The biophysical role of hemodynamics in the pathogenesis of cerebral aneurysm formation and rupture.

The pathogenesis of intracranial aneurysms remains complex and multifactorial. While vascular, genetic, and epidemiological factors play a role, nascent aneurysm formation is believed to be induced by hemodynamic forces. Hemodynamic stresses and vascular insults lead to additional aneurysm and vessel remodeling. Advanced imaging techniques allow us to better define the roles of aneurysm and vessel morphology and hemodynamic parameters, such as wall shear stress, oscillatory shear index, and patterns of flow on aneurysm formation, growth, and rupture. While a complete understanding of the interplay between these hemodynamic variables remains elusive, the authors review the efforts that have been made over the past several decades in an attempt to elucidate the physical and biological interactions that govern aneurysm pathophysiology. Furthermore, the current clinical utility of hemodynamics in predicting aneurysm rupture is discussed.

Strongyloides hyperinfection syndrome due to corticosteroid therapy after resection of meningioma: illustrative case.

BACKGROUND: Strongyloidiasis is an underdiagnosed and preventable life-threatening disease caused by infection with the helminth Strongyloides stercoralis. Chronic asymptomatic infection can be sustained for decades, and immunosuppression can lead to disseminated infection, with a mortality rate of 70%-100%. In the neurosurgical population, corticosteroids are the most consistent cause of hyperinfection. OBSERVATIONS: The authors present the case of a 33-year-old woman of Paraguayan origin who was diagnosed with sphenoid planum meningioma and treated with a high dose of corticosteroids on the basis of the diagnosis. She underwent surgery, and pathological anatomy reflected grade I meningioma. After the surgery, she started with a history of dyspnea, productive cough, fever, and urticarial rash. Later, she presented with intestinal pseudo-obstruction and bacterial meningitis with hydrocephalus. Serology was positive for Strongyloides (enzyme-linked immunosorbent assay), and she was diagnosed with hyperinfection syndrome. Ivermectin 200 µg/kg daily was established. LESSONS: It may be of interest to rule out a chronic Strongyloides infection in patients from risk areas (immigrants or those returning from recent trips) before starting treatment with corticosteroids.

Right hemidiaphragmatic paralysis after cervical transforaminal epidural steroid injection: illustrative case.

BACKGROUND: Cervical radiculopathy is a common cause of neck pain, with radiation into the upper extremity in a dermatomal pattern. Corticosteroid injection is a conservative management option with a low risk of major adverse events. No reviewed literature or case reports have implicated phrenic nerve injury secondary to cervical transforaminal epidural steroid injection (CTFESI). OBSERVATIONS: A 45-year-old man with severe right C6 radiculopathy secondary to a large right-sided C5-6 herniated intervertebral disc presented to the pain management clinic, where he received a right-sided C6 CTFESI. An hour after injection, the patient experienced shortness of breath, which was found to be caused by right diaphragmatic paralysis. The patient underwent a C5-6 anterior cervical discectomy and fusion, which provided complete relief of his radicular symptoms. However, the right hemidiaphragmatic paralysis remained at the 1-year postoperative visit. LESSONS: Thorough literature review showed no established explanations for phrenic nerve injury after CTFESI. In this study, the authors explored the suspected mechanisms of possible injury to the phrenic nerve. Epidural corticosteroid injection is considered to be a safe option for conservative management of cervical radiculopathy. This study unveiled a unique and important adverse event that should be considered before a patient receives CTFESI.

Cerebral vasculopathy and strokes in a child with COVID-19 antibodies: illustrative case.

BACKGROUND: The ability of coronavirus disease 2019 (COVID-19) to cause neurological insults in afflicted adults is becoming increasingly understood by way of an ever-growing amount of international data. By contrast, the pandemic illness's neurological effects in the pediatric population are both poorly understood and sparsely reported. OBSERVATIONS: In this case, the authors reported their experience with a preschool-age child with hydrocephalus who suffered multiterritory strokes presumed secondary to immune-mediated cerebral vasculopathy as a result of asymptomatic COVID-19 infection. LESSONS: Growing evidence indicates that COVID-19 can cause neurological sequelae such as encephalitis and strokes. In this case report, the authors discussed a case of cerebral vasculopathy and strokes in a pediatric patient who was positive for COVID-19.

When the air hits your brain: decreased arterial pulsatility after craniectomy leading to impaired glymphatic flow.

OBJECTIVECranial neurosurgical procedures can cause changes in brain function. There are many potential explanations, but the effect of simply opening the skull has not been addressed, except for research into syndrome of the trephined. The glymphatic circulation, by which CSF and interstitial fluid circulate through periarterial spaces, brain parenchyma, and perivenous spaces, depends on arterial pulsations to provide the driving force for bulk flow; opening the cranial cavity could dampen this force. The authors hypothesized that a craniectomy, without any other pathological insult, is sufficient to alter brain function due to reduced arterial pulsatility and decreased glymphatic flow. Furthermore, they postulated that glymphatic impairment would produce activation of astrocytes and microglia; with the reestablishment of a closed cranial compartment, the glymphatic impairment, astrocytic/microglial activation, and neurobehavioral decline caused by opening the cranial compartment might be reversed.METHODSUsing two-photon in vivo microscopy, the pulsatility index of cortical vessels was quantified through a thinned murine skull and then again after craniectomy. Glymphatic influx was determined with ex vivo fluorescence microscopy of mice 0, 14, 28, and 56 days following craniectomy or cranioplasty; brain sections were immunohistochemically labeled for GFAP and CD68. Motor and cognitive performance was quantified with rotarod and novel object recognition tests at baseline and 14, 21, and 28 days following craniectomy or cranioplasty.RESULTSPenetrating arterial pulsatility decreased significantly and bilaterally following unilateral craniectomy, producing immediate and chronic impairment of glymphatic CSF influx in the ipsilateral and contralateral brain parenchyma. Craniectomy-related glymphatic dysfunction was associated with an astrocytic and microglial inflammatory response, as well as with the development of motor and cognitive deficits. Recovery of glymphatic flow preceded reduced gliosis and return of normal neurological function, and cranioplasty accelerated this recovery.CONCLUSIONSCraniectomy causes glymphatic dysfunction, gliosis, and changes in neurological function in this murine model of syndrome of the trephined.

Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors.

OBJECTIVE: Placental alkaline phosphatase (PLAP) in CSF can provide a very high diagnostic value in cases of intracranial germ cell tumors (GCTs), especially in pure germinomas, to the level of not requiring histological confirmation. Unlike other tumor markers, reliable data analysis with respect to the diagnostic value of PLAP serum or CSF levels has not been available until now. This is the first systematic and comprehensive study examining the diagnostic value of CSF PLAP in patients with intracranial GCTs. METHODS: From 2004 to 2014, 74 patients (average age 19.6 ± 10.6 years) with intracranial GCTs were evaluated using PLAP from their CSF and histological samples. Chemiluminescent enzyme immunoassay was utilized to measure CSF PLAP in the following tumor sites: pineal (n = 32), pituitary stalk, suprasellar (n = 16), basal ganglia (n = 15), intraventricular (n = 9), and cerebellar (n = 5) regions. In addition to classifying GCT cases, all patients underwent tumor biopsy for correlation with tumor marker data. RESULTS: PLAP in combination with other tumor markers resulted in extremely high sensitivity and specificity of the diagnostic value of intracranial GCTs. Intracranial GCT cases were classified into 1) germinomas, both "pure" and syncytiotrophoblastic giant cell types (n = 38); 2) nongerminomatous GCTs, choriocarcinomas (n = 9) and teratomas (n = 4); and 3) nongerminomas, other kinds of tumors (n = 23). Consequently, all patients received chemoradiation therapy based on elevation of PLAP and the histopathological results. It was also speculated that the level of PLAP could show the amount of intracranial germ cell components of a GCT. PLAP was 100% upregulated in all intracranial germinoma cases. The absence of CSF PLAP proved that the tumor was not a germinoma. CONCLUSIONS: The current study is the first systematic and comprehensive examination of the diagnostic value of the tumor marker PLAP in pediatric patients with intracranial GCT. Using the level of PLAP in CSF, we were able to detect the instances of intracranial germinoma with very high reliability, equivalent to a pathological diagnosis.

The role of spinal thrombin through protease-activated receptor 1 in hyperalgesia after neural injury.

OBJECTIVE Painful neuropathic injuries induce blood-spinal cord barrier (BSCB) breakdown, allowing pro-inflammatory serum molecules to cross the BSCB, which contributes to nociception. The goal of these studies was to determine whether the blood-borne serine protease thrombin also crosses a permeable BSCB, contributing to nociception through its activation of protease-activated receptor-1 (PAR1). METHODS A 15-minute C-7 nerve root compression, which induces BSCB breakdown and painful behaviors by Day 1, was administered in the rat (n = 10); sham operation (n = 11) and a 3-minute compression (n = 10) that does not induce sensitivity were administered as controls. At Day 1 after root compression, spinal cord tissue was co-immunolabeled for fibrin/fibrinogen, the enzymatic product of thrombin, and IgG, a serum protein, to determine whether thrombin acts in areas of BSCB breakdown. To determine whether spinal thrombin and PAR1 contribute to hyperalgesia after compression, the thrombin inhibitor hirudin and the PAR1 antagonist SCH79797, were separately administered intrathecally before compression injuries (n = 5-7 per group). Rat thrombin was also administered intrathecally with and without SCH79797 (n = 6 per group) to determine whether spinal thrombin induces hypersensitivity in naïve rats through PAR1. RESULTS Spinal fibrin(ogen) was elevated at Day 1 after root compression in regions localized to BSCB breakdown and decreased in those regions by Day 7. Blocking either spinal thrombin or PAR1 completely prevented compression-induced hyperalgesia for 7 days. Intrathecal thrombin induced transient pain that was prevented by blocking spinal PAR1 before its injection. CONCLUSIONS The findings of this study suggest a potent role for spinal thrombin and its activation of PAR1 in pain onset following neuropathic injury.

(Pro)renin receptor is crucial for glioma development via the Wnt/ß-catenin signaling pathway.

OBJECTIVE The (pro)renin receptor (PRR) plays an essential role in the early development of the central nervous system by activating the Wnt/ß-catenin signaling pathway. The authors investigated the potential role of the PRR in the pathogenesis of glioma. METHODS The authors performed immunohistochemical analysis to detect both the PRR and isocitrate dehydrogenase 1 with mutations involving arginine 132 ( IDH1R132H) in paraffin sections of 31 gliomas. Expression of the PRR and Wnt pathway components in cultured human glioma cell lines (U251MG, U87MG, and T98G) was measured using Western blotting. The effects of PRR short interfering RNA (siRNA) on glioma cell proliferation (WST-1 assay and direct cell counting) and apoptosis (flow cytometry and the caspase-3 assay) were also examined. RESULTS PRR expression was significantly higher in glioblastoma than in normal tissue or in lower grade glioma, regardless of IDH1R132H mutation. PRR expression was also higher in human glioblastoma cell lines than in human astrocytes. PRR expression showed a significant positive correlation with the Ki-67 labeling index, while it had a significant negative correlation with the survival time of glioma patients. Treatment with PRR siRNA significantly reduced expression of Wnt2, activated ß-catenin, and cyclin D1 by human glioblastoma cell lines, and it reduced the proliferative capacity of these cell lines and induced apoptosis. CONCLUSIONS This is the first evidence that the PRR has an important role in development of glioma by aberrant activation of the Wnt/ß-catenin signaling pathway. This receptor may be both a prognostic marker and a therapeutic target for glioma.

Aquaporin-4 autoimmunity masquerading as a brainstem tumor.

Brainstem glioma is a highly devastating disease, and any mass-like lesion in the brainstem can raise suspicion of this diagnosis. However, other inflammatory, demyelinating, or degenerative diseases can mimic brainstem glioma in clinical presentation and imaging features. Therefore, diagnosis based solely on imaging is often insufficient for brainstem lesions and may lead to incorrect diagnosis and treatment. This case report is the first description of central nervous system aquaporin-4 (AQP4) autoimmunity confined mainly to the brainstem. It demonstrates the wide spectrum of neuroinflammatory diseases in children and highlights the utility of surgical biopsy for suspicious brainstem lesions with atypical imaging features for glioma.