Raffaele Lodi - Academia.edu (original) (raw)

Papers by Raffaele Lodi

Pediatric Research, 2005

ABSTRACT Introduction: several neuropathological studies have documented brain damage following h... more ABSTRACT Introduction: several neuropathological studies have documented brain damage following hypoglycaemia. In a few cases damage has been reported in vivo using CT, MRI and US. Here we report a functional and anatomic study of the brain in a case of transient symptomatic hypoglycaemia.

Neuromuscular Disorders, 2010

Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal reces... more Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal recessive disorder characterized by bilateral congenital cataracts, developmental delay, peripheral; hypodemyelinating neuropathy, mild facial dysmorphisms, and other rare signs. Cerebral and spinal cord atrophy is the main neuroimaging finding but other less common abnormalities have been previously described. We describe progressive focal lesions of supratentorial white matter in a 10-year-old boy affected by CCFDN. Other etiologies have been excluded and these lesions can be considered a new finding of the disease. We discuss a possible demyelinating mechanism affecting both peripheral and central myelin.

Sleep Medicine, 2012

Studying the thalamic role in the cortical expression of the Sleep Slow Oscillation (SSO) in huma... more 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, 2014

We aimed to report the clinical picture of two asymptomatic daughters of a patient with autosomal... more We aimed to report the clinical picture of two 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. Clinical assessment based on history, neurologic examination, sleep recordings, neurophysiologic neuroimaging, and genetic tests was performed. History and neurologic examination in both subjects were unremarkable. Genetic analysis disclosed in both the paternally-inherited heterozygous point 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. The two 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.

Radiology, 2007

To retrospectively compare sensitivity and specificity of magnetic resonance (MR) imaging, three-... more To retrospectively compare sensitivity and specificity of magnetic resonance (MR) imaging, three-dimensional (3D) MR spectroscopy, combined MR imaging and 3D MR spectroscopy, and carbon 11 (11C)-choline positron emission tomography (PET)/computed tomography (CT) for intraprostatic tumor sextant localization, with histologic findings as reference standard. The local ethics committee on human research provided approval and a waiver of informed consent for the retrospective study. MR imaging, 3D MR spectroscopy, and 11C-choline PET/CT results were retrospectively reviewed in 26 men with biopsy-proved prostate cancer (mean age, 64 years; range, 51-75 years) who underwent radical prostatectomy. Cancer was identified as areas of nodular low signal intensity on T2-weighted MR images. At 3D MR spectroscopy, choline-plus-creatine-to-citrate and choline-to-creatine ratios were used to distinguish healthy from malignant voxels. At PET/CT, focal uptake was visually assessed, and maximum standardized uptake values (SUVs) were recorded. Agreement between 3D MR spectroscopic and PET/CT results was calculated, and ability of maximum SUV to help localize cancer was assessed with receiver operating characteristic analysis. Significant differences between positive and negative sextants with respect to mean maximum SUV were calculated with a paired t test. Sensitivity, specificity, and accuracy were, respectively, 55%, 86%, and 67% at PET/CT; 54%, 75%, and 61% at MR imaging; and 81%, 67%, and 76% at 3D MR spectroscopy. The highest sensitivity was obtained when either 3D MR spectroscopic or MR imaging results were positive (88%) at the expense of specificity (53%), while the highest specificity was obtained when results with both techniques were positive (90%) at the expense of sensitivity (48%). Concordance between 3D MR spectroscopic and PET/CT findings was slight (kappa=0.139). In localizing cancer within the prostate, comparable specificity was obtained with either 3D MR spectroscopy and MR imaging or PET/CT; however, PET/CT had lower sensitivity relative to 3D MR spectroscopy alone or combined with MR imaging.

NMR in Biomedicine, 2009

This study extensively investigates different strategies for the absolute quantitation of N-acety... more This study extensively investigates different strategies for the absolute quantitation of N-acetyl aspartate, creatine and choline in white and grey matter by 1 H-MRS at 1.5 T. The main focus of this study was to reliably estimate metabolite concentrations while reducing the scan time, which remains as one of the main problems in clinical MRS. Absolute quantitation was based on the water-unsuppressed concentration as the internal standard. We compared strategies based on various experimental protocols and post-processing strategies. Data were obtained from 30 control subjects using a PRESS sequence at several TE to estimate the transverse relaxation time, T 2 , of the metabolites. Quantitation was performed with the algorithm QUEST using two different metabolite signal basis sets: a whole-metabolite basis set (WhoM) and a basis set in which the singlet signals were split from the coupled signals (MSM). The basis sets were simulated in vivo for each TE used. Metabolites' T 2 s were then determined by fitting the estimated signal amplitudes of the metabolites obtained at different TEs. Then the absolute concentrations (mM) of the metabolites were assessed for each subject using the estimated signal amplitudes and either the mean estimated relaxation times of all subjects (mean protocol, MP) or the T 2 estimated from the spectra derived from the same subject (individual protocol, IP). Results showed that MP represents a less time-consuming alternative to IP in the quantitation of brain metabolites by 1 H-MRS in both grey and white matter, with a comparable accuracy when performed by MSM. It was also shown that the acquisition time might be further reduced by using a variant of MP, although with reduced accuracy. In this variant, only one water-suppressed and one waterunsuppressed spectra were acquired, drastically reducing the duration of the entire MRS examination. However, statistical analysis highlights the reduced accuracy of MP when performed using WhoM, particularly at longer echo times.

NMR in Biomedicine, 1993

In this study we compared the kinetics of phosphocreatine (PCr) and P(i) recovery, and their depe... more In this study we compared the kinetics of phosphocreatine (PCr) and P(i) recovery, and their dependency on cytosolic pH in 38 normal individuals. Spectra were acquired during rest, work and recovery. A time resolution of 10 s was used to obtain detailed information. The kinetics of PCr and P(i) recovery almost overlapped when the lowest value of cytosolic pH reached during recovery (termed the minimum pH) was < 6.95, while they were completely dissociated when the minimum pH was > 6.95. This result is interpreted as indirect in vivo evidence of the kinetic control exerted by ADP on mitochondrial oxidation. Our results represent a rationale for new experimental conditions to be used in clinical routine studies of pathologies due to primary or secondary mitochondrial malfunction.

Neuromuscular Disorders, 2007

proximal and concerned mainly deltoids and iliopsoas with preservation of distal muscles. Neck fl... more proximal and concerned mainly deltoids and iliopsoas with preservation of distal muscles. Neck flexors were severely affected in majority of cases. Two patterns of muscle weakness and wasting were noted: (1) a proximal and symmetric in 4 patients, and (2) an asymmetric, mimicking FSHD (facioscapulohumeral dystrophy) in 4 patients. However, FSHD was excluded by genetic investigations. The muscle weakness was slowly progressive but 2 patients became wheelchair users respectively at the age of 65 and 74 years. CT scan showed fatty infiltration in the shoulder and pelvic girdle muscles. There was no clear correlation between the genotype and the severity of muscle weakness. Proximal fixed muscle weakness affects 10% of patients in our series of 80 patients with McArdle disease and always appears after the age of 40. The pattern of muscle involvement may be proximal and symmetric or more peculiar with asymmetric shoulder girdle weakness mimicking FSHD.

Neuromuscular Disorders, 1998

It has been shown previously that some patients with chronic fatigue syndrome show an abnormal in... more It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET). This cannot be explained satisfactorily by the effects of 'inactivity' or 'deconditioning', and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers. There were no differences in resting spectra between these groups but at the end of exercise, intracellular pH in the SATET +ve patients was significantly lower than in both the SATET -ve cases and controls (P < 0.03), and the SATET +ve patients also showed a significantly lower ATP synthesis rate during recovery (P < 0.01), indicating impaired mitochondrial oxidative phosphorylation. These observations support other evidence which indicates that chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that some chronic fatigue syndrome patients have a peripheral component to their fatigue.

Neuromuscular Disorders, 1997

We combined magnetic resonance (MR) imaging and phosphorus magnetic resonance spectroscopy (31P-M... more We combined magnetic resonance (MR) imaging and phosphorus magnetic resonance spectroscopy (31P-MRS) to study skeletal muscle in seven patients with limb girdle muscular dystrophy (LGMD) with a variable deficiency of the alpha-, beta-, and gamma-sarcoglycan but normal dystrophin expression on muscle biopsy. T1- and T2-weighted spin-echo axial leg images showed the highest degree of fat replacement in soleus, tibialis anterior and peroneal muscles while gastrocnemius and tibialis posterior were less affected. In LGMD patients as a group, calf muscle phosphorylated compound content did not differ from controls, but the cytosolic pH was increased (P = 0.02). The degree of calf muscle fat replacement correlated inversely with cytosolic pH (r = 0.74) and directly with PCr/ATP (r = 0.74). Muscle oxidative metabolism was normal in LGMD patients. Our findings show that primary deficits of sarcoglycan complex lead to specific morphological and metabolic patterns of skeletal muscle involvement.

Neurology, 2010

http://www.neurology.org/content/74/12/988.full.html located on the World Wide Web at:

Neurology, 2009

The cause of hyperintense magnetic resonance changes and reduced apparent diffusion coefficient (... more The cause of hyperintense magnetic resonance changes and reduced apparent diffusion coefficient (ADC) in specific brain regions of patients with Creutzfeldt-Jakob disease (CJD) is unknown. Our aim was to determine the neuropathologic correlates of antemortem water ADC and normalized T2-weighted changes in patients with CJD. Ten patients with CJD and 10 sex- and age-matched healthy controls were studied by DWI and T2-weighted echoplanar MRI. At postmortem, patients with CJD were evaluated for semiquantitative assessment of gliosis and neuronal loss, spongiform changes, and abnormal PrP protein deposition in four cortical regions (occipital, parietal, and temporal cortex, and cingulate gyrus), thalamus, and striatum for a total of 60 regions of interest (ROI). Gliosis and neuronal loss correlated very highly with each other in the 60 ROIs. Where status spongiosus was absent, spongiform change correlated very highly with gliosis and neuronal loss in the cortex, but not in deep gray matter. Spongiform change was also significantly correlated with PrPSc load in both cortical and deep gray ROIs. In deep gray matter, ADC decreased with increasing spongiform change (R2 = 0.78; p &amp;lt; 0.001) and PrPSc load (R2 = 0.51; p = 0.003). In the cortex, ADC decreased with increases in all three, highly correlated, pathologic scores. Antemortem reductions in ADC values, typically found in patients with Creutzfeldt-Jakob disease (CJD), are correlated with spongiform changes seen at autopsy. This could be clearly established in the striatum and thalamus of our patients with CJD where the extent of spongiform change was not significantly correlated with gliosis or neuronal loss.

Neurology, 2008

recurrence of myoclonus Rare mtDNA variants in Leber hereditary optic neuropathy families with Th... more recurrence of myoclonus Rare mtDNA variants in Leber hereditary optic neuropathy families with This information is current as of July 25, 2008 http://www.neurology.org/cgi/content/full/70/10/762 located on the World Wide Web at:

Neurology, 2004

Narcolepsy is a disabling neurological disease affecting approximately 1 in 2000 individuals and ... more Narcolepsy is a disabling neurological disease affecting approximately 1 in 2000 individuals and characterised by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep 1 . Cataplexy, a sudden muscle tone loss brought on by emotions, is a clinical feature almost exclusive to narcolepsy that occurs in around 60% of patients 2 . A dysfunction of the orexin (hypocretin) system in the hypothalamus has recently been linked to the pathogenesis of narcolepsy 3 . Severe reduction in hypothalamic orexin-containing neurons and axons were detected in narcoleptic patients 4 . Conversely, the large majority of narcoleptic patients with cataplexy do not show detectable orexin in their cerebrospinal fluid (CSF) 5 . A recent magnetic resonance study using the voxel-based morphometry technique disclosed a marked bilateral decrease in the hypothalamic grey matter content in narcolepsy patients, not evident on conventional structural MRI 6 . In the present study we used 1 H-MRS to look for direct evidence of hypothalamic neurodegeneration in narcolepsy patients.

Neurological Sciences, 2010

We report a new case of infantile idiopathic hemiconvulsion-hemiplegia syndrome (HH). A prolonged... more We report a new case of infantile idiopathic hemiconvulsion-hemiplegia syndrome (HH). A prolonged right-sided febrile convulsion was followed 4 days later, by right hemiconvulsive status epilepticus, documented by video-electroencephalogram (EEG) recording. The child developed an ipsilateral hemiplegia, partially improved during the first month of follow-up. Sequential cerebral magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) at 6, 15, 30 days of follow-up showed a cytotoxic edema in the left hemisphere and a subsequent necrosis. At 1-year of follow-up, we performed MRI control because of febrile convulsion lasting few minutes that confirmed a non-progressive left hemisphere atrophy. After 2 years, the patient was seizurefree, with a mild right hemiplegia and language skills deficit. We discuss the unclear pathogenesis of HH through sequential neuroradiological evaluation.

Muscle & Nerve, 2008

McArdle's disease causes limitation in exercise capacity as well as disability, the severity of w... more McArdle's disease causes limitation in exercise capacity as well as disability, the severity of which has been associated with the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) haplotype-patients with the genotype associated with higher ACE activity show the most severe phenotype. Modulation of ACE activity through the use of inhibitors may thus positively affect disease expression. In a double-blind, randomized, placebo-controlled trial, we assessed the efficacy of an ACE inhibitor (2.5 mg ramipril) in 8 patients with McArdle's disease. End-points were changes in parameters of exercise physiology (cycloergometer and muscle 31 P-magnetic resonance spectroscopy), quality of life (QoL) according to the Short Form 36 (SF-36), and disability according to the World Health Organization-Disability Assessment Scale II (WHO-DAS II). Patients had lower QoL and higher disability than controls. Measures of exercise physiology were not changed by ramipril in the whole group, but treatment induced higher peak VO 2 (P ϭ 0.017) in ACE D/D patients, yet not in I/D patients. Treatment significantly improved disability (P Ͻ 0.05). McArdle's disease is a disabling condition affecting patients' QoL. Treatment with ramipril improves disability and modifies exercise physiology only in D/D patients, raising the possibility of a differential haplotype-linked sensitivity to the treatment.

Movement Disorders, 2008

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinic... more The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA-P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA-P in order to evaluate its differential diagnostic value in vivo. Twenty-eight patients with PSP (14 with possible-PSP and 14 with probable-PSP), 15 PD, 15 MSA-P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r 5 0.98, P < 0.001) and interrater reli-ability (r 5 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 3 10 23 mm 2 /s) than patients with PD (median 0.79 3 10 23 mm 2 /s, P < 0.001), MSA-P (median 0.79 3 10 23 mm 2 /s, P < 0.001), and healthy controls (median 0.80 3 10 23 mm 2 /s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA-P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms.

Movement Disorders, 2010

SCA12 is an autosomal dominant cerebellar ataxia characterized by onset in the fourth decade of l... more SCA12 is an autosomal dominant cerebellar ataxia characterized by onset in the fourth decade of life with action tremor of arms and head, mild ataxia, dysmetria, and hyperreflexia. The disease is caused by an expansion of 51 CAGs in the 5 0 region of the brainspecific phosphatase 2 regulatory subunit B-beta isoform (PPP2R2B) gene. SCA12 is very rare, except for a single ethnic group in India. We screened 159 Italian ataxic patients for SCA12 and identified two families that segregated an expanded allele of 57 to 58 CAGs, sharing a common haplotype. The age at onset, phenotype, and variability of symptoms were compatible with known cases. In one family, the disease was apparently sporadic due to possible incomplete penetrance and/or late age at onset. Our data indicate that SCA12 is also present in Italian patients, and its genetic testing should be applied to both sporadic and familial ataxias.

Movement Disorders, 2007

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilat... more The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and 1 H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.