Extensive mixed vascular malformation clinically imitating multiple sclerosis--case report.

Vascular malformations usually develop as a result of influence of teratogenic factor(s) acting in the defined embryonic/fetal period. However, in the case examined by us, various types of vascular malformations formed in different periods of the ontogenic development were found. They were seen in all parts of the central nervous system and clinically mimicked multiple sclerosis. On the background of generalized ischemic lesions of the CNS, certain kinds of vascular malformations were seen: cavernous or fetallike vessels within meninges, superficially located capillary angioma penetrating into the brain and spinal cord white matter, and arterio-venous pathological conglomerates forming meningeal angiomatosis. In pathological vessels, immunocytochemical assessment of vascular endothelium with antibodies against antigens CD31, CD34, von Willebrand factor and lectin Ulex europaeus was normal but examination of the vascular basal membrane compounds revealed poor immunoreactivity to laminin and fibronectin. There were no disturbances in expression of angiopoietin, platelet-derived growth factor, transforming growth factor beta and vascular endothelial growth factor receptors Tie-1/2, PDGFR-alpha/beta, endoglin and Flk-1, respectively. The presence of various types of pathological vessels originating from different ontogenic periods indicates remittent or prolonged influence of teratogenic factor(s) in all periods of fetal vessel development.

Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis.

The importance of apolipoprotein E (ApoE) and myeloperoxidase (MPO) genotypes in the clinical characteristics of multiple sclerosis (MS) has been recently emphasized. In a large group of Polish patients we have tested the hypothesis that polymorphism in ApoE and MPO genes may influence the course of the disease. Genotypes were determined in 117 MS patients (74 females and 43 males; 99 sporadic and 18 familial cases) with mean EDSS of 3.6, mean age of 44. 1 years, mean duration of the disease 12.8 years and mean onset of MS at 31.2 years, and in 100 healthy controls. The relationship between ApoE and MPO genes' polymorphism and the MS activity as well as the defect of remyelination (diffuse demyelination) and brain atrophy on MRI were analysed. The ApoE epsilon4 allele was not related to the disease course or the ApoE epsilon2 to the intensity of demyelination on MRI. The genotype MPO G/G was found in all familial MS and in 57% (56/99) of sporadic cases. This genotype was also related to more pronounced brain atrophy on MRI. The MPO G/G subpopulation was characterized by a significantly higher proportion of patients with secondary progressive MS (P < 0.05) and by a higher value of EDSS. According to our results the MPO G allele is frequently found (in 96% of cases) among Polish patients with MS. More severe nervous tissue damage in the MPO G/G form can be explained by the mechanism of accelerated oxidative stress. It seems that MPO G/G genotype may be one of the genetic factors influencing the progression rate of disability in MS patients.

CADASIL: new cases and new questions.

We described the first two unrelated Polish families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In the morphological examination with light microscopy, two kinds of changes were observed: (1). panarteritis nodosa-like changes with eosinophilic fibrinoid necrosis of the vessel wall and perivascular inflammatory infiltrates and (2). basophilic granular material in the tunica media characteristic of CADASIL. At electron microscopy, we found deposits of granular osmophilic material (GOM) within the wall of arteries, veins and capillary vessels. Our findings imply two questions requiring further investigation: Why in the genetically determined vascular disorder are the features of systemic inflammatory vascular disease present? Why in capillary walls deprived of smooth muscle cells are deposits of GOM present?

Early ontogenic disturbances in cell migration in mentally disabled adult.

Disturbances in cell migration are heterogenic disorders of brain development commonly associated with epilepsy and mental retardation. We report a 45-year-old oligophrenic man with defect of lower limbs and family history of mental retardation who died because of brainstem hemorrhage. At post-mortem and histopathological examination, complex brain malformation characterized by bilateral periventricular heterotopia, cortical dysgenesia, partial agenesia of corpus callosum and thin-walled blood vessels was found. Immunohistochemical examination revealed the presence of fibronectin, collagen IV and laminin in wall of pathological vessels. Cyclooxygenase-2 (COX-2) expression in neurons within heterotopias and dysgenic cortex was negative. It may indicate their maturity and indirectly, normal activity of postsynaptic NMDA receptors that explains absence of epileptic attacks in our patient. The presence of COX-2-negative neurons and compounds of basal lamina in fetal-like vessels within heterotopias and dysgenic cortex, suggests that these probably initially immature structures became mature during 45 years of patient's life.

Correlative ultrastructural and immunohistochemical study of developing vascular basement membrane in postnatal rat spinal cord.

We investigated the development of vascular basement membrane in immature spinal cord vessels during rat spinal cord myelination. Correlative ultrastructural and immunohistochemical study indicated that fibronectin was the first component of extracellular matrix. Then, on the 9th postnatal day, laminin appeared. At that time, lamina lucida of vascular basement membrane was not detectable. On the 15th day, when collagen IV was visible, lamina densa and lamina lucida were occasionally observed. All components of basement membrane--fibronectin, laminin, collagen IV, alpha-2 laminin (merosin)--and ultrastructural division into two layers were detected on the 25th postnatal day. The results of this study indicates that a gradual development of endothelium in immature rat spinal cord blood vessels leads to a gradual increase of synthesis of extracellular matrix components.

Do astrocytes participate in rat spinal cord myelination?

Astrocytes play an important role in CNS development phenomena, such as neuron migration and blood-brain barrier formation, but only a little is known of their role in the process of myelination. The aim of our investigation was to examine the relationship between astrocytes and myelin formation. We evaluated rat spinal cords using hematoxylin-eosin and Klüver-Barrera staining methods as well as immunohistochemical methods with antibodies against myelin basic protein (MBP), glial fibrillary acidic protein (GFAP) and lamins A/C and B2. Our investigation revealed that myelination in the rat spinal cord tracts began between the 6th and 9th postnatal day involving the anterior funiculi, then the lateral funiculi and later the posterior ones. The process of myelination finished about the 25th postnatal day. More GFAP immunoreactive astrocytes were detected in parallel to the increase of MBP reactivity. We suggest that the temporary increase of GFAP positive cells accompanying the process of myelination is necessary for normal myelin development and may be connected with local secretion of growth factors by astrocytes.

Does the pathological factor in amyotrophic lateral sclerosis (ALS) damage also astrocytes?

Introduction of immunocytochemical reaction to glial fibrillary acidic protein (GFAP) made possible more accurate estimation of astrocytes reactivity in various diseases of CNS, among others, in amyotrophic lateral sclerosis (ALS). Lack of present studies concerning reactive astroglia in spinal cord, inclined us to examine the reaction of astrocytes in cervical, thoracic and lumbar spinal cord. Material included 11 sporadic ALS patients. Sections of formalin-fixed, paraffin-embedded tissue were stained with hematoxylin and eosin, Kluver-Barrera method and with antibody against GFAP. In all cases various degree of nerve cells loss in the anterior horn, pigmentary degeneration of remaining neurons, the pallor of myelin in the white matter of anterior and lateral columns were observed. In a part of cases background tissue rarefaction within anterior horn was seen. Intensity of morphological changes within anterior horns made possible to divide material into two groups and separate one senile case. Very intensive neuronal changes associated with weak reaction of astrocytes in the anterior horn allow us to pose the hypothesis of influence of an unknown pathological factor on both anterior horn neurons and astrocytes.

Vascular changes in tuberculous meningoencephalitis.

Our report refers two cases of tuberculous encephalomeningitis which differ in the course and pathological changes. In case 1 blood vessels showed features of peri, endo-, or panvasculites. In some vessels endothelium proliferation leading to the stenosis or obliteration of the vascular lumen was observed. Necrosis was an effect of vessels occlusion. In case 2 many fewer vessel were involved in onflammation process. Vascular changes were also less extensive and were observed more rarely. Tuberculous infection often caused less tissue lesions than vascular changes. Different pathological changes probably depend on the type and virulence of Myobacterium tuberculosis and on the host immune response to the infection.