Raffaele Rocchi

Università degli Studi di Siena, Siena, Tuscany, Italy

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Publications (37)89.78 Total impact

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    ABSTRACT: A correlation between epilepsy and cellular redox imbalance has been suggested, although the mechanism by which oxidative stress (OS) can be implicated in this disorder is not clear. In the present study several oxidative stress markers and enzymes involved in OS have been determined. In particular, we examined the levels of 4-hydroxy-2-nonenal protein adducts (HNE-PA), a by-product of lipid peroxidation, and the activation of NADPH oxidase 2 (NOX2), as cellular source of superoxide (O2(-)), in surgically resected epileptic tissue from drug-resistant patients (N=50). In addition, we investigated whether oxidative-mediated protein damage can affect aquaporin-4 (AQP4), a water channel implicated in brain excitability and epilepsy. Results showed high levels of HNE-PA in epileptic hippocampus, in both neurons and glial cells and cytoplasmic positivity for p47(phox) and p67(phox) suggesting NOX2 activation. Interestingly, in epileptic tissue immunohistochemical localization of AQP4 was identified not only in perivascular astrocytic endfeet, but also in neurons. Nevertheless, negativity for AQP4 was observed in neurons in degeneration. Of note, HNE-mediated post-translational modifications of AQP4 were increased in epileptic tissues and double immunofluorescence clearly demonstrated co-localization of AQP4 and HNE-PA in epileptic hippocampal structures. The idea is that sudden, disorderly, and excessive neuronal discharges activates NOX2 with O2(-) production, leading to lipid peroxidation. The resulting generation of HNE targets AQP4, affecting water and ion balance. Therefore, we suggest that seizure induces oxidative damage as well as neuronal loss, thereby promoting neuronal hyperexcitability, also affecting water and ion balance by AQP4 modulation, and thus generating a vicious cycle. Copyright © 2014. Published by Elsevier B.V.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 11/2014; 1852(3). DOI:10.1016/j.bbadis.2014.11.016 · 5.09 Impact Factor
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    ABSTRACT: Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated.
    Neurological Sciences 07/2014; 35(9). DOI:10.1007/s10072-014-1873-7 · 1.50 Impact Factor
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    ABSTRACT: Rhabdomyolysis precipitated by multitherapy is most frequently described during statin treatment, due to impairment of statin clearance by drugs sharing cytochrome P450 biotransformation pathway. Modulation of membrane transporters for drug efflux, operated by substrates, can also affect drugs' tissue levels. We report rhabdomyolysis in an elderly patient, in multitreatment with different potentially myotoxic medications, taking place seven months after atorvastatin discontinuation. Affected by ischaemic heart disease, arterial hypertension and dementia-related behaviour disturbances, the patient was receiving angiotensin 2-receptor inhibitors, beta-blockers, vasodilators, diuretics, salycilates, allopurinol, proton pump inhibitors, antipsychotics and antidepressants. He had taken atorvastatin for 14years, with constantly normal creatine-kinase plasma levels. Two months after addition of the antianginal drug ranolazine, creatine-kinase mildly increased and atorvastatin was withdrawn. Nonetheless, creatine-kinase progressively rose, with severe weakness and rhabdomyolysis developing seven months later. Muscle biopsy showed a necrotizing myopathy with no inflammation or autoimmune changes. After ranolazine withdrawal, creatine-kinase and myoglobin returned to normal levels and strength was restored. Several psychotropic and cardiovascular medications prescribed to the patient share either cytochrome P450 biotransformation and permeability-glycoprotein efflux transport. In the event of cardiovascular/neuropsychiatric polypharmacy in geriatric patients, the risk of muscle severe adverse effects from pharmacokinetic drug-drug interaction should be considered beyond the direct myotoxicity of statins.
    Journal of the neurological sciences 11/2013; 336(1-2). DOI:10.1016/j.jns.2013.10.040 · 2.26 Impact Factor
  • Journal of Neurology 01/2013; 260(4). DOI:10.1007/s00415-012-6820-z · 3.84 Impact Factor
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    ABSTRACT: Obstructive sleep apnoea (OSA) syndrome is the most common sleep-related breathing disorder, characterized by excessive snoring and repetitive apnoeas and arousals, which leads to fragmented sleep and, most importantly, to intermittent nocturnal hypoxaemia during apnoeas. Considering previous studies about morphovolumetric alterations in sleep apnoea, in this study we aimed to investigate for the first time the functional connectivity profile of OSA patients and age-gender-matched healthy controls, using resting-state functional magnetic resonance imaging (fMRI). Twenty severe OSA patients (mean age 43.2 ± 8 years; mean apnoea-hypopnoea index, 36.3 h(-1) ) and 20 non-apnoeic age-gender-body mass index (BMI)-matched controls underwent fMRI and polysomnographic (PSG) registration, as well as mood and sleepiness evaluation. Cerebro-cerebellar regional homogeneity (ReHo) values were calculated from fMRI acquisition, in order to identify pathology-related alterations in the local coherence of low-frequency signal (<0.1 Hz). Multivariate pattern classification was also performed using ReHo values as features. We found a significant pattern of cortical and subcortical abnormal local connectivity in OSA patients, suggesting an overall rearrangement of hemispheric connectivity balance, with a decrease of local coherence observed in right temporal, parietal and frontal lobe regions. Moreover, an increase in bilateral thalamic and somatosensory/motor cortices coherence have been found, a finding due possibly to an aberrant adaptation to incomplete sleep-wake transitions during nocturnal apnoeic episodes, induced by repetitive choke sensation and physical efforts attempting to restore breathing. Different hemispheric roles into sleep processes and a possible thalamus key role in OSA neurophysiopathology are intriguing issues that future studies should attempt to clarify.
    Journal of Sleep Research 11/2012; DOI:10.1111/jsr.12006 · 2.95 Impact Factor
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    ABSTRACT: Neurenteric cyst is a rare developmental lesion that very infrequently is localised supratentorially. Intraparenchymal subependymoma is an even more rare benign tumour. The authors report the case of a 45-year-old gentleman with a background of drug resistant epilepsy. An MRI was performed which showed a left frontal cystic lesion with a solid component. Histopathology confirmed a type C neurenteric cyst associated with an intraparenchymal subependymoma. Following enlargement of the lesion and worsening of symptoms he was referred to our institution for further management. A frontotemporal craniotomy was performed for excision of the lesion but recurrence occurred within 1 year. The lesion was further excised and 19 months post re-excision the patient is seizure free with no evidence of recurrence on MRI.
    Case Reports 08/2012; 2012. DOI:10.1136/bcr.01.2012.5566
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    F Orzi, B Casolla, R Rocchi, F Fornai
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    ABSTRACT: Epilepsy often follows a focal insult, and develops with a time delay so to reveal a complex cascade of events. Both clinical and experimental findings suggest that the initial insult triggers a self-promoted pathological process, currently named epileptogenesis. An early phase reflects the complex response of the nervous system to the insult, which includes pro-injury and pro-repair mechanisms. Successively, the sprouting and probably neurogenesis and gliosis set up the stage for the onset of spontaneous seizures. Thus, local changes in excitability would cause a functional change within a network, and the altered circuitry would favor the seizures. A latent or clinically silent period, as long as years, may precede epilepsy. In spite of the substantial knowledge on the biochemical and morphological changes associated with epileptogenesis, the mechanisms supposedly underlying the process are still uncertain. The uncertainty refers mostly to the silent period, a stage in which most, if not all, the receptor and ion changes are supposedly settled. It is tempting to explore the nature of the factors promoting the epileptogenesis within the notional field of neurodegeneration. Specifically, several observations converge to support the hypothesis that a prion-like mechanism promotes the "maturation" process underlying epileptogenesis. The mechanism, consistently with data from different neurodegenerative diseases, is predictably associated with deposition of self-aggregating misfolded proteins and changes of the ubiquitin proteasome and autophagy-lysosome pathways.
    Neurological Sciences 07/2012; DOI:10.1007/s10072-012-1148-0 · 1.50 Impact Factor
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    ABSTRACT: Background. Periodic lateralised epileptiform discharges (PLEDs) are EEG patterns consisting of periodic or pseudoperiodic unilateral, focal or hemispheric epileptiform discharges at a rate of 1-2 Hz. PLEDs may be triggered by acute brain injuries or systemic metabolic changes such as fever, hyperglycaemia or electrolyte imbalance and may result in disturbance of consciousness and/or neurological deficits. Case report. A 58-year-old female with a history of focal epilepsy and deep brain haematoma presented with acute change in awareness, associated with EEG evidence of PLEDs, three days after a left internal carotid artery stenting procedure. Clinical examination, laboratory testing and MRI were unchanged with respect to pre-stenting investigations. Conclusion. In this patient, PLEDs may have been triggered by local haemodynamic changes due to reperfusion after stenting in a previously damaged brain area.
    Epileptic disorders: international epilepsy journal with videotape 03/2012; 14(1):85-9. DOI:10.1684/epd.2012.0487 · 0.90 Impact Factor
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    ABSTRACT: People lacking judgmental ability (newborn infants [NIs] and persons with mental impairment [PMI]) are reported to receive less analgesic treatments than people who can give adequate informed consent. We performed the present study to assess whether this also happens in clinical trials that should statutorily guarantee basic patients' rights. We examined those trials in which patients undergo painful minor procedures (PMP) because these procedures are frequent and severely stressful for NI and PMI. We performed a Medline search to retrieve the studies published in 2009 and 2010, in which NI and PMI underwent PMP. We retrieved 46 studies that exposed NI to PMP; only in 14.2% of the studies, a validated analgesic treatment was administered to the control group. We retrieved only one article where PMP was performed in PMI for clinical reasons (venipuncture); in 13 more studies, pain was experimentally provoked by noxious stimuli such as heat, electricity, or arm mobilization. All these studies were not performed to evaluate a possible analgesic strategy but to assess PMI's pain responsiveness and no analgesia was used. PMI and NI enrolled in clinical trials as controls rarely receive analgesia; and few studies exist to find out analgesic treatments shaped on PMI's exigencies. These data raise concern about the actual guarantees for persons lacking judgmental ability enrolled in potentially painful trials. We also recommend more effort to find out analgesic treatments tailored to the specific exigencies of PMI.
    Pain Medicine 02/2012; 13(3):427-33. DOI:10.1111/j.1526-4637.2011.01325.x · 2.24 Impact Factor
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    ABSTRACT: Background/Aims: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. Methods: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. Results: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. Conclusion: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients
    Dementia and Geriatric Cognitive Disorders 01/2012; 33(1-1):50-58. DOI:10.1159/000335363 · 2.81 Impact Factor
  • European Journal of Pain Supplements 09/2011; 5(1):167-167. DOI:10.1016/S1754-3207(11)70574-0
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    ABSTRACT: Arterial baroreflex and cardiac autonomic control play important roles in hemodynamic instability after carotid artery stenting (CAS). Spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and blood pressure variability (BPV) are established tools for the assessment of arterial baroreflex and cardiac autonomic activity. Aim of the study was to evaluate cardiac autonomic activity (by means of HRV, BPV and BRS) after CAS and to explore the impact of internal carotid artery stenosis on BRS changes after CAS. 37 patients (68±10.45 years) with internal carotid stenosis underwent CAS. HRV, BPV and BRS were measured in all subjects before and at 1 and 72h after CAS. ANOVA was performed to compare BRS, HRV and BPV parameters before and after CAS. Spearman analysis was performed to determine a possible correlation between carotid stenosis degree (or carotid plaque diameter) and BRS changes (ΔBRS). LF/HF (index of sympatho-vagal balance) decreased during postoperative period, in comparison with baseline (2.32±1.70 vs 1.65±1.40, p<0.05). There was a significant negative correlation between carotid stenosis degree and ΔBRS (r=-0.35, p=0.03) and between carotid plaques thickness and ΔBRS (r=-0.36, p=0.02). CAS procedure may cause an alteration of carotid wall mechanical properties, increasing baroreflex sensitivity. BRS does not increase in all the patients, because arterial wall damage and nerve destruction determined by atherosclerotic plaque may reduce ΔBRS.
    Neuroscience Letters 03/2011; 491(3):221-6. DOI:10.1016/j.neulet.2011.01.044 · 2.06 Impact Factor
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    ABSTRACT: Mitochondrial diseases due to mitochondrial tRNA genes mutations are usually multisystem disorders with infantile or adult onset. To identify the molecular defect underlying a mitochondrial encephalomyopathy. Case report of a 51year-old woman presenting with late-onset myoclonic epilepsy plus additional features. Proband's mother presented hypothyroidism and diabetes. Muscle biopsy showed mitochondrial changes. Respiratory chain activities were reduced. The novel G5538A mutation was identified in different tissues DNAs from the proband and from her mother. We were able to identify a novel mtDNA tRNA((Trp)) gene pathogenic mutation.
    Journal of the neurological sciences 10/2010; 297(1-2):105-8. DOI:10.1016/j.jns.2010.06.009 · 2.26 Impact Factor
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    ABSTRACT: Even after the introduction of new antiepileptic drugs, phenobarbital continues to be largely used in the treatment of epilepsy. We report the case of a 59-year-old woman with focal seizures with secondary generalization, treated with phenobarbital with normal serum levels. After thirty days she showed Sjogren-like symptoms, which resolved after the replaced of phenobarbital with oxcarbazepine. Although many antiepileptic drugs are known to induce autoimmune disorders, a "Sicca Syndrome" has never been reported as an adverse effect of phenobarbital. We think this case report leads to take into consideration the possibility of a drug-induced disorder whenever patients treated with barbiturates develop symptoms suggestive of Sjogren's Syndrome.
    Journal of the neurological sciences 10/2010; 300(1-2):164. DOI:10.1016/j.jns.2010.09.028 · 2.26 Impact Factor
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    ABSTRACT: Hypnotizability is a cognitive multidimensional trait that involves peculiar imagery characteristics. Subjects with high- (Highs) and low (Lows)-susceptibilities to hypnosis have shown different levels of skill at visual and somesthetic-guided imageries performed during upright stance. The aim of this experiment is to study the modulation of the EEG alpha and theta band amplitude during guided visual and somesthetic imageries in Highs and Lows, as these rhythms are responsive to the cognitive activities involved in mental imagery. Our results show that, at variance with standing subjects, subjects in both groups in a semi-reclined position report higher vividness and lower effort for visual than for somesthetic imagery. EEG patterns however are different between the two groups. Highs exhibit a more widespread alpha desynchronization and slightly different EEG patterns during visual and somesthetic imageries, while Lows show segregated alpha- and theta-desynchronization, without any difference between the tasks. Our results indicate that different, hypnotizability-related cognitive strategies, that are revealed by differences in EEG modulation, are responsible for the similar subjective experience associated with visual and somesthetic imageries in Highs and Lows. In addition, in both groups higher order mental representation of different sensory modalities might be subserved by a unique integrated neural network.
    Neuroscience Letters 02/2010; 470(1):13-8. DOI:10.1016/j.neulet.2009.12.044 · 2.06 Impact Factor
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    ABSTRACT: Delirium is a transient global disorder of cognition related to a variety of structural or functional neural disorders. Descriptions and characterizations of delirium associated with obstructive sleep apnea syndrome (OSAS) are rare. We describe a 52-year-old man with severe OSAS associated with sudden onset of delirium and with a fluctuating nighttime course, prolonged for several days. The delirium disappeared after treatment with continuous positive airway pressure (CPAP). The patient remained free of symptoms under CPAP during a follow-up of 8 years.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 12/2009; 5(6):569-70. · 2.83 Impact Factor
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    ABSTRACT: Spinal anesthesia (SA), accounting for more than 50% of regional anesthesias in the spinal region, is generally perceived as simple and safe. Our purpose is to increase awareness of hemorrhagic complications following SA. A 69-year-old male without either coagulation disorders or anticoagulant/antiplatelet therapy developed acute radiculopathy, and severe mental confusion after SA for prostatectomy. CT showed intracranial subarachnoid and intraventricular acute hemorrhage. Cerebral angiography was negative. MRI showed subarachnoid and subdural hematoma in the dorsolumbar spine. Seven-year follow-up showed permanent cognitive and radicular damage. Multiple attempts for SA most likely caused spinal vessels rupture, either directly or indirectly by inducing differential pressure changes between cerebrospinal fluid and intravascular spaces; however, definite mechanisms have not been completely understood. Patients undergoing spinal puncture must report any neurological abnormality, which may result in irreversible damage. Cases of altered consciousness require an extensive neuroradiological evaluation. Proper competency of physicians responsible for spinal puncture is mandatory.
    Neurological Sciences 07/2009; 30(5):393-6. DOI:10.1007/s10072-009-0103-1 · 1.50 Impact Factor
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    ABSTRACT: Adenosine, a potent anticonvulsant, can be produced in the body by the hydrolysis of adenine nucleotides through the action of ecto- or soluble nucleotidases. Changes in nucleotide hydrolysis occur after pentylenetetrazol-induced epileptic events. We evaluated serum ATP, ADP and AMP hydrolysis rates and soluble nucleotide phosphodiesterase (PDEase) activity at 5, 10, 15, 30 and 60 min, and 12h following an epileptic event. Fifteen patients (seven female, eight male; mean age 15.5 years) were included in the study. The type of seizure was generalized in four patients and was localization related in the remaining 11. There were no differences in adenine nucleotide hydrolysis rates between patients and healthy subjects in the interictal stage. In comparison with controls, ATP, ADP and AMP hydrolysis rates were significantly increased at 5 min (53+/-1.4%, 79.2+/-2.8% and 37.0+/-2.6%, respectively) and up to 30 min following the epileptic event. In contrast to ADP and AMP, ATP hydrolysis remained significantly increased at 60 min (71.4+/-1.6%), returning to the basal level after 12h. Serum PDEase activity was also significantly higher in the patients than in healthy subjects, peaking at 15 min (61+/-2.9%) and remaining significantly increased up to 60 min (4.6+/-1.2%) following the epileptic episode. Globally, the variations in the postictal serum ADP hydrolysis rate almost overlapped those of AMP hydrolysis, whereas changes in the ATP hydrolysis rate overlapped those of PDEase activity. The clinical significance of this elevation in postictal soluble serum nucleotidase activity remains to be clarified. However, it is possible to hypothesize that the higher nucleotidase activity might play a role in the modulation of epileptic events.
    Epilepsy research 02/2009; 84(1):15-20. DOI:10.1016/j.eplepsyres.2008.11.020 · 2.19 Impact Factor
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    ABSTRACT: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Prospective, multicenter, case-control epidemiologic survey. Twenty sleep centers certified by the Italian Association of Sleep Medicine. Eight hundred and sixty-one patients affected by MS and 649 control subjects. N/A. Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.
    Sleep 07/2008; 31(7):944-52. · 5.06 Impact Factor
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    ABSTRACT: To establish a link between rCBF assessed with Tc-ECD SPET and the clinical manifestation of the disease. We performed the study on 11 patients (five girls and six boys; mean age 11.2 years) displaying autistic behaviour and we compared their data with that of an age-matched reference group of eight normal children. A quantitative analysis of rCBF was performed calculating a perfusion index (PI) and an asymmetry index (AI) in each lobe. Images were analysed with statistical parametric mapping software, following the spatial normalization of SPET images for a standard brain. A statistically significant (P=0.003) global reduction of CBF was found in the group of autistic children (PI=1.07+/-0.07) when compared with the reference group (PI=1.25+/-0.12). Moreover, a significant difference was also observed for the right-to-left asymmetry of hemispheric perfusion between the control group and autistic patients (P=0.0085) with a right prevalence greater in autistic (2.90+/-1.68) with respect to normal children (1.12+/-0.49). Our data show a significant decrease of global cerebral perfusion in autistic children in comparison with their normal counterparts and the existence of left-hemispheric dysfunction, especially in the temporo-parietal areas devoted to language and the comprehension of music and sounds. We suggest that these abnormal areas are related to the cognitive impairment observed in autistic children, such as language deficits, impairment of cognitive development and object representation, and abnormal perception and responses to sensory stimuli. Tc-ECD SPET seems to be sensitive in revealing brain blood flow alterations and left-to-right asymmetries, when neuroradiological patterns are normal.
    Nuclear Medicine Communications 03/2008; 29(2):150-6. DOI:10.1097/MNM.0b013e3282f1bb8e · 1.37 Impact Factor

Publication Stats

668 Citations
89.78 Total Impact Points

Institutions

  • 1986–2014
    • Università degli Studi di Siena
      • • Department of Medicine, Surgery and Neuroscience
      • • Department of Molecular & Developmental Medicine
      Siena, Tuscany, Italy
  • 2007
    • Azienda Ospedaliera Universitaria Senese
      Siena, Tuscany, Italy