Biomedical subjects

Paolo Livrea

Publications and source records attributed to Paolo Livrea.

At least 19 recordsLinked to original sources

PubMed2006

Influence of Interferon beta treatment on quality of life in multiple sclerosis patients.

BACKGROUND: Interferon-beta (IFN-beta) shows beneficial effect on the course of multiple sclerosis (MS), nevertheless its route and frequency of administration and side effects might impact negatively the quality of life (QoL) of MS patients. The objective of this study was to evaluate the influence of IFN-beta on QoL in MS patients. METHODS: Seventy-seven disease modifying treatment (DMT) free and 41 IFN-beta treated MS patients were evaluated. QoL, assessed by MSQoL-54, was related to IFN-beta treatment and to clinical and demographic parameters at baseline and after two years. Multivariate hierarchical linear model for repeated measurements was used. RESULTS: Treated patients showed a younger age, a lower disease duration and a higher relapse rate in the two years preceding study entry. At inclusion time treated and untreated patients did not differ in relapse rate, expanded disability status scale (EDSS), fatigue, depression, physical and mental QoL. IFN-beta did not influence QoL at inclusion time, but when QoL was evaluated after two years, treatment negatively affected mental QoL. Depression and fatigue negatively influenced physical and mental QoL both at baseline and after two years. EDSS correlated with a poor physical QoL only at baseline. CONCLUSION: IFN-beta had a negative impact on QoL over the time in MS patients, influencing mainly mental QoL. The impairment of QoL in MS was strongly associated with increasing fatigue and depression, whereas clinical disability had a minor unfavourable role.

Adult↗

PubMed2006

Planning genetic studies on primary adult-onset dystonia: sample size estimates based on examination of first-degree relatives.

Primary adult-onset dystonia is thought to be partly genetic, but families large enough for a genome wide search are difficult to find. We examined the first-degree relatives of 76 primary adult-onset dystonia patients to assess the feasibility of model-free nonparametric methods that allow either screening of candidate loci (case-control design, transmission disequilibrium test [TDT], and sibling-TDT [S-TDT]) or identification of novel genes (affected sib-pair [ASP] method). Among the examined relatives, 1/34 parents, 13/149 siblings and 10/125 offspring were affected by adult-onset dystonia. The predicted sample sizes to detect a gene conferring an Odds ratio of 3.0 were 99 for case-control and TDT methodology, 148 for S-TDT, and 107 to 173 for an ASP study assuming three major loci. Based on our family structure, TDT, S-TDT, and ASP methods would required screening of about 220, 700, and 580 to 939 probands respectively. Analysing subpopulations with different types of dystonia, TDT required fewer probands with cervical/hand dystonia, S-TDT needed fewer probands with cranial dystonia. These sample size estimates suggest that the S-TDT may be feasible, whereas collection of cases for both TDT and ASP approaches would represent a major collaborative challenge.

Adolescent↗

PubMed2006

Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study.

BACKGROUND: In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. METHODS: Eighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance. RESULTS AND DISCUSSION: Both the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment.Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaboration CONCLUSION: The results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.

Journal Article↗

PubMed2006

Topographic analysis of laser evoked potentials in chronic tension-type headache: correlations with clinical features.

In the present study, we examined clinical and laser-evoked potentials (LEP) features in a group of chronic tension-type headache (CTTH) patients, in order to perform a topographic analysis of Laser evoked potentials (LEPs) and a correlation with clinical features. Eighteen patients suffering from CTTH [Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders 2nd ed. Cephalalgia 2004; 24 Suppl 1, 1-159.] participated in the study. Twelve age- and sex-matched controls were also examined. We performed a basal evaluation of clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained by the hand and the pericranial points stimulation in all patients vs healthy subjects. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group, specially when the pericranial points were stimulated. The P2 wave amplitude was correlated with TTS levels and anxiety scores. The results of this study confirm that pericranial tenderness is a phenomenon initiating a self-sustaining circuit, involving central sensitization at the level of the cortical nociceptive areas devoted to attentional and emotional components of pain.

Adult↗

PubMed2006

Reversible Parkinsonian syndrome associated with anti-neuronal antibodies in acute EBV encephalitis: a case report.

We report a case of subacute-onset isolated parkinsonian syndrome in a 16 years old patient. Epstein-Barr infection was diagnosed according to serologic evidences. Parkinson-like syndrome completely recovered after 60 days. Autoantibodies reacting against a 130 Kda antigens expressed in human neuroblastoma cell line were detected. Pathogenesis and differential diagnosis are briefly discussed. EBV testing could be worthwhile in juvenile, acute-onset, parkinsonism.

Acute Disease↗

PubMed2006

Sensitivity and specificity of a self-administered questionnaire for familial screening of adult-onset dystonia.

We developed a self-administered questionnaire for screening the most common adult-onset dystonias. It was tested in 90 first-degree relatives of 22 adult-onset dystonia patients, yielding 79% sensitivity and 94% specificity. Simulation of a case-finding procedure based on serial application of the questionnaire and clinical examination of both subjects screening positive and subjects screening negative who had < 8 years of schooling increased sensitivity to 95% and specificity to 100%. This questionnaire may be an important screening resource for familial aggregation studies to be used in the context of a complex case-finding procedure.

Aged↗

PubMed2006

The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Adjuvants, Immunologic↗

PubMed2006

Elevated plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with dyskinesias.

BACKGROUND: Elevated plasma homocysteine (Hcy) concentrations are associated with increased risk of systemic vascular diseases, Alzheimer's disease and vascular dementia. Several cross-sectional reports and two prospective clinical studies have recently reported elevated plasma Hcy levels in L-dopa-treated Parkinson's disease (PD) patients and Hcy has been proposed as a possible mediator for the development of long-term L-dopa motor complications (such as wearing off and on-off phenomena, and dyskinesias). The aim of the study was to elucidate a possible role of L-dopa-related hyperhomocysteinemia in the development of dyskinesias. METHODS: In this cross-sectional study we compared Hcy, B(12) and folate levels in 53 PD patients treated with L-dopa (29 with dyskinesias, 24 without dyskinesias). RESULTS: Mean plasma Hcy levels were higher in the group of PD patients with dyskinesias (19 vs. 15.4 micromol/L; T: 2.12; p=0.04). After taking into account potential confounding factors, analysis of the data revealed that the occurrence of dyskinesias progressively increased with plasma Hcy levels (relative risk 1.2, 95% CI 1.015-1.4; p=0.03). CONCLUSIONS: Our results raise the possibility that Hcy plays a role in the development of dyskinesias, through its toxic effects on both dopaminergic neurons and non-substantia nigra, non-dopaminergic neurons.

Cross-Sectional Studies↗

PubMed2006

Hyperhomocysteinemia in movement disorders: Current evidence and hypotheses.

Elevated plasma levels of homocysteine (Hcy) are a risk factor for systemic vascular diseases, stroke and vascular dementia. In recent years, increasing Hcy levels have been detected in neurological disorders that are not vascular in origin including Alzheimer's Disease and movement disorders (MD) such as idiopathic Parkinson's Disease (PD), Huntington's Disease (HD) and primary dystonia. Hyperhomocysteinemia (HHcy) in PD results from L-Dopa administration and its O-methylation dependent from catechol-O-methyltransferase and may be implicated in the development of motor complications and non-motor symptoms, such as dementia. In a recent study, HHcy has been evidenced in HD patients, compared to controls. Because mutated Huntington protein influences Hcy metabolism by modulating cystathionine-beta-synthase activity, Hcy could represent a biological marker of neurodegeneration and could explain the leading role of cardiovascular and cerebrovascular diseases as causes of death in HD. Finally, several cases of homocystinuria associated with dystonia, and some recent reports of elevated Hcy in patients with primary adult onset dystonia have been published. Increased Hcy plasma levels may have important implications in patients affected by these basal ganglia disturbances, by exerting neurotoxic effects, contributing to neurotransmitter imbalance in motor circuits, and increasing the risk for vascular insults and cognitive dysfunctions.

Adolescent↗

PubMed2005

Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis.

There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of brain magnetic resonance imaging (MRI) lesions in MS patients. Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients. Seventy-three patients (36.5%) showed at least one enhancing lesion. Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004). The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age. Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p<0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions. This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.

Adult↗

PubMed2005

Lack of habituation of nociceptive evoked responses and pain sensitivity during migraine attack.

OBJECTIVE: The aim of the present study was to investigate the habituation of subjective pain sensation to CO(2) laser stimulus, in relation to the amplitude modifications of the cortical evoked responses (LEPs), during both the migraine attack and the not symptomatic phase. METHODS: Fourteen migraine patients were selected and compared with 10 healthy controls. Eight patients were evaluated during both the pain-free and the attack phases. Three following series of 20 averaged LEPs were recorded, stimulating the hands and the supraorbital zones: during the attack, two consecutive series of 20 averaged LEPs were carried out. The subjective sensation was requested for each laser stimulus, using a 0-10 points Verbal Rating Scale (VRS). RESULTS: In normal subjects the N2-P2 waves amplitude showed habituation across the three repetitions, which correlated with the habituation of the subjective rating of the stimulus. During the not symptomatic phase, patients showed a lack of habituation of the N2-P2 amplitude when the hand and the face was stimulated, with a pattern of increase of the pain rating across the three repetitions; in addition there was a lack of correlation between the LEPs amplitude and the subjective sensation. During the attack, the LEPs amplitude and the pain rating were increased when the face was stimulated, but they did not habituate across the two repetitions, likely the pain-free condition. The percent LEPs amplitude variation across the three repetitions correlated with the main indices of migraine severity, mainly when the supraorbital zone was stimulated. CONCLUSIONS: The abnormal cortical excitability in migraine could condition an anomalous behavior of nociceptive cortex during the interictal phase of migraine: it persists during the acute phase, and correlates with the frequency and duration of migraine. SIGNIFICANCE: The reduced habituation of the nociceptive cortex may concur with the onset and evolution of headache.

Adolescent↗

PubMed2005

Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients.

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT-I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT-I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT-I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa-treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT-I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT-I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT-I effectively reduces HHcy.

Aged↗

PubMed2005

Relationship between eye symptoms and blepharospasm: a multicenter case-control study.

Although patients with primary blepharospasm (BSP) commonly report experiencing ocular symptoms before the onset of orbicular spasms, the precise frequency and pathogenic role of this subjective ocular discomfort are poorly understood. We conducted a multicenter case-control study to investigate symptoms related to disorders of the anterior segment of the eye, administering a questionnaire to 165 patients with BSP and 180 age- and gender-matched control patients with hemifacial spasm. On a validation sample, our questionnaire yielded high accuracy in detecting eye diseases (predominantly, dry eye syndrome) using detailed ophthalmological examination as the criterion. Logistic regression analysis indicated a significant association between ocular symptoms at disease onset and BSP. Ocular symptoms starting in the year preceding disease onset (short-latency symptoms) showed a stronger association with BSP than ocular symptoms occurring earlier in time (long-latency symptoms). The association was stronger when short-latency symptoms developed from 40 to 59 years of age, whereas this was not observed for long-latency symptoms. Our findings support the view that eye symptoms associated with BSP result from eye diseases and may be involved in the pathogenesis of BSP. The differential risk of developing BSP, based on age at onset of ocular symptoms, suggests that age and eye diseases may interact in giving rise to BSP.

Age of Onset↗

PubMed2005

Habituation of single CO2 laser-evoked responses during interictal phase of migraine.

A reduced habituation of averaged laser-evoked potential (LEP) amplitudes was previously found in migraine patients. The aim of the present study was to assess the habituation of single LEP responses and pain sensation during the interictal phase in migraine patients. Fourteen migraine patients were compared with ten control subjects. The pain stimulus was laser pulses, generated by CO2 laser, delivered to right supraorbital zone. Patients were evaluated during attack-free conditions. The LEP habituation was studied by measuring the changes of LEP amplitudes across and within three consecutive repetitions of 21 non-averaged trials. In migraine patients the N2-P2 wave amplitudes did not show a tendency toward habituation across and, above all, within the three repetitions. Anomalous behaviour of nociceptive cortex during the interictal phase of migraine may predispose patients to headache occurrence and persistence.

Adult↗

PubMed2005

The comorbidity of migraine and hypertension. A study in a tertiary care headache centre.

Literature data concerning the comorbidity of migraine and hypertension are conflicting and lacking in consistency. This study was designed to evaluate the distribution of hypertension in a sample of migraineurs in comparison with a group of tension type headache (TTH) patients. Hypertension prevalence was more elevated in headache sufferers than in the general population. This finding might be due to a Berkson's bias; in fact individuals seeking medical care often show a high rate of association between two medical conditions which may be independent in the general population. The highest hypertension prevalence was found in patients with TTH, supporting the hypothesis that this type of headache might be based upon vascular mechanisms.

Adult↗

PubMed2005

Tertiary treatment for psychiatric comorbidity in headache patients.

The presence of significant and confounding psychiatric comorbidity is greater in patients attending headache clinics than in headache patients from the general population. The frequent comorbidity of headache with generalized anxiety disorder can take advantage of the administration of benzodiazepines. With regard to depression-related headache, it's wellknown that the antidepressive drugs can improve migraine as well as tension-type headache. Antiepileptic drugs give one more good opportunity. The recognition of a psychiatric comorbidity is mandatory for an accurate management of the patient because prevents the clinicians from using any drug that might be dangerous for a mysdiagnosed psychiatric disturbance and often permits to administer medications that can efficaciously control both headache and psychiatric disorders.

Anxiety Disorders↗

PubMed2005

Soluble adhesion molecules in acute disseminated encephalomyelitis.

Soluble adhesion molecules are overexpressed in neuroinflammatory disorders. Their synthesis parallels that of their membrane-bound counterparts, which modulate lymphocyte transmigration through the blood-brain barrier. Blood-brain barrier cellular migration may be essential in the evolution of postinfectious inflammatory central nervous system disease. The serum levels of soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E-selectin were measured in 12 children with acute disseminated encephalomyelitis and in two control groups (35 healthy and 35 affected by noninflammatory neurologic diseases) of similar age. In patients with acute disseminated encephalomyelitis, soluble E-selectin serum levels were significantly higher (median 113 ng/mL, range 54-144) than in both control groups (median 44, range 31-63, and median 58, range 43-89, respectively; one-way analysis of variance, P < 0.0001); a statistical trend for higher levels of soluble intercellular adhesion molecule-1 was observed in acute disseminated encephalomyelitis subjects, whereas soluble vascular adhesion molecule-1 titers did not differ between the three groups. The specific role played by each of these molecules in lymphocyte extravasation and the differential cytokine modulation of their expression might explain the result. Further larger studies are required including serial measurements and cerebrospinal fluid analysis.

Adolescent↗

PubMed2005

Dopamine fails to regulate activation of peripheral blood lymphocytes from multiple sclerosis patients: effects of IFN-beta.

The neurotransmitter dopamine counteracts T cell functions through its specific receptor subtype D5R but favors T cell proliferation and adhesion when acting on D3R. We found diminished mRNA and protein levels of D5R, but not of D3R, in peripheral blood mononuclear cells (PBMCs) from untreated multiple sclerosis (MS) patients. Dopamine reduced T cell proliferation, secretion of interferon-gamma (IFN-gamma), and production of matrix metalloproteinase-9 (MMP-9) mRNA in PBMCs from controls but not from MS patients. By contrast, reduced levels of D3R and renewed dopamine-associated regulatory functions were found in PBMCs from IFN-beta treated MS patients. Failure of the dopaminergic system of lymphocytes may lessen the threshold of T cell activation and sustain the pathogenic cascade of MS.

Adult↗