The pathology of encephalic arteriovenous malformations treated by prior embolotherapy

Summary A pathologic study was undertaken of seven encephalic arteriovenous malformations, including five resected from one to seven days after balloon embolization, one resected 10 days after embolization with polyvinyl alcohol foam (PVA), and a large mesencephalic AVM in a patient who died eight weeks after a series of embolization procedures with PVA and silicone spheres. AVM's resected 6–7 days following balloon embolization showed focal mural and adventitial inflammatory infiltrates and parenchymal (i.e. non-vascular) necrosis of a large portion of one AVM. The AVM examined 7 days post-balloon embolization showed an intraluminal thrombus containing refractile particles surrounded by foreign body giant cells (FBGC's). The AVM removed 10 days after PVA embolotherapy showed mural and perivascular necrosis with infiltration by polymorphonuclear leukocytes. The single autopsy case showed FBGC's surrounding residual PVA, refractile particles deep within vascular walls, and marked mural thickening of AVM channel walls, changes that may represent a response to previous angionecrosis and inflammation at the time of embolization. These findings, the pathogenesis of which is discussed in detail, may help to explain some of the rare complications of iatrogenic embolotherapy with these materials, as well as providing evidence for the basis of their efficacy.Presented in part at the 63rd Annual meeting of the American Association of Neuropathologists, Seattle, Washington, June, 1987     

A prospective, randomized, cross-over comparison of two methods of artificial insemination by donor on the incidence of conception: intracervical insemination by straw versus cervical cap

In a prospective, randomized study of insemination with donor semen, intracervical insemination by straw was compared with insemination using a cervical cap with an intracervical reservoir. A total of 91 patients completed 486 treatment cycles. There were no significant differences in age, parity, indication for insemination by donor, or method of cycle monitoring between women who became pregnant and those who did not conceive with either insemination method. In 236 standard intracervical insemination cycles, 14 patients became pregnant (5.9% per cycle), whereas 38 patients conceived in 250 cervical cap cycles (15.2% per cycle). Both the crude pregnancy rates and the cumulative pregnancy rates calculated by the Kaplan-Meier life-table method were significantly different (chi(2)-test, P < 0.001, and log-rank test, P < 0.005 respectively). Pregnancy rates in artificial insemination with cryopreserved donor semen may be improved by the use of a cervical cap when compared to cervical insemination by straw. The use of the cervical cap may prolong the exposure of the spermatozoa to the cervical mucus and prevent the backflow of semen into the vagina.      

Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells.

Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration (one log greater than control spinal cords) involving the white and gray matter, with heaviest infiltration of lateral and ventral columns and, in one patient, prefrontal gyrus and the occipital lobes of the brain. Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) (one log greater than control tissues) and inducible nitric oxide synthase. In the gray matter, macrophages surrounded and appeared to phagocytize neurons (NeuN-positive) that appeared to be dying. Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes. ALS spinal cords, but not control cords, were sparsely infiltrated with mast cells. In control cases with corticospinal tract degeneration following hemispheric cerebral infarction, macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts. Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells.     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.     

Lymphomatoid granulomatosis and malignant lymphoma of the central nervous system in the acquired immunodeficiency syndrome

While primary and secondary malignant lymphomas have been well-documented in the CNS of patients with the acquired immunodeficiency syndrome (AIDS), only one case of lymphomatoid granulomatosis (LG) involving the CNS has been reported. We present three AIDS patients with multiple grossly evident foci of necrosis in the cerebral hemispheres which, on histologic evaluation, were seen to contain angiocentric mixed chronic inflammatory infiltrates with atypical mononuclear cells, luminal thrombosis, and infarction, which is typical of LG. LG was also identified in sections of the lung in one case. Lymphoma was found in other regions of the brain in two cases, suggesting the evolution of LG into cerebral lymphoma. In addition, widespread perivascular multinucleate syncytial giant cells, associated with human immunodeficiency virus (HIV) infection of the CNS, were identified in all patients. The features of LG, its relationship to lymphoma, and the possible etiologic role of an immunodeficiency state or the HIV virus in the pathogenesis of LG are discussed.     

Brain Parenchymal and Microvascular Amyloid in Alzheimer's Disease

Brains of patients with Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily in the form of characteristic parenchyma!'plaques' (senile or neuritic plaques/SP's) and as mural deposits in the walls of capillaries and arterioles (cerebral amyloid angiopa-thy/CAA). A major component of this amyloid is a small and unique peptide composed of 39–43 amino acids, beta/A4, which is cleaved from a much larger precursor protein (APP) that has several isoforms. Brain amyloid can be detected in autopsy or biopsy brain tissue by classical, immunohistochemical and ultrastructural (including immuno-electron microscopic) methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is remarkably variable (e.g. predominantly parenchyma! or vascular, or a mixture of parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis of the neurological deficit, neocortical atrophy and progressive synapse loss associated with AD/SDAT has yet to be determined. However, mutations in the gene that encodes APP are clearly associated with familial AD syndromes in which there is significant brain amyloid deposition. CAA, in addition to its association with AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work with recently developed transgenic mice which express large amounts of beta/A4 in the central nervous system is likely to elucidate mechanisms by which the protein is selectively deposited in the brain in a parenchymal or microvascular form, and how it contributes to the pathogenesis of neurodegeneration.     

Primary intraventricular hemorrhage in adults

Five adults with primary intraventricular hemorrhage are described. The presenting features included headache, confusion and drowsiness. Focal neurological signs were minimal or absent. All five had a history of hypertension, three patients had bilateral internal carotid occlusion at its origin, one had unilateral occlusion of the left internal carotid artery with severe stenosis of the contralateral siphon. Unilateral occlusion of the middle cerebral artery were present in the fifth patient. Pathological examination of the brain from one patient showed the presence of severe hemorrhagic "lacunar" infarcts adjacent to the left lateral ventricle, one showing direct continuity of blood in the lacune with the massive intraventricular hematoma. We hypothesize that such a finding illustrates one possible mechanism for this unusual type of hemorrhage. Patients with longstanding hypertension and severe occlusive disease of the internal carotid arteries may be predisposed to this unusual complication.     

Use of a new mixture for embolization of intracranial vascular malformations

Summary The internal carotid artery system in swine has a special anatomic configuration similar to a brain arterial-arterial malformation. The internal carotid artery breaks up into a multitude of fine channels (rete mirabile) situated at the base of the skull on the side of the hypophysis. This anatomic arterial model was used to analyze acute and chronic angiographic and histological changes after occlusion of the rete mirabile with I) avitene, II) avitene, and 50% ethanol, III) avitene, 30% ethanol and Polyvinyl alcohol, IV) avitene 50% ethanol and Polyvinyl alcohol, V) IBCA and VI) silk. Histopathological changes observed in the rete mirabile six weeks following occlusion demonstrated that a mixture of avitene, 30% ethanol and Polyvinyl alcohol and IBCA produced the best anatomic results. Embolization with avitene, PVA and ethanol induced a more bland histological reaction than the one observed with IBCA. Preliminary clinical experience with this mixture is reassuring in those cases in which the AVM was surgically resected. The partially thrombosed AVM was easily depressed and compressed by the neurosurgeon allowing for satisfactory hemostasis in and around the nidus of the AVM.This paper was presented in part at the International Symposium on Cerebral Stroke, Sendai, Japan, 1987     

Development of the biologically active Guglielmi detachable coil for the treatment of cerebral aneurysms. Part II: an experimental study in a swine aneurysm model

BACKGROUND AND PURPOSE: Ion implantation is a surface-modification technology that creates a borderless surface on protein-coated platinum; this change in physical and chemical properties on the surface of Guglielmi detachable coils (GDCs) appears to enhance cell proliferation and adhesion. Our purpose was to evaluate the effect of ion implantation on GDCs in an experimental aneurysm model. METHODS: GDCs were coated with either type I collagen, fibronectin, vitronectin, laminin, or fibrinogen. Using He+ or Ne+ 1 x 10(14-15) ions/cm2, ion implantation was performed on these protein-coated GDCs (GDC-Is). A total of 56 experimental aneurysms were constructed microsurgically in the common carotid arteries of 28 swine. These experimental aneurysms were embolized with standard GDCs (n = 23), collagen GDC-Is (n = 11), vitronectin GDC-Is (n = 6), laminin GDC-Is (n = 4), fibrinogen GDC-Is (n = 6), and fibronectin GDC-Is (n = 6). The animals were sacrificed at day 14 after coil embolization. The physical properties of the new coils (friction on delivery, deployment into aneurysms, trackability, etc) and the development of tissue scarring and neoendothelium across the aneurysm's orifice were evaluated macroscopically and microscopically. RESULTS: No evidence of increased coil friction/stiffness was observed during delivery of GDC-Is through microcatheters in this aneurysm model. A more intense scar formation and neoendothelium at the neck of aneurysms were observed macroscopically when treated with GDC-Is. Significant differences in the proportion of neck coverage between standard GDCs (48.3% +/- 20.5%) and all GDC-I groups were observed (collagen GDC-I-89.4% +/- 14.9%, P < .01; vitronectin GDC-I-71.5% +/- 7.0%, P < .05; laminin GDC-I-76.5% +/- 11.0%, P < .05; fibrinogen GDC-I-74.8% +/- 13.9%, P < .05; fibronectin GDC-I-87.5% +/- 15.0%, P < .01). Light microscopy showed a well-organized fibrous tissue bridging the aneurysm's neck when using GDC-Is, whereas only a fibrin-like thin layer covered the standard GDC surfaces. CONCLUSION: GDC-Is indicated a more intense inflammatory response in the aneurysm body and dome and faster re-endothelial coverage of the neck of the aneurysm. This accelerated histologic response may decrease the chances of coil compaction and aneurysm recanalization. This technology may improve anatomic and clinical outcomes in patients harboring intracranial aneurysms.