S Bernardini

Università di Pisa, Pisa, Tuscany, Italy

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Publications (19)57.3 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson's disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with (99m)Tc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions (p<0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy (p<0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion (p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal "re-afferentation".
    Journal of Neural Transmission 11/2006; 113(11):1787-90. · 3.05 Impact Factor
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    ABSTRACT: The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.
    Neurological Sciences 03/2005; 25(6):316-21. · 1.41 Impact Factor
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    ABSTRACT: The occurrence of parkinsonism in Alzheimer's disease (AD) is quite common, however the molecular and neurochemical changes underlying such extrapyramidal features in AD have been not fully understood. Post-mortem as well as in vivo imaging study have produced conflicting results as regards the existence of dopaminergic changes in AD. Aim of the present study was to investigate in vivo the nigro-striatal dopaminergic function in a group of AD patients with parkinsonism. Thirteen patients with AD and extrapyramidal features not related to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of dopamine transporter, and the data were compared with those obtained in 15 patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson's disease (PD), and 8 healthy elderly controls. The analysis of the data was performed by regions-of-interest approach and calculations of the striatal-to-non specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT striatal uptake in patients with AD-P was similar to that obtained in the control population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT uptake in all striatal areas with respect to AD-P and control groups (p < 0.005). The lack of dopamine transporter changes in our series of AD-P patients can indicate that dopaminergic presynaptic function is preserved in this population and that different dopaminergic changes such as postsynaptic ones, or different neurotransmitter alterations might underlie the extrapyramidal features in AD.
    Journal of Neural Transmission 08/2004; 111(8):1065-73. · 3.05 Impact Factor
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    ABSTRACT: Excessive daytime somnolence is a common adverse effect of dopamine-agonist treatment of Parkinson's disease (PD). Many factors, such as age and sleep disturbances, could be involved in the pathogenesis of this phenomenon. However, pharmacokinetic factors have never been considered. In this open, prospective, pilot study, nine consecutive non-demented PD patients in early disease stages on monotherapy treatment with dopamine agonists and with no significant sleep problems, were enrolled. They were selected based on the presence of excessive daytime sleepiness induced by the dopaminergic treatment. A fast switch-over from the dopamine agonist currently used to a single equivalent dose of cabergoline, a long-acting dopamine agonist, administered at bedtime was performed. All patients were evaluated by means of UPDRS and Epworth Sleepiness Scale (ESS). A significant 70% reduction of daytime sleepiness was observed during the 3-month study compared with baseline. Data from this study suggest that both pharmacodynamic and pharmacokinetic mechanisms are involved in the pathophysiology of dopamine agonist-induced sleepiness.
    Neurological Sciences 11/2003; 24(3):170-1. · 1.41 Impact Factor
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    ABSTRACT: It is accepted that orthostatic hypotension is a clinical marker for the diagnosis of multiple system atrophy, but conflicting data indicate that it may also be present in Parkinson disease (PD). To evaluate the prevalence of autonomic cardiovascular impairment and orthostatic hypotension in a large group of patients with de novo PD, followed up for at least 7 years, to clinically confirm the diagnosis of the disease. During a 2-year recruiting period, 60 untreated patients diagnosed as having idiopathic PD underwent autonomic cardiovascular function evaluation using the Ewing test. Patients subsequently received dopaminergic therapy and their condition was followed up for at least 7 years. Nine (15%) of 60 patients were excluded from the study because during the follow-up period a parkinsonian syndrome was diagnosed (5 had multiple system atrophy and 4 had progressive supranuclear palsy). Data from 51 patients with PD underwent final statistical analysis and the results were compared with those of 51 age-matched healthy control subjects who had taken the same battery of autonomic tests. A statistically significant difference was found in postural hypotension (P =.02) and deep breathing test results (P =.03) between patients and controls. Seven (14%) of 51 patients with PD and 3 (60%) of 5 patients with multiple system atrophy had a decrease of more than 20 mm Hg in systolic blood pressure on standing. Data from this study indicate a high prevalence of sympathetic and parasympathetic failure in patients with de novo PD, and when using a decrease of at least 20 mm Hg in systolic blood pressure, manometric orthostatic hypotension was found in 7 (14%) of the 51 patients with de novo PD.
    JAMA Neurology 10/2003; 60(10):1400-4. · 7.58 Impact Factor
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    ABSTRACT: The acute antidyskinetic effects of IV amantadine in HD were evaluated. A 2-hour IV infusion of amantadine or placebo was administered to nine patients with HD on two different days in a double-blind, randomized crossover fashion. All patients subsequently received oral amantadine unblinded for a 1-year period. A reduction of dyskinesia scores was reported during both IV and oral amantadine treatment (p < 0.05). No significant changes were observed in neuropsychological tests or psychiatric rating scales.
    Neurology 06/2003; 60(12):1995-7. · 8.25 Impact Factor
  • Journal of Sleep Research 01/2003; 12:255-257. · 3.04 Impact Factor
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    ABSTRACT: We investigated the presence of cytogenetic alterations in peripheral blood lymphocytes of Alzheimer's disease (AD) and Parkinson's disease (PD) patients. Detection of spontaneous structural and/or numerical chromosome damage has been assessed by micronucleus (MN) assay coupled with fluorescence in situ hybridization (FISH). The cytogenetic investigation was performed on 22 AD patients, 18 PD patients, and 20 controls. The spontaneous frequencies of micronuclei (MN) in human lymphocytes of both AD and PD patients were significantly higher than in controls. The majority of MN was composed of whole chromosomes in AD patients, while a prevalence of MN arising from chromosome breakage was observed in PD patients. Different molecular mechanisms underlie cytogenetic alterations observed in peripheral lymphocytes of AD and PD patients.
    Neurological Sciences 10/2002; 23 Suppl 2:S97-8. · 1.41 Impact Factor
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    ABSTRACT: Huntington's disease (HD) is characterized by chorea, cognitive and behavioral changes. Amantadine, a non-competitive NMDA receptor antagonist, has shown an antidyskinetic effect on levodopa-induced dyskinesias, which are known to have strict pathogenetic analogies with choreic hyperkinesias. The antidyskinetic efficacy of amantadine and its effects on cognitive and behavioural symptoms were evaluated. Eight HD patients received oral amantadine (100 mg tid) unblinded for a 1-year period. A significant reduction of dyskinesias was reported ( p<0.01). No changes were observed in neuropsychologic and psychiatric assessments after 6 and 12 months of therapy. These data may have relevance to the treatment of HD with amantadine.
    Neurological Sciences 09/2002; 23 Suppl 2:S83-4. · 1.41 Impact Factor
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    ABSTRACT: Postmortem studies suggest excessive free radical toxicity in the substantia nigra of patients with PD. Increased lipid peroxidation and oxidative DNA damage have been reported in the CNS. Markers of oxidative stress have been identified in the blood of patients with PD. To assess the presence of spontaneous chromosome and primary or oxidative DNA damage in peripheral blood leukocytes of patients with untreated PD. Patients with de novo PD (20) and control subjects (16), matched for age, sex, and smoking habits, underwent cytogenetic analysis using the human lymphocyte micronucleus assay coupled with the fluorescence in situ hybridization technique and the Comet assay. Compared with controls, patients with PD showed an increase in the incidence of spontaneous micronuclei (p < 0.001); single strand breaks (p < 0.001); and oxidized purine bases (p < 0.05). Fluorescence in situ hybridization analysis showed micronuclei harboring acentric fragments. There is chromosomal, primary DNA damage and oxidative DNA damage demonstrable in lymphocytes of patients with untreated PD.
    Neurology 06/2002; 58(12):1809-15. · 8.25 Impact Factor
  • Movement Disorders 01/2002; 17:S147-S148. · 4.56 Impact Factor
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    ABSTRACT: Tardive dystonia represents a complication of long-term use of neuroleptics and its treatment is often unsatisfactory. Atypical neuroleptics appear to improve tardive dystonia, and cases of tardive dystonia successfully managed with clozapine have been reported. The aim of this open-label video-blinded study was to evaluate the antidystonic efficacy of olanzapine, a new atypical neuroleptic with a low risk of agranulocytosis, in a group of four patients (one man and three women) with tardive cervical dystonia. They developed severe dystonia after several years of neuroleptic treatment. Extensive laboratory evaluations, as well as neurophysiologic and neuroradiologic investigations, were negative. Olanzapine was started at a dose of 5 mg/d and increased up to 7.5 mg/d. All patients were evaluated at baseline and after 2, 4, 8, and 12 weeks of treatment, using the Toronto Western Spasmodic Torticollis Rating Scale, and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. A self-rating visual analog scale completed the disability evaluation.A moderate to marked improvement in dystonia was observed in all patients, and significant differences were observed in Toronto Western Spasmodic Torticollis Rating Scale scores and videotape ratings after 8 and 12 weeks of treatment compared with the basal values (p < 0.05). The average percentage of improvement in Toronto Western Spasmodic Torticollis Rating Scale score and visual analog scale was 26.4% and 42.6%, respectively. No serious side effects were reported at the maximum dosage reached (7.5 mg/d). This study warrants a larger controlled study to conclusively demonstrate the efficacy of olanzapine in tardive dystonia.
    Clinical Neuropharmacology 01/2002; 25(2):71-4. · 1.82 Impact Factor
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    ABSTRACT: Experimental evidence suggests that glutamatergic receptor blockade may improve the motor response complications associated with long-term levodopa treatment in Parkinson's disease (PD) patients. Our objective was to evaluate the acute effect of amantadine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on levodopa-induced dyskinesias, and to gain further insights into the antidyskinetic mechanism of this drug. Nine PD patients with motor fluctuations and severely disabling peak of dose dyskinesias received their first morning levodopa dose, followed by a 2-hour intravenous amantadine (200 mg) or placebo infusion, on two different days. Parkinsonian symptoms and dyskinesias were assessed every 15 minutes during the infusion and for 3 hours thereafter, while patients were taking their usual oral antiparkinsonian therapy, by means of Unified Parkinson's Disease Rating Scale (UPDRS, motor examination), tapping test, and a modified Abnormal Involuntary Movement Scale (AIMS). Intravenous amantadine acutely improved levodopa-induced dyskinesias by 50%without any loss of the anti-parkinsonian benefit from levodopa. This study confirms the antidyskinetic effect of amantadine and strengthens the rationale for using antiglutamatergic drugs in the treatment of parkinsonian motor fluctuations.
    Movement Disorders 06/2001; 16(3):515-20. · 4.56 Impact Factor
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    ABSTRACT: Several lines of evidence support the presence of DNA damage in somatic cells of Parkinson's disease (PD) patients due to the formation of free radical species. In order to detect spontaneous chromosome and primary or oxidative DNA damage, we performed the human lymphocyte micronucleus assay (HLMNA) and comet assay in 19 PD patients and 16 healthy controls. Compared with controls, PD patients showed a significant increase in: (I) spontaneous micronucleus (MN) frequency (p<0.001); (2) single strand break (SSB) levels (p<0.001); and (3) oxidized purine base levels (p<0.05). The chromosome damage and the increased levels of oxidized purine bases observed in our patients support the hypothesis of oxidative stress as a relevant factor in the pathogenesis of PD.
    Neurological Sciences 02/2001; 22(1):83-4. · 1.41 Impact Factor
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    ABSTRACT: Proton MR spectroscopy (1H-MRS) has been previously performed in Parkinson's disease (PD) and parkinsonian syndromes to evaluate in vivo concentrations of basal ganglia and cerebral cortex metabolites such as N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). However, this technique has never been used to evaluate motor cortex in untreated PD patients. In this study, single-voxel 1H-MRS of basal ganglia and motor cortex was carried out in 10 de novo patients with PD and 10 age-matched healthy controls. A significant reduction in the NAA/Cr ratio was observed in the motor cortex of PD patients compared with controls (p)<(0.01). Basal ganglia spectra did not allow any evaluation due to the presence of artefacts related to inorganic paramagnetic substances. The motor cortex reduction of the NAA/Cr ratio in de novo PD patients may reflect an altered neuronal functioning due to a loss of thalamocortical excitatory inputs and may represent an in vivo marker for the diagnosis of PD.
    Neurological Sciences 02/2001; 22(1):69-70. · 1.41 Impact Factor
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    ABSTRACT: Mexiletine is an antiarrhythmic drug that has been reported to exert antidystonic properties. We performed an open-label study to collect further evidence of the antidystonic effect of mexiletine in spasmodic torticollis (ST) and to evaluate its possible use in generalized dystonia. We administered mexiletine to six patients with dystonia (three with generalized dystonia and three with ST) who had failed to respond to previous pharmacotherapy. The drug was started at a dose of 200 mg/d by mouth and increased up to a maximum dose of 800 mg/d. Patients were evaluated at regular intervals over a 6-week period with use of the Fahn & Marsden Dystonia Scale and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. Patients were then followed for at least 1 year and evaluated every 3 months at the dose reached during the study period. No adverse effects were reported in five patients; in one patient, dizziness developed at the dosage of 800 mg/d, requiring a reduction of the dose. At the end of a 6-week period, a significant improvement in the rating scale for dystonia and in videotape ratings was observed after mexiletine treatment (p < 0.01). Our data indicate that mexiletine is a useful drug in dystonia treatment.
    Clinical Neuropharmacology 06/2000; 23(4):186-9. · 1.82 Impact Factor
  • Clin Neuropharmacol. 01/2000;
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    ABSTRACT: Cervical hyperextension injuries are common and are associated with significant morbidity. Clinically two syndromes are described: "acute" whiplash syndrome and "late" whiplash syndrome (in which the patients are still symptomatic after six months despite normal physical and radiological examination). In order to clarify the pathology of the persistent pain in late whiplash syndrome we performed a cervical spine magnetic resonance imaging (MRI) in 33 consecutive patients suffering from this condition. Twenty-six patients (78.8%) showed MRI abnormalities, the most common MRI finding (57.6%) was pre-existent spondylosis. Indeed, the group of patients with spondylosis and other MRI changes had higher clinical scores than those without MRI abnormalities as measured by a three-point grading system based upon the symptoms and signs shown. Several MRI changes, most of them already demonstrable by standard X-ray were seen among 33 patients suffering from late whiplash syndrome. Although no one of these findings appears to be specific and certainly related to the previous neck injury, they could represent a risk factor for a longer pain duration.
    Functional neurology 01/1999; 14(4):219-25. · 1.04 Impact Factor
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    ABSTRACT: Patients with Parkinson's disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The pathophysiology of this phenomenon is not known. We evaluated the motor response to repeated doses of levodopa during a 12-hour period in 52 parkinsonian patients (19 de novo, 20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a.m., 12:00 noon, and 4:00 p.m. Motor measurements such as tapping test, walking time, and tremor score, and blood samples for levodopa and 3-O-methyldopa (3OMD) plasma analysis, were performed hourly. Mean motor scores and pharmacokinetic data, evaluated for a period of 3 hours after each levodopa dose, were compared. In de novo patients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in stable and wearing-off patients. No significant difference in levodopa pharmacokinetics after each levodopa dose was observed within each patient group, whereas 3OMD plasma levels significant increased with repeated levodopa administrations. However, no significant correlation between motor scores and 3OMD plasma levels was observed, suggesting that the diminishing motor response to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does not relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of tolerance to repeated doses of levodopa.
    Clinical Neuropharmacology 23(1):28-33. · 1.82 Impact Factor