Clinical outcomes and complications of eyelid versus eyebrow approaches to supraorbital craniotomy: systematic review and indirect meta-analysis.

OBJECTIVE: Eyebrow supraorbital craniotomy is a versatile keyhole technique for treating intracranial pathologies. The eyelid supraorbital approach, an alternative approach to an eyebrow supraorbital craniotomy, has not been widely adopted among most neurosurgeons. The purpose of this systematic review and meta-analysis was to perform a pooled analysis of the complications of eyebrow or eyelid approaches for the treatment of aneurysms, meningiomas, and orbital tumors. METHODS: A systematic review of the literature in the PubMed, Embase, and Cochrane Review databases was conducted for identifying relevant literature using keywords such as "supraorbital," "eyelid," "eyebrow," "tumor," and "aneurysm." Eyebrow supraorbital craniotomies with or without orbitotomies and eyelid supraorbital craniotomies with orbitotomies for the treatment of orbital tumors, intracranial meningiomas, and aneurysms were selected. The primary outcomes were overall complications, cosmetic complications, and residual aneurysms and tumors. Secondary outcomes included five complication domains: orbital, wound-related, scalp or facial, neurological, and other complications. RESULTS: One hundred three articles were included in the synthesis. The pooled numbers of patients in the eyebrow and eyelid groups were 4689 and 358, respectively. No differences were found in overall complications or cosmetic complications between the eyebrow and eyelid groups. The proportion of residuals in the eyelid group (11.21%, effect size [ES] 0.26, 95% CI 0.12-0.41) was significantly higher (p < 0.05) than that in the eyebrow group (6.17%, ES 0.10, 95% CI 0.08-0.13). A subgroup analysis demonstrated significantly higher incidences of orbital, wound-related, and scalp or facial complications in the eyelid group (p < 0.05), but higher other complications in the eyebrow group. Performing an orbitotomy substantially increased the complication risk. CONCLUSIONS: This is the first meta-analysis that quantitatively compared complications of eyebrow versus eyelid approaches to supraorbital craniotomy. This study found similar overall complication rates but higher rates of selected complication domains in the eyelid group. The literature is limited by a high degree of variability in the reported outcomes.

Relationship of Pressure Reactivity Index and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

AIM: Patients with aneurysmal subarachnoid hemorrhage (SAH) continue to have poor functional outcome due to the occurrence of delayed cerebral ischemia (DCI). Although vasospasm represents the primary therapeutic target for mitigating DCI, DCI occurs through multifocal etiologies that involve impaired cerebral autoregulation. Worse pressure reactivity index (PRx) values, which consists of a moving correlation coefficient between intracranial pressures and mean arterial pressures, have been shown to be associated with DCI in non-randomized clinical trials. RESULTS: We discuss two patients that presented with high-grade SAH and comatose exams. Patient one was a 34-year-old male diagnosed with SAH from a ruptured right middle cerebral artery aneurysm. He had intact PRx values (Mean: -0.07 during hospital days 9-19), while having severe, refractory vasospasm. At the conclusion of his hospitalization, he was functionally independent, had negligible DCI, and was successfully discharged home. Patient two was a 78-year-old female diagnosed with SAH from a ruptured anterior communicating artery aneurysm. She had an improving PRx ranging from -0.1 to 0.1 early in her hospitalization. However, upon developing severe vasospasm, her PRx increased to 0.6 (overall PRx from hospital days 4-16 was 0.3), and she suffered from extensive DCI in bilateral middle cerebral and anterior cerebral artery distributions that ultimately resulted in malignant cerebral edema and brain death. CONCLUSION: Cerebral autoregulation as measured by PRx may represent a viable target for neuroprognostication by evaluating DCI risk in patients with SAH who develop severe or refractory vasospasm. Further studies evaluating the role of cerebral autoregulation, PRx, and its pathophysiological role in DCI are warranted.

Decompressive hemicraniectomy and cranioplasty using subcutaneously preserved autologous bone flaps versus synthetic implants: perioperative outcomes and cost analysis.

OBJECTIVE: It has not been well-elucidated whether there are advantages to preserving bone flaps in abdominal subcutaneous (SQ) tissue after decompressive hemicraniectomy (DHC), compared to discarding bone flaps. The authors aimed to compare perioperative outcomes and costs for patients undergoing autologous cranioplasty (AC) after DHC with the bone flap preserved in abdominal SQ tissue, and for patients undergoing synthetic cranioplasty (SC). METHODS: A retrospective review was performed of all patients undergoing DHC procedures between January 2017 and July 2021 at two tertiary care institutions. Patients were divided into two groups: those with flaps preserved in SQ tissue (SQ group), and those with the flap discarded (discarded group). Additional analysis was performed between patients undergoing AC versus SC. Primary end points included postoperative and surgical site complications. Secondary endpoints included operative costs, length of stay, and blood loss. RESULTS: A total of 248 patients who underwent DHC were included in the study, with 155 patients (62.5%) in the SQ group and 93 (37.5%) in the discarded group. Patients in the discarded group were more likely to have a diagnosis of severe TBI (57.0%), while the most prevalent diagnosis in the SQ group was malignant stroke (35.5%, p < 0.05). There were 8 (5.2%) abdominal surgical site infections and 9 (5.8%) abdominal hematomas. The AC group had a significantly higher reoperation rate (23.2% vs 12.9%, p = 0.046), with 11% attributable to abdominal reoperations. The average cost of a reoperation for an abdominal complication was $40,408.75 ± $2273. When comparing the AC group to the SC group after cranioplasty, there were no significant differences in complications or surgical site infections. There were 6 cases of significant bone resorption requiring cement supplementation or discarding of the bone flap. Increased mean operative charges were found for the SC group compared to the AC group ($72,362 vs $59,726, p < 0.001). CONCLUSIONS: Autologous bone flaps may offer a cost-effective option compared to synthetic flaps. However, when preserved in abdominal SQ tissue, they pose the risk of resorption over time as well as abdominal surgical site complications with increased reoperation rates. Further studies and methodologies such as cryopreservation of the bone flap may be beneficial to reduce costs and eliminate complications associated with abdominal SQ storage.

Middle meningeal artery embolization with subdural evacuating port system for primary management of chronic subdural hematomas.

Optimal treatment for chronic subdural hematomas remains controversial and perioperative risks and comorbidities may affect management strategies. Minimally invasive procedures are emerging as alternatives to the standard operative treatments. We evaluate our experience with middle meningeal artery (MMA) embolization combined with Subdural Evacuating Port System (SEPS) placement as a first-line treatment for patients with cSDH. A single institution retrospective review was performed of all patients undergoing intervention. Patients were stratified by treatment with MMA embolization and SEPS placement, MMA embolization and surgery, SEPS placement only, and surgery only for cSDH from 2017 to 2020, and cohorts were compared against each other. Patients treated with MMA/SEPS were more likely to be older, be on anticoagulation, have significant comorbidities, have shorter length of stay, and less likely to have symptomatic recurrence compared to SEPS only cohort. Thus, MMA/SEPS appears to be a safe and equally effective minimally invasive treatment for cSDH patients with significant comorbidities who are poor surgical candidates.

Abnormal neurological pupil index is associated with malignant cerebral edema after mechanical thrombectomy in large vessel occlusion patients.

BACKGROUND AND OBJECTIVES: Malignant cerebral edema (MCE) is a feared complication in patients suffering from large vessel occlusion. Variables associated with the development of MCE have not been clearly elucidated. Use of pupillometry and the neurological pupil index (NPi) as an objective measure in patients undergoing mechanical thrombectomy (MT) has not been explored. We aim to evaluate variables significantly associated with MCE in patients that undergo MT and hypothesize that abnormal NPi is associated with MCE in this population. METHODS: A retrospective analysis of patients with acute ischemic stroke who had undergone MT at our institution between 2017 and 2020 was performed. Baseline and outcome variables were collected, including NPi values from pupillometry readings of patients within 72 h after the MT. Patients were divided into two groups: MCE versus non-MCE group. A univariate and multivariate analysis was performed. RESULTS: Of 284 acute ischemic stroke patients, 64 (22.5%) developed MCE. Mean admission glucose (137 vs. 173; p < 0.0001), NIHSS on admission (17 vs. 24; p < 0.01), infarct core volume (27.9 vs. 17.9 mL; p = 0.0036), TICI score (p = 0.001), and number of passes (2.9 vs. 1.8; p < 0.0001) were significantly different between the groups. Pupillometry data was present for 64 patients (22.5%). Upon multivariate analysis, abnormal ipsilateral NPi (OR 21.80 95% CI 3.32-286.4; p = 0.007) and hemorrhagic conversion were independently associated with MCE. CONCLUSION: Abnormal NPi and hemorrhagic conversion are significantly associated with MCE in patients following MT. Further investigation is warranted to better define an association between NPi and patient outcomes in this patient population.

Flow diversion radial artery bypass graft coupled with terminal basilar artery occlusion for the treatment of complex basilar apex aneurysms: operative nuances.

BACKGROUND: A subset of basilar apex aneurysms are unsuitable for either primary microsurgical clipping or endovascular coiling. These complex aneurysms can be treated by terminal basilar artery occlusion, but only if collateral circulation is adequate. To circumvent these complications, a high-flow vertebral artery-posterior cerebral artery or middle cerebral artery-posterior cerebral artery bypass may be performed to create an adequate collateral circulation to allow treatment of the aneurysm by basilar artery occlusion and/or clipping. OBJECTIVE: To discuss the operative nuances of this approach in the case of a 47-year-old man with progressive hemiparesis resulting from brainstem compression from a giant, unruptured basilar apex aneurysm with absent posterior communicating artery collaterals and incorporation of bilateral superior cerebellar arteries and posterior cerebral arteries within the aneurysm neck. METHODS: The patient underwent a staged bypass from V3 to P2 coupled with terminal basilar artery occlusion. RESULTS: The patient initially presented as modified Rankin Scale score 2 with right hemiparesis. The aneurysm ruptured after the first stage of the operation, and the patient underwent a V3 to P2 bypass the next day. His postprocedural neurologic decline improved at the 14-month follow-up to modified Rankin Scale score 2, with substantial reduction in aneurysm size observed at 9 months. The outcomes for 3 other bypass cases for basilar apex aneurysms are also summarized. CONCLUSION: : We discuss the indications, preoperative diagnostic workup, operative management, and postoperative outcomes in managing challenging basilar apex aneurysms. In our experience, high-flow bypass procedures with or without hunterian ligation in the treatment of these aneurysms are well tolerated with good long-term results.

Surgical resection of cavernous malformations of the brainstem: evolution of a minimally invasive technique.

OBJECTIVE: The purpose of this study is to provide an institutional retrospective review of surgically treated brainstem cavernous malformations. METHODS: Between 2005 and 2010, 22 consecutive patients with brainstem cavernous malformations (15 female and 7 male) with a mean age of 43 years underwent surgical treatment. Mean volume of the resected cavernous malformations was 0.65 cm(3). A minimally invasive resection technique was used for these cases, in conjunction with skull base approaches. RESULTS: The mean follow-up period was 26.6 months (range, 4-68 months). Of the 22 patients, 9% did not have clear evidence of hemorrhage at the time of presentation. Of the remainder, 22% had two or more instances of hemorrhage documented by magnetic resonance imaging. After resection and during follow-up, 54% of patients had an improvement in their modified Rankin scale, whereas 14% were worse compared with their preoperative presentation; 32% were unchanged and 9% of patients were found to have residual cavernoma post-surgery. CONCLUSION: Our longitudinal experience has guided us to emphasize minimally invasive approaches during resection of the brainstem cavernous malformations, occasionally at the expense of achieving a complete resection, to improve patient outcomes.

Endovascular treatment of intracranial aneurysms in Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by extensive arterial aneurysms. The successful clipping of intracranial aneurysms in patients with LDS has been reported in a limited number of patients but endovascular treatment of intracranial aneurysms in LDS has never before been described. The first successful cases of endovascular management of five intracranial aneurysms in two patients with LDS are reported. CLINICAL PRESENTATION: The first patient was an asymptomatic 45-year-old woman with LDS and two incidentally discovered, unruptured wide necked aneurysms (6×5 mm and 4×2 mm) arising from the ophthalmic segment of the left internal carotid artery. Both aneurysms were successfully embolized via Neuroform stent assisted coiling. The second patient was an asymptomatic middle 40s woman with LDS found to have an unruptured anterior communicating artery aneurysm (7×4 mm) as well as two ophthalmic segment aneurysms (2.5×3.7 mm and 2.9×3.5 mm). All three aneurysms were successfully embolized via Neuroform stent assisted coiling in two staged procedures. There were no periprocedural complications in either patient. Long term follow-up imaging demonstrated durable embolization in all aneurysms in both patients. CONCLUSION: This is the first reported case series of endovascular management of intracranial aneurysms in the setting of LDS. The endovascular approach was safe, effective and durable in all aneurysms in both patients, and should be considered when treating patients with LDS and intracranial aneurysms.

Balloon test occlusion with the Doppler velocity guidewire.

Transcranial Doppler ultrasonography is the most commonly used method of cerebrovascular blood flow velocity measurement, but it is subject to certain technical and anatomic limitations. The Doppler velocity guidewire measures blood flow velocity within any vessel during cerebral angiography, overcoming these limitations. We report the first use of this guidewire in the measurement of blood flow velocity during balloon test occlusion, with results similar to simultaneously measured transcranial Doppler ultrasonography. Velocity measurement by Doppler guidewire could be useful in balloon test occlusion for vertebrobasilar circulation, where transcranial Doppler ultrasonography is limited, and provide anatomically specific blood flow velocity measurements in the diagnosis and treatment of stroke and other cerebrovascular diseases.

Brainstem hypertrophy, acquired Chiari malformation, syringomyelia, and hydrocephalus: diagnostic dilemma.

This 18-year-old woman presented with symptoms of right upper-extremity ataxia and imaging evidence of syringomyelia and an acquired Chiari malformation after a previous suboccipital decompression for cerebellar hemorrhage. The patient underwent posterior fossa reexploration to detether any adhesions and release scar tissue in the fourth ventricular outlet. Her symptoms of syringomyelia resolved but she then developed symptoms of lethargy, confusion, and amnesia in addition to ataxia. Repeat neural axis imaging revealed resolution of the syrinx but prominent brainstem hypertrophy. Eventually, the placement of a ventriculoperitoneal shunt resulted in the resolution of both symptoms and brainstem hypertrophy. In the present article, the authors elaborate on this first reported case of a reversible brainstem hypertrophy responsive to CSF shunting.

Is postoperative CT scanning predictive of subdural electrode placement complications in pediatric epileptic patients?

AIMS: To understand the reliability of postoperative CT scans to predict the development of intracranial hemorrhagic complications associated with subdural electrode implants for monitoring intractable seizure, we reviewed the data of a consecutive series of children treated at our institution. METHODS: Forty children (mean age: 11.4 years) with subdural electrode implants were reviewed. The immediate postoperative CT scans were evaluated for the presence of hemorrhagic complications and/or brain swelling resulting in a midline shift. RESULTS: Twenty-six patients (65%) presented a postoperative midline shift (range = 2-10 mm; mean shift = 4.0 mm). Two children had a midline shift of >5 mm. Two patients with a shift of <5 mm at the first CT scan required a repeat craniotomy. These patients experienced worsening neurologic symptoms in a delayed fashion on postoperative days 1 and 4, respectively. This was correlated to an increase in midline shift of >5 mm. CONCLUSIONS: Subdural electrode implants in children are safe. The presence of a midline shift of <5 mm is common postoperatively. The presence and extension of the midline shift at the first CT scan does not seem to be predictive of the development of symptomatic complications with a mass effect. Complications happened in a delayed fashion.

Boost Gamma Knife surgery during multimodality management of adult medulloblastoma.

OBJECT: The aim of this paper was to determine prognostic factors for adult medulloblastoma treated with boost Gamma Knife surgery (GKS) following resection and craniospinal irradiation. METHODS: The authors performed a retrospective analysis of 12 adult patients with histologically proven medulloblastoma or supratentorial primitive neuroectodermal tumor who between February 1991 and December 2004 underwent >or=1 sessions of GKS for posttreatment residual or recurrent tumors (6 tumors in each group). Before GKS, all patients had undergone a maximal feasible resection followed by craniospinal irradiation. Nine patients also received systemic chemotherapy. Stereotactic radiosurgery was applied to residual and recurrent posterior fossa tumor as well as to foci of intracranial medulloblastoma metastases. The median time interval from initial diagnosis and resection to the first GKS treatment was 24 months (range 2-37 months). The mean GKS-treated tumor volume was 9.4 cm3 (range 0.5-39 cm3). RESULTS: Following adjunctive radiosurgery, 5 patients had no evidence of tumor on magnetic resonance (MR) imaging, 3 patients had stable tumor burden on MR imaging, and 4 patients had evidence of tumor progression locally with or without intracranial metastases. All patients with tumor progression died. Eight patients survive with a mean cumulative follow-up of 72.4 months (range 21-152 months). No acute radiation toxicity or delayed radiation necrosis was observed among any of the 12 patients. The majority of patients who achieved tumor eradication (80%) and tumor stabilization (67%) after GKS had residual tumor as the reason for their referral for GKS. The best outcomes were attained in patients with residual disease who were younger, had smaller tumor volumes, had no evidence of metastatic disease, and had received higher cumulative GKS doses. CONCLUSIONS: Single or multiple GKS sessions were a well-tolerated, feasible, and effective adjunctive treatment for posterior fossa residual or recurrent medulloblastoma as well as intracranial metastatic medulloblastoma in adult patients.

Evaluation of peptide-mediated transduction in human CD34+ cells.

Protein transduction domains (PTDs) have been used increasingly to deliver biologically active agents to a variety of cell types in vitro and in vivo. To define the most effective PTDs for transducing hematopoietic cells, we have screened a panel of PTD peptides in human CD34(+) cells for delivery of a 60-kd marker protein and assessed its impact on phenotypic maintenence in vitro. Compared to the HIV-TAT peptide, most peptide complexes displayed high efficiency in transducing the CD34(+) cells, except for those based on shorter peptides (4R, 4K, and 5RQ). In particular, the arginine homopolymers including 8R, 10R, and 12R, were internalized by the cells to a greater extent than the other PTDs. Transduction was significantly potentiated by preincubation of cells with dextran sulfate. Importantly, colony forming ability and CD34(+) CD38(-) primitive phenotype were not significantly altered in the presence of these peptides during a short-term liquid culture. Together, these data suggest the potential usefulness of arginine homopolymers in hematopoietic stem and progenitor cell manipulations.

Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium.

Synovial hyperplasia, resulting in erosion of cartilage and bone, represents one of the major pathologies associated with rheumatoid arthritis. To develop an approach for efficient delivery of proteins or agents to synovium to induce targeted apoptosis of hyperplastic synovial tissue, we have screened an M13 peptide phage display library for synovial-specific transduction peptides. We identified a novel synovial-targeted transduction peptide, HAP-1, which is able to facilitate specific internalization of protein complexes into human and rabbit synovial cells in culture and rabbit synovial lining in vivo. HAP-1 and a non-tissue-specific cationic protein transduction domain, PTD-5, were fused to an antimicrobial peptide, (KLAK)(2), to generate two proapoptotic peptides termed DP2 and DP1, respectively. Administration of these peptides was able to induce apoptosis of rabbit and human synovial cells in culture, with DP2 inducing synovial cell-specific apoptosis. Intra-articular injection of DP1 and DP2 into arthritic rabbit joints with synovial hyperplasia induced extensive apoptosis of the hyperplastic synovium, while reducing the leukocytic infiltration and synovitis. These results suggest that proapoptotic peptides and, in particular, DP2 can be clinically useful for treatment of synovial hyperplasia, as well as inflammation. Moreover, the results demonstrate the feasibility of identifying tissue-specific transduction peptides capable of mediating efficient transduction in vivo.

Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth.

The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation.

Protection of islets by in situ peptide-mediated transduction of the Ikappa B kinase inhibitor Nemo-binding domain peptide.

We have previously demonstrated that adenoviral gene transfer of the NF-kappaB inhibitor IkappaB to human islets results in protection from interleukin (IL)-1beta-mediated dysfunction and apoptosis. Here we report that human and mouse islets can be efficiently transduced by a cationic peptide transduction domain (PTD-5) without impairment of islet function. PTD mediated delivery of a peptide inhibitor of the IL-1beta-induced IkappaB kinase (IKK), derived from IKKbeta (NBD; Nemo-binding domain), and completely blocked the detrimental effects of IL-1beta on islet function and NF-kappaB activity, in a similar manner to Ad-IkappaB. We also demonstrate that mouse islets can be transduced in situ by infusion of the transduction peptide through the bile duct prior to isolation, resulting in 40% peptide transduction of the beta-cells. Delivery of the IKK inhibitor transduction fusion peptide (PTD-5-NBD) in situ to mouse islets resulted in improved islet function and viability after isolation. These results demonstrate the feasibility of using PTD-mediated delivery to transiently modify islets in situ to improve their viability and function during isolation, prior to transplantation.