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Biomedical subjects

J Mikol

Publications and source records attributed to J Mikol.

At least 55 records · Page 3Linked to original sources
PubMed1995

AIDS-associated progressive multifocal leukoencephalopathy revealed by new-onset seizures.

PURPOSE: To describe the clinical features of new-onset seizures in HIV-1-infected persons with progressive multifocal leukoencephalopathy (PML), and to discuss potential mechanisms. PATIENTS AND METHODS: Forty-nine consecutive HIV-1-infected patients with PML attended our institutions between January 1988 and September 1993. We retrospectively analyzed cases with seizures as the presenting symptom of PML. RESULTS: Twenty percent of the HIV-1-infected patients with PML presented with new-onset seizures of various types, generalized or partial. None of them met the criteria of the AIDS dementia complex or had a concomitant opportunistic infection. Their mean CD4 cell count was < 60/mm3. Brain magnetic resonance imaging showed areas of increased signal intensity on T2-weighted images in 9 cases, and atrophy in only 1 case. Lesions most often involved subcortical white matter in parieto-occipital or frontal lobes, but 2 patients had posterior fossa lesions. Image-guided stereotactic brain biopsies in 8 cases and postmortem examination in 2 confirmed the diagnosis of PML. Typical histological lesions were observed in all cases, and positive immunolabelling of oligodendroglial nuclei was obtained in all cases with the polyclonal antibody directed against late SV40 antigens. Putative causative factors for the seizures include demyelinated lesions adjacent to the cerebral cortex acting as irritative foci, axonal conduction abnormalities, or disturbances of the neuron-glia balance. CONCLUSION: These cases illustrate that PML should be considered as a possible cause of new-onset seizures in patients with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Deletion of mitochondrial DNA in patient with chronic tubulointerstitial nephritis.

We report a mitochondrial DNA deletion (2.6 kb) in a boy with tubulointerstitial nephritis in whom chronic renal failure and leukodystrophy subsequently developed. Elevated lactate values in plasma and cerebrospinal fluid were suggestive of a defect in the mitochondrial respiratory chain. High amounts of deleted mitochondrial DNA were present in muscle and cerebral white matter. On the basis of this observation, we suggest giving consideration to genetic defects of oxidative phosphorylation in any attempt to determine the origin of unexplained chronic tubulointerstitial nephritis, especially when seemingly unrelated organs are involved.

Base Sequence↗
PubMed1995

Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies). Clinical and neuropathological analysis of 53 patients from three unrelated SCA2 families.

Autosomal dominant cerebellar ataxia type I was diagnosed in three unrelated families from Martinique (French West Indies), and linkage to the locus for spinocerebellar ataxia 2 (SCA2) was established. Neuropathological findings in two patients were those of olivopontocerebellar atrophy without oligodendroglial cytoplasmic inclusions. Cerebellar ataxia was associated with hyporeflexia in 68% of 31 examined patients, with slowed and/or limited eye movements in 65% and with dementia in 29%. No patients had optic atrophy, pigmentary retinal degeneration, spasticity or parkinsonism. Mean age at onset was 33 +/- 16 years, and onset before the age of 20 years was correlated with a more rapid and severe course of the disease. Movement disorders, oculomotor disturbances, sphincter disturbances and cognitive impairment were significantly more frequent in early than in late onset patients. This explains why the phenotype was strikingly different in one family, in which mean age at onset was much earlier. Comparison with previously described SCA2 families indicated similarities, such as reduced saccade velocity, supranuclear ophthalmoplegia and decreased reflexes, although phenotypic heterogeneity remains the outstanding feature of this disorder.

Adolescent↗
PubMed1995

[The epidemiology of cerebral lymphoma in AIDS].

Cerebral lymphomas are one of the complications of AIDS. Their increasing frequency, especially in the last decade, has to be correlated with the incidence of systemic lymphomas and especially central nervous system (CNS) lymphomas in non immuno-compromised patients. CNS involvement is found in 40% of systemic lymphomas. Primary lymphomas have an incidence of 0.4-0.56% in epidemiological studies and 7.6% in post-mortem series. Primary lymphomas are noted in all patients, homosexuals, drug-addicts, children, with a lower rate in the haemophiliacs. Known risk factors are HIV itself Epstein-Barr virus almost constantly demonstrated in tumour cells. Epidemiological studies on cerebral lymphomas must still be completed as, until recently, they were included in the group entitled lymphomas, and risk factors have to be specified with more accuracy.

Brain Neoplasms↗
PubMed1994

Cerebral glial tumors and human immunodeficiency virus-1 infection. More than a coincidental association.

BACKGROUND: The authors describe the clinical and morphologic patterns in four patients with acquired immune deficiency syndrome (AIDS) who developed intracranial glial tumors. METHODS: This retrospective study reports 70 patients at various stages of human immunodeficiency virus-1 (HIV-1) infection who underwent stereotactic brain biopsy for an intracerebral space-occupying lesion. RESULTS: Of these patients, four had glial tumors: one astroblastoma, two astrocytomas, and one glioblastoma. Glial tumors probably arise from a complex interplay of factors; possibilities include the activation of a dominant oncogene or viral inactivation of a tumor suppressor gene by a viral promoter (like the tat protein), impairment of immune defenses (which facilitates the growth of astrocytomas in acute lymphoblastic leukemia), production of cellular growth factors, cytokines, possible infection of glial cells by HIV, and the potentiation of a coinfectious agent. CONCLUSIONS: These cases illustrate that glial tumors should be considered in the differential diagnosis of brain masses in HIV-1 infection, especially because specific treatment for these tumors is available. Moreover, the occurrence of glial tumors in AIDS patients is not only an important event from a clinical point of view, but may also have implications for the pathogenesis of tumors in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism.

Fatal familial insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.

Codon↗
PubMed1994

Creutzfeldt-Jakob disease and cerebral amyloid angiopathy.

An 83-year-old female with no personal or familial neurological history developed progressive gait and speech disturbance and left motor deficit. She suffered intractable seizures and died 3 months after the onset of neurological signs. Neuropathology showed severe spongiosis and gliosis in the cortex and basal ganglia, and diffuse cerebral amyloid angiopathy. Immunostaining for prion protein (PrP) showed intense PrP positivity in areas of confluent spongiosis and some granular staining in astrocytes. The cortical vessel walls stained positively for beta/A4 amyloid but not for PrP amyloid. Both types of amyloid were only observed in pericapillary parenchyma, in areas with severe spongiosis. There were only a few tangles and neuritic plaques in the temporal cortex; amyloid plaques were not present either by silver stains or immunostains. There was neither arteriopathic leukoencephalopathy nor cerebral hemorrhage. Immunoblot analysis of brain extracts revealed an abnormal proteinase K-resistant isoform of PrP. Association of Creutzfeldt-Jakob disease and Cerebral amyloid angiopathy in the absence of Alzheimer changes in unusual. The association of PrP and beta/A4 amyloid deposits could have been fortuitous in an 83-year-old patient. An etiopathogenic relationship between beta/A4 amyloid deposition and PrP accumulation may also be considered.

Aged↗
PubMed1994

Diarrhea and autonomic dysfunction in a patient with hexosaminidase B deficiency (Sandhoff disease).

The causal factors and the physiopathology of motor diarrhea are still unclear. This case report describes a 60-year-old white man with severe diarrhea for more than 10 years and minor signs of autonomic dysfunction. Extensive investigation showed that small intestinal motility and absorption were normal but that accelerated colon transit precluded water and solute absorption from the large bowel. Orthostatic hypotension, sexual dysfunction, and loss of sweating suggested dysfunction of the autonomous nervous system, which was confirmed by reduced plasma concentrations of norepinephrine and dopamine. Rectal biopsy specimens showed enlarged enteric ganglion cells filled with lipidic material. Levels of total hexosaminidase and hexosaminidase B in plasma, white blood cells, and fibroblasts were decreased, as found in Sandhoff disease. The pedigree of the proband's family showed several affected and heterozygous individuals, detected by examination of total hexosaminidase and hexosaminidase B levels in plasma. Among the five homozygous subjects, three had a clinical picture of diarrhea and orthostatic hypotension since the age of 50. Therefore, hexosaminidase B deficiency should probably be regarded as a cause for dysautonomia; dysfunction of the gastrointestinal tract, manifested by motor diarrhea or esophageal dysmotility, could be the initial and prevalent presentation of dysautonomia.

Autonomic Nervous System Diseases↗
PubMed1994

Calcitonin genes (I and II) expression in human nervous and medullary thyroid carcinoma tissues.

The calcitonin gene family comprises two main genes: CALC I which encodes for calcitonin (CT) mRNA in thyroid and calcitonin gene-related peptide I (CGRP I) mRNA in neuronal tissues and CALC II gene which encodes for CGRP II mRNA only. Recently, in normal thyroid and in medullary thyroid carcinoma (MTC), we detected an additional splicing pathway involving the splicing of exon 4 to exon 5 and leading to the expression of a third CALC I mRNA: CT mRNA II. In the present study, we analyzed by polymerase chain reaction the expression of CT mRNAs I and II, CGRP I and II mRNAs in MTC and in human tumors of the nervous system (3 pituitary adenomas, 3 astrocytomas, 2 schwanomas). In pituitary tissues, CGRP II expression was constant and easily detectable in comparison to other tissues. CT mRNA II signal was very low, but clearly detectable after a reamplification indicating that the factors responsible for the splicing of exon 4 to exon 5 are poorly operative in neuronal tissues.

Adenoma↗
PubMed1994

Autosomal dominant arteriopathic leuko-encephalopathy and Alzheimer's disease.

A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space, displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, C1q and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma-trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in nonfamilial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.

Alzheimer Disease↗
PubMed1994

[Intramedullary localization of a primary cerebral lymphoma in AIDS].

A 36 years-old male with AIDS, presented with left hemiparesis revealing a right parietal tumour. Stereotactic biopsy demonstrated a malignant non-Hodgkin's lymphoma. His condition partially improved following radiotherapy and chemotherapy. Three months later he was re-admitted with progressive bilateral root pain and urinary incontinence resulting in paraplegia with sensory loss below T10. He died one month later from generalized sepsis. Neuropathology confirmed an immunoblastic B-cell malignant non-Hodgkin's lymphoma in the white matter of the right parietal lobe and revealed a centrospinal localisation of the lymphoma in the thoracic cord at T10. There was no visceral localisation of the tumour. Secondary spread to the spinal cord of malignant non Hodgkin's lymphomas, usually causes meningo-myelo-radiculitis. Intraspinal deposits of primary cerebral lymphomas are uncommon and have never been previously described in AIDS, to our knowledge. Their pathogenesis is unclear. In our case, neuropathological findings are consistent with diffusion of the primary tumour to leptomeninges and secondary infiltration of the spinal cord along the perivascular spaces.

Adult↗
PubMed1994

[GM2-Gangliosidosis variant B1 disclosed during adolescence by an isolated multi-systemic involvement of the central and peripheral nervous systems].

The authors report on a Portuguese family with 3 adult brothers affected with GM2-gangliosidosis (B1 variant) in a sibship of 4, and more specifically on one of these brothers with neurological onset at the age of 17. Psychosis, lower motoneuron involvement and dysarthria were predominant in two of the cases; the third had a cerebellar symptomatology. Hexosaminidase A activity, studied in leukocytes, was profoundly deficient when measured using the specific sulfated substrate, but nearly normal using a conventional assay (non-sulfated substrate). These results established the diagnosis of the unusual enzymological form of GM2-gangliosidosis known as the B1 variant, which had so far not been associated with an adult phenotype. Molecular studies are in progress to study genotype/phenotype correlations in this family in comparison with known mutations in the B1 variant and in adult GM2-gangliosidosis. This report also emphasizes that a metabolic etiology, leading to genetic counselling, should be considered in some familial degenerative neurological disorders.

Adolescent↗
PubMed1994

[Seven cases of subependymoma. Anatomoclinical study and review of the literature].

Subependymomas are uncommon, benign, slowly growing lesions usually located in the fourth ventricle. Their morphology is characteristic, but their histogenesis remains controversial. Seven cases observed in our laboratory over a period of 7 years are reported. Most tumors were located axially in the brain stem, and symptoms were more variable than usually reported. The histological appearance was fairly uniform. Immunohistochemistry showed that the fibrillary component was composed of glial fibers. Ependymary differentiation is inconstant on electron microscopy. The pathogenesis of the lesion (tumor, hamartoma or reactive proliferation) is debated in the literature as is the histogenesis.

Adult↗
PubMed1994

Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia.

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.

B-Lymphocytes↗
PubMed1993

The Golgi apparatus of motor neurons in amyotrophic lateral sclerosis.

The Golgi apparatus plays a key role in the posttranslational processing of polypeptides destined for secretion, incorporation into plasma membranes, and fast axoplasmic transport. Dispersion or fragmentation of the Golgi apparatus, experimentally induced by microtubule-disrupting agents, is associated with decreased secretion of immunoglobulins and insulin. The Golgi apparatus is also involved in targeting of lysosomal enzymes and in the endocytosis of certain hormones, receptors, and toxins. There is a paucity of information on this important organelle in human neuropathological conditions. Using an organelle-specific antiserum we have examined by immunocytochemistry the Golgi apparatus of motor neurons in the spinal cord in 4 patients with amyotrophic lateral sclerosis and 1 patient with Werdnig Hoffmann's disease, 1 with infantile neuronal degeneration, 1 with adult-type familial bulbospinal atrophy, 1 with mitochondrial myopathy with cytochrome c oxidase deficiency, 1 with centronuclear myopathy, and 1 with Duchenne's muscular dystrophy, and in 9 age-matched control subjects. In all motor neuronopathies examined and in the patient with mitochondrial myopathy, 20 to 85% of neurons counted had "fragmented" Golgi apparatus. In age-matched control subjects and the other 2 patients with myopathies, 0 to 1.65% of motor neurons had fragmented Golgi apparatus. These findings suggest that the Golgi apparatus of motor neurons is involved in patients with amyotrophic lateral sclerosis and related motor neuron diseases, and perhaps in patients with certain fatal primary myopathies.

Adolescent↗
PubMed1993

Primary T-cell malignant lymphoma of the central nervous system. Histological, immunohistochemical and ultrastructural study of a case.

Most primary malignant lymphomas (ML) of the central nervous system (CNS) are derived from B-cells, whereas T-malignant lymphomas (T-ML) primarily arising in the CNS are extremely rare. We report on a patient with a primary T-ML of the CNS localised in the posterior fossa. On the basis of histological, ultrastructural and immunohistochemical studies, this tumour was classified as a pleomorphic T-ML, medium and large cell type with peripheral helper/inducer T-cell phenotype (CD 1-, CD 2+, CD 3+, CD 5+, CD 7-, CD 4+, CD 8-, CD 19-, CD 22-, UCHL 1+/CD 45 RO, L 26-/CD 20, LN 1-/CDW75, LN 2-/CD 74, MB 2-). Furthermore, the positivity of the markers CD 25 and HLA-DR on many medium-sized and large lymphoma cells suggests activation of these cells. The nuclear marker of proliferative activity Ki-67 was expressed in some large cells, whereas the natural killer cell-related markers CD 16 and Leu 7/CD 57 did not react with lymphoma cells. This study emphasises the value of extensive immunohistochemical investigations on frozen and paraffin sections in order to identify and characterize the T-cell malignancies, particularly in their rare CNS location.

Antigens, CD↗