Papers by Graziano Gusmaroli
Archives of Disease in Childhood, 1987
Electroencephalography and Clinical Neurophysiology, 1986
Nutrients
As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, ... more As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitaliz...
Journal of Neural Transmission, 2017
Transcranial sonography (TCS) shows an increased echogenic area of the substantia nigra (SN) in p... more Transcranial sonography (TCS) shows an increased echogenic area of the substantia nigra (SN) in patients with Parkinson disease (PD). It has been increasingly used in the diagnosis of PD and its differentiation from atypical parkinsonian syndromes. Here, we studied the diagnostic accuracy of SN TCS in Italian patients. In this blinded cross-sectional study (NOBIS study), two expert neuro-sonologists performed TCS in 25 PD patients and 29 age-and sex-matched controls. The study participants were completely hidden to the TCS investigators using large drapery. One month later, the SN TCS recordings were re-read by the initial investigator, and cross-read by the second reader. Diagnostic accuracy was estimated on the first reading, intra-reader reliability on rereading, and inter-reader reliability on cross-readings. The mean SN echogenic area was larger in the patients (0.24 cm 2) than in the controls (0.15 cm 2 ; Mann-Whitney test, p \ 0.001). SN measures did not differ between right and left, or between ipsilateral and contralateral to the clinically more affected side. There was no correlation between SN echogenicity and PD severity or duration. High intra-reader (concordance correlation coefficient 0.93) and inter-reader (0.98) agreement of SN measurements was found. The diagnostic accuracy for the detection of PD was high (area under receiver-operating characteristic curve 0.91; 95% CI 0.83-1.00) with an optimum cutoff value for SN echogenic area of 0.18 cm 2 with the device used here (specificity 0.83-0.90; sensitivity 0.72-0.92). This study supports the use of SN TCS in the diagnostic workup of PD if performed by trained readers.
Parkinsonism & Related Disorders, 2016
Minerva medica, 1991
A nervous system involvement is common in systemic lupus erythematosus, and may be the initial ma... more A nervous system involvement is common in systemic lupus erythematosus, and may be the initial manifestation of the disease. The spectrum of nervous system involvement is wide, and encompasses almost the whole range of neurological diseases. The neurological lupus is divided into a primary and a secondary group, and in the latter the pathogenetic role is supported by drugs and by organic and functional changes in the other organs and systems. In secondary neurological lupus, when a clinical picture of a focal cerebral injury is sustained by the presence of lupus anticoagulants, the prognosis is strict and the treatment problematic. Finally, among the primary neurological lupus it is important to distinguish two subsets of acute and subacute neurological lupus, because of differences in its management and prognosis.
Basal Ganglia, 2012
ABSTRACT
Parkinsonism & Related Disorders, 2013
Levodopa-carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastr... more Levodopa-carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson's disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson's Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean "Off" time was 6.7 h/day. "Off" time was reduced by a mean of 3.9 (±3.2) h/day and "On" time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally welltolerated; however, device and procedural complications, while generally of mild severity, were common.
Electroencephalography and Clinical Neurophysiology, 1993
Figure S1. Neuropathology of case 3. The neuropathological study on brain sample from case 3 show... more Figure S1. Neuropathology of case 3. The neuropathological study on brain sample from case 3 showed findings overlapping those found in case 1 and 4. Severe neuronal loss and spongiform changes (a: frontal cortex, Haematoxylin-Eosin) associated with astrogliosis (b: frontal cortex, GFAP immunostaining) were observed in cerebral cortex. The pattern of PrPSc deposition was the same of cases 1 and 4, and consisted of diffuse, synaptic-like immunoreactivity (c: 3F4 immunostaining, frontal cortex). Similar changes were found in cerebellum: loss of Purkinje cells and spongiosis in the molecular layer (d: Haematoxylin-Eosin), diffuse astrogliosis in the granular layer (e: GFAP immunostaining) and finely granular PrP deposits in the molecular layer (f: 3F4 immunostaining). As in the other cases carrying the V189I mutation, coarse spots of PrP immunostaining were evident in the granular layer (f: 3F4 immunostaining). Scale bars: in (a) = 100 μm (a, b, d and f are the same magnification); in ...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of... more Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Across environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for pert...
Basal Ganglia, 2012
ABSTRACT
Neurological Sciences
Introduction The GLORIA registry included 375 advanced Parkinson’s disease (PD) patients and eval... more Introduction The GLORIA registry included 375 advanced Parkinson’s disease (PD) patients and evaluated the efficacy and safety of a 24-month levodopa-carbidopa intestinal gel (LCIG) treatment in routine medical care. This analysis focuses on the Italian population, 60 patients treated with LCIG in 7 specialised PD care centres. Methods Hours of “Off” and “On” time were assessed with a modified version of the Unified Parkinson’s Disease Rating Scale (UPDRS) part IV items 39 and 32. Motor fluctuations, dyskinesia, non-motor symptoms, quality of life and safety were evaluated. Results Overall, 42 (70%) out of 60 patients completed the registry. LCIG treatment reduced “Off” time (− 3.3 ± 2.7 h at month 24 (M24), P
Journal of Neurology
Introduction The GREENFIELD observational study assessed the effect of levodopa/carbidopa intesti... more Introduction The GREENFIELD observational study assessed the effect of levodopa/carbidopa intestinal gel (LCIG) on motor and non-motor symptoms, and the related impact on patient quality of life and caregiver burden up to 8 years. Methods Final results of a large Italian cohort of patients who started LCIG in routine care between 2007 and 2014 are presented. Comparison between baseline (before LCIG) and follow-up visits on yearly basis (visit 2/3) is reported. Primary endpoint was Unified Parkinson's Disease Rating Scale (UPDRS-IV) Item 39; secondary endpoints were UPDRS I and II, dyskinesia items, PD Quality of Life Questionnaire-39, Parkinson's Disease Sleep Scale-2, Gait and Falls Questionnaire, Questionnaire on Impulsive Disorders, and Relative Stress Scale. Results Overall, 145 patients from 14 centers were assessed with a mean time since LCIG start of 2.8 ± 1.7 years at visit 2. The mean UPDRS-IV item 39 score showed significant reductions compared to baseline (mean score 2.0 ± 0.81) at visit 2 (mean score 0.9 ± 0.69; − 55%; p < 0.001) and at visit 3 (mean score 1.0 ± 0.75; − 50%; p < 0.001). At visit 3, significant reductions were observed for dyskinesia duration score (− 28%; p < 0.001), dyskinesia disability (− 40%; p < 0.001), and painful dyskinesia (− 50%; p < 0.001). Overall, 40 (27.6%) patients experienced 49 serious adverse events which were considered related to PEG/J procedure or to device in 16.3% of the cases. Conclusions The results of this study support the long-term efficacy of LCIG on PD symptoms as well as on activities of daily living. The adverse events were consistent with the established LCIG safety profile.
Acta Neuropathologica Communications
Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnorma... more Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrP Sc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85-90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10-15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases. We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities, ataxia and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrP Sc detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrP res), and type 1 PrP res was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD. Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrP Sc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes.
Parkinsonism & related disorders, Jan 21, 2017
To report the results of a national survey aimed at quantifying the current level of diffusion of... more To report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. Sixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy. Clinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation...
Archives of Neurology, Nov 1, 1985
Three patients with dystrophia myotonica and echocardiographic signs of subclinical cardiopathy h... more Three patients with dystrophia myotonica and echocardiographic signs of subclinical cardiopathy had cardiac side effects during oral treatment with phenytoin sodium or carbamazepine. These side effects were dose related: ventricular tachycardia appeared at a toxic serum phenytoin level in one patient and disappeared as the concentration fell within the therapeutic range, and atrioventricular block grade 1 developed in two patients at low serum carbamazepine levels, its severity increasing with the drug level. Given the risk of dangerous side effects, cardiac status needs to be carefully assessed before administration of phenytoin or carbamazepine in the treatment of dystrophia myotonica.
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Papers by Graziano Gusmaroli