Cerebral amyloid angiopathy as a cause of an extensive brain hemorrhage in adult patient with Down's syndrome - a case report.

A case of 54-year old woman who deceased due to consequence of extensive brain hemorrhage is presented. The patient was admitted to our Department of Neurology due to progressive quadriparesis as a complication of the cervical spinal cord compressive myelopathy. On the third day after neurosurgical decompression of the spinal cord sudden worsening of neurological and general condition was observed, finally caused death. An autopsy study revealed an extensive brain lobar hemorrhage and a dorsal-ventral compression of the cervical spinal cord. Alzheimer's disease-type degenerative changes with concomitant CAA were seen in light microscope examination. Extensive foci of demyelination were found especially in dorsal funiculi of the cervical spinal cord. Smaller foci of demyelination were present in anterior funiculi due to the stenosis of vertebral canal.

Complications of severe cerebral amyloid angiopathy in the course of dementia with Lewy bodies. A case report.

A 68-year-old male who suffered from dementia, progressing for four months without Parkinson's symptoms, was admitted to the Department of Neurology because of vertigo, slight left hand paresis and positive Romberg test. During hospitalization the patient's status deteriorated. The intracerebral lobar haemorrhage, subarachnoid haemorrhage and ischaemic lesions observed on CT scans suggested the clinical diagnosis of CAA. He died after 53 days due to pneumonia. On macroscopic examination, the brain showed general cortical atrophy and ventricular dilatation. Frontal lobar haemorrhage and focal subarachnoid haemorrhage were seen on the brain autopsy. Microscopic observation demonstrated neuronal loss and microspongiosis in the hippocampus, severe neuronal loss and depigmentation in the substantia nigra pars compacta and locus coeruleus. Lewy bodies were visible in the substantia nigra and amyloid angiopathy, predominantly severe CAA according to the Vonsattel scale, in the meningeal and cortical vessels. In the presented case, the microscopic findings were typical for DLB with concomitant severe CAA. In progressive dementia, neurological deterioration, presence of lobar hemorrhagic infarcts and ischaemic lesions suggest CAA coexistent with DLB and/or AD.

Amyloid angiopathy in idiopathic Parkinson's disease. Immunohistochemical and ultrastructural study.

The prevalence of cerebral amyloid angiopathy (CAA) and its association with intellectual decline in idiopathic Parkinson's disease (iPD) remain unclear. To identify the role of CAA in iPD dementia the prevalence and severity of CAA were investigated, with particular respect to changes in vessel wall structure. Twenty-eight autopsy Parkinsonian brains and fourteen age-matched controls, post-mortem revised histopathologically for the presence of alpha-synuclein and Alzheimer's disease (AD)-type pathology, using standardized clinico-neuropathological criteria, underwent further investigation. Histological, immunohistochemical staining methods with antibodies to amyloid beta-peptide, alpha-actin, collagen III, collagen IV and CD34 as well as ultrastructural methods were used. The findings showed that the prevalence of CAA in the iPD cohort was higher (53%) than in controls (28%). CAA occurred more frequently in the iPD+AD (70%) sub-set than in the iPD-AD (44%) one. The progression of CAA was differentiated, with predominance of mild stage. Diminished smooth muscle actin and collagen IV expression in the vascular media with concomitant collagen III positive immunoreactivity in the intima were observed only in very severe CAA. Ultrastructural assay revealed degenerative changes in vessel smooth muscle cells and thickening of their basement membrane with the focal accumulation of amyloid fibres and fibrillar collagen in both iPD -AD and iPD+AD cases, but the most severe CAA-type changes were visible in the iPD+AD sub-set. The same type of immunoreactivity (Abeta42 positive and Abeta40 positive) of arterial CAA and parenchymal neuritic plaques, as well as capillary CAA and diffuse plaques (Abeta42 positive and Abeta40 negative), may indicate pathogenic similarities and differences between both types of degenerative changes on the one hand and time-different changes or local different processing of amyloid precursor protein on the other.

Small cerebral vessel disease in familial amyloid and non-amyloid angiopathies: FAD-PS-1 (P117L) mutation and CADASIL. Immunohistochemical and ultrastructural studies.

Three patients (of two unrelated Polish families) with early-adult onset dementia were subjects of the study. Two cases, previously diagnosed as familial Alzheimer's disease (FAD) with cerebral amyloid angiopathy (CAA), were confirmed by genetic and neuropathological studies, and one case of CADASIL was ultrastructurally confirmed by the presence of vascular granular osmiophilic material. Now the brain autopsy material has been reinvestigated using immunohistochemical (IHC) markers for vascular smooth muscle cells, paying special attention to collagen markers for extracellular matrix components and ultrastructural microvascular changes. In both diseases, IHC examination showed a reduction or loss of expression of smooth muscle actin (SMA) in tunica media of the cerebral arterioles. Fibrous thickening of the wall of the small meningeal arteries, intracerebral arterioles and numerous capillaries, with amyloid or granular deposits, drew our attention. In these vessels, marked expression of fibrillar collagen type III as well as strong immunoreactivity of the basement membrane (BM) component collagen type IV were found. The most damage was observed in the FAD/CAA double-barrel vessel wall and in some CADASIL arterioles changed by fibrinoid necrosis. The fibrous changes of the small vessels were more distinct in CADASIL t han in FAD/CAA. In FAD,electronmicroscopic examination revealed both amyloid and collagen fibres within the thickened BM of capillaries and the small arterioles. Clusters of collagen fibres between lamellae of BM, frequently in a pericyte position,were observed,and some were seen in the degenerated pericytes as well. Typical changes of the pericytes were accumulation of lipofuscin-like material and their degeneration. The mitochondria of the pericytes and of the endothelium were rare and swollen, with damaged and reduced cristae. The VSMCs of the arteriolar walls exhibited degenerative changes with atrophy of the cellular organelles. The fibrous,collagen-richCADASILsmallcerebralvessels,despite the weakness of the vessel wall due to reduction of VSMCs, appeared to be stronger than in FAD/CAA. These findings may suggest an accelerated process of transformation of the small cerebral vessels in which early onset of VSMCs loss is a predominant feature of the vascular changes in both presented diseases.

The brain immune response in human prion diseases. Microglial activation and microglial disease. I. Sporadic Creutzfeldt-Jakob disease.

A study of microglial activation and its contribution to the CNS immune response was performed on the brain autopsy material of 40 patients with definite sporadic Creutzfeldt-Jakob disease (sCJD). Spatial patterns of microglial activation and prion protein disease-associated (PrPd) deposition were compared in cerebellar and cerebral cortices using immunohistochemical (IHC) activation markers. Morphological phenotype forms of microglial cells in activation stages were assessed immunohistochemically (IHC). The immune inflammatory response dominated by microglia was found to be a characteristic feature in CJD. Differences in the intensity and patterns of microglial activation corresponded to variable patterns of PrP deposition, whereas the morphological phenotype forms of microglia were specific for activation stages. The presence of activated microglial cells in the various activation stages regardless of illness duration indicates continuous microglial activity and microglial contribution to the spread of infection for the whole symptomatic period of the disease. Remarkable vacuolar degeneration changes of numerous microglial cells in different activation stages including homing stage may suggest dysfunction of microglial immune surveillance in human sCJD that can significantly contribute to transmissible spongiform encephalopathy (TSE) pathogenesis.

Limbic neuropathology in idiopathic Parkinson's disease with concomitant dementia.

To study pathological background of dementia in idiopathic Parkinson's disease (PD), 41 autopsy brains (31 cases with and 10 cases without dementia) were investigated. The severity of degenerative changes was evaluated in selected limbic regions (trans- and entorhinal cortex, hippocampus, and amygdala). The densities of Lewy bodies (LBs), Lewy neurites (LNs), neurofibrillary tangles (NFTs), and amyloid neuritic plaques (NPs) were determined on immunohistochemically stained sections using antibodies against alpha-synuclein, tau-protein, and amyloid-beta. Precisely defined modern criteria for selecting study cohort (Newcastle, CERAD and Braak et al.) ensured homogeneity of the study sample and reliability of the results. Comparisons between the cases of Parkinson's disease with dementia (PDD) and those without (PD-only) revealed that the former were characterised by significantly higher densities of LBs and LNs in transentorhinal and entorhinal cortices as well as in the CA2-3 region of the hippocampus and cortical complex of amygdala. In the PDD sub-set we found statistically significant correlation of LBs with LNs counts in CA2-3 region of hippocampus as well as of LBs counts in transentorhinal cortex with LNs counts in CA2-3 hippocampal region. The relationship was also observed between LBs counts in CA2-3 region of the hippocampus and LNs counts in cortical complex of amygdala. Our studies suggest that dementia in PD may be associated with the presence of degenerative changes of PD-type in leading limbic structures, without co-existent Alzheimer's disease (AD). They also imply that LBs and LNs may appear to be morphological hallmarks of the pathological process associated with dementia in PD. LBs and LNs distribution pattern and correlations of LBs with LNs counts in limbic regions observed in our study suggest the cumulative patomechanism of changes dependent on transsynaptic alpha-syn pathology and indicate the spread of the pathological process via axonal transport. The coexistence of the small number of changes of AD-type may exacerbate cognitive deficits in PDD.

Ultrastructural evaluation of activated forms of microglia in human brain in selected neurological diseases (SSPE, Wilson's disease and Alzheimer's disease).

Activated forms of microglia were ultrastructurally evaluated in three neurological diseases of different aetiology (subacute sclerosing panencephalitis--SSPE, Wilson's disease and Alzheimer's disease). The occurrence of activated rod, ramified and amoeboid microglia was found in the investigated diseases. The widest ultrastructural variability of microglia was in SSPE, including the presence of mitotic chromosomes or centrioles in its cytoplasm, which indicates microglia proliferation. In the nuclei of activated microglia, some nuclear bodies with different structures were frequently seen, whereas lamellar structures (similar to developing Birbeck's bodies--pathognomonic to Langerhans-type dendritic cells) were observed in the cytoplasm. The activated forms of microglia with apoptotic features were found only in SSPE cases. Some apoptotic nuclei were filled with nucleocapsids of measles virus. In Alzheimer's disease, activated microglia was most frequently bound to senile plaques. Ramified microglia was in contact with amyloid fibrils, which penetrated its cytoplasm and reached the nuclear membrane and channels of rough endoplasmic reticulum, or was situated among dystrophic neurites. Rod microglia was found predominantly at the edge of senile plaques. In Wilson's disease, the ultrastructure of activated microglia showed mostly indirect forms between rod, ramified and amoeboid microglia. The microglia ultrastructure suggests that its morphological form may express functional involvement in the pathogenesis of a given disease entity.

Neuropathological and anatomopathological analyses of acardiac and "normal" siblings in an acardiac-twin pregnancy.

Acardiac twinning is a very rare complication of multiple pregnancy. The authors present the neuropathological and anatomopathological description of the twins of the multiple pregnancy complicated by the acardiac foetus and terminated at 26 weeks of gestation. An anatomopathological examination of the "normal" twin showed hyaline membrane syndrome, cardiomegaly and hepatomegaly. Neuropathologically, numerous hypoxic-ischaemic lesions, most likely associated with haemodynamic disorders during pregnancy as well as less pronounced perinatal changes were revealed. The acardiac foetus, classified as acardius acephalus, demonstrated the presence of some abdominal organs and a histologically well-developed spinal cord. In view of the neuropathological changes, monitoring "normal" twins for discreet pathological central nervous system signs, which may be similar in character to those described, may play a significant role.

Degenerative axonal changes in the hippocampus and amygdala in Parkinson's disease.

The morphological background of cognitive and emotional impairments in Parkinson's disease (PD) has not yet been fully explained. We evaluated the expression of synaptic proteins: alpha- and beta-synuclein, synaptophysin and synaptobrevin and ultrastructural changes of perikaryons and axons in limbic structures at post-mortem from cases of PD to estimate degenerative axonal pathology in the hippocampus and amygdala [corrected]. Limbic structures (enthorinal cortex, hippocampus, and amygdala) are essential for the cognitive processes and emotional behaviour. We found that presynaptic axon pathology is mostly connected with hippocampal CA2-3 and dentate hilar regions as well as with the cortical and medio-central complexes of amygdala. Heterogeneous immunoreactivity of alpha-synuclein and diversified ultrastructure of Lewy bodies (LBs) and Lewy neurites (LNs) indicate their consecutive developmental stages. We observed an excessive perineuroneal expression of synaptophysin in the dentate hilar region in all PD cases, except one. This suggests that the dysfunction of synapses in this region may result from axonal pathology. Our study indicates a relation between cognitive and behavioural symptomatology in PD and alpha-synuclein dependent axonal pathology in the hippocampus and amygdala.

[Neurodegeneration with brain iron accumulation, type-I (NBIA-I) (formerly Hallervorden-Spatz, disease). Par I: clinical manifestation and treatment]. / Zwyrodnienie osrodkowego ukladu nerwowego z odkladaniem sie zelaza w mózgu, typu pierwszego (dawniej choroba Hallervordena-Spatza). Czesc i--obraz kliniczny oraz leczenie.

This is a rare syndrome, most likely of several genetically determined neurodegenerative disorders with similar pathogenesis. Two forms of the disease are distinguished: familial occurring in about 50% of cases and sporadic with about 15% of cases in which parental consanguinity is found. Clinically, NBIA-1 is characterised by a slow progression of extrapyramidal symptoms and progressive dementia, mostly in children. Relentlessly progressive course is obvious, but the progress may be very slow, taking sometimes several dozen of years. Four subtypes of the disease have been thus far distinguished: early childhood, late childhood, adult onset and with protracted course. The clinical diagnosis of NBIA-1 is only probable because specific abnormalities have not as yet been detected in laboratory investigations. However, NBIA-1 should be suspected, if extrapyramidal symptoms are observed, such as dystonia, choreoathetosis, muscular rigidity, moreover dementia, retinal degeneration and/or optic nerve atrophy and characteristic magnetic resonance imaging (so called "the eye-of-the tiger" sign). At present, only comprehensive symptomatic treatment is possible.

[Type I neurodegeneration with brain iron accumulation, (NBIA-I, formerly Hallervorden-Spatz disease). Part II -- neuropathologic manifestation, novel genetic aspects and pathogenesis]. / Zwyrodnienie osrodkowego ukladu nerwowego z odkladaniem sie zelaza w mózgu, typu pierwszego (dawniej choroba Hallervordena-Spatza). Czesc II--Obraz histopatologiczny, nowe aspekty genetyczne oraz patogeneza.

In NBIA-1 major histopathological changes in the central nervous system are observed mostly in the subcortical pallido-nigral system. They consist in the presence of brown pigment deposits (containing iron), axonal spheroids, as well as Lewy neurities and cytoplasmic inclusions in the oligodendroglia (both the latter contain pathological alfa-synuclein). However, the histopathological pattern is most the diversified as regards the intensity and range of typical structural changes. The gene of the disease has been very recently identified and mapped on the short arm of the chromosome 20p13.-p12.3. The discovery of the NBIA-1 gene is a great advance in the search for a causal cure for this devastating disease. Its etiopathogenesis has not been fully explained yet. However, the gene identification allows to hypothesize that vitamin B5 metabolism may be disturbed at least in some NBIA-1 patients. Disturbance of vitamin B5 metabolism may cause an oxidative stress leading to degenerative and atrophic changes, most pronounced in the subcortical pallido-nigral system and in the retina.

Morphological analysis of active microglia--rod and ramified microglia in human brains affected by some neurological diseases (SSPE, Alzheimer's disease and Wilson's disease).

The activation of microglial cells in pathological conditions is manifested primarily by their proliferation, as well as by the occurrence of a new morphological form--rod microglia. In the present study immunohistochemical identification of rod microglial phenotype against ramified microglia was performed on segments of 17 brains derived from 7 cases of encephalitis of viral aetiology (including 5 SSPE cases), 6 cases of Wilson's disease and 4 cases of Alzheimer's disease. Segments from frontal, temporal and occipital lobes, cerebellum and brainstem were subjected to histological, histochemical and immunohistochemical reactions. The presence of activated rod and ramified microglia was observed in sections derived from all structures of the brains under study. Both morphological forms of activated microglia reacted to antibodies: HLA II, CD68, HAM56 and lectin RCA-1. Expression of HLA II molecules was less intensive on the surface of microglial rod cells. A positive reaction to PCNA antibody was mainly observed in rod/elongated/cylinder-shaped nuclei, which is a characteristic feature of rod microglia. In the study material, the localisation of microglial processes seemed to depend rather on the structural topography of the cell in the brain than on the nuclear shape of the activated microglial cell. Our observations revealed a strong similarity between immunohistochemical phenotypes of both morphological forms of microglia with the indication that rod microglia is a first developmental form of activated microglia.