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L Roccatagliata

Publications and source records attributed to L Roccatagliata.

9 recordsLinked to original sources
PubMed2002

An Italian severe Salla disease variant associated with a SLC17A5 mutation earlier described in infantile sialic acid storage disease.

The present study reports two Italian brothers affected by severe Salla disease (sialic acid storage disease), a slowly progressive autosomal recessive neurodegenerative disorder prevalent in the Finnish population. Mutations of the SLC17A5 gene, which encodes a protein called sialin, are the primary cause of both Salla disease and infantile sialic acid storage disease (ISSD), a clinically distinct severe disorder. All Finnish patients with Salla disease show a R39C mutation. Both patients showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar atrophy on magnetic resonance imaging (MRI), and lysosomal storage, all typical of Salla disease. Mutation analysis of the SLC17A5 gene in the younger brother revealed no R39C mutation, but a 15-bp deletion in exon 6 on one of the alleles. This mutation is the same described in French-Canadian patients with ISSD. Salla disease must be suspected in patients with unexplained psychomotor retardation associated with ataxia and/or pyramidal symptoms, and MRI findings consistent with cerebral hypomyelination, irrespective of the patient's ethnic origin. A mutation screening based on R39C change does not exclude Salla disease outside Finland. Conversely, mutations found in ISSD can be expected, even in patients showing the Salla phenotype (e.g. symptoms at the milder end of the spectrum).

Adolescent↗
PubMed2001

Epilepsy.

Explore the source record for details and available documents.

Adult↗
PubMed2001

Demyelination and axonal damage in a non-human primate model of multiple sclerosis.

The demyelinating plaque is the paradigmatic lesion of multiple sclerosis (MS), but only recently attention has been given to axonal damage and to its role in the pathophysiology of disease. Albeit the possible relevance of axonal loss in MS and its experimental models, the amount and timing of axonal sufferance has been addressed only in experimental autoimmune encephalomyelitis (EAE) of rodents. In this report we observed that, in the marmoset model of EAE, axonal damage occurs early during the demyelinating process as assessed by immunoreactivity for amyloid precursor protein (APP) and non-phosphorylated neurofilaments (SMI-32 positive) detected mostly in early active lesions compared to late active and normal appearing white matter. The rare occurrence of morphological features of axonal transection, such as APP or SMI-32 positive spheroids and swellings, as well as an increase of neurofilament density in the demyelinated axons without accumulation of electron dense organelles or osmiophilic bodies, at electron microscopy, suggests that early axonal damage may be, at least in part, a reversible process. These findings are of relevance for the development of therapies, which can protect axons and enhance their function and survival.

Amyloid beta-Protein Precursor↗
PubMed2001

Tumor-like multiple sclerosis (MS) lesions: neuropathological clues.

The neuroradiological evidence of a single, large white matter lesion with mass effect, clinically revealed by signs of endocranial hypertension, is highly suspicious for central nervous system neoplasm. In rare cases, a demyelinating disorder can start with atypical features suggestive of a brain tumor; in these cases a brain biopsy is often carried out. We report our experience regarding cases of multiple sclerosis (MS) with atypical tumor-like presentation. None of our patients underwent biopsy. Serial magnetic resonance imaging performed during steroid treatment, together with other paraclinical data, were sufficient for the final diagnosis of MS. These cases are characterized by a severe clinical course and a rapid clinical deterioration, only partially modified by medical treatments. Atypical severe cases, misdiagnosed as MS, can be indeed due to primary CNS vasculitis.

Adult↗
PubMed2000

Restricted immune responses lead to CNS demyelination and axonal damage.

Although autoreactive T-cells have a pivotal role in initiating the inflammatory process in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS), recent evidence suggests a relevant role for autoantibodies specific for myelin proteins as well. To examine the role of B-cells in the cerebrospinal fluid of patients with MS, we analyzed the V(H) gene usage in ten MS patients by PCR technologies. Analysis of HCDR3 length revealed an oligoclonal accumulation of B-cells. Sequence analysis of the V(H)3 and V(H)4 gamma transcripts of two MS individuals demonstrated that this accumulation was related to the expansion and somatic diversification of a limited groups of B-cell clones. These findings are indicative of a chronic and intense antigenic stimulation occurring in the CNS. Animal models, such as EAE, are of particular importance in order to elucidate the pathogenetic effector mechanisms in autoimmune demyelination. In a non-human primate model of EAE, we describe that the immunodominant T-cell epitope is presented exclusively by a monomorphic DRB1 allele, suggesting that susceptibility to EAE may be linked to this unique restriction and, therefore, providing a possible mechanism for MHC linkage to diseases. Moreover, we report on the presence of inflammation, sharp demyelination and axonal damage in EAE induced with whole myelin as well as with recombinant myelin oligodendrocyte glycoprotein (MOG), but not with myelin basic protein alone. The presence of axonal pathology was supported by immunohistochemistry with anti-amyloid precursor protein and anti-non phosphorilated neurofilaments monoclonal antibodies within early active demyelinated plaques. These findings suggest that axonal damage may be an early event in the pathogenesis of autoimmune demyelinating diseases of the CNS and highlights the importance of animal models in which therapies targeting repair and axonal survival may be exploited.

Animals↗
PubMed2000

Myelin/oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in common marmosets: the encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule.

Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14-36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.

Animals↗
PubMed2000

Acute axonal form of Guillain-Barré syndrome in a multiple sclerosis patient: chance association or linked disorders?

Multiple sclerosis (MS) is characterized by inflammation, demyelination and gliosis, involving the central nervous system (CNS) and commonly sparing the peripheral nervous system (PNS). Coexistence of CNS and PNS chronic demyelination has been rarely demonstrated in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) and in MS, but the occurrence of acute polyradiculoneuropathy in a patient with MS is even more unusual. We describe the case of a woman with relapsing-remitting MS who presented with an acute severe tetraparesis. Cerebrospinal fluid (CSF) examination together with neurophysiological data and sural nerve biopsy study demonstrated an axonal form of Guillain-Barré Syndrome (GBS). It remains unresolved if the association of an axonal form of GBS and MS is fortuitous or, on the contrary, is indicative of the coexistence in some individuals of common pathogenetic mechanisms.

Acute Disease↗
PubMed1999

Subacute measles encephalitis in a young man immunosuppressed for ankylosing spondylitis.

Subacute measles encephalitis occurred 1 month after measles onset in a 26-year-old HIV-negative man undergoing immunosuppressive treatment for ankylosing spondylitis. He had seizures, a decline in mental status, and progressive impairment of consciousness, with a fatal outcome. Despite severely deficient cellular immunity, the elevated antimeasles antibody titers and CSF findings indicated that humoral immunity was not impaired. Histologic, electron microscopic, and immunocytochemical studies revealed the typical intranuclear inclusions of paramyxovirus nucleocapsids, and measles virus antigen in neurons and oligodendrocytes.

Adult↗