Marcus A. Stoodley, Cornelia Hermann and Bryce Weir
Sarah J. Hemley, Lynne E. Bilston, Shaokoon Cheng and Marcus A. Stoodley
Noncommunicating canalicular syringomyelia occurs in up to 65% of patients with Chiari malformation Type I. The pathogenesis of this type of syringomyelia is poorly understood and treatment is not always effective. Although it is generally thought that syringomyelia is simply an accumulation of CSF from the subarachnoid space, the pathogenesis is likely to be more complex and may involve cellular and molecular processes. Aquaporin-4 (AQP4) has been implicated in numerous CNS pathological conditions involving fluid accumulation, including spinal cord edema. There is evidence that AQP4 facilitates the removal of extracellular water following vasogenic edema. The aim of this study was to investigate AQP4 expression and the structural and functional integrity of the blood–spinal cord barrier (BSCB) in a model of noncommunicating canalicular syringomyelia.
A kaolin-induced model of canalicular syringomyelia was used to investigate BSCB permeability and AQP4 expression in 27 adult male Sprague-Dawley rats. Control groups consisted of nonoperated, laminectomy-only, and saline-injected animals. The structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen. Functional integrity of the BSCB was assessed by extravasation of systemically injected horseradish peroxidase (HRP) at 1, 3, 6, or 12 weeks after surgery. Immunofluorescence was used to assess AQP4 and glial fibrillary acidic protein (GFAP) expression at 12 weeks following syrinx induction.
Extravasation of HRP was evident surrounding the central canal in 11 of 15 animals injected with kaolin, and in 2 of the 5 sham-injected animals. No disruption of the BSCB was observed in laminectomy-only controls. At 12 weeks the tracer leakage was widespread, occurring at every level rostral to the kaolin injection. At this time point there was a decrease in EBA expression in the gray matter surrounding the central canal from C-5 to C-7. Aquaporin-4 was expressed in gray- and white-matter astrocytes, predominantly at the glia limitans interna and externa, and to a lesser extent around neurons and blood vessels, in both control and syrinx animals. Expression of GFAP and APQ4 directly surrounding the central canal in kaolin-injected animals was variable and not significantly different from expression in controls.
This study demonstrated a prolonged disruption of the BSCB directly surrounding the central canal in the experimental model of noncommunicating canalicular syringomyelia. The disruption was widespread at 12 weeks, when central canal dilation was most marked. Loss of integrity of the barrier with fluid entering the interstitial space of the spinal parenchyma may contribute to enlargement of the canal and progression of syringomyelia. Significant changes in AQP4 expression were not observed in this model of canalicular syringomyelia. Further investigation is needed to elucidate whether subtle changes in AQP4 expression occur in canalicular syringomyelia.
Lynne E. Bilston, Marcus A. Stoodley and David F. Fletcher
The mechanisms of syringomyelia have long puzzled neurosurgeons and researchers alike due to difficulties in identifying the driving forces behind fluid flow into a syrinx, apparently against a pressure gradient between the spinal cord and the subarachnoid space (SAS). Recently, the synchronization between CSF flow and the cardiac cycle has been postulated to affect fluid flow in the spinal cord. This study aims to determine the effect of changes in the timing of SAS pressure on perivascular flow into the spinal cord.
This study uses a computational fluid dynamics model to investigate whether the relative timing of a spinal artery cardiovascular pulse wave and fluid pressure in the spinal SAS can influence CSF flow in the perivascular spaces.
The results show that the mass flow rate of CSF through a model periarterial space is strongly influenced by the relative timing of the arterial pulse wave and the SAS pressure.
These findings suggest that factors that might alter the timing of the pulse wave or the fluid flow in the SAS could potentially affect fluid flow into a syrinx.
Manuri Gunawardena, Jeffrey M. Rogers, Marcus A. Stoodley and Michael K. Morgan
Previous trials rejected a role of extracranial-to-intracranial bypass surgery for managing symptomatic atheromatous disease. However, hemodynamic insufficiency may still be a rationale for surgery, provided the bypass can be performed with low morbidity and patency is robust.
Consecutive patients undergoing bypass surgery for symptomatic non-moyamoya intracranial arterial stenosis or occlusion were retrospectively identified. The clinical course and surgical outcomes of the cohort were evaluated at 6 weeks, 6 months, and annually thereafter.
From 1992 to 2017, 112 patients underwent 127 bypasses. The angiographic abnormality was arterial occlusion in 80% and stenosis in 20%. Procedures were performed to prevent future stroke (76%) and stroke reversal (24%), with revascularization using an arterial pedicle graft in 80% and venous interposition graft (VIG) in 20%. A poor outcome (bypass occlusion, new stroke, new neurological deficit, or worsening neurological deficit) occurred in 8.9% of patients, with arterial pedicle grafts (odds ratio [OR] 0.15), bypass for prophylaxis against future stroke (OR 0.11), or anterior circulation bypass (OR 0.17) identified as protective factors. Over the first 8 years following surgery the 66 cases exhibiting all three of these characteristics had minimal risk of a poor outcome (95% confidence interval 0%–6.6%).
Prophylactic arterial pedicle bypass surgery for anterior circulation ischemia is associated with high graft patency and low stroke and surgical complication rates. Higher risks are associated with acute procedures, typically for posterior circulation pathology and requiring VIGs. A carefully selected subgroup of individuals with hemodynamic insufficiency and ischemic symptoms is likely to benefit from cerebral revascularization surgery.
Sarah J. Hemley, B. Biotech, Jian Tu and Marcus A. Stoodley
Posttraumatic syringomyelia produces a significant burden of pain and neurological deficits in patients with spinal cord injury. The mechanism of syrinx formation is unknown and treatment is often ineffective. A possible explanation for syrinx formation is fluid leakage from the microcirculation in the presence of a compromised blood-spinal cord barrier (BSCB). The aim of this study was to investigate the structural and functional integrity of the BSCB in a model of posttraumatic syringomyelia.
The excitotoxic amino acid and arachnoiditis model of syringomyelia was used in 27 Sprague-Dawley rats. Structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen (EBA), and loss of functional integrity was assessed by extravasation of intravascular horseradish peroxidase. Animals were studied after 3 days, or at 1, 3, 6, or 12 weeks after surgery. There were laminectomy-only and saline injection control animals for comparison at each time point.
Syrinxes formed in 16 of the 17 animals injected with excitotoxic amino acid. Loss of structural and functional integrity of the BSCB in syrinx animals was noted at all time points. Disruption of the BSCB was most dramatic in tissue adjacent to the syrinx, and in the central and dorsal gray matter. Changes in EBA expression generally corresponded with altered vascular permeability, although in the acute stages, widespread vascular permeability occurred without a corresponding decrease in EBA expression. At the later time points (3–12 weeks) EBA expression was often absent, although no vascular leakage was observed.
This study demonstrated a prolonged structural and functional disruption of the BSCB in this model of posttraumatic syringomyelia. Loss of functional integrity of the BSCB, with fluid entering the interstitial space of the spinal cord, may contribute to initial cyst formation after spinal cord injury and subsequent enlargement of the cyst, to produce posttraumatic syringomyelia.
Michael G. Fehlings and James W. Austin
Vannessa Leung, John S. Magnussen, Marcus A. Stoodley and Lynne E. Bilston
The pathogenesis of syringomyelia associated with Chiari malformation type I (CM-I) is unclear. Theories of pathogenesis suggest the cerebellar tonsils may obstruct CSF flow or alter pressure gradients, or their motion might act as a piston to increase CSF pressure in the spinal subarachnoid space. This study was performed to measure cerebellar tonsillar and hindbrain motion in CM-I and assess the potential contributions to syrinx formation.
Sixty-four CM-I patients and 25 controls were retrospectively selected from a clinical database, and all subjects had undergone cardiac-gated cine balanced fast-field echo MRI. There were a total of 36 preoperative CM-I scans, which consisted of 15 patients with and 21 patients without syringomyelia. Nineteen patients underwent paired pre- and postoperative imaging. Anteroposterior (AP) and superoinferior (SI) movements of the tip of the cerebellar tonsils, obex, fastigium of the fourth ventricle, pontomedullary junction, and cervicomedullary junction were measured. The distance between the fastigium and tip of the tonsils was used to calculate tonsillar tissue strain (Δi/i 0).
CM-I patients had significantly greater cerebellar tonsillar motion in both the AP and SI directions than controls (AP +0.34 mm [+136%], p < 0.001; SI +0.49 mm [+163%], p < 0.001). This motion decreased after posterior fossa decompression (AP −0.20 mm [−33%], p = 0.001; SI −0.29 mm [−36%]; p < 0.001), but remained elevated above control levels (AP +56%, p = 0.021; SI +67%, p = 0.015). Similar trends were seen for all other tracked landmarks. There were no significant differences in the magnitude or timing of motion throughout the hindbrain between CM-I patients with and without syringomyelia. Increased tonsillar tissue strain correlated with Valsalva headaches (p = 0.03).
Cerebellar tonsillar motion may be a potential marker of CM-I and may have use in tailoring surgical procedures. The lack of association with syringomyelia suggests that tonsillar motion alone is not the driver of syrinx formation. Tonsillar tissue strain may play a part in the pathophysiology of Valsalva headaches.