Displacement of the cerebellar tonsils in Chiari type I malformation (CMI) can affect functions controlled by the cerebellum and brainstem. While playing an integral role in the control of movement, ...the cerebellum also has widespread cortical connections, influencing a range of cognitive process. A systematic literature review was conducted to examine the relationship between cognition and CMI, assessing evidence for general or domain-specific cognitive change. The search protocol examined the AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and Scopus databases. Articles meeting the following criteria were included in this review (i) examined children or adults with a clinically defined diagnosis of CMI, (ii) assessed cognitive function with a prospective examination, (iii) included at least one standardized instrument designed to measure general or specific domains of cognitive function, and (iv) were published in English in a peer-reviewed journal. Twelve articles were identified, including 783 cases aged 3 months to 64 years. General cognition, processing speed, and learning and memory appeared less affected, while language deficits appeared to diminish with age. Executive dysfunction was the most commonly reported cognitive impairment, while attention and working memory, and visuospatial and perceptual skills also appeared vulnerable. Numerous methodological limitations were identified that should be considered in interpreting the impact of CMI and planning future investigations. Overall, there is currently insufficient evidence to describe a valid and reliable profile of cognitive impairment in CMI. Further research is required to confirm these preliminary psychometric results and integrate them with pathophysiological models
Key points
Respiration plays a key role in the circulation of cerebrospinal fluid (CSF) around the central nervous system.
During inspiration increased venous return from the cranium is believed to ...draw CSF rostrally. However, this mechanism does not explain why CSF has also been observed to move caudally during inspiration.
We show that during inspiration decreased intrathoracic pressure draws venous blood from the cranium and lumbar spine towards the thorax. We also show that the abdominal pressure was associated with rostral CSF displacement. However, a caudal shift of cervical CSF was seen with low abdominal pressure and comparably negative intrathoracic pressures.
These results suggest that the effects of epidural blood flow within the spinal canal need to be considered, as well as the cranial blood volume balance, to understand respiratory‐related CSF flow. These results may prove useful for the treatment of CSF obstructive pathology and understanding the behaviour of intrathecal drug injections.
It is accepted that during inspiration, cerebrospinal fluid (CSF) flows rostrally to compensate for decreased cranial blood volume, caused by venous drainage due to negative intrathoracic pressure. However, this mechanism does not explain observations of caudal CSF displacement during inspiration. Determining the drivers of respiratory CSF flow is crucial for understanding the pathophysiology of CSF flow disorders. To quantify the influence of respiration on CSF flow, real‐time phase‐contrast magnetic resonance imaging (MRI) was used to record CSF and blood flow, while healthy subjects (5:5 M:F, 25–50 years) performed either a brief expiratory or inspiratory effort between breaths. Transverse images were taken perpendicular to the spinal canal in the middle of the C3 and L2 vertebrae. The same manoeuvres were then performed after a nasogastric pressure catheter was used to measure the intrathoracic and abdominal pressures. During expiratory‐type manoeuvres that elevated abdominal and intrathoracic pressures, epidural blood flow into the spinal canal increased and CSF was displaced rostrally. With inspiratory manoeuvres, the negative intrathoracic pressure drew venous blood from C3 and L2 towards the thoracic spinal canal, and cervical CSF was displaced both rostrally and caudally, despite the increased venous drainage. Regression analysis showed that rostral displacement of CSF at both C3 (adjusted R2 = 0.53; P < 0.001) and L2 (adjusted R2 = 0.38; P < 0.001) were associated with the abdominal pressure. However, with low abdominal pressure and comparably negative intrathoracic pressure, cervical CSF flowed caudally. These findings suggest that changes in both the cranial and spinal pressures need to be considered to understand respiratory CSF flow.
Key points
Respiration plays a key role in the circulation of cerebrospinal fluid (CSF) around the central nervous system.
During inspiration increased venous return from the cranium is believed to draw CSF rostrally. However, this mechanism does not explain why CSF has also been observed to move caudally during inspiration.
We show that during inspiration decreased intrathoracic pressure draws venous blood from the cranium and lumbar spine towards the thorax. We also show that the abdominal pressure was associated with rostral CSF displacement. However, a caudal shift of cervical CSF was seen with low abdominal pressure and comparably negative intrathoracic pressures.
These results suggest that the effects of epidural blood flow within the spinal canal need to be considered, as well as the cranial blood volume balance, to understand respiratory‐related CSF flow. These results may prove useful for the treatment of CSF obstructive pathology and understanding the behaviour of intrathecal drug injections.
Moyamoya vasculopathy is a rare steno-occlusive cerebrovascular disorder presenting with ischemia or hemorrhage. There are racial and geographic differences in presentation and outcome. There is ...little information regarding moyamoya in Australia.
Moyamoya patients undergoing surgery from 2001 to 2022 were studied retrospectively. The outcomes of revascularization surgery in adult and pediatric patients, with ischemic and hemorrhagic disease were analyzed, including functional outcomes, postoperative complications, bypass patency, and long-term rates of ischemic and hemorrhagic events.
A total of 68 patients with 122 revascularized hemispheres and 8 posterior circulation revascularizations were included in this study. Eighteen patients were of Asian descent and 46 were of Caucasian origin. Presentation was with ischemia in 124 hemispheres and hemorrhage in six hemispheres. There were 92 direct, 34 indirect, and 4 combined revascularization surgeries performed. Early postoperative complications occurred in 3.1% (n = 4) of operations and delayed complications (infection, subdural hematoma) occurred after 4.6% (n = 6) of operations. Mean follow-up was 6.5 years (3–252 months). There was 100% patency of direct grafts at last follow-up. There were no hemorrhagic events following surgery and 1 new ischemic event 2 years after surgery. There was significant improvement in physical health functional outcomes at most recent follow-up (P < 0.05); mental health outcomes were not different between preoperative and postoperative assessments.
The majority of Australian moyamoya patients are Caucasian and the most common clinical presentation is ischemia. Revascularization surgery had excellent outcomes with very low rates of ischemia and hemorrhage, comparing favorably to the natural history of moyamoya vasculopathy.
Endothelial cells are highly sensitive to ionizing radiation, and exposure leads to multiple adaptive changes. Remarkably, part of this response is the translocation of normally intracellular ...proteins to the cell surface. It is unclear whether this ectopic expression has a protective or deleterious function, but, regardless, these surface-exposed proteins may provide unique discriminatory targets for radiation-guided drug delivery to vascular malformations or tumor vasculature. We investigated the ability of an antibody–thrombin conjugate targeting mitochondrial PDCE2 (E2 subunit of pyruvate dehydrogenase) to induce precision thrombosis on irradiated endothelial cells in a parallel-plate flow system. Click-chemistry was used to create antibody–thrombin conjugates targeting PDCE2 as the vascular targeting agent (VTA). VTAs were injected into the parallel-plate flow system with whole human blood circulating over irradiated cells. The efficacy and specificity of fibrin-thrombus formation was assessed relative to non-irradiated controls. The PDCE2-targeting VTA dose-dependently increased thrombus formation: minimal thrombosis was induced in response to 5 Gy radiation; doses of 15 and 25 Gy induced significant thrombosis with equivalent efficacy. Negligible VTA binding or thrombosis was demonstrated in the absence of radiation or with non-targeted thrombin. PDCE2 represents a unique discriminatory target for radiation-guided drug delivery and precision thrombosis in pathological vasculature.
Chiari malformation is characterised by the herniation of the cerebellar tonsils through the foramen magnum. However, tonsillar herniation and other 2D morphometric measurements of the posterior ...cranial fossa (PCF) have a weak association with patients’ symptoms and clinical outcomes. This study aimed to contrast current 2D metrics with a novel 3D shape analysis of the PCF and the hindbrain, to determine if 3D measurements provides further insight into the pathophysiology of Chiari. The cranium of 12 controls and 21 Chiari malformation patients with (N = 9) and without (N = 12) a syrinx were scanned. The morphology of the PCF was quantified with typical 2D measurements. Additionally, a correspondence-based shape model that normalised the PCF volume, was used to find 3D differences in the shape of the PCF, and the distance of the hindbrain from the inner surfaces of the PCF. Shape analysis showed that, compared to controls, the caudal (p = 0.007; 2.3 mm, IQR: 1.6–3.3 mm) and anterior (p = 0.027; 1.3 mm,IQR: 1.1–1.6 mm) surfaces of the hindbrain were closer to the PCF in patients with and without a syrinx, respectively. However, there were negligible differences in the shape of the PCF between patient groups (p > 0.39). Current morphometric measures should be normalised for variation in PCF volume, so that shape measures are not biased. The reduced CSF space between the hindbrain and PCF will alter CSF dynamics, which may compress cerebellar vasculature and contribute to patient symptomatology.
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.
Purpose
To train deep learning convolutional neural network (CNN) models for classification of clinically significant Chiari malformation type I (CM1) on MRI to assist clinicians in diagnosis and ...decision making.
Methods
A retrospective MRI dataset of patients diagnosed with CM1 and healthy individuals with normal brain MRIs from the period January 2010 to May 2020 was used to train ResNet50 and VGG19 CNN models to automatically classify images as CM1 or normal. A total of 101 patients diagnosed with CM1 requiring surgery and 111 patients with normal brain MRIs were included (median age 30 with an interquartile range of 23–43; 81 women with CM1). Isotropic volume transformation, image cropping, skull stripping, and data augmentation were employed to optimize model accuracy. K-fold cross validation was used to calculate sensitivity, specificity, and the area under receiver operating characteristic curve (AUC) for model evaluation.
Results
The VGG19 model with data augmentation achieved a sensitivity of 97.1% and a specificity of 97.4% with an AUC of 0.99. The ResNet50 model achieved a sensitivity of 94.0% and a specificity of 94.4% with an AUC of 0.98.
Conclusions
VGG19 and ResNet50 CNN models can be trained to automatically detect clinically significant CM1 on MRI with a high sensitivity and specificity. These models have the potential to be developed into clinical support tools in diagnosing CM1.
Perivascular spaces play a pivotal role in the exchange between cerebrospinal and interstitial fluids, and in the clearance of waste in the CNS, yet their precise anatomical components are not well ...described. The aim of this study was to characterise the ultrastructure of perivascular spaces and their role in the transport of fluid, in the spinal cord of healthy rats, using transmission electron microscopy. The distribution of cerebrospinal fluid tracers injected into the subarachnoid space was studied using light, confocal and electron microscopy. Perivascular spaces were found around arterioles and venules, but not capillaries, throughout the spinal cord white and grey matter. They contained fibroblasts and collagen fibres, and were continuous with the extracellular spaces of the surrounding tissue. At 5 min post injection, tracers were seen in the subarachnoid space, the peripheral white matter, the perivascular spaces, basement membranes, extracellular spaces of the surrounding tissue, and surprisingly, in the lumen of blood vessels, suggesting trans-vascular clearance. These findings point out an unrecognised outflow pathway for CNS fluids, with potential implications for volume regulation in health and disease states, but also clinically for the detection of CNS-derived biomarkers in plasma, the immune response and drug pharmacokinetics.
Abstract
Posttraumatic syringomyelia (PTS) is an enigmatic condition characterized by the development of fluid-filled cysts (syrinxes) within the spinal cord. Perivascular spaces (PVS) are a critical ...component of fluid transport within the central nervous system (CNS), with dilated PVSs variably implicated in the pathogenesis of syringomyelia. The extent and spatial distribution of dilated PVSs in syringomyelia, however, remains unclear. This study aims to develop a method to assess PVS dimensions across multiple spinal cord segments in rats with PTS. Syrinxes were induced in two Sprague–Dawley rats at C6/7 with computer-controlled motorized spinal cord impaction; two control rats underwent sham laminectomies. Spinal cord segments were obtained at C4, C6 and C8, cleared via tissue clearing protocols, stained with immunofluorescent antibodies and imaged under confocal microscopy. Qualitative and quantitative analyses of PVS size were performed. Arteriolar PVSs were enlarged in the perisyringeal region of the spinal cord, compared to the control cord. No PVS enlargement was observed above or below the syrinx. These results confirm previous incidental findings of enlarged PVSs in the perisyringeal region, providing new insights into PVS dimensions across multiple spinal segments, and providing a novel method for quantifying spinal cord perivascular space size distributions.
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