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Biomedical subjects

P Pasqualetti

Publications and source records attributed to P Pasqualetti.

At least 37 records · Page 2Linked to original sources

Elevation of serum copper levels in Alzheimer's disease.

OBJECTIVE: To determine whether serum trace metals and oxidative species are related to abnormal cognition in AD. METHODS: The authors studied serum peroxides, copper, iron, transferrin, and antioxidant capacity in 79 patients with AD (mean age 74.3 years; 25 men, 54 women) and in 76 cognitively normal individuals (mean age 70.1 years; 33 men, 43 women). The relation of these oxidative and trace metals to APOE epsilon4 allele frequency, neuropsychological performance, and cerebrovascular or atrophic burden, as estimated by brain MRI and ultrasonography of cerebral vessels, was evaluated. RESULTS: Copper level was higher (p < 0.001) in subjects with AD than control subjects (specificity = 95%, sensitivity = 60%) with a cutoff serum level of 16 micro mol/L (1.02 mg/L). An increase of 1 micro mol/L in serum copper accounted for 80% of the risk of having AD and correlated with poor neuropsychological performance and medial temporal lobe atrophy (p < 0.03). Antioxidant capacity decreased and correlated with medial temporal lobe atrophy (p < 0.009) and with APOE epsilon4 allele (p = 0.004). CONCLUSIONS: Copper may play a role in neurodegenerative processes in AD, and serum copper measurement may prove to be a peripheral diagnostic marker for AD.

Aged↗

A one-year study on the pharmacodynamic profile of interferon-beta1a in MS.

Interferon (IFN)-beta1a induction of neopterin and beta2-microglobulin (beta2-MG) were evaluated over 1 year in patients with MS. Neopterin and beta2-MG levels peaked 24 to 48 hours after weekly injections of IFNbeta1a over the entire study period. Predose levels of neopterin decreased significantly, consistent with a long-term decrease in IFNgamma expression and macrophage activation during IFNbeta-1a treatment. Predose levels of beta2-MG increased, the significance of which is as yet unclear.

Adult↗

Somatosensory processing during movement observation in humans.

OBJECTIVES: A neural system matching action observation and execution seems to operate in the human brain, but its possible role in processing sensory inputs reaching the cortex during movement observation is unknown. METHODS: We investigated somatosensory evoked potentials (SEPs), somatosensory evoked fields (SEFs) and the temporal spectral evolution of the brain rhythms (approximately 10 and approximately 20 Hz) following electrical stimulation of the right median nerve in 15 healthy subjects, during the following randomly intermingled conditions: a pure cognitive/attentive task (mental calculation); the observation of a motoric act (repetitive grasping) with low cognitive content ('Obs-grasp'); and the observation of a complex motoric act (finger movement sequence), that the subject had to recognize later on, therefore reflecting an adjunctive cognitive task ('Obs-seq'). These conditions were compared with an absence of tasks ('Relax') and actual motor performance. RESULTS: The post-stimulus rebound of the approximately 20 Hz beta magnetoencephalographic rhythm was reduced during movement observation, in spite of little changes in the approximately 10 Hz rhythm. Novel findings were: selective amplitude increase of the pre-central N(30) SEP component during both 'Obs-grasp' and 'Obs-seq', as opposed to the 'gating effect' (i.e. amplitude decrease of the N(30)) occurring during movement execution. The strength increase of the 30 ms SEF cortical source significantly correlated with the decrease of the approximately 20 Hz post-stimulus rebound, suggesting a similar pre-central origin. CONCLUSIONS: Changes took place regardless of either the complexity or the cognitive content of the observed movement, being related exclusively with the motoric content of the action. It is hypothesized that the frontal 'mirror neurons' system, known to directly facilitate motor output during observation of actions, may also modulate those somatosensory inputs which are directed to pre-central areas. These changes are evident even in the very first phases (i.e. few tens of milliseconds) of the sensory processing.

Adult↗

d-penicillamine reduces serum oxidative stress in Alzheimer's disease patients.

BACKGROUND: Several lines of evidence address the emerging role for copper in Alzheimer's disease (AD) for sustaining oxidative mechanisms. Studies indicate that peripheral markers of oxidative stress in AD patients could be informative about the pathophysiology of this brain condition. Here, we present a pilot study examining the efficacy of the copper-chelating agent d-penicillamine in reducing oxidative stress in AD patients. DESIGN: Serum levels of copper sampled in AD patients and healthy controls indicate a copper homeostasis imbalance in AD. On this basis, 34 AD patients were enrolled in a 6-month, double-blind, placebo-controlled trial with the copper d-penicillamine-chelating agent. Nine patients for each group completed the trial. Oxidative stress, trace metals and clinical parameters were evaluated. RESULTS: At the start of the study (t0) total peroxides and copper serum content of AD patients were higher (P < 0.0001, P < 0.0001, respectively) and antioxidants were lower (P < 0.05) than in healthy controls. Copper and peroxides were correlated in the AD population (Pearson's r = 0.61, P < 0.001). After treatment with d-penicillamine, the extent of oxidative stress (P < 0.05) was decreased, but no difference was observed in the rate of cognitive decline. CONCLUSION: Data from this pilot study suggest that copper could play a role in the production of peroxides in AD, and that d-penicillamine has an effect in reducing oxidative damage, however, results are still inconclusive in terms of drug efficacy on the clinical progression of AD. Studies with larger cohorts are needed to elucidate the real effectiveness of d-penicillamine treatment in AD.

Aged↗

Carotid artery intima-media thickness and lacunar versus nonlacunar infarcts.

BACKGROUND AND PURPOSE: Increases in the thickness of the intima and media of the carotid artery have been associated with an increased risk of myocardial infarction and stroke in subjects without a history of cardiovascular disease. Lacunar infarcts, one of the most common subtype of ischemic stroke, show unique pathological and clinicoradiological characteristics. The present study examines the relationship between vascular risk factors, including carotid artery intima-media thickness (IMT), and lacunar versus nonlacunar infarcts. METHODS: We collected data from patients with acute ischemic stroke admitted to hospital. Patients and 129 control subjects underwent B-mode ultrasonographic measurements of IMT of the common carotid artery. We examined the association of lacunar and nonlacunar infarcts with age, sex, and potential vascular risk factors. RESULTS: Of 292 adult patients with an acute first-ever ischemic stroke, 96 were considered lacunar and 196 were considered nonlacunar strokes. We did not find a significantly different percentage of diabetes, smoking, hypertension, dyslipidemia, myocardial infarction, and previous transient ischemic attack between the 2 groups of patients. The multinomial logistic regression procedure selected carotid artery IMT and atrial fibrillation as the only independent factors able to discriminate between lacunar and nonlacunar patients. IMT values were significantly higher in patients with nonlacunar stroke versus both those with lacunar stroke and control subjects. CONCLUSIONS: The present results indicate the usefulness of noninvasive measurement of IMT with ultrasonic techniques as a diagnostic tool that may help to identify different subtypes of ischemic stroke patients. The noninvasive measurements may have predictive power with respect to lacunar versus nonlacunar infarcts.

Acute Disease↗

Effects of motor imagery on motor cortical output topography in Parkinson's disease.

BACKGROUND: The motor impairment in Parkinson's disease (PD) could partly reflect a failure to activate processes of motor imagery. OBJECTIVE: To verify any selective changes of motor output during motor imagery, lateralized to the hemisphere contralateral to the clinically affected side of hemiparkinsonian patients. METHODS: Transcranial magnetic stimulation (TMS) was used to map the cortical representations of the contralateral abductor digiti minimi muscle (ADM) during rest, contraction, and motor imagery in a group of patients with hemi-PD and in a group of healthy volunteers. Seven patients with hemi-PD and seven healthy subjects were examined. Focal TMS was applied over a grid of 20 scalp positions on each hemiscalp. Maps were characterized by area (number of excitable positions), volume (the sum of motor evoked potential amplitudes at all scalp positions), and center of gravity (a map position representing an amplitude-weighted calculation of the excitable area). RESULTS: In healthy control subjects, the area of cortical representation of ADM was symmetrically increased in both hemispheres by mental simulation of movement and real muscle contraction. In patients with hemi-PD, there was a hemispheric asymmetry in the area of cortical representation elicited by motor imagery. The area was reduced in the clinically affected hemisphere. The volume of cortical representation was increased under all conditions and in both hemispheres in patients with PD. However, largely because the volume was so high at rest in patients, the increment in volume associated with contraction was smaller than in control subjects. CONCLUSION: This study demonstrates the presence of a tonic hyperactivation of motor cortical circuitry in PD in conjunction with an abnormality of either motor imagery or the process by which motor imagery engages the sensorimotor cortices in the clinically affected hemisphere.

Brain Mapping↗

Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.

OBJECTIVE: To assess the course of untreated carpal tunnel syndrome (CTS). METHODS: The Italian CTS Study Group prospectively followed up (10 to 15 months) 196 untreated patients (274 hands) with idiopathic CTS with multiple measurements of CTS. Baseline factors were used to predict the evolution of untreated CTS in multiple regression analysis. RESULTS: Comparison of baseline and follow-up data showed a significant spontaneous improvement of patient-oriented and neurophysiologic measurements. A significant correlation between evolution and initial severity of CTS was observed. CTS measurements improved in patients with more severe initial impairment whereas they worsened in patients with milder initial impairment. The main positive prognostic factor was short duration of symptoms. Similarly, spontaneous improvement was more frequently associated with young age. Conversely, baseline bilateral symptoms and positive Phalen predicted a poor prognosis. CONCLUSIONS: Some patients with CTS improve spontaneously without surgical treatment.

Adult↗

Interhemispheric differences of sensory hand areas after monohemispheric stroke: MEG/MRI integrative study.

Seventeen clinically stabilized monohemispheric stroke patients were studied in order to investigate the chronic topographical modifications induced on primary sensory cortical hand areas by a monohemispheric stroke within the middle cerebral artery territory. Magnetoencephalographic (MEG) localization of the cortical areas activated following electrical separate stimulation of the median nerve, thumb, and little fingers was integrated with magnetic resonance imaging. Spatial localization of Equivalent Current Dipoles (ECDs) of the short-latency cortical responses generated in primary sensory cortices, "hand area" (distance between 1st and 5th digits ECDs), interhemispheric differences of such parameters, as well as of somatosensory-evoked fields waveshapes were investigated and compared with a control population. Lesions involving the cortico-subcortical areas receiving sensory input from the hand induced excessive asymmetry of MEG spatial parameters and response morphology between the unaffected (UH) and the affected hemisphere (AH). "Hand area" was significantly larger on AH in 20% of cases after a subcortical, and in 13% after a cortical, lesion. Responses from AH were excessively delayed in 20% ECDs. Interhemispheric ECDs strength differences were larger than normal in 25% of cases after both types of lesions; the strength in the AH being enlarged after all cortical, and only 24% of subcortical strokes. In a significant percentage of monohemispheric strokes, excessive interhemispheric differences were found between AH and UH, suggesting that brain areas outside the normal boundaries and usually not reached by a dense sensory input from the opposite hand and fingers may act as somatosensory "hand" centers. Correlation analysis between clinical outcome and cortical reorganization in the AH suggests that this mechanism is linked with hand sensorimotor recovery.

Aged↗

Urinary N-acetyl-beta-D-glucosaminidase concentration in patients with spinal cord injury: relationship with urodynamic parameters.

OBJECTIVES: To investigate the relationships between urinary N-acetyl-beta-D-glucosaminidase (NAG) concentrations and urodynamic parameters in patients with spinal cord injury (SCI). NAG has been proposed as a marker of renal damage. METHODS: Twenty-three patients with SCI were evaluated with urodynamic studies. Urine samples were collected from the 23 patients and 10 healthy volunteers, the NAG levels were evaluated, and the urodynamic parameters were compared with the urinary NAG levels. The patients were divided into two groups according to the amplitude of the hyperreflexic detrusor contractions (HDCs): group A, patients with an HDC amplitude of 40 cm H(2)O or greater, and group B, patients with an HDC amplitude of less than 40 cm H(2)O; group C was composed of healthy volunteers. The urinary NAG concentrations in the three groups were compared. RESULTS: A positive correlation was found between the urinary NAG levels and the HDC amplitude and detrusor leak point pressure (P = 0.015 and 0.007, respectively). The urinary NAG concentration was 3.38 U/g in group A, 2.14 U/g in group B, and 2.12 U/g in group C. The differences in the urinary NAG concentrations between groups A and B and between groups A and C were statistically significant (P = 0.03 and P <0.001, respectively). The concentrations between groups B and C were comparable. CONCLUSIONS: In our experience, the only urodynamic parameters that clearly and positively correlated with the urinary NAG levels were those expressing the amplitude of intravesical pressure. This result stresses the importance of reducing the intravesical pressure in patients with SCI using alternative treatments or surgical procedures if the usual conservative therapies are not effective.

Acetylglucosaminidase↗

Attitude towards psychiatric patients: a pilot study in a northern Italian town.

The stigmatisation of the psychiatric patient is still a strong barrier to the integration process of these subjects in our society. Therefore, it is necessary to identify what types of prejudices exist and the types of variables with which they are linked, in order to plan strategies to reduce them. In this exploratory study we administered a semi-structured interview to 303 subjects in order to examine the relationships between social attitudes towards mental disorders and some social demographic variables, the information about mental disorders and the previous 'contacts' with psychiatric patients. The data analysis shows that there is a relationship between knowledge of psychiatric patients and a more positive attitude towards them (i.e., less fear, more integration and work opportunities). This study is to be considered preliminary as far as people's attitudes towards psychiatric patients are concerned. This result encourages the planning and implementation of sensitisation and information programs concerning mental disorders, in the sense that increasing the knowledge of mental disorders could lead to significant achievements in the important fight against the stigma surrounding psychiatric patients.

Adolescent↗

Prefrontal [correction of Prefontal] cortex in long-term memory: an "interference" approach using magnetic stimulation.

Neuroimaging has consistently shown engagement of the prefrontal cortex during episodic memory tasks, but the functional relevance of this metabolic/hemodynamic activation in memory processing is still to be determined. We used repetitive transcranial magnetic stimulation (rTMS) to transiently interfere with either left or right prefrontal brain activity during the encoding or retrieval of pictures showing complex scenes. We found that the right dorsolateral prefrontal cortex (DLPFC) was crucial for the retrieval of the encoded pictorial information, whereas the left DLPFC was involved in encoding operations. This 'interference' approach allowed us to establish whether a cortical area activated by a memory task actually contributes to behavioral performance.

Adult↗

Effect of collateral blood flow and cerebral vasomotor reactivity on the outcome of carotid artery occlusion.

BACKGROUND AND PURPOSE: Evidence suggests that an alteration in cerebral hemodynamics plays a relevant role in the occurrence of stroke in patients with carotid occlusion. The purpose of the present study was to evaluate the relationships among baseline characteristics, type and number of collateral pathways, cerebral vasomotor reactivity (VMR), and outcome of patients with carotid occlusion. METHODS: One hundred four patients with symptomatic or asymptomatic internal carotid artery occlusion were followed up prospectively for a median period of 24 months. Cerebral VMR to apnea was calculated with transcranial Doppler ultrasonography by means of the breath-holding index (BHI) in the middle cerebral arteries. The patency of the 3 major intracranial collateral vessels was also evaluated. RESULTS: During the follow-up period, 18 patients experienced an ischemic stroke ipsilateral to internal carotid artery occlusion. Among factors considered, only older age, number of collateral pathways, and BHI values in the middle cerebral artery ipsilateral to the occluded side were significantly associated with the risk of ipsilateral stroke (P<0.001, P=0.008, and P<0.001, respectively; multiple Cox regression analysis). A normal VMR and favorable prognosis characterized patients with full collateral development; in this group, no patient experienced an ischemic event. On the other hand, an impaired VMR and increased probability of experiencing a stroke were found in patients without collateral pathways; the annual risk of ipsilateral stroke in this group was 32.7%. Patients with 1 or 2 collateral pathways showed a different VMR ranging from normal to strongly reduced BHI values. The ipsilateral stroke event risk was 17.5% in patients with 1 collateral vessel and 2.7% in patients with 2 collateral pathways. In this case, the risk of cerebrovascular events occurring during the follow-up period was significantly related to VMR. CONCLUSIONS: These data suggest that cerebral hemodynamic status in patients with carotid occlusive disease is influenced by both individual anatomic and functional characteristics. The planning of strategies to define the risk profile and any attempt to influence patients' outcome should be based on the evaluation of the intracranial hemodynamic adaptive status, with particular attention to the number of collateral vessels and the related VMR.

Aged↗

Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine.

Previous studies suggest that aminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. Although the mechanism underlying the beneficial effect on fatigue remains unclear, it has been proposed that aminopyridines may help to improve conduction in demyelinated central pathways, implicating both axonal and synaptic mechanisms. The objective of the present study is to determine whether 4-AP decreases daily-living fatigue in progressive multiple sclerosis. The effect of 4-AP on other neurophysiological and neuropsychological parameters was also considered. A 'double-blind', randomized, 'placebo-controlled', crossover trial was conducted on 54 patients with progressive multiple sclerosis. All patients received treatment with placebo and 32 mg per day of 4-AP, each for 6 months. The main outcome measure was the Fatigue Severity Scale. Secondary measures were EDSS, cognitive functions and neurophysiological parameters. Forty-nine patients (91%) completed the study. Changes in fatigue scores, EDSS and cognitive functions were not significantly different between 4-AP and placebo. However, when patients treated with 4-AP were divided into two groups according to the serum level of 4-AP, a significant effect on fatigue compared with placebo was observed in the 'high level' (>30 ng/ml) group (P=0.05). Synchronization of motor evoked potentials improved during 4-AP with respect to placebo (P=0.019) and this correlated positively with fatigue reduction (P=0.010). No relevant side effects were observed.

4-Aminopyridine↗

Cerebral hemodynamics in patients with carotid artery occlusion and contralateral moderate or severe internal carotid artery stenosis.

OBJECT: The purpose of this study was to evaluate cerebral hemodynamics in patients suffering from occlusion of the carotid artery (CA) and contralateral CA stenosis. METHODS: Using transcranial Doppler ultrasonography, the cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was evaluated by calculating the breath-holding index (BHI) of 69 symptomatic patients suffering from internal CA (ICA) occlusion and moderate or severe contralateral ICA stenosis. To evaluate which variables influenced BHIs ipsilateral to the site of ICA occlusion, a multiple stepwise linear regression analysis was performed that included the following factors: patient age, percentage of contralateral ICA stenosis, contralateral BHI, number of collateral pathways, and presence of hypertension, diabetes, smoking, and hyperlipidemia. An analysis of variance was conducted to evaluate the impact of the type of collateral vessels on the BHI. A regression analysis showed that the BHI ipsilateral to the site of ICA occlusion could be accounted for by the contralateral BHI (which was entered at the first step of the analysis, p < 0.001) and by the number of collateral pathways (which was entered at the second step, p = 0.033). Neither the degree of contralateral ICA stenosis nor the other variables could be added to improve the model. The analysis demonstrated that the absence of collateral pathways and the presence of the anterior communicating artery (ACoA) alone were associated with lower BHI values than those found in the presence of two or three collateral vessels, regardless of the presence of an anterior collateral pathway. CONCLUSIONS: On the basis of these data one can infer that the cerebral hemodynamic status of patients with occlusive disease of the CA is influenced by individual anatomical and functional characteristics. Because improvement in contralateral hemodynamics after surgical correction of an ICA stenosis can only be expected in the presence of an ACoA, the planning of strategies for influencing cerebral blood flow distal to an ICA occlusion and, in particular, the consideration of a contralateral carotid endarterectomy, should be preceded by a careful evaluation of the intracranial hemodynamic adaptive status of the patient. Particular attention should be paid to cerebrovascular reactivity and the number and type of collateral vessels that are present.

Aged↗

Botulinum toxin type-A treatment in spastic paraparesis: a neurophysiological study.

OBJECTIVE: The aim of this study was to verify the action of Botulinum toxin type-A (BoNT-A) by means of neurophysiological techniques, in patients presenting lower limb spasticity and requiring BoNT-A injections in the calf muscles, due to the poor response to medical antispastic treatment. SUBJECTS AND METHOD: Patients presenting paraparesis were enrolled. They underwent clinical evaluation for spasticity according to the Ashworth scale and neurophysiological recordings including: motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the leg area; compound motor action potential (cMAP) to tibial nerve stimulation, F-wave, and H-reflex before the treatment and 24 h, 2 weeks and 1 month after the injection of BoNT-A. In all patients, gastrocnemius was treated and in some cases soleus or tibialis posterior muscles were also injected. RESULTS: In all patients, BoNT-A injections induced a clear clinical improvement as showed by the reduced spasticity values of the Ashworth scale. A significant increment of MEP latency and central conduction time (CCT) duration were observed 2 weeks after the treatment only in the injected muscles. CONCLUSIONS: Prolonged MEP latencies and CCT after BoNT-A injections is probably due to a central alteration in responsiveness of spinal motor neurons to descending impulses from the corticospinal tracts. Such changes represent objective parameters heralding clinical efficacy of treatment.

Adult↗

Paired transcranial magnetic stimulation protocols reveal a pattern of inhibition and facilitation in the human parietal cortex.

Intracortical inhibition (ICI) and facilitation (ICF) of the human motor cortex can be induced by paired transcranial magnetic stimulation (TMS). Although demonstrated in experimental animals, the existence of intracortical inhibitory and excitatory circuits in parietal sensory cortex has not been documented in humans. The aim of this study was to investigate the effects of paired TMS of the parietal cortex on contralateral tactile perception. Fifteen healthy subjects were involved in a task of discrimination of electrical stimuli delivered at near-threshold intensity of sensory perception over the left thumb. Paired TMS was delivered with a focal coil on the right posterior parietal lobe after various delays from the presentation of finger stimuli. The effects of different interstimulus intervals (ISI: 1, 3, 5, 7, 10 and 15 1 1 Bms1B) between the conditioning and the test TMS stimulus on tactile perception were studied. The conditioning stimulus intensity was set at 70 % of motor threshold, while test TMS intensity was 130 % of motor threshold. Single pulse suprathreshold TMS interfered with the perception of finger stimuli, while subthreshold stimuli such as the 'conditioning' stimuli had no effect on sensory perception. Paired TMS differentially influenced the performance depending on the ISI. At an ISI of 1 1 1 Bms1B, paired TMS stimuli induced a significant worsening of the performance compared with single pulse TMS; at an ISI of 5 1 1 Bms1B, paired TMS stimuli induced a significant facilitation of the performance compared with single pulse TMS, restoring baseline performance levels. These results suggest that paired TMS can reveal a selective pattern of ICI and ICF in the human parietal cortex.

Adult↗

Are autonomic signals influencing cortico-spinal motor excitability? A study with transcranial magnetic stimulation.

In order to investigate the role of visceral afferent inputs flowing along autonomic fibers on corticospinal tract excitability, the variability of Motor Evoked Potentials (MEPs), elicited by Transcranial Magnetic Stimulation (TMS), was analysed during simultaneous monitoring of electrocardiogram (EKG) phases, breathing phases and sudomotor skin responses (SSRs) in a group of 10 healthy subjects. A cascade of at least 60 consecutive magnetic stimuli, with an interstimulus interval randomly varying between 20 and 40 s, was acquired. At the end of the recording session, the subject was asked to make at random five not consecutive self-paced forced inspirations. TMS was carried out at an intensity 10% above motor threshold excitability via a circular coil placed over the motor area of the right hemisphere. MEPs were recorded from the contralateral abductor digiti minimi muscle (ADM). Sudomotor Skin Responses (SSRs) were recorded on both hand palms. MEPs latency and amplitude did not show significant correlation with any of the EKG and respiratory phases. During forced inspiration, a significant latency shortening was found. TMS elicited SSRs, whose amplitudes were not correlated with MEP parameters. During forced inspiration a significant SSR amplitude increment, not correlated with MEP latency shortening, was also observed. These results assign a minor if any role to the considered autonomic parameters in modulating corticospinal motor excitability.

Adult↗