Carlo Cosimo Quattrocchi

Magnetic resonance imaging markers of Parkinson's disease nigrostriatal signature

One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinsons disease and 22 control subjects underwent 3-T magnetic resonance imaging with T₂*-weighted, whole-brain T₁-weighted and diffusion tensor imaging scans. The mean R₂* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinsons disease and control subjects. Comparisons were also performed using voxel-based analysis of R₂*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinsons disease displayed significantly higher R₂* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinsons disease from controls. The markers comprising discriminating combinations were R₂* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinsons physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R₂*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinsons disease and, possibly, of other subcortical pathologies.

Gadodiamide and Dentate Nucleus T1 Hyperintensity in Patients With Meningioma Evaluated by Multiple Follow-Up Contrast-Enhanced Magnetic Resonance Examinations With No Systemic Interval Therapy.

The dentate nucleus of the cerebellum may appear as hyperintense on unenhanced T1 magnetic resonance images (MRIs) of the brain. Recently, T1 signal hyperintensity has received attention owing to data on the association of this finding with the history of multiple injections of gadolinium-based contrast agents, specifically gadodiamide, in patients with multiple sclerosis and brain metastases. We conducted a retrospective study on patients with a meningioma who had routinely undergone follow-up enhanced MRI scans with gadodiamide. Across a time interval of 18 months (from January 2013 to July 2014), we identified 102 consecutive patients eligible for this study. A significant increase in T1 hyperintensity of the dentate nuclei of the cerebellum on nonenhanced scans was observed between the first and the last MRI in the group of patients with a history of at least 6 enhanced MRI scans (P < 0.01), whereas no differences were observed in the group with 1 to 5 enhanced MRI scans (P = 0.74). Further research is necessary to shed light on the mechanism of the T1 hyperintensity as well as on the histological and microstructural appearance of the dentate nucleus after multiple intravenous injections of gadodiamide. The finding raises the question of substantial dechelation of this agent in patients with normal renal function.

Resting state cortical electroencephalographic rhythms are related to gray matter volume in subjects with mild cognitive impairment and Alzheimer's disease

Cortical gray matter volume and resting state cortical electroencephalographic rhythms are typically abnormal in subjects with amnesic mild cognitive impairment (MCI) and Alzheimers disease (AD). Here we tested the hypothesis that in amnesic MCI and AD subjects, abnormalities of EEG rhythms are a functional reflection of cortical atrophy across the disease. Eyes‐closed resting state EEG data were recorded in 57 healthy elderly (Nold), 102 amnesic MCI, and 108 AD patients. Cortical gray matter volume was indexed by magnetic resonance imaging recorded in the MCI and AD subjects according to Alzheimers disease neuroimaging initiative project (http://www.adni‐info.org/). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), beta2 (20–30 Hz), and gamma (30–40 Hz). These rhythms were indexed by LORETA. Compared with the Nold, the MCI showed a decrease in amplitude of alpha 1 sources. With respect to the Nold and MCI, the AD showed an amplitude increase of delta sources, along with a strong amplitude reduction of alpha 1 sources. In the MCI and AD subjects as a whole group, the lower the cortical gray matter volume, the higher the delta sources, the lower the alpha 1 sources. The better the score to cognitive tests the higher the gray matter volume, the lower the pathological delta sources, and the higher the alpha sources. These results suggest that in amnesic MCI and AD subjects, abnormalities of resting state cortical EEG rhythms are not epiphenomena but are strictly related to neurodegeneration (atrophy of cortical gray matter) and cognition. Hum Brain Mapp, 2013.

Neural basis of a multidimensional model of body image distortion in anorexia nervosa

Body image distortion is a key symptom of anorexia nervosa (AN). The majority of the neuroimaging studies on body image distortion in AN conceptualized it as an unidimensional symptom. However, behavioural research considers such symptom as a multidimensional construct. Our paper systematically reviews the functional magnetic resonance (fMRI) studies on body image distortion in AN and classifies them according to a speculative model of body image distortion, that consists of the three most widely accepted components in the behavioural research: perceptive, affective and cognitive. We found that: (1) the perceptive component is mainly related to alterations of the precuneus and the inferior parietal lobe; (2) the affective component is mainly related to alterations of the prefrontal cortex, the insula and the amygdala; (3) the cognitive component has been weakly explored. These evidences seem to confirm that specific neural alterations are related to the components of the body image distortion in AN. Further neuroimaging studies are needed to better understand the complexity of the body image distortion in AN.

Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer's disease

A dysfunction in copper homeostasis seems to occur in Alzheimer’s disease (AD). We recently demonstrated that an excess of non-ceruloplasmin-copper (i.e. ‘free’ copper) correlates with the main functional and anatomical deficits as well as the cerebrospinal markers of the disease, thus suggesting that copper contributes to AD neurodegeneration. Aim of this study was to investigate the profile of serum ceruloplasmin isoforms immunoreactive protein in relation to copper dysfunction in AD. Twenty-five AD patients and 25 controls were included in the study. All subjects underwent individual measurements of serum ceruloplasmin and copper concentrations, and the amount of ‘free’ copper was computed for each copper and ceruloplasmin pair. Serum samples were also pooled and analyzed by two dimensional polyacrylamide gel electrophoresis (2-D PAGE) and western blot analysis. The mean concentration of ’free’ copper resulted higher in AD patients than in controls. Ceruloplasmin 2-D PAGE western blot analysis of pooled sera showed in the AD samples low-molecular-weight spots in the <50 kDa range that were not detected in controls’ pooled sera (p < 0.029). Our data indicate a ceruloplasmin fragmentation in the serum of AD patients, possibly related to ‘free’ copper deregulation in this disease.

Diffusion-weighted lesions after carotid artery stenting are associated with cognitive impairment.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.

Resting State Cortical Electroencephalographic Rhythms and White Matter Vascular Lesions in Subjects with Alzheimer's Disease: An Italian Multicenter Study

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimers disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.

Posterior pelvic floor disorders: a prospective comparison using introital ultrasound and colpocystodefecography

To compare introital ultrasound with colpocystodefecography (CCD) in quantifying the anorectal angle and in the diagnosis of posterior pelvic floor disorders.

Bone metastases in breast cancer: higher prevalence of osteosclerotic lesions

PurposeIt is well known that bone metastases from breast cancer usually show osteolytic changes. We retrospectively analysed the computed tomography (CT) appearance of bone metastases to quantify the distribution of lytic, mixed and sclerotic changes in a series of patients presenting with neoplastic bone involvement from breast cancer.Materials and methodsBetween 1996 and 2005, 468 women with a diagnosis of breast cancer were referred to our department for staging or follow-up CT examinations. Staging CT examinations detected systemic metastases in 142/468 patients, 60 of which had bone involvement. Patients with a second primary tumour or bone metabolic disorders were excluded from this retrospective analysis.ResultsIn patients with bone metastases, CT identified 18 with osteolytic lesions (30%), 32 with osteosclerotic lesions (53.3%) and ten with mixed lesions (16.7%). Analysis of the cases observed for the first time during the 1996–2000 period showed osteolytic lesions in 53.6% (15/28), osteosclerotic lesions in 32.1% (9/28) and mixed lesions in 14.3% (4/28). Results were 9.4% (3/32), 71.9% (23/32) and 18.7% (6/32), respectively, for the same groups in the 2001–2005 period. Histological analysis of all cases included 81.9% of infiltrative ductal carcinoma, 11.2% of infiltrative lobular carcinoma, 3.7% of ductal lobular mixed carcinoma and 3% of medullar carcinoma. We found no statistically significant correlation between histological type of breast cancer and radiological appearance of bone metastasis. A significant difference between patients treated with or without zoledronic acid was observed, with a higher prevalence of osteosclerotic lesions in the former group of patients (p<0.05).ConclusionsWe observed an increasing prevalence of osteosclerotic bone metastasis when comparing the 1996–2000 period with the 2001–2005 period. The significance of these distribution changes is not clear. However, we found a significant correlation of osteosclerotic lesions with zoledronic acid treatment. The advent of third generation bisphosphonates may have changed the CT appearance of bone metastasis from breast cancer.RiassuntoObiettivoÈ ormai accertato che le metastasi ossee da carcinoma della mammella spesso si presentano come lesioni osteolitiche. Abbiamo analizzato retrospettivamente le immagini TC di metastasi ossee al fine di quantificare la distribuzione delle lesioni litiche, miste o addensanti in una serie di pazienti che presentavano localizzazione ossea metastatica da carcinoma della mammella.Materiali e metodiTra il 1996 e il 2005, 468 pazienti con carcinoma della mammella sono stati sottoposti presso il nostro dipartimento ad una TC di stadiazione o per follow-up. La TC di stadiazione ha rilevato la presenza di metastasi sistemiche in 42/468 pazienti, 60 delle quali presentavano coinvolgimento del tessuto osseo. Pazienti con secondo tumore primitivo o pazienti con disordini metabolici ossei sono stati esclusi dallo studio.RisultatiIn pazienti con metastasi ossee, la TC ha rilevato 18 pazienti con lesioni osteolitiche (30%), 32 con lesioni osteoaddensanti (53,3%) e 10 (16,7%) con lesioni miste. L’analisi dei casi osservati per la prima volta nel periodo compreso tra il 1996 e 2000, ha mostrato lesioni osteolitiche nel 53,6% dei casi (15/28), lesioni osteoaddensanti nel 32,1% dei casi (9/28) e miste nel 14,3% dei casi (4/28) mentre i risultati erano rispettivamente del 9,4% (3/32), 71,9% (23/32) e 18,7% (6/32) per gli stessi gruppi nel periodo compreso tra il 2001 e 2005. L’analisi istologica di tutti i casi evidenziava la presenza di carcinoma duttale infiltrante nel 81,9% dei casi, di carcinoma lobulare infiltrante nel 11,2% dei casi, di carcinoma duttale lobulare misto nel 3,7% dei casi e nel 3% dei casi di carcinoma midollare. Non abbiamo rilevato una correlazione statisticamente significativa tra il tipo istologico di carcinoma della mammella e l’aspetto radiologico delle metastasi ossee. È stata osservata una differenza significativa tra i pazienti trattati con o senza acido zoledronico, con una maggiore prevalenza di lesioni osteoaddensanti nel gruppo di pazienti trattati (p<0,05).ConclusioniAbbiamo osservato un aumento della prevalenza delle metastasi ossee osteoaddensanti nel periodo compreso tra il 2001–2005 rispetto a quello compreso tra il 1996–2000. Il significato del cambiamento di tale distribuzione non è ancora chiaro. Tuttavia abbiamo rilevato una correlazione significativa tra le lesioni osteoaddensanti e il trattamento con acido zoledronico. L’avvento dei bifosfonati di terza generazione può aver cambiato l’aspetto TC delle metastasi ossee da carcinoma della mammella.

Neuronal functionality assessed by magnetoencephalography is related to oxidative stress system in acute ischemic stroke

The hypoxic brain damage induced by stroke is followed by an ischemia-reperfusion injury modulated by oxidative stress. Magnetoencephalographic (MEG) recording of rest and evoked cortical activities is a sensitive method to analyse functional changes following the acute ischemic damage. We aimed at investigating whether MEG signals are related to oxidative stress compounds in acute stroke. Eighteen stroke patients and 20 controls were enrolled. All subjects underwent MEG assessment to record background activity and somatosensory evoked responses (M20 and M30) of rolandic regions, neurological examination assessed by National Institute of Health Stroke Scale (NIHSS) and plasmatic measurement of copper, iron, zinc, ceruloplasmin, transferrin, total peroxides and Total Anti-Oxidant Status. Magnetic Resonance was performed to estimate the lesion site and volume. Delta power and M20 equivalent current dipole (ECD) strength in the affected hemisphere (AH) correlated with NIHSS scores (respectively, rho=.692, p=.006 and rho=-.627, p=.012) and taken together explained 67% of NIHSS variability (p=.004). Higher transferrin and lower peroxides levels correlated with better clinical status (respectively, rho=-.600, p=.014 and rho=.599, p=.011). Transferrin also correlated with AH M20 ECD strength (rho=.638 p=.014) and inversely with AH delta power (rho=-.646 p=.023) and the lesion volume, especially in cortico-subcortical stroke (p=.037). Our findings strengthen MEG reliability in honing the evaluation of neuronal damage in acute ischemic stroke also demonstrating an association between the MEG parameters most representing the clinical status and the oxidative stress compounds. Our results meet at a possible protective role of transferrin in limiting the oxidative damage in acute stroke.