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Biomedical subjects

A Federico

Publications and source records attributed to A Federico.

At least 55 records · Page 3Linked to original sources
PubMed2004

A syndrome of bilateral hemorrhage of the thalamus and myocarditis with fatal course.

We report the case of a 41-year-old patient with bilateral hemorrhage of the thalamus, leading to death. Post-mortem examination showed acute myocarditis. Neuropathological study showed perivascular infiltrates in affected thalamic regions. Laboratory investigation failed to find any causal agent. We hypothesize an infective agent, affecting the heart and thalamus, as the cause of this syndrome. Diaschisis due to the strategic anatomical position of the thalamus may have been responsible for coma state and death.

Adult↗
PubMed2004

Late diagnosis in severe and mild intellectual disability in adulthood.

BACKGROUND: The diagnosis of intellectual disability (ID) is highly dependent on a comprehensive personal and family medical history, a complete physical examination and a careful developmental assessment of the patient. Our study intended to: (1) classify the aetiology of mild and severe ID in an adult population of 140 Italian subjects; (2) evaluate the frequency of associated medical conditions; (3) evaluate the age of diagnosis in both groups; and (4) underline the importance of aetiological diagnosis for adult ID patients also. METHODS: The study involved 140 consecutive adult Italian ID inpatients and outpatients neurologically investigated at the Neurological Institute C. Mondino of Pavia Service for Mental Retardation. A total of 80 patients had mild ID (MID group) (39 females, 41 males), mean age 34 years (range 19-61 years), mean IQ = 64 (range 51-75), and 60 had severe ID (SID group) (32 females, 28 males), mean age 30 years (range 19-69 years). They underwent a complete diagnostic work-up that comprised prenatal, perinatal and postnatal history, physical examinations, laboratory investigations, genetic survey and neuroradiological investigations to determine the aetiology of ID and to evaluate the presence of associated medical conditions. RESULTS: ID aetiology was classified as prenatal in 34% of the MID and 28% of the SID group. Perinatal and postnatal events were found in 6% of the MID and in 5% of the SID group. Associated medical conditions were found in 97 patients (47% MID and 26% SID). A genetic diagnosis was possible in 6% of patients above 20 years of age and in 5% of patients above 40 years. A diagnosis of cerebral dysgenesis was possible in 5% of patients above 20 years and 4% of patients above 40 years. CONCLUSIONS: A long interval between the diagnosis of ID and the aetiological definition can be observed in a significant percentage (24%) of our population, leading to unfortunate consequences of late diagnosis: late onset of a specific therapeutic program, genetic counselling that is frequently no more useful, and ineffective prenatal diagnosis, leading to the birth of other affected subjects (for familiar ID).

Adult↗
PubMed2004

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.

Aged↗
PubMed2004

DNA end labelling (TUNEL) in a 3 year old girl with Leigh syndrome and prevalent cortical involvement.

Neuropathological study of a 3 1/2 year old girl with familial Leigh syndrome who also harboured a rare ATPase gene mutation disclosed extensive and unusual lesions in the cerebral cortex, despite a typical histological pattern. Early lesions in the periacqueductal grey matter of the brainstem, characterised by capillary congestion and initial regressive neuronal changes, were also observed, along with TUNEL reactive neuronal cells showing morphological signs typical of apoptosis in cortical areas with neuronal cell loss. The finding of lesions in atypical brain areas and for the first time, very early regressive neuronal phenomena, suggest that early changes in crucial brain areas may have been a cause of death. The abundance of TUNEL positive nuclei in cortical areas in the present case suggests that the apoptosis may be involved in the mechanism of neuronal death in Leigh syndrome.

Adenosine Triphosphatases↗
PubMed2004

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis.

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

Adolescent↗
PubMed2004

Cell response to oxidative stress induced apoptosis in patients with Leber's hereditary optic neuropathy.

OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease in which acute or subacute bilateral visual loss occurs preferentially in young men. Over 95% of LHON cases are associated with one of three mitochondrial DNA (mtDNA) point mutations, but only 50% of men and 10% of women who harbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete penetrance and preference for men suggests that additional genetic (nuclear or mitochondrial) and/or environmental factors must modulate phenotype expression in LHON. A role for reactive oxygen species (ROS) in mitochondrial diseases, secondary to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpose of this study was to investigate the role of oxidative stress induced apoptosis in LHON. METHODS: The 2-deoxy-D-ribose induced apoptotic response of peripheral blood lymphocytes from six patients with LHON and six healthy subjects was investigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential. RESULTS: Cells of patients with LHON had a higher rate of apoptosis than those of controls and there was evidence of mitochondrial involvement in the activation of the apoptotic cascade. CONCLUSIONS: These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expression of genetic mutations in different individuals and could represent a potential target in the development of new therapeutic strategies.

Antimetabolites↗
PubMed2004

Mitochondrial alterations in muscle biopsies of patients on statin therapy.

Clinical and biopsy study of nine patients on statin therapy suffering from various myopathic syndromes is reported. Biopsy findings showed non specific myopathic signs and mitochondrial changes, such as subsarcolemmal accumulation, morphological alterations, lipid increase and Cox-negative fibers. These findings confirm that statins may cause muscle damage and impair oxidative metabolism.

Adult↗
PubMed2003

Retinochoroidal atrophy in two adult patients with Angelman syndrome.

We describe a new ocular finding, retinochoroidal atrophy (RCA), associated with optic disk paleness in two adult patients with Angelman syndrome (AS) due to maternal 15q11-13 deletion. The ocular involvement described in children with AS consists iris and choroids hypopigmentation due to loss of function of one copy of P gene involved in maternal deletion. The loss of one copy of the same gene of paternal origin leads to a similar ocular phenotype as in Prader-Willi syndrome (PWS). However to our knowledge, RCA has never been described before in PWS, suggesting that other maternally expressed genes, particularly UBE3A, could be responsible for the retinal changes observed in the adult AS phenotype. Although, further investigations would be necessary to better understand the role of the UBE3A in the retina, the findings reported here should prompt a systematic ophthalmologic evaluation adult patients with AS in order to establish the real incidence of RCA and prevent further disability in these patients.

Adult↗
PubMed2003

Genetic heterogeneity of megalencephalic leukoencephalopathy and subcortical cysts.

Reported are the clinical, neuroradiologic, and molecular findings in 18 patients with megalencephalic leukoencephalopathy and subcortical cysts (MLC) syndrome. Marked clinical intrafamilial and interfamilial variability in mutation-proven cases was found. A broad spectrum of pathogenetic mutations (missense, splice site, insertion, and deletions) were identified in the MLC1 gene, enlarging the spectrum of allelic variants without a straightforward genotype-phenotype correlation. Five patients did not harbor mutations in MLC1, supporting the existence of at least one other MLC locus.

Adolescent↗
PubMed2003

Evidence of early cortical atrophy in MS: relevance to white matter changes and disability.

OBJECTIVE: To assess cortical gray matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of white matter (WM) in patients with the relapsing-remitting (RR) and primary progressive (PP) forms of the disease. METHODS: Conventional MRI examinations were obtained in patients with definite MS who had either the RR or the PP form of the disease. An automated analysis tool was used with conventional T1-weighted MR images to obtain total and cortical brain volumes normalized for head size. Total brain lesion load was estimated on conventional proton density and T2-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed. RESULTS: Normalized cortical volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects (p < 0.001) but were similar between the two patient groups (p > 0.5). NCV decreases in both patients groups were detected even in those patients with short disease duration (<5 years; p < 0.001 in RR MS and p < 0.05 in PP MS) and minimal brain lesion volume (<5 mL; p < 0.0001 in RR MS and p < 0.005 in PP MS). Measures of NCV in individual patients were negatively correlated with T2-weighted lesion volume (r = -0.47, p < 0.001) and disease duration (r = -0.25, p < 0.05) only in the patients with RR MS. NCV correlated with Expanded Disability Status Scale scores across all of the patients, but the strength of the correlation was stronger (p < 0.05) for PP (r = -0.64, p < 0.0001) than for RR (r = -0.27, p = 0.04) MS patients. CONCLUSIONS: These data confirm substantial neocortical volume loss in MS patients and suggest that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment. Although a proportion of this neocortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent neurodegenerative process also is active.

Adolescent↗
PubMed2003

De novo double translocation 3;13 and 4;8;18 in a patient with mental retardation and skeletal abnormalities.

A de novo, apparently balanced complex chromosome rearrangement (CCR) involving five chromosomes and six chromosome breakpoints was found in a child with Marfanoid habitus, kyphoscoliosis, axillary pterygium, camptodactyly, joint laxity, and mild mental retardation. Fluorescence in situ hybridization (FISH) revealed a simple translocation involving chromosomes 3 and 13, and a complex rearrangement involving chromosomes 4, 8, and 18 with four breakpoints.

Abnormalities, Multiple↗
PubMed2003

Imaging neuronal and axonal degeneration in multiple sclerosis.

Neuronal and axonal damage has become an important issue in multiple sclerosis. This has been emphasised by recent magnetic resonance imaging (MRI) studies that have shown evidence of axonal damage in both lesional and non-lesional white matter and in grey matter. In this respect, proton MR spectroscopy (by monitoring levels of Nacetylaspartate, a putative marker of axonal integrity) and computed measurements of cerebral volumes have been particularly illuminating. Recent studies using these MRI measures have demonstrated that cerebral neuro-axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of neuronal pathology in the pathogenesis of the disease should be given due importance and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards neuronal protection.

Aspartic Acid↗
PubMed2003

Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene.

The authors report on a family with dominantly inherited progressive external ophthalmoplegia and a diagnostic and statistical manual (fourth revised edition) diagnosis of bipolar psychiatric disorder in several members. Skeletal muscle biopsy from the proposita showed decreased cytochrome c oxidase staining, several ragged-red fibers, and multiple mtDNA deletions. The authors identified a missense mutation (leucine 98-->proline) in the adenine nucleotide translocator 1 gene. The presence of bipolar affective disorder expands the phenotype of adenine nucleotide translocator 1 allelic variants.

Adenine Nucleotide Translocator 1↗
PubMed2003

Evidence of apoptosis via TUNEL staining in muscle biopsy from patients with mitochondrial encephaloneuromyopathies.

Apoptosis is an evolution-conserved form of cell death essential for development and maintenance of tissue homeostasis. Dysregulation of apoptosis has been implicated in several pathological conditions, including neurodegenerative disorders. The crucial role of mitochondria in regulation of the apoptotic pathway prompted us to investigate the pattern of apoptosis in muscle biopsies from 17 patients with mitochondrial encephaloneuromyopathies caused by mtDNA defects. The results were compared with muscle biopsies from controls and from patients with myopathies without mitochondrial impairment. The terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling (TUNEL) reaction was used as marker of apoptosis. Our findings were very heterogeneous, even between patients with the same mtDNA mutations, suggesting that tissue evaluation of apoptotic process is less useful than in vitro techniques, for investigating the role of apoptosis in mitochondrial pathologies.

Adult↗
PubMed2003

Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Results of a double-blind clinical study.

BACKGROUND: Chronic hepatic encephalopathy (HE) represents a frequent and serious complication of chronic liver disease. Aim of the study is to comparatively evaluate the effect of rifaximin, lactitol and their combination in treating chronic HE. METHODS: Forty out-patients (29 males, 11 females, mean age: 59 years, range 40-70), with viral liver cirrhosis and chronic HE (1st-2nd degree) were studied. HE was assessed by considering: mental state, asterixis, number connection test (NCT), arterial blood ammonia levels. Patients were randomly assigned to the following treatments: rifaximin (plus sorbitol as placebo) (group R); lactitol (group L); rifaximin plus lactitol (group RL). All treatments were continued for 15 days for 3 cycles, intervalled by 15 days of washout. RESULTS: The 3 treatments reduced HE, but with different efficacy: patients of group R and RL significantly (p<0.05) documented a faster improvement in HE degree, a higher percentage of patients which normalized mental state and NCT, a faster improvement of asterixis and a longer persistence of normal ammonia levels than patients of group L. CONCLUSIONS: Rifaximin in combination with lactitol or sorbitol represents an effective and safe treatment of chronic HE.

Journal Article↗
PubMed2002

A Rett syndrome MECP2 mutation that causes mental retardation in men.

OBJECTIVE: To characterize the clinical features of a new type of X-linked mental retardation associated with MECP2 mutation in the index family. BACKGROUND: MECP2 mutations, originally described in a high percentage of patients with classic Rett syndrome, were considered lethal in men. The authors recently described a novel A140V MECP2 missense mutation in an Italian family with X-linked semidominant mental retardation. METHODS: The neurologic features of six symptomatic relatives (two women and four men) carrying the mutation were compiled. Laboratory investigations included EEG, EMG, conduction velocity (CV) of peripheral nerves, brain MRI, and (1)H-MR spectroscopy. RESULTS: Mental retardation and signs of neurologic impairment were present in all the affected members, but more pronounced in men. Neurologic features included slowly progressive spastic paraparesis/pyramidal signs (6/6), distal atrophy of the legs (6/6), ataxia (2/6), and postural tremor of the hands (3/6). Speech was preserved (6/6) but was dysarthric in the oldest brothers (2/6). Mild dysmorphic features were present in all cases. CONCLUSION: The neurologic disorder associated with A140V MECP2 mutation is not necessarily lethal in men, but they are more severely affected than women of the same family.

Adult↗
PubMed2002

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

Chorea↗