PubMed Health⌕ Search

Biomedical subjects

Orso Bugiani

Publications and source records attributed to Orso Bugiani.

13 recordsLinked to original sources
PubMed2006

Periodic electroencephalogram complexes in a patient with variant Creutzfeldt-Jakob disease.

OBJECTIVE: Based on the current criteria, the diagnosis of "possible" or "probable" variant Creutzfeldt-Jakob disease (vCJD) implies the absence of periodic sharp wave complexes (PSWCs) in the electroencephalogram (EEG). To verify this point, we investigated the development of the EEG changes along the course of the disease in a pateint with vCJD. METHODS: Long-lasting EEG-polygraphic recordings were performed once a month during the last year of illness. RESULTS: We found the occurrence of a typical EEG periodic pattern in the late clinical stage of the vCJD patient. INTERPRETATION: In the light of our finding, the diagnostic criteria for vCJD should be amended to include the possibility of a typical periodic EEG in advanced stages of disease in cases with long survival.

Adult↗
PubMed2006

Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe Consortium.

This interlaboratory study evaluated the reproducibility of the assessments of neuritic plaques and neurofibrillary tangles (NFTs)--the hallmark lesions of Alzheimer disease--and compared the staining between the BrainNet Europe centers. To reduce the topography-related inconsistencies in assessments, we used a 2-mm tissue microarray (TMA) technique. The TMA block included 42 core samples taken from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas silver stains using an immunohistochemical (IHC) method with antibodies directed to beta-amyloid (IHC/Abeta) and hyperphosphorylated tau (IHC/HPtau). The staining quality and the assessments differed between the participants, being most diverse with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas (good/acceptable stain in 57%) and IHC/Abeta (good/acceptable stain in 71%). The most uniform staining quality and assessment was obtained with the IHC/HPtau method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute) that was used significantly influenced the agreement, being highest with NIA-Reagan (54%) recommendations. This agreement was improved by visualization of NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to visualize NFTs and neuropil threads should be considered as a method of choice in a future diagnostic protocol for Alzheimer disease.

Aged↗
PubMed2005

Stimulation of the posterior hypothalamus for medically intractable impulsive and violent behavior.

OBJECTIVE: To describe the therapeutic effect of deep brain stimulation for the treatment of patients with below-average IQs who are affected by aggressive and disruptive behavior and who are resistant to any drug and/or conservative treatment (including occupational therapy). PATIENTS AND METHODS: Two consecutive patients suffering from mental retardation with aggressive and disruptive behavior and resistant to any pharmacological treatment underwent deep brain stimulation electrode placement in the posteromedial hypothalamus for continuous chronic high-frequency stimulation (HFS). The stereotactic coordinates of the target were chosen according to the study by Sano et al., which involved hypothalamic stereotactic lesions. RESULTS: HFS of the posteromedial hypothalamus demonstrated consistent improvement of disruptive behavior in both patients at the follow-up evaluation 1 year later. CONCLUSIONS: HFS of the posteromedial hypothalamus showed similar results to those obtained by Sano et al. in the 1960s with radiofrequency lesions of the same target volume. The reversibility of neurostimulation allows HFS to control disruptive behavior when conservative treatments are ineffective, and drug therapy is uneventful or causes severe side effects. In conclusion, this neuromodulation procedure improved the quality of life and the range of social relationships for both of the treated patients.

Adult↗
PubMed2005

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.

Adult↗
PubMed2005

Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc.

In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.

Adult↗
PubMed2005

Long-term high-frequency bilateral pallidal stimulation for neuroleptic-induced tardive dystonia. Report of two cases.

The authors report the results of long-term bilateral high-frequency pallidal stimulation in two patients affected by neuroleptic-induced dystonia. The first patient, a 33-year-old man, experienced a dystonic posture of the trunk, with involvement of the neck and upper and lower limbs after 11 years of treatment with neuroleptic drugs. The second patient, a 30-year-old man, presented with a torsion dystonia, spasmodic torticollis, and involuntary movements of the upper limbs, which appeared after 4 years of neuroleptic treatment. Both of these dystonias worsened even after the neuroleptic treatment had been discontinued, and neither patient responded to clozapine or benzodiazepine therapy. The time lapse between the first appearance of dystonia and surgery was, respectively, 5 and 3 years. In each case bilateral stereotactic implantation of electrodes within the globus pallidus internus (GPI) was performed while the patient was in a state of general anesthesia. The electrodes were placed at the following anterior commissure-posterior commissure line-related coordinates: 20 mm lateral to the midline, 6 mm below the intercommissural plane, and 3 mm anterior to the midcommissural point. Electrical stimulation (130 Hz, 1 V, 90 microsec) was begun on the 1st postoperative day. In both patients, a genetic analysis positively ruled out a mutation in the DYT1 gene, and magnetic resonance imaging yielded normal findings in both cases. Extrapyramidal symptoms and dystonia disappeared almost completely and dramatically in both patients just a few days after high-frequency bilateral pallidal stimulation commenced. Both patients regained autonomy and neuroleptic treatment was reinitiated. The follow-up period for both cases was 1 year. Long-term bilateral high-frequency stimulation of GPI resulted in a dramatic and long-lasting improvement of neuroleptic-induced tardive dystonia.

Adult↗
PubMed2004

Neuropathological and clinical phenotype of an Italian Alzheimer family with M239V mutation of presenilin 2 gene.

Presenilin 1 and 2 are 2 highly homologous genes involved in familial Alzheimer disease. While more than 100 mutations in presenilin 1 are known to segregate with the disease in familial Alzheimer disease, only 9 mutations of presenilin 2 have been identified to date. We report the clinical and neuropathological phenotype of FLO10, the large Italian Alzheimer kindred associated with methionine to valine substitution at residue 239 of presenilin 2. The patients showed a remarkable variability in age of onset of symptoms, disease duration, and clinical presentation. The neuropathological study of 2 patients revealed peculiar features in addition to neurofibrillary changes and A beta amyloid deposits in the neuropil and vessel wall. Ectopic neurons in the subcortical white matter, often containing neurofibrillary tangles, were found in both patients, one of whom presented with epilepsy. Furthermore, 1 patient showed an unusually high number of ghost tangles in the cerebral cortex. These observations indicate that the Alzheimer kindred FLO10 associated with M239V mutation of presenilin 2 is characterized by some peculiarities of the clinical and neuropathologic phenotype compared to sporadic Alzheimer disease.

Age of Onset↗
PubMed2003

Structural properties of Gerstmann-Straussler-Scheinker disease amyloid protein.

Prion protein (PrP) amyloid formation is a central feature of genetic and acquired forms of prion disease such as Gerstmann-Sträussler-Scheinker disease (GSS) and variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP fragment spanning residues approximately 82-146. To investigate the determinants of the physicochemical properties of this fragment, we synthesized PrP-(82-146) and variants thereof, including entirely and partially scrambled peptides. PrP-(82-146) readily formed aggregates that were partially resistant to protease digestion. Peptide assemblies consisted of 9.8-nm-diameter fibrils having a parallel cross-beta-structure. Second derivative of infrared spectra indicated that PrP-(82-146) aggregates are primarily composed of beta-sheet (54%) and turn (24%) which is consistent with their amyloid-like properties. The peptide induced a remarkable increase in plasma membrane microviscosity of primary neurons. Modification of the amino acid sequence 106-126 caused a striking increase in aggregation rate, with formation of large amount of protease-resistant amorphous material and relatively few amyloid fibrils. Alteration of the 127-146 region had even more profound effects, with the inability to generate amyloid fibrils. These data indicate that the intrinsic properties of PrP-(82-146) are dependent upon the integrity of the C-terminal region and account for the massive deposition of PrP amyloid in GSS.

Amino Acid Sequence↗
PubMed2003

A case of dementia parkinsonism resembling progressive supranuclear palsy due to mutation in the tau protein gene.

BACKGROUND: Few cases of frontotemporal dementia parkinsonism (FTDP-17) have been described in the literature. To our knowledge, this is the first Italian case. OBJECTIVE: To report a case of FTDP linked to chromosome 17, exhibiting progressive supranuclear palsy on initial examination. PATIENT: A 50-year-old woman had a 4-year history of behavior changes associated with slowly progressive mental decay and parkinsonism, with poor balance, supranuclear vertical gaze palsy, and bradykinesia. The symptoms were not responsive to dopaminergic therapy. Her father had died at age 46 years after a 7-year history of parkinsonism, and her brother, diagnosed as having progressive supranuclear palsy, died at age 45 years. RESULTS: Magnetic resonance imaging showed mild midbrain atrophy, results of an electroencephalogram were normal, and cognitive evaluation showed moderate cognitive impairment, especially evident in the executive and attentional functions. Genetic testing revealed a tau gene mutation at codon 279 (AAT-->AAG) of exon 10. CONCLUSION: Exon 10 mutations (including the N279K mutation) that result in overproduction of the tau isoform with 4 microtubule binding motifs seem to be associated with a mainly parkinsonian phenotype at disease onset.

Chromosomes, Human, Pair 17↗
PubMed2003

Therapeutic approaches to prion diseases.

Prion diseases are unique in that they comprise sporadic, genetic, and iatrogenically or environmentally acquired forms. When disease is acquired by peripheral route, neuroinvasion occurs via at least two different neural pathways (vague and splanchnic nerves) and is usually preceded by prion propagation in secondary lymphoid organs. Conversely, in the other etiologic forms, PrPSc formation occurs within, and is apparently limited to, the CNS. Longitudinal studies on experimental scrapie indicate that substantial neuropathologic changes (i.e., glial activation and nerve cell degeneration) already are present before the onset of symptoms and are topographically related to PrPSc deposits. Accordingly, any effective intervention should start during the preclinical stage of disease, and be aimed at preventing neuroinvasion or PrPSc propagation in the CNS. Unfortunately, no tests are available currently to detect presymptomatic individuals, except for carriers of pathogenic mutations of the PRNP gene. Inhibition of PrPSc formation can be achieved through (1) abrogation of PrPC synthesis or prevention of its transport to the cell surface; (2) stabilization of the PrPC structure to make its conformational change unfavorable; (3) sequestration of PrPSc; (4) reversion of PrPSc to a protease-sensitive form; or (5) interference with the interaction between PrPC, PrPSc, and other macromolecules that feature in the conversion process. The compounds that have some effectiveness in in vitro, cell culture, or animal models of prion disease seem to operate through one of these mechanisms (see Table 1); however, even the most effective drugs only work when administered at the time of infection or very short thereafter, and these conditions are incurable at present. The heterogeneity and complexity of the etiopathogenesis of prion diseases suggest that various strategies and a combination of several compounds with different modes of actions are likely necessary for prevention and treatment. Major efforts should be focused on the development of preclinical diagnostic tests in conjunction with immunization strategies for diseases acquired by peripheral route and identification of more effective compounds for the other etiological forms.

Animals↗
PubMed2003

Hereditary prion protein amyloidoses.

Prion protein (PrP) amyloid accumulation is the pathologic hallmark of some inherited prion diseases such as Gerstmann-Sträussler-Scheinker disease (GSS) and PrP cerebral amyloid angiopathy (PrP-CAA). In GSS, parenchymal amyloidosis may coexist with spongiform degeneration or neurofibrillary tangles, whereas in PrP-CAA, vascular amyloid coexists with neurofibrillary tangles. In GSS, N-truncated and C-truncated proteinase K-resistant PrP isoforms are present in the brain.

Amyloid↗
PubMed2002

Tetracyclines affect prion infectivity.

Prion diseases are transmissible neurodegenerative disorders of humans and animals for which no effective treatment is available. Conformationally altered, protease-resistant forms of the prion protein (PrP) termed PrP(Sc) are critical for disease transmissibility and pathogenesis, thus representing a primary target for therapeutic strategies. Based on previous findings that tetracyclines revert abnormal physicochemical properties and abolish neurotoxicity of PrP peptides in vitro, we tested the ability of these compounds to interact with PrP(Sc) from patients with the new variant of Creutzfeldt-Jakob disease (vCJD) and cattle with bovine spongiform encephalopathy (BSE). The incubation with tetracycline hydrochloride or doxycycline hyclate at concentrations ranging from 10 microM to 1 mM resulted in a dose-dependent decrease in protease resistance of PrP(Sc). This finding prompted us to investigate whether tetracyclines affect prion infectivity by using an animal model of disease. Syrian hamsters were injected intracerebrally with 263K scrapie-infected brain homogenate that was coincubated with 1 mM tetracycline hydrochloride, 1 mM doxycycline hyclate, or vehicle solution before inoculation. Hamsters injected with tetracycline-treated inoculum showed a significant delay in the onset of clinical signs of disease and prolonged survival time. These effects were paralleled by a delay in the appearance of magnetic-resonance abnormalities in the thalamus, neuropathological changes, and PrP(Sc) accumulation. When tetracycline was preincubated with highly diluted scrapie-infected inoculum, one third of hamsters did not develop disease. Our data suggest that these well characterized antibiotics reduce prion infectivity through a direct interaction with PrP(Sc) and are potentially useful for inactivation of BSE- or vCJD-contaminated products and prevention strategies.

Animals↗