Surfactant Protein-G in Wildtype and 3xTg-AD Mice: Localization in the Forebrain, Age-Dependent Hippocampal Dot-like Deposits and Brain Content

The classic surfactant proteins (SPs) A, B, C, and D were discovered in the lungs, where they contribute to host defense and regulate the alveolar surface tension during breathing. Their additional importance for brain physiology was discovered decades later. SP-G, a novel amphiphilic SP, was then identified in the lungs and is mostly linked to inflammation. In the brain, it is also present and significantly elevated after hemorrhage in premature infants and in distinct conditions affecting the cerebrospinal fluid circulation of adults. However, current knowledge on SP-G-expression is limited to ependymal cells and some neurons in the subventricular and superficial cortex. Therefore, we primarily focused on the distribution of SP-G-immunoreactivity (ir) and its spatial relationships with components of the neurovascular unit in murine forebrains. Triple fluorescence labeling elucidated SP-G-co-expressing neurons in the habenula, infundibulum, and hypothalamus. Exploring whether SP-G might play a role in Alzheimer’s disease (AD), 3xTg-AD mice were investigated and displayed age-dependent hippocampal deposits of β-amyloid and hyperphosphorylated tau separately from clustered, SP-G-containing dots with additional Reelin-ir—which was used as established marker for disease progression in this specific context. Semi-quantification of those dots, together with immunoassay-based quantification of intra- and extracellular SP-G, revealed a significant elevation in old 3xTg mice when compared to age-matched wildtype animals. This suggests a role of SP-G for the pathophysiology of AD, but a confirmation with human samples is required.

Does Impaired Glymphatic Drainage Cause Glymphedema? A Review Tailored to Neurocritical Care and Neurosurgery

Research into the glymphatic system reached an inflection point with steep trajectory in 2012 when it was formally recognized and named, but the historical roots for it are solid and deep, dating back to pioneers such as Cushing, Weed, and Dandy. We provide an overview of key discoveries of the glymphatic system, which promotes bulk flow of fluid and solutes throughout the brain parenchyma. We also discuss the lymphatic drainage of the central nervous system. Evidence is building that failure of the glymphatic system causes glymphedema in patients commonly managed by neurocritical care and neurosurgery specialists. We review research supporting this for decompressive craniectomy, subarachnoid hemorrhage, and normal-pressure hydrocephalus. We argue that it is time for a paradigm shift from the traditional model of cerebrospinal fluid circulation to a revised model that incorporates the glymphatic pathway and lymphatic clearance. These recent breakthroughs will inspire new therapeutic approaches to recognize, reverse, and restore glymphatic dysfunction and to leverage this pathway to deliver brain-wide therapeutics.

Neuronavigation device for stereotaxic external ventricular drainage insertion

Background: The insertion of an external ventricular drainage (EVD) is one of the most frequently used neurosurgical procedures. It is performed to adjust intracranial hypertension in cases of severe craniocerebral injury, acute posthemorrhagic hydrocephalus, meningitis, and oncological diseases related to impaired circulation of cerebrospinal fluid circulation (CSF). Methods: In 2020, three patients with subarachnoid aneurysmal hemorrhage underwent insertion of an EVD navigation percutaneous stereotaxic device. Three cases introduced. Results: In all cases, satisfactory EVD functioning was noted during the surgery and during the early postoperative period. The EVD insertion procedure took an average of 10 min. The EVD insertion route calculations using the software took about 5–15 min. No cases showed any infection, hemorrhagic complications, or EVD dysfunction. According to the control brain computed tomography data, the catheter position was satisfactory and corresponded to the target coordinates in all cases. Conclusion: The use of the device, with its high accuracy and efficiency, can reduce the incidence of unsatisfactory EVD implantation cases in patients with neurosurgical pathology.

A Shunt Method for the Treatment of Syringomyelia Secondary to Trauma and Tuberculous Meningitis

The pathogenesis and surgical treatment of syringomyelia (SM) secondary to trauma and tuberculous meningitis are not clear. We hypothesize that the main cause of SM is impaired cerebrospinal fluid circulation in the subarachnoid space due to spinal arachnoid adhesion induced by trauma or tuberculous meningitis. Using trans-segmental subarachnoid shuntsurgery, we re-established normal cerebrospinal fluid circulation in the subarachnoid space, which resolved the potential cause of SM formation. This study aimed to evaluate the efficacy of trans-segmental subarachnoid shunt surgery in the treatment of SM secondary to trauma or tuberculous meningitis. A total of 143 patients with SM after trauma and tuberculous meningitis were recruited between September 2014 and February 2017. Among these patients, 64 had posttraumatic SM, including 39 males and 25 females with an age range of 21–65 years and an average age of 40.02 years, and 79 patients had SM secondary to tuberculous meningitis, including 49 males and 30 females with an age range of 23–62 years and an average age of 44.95 years. All patients underwent trans-segmental subarachnoid shunt surgery and were subjected to magnetic resonance imaging (MRI) examination between 6 months and 1 year and between 2 and 2.5 years after surgery. Clinical efficacy was assessed by the Tator method. The main symptoms or signs were evaluated by improvement, stabilizationor aggravation of symptoms. Patients were followed-up twice, once at 6 months to 1 year after surgery and once at 2 to 2.5 years after surgery. A total of 143 patients were followed-up for the first time, among whom, the clinical symptoms were improved in 59 patients(41.26%), stable in 51 patients (35.66%) and aggravated in 36 patients (23.08%). MRI exaination showed that the spinal cord cavities completely disappeared in 27 patients (18.88%), shrank significantly in 71 patients (49.65%), did not change or shrink significantly in 32 patients (22.38%) and expanded in 13 patients (9.09%). A total of 122 patients were followed-up for the second time, and the clinical symptoms were improved in 69 patients (56.56%), stable in 25 patients (20.49%) and aggravated in 28 patients (22.95%). Compared to the condition in the first follow-up, 14 patients who were stable were improved, 5 patients who were aggravated were improved, and the symptoms did not change significantly among other patients. The imaging examination did not show any significant change compared to that of the first follow-up. We suggest that trauma or tuberculous meningitis can induce spinal arachnoid adhesion, leading to impaired cerebrospinal fluid circulation in the subarachnoid space, which then causes SM. Trans-segmental subarachnoid shunt surgery is a noninvasive, safe and effective treatment for SM secondary to trauma and tuberculous meningitis.

The orthopedic characterization of cfap298tm304 mutants validate zebrafish to faithfully model human AIS

Cerebrospinal fluid (CSF) circulation relies on the beating of motile cilia projecting in the lumen of the brain and spinal cord cavities Mutations in genes involved in cilia motility disturb cerebrospinal fluid circulation and result in scoliosis-like deformities of the spine in juvenile zebrafish. However, these defects in spine alignment have not been validated with clinical criteria used to diagnose adolescent idiopathic scoliosis (AIS). The aim of this study was to describe, using orthopaedic criteria the spinal deformities of a zebrafish mutant model of AIS targeting a gene involved in cilia polarity and motility, cfap298tm304. The zebrafish mutant line cfap298tm304, exhibiting alteration of CSF flow due to defective cilia motility, was raised to the juvenile stage. The analysis of mutant animals was based on micro-computed tomography (micro-CT), which was conducted in a QUANTUM FX CALIPER, with a 59 µm-30 mm protocol. 63% of the cfap298tm304 zebrafish analyzed presented a three-dimensional deformity of the spine, that was evolutive during the juvenile phase, more frequent in females, with a right convexity, a rotational component and involving at least one dislocation. We confirm here that cfap298tm304 scoliotic individuals display a typical AIS phenotype, with orthopedic criteria mirroring patient’s diagnosis.

Acute Necrotizing Encephalopathy in a Four-Year-Old Boy

Acute necrotizing encephalopathy is a devastating clinico-radiological syndrome characterized by fulminant neurological deterioration after an antecedent febrile illness, as well as the imaging hallmark of bilateral thalamic involvement. Herein, we describe a 4-year-old boy with typical clinical and neuroimaging features of acute necrotizing encephalopathy. The bithalamic swelling led to a block of cerebrospinal fluid circulation at the foramen of Monro, thereby causing the mild dilatation of lateral ventricles. The periventricular areas could, therefore, have been potentially affected by the acute necrotizing encephalopathy per se and/or transependymal edema secondary to obstructive hydrocephalus. The information from diffusion imaging allows for differentiation between these two pathophysiological processes.

Aerospace Implications of Key Neurological Conditions

INTRODUCTION: The neurological impact (or lack thereof) of certain medical histories and imaging findings is important to understand in the context of air and spaceflight. There are a number of neurological conditions that, if present in pilots and astronauts, carry variable (and sometimes adverse) functional implications for safety and overall mission success. In this systematic overview, the authors will refer to the relevant clinical and radiological features of brain tumors and vascular anomalies, cerebral edema and intracranial hypertension, concussion and the traumatic brain injury (TBI) spectrum, hematomas, cerebrospinal fluid circulation anomalies including hydrocephalus and sequestrations, spinal degenerative changes, and cerebral ischemia and demyelination. It is notable that these last two conditions have recently been reported to be a complication in some people with coronavirus disease 2019 (COVID-19). A paradigm for practical neurological workup of symptomatic pilots and astronauts will be discussed, as will the controversial notion of pre-emptive radiological screening (vs. not screening) in asymptomatic or clinically occult situations. The concepts of medical surveillance in the setting of known or diagnosed pathologies, and expert panel review and simulator and flight checks in complex neurological cases, are also elaborated on in this paper. We believe this overview will contribute toward the enhancement of a broad understanding of neurological conditions, their clinical workup, and their precautionary management in the setting of aviation and aerospace.Khurana VG, Jithoo R, Barnett M. Aerospace implications of key neurological conditions. Aerosp Med Hum Perform. 2021; 92(2):113119.