Latest PUBLICATIONS

  • Cognitive and affective theory of mind in patients with essential tremor.
    Publication Date: 01/02/2013, on Journal of neurology
    by Santangelo G, Trojano L, Barone P, Errico D, Improta I, Agosti V, Grossi D, Sorrentino G, Vitale C
    DOI: 10.1007/s00415-012-6668-2

    The theory of mind (ToM) is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the present study was to explore the neuropsychological correlates of cognitive and affective ToM in patients affected by essential tremor (ET). Thirty consecutive ET outpatients and 30 healthy age-, sex- and education-matched control subjects underwent tasks assessing short-term memory, verbal learning and executive functions, as well as tasks assessing "cognitive" and "affective" ToM; questionnaires evaluating behavioral disorders and quality of life were also administered. Although the two groups did not differ on demographic variables, ET patients scored worse on memory tasks, and showed more apathy and worse quality of life than controls. After covarying for mnestic, behavioral and quality of life scores, ET patients achieved significantly lower scores than controls on task assessing cognitive ToM, whereas no difference was found between the two groups on task assessing affective ToM. In ET, "Cognitive" ToM was significantly associated with frontal tasks, whereas "Affective" ToM was not correlated with cognitive, behavioral or quality of life scales. Our results indicate that cognitive aspects of ToM may be selectively impaired in ET. Possible underlying neural mechanisms of the deficits are discussed.

  • Neuropsychological profile of adult patients with nonsymptomatic occipital lobe epilepsies.
    Publication Date: 01/02/2013, on Journal of neurology
    by Bilo L, Santangelo G, Improta I, Vitale C, Meo R, Trojano L
    DOI: 10.1007/s00415-012-6650-z

    To explore the neuropsychological and neurobehavioral profile in adult patients affected by nonsymptomatic (cryptogenic and idiopathic) occipital lobe epilepsy (OLE), with normal intelligence, we enrolled 20 adult patients with nonsymptomatic OLE and 20 age-, sex-, and education-matched healthy subjects. All participants underwent neuropsychiatric assessment scales, and standardized neuropsychological tests tapping memory, executive functions, constructional, visuospatial and visuoperceptual skills. After Bonferroni correction for multiple comparisons, patients performed significantly worse than controls on several tests tapping complex visuospatial skills and frontal lobe functions. The analysis of single patients' performance revealed that a significantly higher number of OLE patients achieved age- and education-adjusted pathological scores on three tests (Benton Judgment of Line Orientation Test, Freehand Copying of Drawings Test, color-word interference task of Stroop test) with respect to controls. Patients did not differ from control subjects on neuropsychiatric aspects. The direct comparison between OLE subtypes showed that cryptogenetic OLE patients tended to achieve lower scores than idiopathic OLE patients on most tests, but no difference between the two groups was fully significant. In summary, patients with nonsymptomatic OLE can be affected by clinically relevant impairments in selected neuropsychological domains: complex visuospatial skills and executive functions. It could be speculated that frontal and visuospatial cognitive deficits might be the result of epileptic activity spreading within a neural network that includes structures far beyond the occipital lobe.

  • Similarities and differences in the biogenesis, processing and lysosomal targeting between zebrafish and human pro-Cathepsin D: functional implications.
    Publication Date: 01/02/2013, on The international journal of biochemistry & cell biology
    by Follo C, Ozzano M, Montalenti C, Ekkapongpisit M, Isidoro C
    DOI: 10.1016/j.biocel.2012.10.010

    The lysosomal protease Cathepsin D (CD) plays a role in neurodegenerative diseases, cancer, and embryo-fetus abnormalities. It is therefore of interest to know how this protein is synthesized in animal species used for modeling human diseases. Zebrafish (Danio rerio) is emerging as a valuable 'in vivo' vertebrate model for several human diseases. We have characterized the biogenetic pathways of zebrafish and human CD transgenically expressed in both human SH-SY5Y cells and zebrafish PAC2 cells. Differently from human CD, zebrafish CD was synthesized as a mono-glycosylated precursor (pro-CD) that was eventually processed into a single-chain mature polypeptide. In PAC2 cells, ammonium chloride and chloroquine impaired the N-glycosylation, and greatly stimulated the secretion, of pro-CD; still, a portion of un-glycosylated pro-CD reached the lysosomes and was processed to mature CD. The treatment with tunicamycin, which abrogates N-glycosylation, resulted in a similar effect. Zebrafish pro-CD was correctly processed when expressed in human cells, and its glycosylation, transport and maturation were not impaired by ammonium chloride. On the contrary, the transport and processing of human pro-CD expressed in zebrafish cells were profoundly altered: while the intermediate single-chain was not detectable, a small amount of double-chain mature CD still formed. This fact indicates that the enzyme machinery for single- to double-chain processing of mammal CD is present in zebrafish. Our data highlight the respective impact of the information imparted by the primary sequence and of the cellular transport and processing machineries in the biogenesis of lysosomal CD.

  • Clinical and genetic features in Italian Bietti crystalline dystrophy patients.
    Publication Date: 01/02/2013, on The British journal of ophthalmology
    by Rossi S, Testa F, Li A, Yaylacioğlu F, Gesualdo C, Hejtmancik JF, Simonelli F
    DOI: 10.1136/bjophthalmol-2012-302469

    The aim of the study was to describe the clinical and genetic features of 15 Italian patients with Bietti crystalline dystrophy (BCD).

  • Predictors of recovery of responsiveness in prolonged anoxic vegetative state.
    Publication Date: 29/01/2013, on Neurology
    by Estraneo A, Moretta P, Loreto V, Lanzillo B, Cozzolino A, Saltalamacchia A, Lullo F, Santoro L, Trojano L
    DOI: 10.1212/WNL.0b013e31827f0f31

    The number of patients in prolonged postanoxic vegetative state (VS) is increasing. However, little information is available about prognostic markers of long-term outcome in patients who remain in VS more than 1 month postonset. The present 2-year prospective clinical study aimed to identify prognostic markers, recorded in the chronic phase, that might be useful for predicting recovery of responsiveness in a cohort of postanoxic VS patients.

  • The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy.
    Publication Date: 28/01/2013, on Orphanet journal of rare diseases
    by Peluso I, Conte I, Testa F, Dharmalingam G, Pizzo M, Collin RW, Meola N, Barbato S, Mutarelli M, Ziviello C, Barbarulo AM, Nigro V, Melone MA, , Simonelli F, Banfi S
    DOI: 10.1186/1750-1172-8-16

    Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes.

  • Cross-talk between prion protein and quadruplex-forming nucleic acids: a dynamic complex formation.
    Publication Date: 07/01/2013, on Nucleic acids research
    by Cavaliere P, Pagano B, Granata V, Prigent S, Rezaei H, Giancola C, Zagari A
    DOI: 10.1093/nar/gks970

    Prion protein (PrP) is involved in lethal neurodegenerative diseases, and many issues remain unclear about its physio-pathological role. Quadruplex-forming nucleic acids (NAs) have been found to specifically bind to both PrP cellular and pathological isoforms. To clarify the relevance of these interactions, thermodynamic, kinetic and structural studies have been performed, using isothermal titration calorimetry, surface plasmon resonance and circular dichroism methodologies. Three quadruplex-forming sequences, d(TGGGGT), r(GGAGGAGGAGGA), d(GGAGGAGGAGGA), and various forms of PrP were selected for this study. Our results showed that these quadruplexes exhibit a high affinity and specificity toward PrP, with K(D) values within the range 62÷630 nM, and a weaker affinity toward a PrP-β oligomer, which mimics the pathological isoform. We demonstrated that the NA quadruplex architecture is the structural determinant for the recognition by both PrP isoforms. Furthermore, we spotted both PrP N-terminal and C-terminal domains as the binding regions involved in the interaction with DNA/RNAs, using several PrP truncated forms. Interestingly, a reciprocally induced structure loss was observed upon PrP-NA interaction. Our results allowed to surmise a quadruplex unwinding-activity of PrP, that may have a feedback in vivo.

  • Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy.
    Publication Date: 01/01/2013, on Mediators of inflammation
    by Azzolini C, Pagani IS, Pirrone C, Borroni D, Donati S, Al Oum M, Pigni D, Chiaravalli AM, Vinciguerra R, Simonelli F, Porta G
    DOI: 10.1155/2013/857380

    Proliferative vitreoretinopathy (PVR) is a severe inflammatory complication of retinal detachment. Pathological epiretinal membranes grow on the retina surface leading to contraction, and surgery fails in 5% to 10% of the cases. We evaluated the expression of VEGF-A, Otx1, Otx2, Otx3, and p53 family members from PVR specimens to correlate their role in inducing or preventing the pathology.

  • Early cell changes and TGFβ pathway alterations in the aortopathy associated with bicuspid aortic valve stenosis.
    Publication Date: 01/01/2013, on Clinical science (London, England : 1979)
    by Forte A, Della Corte A, Grossi M, Bancone C, Provenzano R, Finicelli M, De Feo M, De Santo LS, Nappi G, Cotrufo M, Galderisi U, Cipollaro M
    DOI: 10.1042/CS20120324

    Previous studies on BAV (bicuspid aortic valve)-related aortopathy, whose aetiology is still debated, have focused mainly on severe dilatations. In the present study, we aimed to detect earlier signs of aortopathy. Specimens were collected from the 'concavity' (lesser curvature) and the 'convexity' (greater curvature) of mildly dilated AAs (ascending aortas; diameter ≤4 cm) with stenotic TAV (tricuspid aortic valve) or BAV and from donor normal aortas. Specimens were submitted to morphometry, immunohistochemistry and differential gene-expression analysis, focusing on SMC (smooth muscle cell) phenotype, remodelling, MF (myofibroblast) differentiation and TGFβ (transforming growth factor β) pathway. Smoothelin and myocardin mRNAs decreased in all the samples from patients, with the exception of those from BAV convexity, where a change in orientation of smoothelin-positive SMCs and an increase of α-SMA (α-smooth muscle actin) mRNA occurred. Dilated aortas from BAV and TAV patients showed both shared and distinct alterations concerning the TGFβ pathway, including an increased TGFβ and TGFβR2 (TGFβ receptor 2) expression in both groups and a decreased TGFβR1 expression in BAV samples only. Despite a decrease of the mRNA coding for the ED-A (extra domain-A) isoform of FN (fibronectin) in the BAV convexity, the onset of the expression of the corresponding protein in the media was observed in dilated aortas, whereas the normal media from donors was negative for this isoform. This discrepancy could be related to modifications in the intima, normally expressing ED-A FN and showing an altered structure in mild aortic dilatations in comparison with donor aorta. Our results suggest that changes in SMC phenotype and, likely, MF differentiation, occur early in the aortopathy associated with valve stenosis. The defective expression of TGFβR1 in BAV might be a constitutive feature, while other changes we reported could be influenced by haemodynamics.

  • Apathy in Parkinson's disease: diagnosis, neuropsychological correlates, pathophysiology and treatment.
    Publication Date: 01/01/2013, on Behavioural neurology
    by Santangelo G, Trojano L, Barone P, Errico D, Grossi D, Vitale C
    DOI: 10.3233/BEN-129025

    Apathy has been defined as lack of motivation. It has been traditionally considered as a symptom of psychiatric disorders, such as major depression and schizophrenia, but more recently it has been recognized as a specific neuropsychiatric syndrome associated with neurodegenerative such as Parkinson's disease (PD). As a consequence the reported prevalence of apathy in PD ranges from 13.9% to 70%; the mean prevalence is 35%. Prevalence of "pure apathy" (i.e., of apathy without comorbid depression and dementia) seems to be substantially lower, from 3 to 47.9%. High levels of apathy in PD are associated with decreased daily function, specific cognitive deficits and increased stress for families. Although neuroimaging studies do not provide a unique anatomic pattern, several data suggest that the ventromedial prefrontal cortex and the basal ganglia connected through frontal-subcortical circuits, are particularly involved in the genesis of apathy. At present, there are no approved medications for the treatment of apathy in and no proof of efficacy exists for any drug in current use. Further studies and innovative pharmacologic approaches are thus needed to ameliorate our understanding and treatment of apathy in PD.

  • Apathy and related executive syndromes in dementia associated with Parkinson's disease and in Alzheimer's disease.
    Publication Date: 01/01/2013, on Behavioural neurology
    by Grossi D, Santangelo G, Barbarulo AM, Vitale C, Castaldo G, Proto MG, Siano P, Barone P, Trojano L
    DOI: 10.3233/BEN-129023

    Apathy is defined as a lack of motivation and has been reported to be common in Alzheimer's disease (AD) and Parkinson's disease (PD). To explore the neuropsychological correlates of apathy in patients with PD related dementia (PDD) and AD and to identify the specific cognitive profile of apathy in the two forms of neurodegenerative disease, 61 non-depressed patients (29 PDD and 32 AD) were selected. Out of these, 29 patients (47.5%) were detected as apathetic (14 PDD-A+ and 15 AD-A+), and 32 patients as non-apathetic (15 PDD-A- and 17 AD-A-). All patients underwent cognitive tasks tapping memory, visuospatial and executive functions, behavioral rating scales and Clinical Judgment for Apathy Syndrome (CJ-AS), an inventory developed to measure severity of apathy. The four subgroups differed significantly on memory and frontal tasks. The PDD-A+ performed significantly worse than PDD-A- on frontal tasks. The AD-A+ had poorer performance than AD-A- on frontal tasks. Last, PDD-A+ achieved significantly higher scores than AD-A+ on memory tasks. The four groups differed significantly on CJ-AS and behavioral rating scales.The results showed that apathetic patients with both forms of dementia showed a common neuropsychological and behavioral picture, characterized by defects on frontal tasks, thus strongly supporting the existence of an 'apathetic syndrome', characterized by specific cognitive and psychological symptoms.

  • Compulsive drumming induced by dopamine agonists in Parkinson's disease: Another aspect of punding.
    Publication Date: 01/01/2013, on Behavioural neurology
    by Vitale C, Trojano L, Barone P, Errico D, Agosti V, Sorrentino G, Grossi D, Santangelo G
    DOI: 10.3233/BEN-129024

    We report the case of a man affected by Parkinson's disease who developed an unusual, severe, repetitive behavior characterized by an irrepressible need to drum and beat percussion instruments following to the introduction of pramipexole. This compulsive behavior was not associated to a pattern of chronic inappropriate overuse of dopaminergic medication or other psychiatric symptoms. Sharing many features with other repetitive behaviors, compulsive drumming might be considered a distinct manifestation of punding in Parkinson's disease.

  • Towards a deeper comprehension of relationships among cognitive, behavioral and psychiatric symptoms in Parkinson's disease.
    Publication Date: 01/01/2013, on Behavioural neurology
    by Trojano L, Santangelo G, Conson M, Grossi D
    DOI: 10.3233/BEN-129015

  • Innate immunity probed by lipopolysaccharides affinity strategy and proteomics.
    Publication Date: 01/01/2013, on Analytical and bioanalytical chemistry
    by Giangrande C, Colarusso L, Lanzetta R, Molinaro A, Pucci P, Amoresano A
    DOI: 10.1007/s00216-012-6204-3

    Lipopolysaccharides (LPSs) are ubiquitous and vital components of the cell surface of Gram-negative bacteria that have been shown to play a relevant role in the induction of the immune-system response. In animal and plant cells, innate immune defenses toward microorganisms are triggered by the perception of pathogen associated molecular patterns. These are conserved and generally indispensable microbial structures such as LPSs that are fundamental in the Gram-negative immunity recognition. This paper reports the development of an integrated strategy based on lipopolysaccharide affinity methodology that represents a new starting point to elucidate the molecular mechanisms elicited by bacterial LPS and involved in the different steps of innate immunity response. Biotin-tagged LPS was immobilized on streptavidin column and used as a bait in an affinity capture procedure to identify protein partners from human serum specifically interacting with this effector. The complex proteins/lipopolysaccharide was isolated and the protein partners were fractionated by gel electrophoresis and identified by mass spectrometry. This procedure proved to be very effective in specifically binding proteins functionally correlated with the biological role of LPS. Proteins specifically bound to LPS essentially gathered within two functional groups, regulation of the complement system (factor H, C4b, C4BP, and alpha 2 macroglobulin) and inhibition of LPS-induced inflammation (HRG and Apolipoproteins). The reported strategy might have important applications in the elucidation of biological mechanisms involved in the LPSs-mediated molecular recognition and anti-infection responses.

  • Affective saliency modifies visual tracking behavior in disorders of consciousness: a quantitative analysis.
    Publication Date: 01/01/2013, on Journal of neurology
    by Trojano L, Moretta P, Loreto V, Santoro L, Estraneo A
    DOI: 10.1007/s00415-012-6717-x