Brain solute transport is more rapid in periarterial than perivenous spaces

Fluid flow in perivascular spaces is recognized as a key component underlying brain transport and clearance. An important open question is how and to what extent differences in vessel type or geometry affect perivascular fluid flow and transport. Using computational modelling in both idealized and image-based geometries, we study and compare fluid flow and solute transport in pial (surface) periarterial and perivenous spaces. Our findings demonstrate that differences in geometry between arterial and venous pial perivascular spaces (PVSs) lead to higher net CSF flow, more rapid tracer transport and earlier arrival times of injected tracers in periarterial spaces compared to perivenous spaces. These findings can explain the experimentally observed rapid appearance of tracers around arteries, and the delayed appearance around veins without the need of a circulation through the parenchyma, but rather by direct transport along the PVSs.

Reorganization of Thalamic Inputs to Lesioned Cortex Following Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) disrupts thalamic and cortical integrity. The effect of post-injury reorganization and plasticity in thalamocortical pathways on the functional outcome remains unclear. We evaluated whether TBI causes structural changes in the thalamocortical axonal projection terminals in the primary somatosensory cortex (S1) that lead to hyperexcitability. TBI was induced in adult male Sprague Dawley rats with lateral fluid-percussion injury. A virus carrying the fluorescent-tagged opsin channel rhodopsin 2 transgene was injected into the ventroposterior thalamus. We then traced the thalamocortical pathways and analyzed the reorganization of their axonal terminals in S1. Next, we optogenetically stimulated the thalamocortical relays from the ventral posterior lateral and medial nuclei to assess the post-TBI functionality of the pathway. Immunohistochemical analysis revealed that TBI did not alter the spatial distribution or lamina-specific targeting of projection terminals in S1. TBI reduced the axon terminal density in the motor cortex by 44% and in S1 by 30%. A nematic tensor-based analysis revealed that in control rats, the axon terminals in layer V were orientated perpendicular to the pial surface (60.3°). In TBI rats their orientation was more parallel to the pial surface (5.43°, difference between the groups p < 0.05). Moreover, the level of anisotropy of the axon terminals was high in controls (0.063) compared with TBI rats (0.045, p < 0.05). Optical stimulation of the sensory thalamus increased alpha activity in electroencephalography by 312% in controls (p > 0.05) and 237% (p > 0.05) in TBI rats compared with the baseline. However, only TBI rats showed increased beta activity (33%) with harmonics at 5 Hz. Our findings indicate that TBI induces reorganization of thalamocortical axonal terminals in the perilesional cortex, which alters responses to thalamic stimulation.

Single-hole, ruptured parenchymal arteriovenous fistula of the mesencephalon : Not known vascular malformation of the brain or a posthemorrhagic entity?

The subtypes of brain arteriovenous malformations, with direct, single-hole fistulas without co-existing nidus are not described as existing entities inside the brain parenchyma but on the pial surface. True parenchymal arteriovenous malformations present with nidal structure, even if they are small, whereas surface lesions may present a direct fistulous configuration. In this case of midbrain haemorrhage a direct arteriovenous fistula was detected at the level of the red nucleus between a paramedian midbrain perforator artery and a paramedian parenchymal vein, with pseudo-aneurysm formation at the fistulous connection, without signs of adjacent nidus structure. The hypothesis whether a pre-existing arteriovenous fistula ruptured or a spontaneous haemorrhage has caused the fistulous connection is discussed.

Coupling one-dimensional arterial blood flow to three-dimensional tissue perfusion models for in silico trials of acute ischaemic stroke

An acute ischaemic stroke is due to the sudden blockage of an intracranial blood vessel by an embolized thrombus. In the context of setting up in silico trials for the treatment of acute ischaemic stroke, the effect of a stroke on perfusion and metabolism of brain tissue should be modelled to predict final infarcted brain tissue. This requires coupling of blood flow and tissue perfusion models. A one-dimensional intracranial blood flow model and a method to couple this to a brain tissue perfusion model for patient-specific simulations is presented. Image-based patient-specific data on the anatomy of the circle of Willis are combined with literature data and models for vessel anatomy not visible in the images, to create an extended model for each patient from the larger vessels down to the pial surface. The coupling between arterial blood flow and tissue perfusion occurs at the pial surface through the estimation of perfusion territories. The coupling method is able to accurately estimate perfusion territories. Finally, we argue that blood flow can be approximated as steady-state flow at the interface between arterial blood flow and tissue perfusion to reduce the cost of organ-scale simulations.

Dissociation of broadband high-frequency activity and neuronal firing in the neocortex

Broadband high-frequency activity (BHA; 70 to 150 Hz), also known as “high gamma,” a key analytic signal in human intracranial (electrocorticographic) recordings, is often assumed to reflect local neural firing [multiunit activity (MUA)]. As the precise physiological substrates of BHA are unknown, this assumption remains controversial. Our analysis of laminar multielectrode data from V1 and A1 in monkeys outlines two components of stimulus-evoked BHA distributed across the cortical layers: an “early-deep” and “late-superficial” response. Early-deep BHA has a clear spatial and temporal overlap with MUA. Late-superficial BHA was more prominent and accounted for more of the BHA signal measured near the cortical pial surface. However, its association with local MUA is weak and often undetectable, consistent with the view that it reflects dendritic processes separable from local neuronal firing.

Pial surface CSF-contacting texture, subpial and funicular plexus in the thoracic spinal cord in monkey: NADPH diaphorase histological configuration

In spinal cord, white matter is distinguished from grey matter in that it contains ascending and descending axonal tracts. While grey matter gets concentrated with neuronal cell bodies. Notable cell bodies and sensory modality of cerebral spinal fluid (CSF) in white matter are still elusive in certain segment of the spinal cord. Monkey Spinal cord was examined by NADPH diaphorase (NADPH-d) histochemistry. We found that NADPH-d positive neurons clustered and featured flat plane in mediolateral funiculus in caudal thoracic and rostral lumber spinal cord, especially evident in the horizontal sections. Majority of NADPH-d funicular neurons were relatively large size and moderately-or lightly-stained neurons. In horizontal section, the multipolar processes of the neurons were thicker than that of regular other neurons. The processes oriented laterally or obliquely in the lateral funiculus. Some of neuronal cell bodies and proximal processes attached NADPH-d positive buttons or puncta. The neuronal processes interlaced network medially linked to lateral horn (intermediolateral nucleus, IML) and laterally to subpial region, in which formed subpial plexus with subpial NADPH-d neurons. Subpial plexus appeared to contacting externally with CSF. The subpial plexus patterned like round brackets located in lateromarginal pial surface. Compared with sympathetic IML in rostral thoracic segments and sacral parasympathetic IML, the funicular plexus configurated a specialized neuro-texture in caudal thoracic segments. The dendritic arbor of funicular neuron featured variety geometric plane shapes. The funicular plexus oriented exclusive layered flat-plane organization between lateral horn and subpial region in caudal thoracic and rostral lumber spinal cord. The subpial plexus may work as CSF sensor outside of spinal cord. The cluster of funicular neurons may function as locomotion sensor, besides visceral regulation. Different to periventricular CSF contacting or pericentral canal structures, NADPH-d funicular neurons and subpial plexus that located in the pial surface. With advantage of NADPH-d, we found funicular neurons which termed academically as funicular plexus and specialized localization for subpial structure we termed subpial plexus. The funicular texture was regarded as neuronal bridge between the interior CSF in the central canal and external CSF out of the pial surface.

The lateral supracerebellar infratentorial, translateral mesencephalic sulcus approach to the mesencephalopontine junction

The lateral supracerebellar infratentorial (SCIT) approach provides advantageous access to lesions located in the lateral mesencephalon and mesencephalopontine junction. For lesions that abut the pial surface, a direct approach is ideal and well tolerated. For deep-seated lesions, the lateral mesencephalic sulcus (LMS) can be used to access lesions with minimal morbidity to the patient. This video demonstrates the use of the SCIT approach via the LMS to remove a cavernous malformation at the level of the mesencephalopontine junction. The use of somatosensory and motor evoked potential monitoring and intraoperative neuronavigation is essential for optimizing patient outcomes. Meticulous, multilayered closure is critical for optimal results in the posterior fossa. For optimal patient outcomes, approach selection for deep-seated lesions should combine the two-point method with safe entry zones. At follow-up, the patient had persistent sensory changes but was otherwise neurologically intact.The video can be found here: https://youtu.be/bHFEZhG8dHw.

Brainstem Tumor Resection via Occipital Interhemispheric Transtentorial Infracollicular Approach: 2-Dimensional Operative Video

A brainstem tumor located at the upper pons or pontomesencephalic region is surgically challenging because of the deep-seated location and difficulty to approach, especially if the lesion is intra-axial and extends anteriorly without appearing on the pia surface. In our experience, the infracollicular entry point is feasible for such lesions and can be approached by an occipital interhemispheric transtentorial corridor through a straightforward trajectory, which ensures surgical ergonomics. Herein, we present a case of a 55-yr-old woman with a pontomesencephalic lesion removed via an occipital interhemispheric transtentorial infracollicular approach. Informed consent was obtained from the patient. Her preoperative medical course and radiological findings strongly indicated the lesion as a brainstem cavernous malformation. Although the overlying brainstem parenchyma was thin, the lesion did not appear on the pial surface. The lesion was removed via an occipital interhemispheric transtentorial infracollicular approach. During the operation, the lesion was observed to have an old hemorrhagic component and an obvious gliotic boundary, resembling the typical macropathology of a brainstem cavernous malformation. We easily dissected the lesion circumferentially off the brainstem parenchyma after thorough debulking, and a gross total resection was performed en bloc. However, postoperative pathology confirmed a diagnosis of a metastatic neuroendocrine tumor, and further systematic examination revealed cancerous lesions in the lungs. The patient experienced slight hypophrasia but recovered within 3 d postoperatively and then was discharged for further treatment. This case demonstrates the safety and efficacy of an occipital interhemispheric transtentorial infracollicular approach for brainstem tumor resection.

Moyamoya Disease in Infancy: Application of a Novel Indirect Revascularization Technique for Bihemispheric Cortical Synangiosis

INTRODUCTION Moyamoya disease (MMD) is a rare progressive cerebral arteriopathy characterized by nonatherosclerotic steno-occlusive lesions of the Circle of Willis. Presentation in infancy is rare and usually presents with ischemic stroke. We present a 7-mo old female with bilateral MMD who presented for indirect revascularization after 2 successive strokes in multiple vascular territories. METHODS We demonstrate a novel indirect revascularization technique in infant MMD whereby the patient's multifocal ischemic burden and STA caliber precluded arterial and myosynangiosis. We instead utilized bihemispheric pericranium for revascularization of bilateral oligemic cerebrum. Through a bicoronal scalp incision and inverted T-shaped pericranial incision, large anteriorly-based pericranial flaps were applied to the exposed pial surface using bilateral hemicraniotomies. Synangiosis extended from the frontal pole into parieto-occipital territories. We additionally performed a literature search on bypass approaches used for infant MMD. RESULTS A total of 10 infant MMD cases have been reported in the literature. Our case represents the only use of a pericranial graft in an infant without a combined approach. Pial synangiosis, EDAS, and conservative management represent techniques described in this population. Two case series utilized pericranial flaps with EDAS, however, no infants were included nor did revascularization extend beyond traditional margins. Our patient remains stroke and seizure-free for at least 16-months. She is ambulating independently and meeting her pediatric milestones. CONCLUSION Indirect revascularization is favored in pediatric MMD with approaches primarily utilizing native vessel donor grafts. Bilateral revascularization is performed in a delayed, sequential fashion if indicated. Further, collateralization is limited by the anatomical graft parameters, making hemispheric pathology difficult to comprehensively treat with these approaches. Our case demonstrates the safety and efficacy of utilizing a large bihemispheric pericranial flap on its native pedicle with bilateral hemicraniotomies for revascularization of multiple cerebrovascular territories in severe infant MMD. Our technique also allows for preservation of critical native vessels should the need for reoperation arise.