs are technically demanding but can be performed safely with excellent results and an acceptable risk profile. Meticulous attention to the subtleties of surgical management helps optimize outcomes.

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Scott D. Wait, Adib A. Abla, Brendan D. Killory, Robert M. Starke, Robert F. Spetzler, and Peter Nakaji

Object

Many patients undergoing carotid endarterectomy (CEA) regularly take clopidogrel, a permanent platelet inhibitor. The authors sought to determine whether taking clopidogrel in the period before CEA leads to more bleeding or other complications.

Methods

The authors performed a retrospective, institutional review board–approved review of 182 consecutive patients who underwent CEA. Clinical, radiographic, and surgical data were gleaned from hospital and clinic records. Analysis was based on the presence or absence of clopidogrel in patients undergoing CEA and was performed twice by considering clopidogrel use within 8 days and within 5 days of surgery to define the groups.

Results

Taking clopidogrel within 8 days before surgery resulted in no statistical increase in any measure of morbidity or death. Taking clopidogrel within 5 days was associated with a small but significant increase in operative blood loss and conservatively managed postoperative neck swelling. No measure of permanent morbidity or death was increased in either clopidogrel group.

Conclusions

Findings in this study support the safety of preoperative clopidogrel in patients undergoing CEA.

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Jay D. Turner, Richard Williamson, Kaith K. Almefty, Peter Nakaji, Randall Porter, Victor Tse, and M. Yashar S. Kalani

MicroRNAs (miRNAs) are now recognized as the primary RNAs involved in the purposeful silencing of the cell's own message. In addition to the established role of miRNAs as developmental regulators of normal cellular function, they have recently been shown to be important players in pathological states such as cancer. The authors review the literature on the role of miRNAs in the formation and propagation of gliomas and medulloblastomas, highlighting the potential of these molecules and their inhibitors as therapeutics.

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Pakrit Jittapiromsak, Pushpa Deshmukh, Peter Nakaji, Robert F. Spetzler, and Mark C. Preul

Object

The standard superior craniotomy approach through the orbital roof is obstructed by numerous muscles, nerves, and vessels. Accessing the medial intraconal space also involves considerable brain retraction. The authors present a modified approach through the frontal sinus that overcomes these limitations.

Methods

Seven fixed silicone-injected cadaveric specimens were dissected bilaterally. In addition to the superior orbital wall, the ethmoidal sinuses and medial orbital wall were removed. The anatomical relationships between the major neurovascular complexes in the medial intraconal space and the optic nerve were observed.

Results

Intraconally, working space was created both in a “superior window” between the superior oblique and levator palpebrae muscle and in a “medial window” between the superior oblique and medial rectus muscle. The superior window mainly created an ipsilateral trajectory to the deep target. The medial window, which created a contralateral trajectory, provided a more inferior view of the medial intraconal space. Removal of the medial orbital wall further widened the exposure obtained from the superior window. The combination of these working windows makes the medial surface of the optic nerve available for exploration from multiple angles. Most of the major neurovascular complexes of the posterior orbit can be retracted safely without impinging on the optic nerve.

Conclusions

This novel extradural transfrontoethmoidal approach affords a direct view to the medial posterior orbit without major conflicts with intraconal neurovascular structures and requires minimal brain manipulation. The approach appears to offer advantages for medially located intraconal lesions.

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Matthew Quigley

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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.

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Pankaj A. Gore, Harvinder Maan, Steve Chang, Alan M. Pitt, Robert F. Spetzler, and Peter Nakaji

Object

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.

Methods

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.

Results

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.

Conclusions

Administration of postsurgical supplemental O2 through a nonrebreather mask significantly increases the absorption rate of postcraniotomy pneumocephalus as compared with breathing room air.