Biomedical subjects

Letterio Morgante

Publications and source records attributed to Letterio Morgante.

At least 19 recordsLinked to original sources

PubMed2006

Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy.

Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) from Parkinson's disease is difficult in the early stage of the disease. In order to identify objective markers for differential diagnosis, we studied these three groups of patients with diffusion-weighted MRI (DWI). Sixteen MSA-P patients, 16 with PSP, 16 with Parkinson's disease and 15 healthy volunteers were studied. Regional apparent diffusion coefficients (rADC) were determined in different brain regions including basal ganglia, thalamus, white matter, pons and middle cerebellar peduncles (MCPs). rADC calculated in the MCP completely differentiated MSA-P patients (median: 0.93 x 10(-3) mm2/s) from PSP patients (median: 0.82 x 10(-3) mm2/s, P < 0.001), Parkinson's disease patients (median: 0.79 x 10(-3) mm2/s, P < 0.001) and healthy volunteers (median: 0.81 x 10(-3) mm2/s, P < 0.001). Other regions considered showed an overlapping among groups. DWI discriminates MSA-P from PSP and Parkinson's disease and healthy volunteers on the basis of MCP rADC values. These in vivo results confirm the pathological findings that the majority of MSA-P patients have moderate or severe degenerative changes not only in the nigrostriatal but also in the olivopontocerebellar systems. Our findings indicate that, in order to substantially contribute to the in vivo differential diagnosis of MSA-P, PSP and Parkinson's disease, rADC measurements should not be limited to the basal ganglia but should also include the MCP.

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PubMed2006

Pramipexole versus sertraline in the treatment of depression in Parkinson's disease: a national multicenter parallel-group randomized study.

In addition to treating the motor symptoms of Parkinson's disease, the dopamine agonist pramipexole has shown an antidepressant effect. The trials, however, included patients with motor complications, raising the question of whether the antidepressant benefit represented only a treatment-related motor improvement. To address this issue, we have conducted a 14-week randomized trial comparing pramipexole with an established antidepressant in patients without motor complications. At seven Italian centers, 67 Parkinsonian outpatients with major depression but no history of motor fluctuations and/or dyskinesia received open-label pramipexole (at 1.5 to 4.5 mg/day) or sertraline (at 50 mg/day). In both groups, the Hamilton Depression Rating Scale (HAM-D) score decreased throughout 12 weeks of treatment, but in the pramipexole group the proportion of patients who recovered, as defined by a final HAM-D score </= 8,was significantly higher, at 60.6% versus 27.3% (p = 0.006). Patients' self-ratings improved in both groups. All adverse events were mild or moderate, but five patients (14.7%) withdrew from the sertraline group. Despite the absence of motor complications, the pramipexole recipients showed improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore. We conclude that dopamine agonists may be an alternative to antidepressants in Parkinson's disease.

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PubMed2006

Unilateral cerebellar stroke disrupts movement preparation and motor imagery.

OBJECTIVE: To assess motor cortex excitability, motor preparation and imagery in patients with unilateral cerebellar stroke with damage of the dentate nucleus by using transcranial magnetic stimulation (TMS). METHOD: Eight patients with unilateral cerebellar lesions due to tromboembolic stroke and 10 age matched healthy subjects were enrolled. Resting (RMT) and active (AMT) motor threshold, cortical and peripheral silent period, evaluation of motor imagery, reaction time and premovement facilitation of motor evoked potential (MEP) were tested bilaterally using TMS. RESULTS: The RMT and AMT were found to be increased contra lateral to the affected cerebellar hemisphere while the cortical silent period was prolonged. In addition the amount of MEP facilitation during motor imagery and the pre-movement facilitation were reduced in the motor cortex contra lateral to the affected cerebellar hemisphere. The reaction time, performed with the symptomatic hand, was slower. CONCLUSIONS: On the whole, our data confirm a role for the cerebellum in maintaining the excitability of primary motor area. Furthermore, patients with unilateral cerebellar stroke exhibit lateralized deficit of motor preparation and motor imagery. SIGNIFICANCE: Our results add to evidence that cerebellum contributes to specific aspects of motor preparation and motor imagery.

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PubMed2006

Multiple system atrophy is distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test.

OBJECTIVE: Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. METHODS: We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. RESULTS: The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4 microg/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. INTERPRETATION: The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA.

Antiparkinson Agents↗

PubMed2006

Age at menopause predicts age at onset of Parkinson's disease.

We investigated the association between age at onset of Parkinson's disease (PD) and fertile life characteristics in 145 women. Linear regression analyses showed a significant correlation between age at PD onset and age at menopause (P = 0.003), between age at PD onset and fertile life duration (P = 0.008), and a nonsignificant correlation between PD onset and cumulative duration of pregnancies (P = 0.23). These results support the possible role of estrogens in PD.

Adult↗

PubMed2006

MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease.

PURPOSE: To prospectively assess if middle cerebellar peduncle (MCP) atrophy, evaluated at magnetic resonance (MR) imaging, can help differentiate multiple system atrophy (MSA) from Parkinson disease (PD). MATERIALS AND METHODS: All participants provided informed consent for participation in the study, which was approved by the institutional review board. Sixteen consecutive patients with MSA, 26 consecutive patients with PD, and 14 healthy control subjects were examined with MR imaging. Images were interpreted independently by two experienced neuroradiologists blinded to clinical information, who visually inspected the images for the presence or absence of putaminal atrophy, putaminal hypointensity, slitlike hyperintensity in the posterolateral margin of the putamen, brainstem atrophy, hyperintensity of the MCP, and cruciform hyperintensity of the pons. Measurements of MCP width on T1-weighted volumetric spoiled gradient-echo images were performed in all subjects. Differences in MCP width among the groups were evaluated by using the Kruskall-Wallis test, followed by the Mann-Whitney U test for multiple comparisons and Bonferroni correction. RESULTS: All patients (mean age, 63.88 years; range, 55-72 years) with MSA had at least one of the features commonly observed in this disease on MR images, whereas control subjects (mean age, 66.93 years; range, 61-77 years) and all but one patient with PD (mean age, 65.31 years; range, 51-79 years) had normal MR images. The average MCP width was significantly smaller in patients with MSA (6.10 mm+/-1.18 [standard deviation]) than in those with PD (9.32 mm+/-0.77, P<.001) or control subjects (9.80 mm+/-0.66, P<.001). CONCLUSION: Measurement of MCP width on MR images may be useful for distinguishing patients with MSA from those with PD.

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PubMed2005

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia.

The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3-6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone.

Adult↗

PubMed2004

FRAXE intermediate alleles are associated with Parkinson's disease.

There is evidence that male subjects with a clinical picture of action tremor, Parkinsonism, and cerebellar ataxia may have Fragile X premutations (FRAXA). We analyzed FRAXA and FRAXE triplet repeats in 203 male subjects with Parkinson's disease (PD) and 370 healthy controls. No full mutations or premutations at the FRAXA and FRAXE loci were found in the subjects with PD or in the controls. FRAXA allele distribution was similar in patients and controls. FRAXE intermediate alleles (31-60 repeats CCG) were found in 13 of 203 (6.4%) subjects with PD and in only one of the 370 (0.27%) healthy controls (P < 0.001), thus indicating that these relatively large alleles may be associated with PD.

Adult↗

PubMed2004

Tumor diagnosis preceding Parkinson's disease: a case-control study.

Lower cancer risk in Parkinson's disease (PD) patients compared to the general population has been reported. However, most of the studies were based on death certificates. We designed a case-control study to estimate the association of tumor preceding PD onset and PD. PD patients were matched by age and gender to PD-free individuals, randomly selected from the municipalities of residence of cases. Occurrence of tumors preceding PD onset was assessed through a structured questionnaire. Neoplasms were categorized as benign, malignant, or of uncertain classification, and endocrine-related or not. Odds ratios (OR) were calculated using conditional logistic regression and adjusted for tumor categories and risk factors. We included 222 PD patients. Frequency of cancer was 6.8% for cases, 12.6% for controls. PD patients had a decreased risk for neoplasms (adjusted OR, 0.4; 95% confidence interval [CI], 0.2-0.7). Risk was reduced only for women (adjusted OR, 0.3; 95% CI, 0.1-0.7). PD patients had a decreased risk both for malignant (adjusted OR, 0.6; 95% CI, 0.1-2.5) and nonmalignant neoplasms (adjusted OR, 0.3; 95% CI, 0.1-0.7). Still, risk was decreased for endocrine-related tumors (adjusted OR, 0.3; 95% CI, 0.1-0.9) and non-endocrine-related tumors (adjusted OR, 0.4; 95% CI, 0.1-0.9). Our study confirms the inverse association between PD and neoplasms reported in previous epidemiologic studies.

Aged↗

PubMed2004

Plasma risperidone concentrations during combined treatment with sertraline.

The effect of sertraline on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was studied in 11 patients with schizophrenia or schizoaffective disorder. To treat concomitant depressive symptoms, additional sertraline, at the dose of 50 mg/d, was administered for 4 weeks to patients stabilized on risperidone (4-6 mg/d). Mean plasma concentrations of risperidone, 9-OH-risperidone, and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) did not change significantly during combined treatment with sertraline. At the end of week 4, sertraline dosage was adjusted in some patients on the basis of the individual response and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the 4 patients who were still receiving the initial sertraline dose, but concentrations were slightly but not significantly increased (by a mean 15% over pretreatment) in the subgroup of 5 subjects treated with a final dose of 100 mg/d. In the 2 patients receiving the highest dose of sertraline, 150 mg/d, at week 8 total plasma risperidone concentrations were increased by 36% and 52%, respectively, as compared with baseline values. Sertraline coadministration with risperidone was well tolerated, and no patient developed extrapyramidal symptoms. These findings indicate that sertraline at dosages up to 100 mg/d is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of sertraline may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of sertraline on CYP2D6-mediated 9-hydroxylation of risperidone.

Adult↗

PubMed2003

Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.

Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries. About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache. Although the mode of transmission is controversial, population-based and twin studies have implicated genetic factors, especially in migraine with aura. Familial hemiplegic migraine is a hereditary form of migraine characterized by aura and some hemiparesis. Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM 602481). Functional data indicate that the putative pathogenetic mechanism is triggered by a loss of function of a single allele of ATP1A2. This is the first report associating mutations of Na+K+ pump subunits to genetic diseases.

Animals↗

PubMed2003

Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23.

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder characterized by episodes of transient hemiparesis followed by headache. Two chromosomal loci are associated to FHM: FHM1 on chromosome 19 and FHM2 on chromosome 1q21-23. Mutations of the alpha-1A subunit of the voltage gated calcium channel (CACNA1A) are responsible for FHM1. FHM2 critical region spans 28 cM, hence hampering the identification of the responsible gene. Here, we report the FHM2 locus refining by linkage analysis on two large Italian families affected by pure FHM. The new critical region covers a small area of 0.9Mb in 1q23 and renders feasible a positional candidate approach. By mutation analysis, we excluded the calsequestrin and two potassium channel genes mapping within the narrowed FHM2 locus.

Adolescent↗

PubMed2003

Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinson's disease.

Parkinson's disease (PD) is an extra-pyramidal neurodegenerative disorder, in which alterations of the immune system are involved. Interleukin (IL)-15 stimulates cellular immune response and induces growth and differentiation of various immune cells. RANTES, promoting leukocyte infiltration to sites of inflammation, mediates the trafficking and homing of immune cells. To clarify the potential effect of levodopa on the immunological network of PD, we analyzed IL-15 and RANTES serum levels in PD patients, treated or not with levodopa, and in healthy donors. Levodopa-treated patients showed significantly higher IL-15 and RANTES circulating levels with respect to healthy controls and higher, although not significantly, levels with respect to untreated patients. So, we hypothesize that the immunological alterations found in PD may be linked, at least in part, to levodopa therapy.

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PubMed2002

Fahr's disease.

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Adult↗

PubMedDate not supplied

A screening instrument for a Sicilian neuroepidemiological survey in the elderly.

We evaluated the sensitivity and specificity of a screening instrument developed for use in a two-phase neuroepidemiological survey in Sicily. The Sicilian Epidemiological Dementia Study (SEDES) project will evaluate the prevalence and incidence of dementia, parkinsonisms and essential tremor in four Sicilian municipalities. It is a two-phase door-to-door survey. To identify subjects with possible neurological disorders, in this study, we developed a screening instrument including a symptoms questionnaire and simple physical tasks for parkinsonisms and essential tremor. The Mini-Mental State Examination (MMSE) was chosen for screening dementia. The symptoms questionnaire and simple tasks developed to identify possible patients with parkinsonism and essential tremor, was tested in a hospital setting. To evaluate sensitivity, we selected 20 patients with essential tremor and 40 with Parkinson's disease (20 with Stages I-II and 20 with Stages III-V) [Neurology 17 (1967) 427]. To evaluate specificity we also selected 20 healthy subjects. The screening instrument was administered in a hospital setting by trained interviewers. Sensitivity of the screening instrument (questionnaire plus simple tasks) was 100% for essential tremor and parkinsonisms regardless of the stage. Specificity of the instrument was 90% (95% CI 66.9-98.2); the predictive positive value was 90.9%, while the negative predictive value was 100%. Even if validity was assessed in a hospital setting, the high sensitivity and specificity obtained suggest that the instrument could be an appropriate screening tool for parkinsonisms and essential tremor in a two-phase neuroepidemiological survey.

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PubMedDate not supplied

Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis.

OBJECTIVE: This study aimed to compare the efficacy and safety of quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis in a randomized, open-label, blinded-rater, parallel group trial. METHODS: Forty-five patients with Parkinson disease (PD) and psychosis induced by antiparkinsonian drugs were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. Forty patients, 20 in each treatment group, completed the study. The final dose of quetiapine (mean +/- SD) was 91 +/- 47 mg/d and that of clozapine 26 +/- 12 mg/d. The severity of psychosis was assessed using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale-Severity Subscale (CGI-S). The Unified Parkinson's Disease Rating Scale (UPDRS) III was used to assess motor conditions during the study period. The Abnormal Involuntary Movement Scale (AIMS) was performed to evaluate dyskinesias. RESULTS: Forty patients, 20 on clozapine and 20 on quetiapine, completed the study. The psychopathologic state improved significantly (P < 0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at any assessment time. Motor conditions remained unchanged after clozapine and quetiapine. Dyskinesias decreased significantly (P < 0.05) in both groups. Side effects were mild, generally transient, and well tolerated. CONCLUSIONS: Quetiapine and clozapine appear equally efficacious for treatment of dopaminergic psychosis in patients with PD.

Aged↗

PubMedDate not supplied

Levetiracetam in tardive dyskinesia.

OBJECTIVES: The aim of this study was to evaluate the effect of levetiracetam on tardive dyskinesia (TD), which is known to be a major limitation of chronic antipsychotic drug therapy, particularly with conventional antipsychotics. METHODS: Sixteen patients suffering from chronic psychosis with TD were enrolled consecutively. Levetiracetam was given in gradually increasing doses, starting with 125 twice a day until the best clinical benefit was achieved (mean dosage, 2,290 mg; range, 1,000-3,000 mg). Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale at baseline and after 1 month and 3 months of treatment with levetiracetam. RESULTS: Compared with baseline, there was a significant improvement in the Abnormal Involuntary Movement Scale score after 1 month still present after 3 months (P < 0.001). All patients well tolerated levetiracetam, except one who dropped out of the trial after the first 2 weeks owing to excessive drowsiness. CONCLUSIONS: The results of this open-label observational study suggest that levetiracetam is a well-tolerated drug and effectively controls TD.

Aged↗

PubMedDate not supplied

Impact of sociodemographic characteristics on cognitive performance in an elderly Sicilian population.

OBJECTIVE: To assess cognitive levels in an elderly Sicilian population and to evaluate the role of education and other sociodemographic characteristics in cognitive performance. BACKGROUND: The pattern of cognitive performance in the elderly has not been investigated extensively in well-defined Italian populations. This study was conducted as part of a door-to-door survey of common neurologic disorders (the Sicilian Neuro-Epidemiologic Study project). METHODS: Thirteen physicians administered an Italian version of the Short Portable Mental Status Questionnaire (SPMSQ) to all subjects aged 50 years or older who, on November 1, 1987, resided in either of two Sicilian municipalities (Terrasini, Palermo province, and Riposto, Catania province; n = 3,999). Performance was scored as the number of errors on the SMPSQ. To define cognitive impairment we corrected the score for education as suggested by Pfeiffer [J Am Geriatr Soc 1975;23:433-441]. RESULTS: The median SPMSQ score was equal to 2, and cognitive impairment was present in 4.6% of the subjects. In a bivariate analysis, age, sex, education, employment status at interview and principal lifetime occupation were all significantly associated with cognitive impairment. In a multivariate analysis, the same pattern was seen, except that principal lifetime occupation lost its significance. CONCLUSION: Our findings suggest that age, sex, education and employment status are the sociodemographic characteristics associated with cognitive impairment in the elderly as measured by the SPMSQ.

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