Emergency resection of brainstem cavernous malformations

Brainstem cavernous malformations (CMs) pose significant challenges to neurosurgeons because of their deep locations and high surgical risks. Most patients with brainstem CMs present with sudden-onset cranial nerve deficits or ataxia, but uncommonly patients can present in extremis from an acute hemorrhage, requiring surgical intervention. However, the timing of surgery for brainstem CMs has been a controversial topic. Although many authors propose delaying surgery into the subacute phase, some patients may not tolerate waiting until surgery. To the best of the authors' knowledge, emergency surgery after a brainstem CM hemorrhage has not been described. In cases of rapidly progressive neurological deterioration, emergency resection may often be the only option. In this retrospectively reviewed small series of patients, the authors report favorable outcomes after emergency surgery for resection of brainstem CMs

Spinal Subarachnoid Space Pressure Measurements in an In Vitro Spinal Stenosis Model: Implications on Syringomyelia Theories

Full explanation for the pathogenesis of syringomyelia (SM), a neuropathology characterized by the formation of a cystic cavity (syrinx) in the spinal cord (SC), has not yet been provided. It has been hypothesized that abnormal cerebrospinal fluid (CSF) pressure, caused by subarachnoid space (SAS) flow blockage (stenosis), is an underlying cause of syrinx formation and subsequent pain in the patient. However, paucity in detailed in vivo pressure data has made theoretical explanations for the syrinx difficult to reconcile. In order to understand the complex pressure environment, four simplified in vitro models were constructed to have anatomical similarities with post-traumatic SM and Chiari malformation related SM. Experimental geometry and properties were based on in vivo data and incorporated pertinent elements such as a realistic CSF flow waveform, spinal stenosis, syrinx, flexible SC, and flexible spinal column. The presence of a spinal stenosis in the SAS caused peak-to-peak cerebrospinal fluid CSF pressure fluctuations to increase rostral to the stenosis. Pressure with both stenosis and syrinx present was complex. Overall, the interaction of the syrinx and stenosis resulted in a diastolic valve mechanism and rostral tensioning of the SC. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while the axial pressure distribution in the syrinx remained uniform. These results highlight the importance of the properties of the SC and spinal SAS, such as compliance and permeability, and provide data for comparison with computational models. Further research examining the influence of stenosis size and location, and the importance of tissue properties, is warranted. [DOI:10.1115/1.4000089

Pathological Biomechanics of Cerebrospinal Fluid Pressure in Syringomyelia: Fluid Structure Interaction of an In Vitro Coaxial Elastic Tube System

Full explanation for the formation and pathogenesis of syringomyelia (SM), a neurological pathology characterized by the formation of a cystic cavity (syrinx) in the center of the spinal cord (SC), has not yet been given. The SM pathology forms a coaxial elastic tube system with the inner tube formed by the spinal cord having a syrinx and the outer tube formed by the spinal column (dura and vertebrae)

DNA methylation and hydroxymethylation have distinct genome-wide profiles related to axonal regeneration

Alterations in environmentally sensitive epigenetic mechanisms (e.g., DNA methylation) influence axonal regeneration in the spinal cord following sharp injury. Conventional DNA methylation detection methods using sodium bisulphite treatment do not distinguish between methylated and hydroxymethylated forms of cytosine, meaning that past studies report a composite of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). To identify the distinct contributions of DNA methylation modifications to axonal regeneration, we collected spinal cord tissue after sharp injury from untreated adult F3 male rats with enhanced regeneration of injured spinal axons or controls, derived from folate- or water-treated F0 lineages, respectively. Genomic DNA was profiled for genome-wide 5hmC levels, revealing 658 differentially hydroxymethylated regions (DhMRs). Genomic profiling with whole genome bisulphite sequencing disclosed regeneration-related alterations in composite 5mC + 5hmC DNA methylation levels at 2,260 differentially methylated regions (DMRs). While pathway analyses revealed that differentially hydroxymethylated and methylated genes are linked to biologically relevant axon developmental pathways, only 22 genes harbour both DhMR and DMRs. Since these differential modifications were more than 60 kilobases on average away from each other, the large majority of differential hydroxymethylated and methylated regions are unique with distinct functions in the axonal regeneration phenotype. These data highlight the importance of distinguishing independent contributions of 5mC and 5hmC levels in the central nervous system, and denote discrete roles for DNA methylation modifications in spinal cord injury and regeneration in the context of transgenerational inheritance

Cerebrospinal Fluid Flow Impedance is Elevated in Type I Chiari Malformation

Diagnosis of Type I Chiari malformation (CMI) is difficult because the most commonly used diagnostic criterion, cerebellar tonsillar herniation (CTH) greater than 3–5 mm past the foramen magnum, has been found to have little correlation with patient symptom severity. Thus, there is a need to identify new objective measurement(s) to help quantify CMI severity. This study investigated longitudinal impedance (LI) as a parameter to assess CMI in terms of impedance to cerebrospinal fluid motion near the craniovertebral junction. LI was assessed in CMI patients (N = 15) and age-matched healthy controls (N = 8) using computational fluid dynamics based on subject-specific magnetic resonance imaging (MRI) measurements of the cervical spinal subarachnoid space. In addition, CTH was measured for each subject. Mean LI in the CMI group (551 ± 66 dyn/cm5) was significantly higher than in controls (220 ± 17 dyn/cm5, p \u3c 0.001). Mean CTH in the CMI group was 9.0 ± 1.1 mm compared to −0.4 ± 0.5 mm in controls. Regression analysis of LI versus CTH found a weak relationship (R2 = 0.46, p \u3c 0.001), demonstrating that CTH was not a good indicator of the impedance to CSF motion caused by cerebellar herniation. These results showed that CSF flow impedance was elevated in CMI patients and that LI provides different information than a standard CTH measurement. Further research is necessary to determine if LI can be useful in CMI patient diagnosis