The historical adventures of Takeshi Kawase: the mountaineer who explored the "no man's land" with love for art, nature, and humankind.

The anterior petrosal approach, or Kawase's approach, is a commonly used technique in skull base surgery to access the brainstem in the posterior fossa from the middle fossa, and has the advantages of minimizing brain retraction and preserving hearing. It was first successfully performed by the legendary Japanese neurosurgeon, Takeshi Kawase, for the clipping of a basilar artery aneurysm in 1981. To date, no historical article has shed light on Kawase's intriguing personal history. In this historical vignette, the authors depict Kawase's unique background, talent, passion, as well as struggles that ultimately shaped his career. By sharing Kawase's personal story from the hospital where he first successfully performed his original approach, the authors hope to pass on to future generations Kawase's spirit and philosophy that have impacted the global neurosurgical community.

Safety of responsive neurostimulation in pediatric patients with medically refractory epilepsy.

OBJECTIVE: Approximately 75% of pediatric patients who suffer from epilepsy are successfully treated with antiepileptic drugs, while the disease is drug resistant in the remaining patients, who continue to have seizures. Patients with drug-resistant epilepsy (DRE) may have options to undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation. To date, treatment with responsive neurostimulation (RNS) has not been sufficiently studied in the pediatric population because the FDA has not approved the RNS device for patients younger than 18 years of age. Here, the authors sought to investigate the safety of RNS in pediatric patients. METHODS: The authors performed a retrospective single-center study of consecutive patients with DRE who had undergone RNS system implantation from September 2015 to December 2019. Patients were followed up postoperatively to evaluate seizure freedom and complications. RESULTS: Of the 27 patients studied, 3 developed infections and were treated with antibiotics. Of these 3 patients, one required partial removal and salvaging of a functioning system, and one required complete removal of the RNS device. No other complications, such as intracranial hemorrhage, stroke, or device malfunction, were seen. The average follow-up period was 22 months. All patients showed improvement in seizure frequency. CONCLUSIONS: The authors demonstrated the safety and efficacy of RNS in pediatric patients, with infections being the main complication. ABBREVIATIONS: DBS = deep brain stimulation; DRE = drug-resistant epilepsy; MDC = multidisciplinary conference; MER = microelectrode recording; MSHS = Mount Sinai Health System; RNS = responsive neurostimulation; SEEG = stereo-EEG; VNS = vagus nerve stimulation.

Predictors of Ventriculoperitoneal shunting following Subarachnoid Hemorrhage treated with External Ventricular Drainage.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is commonly associated with hydrocephalus due to subarachnoid hemorrhage blood products obstructing cerebrospinal fluid outflow. Hydrocephalus after aSAH is routinely managed with temporary external ventricular drainage (EVD) followed by standard EVD weaning protocols, which determine the need for ventriculoperitoneal shunting (VPS). We sought to investigate aSAH patients who initially passed EVD weaning trials and had EVD removal, but later presented with recurrent, delayed, symptomatic hydrocephalus requiring a VPS. METHODS: We conducted a retrospective review of all patients at our tertiary care medical center who presented with aSAH, requiring an EVD. We analyzed variables associated with ultimate VPS dependency during hospitalization. RESULTS: We reviewed 489 patients with aSAH over a 6-year period (2008-2014). One hundred and thirty-eight (28.2%) developed hydrocephalus requiring a temporary EVD. Forty-four (31.9%) of these patients died or had withdrawal of care during admission, and were excluded from final analysis. Of the remaining 94 patients, 29 (30.9%) failed their clamp trial and required VPS. Sixty-five (69.1%) patients passed their clamp trial and were discharged without a VPS. However, 10 (15.4%) of these patients developed delayed hydrocephalus after discharge and ultimately required VPS [mean (range) days after discharge, 97.2 (35-188)]. Compared to early VPS, the delayed VPS group had a higher incidence of symptomatic vasospasm (90.0% vs 51.7%; P = 0.03). When comparing patients discharged from the hospital without VPS, delayed VPS patients also had higher 6- and 12-month mortality (P = 0.02) and longer EVD clamp trials (P < 0.01) than patients who never required VPS but had an EVD during hospitalization. Delayed hydrocephalus occurred in only 7.8% of patients who passed the initial EVD clamp trial, compared to 14.3% who failed the initial trial and 80.0% who failed 2 or more trials. CONCLUSION: Patients who failed their initial or subsequent EVD clamp trials had a small, but increased risk of developing delayed hydrocephalus ultimately requiring VPS. Additionally, the majority of patients who presented with delayed hydrocephalus also suffered symptomatic vasospasm. These associations should be further explored and validated in a larger prospective study.

Surgical treatment of bilateral glossopharyngeal neuralgia.

Glossopharyngeal neuralgia (GPN) is a condition characterised by sudden, severe pain in the distribution of the glossopharyngeal nerve. It can be triggered by talking, yawning, coughing and swallowing. Classically, patients experience a unilateral lancinating and excruciating pain described as electrical shock-like pain in the areas around the ear, tongue, or the mandibular angle. Uncommon manifestations include cardiac arrhythmias and syncope during pain episodes. Surgery is indicated in refractory cases. Bilateral GPN is rare, and definitive surgical treatment for bilateral GPN has not yet been reported. In this case report, a young woman with bilateral GPN who underwent staged surgery bilaterally is described. She did not develop life-threatening cardiac abnormalities postoperatively.

Challenges of Managing Patients with Symptomatic Large Traumatic Cervical Pseudomeningoceles.

BACKGROUND: Traumatic cervical pseudomeningoceles (TCPs) occur secondary to traction of the cervical nerve roots resulting in violation of the dura. Surgical repair is not necessary in most cases because pseudomeningoceles have a high propensity to spontaneously resolve with conservative management alone. Currently, there are a limited number of cases of large TCPs (large is defined as ≥6 cm in greatest diameter), and there is no established guideline for the management of such lesions. CASE DESCRIPTION: We describe the cases of 2 young men in their 20s who were involved in a motor vehicle accident. Both patients suffered a brachial plexus injury and developed large TCPs. Patient 1 was treated surgically for TCP using a combined intra-/extradural approach using a fascia lata graft. Patient 2 was ultimately treated nonsurgically because a spontaneous resolution of the pseudomeningocele was achieved over the period of 7 months after the accident. Both patients underwent brachial plexus repair surgery consisting of spinal accessory nerve transfer to the suprascapular nerve and intercostal nerve transfer to the musculocutaneous nerve. CONCLUSIONS: Disease progression of TCPs is a dynamic process, and even large lesions may spontaneously resolve without surgical intervention. When surgery is indicated, a definitive dural repair using a fascia lata graft to cover the dural tear intra- and extradurally is an effective method. Surgery must be planned carefully on a case-by-case basis, and close follow-up with thorough physical examination and serial imaging is critical to monitor disease progression.

Vertebral Venous Collaterals with Underlying Agenesis of the Inferior Vena Cava: Implications for Spinal Surgery.

BACKGROUND: Congenital agenesis of the inferior vena cava (IVC) can lead to the development of a prominent venous collateral system within and around the spine due to the development of venous collaterals. In such patients, surgery can carry a risk of catastrophic bleeding or decompensation of a delicate venous drainage pattern during spinal manipulation or even epidural exploration. CASE DESCRIPTION: A 49-year-old man with a congenital agenesis of the IVC presented with signs and symptoms of an L5 radiculopathy. A computed tomography scan of the lumbar spine showed the characteristic finding of fenestrated or "holey" pedicles within the lumbar spine, due to chronic venous engorgement within the pedicles. CONCLUSIONS: To our knowledge, this is the first report to describe the characteristic sign of "holey" pedicles on radiographic imaging in a patient with an underdeveloped IVC. This finding may be useful for the detection of abnormal spinal venous anatomy. In such patients, spinal surgery may carry greater risks and requires special consideration.

Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer.

Molecular factors that define stem cell identity have recently emerged as oncogenic drivers. For instance, brachyury, a key developmental transcriptional factor, is also implicated in carcinogenesis, most notably of chordoma, through mechanisms that remain elusive. Here, we show that brachyury is a crucial regulator of stemness in chordoma and in more common aggressive cancers. Furthermore, this effect of brachyury is mediated by control of synthesis and stability of Yes-associated protein (YAP), a key regulator of tissue growth and homeostasis, providing an unexpected mechanism of control of YAP expression. We further demonstrate that the brachyury-YAP regulatory pathway is associated with tumor aggressiveness. These results elucidate a mechanism of controlling both tumor stemness and aggressiveness through regulatory coupling of two developmental factors.

NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na+-K+-2Cl- co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD). To determine the potential actin-regulatory mechanisms affected by NKCC1 inhibition, we studied NKCC1 protein interactions. We found that NKCC1 interacts with the actin-regulating protein Cofilin-1 and can regulate its membrane localization. Finally, we analyzed whether NKCC1 could regulate the activity of the small Rho-GTPases RhoA and Rac1. We observed that the active forms of RhoA and Rac1 were decreased in NKCC1-KD cells. In summary, we report that NKCC1 regulates GBM cell migration by modulating the cytoskeleton through multiple targets including F-actin regulation through Cofilin-1 and RhoGTPase activity. Due to its essential role in cell migration NKCC1 may serve as a specific therapeutic target to decrease cell invasion in patients with primary brain cancer.