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F Scaravilli

Publications and source records attributed to F Scaravilli.

At least 37 records · Page 2Linked to original sources
PubMed1995

A new mitochondrial DNA mutation associated with progressive dementia and chorea: a clinical, pathological, and molecular genetic study.

A novel mitochondrial DNA transfer RNA mutation at position 5549 was identified in a patient with dementia, chorea, cerebellar ataxia, deafness, and peripheral neuropathy in the absence of clinical myopathy. Muscle biopsy specimens showed ragged red and cytochrome oxidase-negative fibers, and reduced complex I activity on polarography. There was diffuse neuronal loss and gliosis throughout the brain on postmortem examination. The heteroplasmic mutation had a widespread distribution in autopsy tissues.

Adult↗
PubMed1995

Kearns-Sayre syndrome associated with mitochondrial DNA deletion or duplication: a molecular genetic and pathological study.

The neuropathological findings in 2 patients with Kearns-Sayre syndrome and mitochondrial DNA (mtDNA) rearrangements, one a predominant deletion and the other a predominant duplication, were remarkably similar, showing diffuse vacuolation of white matter. There were some of the pathological features of Leigh's syndrome in the spinal cord of the patient with a duplication. In the patient with a predominant deletion, rearranged mtDNA was undetectable in blood, spleen, and testis, and present in highest amounts in muscle and the brain, but relatively low in cerebellum, reflecting the ratio seen, albeit in much smaller amounts, in normal aged brains. MtDNA rearrangements in this patient were largely deletions or deletion dimers; duplicated mtDNA was present in only trace amounts in some tissues and there was none in skeletal muscle. The patient with a predominant duplication of mtDNA had higher amounts of rearranged mtDNA in blood (mainly duplicated) than muscle (mainly deleted). Correlation of these data with tissue dysfunction is probably complicated by the replicative behaviour of deleted, duplicated and normal mtDNA.

Adolescent↗
PubMed1995

AIDS-associated vacuolar myelopathy. A morphometric study.

The post-mortem pathology in 20 spinal cords of human immunodeficiency virus (HIV) infected patients with vacuolar myelopathy was quantified by evaluating (i) the intensity of myelin change, vacuolation and macrophage density; and (ii) the areas of white matter covered by each feature. Severity scores were constructed for (i) the anterior, lateral, and posterior white matter columns; (ii) each level of spinal cord; and (iii) the whole spinal cord [Cord Total and Cord Average Severity Scores (CTSS, CASS)]. Astroglial activation was scored separately. In 14 cords with mild-moderate vacuolar myelopathy (CASS = 23-259), macrophages were the most prominent pathological feature, and level severity scores were higher at mid-thoracic than cervical levels (P = 0.009). In six cords with severe vacuolar myelopathy (CASS = 396-614), vacuolation, demyelination and macrophages were equally evident and thoracic and cervical level severity scores were similar. The most severe lesions showed evidence of clearing of macrophages from the collapsed centres. A clinical lower limb score correlated with the anterior (P = 0.03) and lateral (P = 0.04) column total scores and with the CTSS (P = 0.04) in the nine patients who had had both myelopathy related disability and all cord levels available. There was no significant longitudinal gradient in score severity in the posterior, lateral or anterior columns and no evidence of a dying-back phenomenon. There was no evidence of Wallerian degeneration occurring as a primary process. Astroglial activation did not correlate with the severity or duration of the vacuolar myelopathy. Detection of HIV p24 antigen in the spinal cord related to the local presence of multinucleated giant cells and to antigen expression in the brain but not with the severity of vacuolar myelopathy. The pathology in vacuolar myelopathy appeared to start in the mid-low thoracic cord, with increasing rostral involvement as the disease became more severe. The relative prominence of macrophages in mild-moderate lesions suggests they may be involved early in the pathogenesis of vacuolar myelopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults.

Two unrelated and previously healthy girls, aged 17 and 18, presented with a subacute encephalopathy, visual and sensory symptoms and signs, and prominent seizures that were difficult to control. Brain MRI showed lesions (high signal on T2 weighted images) in the occipital lobes and thalamus; EEG showed slow wave activity with superimposed polyspikes. Inexorable downhill progression led to death in hepatic failure within eight months of onset. Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.

Adolescent↗
PubMed1995

Severe sensory-autonomic neuropathy and endocrinopathy in insulin-dependent diabetes.

A patient developed insulin-dependent diabetes mellitus at the age of 9 years, complicated by a sensory/autonomic polyneuropathy which presented with a respiratory arrest at the age of 41 years. The neuropathy increased in severity over the subsequent two decades. At the age of 52 years she had hypopituitarism, hypothyroidism and low normal adrenal function. Autopsy at the age of 59 years revealed loss of pituitary tissue with evidence of hypophysitis, a lymphocytic thyroiditis and severe adrenal atrophy with lymphocytic infiltration of the medulla. The pancreas showed reduced numbers and size of the islets of Langerhans with total loss of immunoreactivity for insulin but intact glucagon-producing cells. These features are consistent with a type 2 autoimmune polyendocrine syndrome, in which lymphocytic hypophysitis has not previously been recorded. There was severe loss of myelinated nerve fibres in the sural nerve and rostrally accentuated fibre degeneration in the gracile fasciculi, but only mild cell loss in the dorsal root ganglia. This combination suggests the presence of a central-peripheral distal axonopathy. The cervical sympathetic ganglia were severely atrophic. Minor inflammatory infiltration was observed in the dorsal root and sympathetic ganglia. Significant vascular abnormalities were not present in the peripheral nerves. This, and the pattern of nerve fibre degeneration, suggest that in this case the neuropathy was likely to have been related to metabolic rather than vascular causes. The inflammatory infiltrates in sensory and sympathetic ganglia raise the possibility of an autoimmune inflammatory contribution to the neuropathy.

Autonomic Nervous System Diseases↗
PubMed1995

The effects of formalin fixation on the detection of apoptosis in human brain by in situ end-labelling of DNA.

The technique of DNA in situ end-labelling (ISEL) for the detection of apoptotic cells has recently become the method of choice. The incorporation of a labelled nucleotide to facilitate detection into the single-stranded region of DNA cleaved by endogenous nucleases has proved to be a sensitive and straightforward technique. Previous reports have applied the technique to the study of apoptotic cells in brain tissue, which is normally subjected to relatively long-term formalin fixation. In this study we have examined the effects of long-term formalin fixation on the ability to detect apoptosis using ISEL in a variety of pathologies and in a normal rat testis. In the tissues which had been treated with overnight formalin fixation, apoptotic cells were readily identified in those pathologies where it might be expected to occur. However, in tissue which had been fixed for several weeks or more, apoptotic cells were not detectable. Samples of brain lymphoma tissue and rat testis subjected to a prospective analysis with respect to fixation time showed that the ability to detect apoptotic cells tailed off at around 3-5 weeks. In order to obviate the risk of false negative results it would be desirable to use ISEL in tissues formalin fixed for less than this period.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The neuropathological features of neuroacanthocytosis.

In this article we describe the neuropathological changes in three patients with neuroacanthocytosis and review the neuropathology of the other eight cases reported in the literature. Macroscopically the brains showed enlargement of the lateral ventricles, especially the frontal horns. The most severely and consistently affected brain areas were the caudate nucleus and putamen, which were atrophic and showed by light microscopy marked neuronal loss and gliosis. Small and medium-sized striatal neurons were particularly depleted. The globus pallidus was almost as severely involved as the striatum. In some cases the thalamus, substantia nigra, and anterior horns of the spinal cord showed pathology, mainly neuronal loss and mild gliosis. Brain areas with no pathology included the subthalamic nucleus, cerebral cortex, cerebellum, pons, and medulla. The preservation of these areas may help in the neuropathological distinction of neuroacanthocytosis from Huntington's disease.

Acanthocytes↗
PubMed1994

An immunohistochemical study of p53 and proliferating cell nuclear antigen expression in progressive multifocal leukoencephalopathy.

Nuclear p53 immunoreactivity is demonstrated in infected oligodendroglia, as well as in a proportion of reactive and bizarre astrocytes, in seven progressive multifocal leukoencephalopathy (PML) biopsies. This likely represents binding to, and prolongation of the half-life of, wild-type p53 protein by JC virus T-antigen. Other possible mechanisms are considered. The same cells show proliferating cell nuclear antigen (PCNA) positivity, as do a proportion of morphologically normal oligodendroglia and astrocytes, reflecting proliferating populations of these glial sub-types. It is possible that functional inactivation of p53 in nonlytically infected astrocytes may allow neoplastic astrocyte clones to emerge. However, p53 and PCNA immunoreactivity per se cannot be regarded as indicative of neoplasia in PML, and caution must be exercised in the interpretation of such nuclear staining profiles.

Adult↗
PubMed1994

Dysembryoplastic neuroepithelial tumor. Features in 16 patients.

Dysembryoplastic neuroepithelial tumour (DNT) is a newly recognized brain mass lesion with distinctive pathological features and a favourable prognosis. We reviewed the clinical, electroencephalographic, neuroimaging and pathological features of 16 patients with DNT who underwent surgery; only one patient did not have epilepsy. Mean age at seizure onset was 9.5 years (range: 1 week to 30 years) and surgery 17 years (range: 7 months to 37 years). The mean verbal IQ was 94.6 (range: 79-110) and performance IQ 105 (range: 79-130) (n = 10). The EEG was abnormal in all cases reviewed (n = 13): localized slow activity was seen in 12 and interictal spiking in 10 patients, being less extensive than or concordant with the lesion in three and more extensive than or distant to the lesion in seven. X-ray CT was normal in three out of 11 patients. Magnetic resonance imaging provided detailed anatomical information: the lesion was predominantly intracortical, although in six patients, there was also white matter involvement. The lesion involved the temporal lobe in all but one patient where it was in the cingulate gyrus. Of the temporal lobe cases, MRI showed that the lesion involved, or was in close proximity to, mesial temporal structures in 11 out of 14 patients. Other magnetic resonance features included: circumscribed hyperintensity on long TE/TR images (10 patients), hypointensity on short TR images (12 patients), and cyst formation (five patients). Calcification was seen on CT in four patients. Post surgical follow-up ranged from 8 to 30 months (mean 16.2 months): 12 patients are seizure free and two have a > 80% reduction in seizure frequency (n = 14). Histopathological characteristics included a heterogeneous composition in all cases, calcification (13 cases), dysplastic features (12 cases) and isolated foci of subpial spread (five cases). The presence of occasional mitoses in 12 cases and immunoreactivity to the proliferating cell nuclear antigen in six cases indicate that these lesions have cellular proliferative activity and that there may be a need to follow these patients postoperatively.

Adolescent↗
PubMed1994

Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome.

Productive varicella-zoster virus (VZV) infection of the central nervous system (CNS) was demonstrated in 11 acquired immune deficiency syndrome (AIDS) patients using immunocytochemistry and in situ hybridization. A characteristic zoster skin eruption was seen in only four cases. From our own series and 11 other cases in the literature, we identified five clinico-pathological patterns of VZV infection of the CNS in AIDS patients which could occur simultaneously. (i) Multifocal encephalitis predominantly involving the white matter, likely to be due to haematogenous spread of the infection was found in four cases. (ii) Ventriculitis was found in three cases. In two cases there was complete acute or chronic necrosis of the ventricular wall with marked vasculitis; in the third, the ependymal lining appeared irregular with foci of VZV-infected ependymal cells, some of which protruded into the ventricular lumen. (iii) Acute haemorrhagic meningo-myeloradiculitis with necrotizing vasculitis was observed in two cases. In one, this was associated with ventriculitis and was possibly due to shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the CSF. (iv) Focal necrotizing myelitis was seen in one case. It followed cutaneous herpes zoster and was considered to result from neural spread from the diseased dorsal root ganglion similar to cases previously described of encephalitis limited to the visual system following VZV ophthalmicus, or bulbar encephalitis following a trigeminal zoster. (v) Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts was seen in four cases, it was associated with meningitis in most cases. These findings are in keeping with the observation in non-AIDS patients that VZV spread to the CNS may follow different routes. Our study tends to show that VZV infection of the CNS occurs more frequently in AIDS than previously suspected and suggests that it must be considered as a diagnosis in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Immunohistochemical changes and PCR detection of HIV provirus DNA in brains of asymptomatic HIV-positive patients.

The stage of HIV infection at which the virus enters the nervous system remains poorly understood. Examination of brains of HIV-positive non-AIDS patients often shows lymphocytic meningitis, myelin pallor and gliosis, but no immunohistochemical (IHC) evidence of the virus. In this study we have examined a number of brains from HIV-positive patients with (23) and without (8) AIDS as well as brains from 5 HIV-negative controls by morphological, morphometric, IHC and polymerase chain reaction (PCR) methods in an attempt to establish at what stage of the infection HIV can be detected in the brain and to correlate its presence with the pathological changes in the cortex. HIV-1 proviral DNA was found by PCR in the cortex of the majority of AIDS and in 2 out of 8 non-AIDS cases. Astroglial reaction was observed in the cortex of the majority of AIDS brains but not in most of the non-AIDS brains which showed, in addition, a dramatic reduction of glial fibrillary acidic protein staining around blood vessels; moreover, in this group the density of microglial cells was higher than in the AIDS group. These results show that: 1) HIV proviral DNA can be found in the brains of HIV-positive non-AIDS patients; 2) in the same group there is an increase in density of microglial cells which 3) appears to be transient, since AIDS brains without neuropathology show a lower density of these cells. They also suggest that the status of 'immune reaction' existing in AIDS may predate this period.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

PCR detection of HIV proviral DNA (gag) in the brains of patients with AIDS: comparison between results using fresh frozen and paraffin wax embedded specimens.

AIMS: To adapt the polymerase chain reaction (PCR) technique of HIV detection to paraffin wax embedded brain tissue and to compare the results with those obtained using frozen tissue. METHODS: HIV antigen and HIV proviral DNA were detected in specimens of frontal lobe using immunohistochemistry and PCR, respectively. DNA was extracted from fresh tissue using standard methods whereas the technique for extracting DNA from paraffin wax embedded tissue was partly modified. RESULTS: Twenty cases were examined. HIV DNA was detected in 16 cases in frozen specimens. Of these, 15 were also positive when paraffin wax embedded material was analysed. CONCLUSIONS: This study shows that HIV proviral DNA can be detected in formalin fixed, paraffin wax embedded brain tissue by PCR. The results obtained from paraffin wax embedded specimens showed a similar degree of reliability to those from fresh frozen brain. Factors such as fixative, fixation time, and delay in performing post mortem examinations did not seem to influence PCR amplification as positive results were obtained with specimens left in fixative for up to eight months, as well as in cases where post mortem examinations had been delayed for up to four days.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Development of cortical fibres into the gracile nucleus of the rat: an ultrastructural study.

A study was made on the development of cortical synapses in the gracile nucleus of rats using degeneration methods. A total of 46 animals, 1 adult and 45 neonates whose ages varied from 1 to 7 days, had the right somatosensory motor cortex destroyed. The survival period varied from 1 to 30 days. Identification of axonal terminals in the gracile nucleus was also achieved by tracing the cortical fibres of 1 adult rat using horseradish peroxidase-wheat germ agglutinin (HRP-WGA). Degenerating axodendritic and axosomatic terminals that originated from cortical fibres were seen in the adult animal which survived 2 days. Their origin was confirmed by the presence of HRP-WGA inside the terminals. Light or electron microscopic changes were not seen, and in particular, the gracile nucleus was not smaller than in the control adult animals which survived 30 days or in neonates which survived 8-30 days, consistent with the small component of cortifugal fibres believed to terminate in secondary sensory nuclei. In neonates that survived a shorter period, terminal degeneration was only seen in cases operated at 4 days and later, indicating that cortical axons do not synapse in the gracile nucleus until postnatal day 4. Our results provide further support for the existence of a period in which the fibres approach their target but do not penetrate it to form synaptic junctions during the growth of cortical axons toward their targets, since previous studies have demonstrated that cortical fibres persisting to adulthood decussate completely at the level of the medulla at 12-36 h after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Nigral degeneration in neuroacanthocytosis.

We counted nerve cells in different subregions of the substantia nigra in three patients with neuroacanthocytosis and compared the results with those of age-matched Parkinson's disease and control patients. Two patients with neuroacanthocytosis and clinical parkinsonism in life had a reduced neuronal density in the substantia nigra, while in a third patient without parkinsonism, this number was at the lower limit of the control range. In neuroacanthocytosis with parkinsonism and in Parkinson's disease, the ventrolateral region of the substantia nigra was most severely affected, although in neuroacanthocytosis cases, nigral neuronal loss was more widespread.

Aged↗
PubMed1993

Herpes simplex type 1 encephalitis in acquired immunodeficiency syndrome.

A severe acute necrotizing herpes simplex virus type 1 encephalitis, apparently mediated by macrophages or cytokines or both, was seen in a patient with acquired immunodeficiency syndrome. The necrosis had a distribution similar to that seen in immunocompetent subjects. Viral inclusions were abundant and meningeal reaction was minimal, as previously described in one anergic patient.

Acquired Immunodeficiency Syndrome↗