Maria Rita Piras

Cognitive impairment and neurophysiological correlates in MS

Cognitive impairment in multiple sclerosis (MS) has received considerable interest over the last decades. Heterogeneous patterns of cognitive dysfunction have been reported in literature in relation to the subtype of the disease and the severity of specific cognitive domains affected. Event related potentials (ERPs), especially P300, have been employed to evaluate the cognitive decline in MS and neurophysiological findings agree with data obtained by neuropsychological testing. The objectivity, the reliability and the easy administration are the main features of ERP technique but more specific attention and memory tasks are needed to enhance the clinical value of the methodology. Moreover, ERP recording has the advantage of being feasible even in severe disabled patients. Finally, longitudinal ERP studies are required to investigate the natural course of cognitive dysfunction in MS, to estimate the prognostic value of subclinical defects in different clinical form of the disease and to evaluate clinical benefits of therapeutic and rehabilitative interventions.

Genetic study of Sardinian patients with Alzheimer's disease

We describe the genetic analysis of an Alzheimers disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the gamma-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G>C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimers disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the varepsilon4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.

Presenilin-1 mutation E318G and familial Alzheimer's disease in the Italian population.

Presenilin-1 (PSEN-1) is a component of the gamma-secretase complex involved in beta-amyloid precursor protein (betaAPP) processing. To date about 140 pathogenic mutations in the PSEN-1 gene have been identified and their main biochemical effect is to increase the production of the fibrillogenic peptide Abeta(1-42). An exception is the PSEN-1 [E318G] mutation that does not alter Abeta(1-42) generation and is generally considered a non-pathogenic polymorphism. Nevertheless, this mutation was reported to be a genetic risk factor for familial Alzheimers disease (FAD) in the Australian population. To independently confirm this indication, we performed a case-control association study in the Italian population. We found a significant association (p<0.05, Fishers exact test) between the presence of PSEN-1 [E318G] and FAD. In addition, on measuring the Abeta(1-42) and Abeta(1-40) concentrations in fibroblast-conditioned media cultured from PSEN-1 [E318G] carriers and PSEN-1 [wild type] controls we noted a significant decrease (p<0.05, Mann-Whitney test) in the Abeta(1-42)/Abeta(1-40) ratio in PSEN-1 [E318G] carriers, suggesting a peculiar biochemical effect of this mutation.

P300 and executive function alterations: possible links in a case of Morgagni-Stewart-Morel syndrome

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

Cognitive dysfunction and hepatitis C virus infection

Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging (MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated.

Neuropsychophysiological findings in a case of long-standing overt ventriculomegaly (LOVA).

Long-standing overt ventriculomegaly in adults (LOVA) is a clinical entity characterized by chronic hydrocephalus with infant onset, slow evolution and clinical disturbances during adulthood. Few cases are reported in literature describing the evident contrast between the severity of hydrocephalus and the relatively spared neurological functioning and cognitive aspects. The authors describe a 59-year-old man with congenital hydrocephalus complaining of persistent gait impairment. Neurological examination showed a mild paraparesis, severe higher cortical function impairment but relatively sparing of daily living activity. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a very remarkable ventriculomegaly compressing the brain cortex but sparing the cerebellum and the brainstem. Brain Single Photon Emission Computer Tomography (SPECT) showed a prevalent cerebellar perfusion as well. Neuropsychological testing was consistent with severe cognitive deterioration and attention disorders. Language and praxis functions seemed to be preserved. Auditory oddball ERPs (P300) showed morphological abnormalities especially of late components. This case report demonstrates in vivo the level of adaptation to which human brain can reach under chronic mechanic stress conditions. The striking poor cerebral parenchyma representation and the relatively spared language and praxic abilities account for a functional reorganization of residual structures due to the neural plasticity.

123I-ioflupane brain SPECT and 123I-MIBG cardiac planar scintigraphy combined use in uncertain parkinsonian disorders

Abstract We evaluated the clinical usefulness of the combined use of 123I-ioflupane brain single photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinsons disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases. All patients underwent 123I-ioflupane SPECT with striatal dopaminergic activity determination as binding potentials (BP; cut-off: 3.3). 123I-MIBG cardiac planar scintigraphy was performed 2 weeks later, in early (15 minutes) and delayed (240 minutes) phases also calculating heart to mediastinum (H/M) ratio (cut-off: 1.56). 123I-Ioflupane uptake was normal in 9 patients with BP values >3.3, while it was reduced in 34/43 cases with BP values <3.3 at least in one of the striatal nuclei. 123I-MIBG uptake was normal in 21/43 patients (5 of whom with normal and 16 with 123I-ioflupane striatal defects) showing the H/M ratio >1.56 in all cases; the uptake was reduced in 22/43 cases, (4 of whom were normal and 18 were with 123I-ioflupane striatal defects) with the H/M ratio <1.56 in all cases. No statistical differences were found when early and delayed H/M ratios were mutually compared. Combining the 2 radioisotopic procedures, a more reliable diagnosis was achieved in 39/43 cases properly classifying 13 PD, 10 VP, 7 PS, 5 LBD, and 4 AD. However, the diagnosis remained uncertain in four patients with normal 123I-ioflupane and reduced 123I-MIBG uptake. The results of the present study confirmed that in uncertain parkinsonian syndromes associated with vascular lesions in striatal nuclei, brain 123I-ioflupane SPECT alone did not prove able to discriminate between the different forms of disease. Only the association with 123I-MIBG cardiac scintigraphy, also with the early acquisition alone, allowed the most appropriate diagnosis in 90.7% of our cases. However, patients with normal 123I-ioflupane and reduced 123I-I-MIBG uptakes need a close clinical and instrumental follow-up as sympathetic damage could precede striatal disorders in the early stage of PD and LBD.

Adaptation of the Bilingual Aphasia Test (BAT) to Sardinian: Clinical and social implications

Abstract The Bilingual Aphasia Test (BAT) was developed between 1976 and 1982. At present, it has been adapted to over 60 languages and 150 language pairs. Its main function is to assess and compare the residual linguistic abilities in each language of an aphasic patient. The BAT is not only used for bilingual aphasia assessment, but also for the evaluation of the effects of treatment as well as for the assessment of language disorders in bilinguals and monolinguals. Furthermore, it is also used for research in psycholinguistics experiments and in combination with modern neuroimaging and neurophysiological techniques. This article describes the adaptation of the BAT to the Sardinian variety of Logudorese and in particular to the sub-variety spoken in the town of Bitti (central Logudorese). To our knowledge, this is the first adaptation of the Bilingual Aphasia Test to Sardinian. At the moment, there are no published aphasia tests in Sardinian, and for this reason this adaptation provides the first standardized test for assessment in this language.