Ajith J. Thomas

Endoscopic reconstruction of the cranial base using a pedicled nasoseptal flap.

OBJECTIVE Reconstruction of the cranial base using vascularized tissue promotes rapid and complete healing, thus avoiding complications caused by persistent communication between the cranial cavity and the sinonasal tract. The Hadad-Bassagasteguy flap (HBF), a neurovascular pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery, seems to be advantageous for the reconstruction of the cranial base after endonasal cranial base surgery. METHODS We performed a retrospective review of patients who underwent endonasal cranial base surgery at the University of Pittsburgh Medical Center from January 30, 2006 to January 30, 2007, identifying patients who experienced reconstruction with a vascularized septal mucosal flap (HBF). We analyzed the demographic data, pathological characteristics, site and extent of resection, use of cerebrospinal fluid (CSF) diversion techniques, and outcome. RESULTS Seventy-five patients who underwent endonasal cranial base endoscopic surgery received repair with the HBF. In this population, we encountered eight postoperative CSF leaks (10.66%), all in patients who required intra-arachnoidal dissection. When we correct the statistical analysis to include only patients with intra- arachnoidal lesions, the postoperative CSF leak rate is 14.5% (eight of 55 patients). It is notable that six CSF (33%) leaks occurred in our first 25 repairs, whereas we encountered only two postoperative leaks (4%) in the last 50 patients. The corrected CSF leak rate, considering only intra-arachnoidal lesions, was two (5.4%) of 37 patients. This improvement in the CSF leak rate reflects our growing experience and comfort with this reconstructive technique. All of our failures could be matched to a specific technical mistake. In addition, we modified the flap-harvesting technique to allow for staged procedures and the removal of caudal lesions. These special circumstances require storage of the flap in the antrum during the removal of caudal lesions, and suturing of the flap in its original position for staged procedures. One patient experienced a posterior nose bleed from the posterior nasal artery. This was controlled with bipolar electrocautery, thereby preserving the flap blood supply. We encountered no infectious or wound complications in this series of patients. The donor site accumulates crusting, which requires debridement until mucosalization is complete; this usually occurs 6 to 12 weeks after surgery. CONCLUSION The HBF is a versatile and reliable reconstructive technique for repairing defects of the anterior, middle, clival, and parasellar cranial base. Its use has resulted in a significant decrease in our incidence of CSF leaks after endonasal cranial base surgery. Attention to technical details is of paramount importance to achieve the best outcomes.

Endoscopic endonasal resection of anterior cranial base meningiomas.

OBJECTIVE The endonasal route may be feasible for the resection of anterior cranial base tumors that abut the paranasal sinuses. There are several case reports and mixed case series discussing this approach. Other than pituitary adenomas, there is a lack of literature describing the outcomes of endonasal approaches for single-tumor types such as meningiomas. METHODS In this study, we describe our current endoscopic endonasal technique and demonstrate the feasibility of using it to access anterior cranial base meningiomas from the back wall of the frontal sinus to the sella and laterally to the region of the midorbit. After this discussion, which includes key technical considerations and nuances, we address safety and efficacy by reporting the outcomes of our early experience with endoscopic endonasal resection of 35 anterior cranial base meningiomas. RESULTS A total of 35 patients underwent endoscopic endonasal resection of anterior cranial base meningiomas from October 2002 to October 2005. Degree of resection by tumor location was as follows: 10 of the 12 (83%) patients with olfactory groove meningiomas planned for complete resection underwent gross total (seven of 12) or near-total (>95%) (three of 12) resection (67% of all 15 olfactory tumors); 12 of 13 patients (92%) with tuberculum meningiomas underwent gross (11 of 13) or near (>95%) (one of 13) total resection; five patients diagnosed with petroclival meningiomas had successful resection of the parasellar portion of their tumors with relief of visual symptoms (no patients underwent complete resection of their tumors via the endoscopic, endonasal approach); two giant petroclival meningiomas were debulked with 63 and 89% resection, respectively.All patients experienced resolution or improvement of visual symptoms. No patient experienced permanent worsening of vision after surgery. Only one (3%) patient without preoperative endocrine dysfunction experienced a new, permanent pituitary deficit, diabetes insipidus. One (3%) patient experienced a new neurological deficit after experiencing a hemorrhage 3 weeks after surgery. The postoperative cerebrospinal fluid leak rate was 40% (14 of 35) and varied by tumor location. All leaks were resolved without craniotomy. There were no cases of bacterial meningitis. One patient developed a superinfection of a sterile granuloma from a sinusitis 2 years after surgery. There were two cases of deep venous thrombosis and one pulmonary embolus. There were no operative or perioperative deaths. CONCLUSION Cranial base meningiomas can be successfully managed via a purely endoscopic endonasal approach with acceptable morbidity and mortality rates. The extent of resection is guided by patient factors and symptoms, not by approach. This series had a high cerebrospinal fluid leak rate. With the evolution of new reconstruction techniques, these rates have been substantially reduced.

Progesterone is neuroprotective after acute experimental spinal cord trauma in rats

STUDY DESIGN A standardized rat contusion model was used to test the hypothesis that progesterone significantly improves neurologic recovery after a spinal cord injury that results in incomplete paraplegia. OBJECTIVES To compare the effect of progesterone versus a variety of control agents to determine its effectiveness in promoting neurologic recovery after an incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA Progesterone is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous progesterone has been shown to improve neurologic function after focal cerebral ischemia and facilitates cognitive recovery after cortical contusion in rats. METHODS A standardized rat contusion model of spinal cord injury using the New York University impactor that resulted in rats with incomplete paraplegia was used. Forty mature male Sprague-Dawley rats were randomly assigned to four groups: laminectomy with sham contusion, laminectomy with contusion without pharmacologic treatment, laminectomy with contusion treated with dimethylsulfoxide and dissolved progesterone, and laminectomy with contusion treated with dimethylsulfoxide. Functional status was assessed weekly using the Basso-Beattie-Bresnehan (BBB) locomotor rating scale for 6 weeks, after which the animals were killed for histologic studies. RESULTS Rats treated with progesterone had better outcomes (P = 0.0017; P = 0.0172) with a BBB score of 15.5, compared with 10.0 in the dimethylsulfoxide control group and 12.0 in the spinal cord contusion without pharmacologic intervention group. This was corroborated in histologic analysis by relative sparing of white matter tissue at the epicenter of the injury in the progesterone-treated group (P < 0.05). CONCLUSIONS Rats treated with progesterone had a better clinical and histologic outcome compared with the various control groups. These results indicate potential therapeutic properties of progesterone in the management of acute spinal cord injury.

Atraumatic convexal subarachnoid hemorrhage Clinical presentation, imaging patterns, and etiologies

Objective: To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage. Methods: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases–9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed. Results: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients ≤60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. Conclusion: Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.

Safety, Feasibility, and Short-Term Follow-Up of Drug-Eluting Stent Placement in the Intracranial and Extracranial Circulation

Background and Purpose— The use of bare metal stents to treat symptomatic intracranial stenosis may be associated with significant restenosis rates. The advent of drug-eluting stents (DESs) in the coronary circulation has resulted in a reduction of restenosis rates. We report our technical success rate and short-term restenosis rates after stenting with DESs in the intracranial and extracranial circulation. Methods— This study was a retrospective review of the period between April 1, 2004, and April 15, 2006, of 59 patients with 62 symptomatic intracranial or extracranial atherosclerotic lesions at 2 medical centers (University of Pittsburgh and Borgess Medical Center). Results— The mean age of our cohort was 61±12 years. The location of the 62 lesions was as follows: extracranial vertebral artery 31 (50%), intracranial vertebral artery or basilar artery 18 (29%), extracranial internal carotid artery (ICA) near the petrous bone 5 (8%), and intracranial ICA 8 (13%). There were 2 (3%) periprocedural complications: 1 non—flow-limiting dissection and 1 disabling stroke. Fifty vessels were available for follow-up angiography or computed tomography angiography at a median time of 4.0±2 months. A total of 2 of 36 extracranial stents (7%) and 1 of 26 intracranial stents (5%) were found to have restenosis ≥50% at follow-up. Conclusions— This report demonstrates that DES delivery in the intracranial and extracranial circulation is technically feasible. A small percentage of patients developed short-term in-stent restenosis. Longer-term follow-up is required in the setting of a prospective study to determine the late restenosis rates for DESs in comparison with bare metal stents.

Endoscopic Endonasal Pituitary Transposition for a Transdorsum Sellae Approach to the Interpeduncular Cistern

OBJECTIVE The interpeduncular cistern, including the retroinfundibular area, is one of the most challenging regions to approach surgically. The pituitary gland and the infundibulum guard the region when an endonasal route is undertaken. Superior transposition of the pituitary gland and infundibulum is described as a functional means to access this complex region through a fully endoscopic, completely transnasal route. METHODs Ten consecutive patients in whom a pituitary transposition was performed during an expanded endonasal approach at the University of Pittsburgh Medical Center for resection of retroinfundibular lesions were reviewed. The series consisted of seven men and three women with a mean age of 44.4 years. Pathology consisted of four craniopharyngiomas, four chordomas, and two petroclival meningiomas. RESULTS Five patients (50%) underwent total resection of the tumor, three patients (30%) underwent near total resection (>95% removal), and two patients (20%) had partial resection of petroclival meningiomas with the goal of optic apparatus decompression. All four patients with visual deficits recovered their vision completely. There was no neurological deterioration. Eight patients had normal pituitary function preoperatively, seven of whom (87.5%) had confirmed function preservation postoperatively, with one of these patients experiencing transient diabetes insipidus. The remaining patient with a hypothalamic craniopharyngioma underwent complete resection with obligatory panhypopituitarism and diabetes insipidus. CONCLUSION Endoscopic endonasal transposition of the pituitary gland and its stalk can provide a valuable corridor to the retroinfundibular space and interpeduncular cistern with pituitary function preservation in the majority of patients. This approach should only be pursued once significant experience with endoscopic endonasal approaches has been acquired.

Mechanical Approaches Combined With Intra-Arterial Pharmacological Therapy Are Associated With Higher Recanalization Rates Than Either Intervention Alone in Revascularization of Acute Carotid Terminus Occlusion

Background and Purpose— Acute stroke attributable to internal carotid artery terminus occlusion carries a poor prognosis. Vessel recanalization is crucial to improve clinical outcome. Historically, pharmacological thrombolysis alone has low recanalization rates. We sought to determine whether adjunctive mechanical approaches achieve better vessel recanalization and functional outcome. Methods— We retrospectively reviewed 75 consecutive endovascular cases of acute internal carotid artery terminus occlusions treated at our center between 1998 and 2008. Mechanical approaches (MERCI retrieval/angioplasty/stent) with and without adjunctive intra-arterial pharmacological therapy (urokinase or tissue plasminogen activator) was compared to intra-arterial lytics alone. Univariate and multivariate analyses were performed to determine predictors of recanalization (thrombolysis in myocardial infarction grades 2 to 3) and favorable functional outcome (modified Rankin score ≤2) at 3 months. Results— Lowest recanalization rates were observed with intra-arterial lytics alone (3/17, 17.6%). MERCI embolectomy combined with intra-arterial lytics was associated with the highest recanalization rates (18/21, 85.7%; P<0.0001). MERCI embolectomy alone achieved 46.2% recanalization rates (6/13; P=0.23). Angioplasty or stenting and intra-arterial lytics achieved 25% (2/8; P=0.65) and 40% (4/10; P=0.085) recanalization, respectively. In multivariate analysis, combination of MERCI embolectomy with intra-arterial lytics (OR, 16.2; CI, 4.6–77.6), or any mechanical technique with intra-arterial lytics (OR, 6.7; CI, 2.5–19.5) independently predicted thrombolysis in myocardial infarction 2 to 3 recanalization. Clinically significant parenchymal hemorrhage rates were 7.5% with combination (3/38) and 12.5% with pharmacological therapies (2/16; P=0.46). Using stepwise logistic regression, age (OR, 0.95; CI, 0.90–0.995), baseline NIHSS (OR, 0.82; CI, 0.70–0.96), and thrombolysis in myocardial infarction 2 to 3 recanalization (OR, 4.0; CI, 1.1–14.4) were associated with favorable functional outcome. Conclusions— Combined mechanical and intra-arterial pharmacological therapy is associated with higher recanalization rates than either intervention alone in acute internal carotid artery terminus occlusion revascularization.

Language hemispheric dominance in patients with congenital lesions of eloquent brain.

OBJECTIVEIn 90% of normal subjects, the left hemisphere is dominant for language function. We investigated whether congenital lesions of the left perisylvian regions altered cortical language representation in right-handed individuals. METHODSUsing functional magnetic resonance imaging, we studied language hemispheric dominance in five right-handed adult patients with congenitally acquired arteriovenous malformations (AVMs) originating from left hemispheric cortical language regions. The AVMs had not caused neurological symptoms during early development, but patients presented as adults with migraine, seizure, or minor hemorrhage. Results obtained from the AVM patients were contrasted to those from right-handed brain-injured stroke patients recovering from aphasia and to those from right-handed normal subjects. RESULTSDuring silent picture naming and verb generation tasks, cortical language networks lateralized primarily to the right hemisphere in the AVM group, compared with the left hemisphere in the normal group. This right hemisphere-shifted language network in the AVM group exceeded the shifts toward right hemispheric dominance found in the stroke group. CONCLUSIONPatients with AVMs affecting the left perisylvian regions recruited the right hemisphere into language processing networks during early development, presumably in response to congenitally aberrant circulation. This early right hemisphere recruitment in the AVM patients exceeded the similar process in the brains of stroke patients whose left cortical language networks were damaged in adulthood. Our data provide evidence of effective plasticity in the developing human brain compared with the mature brain response to injury. Knowledge of cortical language representation should assist presurgical planning in patients with developmental anomalies affecting apparently language-dominant brain regions.

Factors Predicting Hemorrhagic Complications after Multimodal Reperfusion Therapy for Acute Ischemic Stroke

BACKGROUND AND PURPOSE: We sought to find predictors for hemorrhagic complications in patients with acute ischemic stroke treated with multimodal endovascular therapy. MATERIALS AND METHODS: We retrospectively reviewed patients with acute ischemic stroke treated with multimodal endovascular therapy from May 1999 to March 2006. We reviewed clinical and angiographic data, admission CT Alberta Stroke Programme Early CT Score (ASPECTS), and the therapeutic endovascular interventions used. Posttreatment CT scans were reviewed for the presence of a parenchymal hematoma or hemorrhagic infarction based on defined criteria. Predictors for these types of hemorrhages were determined by logistic regression analysis. RESULTS: We identified 185 patients with a mean age of 65 ± 13 years and mean National Institutes of Health Stroke Scale score of 17 ± 4. Sixty-nine patients (37%) developed postprocedural hemorrhages: 24 (13%) parenchymal hematomas and 45 (24%) hemorrhagic infarctions. Patients with tandem occlusions (odds ratio [OR] 4.6 [1.4–6.5], P < .016), hyperglycemia (OR 2.8 [1.1–7.7], P < .043), or treated concomitantly with intravenous (IV) tissue plasminogen activator (tPA) and intra-arterial (IA) urokinase (OR 5.1 [1.1–25.0], P < .041) were at a significant risk for a parenchymal hematoma. Hemorrhagic infarction occurred significantly more in patients presenting with an ASPECTS ≤7 (OR 1.9 [1.3–2.7], P < .01). CONCLUSIONS: Hemorrhagic infarctions are related to the extent of infarct based on presentation CT, whereas parenchymal hematomas are associated with the presence of tandem occlusions, hyperglycemia, and treatment with both IV tPA and IA urokinase in patients with acute stroke treated with multimodal endovascular therapy.

Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms.