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Benjamin K. Hendricks, Aaron A. Cohen-Gadol, and James C. Miller

Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood–cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM.

In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.

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Aaron Miller, Daniel W. Griepp, Chase Miller, Mousa Hamad, Rafael De la Garza Ramos, and Saikiran G. Murthy


The authors sought to determine if a consensus could be reached regarding the effectiveness of endotracheal tube cuff pressure (ETTCP) reduction after retractor placement in reducing postoperative laryngeal dysfunction after anterior cervical fusion surgery.


A literature search of MEDLINE (PubMed), EMBASE, Cochrane Central, Google Scholar, and Scopus databases was performed. Quantitative analysis was performed on data from articles comparing groups of patients with either reduced or unadjusted ETTCP after retractor placement in the context of anterior cervical surgery. The incidence and severity of postoperative recurrent laryngeal nerve palsy (RLNP), dysphagia, and dysphonia were compared at several postsurgical time points, ranging from 24 hours to 3 months. Heterogeneity was assessed using the chi-square test, I statistics, and inverted funnel plots. A random-effects model was used to provide a conservative estimate of the level of effect.


Nine studies (7 randomized, 1 prospective, and 1 retrospective) were included in the analysis. A total of 1671 patients were included (1073 [64.2%] in the reduced ETTCP group and 598 [35.8%] in the unadjusted ETTCP group). In the reduced ETTCP group, the severity of dysphagia, measured by the Bazaz-Yoo system in 3 randomized studies at 24 hours and at 4–8 weeks, was significantly lower (24 hours [standardized mean difference: −1.83, p = 0.04] and 4–8 weeks [standardized mean difference: −0.40, p = 0.05]). At 24 hours, the odds of developing dysphonia were significantly lower (OR 0.51, p = 0.002). The odds of dysphagia (24 hours: OR 0.77, p = 0.24; 1 week: OR 0.70, p = 0.47; 12 weeks: OR 0.58, p = 0.20) were lower, although not significantly, in the reduced ETTCP group. The odds of a patient having RLNP were significantly lower at all time points (24 hours: OR 0.38, p = 0.01; 12 weeks: OR 0.26, p = 0.03) when 3 randomized and 2 observational studies were analyzed. A subgroup analysis using only randomized studies demonstrated a similar trend in odds of having RLNP, yet without statistical significance (24 hours: OR 0.79, p = 0.60). All other statistically significant findings persisted with removal of any observational data.


Based on the current best available evidence, reduction of ETTCP after retractor placement in anterior cervical surgery may be a protective measure to decrease the severity of dysphagia and the odds of developing RLNP or dysphonia.

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Aaron A. Cohen-Gadol, J. Michael Homan, Edward R. Laws, John L. D. Atkinson, and Ross H. Miller

✓ Mayo Clinic founders, William J. Mayo and Charles H. Mayo, and Harvey W. Cushing were among the most significant pioneers of modern American surgery. A review of their personal correspondence reveals a special relationship among these three individuals, particularly between William Mayo and Cushing. Their interactions within the Society of Clinical Surgery initiated their close personal and professional association, which would endure for 39 years. William Mayo strongly supported Cushing's efforts to develop the specialty of neurological surgery, and Cushing sought Mayo's advice in making important career-related decisions. Their supportive friendship and professional alliance remains an example for future generations of neurological surgeons.

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Aaron A. Cohen-Gadol, J. Bradley White, James J. Lynch, Gary M. Miller, and William E. Krauss

Object. Thoracic synovial cysts (TSCs) are rare and are usually the subject of case reports. The authors studied the clinical manifestations, radiological aspects, and surgical treatment in a series of patients at their institution who harbored TSCs. They also review the literature to discuss the potential factors involved in the pathogenesis of this lesion.

Methods. A database search of 16,000 patients who underwent decompressive spine surgery at the Mayo Clinic (Rochester, MN) between 1976 and 2003 disclosed nine patients (0.06%) in whom a diagnosis of TSC had been made. All patients were men. The mean age at presentation was 73 ± 5 years and mean duration of symptoms was 5 ± 3 months. The mean duration of follow up was 4 ± 3 years.

The patients had no history of trauma or spine surgery. All patients had spastic paraparesis; two had urinary difficulties. Detailed neurological examination revealed myelopathy and radiculopathy with a sensory level of T10—L4. Magnetic resonance imaging revealed bilateral cysts in four patients and unilateral lesions in five. Three of the cysts were at the T-10 interspace, seven at the T-11 interspace, and three at the T-12 interspace. Seven cysts were on the right and six were on the left. Computerized tomography myelography performed in five patients revealed a gas bubble in the TSC in two patients. All patients underwent laminectomy/partial facetectomy, excision of the cyst, and decompression of the thecal sac and nerve root without any complications. None of these patients underwent a fusion. Eight patients (89%) experienced moderate to excellent relief of their preoperative signs and symptoms and one patient (11%) remained stable. There was no evidence of cyst recurrence at the site of surgery or other spinal segments at follow-up examination in any patient.

Conclusions. When compared with their lumbar and cervical spine counterparts, TSCs are exceedingly rare. Their rarity may be explained by the decreased mobility of the thoracic spinal segments. The origin of TSCs is more likely degenerative rather than traumatic. Based on their experience and the follow-up duration, surgery provided durable relief from symptoms.

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R. Shane Tubbs, Mitchel Muhleman, Samuel G. McClugage, Marios Loukas, Joseph H. Miller, Joshua J. Chern, Curtis J. Rozzelle, W. Jerry Oakes, and Aaron A. Cohen-Gadol

Cysts of the choroidal fissure are often incidentally identified. Symptoms from such cysts appear to be exceedingly rare. Herein, the authors report a case series of symptomatic enlargement of choroidal fissure cysts that were surgically treated. Although cysts of the choroidal fissure do not normally become symptomatic, the neurosurgeon should be aware of such a complication. Based on the authors' experience, surgical fenestration of such cysts has good long-term results.

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Aaron P. Wessell, Matthew J. Kole, Gregory Cannarsa, Jeffrey Oliver, Gaurav Jindal, Timothy Miller, Dheeraj Gandhi, Gunjan Parikh, Neeraj Badjatia, E. Francois Aldrich, and J. Marc Simard


The authors sought to evaluate whether a sustained systemic inflammatory response was associated with shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage.


A retrospective analysis of 193 consecutive patients with aneurysmal subarachnoid hemorrhage was performed. Management of hydrocephalus followed a stepwise algorithm to determine the need for external CSF drainage and subsequent shunt placement. Systemic inflammatory response syndrome (SIRS) data were collected for all patients during the first 7 days of hospitalization. Patients who met the SIRS criteria every day for the first 7 days of hospitalization were considered as having a sustained SIRS. Univariate and multivariate regression analyses were used to determine predictors of shunt dependence.


Sixteen percent of patients required shunt placement. Sustained SIRS was observed in 35% of shunt-dependent patients compared to 14% in non–shunt-dependent patients (p = 0.004). On multivariate logistic regression, female sex (OR 0.35, 95% CI 0.142–0.885), moderate to severe vasospasm (OR 3.78, 95% CI 1.333–10.745), acute hydrocephalus (OR 21.39, 95% CI 2.260–202.417), and sustained SIRS (OR 2.94, 95% CI 1.125–7.689) were significantly associated with shunt dependence after aneurysmal subarachnoid hemorrhage. Receiver operating characteristic analysis revealed an area under the curve of 0.83 for the final regression model.


Sustained SIRS was a predictor of shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage even after adjustment for potential confounding variables in a multivariate logistic regression model.

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R. Shane Tubbs, Joseph Miller, Marios Loukas, Mohammadali M. Shoja, Ghaffar Shokouhi, and Aaron A. Cohen-Gadol


The perineal branch of the posterior femoral cutaneous nerve (PBPFCN) has received little attention in the literature. Because perineal pain syndromes can be disabling and pudendal nerve surgical decompression/block is often not efficacious, an anatomical study of this cutaneous nerve of the perineum seemed warranted.


The authors dissected 20 adult cadavers (40 sides) to identify the branching pattern and landmarks for the PBPFCN.


This branch arose directly from the posterior femoral cutaneous nerve in 55% of sides and from the inferior cluneal nerve in 30% of sides. It was absent in 15% of sides. On average, the nerve coursed 4 cm inferior to the termination of the sacrotuberous ligament onto the ischial tuberosity. No PBPFCN was found to pierce the sacrotuberous ligament. The PBPFCN provided 2–3 branches to the medial thigh that continued on to the scrotum and labia major. In general, 2 small ascending branches were identified. In males, one ascending branch traveled inferior to the corpora cavernosum and anterior to the spermatic cord to cross the midline. The other ascending branch traveled to skin at the junction of the perineum and adductor tendon. A single descending branch, approximately 2 mm in diameter, traveled to the inferior scrotum anterior to the testicle in the male specimens and the lower labia majora in the female specimens. Communications between the PBPFCN and the perineal branch of the pudendal nerve were common.


Entrapment of the PBPFCN may be the cause of some forms of the perineal pain syndrome. Specific knowledge of the PBPFCN may assist surgeons in releasing and anesthetizing this cutaneous nerve of the perineum.