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Biomedical subjects

F Scaravilli

Publications and source records attributed to F Scaravilli.

At least 19 recordsLinked to original sources
PubMed2000

Imaging and radiological-pathological correlation in histologically proven cases of focal cortical dysplasia and other glial and neuronoglial malformative lesions in adults.

Focal cortical dysplasia (FCD) is a pathological entity first described in 1971. Other more subtle cortical malformations found in patients with epilepsy include microdysgenesis (MD), and glioneuronal hamartias. Although these glial and neuronoglial malformations have distinct histological features, there is terminological confusion in the radiological literature. Few cases have been reported in adults with both imaging and histology. We address these issues, giving a radiological-pathological correlation of histologically proven cortical malformations in adults. We describe clinical, radiological and histological features of 12 cases (five FCD, five MD with glioneuronal hamartias, and two hamartomas), unassociated with other conditions, and discuss them in the light of the literature. FCD is usually seen on MRI as cortical thickening, with or without signal change, which may extend into the adjacent white matter. On histology, abnormal neurons and/or glial cells, blurring of the grey-white matter interface, myelin pallor, demyelination, and gliosis may be found. Glioneuronal hamartias and hamartomas usually appear as complex masses on MRI. FCD and hamartias may be associated, and a combination of imaging findings may be seen on MRI. Atrophy of the ipsilateral hippocampus may be present on MRI in patients with hamartias, and minor cell loss on histology, but not definitive hippocampal sclerosis. Although the imaging findings of cortical malformations are protean, some characteristic MRI features, with histological correlates, may be found. The relevance of most of these observations remains unclear.

Adult↗
PubMed2000

The effect of intravesical capsaicin on the suburothelial innervation in patients with detrusor hyper-reflexia.

OBJECTIVE: To determine the effect of intravesical capsaicin on the suburothelial innervation in patients with detrusor hyper-reflexia, in whom a single dose of intravesical capsaicin (1-2 mmol/L) increases the bladder capacity for 3-6 months. PATIENTS AND METHODS: Thirteen patients with detrusor hyper-reflexia underwent cystometry and had flexible cystoscopic biopsies taken before and 6 weeks after receiving instillations of intravesical capsaicin (1 mmol/L). Similar biopsies were also obtained from a control group of 12 neurologically normal patients with microscopic haematuria and normal bladders. Frozen sections were stained using antibodies to S100 and PGP 9.5. Using computerized analysis, the mean nerve density scores were expressed as nerves/mm2 for S100-positive structures and 'red%' and 'red in frame' for PGP 9.5. RESULTS: The mean (SEM) functional bladder capacity increased from 193.2 (28.17) mL before to 396.3 (41.96) mL at 6 weeks after treatment with capsaicin, in nine of the 13 patients. The mean nerve density of S100-positive structures in the control group was 83 (3.18) nerves/mm2. In hyper-reflexic patients who responded to capsaicin by improved bladder capacity, the mean nerve density of S100-positive structures was reduced from 100 (12.2) before to 66 (9.4) nerves/mm2 6 weeks after treatment. In those who did not respond to capsaicin there was no significant difference in these scores. Similarly the 'red%' and 'red in frame' reduced from 3.41 (1.06) to 1.15 (0.32) and 824.7 (246.3) to 297.9 (83.5) units, respectively, before and 6 weeks after capsaicin treatment. The difference in those not responding was not significant. CONCLUSIONS: Intravesical capsaicin causes a reduction in suburothelial nerve densities in the bladder of patients with detrusor hyper-reflexia. This may explain its prolonged beneficial effect in these patients.

Administration, Intravesical↗
PubMed2000

Hereditary vascular dementia linked to notch 3 mutations. CADASIL in British families.

The most common form of familial vascular dementia is considered to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is now also increasingly manifest in the United Kingdom. CADASIL has been previously dubbed as a familial form of Binswanger disease. However, unlike in Binswanger disease CADASIL does not involve hypertension or other risk factors associated with cardiovascular disease. CADASIL appears to be essentially a disorder of the arteries that is linked to single missense mutations in the NOTCH 3 gene locus on chromosome 19. The pathogenesis of the disorder or the genetic mechanism leading to brain infarcts and dementia is not known. The elucidation of the microvascular pathology evident in CADASIL may be an interesting way to delineate effects of defective genes on brain cells from systemic vascular influences.

Cardiovascular Diseases↗
PubMed1999

Inhibition of sensory neuron apoptosis and prevention of loss by NT-3 administration following axotomy.

Following permanent transection of their peripheral axons, a proportion of adult rat dorsal root ganglion neurons undergo programmed cell death (apoptosis) over a period of months. The underlying causes of this neuron loss are unclear, but may involve the interruption of the supply of target-derived neurotrophic factors, the replacement of which could prevent this loss from occurring. To investigate whether the administration of neurotrophic factors can prevent the dorsal root ganglion neuron death in adults, a 1 mg/ml solution of ciliary neurotrophic factor or of NT-3 was applied via a silicon reservoir to the proximal stump after unilateral sciatic transection at mid-thigh level. The incidence of apoptotic neurons and neuronal loss in the L4 and L5 ganglia ipsilateral to sciatic nerve transection when compared with the contralateral ganglia was then measured 1 month later. This was assessed by examining serial sections of ganglia for neurons undergoing apoptosis and expressing the total counted as a percentage of the total number of neurons estimated using a stereological neuron counting technique. Our results show that NT-3 administration significantly reduced the incidence of apoptotic neurons and prevented neuron loss, while CNTF had no effect on either parameter.

Animals↗
PubMed1999

Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation.

The histological features of familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation (FAB) include deposition of amyloid, (supposedly associated with the C-terminal fragments of both alpha- and beta-tubulin), in small cerebral and spinal arteries, hippocampal amyloid plaques and neurofibrillary tangles (NFTs) as well as ischaemic white matter changes. In the present study we report on the cytoskeletal pathology that occurs in association with FAB. Sections from the hippocampus and cerebellum of three cases from three unrelated families were stained with silver impregnation methods and antibodies to antigens including tau, neurofilaments, ubiquitin and glial fibrillary acidic protein. Electron microscopic examination of the hippocampus was carried out in one case. All hippocampal subregions contained large numbers of NFTs and neuropil threads (NT), which were stained with both phosphorylation-dependent and phosphorylation-independent tau antibodies and ultrastructurally were found to be composed of paired helical filaments (PHFs). Although the majority of the amyloid plaques were of the non-neuritic type, distended PHF-containing and tau-positive neurites were seen in close proximity of a minority of the hippocampal plaques. The perivascular amyloid deposits of the cerebellum contained numerous ubiquitin-positive granular elements similar to those seen in cerebellar A beta amyloid plaques in Alzheimer's disease. In FAB severe cytoskeletal pathology is present in areas most affected by amyloid plaque deposits, thus suggesting a localised neurotoxic effect of the poorly characterised amyloidogenic peptide characteristic of this condition.

Biomarkers↗
PubMed1999

Hippocampal sclerosis with hypertrophy of end folium pyramidal cells.

Mesial temporal lobectomy for the treatment of intractable temporal lobe seizures may show dual pathologies for example hippocampal sclerosis (HCS) combined with a malformation. In a lobectomy specimen from a 40-year-old female with typical radiological and pathological features of HCS, an additional histopathological finding was the presence of hypertrophic pyramidal cells in the dentate hilus, in which cytoplasmic accumulations of phosphorylated neurofilament were demonstrated. Although these cells closely resembled dysplastic nerve cells of cortical dysplasia, we argue that the cytoskeletal abnormalities observed are a result of ongoing alterations to hippocampal circuitry in an evolving HCS.

Adult↗
PubMed1999

Detection and localisation of HIV-1 DNA and RNA in fixed adult AIDS brain by polymerase chain reaction/in situ hybridisation technique.

In the brain of patients with AIDS, HIV-1 is localised in a productive form in mononuclear cells. One issue that still needs clarification is whether HIV is localised in cells other than those of mononuclear lineage. Gene amplification by polymerase chain reaction/in situ hybridisation (PCR-IS) could shed light on it. In this study, formalin-fixed, paraffin-embedded brain tissue from ten adult AIDS sufferers was used. Five of them showed evidence of HIV encephalitis (HIVE), five did not show any abnormality. Nested PCR revealed HIV-1 DNA in all HIVE cases and in three of the group without HIVE. HIV-1 DNA and RNA were also detected in situ in seven cases (all seven were also HIV-1 DNA positive in tube). A higher signal was located in the white than in the grey matter. HIV-1 DNA was found in microglia, macrophages, perivascular cells, multinucleated gaint cells (MGC) and in CD68-negative cells. Some of them were identified as endothelial cells, astrocytes and oligodendrocytes. Reverse transcriptase-PCR-IS was positive in macrophages, MGC, endothelial and glial cells. These results confirm infection of endothelial cells and other glial cells and give clues about the route of entry of virus into the central nervous system and the pathogenesis of the disease. This study did not give any convincing evidence supporting an infection of neurons by HIV-1.

AIDS Dementia Complex↗
PubMed1999

Amygdala sclerosis in sudden and unexpected death in epilepsy.

Sclerosis of the amygdala is a not uncommon finding in patients with chronic epilepsy. The amygdala has efferent connections, via the central nuclei, to cardioregulatory centres in the medulla. Experimental studies have suggested that damage to the central nucleus may be of functional significance in patients with sudden and unexpected death in epilepsy (SUDEP) in particular with regard to their susceptibility to cardiac arrhythmias. We investigated this possibility by carrying out a quantitative immunohistochemical analysis of the patterns of neuronal loss and gliosis in three amygdala subnuclei (central, basal and lateral) in post mortem material from 15 SUDEP cases and seven normal controls. We identified significant neuronal loss in the medial division of the lateral amygdaloid nucleus in SUDEP cases but not in central or basal nuclei. These patterns of cell loss in the amygdala do not differ from previous studies in both humans and animal models of chronic epilepsy suggesting that there is not a specific pattern of amygdaloid sclerosis in SUDEP patients which could implicate a functional role for this nucleus in the mechanism of the sudden death.

Adolescent↗
PubMed1999

Ocular, cerebral and systemic interrelationships of cytomegalovirus infection in a post-mortem study of AIDS patients.

PURPOSE: Eighty-six post-mortems of AIDS patients were reviewed microscopically and the presence of cytomegalovirus (CMV) infection in the viscera, brain and eye was recorded. METHODS: Immunohistochemical stains and in situ hybridisation with a CMV probe were performed. RESULTS AND CONCLUSION: CMV infection was observed in 63% of the cases. Visceral, cerebral and ocular involvement were overall 49%, 33% and 29%, respectively. The visceral form with no concomitant ocular and/or cerebral infection was the main cause of death (31%) in the 54 CMV-infected patients. Although CMV retinitis occurred mostly (20%) as a component of systemic disease, in 13% of the CMV-infected patients the eyes only were involved, while there were no cases with CMV limited to the brain. In the absence of systemic involvement, 9% of the cases showed concomitant ocular and cerebral infection, but because we failed to observe CMV optic neuritis without ocular involvement, retrograde viral spread from the brain through the optic nerve appears to be an infrequent mechanism of CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage.

To characterize the distribution of apoptotic neurons and their relationships with the stage of disease, a history of HIV-dementia, and the degree of productive HIV infection, microglial activation and axonal damage, we examined the brains of 40 patients. Samples of frontal and temporal cortex, basal ganglia and brain stem were taken post-mortem from 20 patients with AIDS (including three with HIV-dementia, and eight with cognitive disorders that did not fulfil the criteria for HIV-dementia), 10 HIV-positive asymptomatic cases and 10 seronegative controls. Neuronal apoptosis was demonstrated by in situ end labelling in 18 AIDS cases and two pre-AIDS cases; a single apoptotic neuron was present in the temporal cortex of a control. Semiquantitative evaluation showed that the severity of neuronal apoptosis in the cerebral cortex correlated with the presence of cerebral atrophy, but not with a history of HIV dementia. There was no global quantitative correlation between neuronal apoptosis and HIV encephalitis or microglial activation. However, there was some topographical correlation between these changes. In the basal ganglia, apoptotic neurons were much more abundant in the vicinity of multinucleated giant cells and/or p24 expressing cells. Microglial activation was constantly present in these areas. Axonal damage was identified using beta-amyloid-precursor protein (betaAPP) immunostaining in 17 AIDS and eight pre-AIDS brains. Although no global quantitative correlation could be established between axonal damage and neuronal apoptosis there was an obvious topographic correlation supporting the view that axonal damage, either secondary to local microglial activation or due to the intervention of systemic factors, may also contribute to neuronal apoptosis.

AIDS Dementia Complex↗
PubMed1999

Bilateral symmetrical enhancing brainstem lesions: an unusual presentation of primary CNS lymphoma.

We report a patient with a progressive brainstem syndrome, who on magnetic resonance imaging had large bilateral, symmetrical, contrast-enhancing, infratentorial space-occupying lesions. Biopsy of one of the lesions revealed this unusual appearance to be due to a primary central nervous system (CNS) lymphoma of B-cell type. Symmetry of lesions may be a clue to the diagnosis, perhaps reflecting the mechanism by which CNS lymphomas spread.

Aged↗
PubMed1999

Expression of three oligosaccharide conjugates by neonatal rat dorsal root ganglion neurons: comparison with CGRP and GAP43 immunoreactivity.

Adult dorsal root ganglion neurons express oligosaccharides conjugated to lipids that may be involved in cell-cell recognition, and consequently in the laminar organisation of their central terminations. This paper describes an immunohistochemical study of the developmental expression of 2 lactoseries (LA4 and LD2) and 1 globoseries (SSEA4) oligosaccharide conjugates in rats from embryonic d 19 to postnatal d 60. The expression of calcitonin gene related peptide and the growth associated protein GAP43 was also examined for comparative purposes. We found that these oligosaccharide conjugates begin to be expressed after birth, suggesting that they may be involved in maturation of the central or peripheral terminations, rather than axonal guidance.

Animals↗
PubMed1999

Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals.

There is overwhelming evidence that invasion of the central nervous system (CNS) by HIV-1 takes place at an early stage of the infection. It has been demonstrated that HIV-1 DNA is present in brains of asymptomatic individuals. Evidence of immune activation and increased expression of cytokines suggested that neuropathological changes and neuronal and axonal damage could be the effect of the presence of the virus. The purpose of the study is to ascertain whether target cells for HIV-1 in brain of patients at early stage of the infection are the same as those found in AIDS sufferers or if the distribution seen in AIDS patients results from the late spreading of the infection from cells considered traditionally the reservoir of the virus, i.e. microglial cells. Eighteen brains, all HIV-1 DNA positive, as shown by nested polymerase chain reaction (PCR), were selected among the group of HIV-1 positive asymptomatic cases. In 6 of them, HIV-1 DNA was detected by PCR in situ. Positive cells included astrocytes and endothelial cells, in addition to microglial cells. We conclude that astrocytes and endothelial cells are already infected at an early (asymptomatic) stage of the infection and suggest that they might contribute to the damage of the CNS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Halothane as a neuroprotectant during constant stimulation of the perforant path.

PURPOSE: To determine the neuroprotective effects of halothane during constant stimulation of the perforant path. METHODS: Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer under halothane anaesthesia (1-2% in oxygen). They were then divided into four groups. In group 1 (n = 9), the perforant path was stimulated at 20 Hz for 2 h under halothane anaesthesia (1-2%). In group 2 (n = 3), the animals were unstimulated but maintained under halothane anaesthesia (1-2%) for 2 h with the electrodes in place. Both groups 1 and 2 had the electrodes removed and were then allowed to recover fully from the anaesthetic. In groups 3 and 4, the electrodes were held in place with dental acrylic. Both of these groups were allowed to recover fully from anaesthesia. In group 3 (n = 3), 24-48 h after recovery from anaesthesia, the perforant path was stimulated at 20 Hz for 2 h. Group 4 (n = 3) received no stimulation. After 14-17 days, the rats were killed, and morphometry and cell counts were performed on the hippocampi from rats in groups 1 and 2. RESULTS: Cell densities were not significantly different between control (group 2), unstimulated rats, and animals stimulated under halothane anaesthesia (group 1). Stimulation in the unanaesthetised rats resulted in severe neuronal loss in hilus, CA1, and CA3. CONCLUSIONS: Halothane protects hippocampal neurons against damage induced by constant stimulation of the perforant path.

Anesthesia, Inhalation↗
PubMed1999

The neuropathology of paraneoplastic syndromes.

The term "paraneoplastic neurological syndromes" encompasses a number of uncommon disorders associated with systemic malignancies. In order to be classified a paraneoplastic neurological syndrome, the malignancies must not invade, compress, or metastasize to the nervous system. They can either focally or diffusely involve the central and peripheral nervous system or the neuromuscular junction. This paper reviews the neuropathology of the syndrome. It will first describe the clinical presentation and give an account of the systemic tumors most commonly associated with the various types of disorders. Then it will review the general pathological features that consist of an inflammatory process predominantly affecting the gray matter. Finally, it will describe in detail the main clinico-pathological types, including 1) encephalomyelitis, 2) cortical cerebellar degeneration, 3) peripheral neuropathy, 4) opsoclonus-myoclonus and 5) retinopathy. The Lambert-Eaton myasthenic syndrome will be dealt with separately in another paper in this symposium.

Autoantibodies↗
PubMed1999

Spontaneous intralesional haemorrhage in dysembryoplastic neuroepithelial tumours: a series of five cases.

Five patients with dysembryoplastic neuroepithelial tumour (DNT) showing extensive secondary haemorrhage, a finding not previously associated with these neoplasms, are described. The clinical presentations, neuroimaging findings, and histopathological features of these patients are reviewed. One patient, a previously asymptomatic 12 year old girl, presented with an acute intracerebral haemorrhage into a DNT. A further four young adults with histories of intractable partial and generalised seizures dating from childhood showed significant chronic haemorrhages within DNT, the MRI appearances in one patient giving a false impression of a cavernoma. Histopathology disclosed vascular abnormalities within these tumours which, together with other factors discussed, may have predisposed these tumours to haemorrhage.

Brain Neoplasms↗