Aspirin and immunotherapy: a Faustian bargain?

Fibrinogen-like protein 1 (FGL1) has been associated with improved survival in hepatocellular carcinoma (HCC). However, recent evidence suggests that FGL1 may bind to surface receptors on lymphocytes and induce immune senescence. In this issue of the JCI, Lin and co-authors show that FGL1 may be acetylated by aspirin and targeted for degradation, which is associated with increased antitumor immunity and improved survival. Similar findings were obtained with inhibitors of sirtuin 2 (SIRT2), a histone deacetylase. These findings expand our current understanding of the role of FGL1 in cancer and provide an impetus for the evaluation of alternative immunotherapy combinations in HCC.

The Role of Hyperexcitability in Gliomagenesis.

Glioblastoma is the most common malignant primary brain tumor. Recent studies have demonstrated that excitatory or activity-dependent signaling-both synaptic and non-synaptic-contribute to the progression of glioblastoma. Glutamatergic receptors may be stimulated via neuron-tumor synapses or release of glutamate by the tumor itself. Ion currents generated by these receptors directly alter the structure of membrane adhesion molecules and cytoskeletal proteins to promote migratory behavior. Additionally, the hyperexcitable milieu surrounding glioma increases the rate at which tumor cells proliferate and drive recurrent disease. Inhibition of excitatory signaling has shown to effectively reduce its pro-migratory and -proliferative effects.

Ulnar fascicle to brachialis branch of musculocutaneous nerve for restoration of elbow flexion associated with spinal cord tumor and radiation-induced lower motor neuron disease.

Transfer of the ulnar fascicle to the biceps branch of the musculocutaneous nerve, or Oberlin transfer, has been widely used for the treatment of elbow flexion weakness in the setting of upper trunk brachial plexus palsy. The authors present a modified application of this technique for restoration of functional elbow flexion in a 30-year-old woman with a history of recurrent upper cervical spinal cord pilocytic astrocytoma, complex spinal deformity, and radiation-induced lower motor neuron disease. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2299.

Neurolymphomatosis of the brachial plexus from atypical primary central nervous system lymphoma lesions: A case report and review of the literature.

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and extranodal non-Hodgkin lymphoma limited to the neuroaxis. In immunocompetent individuals, PCNSL is more common in older adults and lacks the association with the Epstein-Barr virus found in individuals with AIDS-associated PCNSL. Because the clinical presentation and radiographic findings of PCNSL are highly variable, stereotactic brain biopsy is typically required for definitive diagnosis. High-dose methotrexate, in combination with other chemotherapeutic agents with or without whole brain radiation, is the mainstay of treatment. Case Description: A 70-year-old HIV-negative woman presented with confusion, acute flaccid left arm weakness, and left hand numbness. Head computed tomography without contrast demonstrated a 1 cm hyperdense round lesion in the suprasellar cistern that prompted further evaluation. Gadolinium-enhanced brain magnetic resonance imaging demonstrated enhancing lesions with heterogeneous signal intensity in the suprasellar, pineal, and right periatrial regions that did not explain the limb weakness and numbness. Serum and cerebrospinal fluid (CSF) studies were unrevealing, and a diagnosis of PCNSL was made following stereotactic biopsy. The patient's liver cirrhosis precluded chemotherapy, but treatment with whole-brain radiation was pursued. Conclusion: The myriad clinical presentations and insidious course of PCNSL contribute to diagnostic difficulties, delays in treatment, and poor outcomes. Stereotactic brain biopsy is the primary method of PCNSL diagnosis since malignant cells are typically not detected in CSF. PCNSL should be considered in the differential diagnosis when immunocompetent elderly patients present with multiple intracranial lesions, even in the presence of lower motor neuron findings.

Oscillopsia following orbitotomy for intracranial tumor resection.

BACKGROUND: Oscillopsia is a visual phenomenon in which an individual perceives that their environment is moving when it is in fact stationary. In this report, we describe two patients with pulsatile oscillopsia following orbitocranial approaches for skull base meningioma resection. CASE DESCRIPTION: Two patients, both 42-year-old women, underwent orbitocranial approaches for resection of a right sphenoid wing (Patient 1) and left cavernous sinus (Patient 2) meningioma. Patient 1 underwent uncomplicated resection and was discharged home without neurologic or visual complaints; she presented 8 days later with pulsatile oscillopsia. This was managed expectantly, and MRA revealed no evidence of vascular pathology. She has not required intervention as of most recent follow-up. Patient 2 developed trochlear and trigeminal nerve palsies following resection and developed pulsatile oscillopsia 4 months postoperatively. After patching and corrective lens application, the patient's symptoms had improved by 26 months postoperatively. CONCLUSION: Oscillopsia is a potential complication following skull base tumor resection about which patients should be aware. Patients may improve with conservative management alone, although the literature describes repair of orbital defects for ocular pulsations in traumatic and with some developmental conditions.

Intraventricular Hemorrhage in Premature Infants: A Historical Review.

Intraventricular hemorrhage (IVH) is common in premature newborns and poses a high risk for morbidity with lifelong disability. We searched the available literature for original and secondary literature regarding the epidemiology, pathogenesis, and treatment of IVH in order to trace changes in the management of this disease over time. We examined IVH pathogenesis and epidemiology and reviewed the history of medical and surgical treatment for intraventricular hemorrhage in preterm children. Initial medical management strategies aimed at correcting coagulopathy and eventually targeted mediators of perinatal instability including respiratory distress. Surgical management centered around cerebrospinal fluid diversion, initially through serial lumbar punctures, progressing to ventriculoperitoneal shunting, with more recent interventions addressing intraventricular clot burden. We provide a historical review of the evolution of treatment for IVH in newborns. While the management of IVH has grown significantly over time, IVH remains a common neurosurgical disease that continues to affect patient and caregiver quality of life and health care costs. Despite advances in treatment over more than a century, IVH remains a significant cause of morbidity and mortality in premature infants, and an understanding of past approaches may inform the development of new treatments.

Cerebellitis as a neurosurgical disease in pediatrics.

The diagnostic evaluation and role of neurosurgery in the treatment of cerebellitis is unclear. We explore the diagnostic evaluation and subsequent role of neurosurgical intervention in pediatric cerebellitis in a case series, highlighting the diagnostic work up and treatments applied. A retrospective review was conducted of all pediatricpatients diagnosed with cerebellitis for whom neurosurgery was consulted at a single center from June 2008 to February 2019. Nine patients, four males (44.4%) and five females (55.6%) were identified. Common presenting symptoms were headache (n = 6, 66.7%), emesis (n = 5, 55.6%), and altered mental status (n = 4, 44.4%). Six (66.7%) had associated infections. Imaging abnormalities included tonsillar ectopia (n = 8, 88.9%), bilateral cerebellar T2 hyperintensity (n = 6, 66.7%), and obstructive hydrocephalus (n = 6, 66.7%). Management included antibiotics, antivirals, corticosteroids, mannitol, and hypertonic saline. Four (44.4%) required external ventricular drain (EVD) placement for a mean 11 days (SD 6.8, range 4-20) for hydrocephalus; none required additional neurosurgical interventions. Seven patients (77.8%) required ICU care for a mean 11.7 days (SD 14.0 range 1-42). At follow-up (mean 20.8 months, SD 28.7, range 0.6-64.9), two patients (n = 2, 22.2%) recovered completely, and six (66.7%) were functionally dependent (mRS > 2); the most common residual deficit was cognitive impairment (n = 5, 55.6%). Neurosurgical consultation should be considered in pediatric patients with cerebellitis. In our experience, temporary CSF diversion via an EVD is employed nearly half of the time. The presence of hydrocephalus requiring neurosurgical intervention may be a predictor of severe disease and poor outcome.

Endoscopic ultrasonic aspiration of an intraparenchymal hematoma in a newborn.

Neonatal intracerebral hemorrhage is associated with substantial morbidity and mortality. Treatment is largely conservative, though interventions to evacuate intraventricular and intraparenchymal hematomas (IPHs) have been applied. Endoscopic ultrasonic aspiration for the treatment of IPH has increasingly been shown to be a useful strategy in adults; however, it has not been studied in children, and the technology has been more commonly applied to intraventricular hemorrhage (IVH). Here, the authors describe, to the best of their knowledge, the first use of endoscopic ultrasonic aspiration for IPH in a newborn.An 8-week-old female presented with IPH secondary to left M3 aneurysm rupture, which was treated with coil embolization for aneurysm securement and vessel sacrifice, followed by IPH evacuation using endoscopic ultrasonic aspiration. Through applying this approach in a newborn, the authors gained technical insight not previously reported in the application of this technique in similar cases in adults or in cases of IVH. They highlight this case to share learning points and technical challenges regarding the application of endoscopic ultrasonic aspiration in a newborn along with learning points for imaging and visualization. Endoscopic ultrasonic aspiration can be used to treat IPH in select newborns. Further study is needed to improve efficacy and ease when applying this approach in very young patients.

Predicting postoperative tracheostomy requirement in children undergoing surgery for posterior fossa tumors.

PURPOSE: Posterior fossa tumor (PFT) resection can be associated with postoperative respiratory failure. We aimed to identify risk factors predicting tracheostomy dependence in children after PFT resection. METHODS: Retrospective chart review of all children undergoing PFT resection from April 2007 to May 2017 at our institution was performed. RESULTS: A total of 197 patients were included; 12 (6.1%) required tracheostomy placement at a mean 69.1 days postoperatively (SD 112.7, range 7-388). Patients requiring tracheostomy were younger (3.4 vs. 6.8 years, p < 0.01), more likely to have postoperative dysphagia (91.7% vs. 17.3%, p < 0.01), and more likely to have an ependymoma (41.7% vs. 15.1%, p < 0.01) or astrocytoma (25.0% vs. 8.1%, p < 0.01). Patients with eventual tracheostomy were less likely extubated immediately postoperatively (45.5% vs. 79.6%, p < 0.01), had longer intubation duration postoperatively (5.7 vs. 0.5 days, p < 0.01), and had higher rates of reintubation within 48 h (63.6% vs. 1.3%, p < 0.01). Patients requiring tracheostomy had longer hospital length of stay (45.8 vs. 15.3 days, p < 0.01) and ICU stay postoperatively (13.5 vs. 2.1 days, p < 0.01). Of those requiring tracheostomy, three (25.0%) were decannulated by 1 year postoperatively. Decannulation rates did not vary by age (p < 0.47), extubation failure (p < 0.24), duration of intubation (p < 0.10), tumor histology (p < 0.23), or tumor grade (p < 0.13). CONCLUSION: Lower cranial neuropathy following PFT resection is common. Identifying risk factors correlated with need for tracheostomy can help identify patients who may benefit from early tracheostomy, reducing prolonged intubation trauma, time on mechanical ventilation, and length of stay.

Surgical strategies for management of pediatric arteriovenous malformation rupture: the role of initial decompressive craniectomy.

INTRODUCTION: Arteriovenous malformations (AVMs) are a common cause of intracranial hemorrhage in children, which can result in elevated intracranial pressure (ICP) and cerebral edema. We sought to explore the role of initial decompressive craniectomy at time of rupture, followed by interval surgical AVM resection, compared to treatment with initial resection, in clinical outcomes and recovery in children. METHODS: A retrospective chart review was conducted examining patients age 0-18 with AVM rupture between 2005 and 2018 who underwent resection for ruptured AVM either initially at presentation or underwent initial decompressive craniectomy followed by interval AVM resection. Clinical, radiographic, surgical, and outcome data were examined. Primary outcomes measured included functional status, AVM obliteration rate, AVM recurrence/residual, and re-hemorrhage. RESULTS: Thirty-six cases were included; 28 (77.8%) underwent initial AVM resection, and 7 (19.4%) underwent initial decompressive craniectomy with interval resection. The mean time between craniectomy and resection was 66.9 days (SD 59.3). Patients undergoing initial decompressive craniectomy with interval resection were younger (mean age 6.1 vs. 9.8 years, p = 0.05) and had a higher mean hematoma volume (52.9 vs. 22.2 mL, p = 0.01), mean midline shift (5.1 vs. 2.1 mm, p = 0.01), and presence of cisternal effacement (p = 0.01). There were no statistically significant associations between surgical strategy and postoperative outcomes, including complications, radiographic outcomes, complete resection, residual, recurrence, and functional outcomes. Those treated by initial craniectomy followed by interval resection were associated with undergoing additional procedures. CONCLUSIONS: Children presenting with AVM rupture who require emergent decompression may safely undergo emergent craniectomy with interval AVM resection and cranioplasty without additional risk of morbidity or mortality. This is reasonable in those with elevated intracranial pressure. This strategy may provide time for initial recovery and allow for natural degradation of the hematoma enhancing the plane for interval AVM resection, perhaps improving outcomes.

Predicting dysphagia in children undergoing surgery for posterior fossa tumors.

PURPOSE: Posterior fossa tumors (PFTs) are the most common type of brain tumor in children. Dysphagia is a known complication of PFT resection in children, but data regarding risk factors and clinical course are sparse. METHODS: The records of all children who underwent resection of posterior fossa tumor between April 2007 and May 2017 at our institution were analyzed. Clinical, radiographic, histologic data were gathered. Swallowing function was assessed immediately postoperatively and at 1-year follow-up. RESULTS: A total of 197 patients were included. Forty-three (21.8%) patients developed dysphagia after surgery. Patients who developed dysphagia were younger (4.5 vs. 7.2 years, p < 0.01), were more likely to have brainstem compression (74.4% vs. 57.8%, p < 0.03) or invasion (14.0 vs. 9.7%, p < 0.03), and were more likely to have ependymoma (27.9% vs. 13.6%, p < 0.01) or ATRT (atypical teratoid/rhabdoid tumor) (9.3% vs. 3.9%, p < 0.01). Patients with postoperative dysphagia also had a longer length of stay (33.7 vs. 12.7 days, p < 0.01) and were more likely to be discharged to inpatient rehabilitation (25.6% vs. 9.1%, p < 0.01). Ten patients (5.1%) were PEG-dependent by 1-year follow-up. These patients were younger (2.7 vs. 5.6 years, p < 0.01), had a longer length of stay (55.5 vs. 27.4 days, p < 0.01), and were more likely to have ATRT (30.0% vs. 0.0%, p < 0.01). Recovery was not associated with tumor grade or extent of resection. CONCLUSIONS: Dysphagia after PFT resection is associated with younger age, aggressive tumor histology, and increased healthcare utilization. While most patients recover, a small percentage are still dependent on enteral feeding at 1-year follow-up. Further research is needed to identify factors associated with persistent deficits.

Temporal Change in Tumor Volume Following Stereotactic Radiosurgery to a Single Brain Metastasis.

BACKGROUND: Stereotactic radiosurgery (SRS) can be used to achieve local control of metastatic brain lesions. However, the temporal response of these lesions to SRS is incompletely understood and quantified. We aimed to examine the temporal response to SRS of single brain metastases from 4 different primary cancers. METHODS: A retrospective chart review was performed of patients who underwent SRS at our institution from 2009 to 2012. Clinical, treatment, and volumetric data were collected. All patients were treated according to Radiation Therapy Oncology Group 90-05 schema. RESULTS: This study included 204 patients (116 men and 88 women) with a median age of 61 years (range, 27-86 years). Of patients, 20 (10%) had breast cancer, 79 (39%) had non-small cell lung cancer, 69 (34%) had melanoma, and 36 (17%) had renal cell carcinoma. Initial overall median tumor volume was 0.8 cm3 (range, 0.02-16.9 cm3). Median tumor volume was 0.5 cm3 (range, 0.02-20.4 cm3) at 1 month after SRS, 0.3 cm3 (range, 0.02-10.8 cm3) at 3 months after SRS, and 0.4 cm3 (range, 0.02-18.6 cm3) at 6 months after SRS. Based on the joint model constructed from our results, we demonstrate a median 16% (95% confidence interval, 11%-20%) reduction in tumor volume every 30 days. CONCLUSIONS: The results of this study demonstrate a consistent reduction in tumor volume following SRS over a 6-month period. Responses were modest over the first 30 days but accelerated at 3 months and varied by tumor type.

Infundibular Epidermoid Cyst: Case Report and Systematic Review.

BACKGROUND: Intracranial epidermoid cysts are benign, congenital, keratinizing, squamous epithelial-lined cysts filled with keratin. They are uncommon and often pose a surgical challenge owing to the adherence to surrounding structures. They are typically found at the cerebellopontine angle or in the parasellar region, where they are associated with abnormal development of the Rathke pouch; involvement of the pituitary stalk is rare. CASE DESCRIPTION: The patient's electronic health record was queried for relevant data. A systematic review of the literature using dedicated search terms for cases of infundibular epidermoid cysts was conducted. We present a unique case of a 55-year-old male who presented with vision changes and was found to have a parasellar epidermoid cyst confined to the pituitary stalk. The patient underwent endoscopic transsphenoidal resection, and gross total resection was achieved. The patient's postoperative course was significant for possible chemical meningitis and the development of panhypopituitarism. The patient's vision subjectively improved after surgery. CONCLUSIONS: Although 3 other cases of epidermoid cysts involving the pituitary stalk were identified, our patient's tumor was unique in that it was confined to the stalk. Our patient's case highlights a surgical approach to parasellar epidermoid cysts and the possible complications associated therewith.

Endovascular "Boost": External Carotid Angioplasty to Augment Flow Before Superficial Temporal-Middle Cerebral Artery Bypass.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass may be used to augment cerebral blood flow in patients with select cerebrovascular pathologies or after failed attempts at revascularization. In this article we describe the use of balloon angioplasty to boost the flow of the external carotid artery (ECA) including the STA to be later used as a donor artery for a STA-MCA bypass procedure. CASE DESCRIPTION: A 67-year-old male with bilateral carotid artery stenosis presented 2 days after a right middle cerebral artery (MCA) stroke and was admitted for medical management. Over the next 4 days his examination worsened; magnetic resonance imaging and computed tomography perfusion confirmed a right MCA stroke with penumbra and angiography revealed complete occlusion of the right internal carotid artery within a prior carotid stent. There was also a right ECA stenosis at its origin, thus limiting options for traditional extracranial-intracranial bypass. Therefore the patient underwent balloon angioplasty of the right ECA by traversing the carotid stent followed by right STA-MCA bypass, resulting in increased flow, clinical stability, and improved cerebral perfusion. CONCLUSIONS: This case highlights a unique strategy for the management of internal carotid artery occlusion in combination with an ipsilateral ECA stenosis. We also demonstrate the utility of endovascular adjuncts to open vascular surgery when complex patterns of stenosis or occlusion exist.

Recurrent Papillary Glioneuronal Tumor.

BACKGROUND: Papillary glioneuronal tumors (PGNTs) are rare World Health Organization grade I neoplasms that are characterized by a benign course and excellent response to surgical resection. A few reports exist of tumors with more aggressive clinical and histologic features. In this report we detail the case of an unusually aggressive PGNT in a 67-year-old woman. CASE DESCRIPTION: The patient had a 3-year history of seizures and was diagnosed with a frontoparietal mass on imaging. She underwent subtotal resection with a histologic diagnosis of PGNT. Less than a year after surgery, the patient experienced recurrence of disease and underwent reresection and adjuvant radiation treatment. The patient's disease continued to progress despite radiation treatment, so adjuvant temozolomide was initiated. Molecular testing was performed and revealed a TERT promotor mutation, an FGFR3-TACC3 oncogenic fusion, and a copy number loss in CDKN2A/CDKN2B. CONCLUSIONS: PGNTs, while typically benign, can rarely recur after surgery. Molecular testing should be performed on all PGNTs to help possibly identify more aggressive tumors and potentially reveal novel treatment options.

Newly Diagnosed Optic Pathway Glioma During Pregnancy.

BACKGROUND: Optic pathway gliomas (OPGs) are relatively rare, and their presentation after the first decade of life is even less common. Although many treatment options exist, surgery is typically reserved for tumors significantly compressing surrounding structures. Pregnancy can complicate the management of these tumors, as fetal developmental considerations limit the ways in which they are imaged and treated. CASE DESCRIPTION: In this report we detail the case of a 27-year-old pregnant woman who was found to have an OPG during her third trimester. After a decline in this patient's vision and clinical status, a decision was made to induce labor at 31 weeks so that her disease could be more thoroughly addressed. CONCLUSIONS: While OPGs are typically benign tumors, pregnancy complicates their management significantly. Contrast media and anesthesia pose significant risks to the fetus, while pregnancy may contribute to increased rates of tumor growth and clinical deterioration. Managing OPGs in pregnant patients thus requires balancing the risks to the fetus and patient.