Raffaele Lodi

University of Bologna, Bolonia, Emilia-Romagna, Italy

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Publications (161)770.06 Total impact

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    ABSTRACT: Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features. Nineteen patients with optic atrophy gene 1-autosomal dominant optic atrophy and 17 with Leber hereditary optic neuropathy older than 18 years of age, all genetically diagnosed, and 19 healthy volunteers underwent DTI by using a 1.5T MR imaging scanner and neurologic and ophthalmologic assessments. Brain white matter DTI metrics were calculated for all participants, and, in patients, their correlations with genetics and clinical findings were calculated. Compared with controls, patients with optic atrophy gene 1-autosomal dominant optic atrophy had an increased mean diffusivity in 29.2% of voxels analyzed within major white matter tracts distributed throughout the brain, while fractional anisotropy was reduced in 30.3% of voxels. For patients with Leber hereditary optic neuropathy, the proportion of altered voxels was only 0.5% and 5.5%, respectively, of which half was found within the optic radiation and 3.5%, in the smaller acoustic radiation. In almost all regions, fractional anisotropy diminished with age in patients with optic atrophy gene 1-autosomal dominant optic atrophy and correlated with average retinal nerve fiber layer thickness in several areas. Mean diffusivity increased in those with a missense mutation. Patients with Leber hereditary optic neuropathy taking idebenone had slightly milder changes. Patients with Leber hereditary optic neuropathy had preferential involvement of the optic and acoustic radiations, consistent with trans-synaptic degeneration, whereas patients with optic atrophy gene 1-autosomal dominant optic atrophy presented with widespread involvement suggestive of a multisystemic, possibly a congenital/developmental, disorder. White matter changes in Leber hereditary optic neuropathy and optic atrophy gene 1-autosomal dominant optic atrophy may be exploitable as biomarkers. © 2015 American Society of Neuroradiology.
    American Journal of Neuroradiology 03/2015; DOI:10.3174/ajnr.A4272 · 3.68 Impact Factor
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    ABSTRACT: Objective Mounting evidence links neurodegenerative disorders such as Parkinson and Alzheimer disease with mitochondrial dysfunction and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link emerged recently, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in post-mitotic tissues. Here, we report two Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia.Methods Patients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, muscle and brain MR spectroscopy, analysis of muscle biopsy and fibroblasts. Candidate genes were sequenced and mtDNA was analyzed for rearrangements.ResultsAffected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed COX negative fibers and mtDNA multiple deletions, and MR spectroscopy displayed defective oxidative metabolism in muscle and brain. We found two heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the GTPase domain, each segregating with affected individuals. Fibroblast studies showed reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy.InterpretationThe association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the link of defective mitochondrial dynamics, mtDNA multiple deletions and altered mitophagy with parkinsonism. This article is protected by copyright. All rights reserved.
    Annals of Neurology 03/2015; DOI:10.1002/ana.24410 · 11.91 Impact Factor
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    Brain 08/2014; 138(1). DOI:10.1093/brain/awu234 · 10.23 Impact Factor
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    ABSTRACT: A novel heteroplasmic mitochondrial DNA (mtDNA) micro-deletion affecting the cytochrome b gene (MT-CYB) was identified in an Italian female patient with a multisystem disease characterized by sensorineural deafness, cataracts, retinal pigmentary dystrophy, dysphagia, postural and gait instability and myopathy with prominent exercise intolerance. The deletion is 18-base pair long and encompasses nucleotide positions 15649-15666, causing the loss of six amino acids (Ile-Leu-Ala-Met-Ile-Pro) in the protein, but leaving the remaining of the MT-CYB sequence in frame. The defective complex III function was co-transferred with mutant mtDNA in cybrids, thus unequivocally establishing its pathogenic role. Maternal relatives failed to show detectable levels of the deletion in blood and urinary epithelium, suggesting a de-novo mutational event. This is the second report of an in-frame intragenic deletion in MT-CYB, which most likely occurred in early stages of embryonic development, associated with a severe multisystem disorder with prominent exercise intolerance. This article is protected by copyright. All rights reserved.
    Human Mutation 08/2014; 35(8). DOI:10.1002/humu.22596 · 5.05 Impact Factor
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    ABSTRACT: Mutations in DDHD1 gene have been associated with the SPG28 subtype of Hereditary Spastic Paraparesis (HSP). Clinical phenotype includes axonal neuropathy, distal sensory loss, and cerebellar eye movement disturbances. We screened 96 index subjects from recessive HSP families for mutation and identified one family with two sibs carrying mutations in DDHD1 gene. Clinical, neuropsychological, and neuroimaging studies were performed, including MR spectroscopy of brain and muscle of the two mutated patients. Two novel heterozygous mutations in DDHD1 were found in the affected members of one family, with clinical features overlapping the SPG28 subtype. Of note, MR spectroscopy of brain and muscle in these patients indicated a mild deficit of brain energy metabolism in the oldest and most severely affected patient, while an impairment of energy metabolism was found in the skeletal muscle of both patients. Unlike the DDHD2 mutated patients, no evidence of lipid accumulation in the brain was found. Our data along with those previously reported suggest a dysfunction in the OXPHOS system possibly due to mitochondrial lipid content modification, which could be a central mechanism in the pathogenesis of SPG28.
    Journal of Neurology 07/2014; 261(9). DOI:10.1007/s00415-014-7418-4 · 3.84 Impact Factor
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    ABSTRACT: Background An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.
    BMC Neurology 05/2014; 14(1):116. DOI:10.1186/1471-2377-14-116 · 2.49 Impact Factor
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    ABSTRACT: Objective We aimed to report the clinical picture of 2 asymptomatic daughters of a patient with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. Methods Clinical assessment based on history, neurologic examination, sleep recording, neurophysiologic neuroimaging, and genetic tests was performed. Results History and neurologic examination in both subjects was unremarkable. Genetic analysis was disclosed in both the paternally inherited heterozygous points of mutation in the DNMT1 gene. Sleep recordings found sleep-onset rapid eye movement periods (SOREMPs) and proton magnetic resonance spectroscopy (MRS) revealed increased cerebellar myoinositol (mI) in both subjects. Auditory and ophthalmologic investigations as well as structural brain magnetic resonance imaging (MRI) scans revealed no abnormalities. Conclusions The 2 asymptomatic carriers of the heterozygous DNMT1 mutation for ADCA-DN, a late-onset neurodegenerative disease, presented with SOREMPs associated with an increase of mI in the brain, a marker of glial cell activity and density characteristic of early stages of neurodegenerative diseases. Therefore, SOREMPs may precede the clinical picture of ADCA-DN as an early polysomnographic marker of central nervous system involvement detected by MRS.
    Sleep Medicine 05/2014; 15(5). DOI:10.1016/j.sleep.2013.09.028 · 3.10 Impact Factor
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    ABSTRACT: We report on the extensive phenotypic characterization of five Italian patients from four unrelated families carrying dominant heterozygous DNMT1 mutations linked to two distinct autosomal dominant diseases: hereditary sensory and autonomic neuropathy with dementia and hearing loss type IE (HSAN IE) and autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Patients underwent genetic analysis of DNMT1 gene, neurophysiological tests investigating sleep, auditory functions and peripheral nervous system, ophthalmological studies including optical coherence tomography, lymphoscintigraphy, brain magnetic resonance and nuclear imaging, cerebrospinal fluid hypocretin-1, total tau, phosphorylated tau, amyloid-β1-42 and 14-3-3 proteins measurement, skin, muscular and sural nerve biopsies. Exome and direct sequencing studies disclosed two different point mutations affecting exon 21 of DNMT1 gene in patients with ADCA-DN, a novel heterozygous point mutation in exon 20 in two affected HSAN IE siblings, and a trinucleotide deletion in exon 20 in the latter patient with HSAN IE. Phenotypic characterization pinpoints that ADCA-DN and HSAN IE represent two discrete clinical entities belonging to the same disease spectrum, with variable degree of overlap. Remarkably, narcolepsy with or without cataplexy with low/intermediate or normal cerebrospinal fluid hypocretin-1 is present in both diseases. The human leukocyte antigen DQB1*06:02 was absent in all patients. Other common symptoms and features observed in our cases, involving the central and peripheral nervous system, include deafness, optic neuropathy-previously not reported in HSAN IE-large and small fibres polyneuropathy and lower limbs oedema. Overall, the two syndromes share more characteristics than previously recognized and narcolepsy is common to both. HSAN IE and ADCA-DN are two extreme phenotypic manifestations of a DNMT1 methylopathy.
    Brain 04/2014; DOI:10.1093/brain/awu069 · 10.23 Impact Factor
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    ABSTRACT: Background The objective of this study was to use phase imaging to evaluate brain iron content in patients with idiopathic restless legs syndrome (RLS). Methods Fifteen RLS patients and 15 healthy controls were studied using gradient-echo imaging. Phase analysis was performed on localized brain regions of interest selected on phase maps, sensitive to paramagnetic tissue. Differences between the 2 subject groups were evaluated using ANCOVA including age as a covariate. ResultsSignificantly higher phase values were present in the RLS patients compared with healthy controls at the level of the substantia nigra, thalamus, putamen, and pallidum, indicating reduced iron content in several regions of the brain of the patients. Conclusions We have used MRI phase analysis to study brain iron content in idiopathic RLS in vivo for the first time. Our results support the hypothesis of reduced brain iron content in RLS patients, which may have an important role in the pathophysiology of the disorder. (c) 2013 International Parkinson and Movement Disorder Society
    Movement Disorders 11/2013; 28(13). DOI:10.1002/mds.25576 · 5.63 Impact Factor
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    ABSTRACT: Even though the pathophysiology of restless legs syndrome is not completely understood, several imaging studies have contributed to our understanding of the disease. Functional and metabolic impairment seems to be the pathophysiological core, tied to a single brain network or multiple connected brain networks, via neurotransmitter modifications. Positron emission tomography and single photon emission computed tomography studies support a dysfunction of dopaminergic pathways, involving not only the nigrostriatal pathway but also the mesolimbic pathway. Furthermore, a possible role of serotonergic neurotransmission has been suggested. Functional magnetic resonance imaging studies have demonstrated in restless legs syndrome patients a pathologic activation of cerebral areas belonging to both the sensorimotor and the limbic networks. Proton magnetic resonance spectroscopy has confirmed abnormality of the limbic system and suggested the presence of a glutamatergic disorder. Finally magnetic resonance studies using iron-sensitive sequences have demonstrated reduced iron content in several regions of the brain of restless legs syndrome patients. In this review we attempt to integrate all current imaging study results into a convergent pathophysiological interpretation.
    Current Neurology and Neuroscience Reports 09/2013; 13(9):372. DOI:10.1007/s11910-013-0372-1 · 3.67 Impact Factor
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    ABSTRACT: INTRODUCTION: MRI, proton magnetic resonance spectroscopy ((1)H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on (1)H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). METHODS: Twenty infants treated with BC underwent conventional MRI and (1)H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. RESULTS: Adverse outcome was observed in 6/20 newborns. Both (1)H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. CONCLUSION: Selective BC in HIE neonates does not affect the early and accurate prognostic value of (1)H-MRS and DTI, which outperform conventional MRI.
    Neuroradiology 05/2013; 55(8). DOI:10.1007/s00234-013-1202-5 · 2.37 Impact Factor
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    ABSTRACT: Purpose:To explore the usefulness of histogram analysis of mean diffusivity (MD) derived from diffusion-weighted imaging of large infratentorial structures to distinguish parkinsonian syndromes.Materials and Methods:Local research ethics committee approval and informed consent were obtained. Ten patients with Parkinson disease (PD), nine with the parkinsonian variant of multiple system atrophy (MSA-P), seven with the cerebellar variant of MSA (MSA-C), 17 with progressive supranuclear palsy-Richardson syndrome (PSP-RS), and 10 healthy subjects were recruited. Histograms of MD values were generated for all pixels in the whole infratentorial compartment and separately for the whole brainstem, vermis, and cerebellar hemispheres. To assess the differences in MD values among groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney U test for pairwise comparisons. All P values resulting from pairwise comparisons were corrected with the Bonferroni method.Results:MSA-P and MSA-C groups had higher median MD values (P < .01) in the brainstem and cerebellum when compared with other groups; this finding was in line with the known consistent neurodegenerative damage in posterior cranial fossa structures in these diseases. Median MD values from cerebellar hemispheres were used to discriminate patients with MSA-C and those with MSA-P from patients with PD and those with PSP-RS (P < .01; sensitivity, specificity, and positive predictive value equaled 100%). Furthermore, patients with PSP-RS had significantly higher MD values in the vermis than did healthy subjects (P < .05) and patients with PD (P < .001).Conclusion:These findings support the clinical usefulness of diffusion imaging in the differential diagnosis of parkinsonism, suggesting that the minimally operator-dependent histogram analysis of the infratentorial structures and particularly of the whole cerebellar hemispheres can be used to distinguish patients with MSA-P and those with MSA-C from patients with PSP-RS and those with PD.© RSNA, 2013.
    Radiology 01/2013; DOI:10.1148/radiol.12120364 · 6.21 Impact Factor
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    ABSTRACT: Complex I (CI) deficiency is a frequent cause of mitochondrial disorders and, in most cases, is due to mutations in CI subunit genes encoded by mitochondrial DNA (mtDNA). In this study, we establish the pathogenic role of the heteroplasmic mtDNA m.3890G>A/MT-ND1 (p.R195Q) mutation, which affects an extremely conserved amino acid position in ND1 subunit of CI. This mutation was found in a young-adult male with optic atrophy resembling Leber's hereditary optic neuropathy (LHON) and bilateral brainstem lesions. The only previously reported case with this mutation was a girl with fatal infantile Leigh syndrome with bilateral brainstem lesions. Transfer of the mutant mtDNA in the cybrid cell system resulted in a marked reduction of CI activity and CI-dependent ATP synthesis in the presence of a normally assembled enzyme. These findings establish the pathogenicity of the m.3890G>A/MT-ND1 mutation and remark the link between CI mutations affecting the mtDNA-encoded ND subunits and LHON-like optic atrophy, which may be complicated by bilateral and symmetric lesions affecting the central nervous system. Peculiar to this mutation is the distribution of the brainstem lesions, with sparing of the striatum in both patients.
    Biochimica et Biophysica Acta 12/2012; 1832(3). DOI:10.1016/j.bbadis.2012.12.002 · 4.66 Impact Factor
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    ABSTRACT: Magnetic resonance imaging represents a validated diagnostic tool in the investigation of neuromuscular disorders. Magnetic resonance imaging can detect key skeletal muscle abnormalities such as size, shape and signal intensity changes reflecting fatty infiltration, muscle atrophy or muscle edema. In vivo phosphorus magnetic resonance spectroscopy is able to provide objective measurements of muscle energy metabolism and cytosolic pH at rest, during exercise, and during recovery from exercise. Its primary role is the investigating of metabolic myopathies, and it has been used to detect the underlying biochemical mechanisms responsible for the development of fatigue. In this mini-review, we report the main contribution provided by conventional and advanced magnetic resonance imaging and phosphorus magnetic resonance spectroscopy in the exploration of fatigue in normal muscle and in neuromuscular disorders.
    Neuromuscular Disorders 12/2012; 22:S187-S191. DOI:10.1016/j.nmd.2012.10.008 · 3.13 Impact Factor
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    ABSTRACT: Leber's hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05) and lack of recovery of visual acuity (B = 0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.
    PLoS ONE 11/2012; 7(11):e50230. DOI:10.1371/journal.pone.0050230 · 3.53 Impact Factor
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    ABSTRACT: Pathophysiology of restless legs syndrome is poorly understood. A role of the thalamus, specifically of its medial portion which is a part of the limbic system, was suggested by functional magnetic resonance imaging and positron emission tomography studies. The aim of this study was to evaluate medial thalamus metabolism and structural integrity in patients with idiopathic restless legs syndrome using a multimodal magnetic resonance approach, including proton magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis. Twenty-three patients and 19 healthy controls were studied in a 1.5 T system. Single voxel proton magnetic resonance spectra were acquired in the medial region of the thalamus. In diffusion tensor examination, mean diffusivity and fractional anisotropy were determined at the level of medial thalamus using regions of interest delineated to outline the same parenchyma studied by spectroscopy. Voxel-based morphometry was performed focusing the analysis on the thalamus. Thalamic volumes were obtained using FMRIB's Integrated Registration and Segmentation Tool software, and shape analysis was performed using the FMRIB Software Library tools. Proton magnetic resonance spectroscopy study disclosed a significantly reduced N-acetylaspartate:creatine ratio and N-acetylaspartate concentrations in the medial thalamus of patients with restless legs syndrome compared with healthy controls (P < 0.01 for both variable). Lower N-acetylaspartate concentrations were significantly associated with a family history of restless legs syndrome (β = -0.49; P = 0.018). On the contrary, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis of the thalami did not show differences between the two groups. Proton magnetic resonance spectroscopic findings in patients with restless legs syndrome indicate an involvement of medial thalamic nuclei of a functional nature; however, the other structural techniques of the same region did not show any changes. These findings support the hypothesis that dysfunction of the limbic system plays a role in the pathophysiology of idiopathic restless legs syndrome.
    Brain 11/2012; DOI:10.1093/brain/aws266 · 10.23 Impact Factor
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    Giovanni Rizzo, Caterina Tonon, Raffaele Lodi
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    ABSTRACT: In recent years an increasing number of studies have demonstrated the usefulness of different magnetic resonance (MR) techniques in diagnosing and understanding Parkinson’s disease (PD). First, several MR-based studies have identified promising markers of substantia nigra degeneration in PD for early diagnosis and the evaluation of disease progression. Second, quantitative MR techniques has been used to improve the differential diagnosis among parkinsonian syndromes. Among these, the most reproducible and consistent are morphometry and diffusion imaging, both of which are able to detect degenerative changes of cerebral structures specifically affected in the different forms of parkinsonism. Finally, advanced MR techniques such as functional MRI, voxel-based morphometry, and diffusion tensor imaging have provided insights into many pathophysiological aspects of PD. Currently, the main limitation to the use of advanced MR techniques is the heterogeneity of results among previous studies. This is due not only to a combination of technical variability in terms of magnetic fields, sequences, and methodological approaches of analysis, but also most likely to the differences in the patient samples examined, given that in most studies the subjects lack a pathological diagnosis. Furthermore, most of the diagnostic studies were performed in patients with long disease duration and it is not clear whether reported MRI findings allows an accurate differential diagnosis to be performed in the early stage of disease. Among pathophysiological studies in particular, there is currently a gap in our understanding of the link between some of the alterations described in the literature and their possible pathogenic role. This especially true of the studies focused on symptoms occurring in later stage of disease, such as L-dopa induced dyskinesia and gait impairment, at a stage when additional clinical features may bias the results. A methodological consensus and a reduction of operator dependence would allow a reduction in inhomogeneity of results related to the technical variability. Regarding the characteristics of the patients examined, future studies should include larger and more homogeneous samples. In the diagnostic setting, the patients should be examined in the early stage of the disease, longitudinal studies should be preferred and a definite pathological diagnosis should be obtained.
    07/2012; 2(4):175-182. DOI:10.1016/j.baga.2012.06.001
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    ABSTRACT: Studying the thalamic role in the cortical expression of the Sleep Slow Oscillation (SSO) in humans by comparing SSO features in a case of Fatal Familial Insomnia (FFI) and a group of controls. We characterize SSOs in a 51-year-old male with FFI carrying the D178N mutation and the methionine/methionine homozygosity at the polymorphic 129 codon of the PRNP gene and in eight gender and age-matched healthy controls. Polysomnographic (21 EEG electrodes, two consecutive nights) and volumetric- (Diffusion tensor imaging Magnetic Resonance Imaging DTI MRI) evaluations were carried out for the patient in the middle course of the disease (five months after the onset of insomnia; disease duration: 10 months). We measured a set of features describing each SSO event: the wave shape, the event-origin location, the number and the location of all waves belonging to the event, and the grouping of spindle activity as a function of the SSO phase. We found that the FFI individual showed a marked reduction of SSO event rate and wave morphological alterations as well as a significant reduction in grouping spindle activity, especially in frontal areas. These alterations paralleled DTI changes in the thalamus and the cingulate cortex. This work gives a quantitative picture of spontaneous SSO activity during the NREM sleep of a FFI individual. The results suggest that a thalamic neurodegeneration specifically alters the cortical expression of the SSO. This characterization also provides indications about cortico-thalamic interplays in SSO activity in humans.
    Sleep Medicine 05/2012; 13(7):946-52. DOI:10.1016/j.sleep.2012.03.007 · 3.10 Impact Factor
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    ABSTRACT:   The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel-based morphometry and diffusion tensor imaging (DTI).   Twenty patients and twenty controls were studied. Voxel-based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL-VBM software tools. For voxel-wise analysis of DTI, tract-based spatial statistics (TBSS) and SPM8 were used.   Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses.   Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.
    European Journal of Neurology 12/2011; 19(7):1045-9. DOI:10.1111/j.1468-1331.2011.03604.x · 3.85 Impact Factor
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    ABSTRACT: In this study we assessed ΔG'(ATP) hydrolysis, cytosolic [ADP], and the rate of phosphocreatine recovery using Phosphorus Magnetic Resonance Spectroscopy in the calf muscle of a group of patients affected by glycogen myo-phosphorylase deficiency (McArdle disease). The goal was to ascertain whether and to what extent the deficit of the glycogenolytic pathway would affect the muscle energy balance. A typical feature of this pathology is the lack of intracellular acidosis. Therefore we posed the question of whether, in the absence of pH decrease, the rate of phosphocreatine recovery depends on the amount of phosphocreatine consumed during exercise. Results showed that at the end of exercise both [ADP] and ΔG'(ATP) of patients were significantly higher than those of matched control groups reaching comparable levels of phosphocreatine concentration. Furthermore, in these patients we found that the rate of phosphocreatine recovery is not influenced by the amount of phosphocreatine consumed during exercise. These outcomes provide experimental evidence that: i) the intracellular acidification occurring in exercising skeletal muscle is a protective factor for the energy consumption; and ii) the influence of pH on the phosphocreatine recovery rate is at least in part related to the kinetic mechanisms of mitochondrial creatine kinase enzyme.
    Biochimica et Biophysica Acta 06/2011; 1807(9):1244-9. DOI:10.1016/j.bbabio.2011.06.013 · 4.66 Impact Factor

Publication Stats

3k Citations
770.06 Total Impact Points

Institutions

  • 1993–2014
    • University of Bologna
      • • Department of Biological, Geological and Environmental Sciences BiGeA
      • • Department of Biomedical Science and Neuromotor Sciences DIBINEM
      • • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      • • Institute of Cancerology
      Bolonia, Emilia-Romagna, Italy
  • 2013
    • Universita' degli Studi "Magna Græcia" di Catanzaro
      • Department of Medical and Surgical Sciences
      Catanzaro, Calabria, Italy
  • 2007–2010
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
  • 1999–2005
    • University of Oxford
      • Department of Biochemistry
      Oxford, England, United Kingdom
    • Oxford University Biochemical Society
      Radcliffe, England, United Kingdom
  • 2001
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
  • 1998
    • Oxford University Hospitals NHS Trust
      • MRC Biochemical and Clinical Magnetic Resonance Unit
      Oxford, England, United Kingdom
  • 1996
    • IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino
      Milano, Lombardy, Italy
  • 1992
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy