Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow.

Appropriate vascular function is essential for the maintenance of central nervous system homeostasis and is achieved through virtue of the blood-brain barrier; a specialized structure consisting of endothelial, mural, and astrocytic interactions. While appropriate blood-brain barrier function is typically achieved, the central nervous system vasculature is not infallible and cerebrovascular anomalies, a collective terminology for diverse vascular lesions, are present in meningeal and cerebral vasculature supplying and draining the brain. These conditions, including aneurysmal formation and rupture, arteriovenous malformations, dural arteriovenous fistulas, and cerebral cavernous malformations, and their associated neurological sequelae, are typically managed with neurosurgical or pharmacological approaches. However, increasing evidence implicates interacting roles for inflammatory responses and disrupted central nervous system fluid flow with respect to vascular perturbations. Here, we discuss cerebrovascular anomalies from an immunologic angle and fluid flow perspective. We describe immune contributions, both common and distinct, to the formation and progression of diverse cerebrovascular anomalies. Next, we summarize how cerebrovascular anomalies precipitate diverse neurological sequelae, including seizures, hydrocephalus, and cognitive effects and possible contributions through the recently identified lymphatic and glymphatic systems. Finally, we speculate on and provide testable hypotheses for novel nonsurgical therapeutic approaches for alleviating neurological impairments arising from cerebrovascular anomalies, with a particular emphasis on the normalization of fluid flow and alleviation of inflammation through manipulations of the lymphatic and glymphatic central nervous system clearance pathways.

Response of the cerebral vasculature following traumatic brain injury.

The critical role of the vasculature and its repair in neurological disease states is beginning to emerge particularly for stroke, dementia, epilepsy, Parkinson's disease, tumors and others. However, little attention has been focused on how the cerebral vasculature responds following traumatic brain injury (TBI). TBI often results in significant injury to the vasculature in the brain with subsequent cerebral hypoperfusion, ischemia, hypoxia, hemorrhage, blood-brain barrier disruption and edema. The sequalae that follow TBI result in neurological dysfunction across a host of physiological and psychological domains. Given the importance of restoring vascular function after injury, emerging research has focused on understanding the vascular response after TBI and the key cellular and molecular components of vascular repair. A more complete understanding of vascular repair mechanisms are needed and could lead to development of new vasculogenic therapies, not only for TBI but potentially vascular-related brain injuries. In this review, we delineate the vascular effects of TBI, its temporal response to injury and putative biomarkers for arterial and venous repair in TBI. We highlight several molecular pathways that may play a significant role in vascular repair after brain injury.

Pediatric multiple sclerosis: pathobiological, clinical, and magnetic resonance imaging features.

In this article, the pathobiological, clinical, and treatment aspects of pediatric-onset multiple sclerosis (MS) are summarized, and the conventional magnetic resonance (MR) imaging (ie, T1-weighted, proton-density, and T2-weighted imaging) features of MS in children are discussed, as well as the application of MR imaging in the diagnosis of pediatric-onset MS and in prediction of MS in children with an incident central nervous system demyelination. Insights gained from studies comparing MR imaging features of pediatric-onset and adult-onset MS are presented.

Cerebral venous thrombosis and anticardiolipin antibodies.

BACKGROUND AND PURPOSE: The association of cerebral venous thrombosis (CVT) with a variety of pathological states is well established. However, there are only rare isolated reports of CVT associated with anticardiolipin antibodies (aCL). METHODS: To clarify the clinical and neuradiological features as well as outcome of patients with CVT associated with aCL, we reviewed the records of all patients with CVT evaluated at our institution between 1989 and 1996 (retrospective and prospective) and systematically reviewed the pertinent literature. RESULTS: We identified 8 aCL+ and 7 aCL- patients with CVT. No patients with lupus anticoagulant (LA) were identified. The mean age was 23 +/- 11.01 (range, < 1 to 36) years in the aCL+ and 38 +/- 9.30 (range, 25 to 54) years in the aCL- patients (P = .016). Six of 8 aCL+ and 5 of 7 aCL- patients were women. The dural sinuses were involved in all aCL+ and in 6 of 7 aCL- patients, while deep venous system thrombosis occurred in 5 of 8 (63%) aCL+ and 1 of 7 (14%) aCL- patients. In the aCL+ patients CVT was associated with puerperium or oral contraceptive use (n = 6), and sickle cell trait (n = 1), and in the aCL- patients CVT was associated with systemic lupus erythromatosus (n = 1), myelodysplasti syndrome (n = 1), colonic cancer (n = 1), oral contraceptive use or puerperium (n = 3), and dehydration (n = 1). Seven aCL+ patients received either intrasinus urokinase or intravenous heparin sulfate, and 1 received aspirin. Four aCL+ patients developed new onset or worsening of preexisting migraine, 2 developed recurrent peripheral venous thrombosis, and 1 went on to have intracranial hypertension. Twenty additional patients with CVT associated with antiphospholipid antibodies (aPL) were found reported in the literature. The overall mean age was 36 +/- 11.6 (range, 21 to 62) years, and 14 (70%) were women. LA was present in 11 of 18 tested, aCL in 7 (35%), LA and aCL in 1, and the type of aPL was not reported in 3. The mean age for the aCL+ only group was 28 years and for the LA+ (with or without aCL+) was 34 years. Only 1 patient, whose aPL type was not specified, had thrombosis of the deep venous system in addition to involvement of the dural sinuses. CONCLUSIONS: Our series and review suggest that aCL may be an important factor contributing to development of CVT even in the presence of other potential etiologies or risk factors. Onset of aCL+ CVT occurs at a relative young age and with relatively more extensive superficial and deep cerebral venous system involvement than aCL- CVT.

Nicotine induces leukocyte rolling and adhesion in the cerebral microcirculation of the mouse.

Nicotine and several related metabolites were examined for their ability to induce leukocyte rolling and adhesion in the cerebral microcirculation of the mouse. A cranial window was surgically prepared for the visualization of the pial microcirculation using an intra-vital microscopy imaging system. Using this technique rhodamine-labeled leukocytes could be visualized and video-recorded as they traveled within the microvessels, and the quantitation of their rolling and adhesion along the pial venule walls was assessed during an off-line video playback analysis. Nicotine was found to produce significant dose-related increases in leukocyte rolling and adhesion. Cotinine, a major nicotine metabolite, did not induce the same degree of leukocyte rolling and adhesion. Mecamylamine, a nicotine antagonist, was found to inhibit the nicotine-induced leukocyte rolling and adhesion. Anti-P-selectin antibody blocked nicotine-induced leukocyte rolling, while anti-CD18 antibody effectively inhibited leukocyte adhesion, but not rolling in similar experiments. Nicotine-induced leukocyte rolling and adhesion were also inhibited by superoxide dismutase and catalase. These data suggest that nicotine, the principle pharmacological agent in cigarette smoke and related tobacco products, acts via a ganglionic-type nicotinic receptor to enhance leukocyte rolling via P-selectin and reactive oxygen radical-dependent mechanisms in cerebral microcirculation of the mouse.

Differential degeneration of the cerebral microvasculature in Alzheimer's disease.

We used immunocytochemical methods to define abnormalities in the cerebral endothelium and the vascular basement membrane in patients with Alzheimer's disease (AD) and in aging control subjects. Double immunostaining with antibodies to the endothelial cell markers CD34 and CD31 revealed an absence of endothelial staining in many capillary profiles that still appeared to retain their basement membranes stained by antibodies to collagen IV. Such differential labeling, clearly suggesting capillaries with collapsed or degenerated endothelium, was frequently (> 90% of cases) evident in AD but relatively lacking in brain regions or other diseases and controls (< 30%) free of amyloid beta (A beta) deposits. We suggest that this profound vascular phenomenon is concomitant with A beta deposition and implies abnormalities in the integrity of brain microvasculature related to neuronal degeneration in AD.

Dural sinus thrombosis and venous infarction associated with antiphospholipid antibodies: MR findings.

OBJECTIVE: Our goal was to describe the neuroradiologic findings in hemorrhagic venous infarction related to a hypercoagulable state caused by antiphospholipid antibodies (aPA). MATERIALS AND METHODS: Magnetic resonance imaging was performed on two patients with superior sagittal thrombosis related to the presence of aPA. RESULTS: A parenchymal region of hyperintense signal due to hemorrhagic venous infarction was demonstrated in both patients, along with abnormal signal within the thrombosed superior sagittal sinus. CONCLUSION: Hemorrhagic venous infarction may result from the hypercoagulable state related to aPA. The presence of these antibodies should be considered in the setting of otherwise unexplained dural sinus thrombosis and/or venous infarction.