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Biomedical subjects

P Pasqualetti

Publications and source records attributed to P Pasqualetti.

At least 19 recordsLinked to original sources

Conversion from mild cognitive impairment to Alzheimer's disease is predicted by sources and coherence of brain electroencephalography rhythms.

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Aged↗

Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau.

OBJECTIVE: To assess whether serum copper in Alzheimer disease (AD) correlates with cognitive scores, beta-amyloid, and other CSF markers of neurodegeneration. METHODS: The authors studied copper, ceruloplasmin, total peroxide, and antioxidants levels (TRAP) in serum; beta-amyloid in plasma; and copper, beta-amyloid, h-tau, and P-tau in the CSF of 28 patients with AD and 25 healthy controls, in relation to clinical status. RESULTS: Serum copper (p < 0.0001), peroxides (p = 0.002), a copper fraction unexplained by ceruloplasmin (p < 0.0001), and CSF h-tau (p = 0.001) were increased in AD, whereas serum TRAP (p = 0.03) and CSF beta-amyloid were decreased (p < 0.0001). Plasma beta-amyloid increased with age in healthy controls (r = 0.6; p = 0.05). CSF markers of AD correlated with serum copper variables. CSF copper was partially dependent on the serum copper fraction unexplained by ceruloplasmin (t = 2.2, p = 0.04). CSF beta-amyloid seemed to be related to serum copper (r = -0.46; p = 0.002). Mini-Mental Status Examination scores correlated positively with beta-amyloid (r = 0.46, p = 0.002) and inversely with copper unexplained by ceruloplasmin (r = -0.45, p = 0.003). CONCLUSIONS: The authors' results confirm the existence of changes in copper component distribution, particularly the copper fraction unexplained by ceruloplasmin and support the hypothesis of a beta-amyloid and copper connection in Alzheimer disease.

Aged↗

Maternal total vascular resistance and concentric geometry: a key to identify uncomplicated gestational hypertension.

OBJECTIVE: To evaluate the prognostic impact of elevated total vascular resistance (TVR) on the outcome of pregnancy in early mild gestational hypertension (EMGH). DESIGN: Prospective observational study. SETTING: Data collected from women with EMGH referred to the obstetrics outpatient clinic of Tor Vergata University from June 2003 to June 2005. POPULATION: A total of 268 women with EMGH (systolic and diastolic blood pressure [BP] 140-150 mmHg and 90-99 mmHg, respectively, without significant proteinuria). METHODS: Women had a maternal echocardiographic examination and BP examination within 24 hours of diagnosis. From this, the TVR was calculated and the geometric pattern of the left ventricle assessed. MAIN OUTCOME MEASURES: Fetal/maternal adverse outcomes (pre-eclampsia, preterm delivery, placental abruption, other maternal medical problems, fetal distress, neonatal low birthweight, admittance to neonatal intensive care unit and perinatal death). RESULTS: Ninety-two out of the 268 pregnancies showed adverse outcomes (34.3%). The best independent predictor for the composite of maternal and fetal complications was TVR (OR 64.4, 95% CI 25.9-160.1). The cutoff value was 1340 dyn seconds/cm(5) with a sensitivity and a specificity of 90 and 91%, respectively. Concentric geometry of the left ventricle was also an independent predictor (OR 4.72, 95% CI 1.85-12.04). CONCLUSIONS: Echocardiography could help in identifying women with EMGH who subsequently develop maternal and fetal complications, allowing a classification in high-risk (TVR > 1340 dyn seconds/cm(5), concentric geometry of the left ventricle) and low-risk women (TVR < 1340 dyn seconds/cm(5), nonconcentric geometry of the left ventricle) for adverse outcomes of pregnancy.

Abruptio Placentae↗

Long-term effects of stroke on neuronal rest activity in rolandic cortical areas.

To understand the relationship between neuronal function and clinical state in the framework of stroke, the long-term poststroke rolandic spontaneous neuronal activity was studied by means of magnetoencephalography. Fifty-six patients who had suffered a unilateral stroke within the middle cerebral artery were enrolled. Median time since stroke was 2.8 years. In association with lesion features and clinical picture, total and relative band powers and the spectral entropy were analyzed in the affected (AH) and unaffected (UH) hemispheres in comparison with an age-matched control group. An increase of absolute and relative slow band powers and a reduction of relative fast band powers were found in patients' AH with respect to both UH and control values. Absolute delta band was higher than in controls also in UH. New findings were the increase of rolandic rest activity power also in the alpha band and the decrease of spectral entropy in AH with respect to both UH and control values. Moreover, our results in chronic stroke patients indicate frequency-selective alterations related to specific dysfunctions: global clinical status was mostly impaired in patients with larger lesions and increased total and slow band activity powers, whereas hand functionality was mostly disrupted in patients with subcortical involvement and reduction of high-frequency rhythms and spectral entropy. Total power increase and spectral richness decrease are in agreement with a higher synchrony of local neuronal activity, a reduction of the intracortical inhibitory network's efficiency, and an increase of neuronal excitability.

Adolescent↗

Alexithymia in Parkinson's disease is related to severity of depressive symptoms.

The authors investigated the possible relationship between depression and alexithymia in a population of hospitalized patients suffering from Parkinson's disease (PD). Fifty-eight PD patients without dementia participated in the study. Alexithymia was screened using the 20 item version of the Toronto Alexithymia Scale (TAS 20). Depression was diagnosed using a Structured Clinical Interview (SCID I) for DSM-IV. Severity of depression was evaluated with the Beck Depression Inventory (BDI). The prevalence of Alexithymia was about 21%. PD patients with major depression were significantly more alexithymic (TAS 20 average score = 61.4) than PD patients without depression (TAS 20 average score = 47.4) and, also, tended to be more alexithymic than PD patients with minor depression (MiD; TAS 20 average score =50.6), whereas no difference was found between PD patients with MiD and PD patients without depression. Moreover, high scores obtained on the BDI were found to strongly predict high level of alexithymia in these patients. These results extend to a cohort of PD patients previous data from the literature evidencing a strong association between alexithymia and severity of depressive symptoms.

Affective Symptoms↗

Cerebral blood flow velocity changes during meaningful and meaningless gestures--a functional transcranial Doppler study.

The aim of the study was to use functional transcranial Doppler to investigate the possibility of revealing different activation patterns during healthy subjects' performance of meaningful and meaningless actions. Mean flow velocity (MFV) changes were recorded in middle cerebral arteries (MCAs) of 26 normal subjects during a rest phase and during performance of meaningful and meaningless actions. The meaningful task consisted of pouring sugar into a cup with a teaspoon. The meaningless action was an arm movement similar to that necessary for pouring sugar in a cup but without any tool and thus without a goal. Performing actions with or without meaning was associated with different patterns of MFV changes, as documented by the triple interaction condition x performing arm x side of recording [F(1, 25)=10.977; P=0.003]. During the meaningful action, MFV in MCAs increased significantly more than during the meaningless action. During the meaningless action, the MFV increase was significantly higher in the contralateral than in the ipsilateral MCA to the arm performing the task and the meaningful action determined a bilateral MFV increase only when the task was performed with the left arm. When the same task was performed with the right arm, the MFV increase was significantly higher in the contralateral than in the ipsilateral MCA. These findings suggest that the content of an action can influence MFV changes and further confirm the usefulness of transcranial Doppler in neuropsychological investigation.

Adult↗

Major and minor depression in Parkinson's disease: a neuropsychological investigation.

Previous studies have failed to distinguish the differential contribution of major and minor depression to cognitive impairment in patients with idiopathic Parkinson's disease (PD). This study was aimed at investigating the relationships among major depression (MD), minor depression (MiD) and neuropsychological deficits in PD. Eighty-three patients suffering from PD participated in the study. MD and MiD were diagnosed by means of a structured interview (SCID-I) based on the DSM-IV criteria, and severity of depression was evaluated by the Beck Depression Inventory. For the neuropsychological assessment, we used standardized scales that measure verbal and visual episodic memory, working memory, executive functions, abstract reasoning and visual-spatial and language abilities. MD patients performed worse than PD patients without depression on two long-term verbal episodic memory tasks, on an abstract reasoning task and on three measures of executive functioning. The MiD patients' performances on the same tests fell between those of the other two groups of PD patients but did not show significant differences. Our results indicate that MD in PD is associated with a qualitatively specific neuropsychological profile that may be related to an alteration of prefrontal and limbic cortical areas. Moreover, the same data suggest that in these patients MiD and MD may represent a gradual continuum associated with increasing cognitive deficits.

Aged↗

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.

Adult↗

Excess of serum copper not related to ceruloplasmin in Alzheimer disease.

OBJECTIVE: To assess the role of serum copper in relation to ceruloplasmin and other peripheral markers of inflammation in Alzheimer disease (AD). METHODS: The authors studied serum levels of copper, ceruloplasmin, and transferrin, as well as total peroxides, antioxidants, and other peripheral markers of inflammation in 47 patients with AD, 24 patients with vascular dementia (VaD), and 44 healthy controls. Biochemical variables were related to the patients' and controls' clinical status. RESULTS: The authors found that copper (p < 0.001), peroxides (p = 0.026), and ceruloplasmin (p = 0.052) were increased and TRAP was decreased (p = 0.006) in patients with AD, while no other markers of inflammation were altered. The calculation of the ratio between copper and ceruloplasmin suggested the presence in the serum of AD patients, but not of VaD or normal controls, of a large pool of non-ceruloplasmin-bound copper. CONCLUSIONS: Changes in the distribution of the serum copper components, consisting of an increase of a copper fraction not explained by ceruloplasmin, seem to be characteristic of Alzheimer disease and may be implicated in the pathogenesis of the disease.

Aged↗

Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: an efficacious therapy for major drug-resistant depression?

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is proposed for the treatment of drug-resistant depression. Studies performed in accordance with evidence-based medicine (EBM) are scarce, particularly in seeking optimal treatment and evaluation parameters. We aimed to test various types of rTMS in a large sample of depressed patients following EBM rules and to investigate treatment-related changes in plasma levels of neurotransmitters involved in depression. METHODS: Seventy-one drug-resistant depressed patients were randomly assigned to low (1 Hz) or high (17 Hz) rate TMS, applied for 5 days over the left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two study designs. One group (20 patients) received only active treatment, while the other entered a double-blind, placebo-controlled, crossover design. Pre- and post-treatment blood samples were taken for evaluation of plasma levels of dopamine and serotonin. RESULTS: After a week of treatment patients had a measurable benefit. However, overall the placebo stimulation did not differ significantly from real stimulation, nor were differences observed between the two rates of rTMS. The only difference emerged when the real stimulation was applied at 17 Hz following placebo treatment. Plasma levels of neurotransmitters between active and placebo rTMS were similar. CONCLUSIONS: Using the treatment schedule of 1 week, although a clinical improvement after active treatment was indeed observed, this was both clinically and biochemically indistinguishable from that seen in the placebo arm. SIGNIFICANCE: This suggests that most of the previous emphasis, for short period of treatment, should be tempered down and that further work is required in order to verify whether optimal stimulation and evaluation parameters for TMS-treatment of depression beyond the placebo effect may be found following EBM rules.

Adult↗

Monthly brain magnetic resonance imaging scans in patients with clinically isolated syndrome.

We investigated if monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can assist the clinician in anticipating the diagnosis of multiple sclerosis (MS) in the very first few months following a clinically isolated syndrome (CIS). A consecutive series of CIS patients with > or = 3 T2-weighted (T2W) hyperintense brain MRI lesions suggestive of MS were followed up for the first six consecutive months after enrollment with monthly triple-dose Gd-enhanced brain MRI scan. MRI conversion to MS was defined by the presence of either > or = 1 new Gd-enhancing lesion or > or = 1 new T2W lesions in the subsequent MRI scan. Sixty patients were included. Of them, 30 (50%) had at least one Gd-enhancing lesion on the baseline MRI scan. After three months, MRI conversion to MS was observed in 80% and 62% of patients based on the appearance of > or = 1 new T2 lesion and > or = 1 new Gd-enhancing lesions, respectively. The presence of > or = 1 new T2W lesion was observed in 90% and 82% of patients who had, at baseline, a Gd-positive MRI scan and dissemination in space based on the new McDonald's criteria, respectively The rate of MRI conversion remained almost stable in the last two MRI scans. Our study suggests that the majority of CIS patients with an abnormal baseline scan showed an MRI conversion to MS after three months. The model of six months as the optimal interval for repeating MRI exam is not supported by the present data.

Brain↗

Changes in motor cortex excitability in facioscapulohumeral muscular dystrophy.

Previous studies found that some patients with severe, early onset facioscapulohumeral muscular dystrophy (FSHD) present epilepsy and mental retardation. This suggests a functional involvement of central nervous system in severe FSHD. It is unknown whether minor functional changes of central nervous system are also present in less severe forms of FSHD. To investigate this, we examined the excitability of neuronal networks of the motor cortex with a range of transcranial magnetic stimulation paradigms in 20 FSHD patients with heterogeneous clinical severity and compared the data with that from 20 age-matched healthy individuals and from 6 age-matched patients with other muscle diseases. There was significantly less intracortical inhibition in FSHD patients (mean responses +/- SD reduced to 58.1+/-43.5% of the test size) than in controls (mean responses +/- SD reduced to 29.3+/-13.5% of the test size; P=0.025) and in patients with other muscle diseases (mean responses +/-SD, reduced to 30.6+/-11.7% of the test size; P=0.046). No significant difference was found between the control group and patients with other muscle diseases (P=0.970).

Adolescent↗

Delayed administration may improve entacapone effects in parkinsonian patients non-responding to the drug.

BACKGROUND: Entacapone is a COMT inhibitor used in Parkinson's disease (PD) patients, as an adjunctive therapy to L-dopa in order to prolong its bioavailability and thus its clinical effect. However, previous studies reported entacapone-induced L-dopa to have lower C(max) and delayed t(max) values, coupled with a delayed onset of the clinical effect, possibly suggesting an interference between the two drugs. The aim of our study was to evaluate whether a delayed entacapone administration in association with standard L-dopa/carbidopa, may in some subjects improve the entacapone effects on L-dopa AUC and thus on the clinical 'on time' duration. METHODS: Twenty-eight idiopathic advanced PD patients were blindly evaluated in three different test days, following administration of carbidopa/L-dopa or carbidopa/L-dopa plus co-administered entacapone or plus entacapone administered with 30 min of delay. RESULTS: The AUC, the 'on time' and UPDRS score of the whole group were improved by both modalities of entacapone administration. An ex post analysis showed that the delayed entacapone administration produced a significant improvement in a subgroup of 10 non-responding patients to the co-administration. CONCLUSION: We suggest that the delayed administration should be attempted in the subjects not improved by entacapone co-administration.

Aged↗

Gross morphology and morphometric sequelae in the hippocampus, fornix, and corpus callosum of patients with severe non-missile traumatic brain injury without macroscopically detectable lesions: a T1 weighted MRI study.

OBJECTIVE: The gross morphology and morphometry of the hippocampus, fornix, and corpus callosum in patients with severe non-missile traumatic brain injury (nmTBI) without obvious neuroradiological lesions was examined and the volumes of these structures were correlated with performance on memory tests. In addition, the predictability of the length of coma from the selected anatomical volumes was examined. METHOD: High spatial resolution T1 weighted MRI scans of the brain (1 mm3) and neuropsychological evaluations with standardised tests were performed at least 3 months after trauma in 19 patients. RESULTS: In comparison with control subjects matched in terms of gender and age, volume reduction in the hippocampus, fornix, and corpus callosum of the nmTBI patients was quantitatively significant. The length of coma correlated with the volume reduction in the corpus callosum. Immediate free recall of word lists correlated with the volume of the fornix and the corpus callosum. Delayed recall of word lists and immediate recall of the Rey figure both correlated with the volume of the fornix. Delayed recall of the Rey figure correlated with the volume of the fornix and the right hippocampus. CONCLUSION: These findings demonstrate that in severe nmTBI without obvious neuroradiological lesions there is a clear hippocampal, fornix, and callosal volume reduction. The length of coma predicts the callosal volume reduction, which could be considered a marker of the severity of axonal loss. A few memory test scores correlated with the volumes of the selected anatomical structures. This relationship with memory performance may reflect the diffuse nature of the damage, leading to the disruption of neural circuits at multiple levels and the progressive neural degeneration occurring in TBI.

Adult↗

Ketamine increases human motor cortex excitability to transcranial magnetic stimulation.

Subanaesthetic doses of the N-methyl-D-aspartate (NMDA) antagonist ketamine have been shown to determine a dual modulating effect on glutamatergic transmission in experimental animals, blocking NMDA receptor activity and enhancing non-NMDA transmission through an increase in the release of endogenous glutamate. Little is known about the effects of ketamine on the excitability of the human central nervous system. The effects of subanaesthetic, graded incremental doses of ketamine (0.01, 0.02 and 0.04 mg kg-1 min-1, I.V.) on the excitability of cortical networks of the human motor cortex were examined with a range of transcranial magnetic and electric stimulation protocols in seven normal subjects. Administration of ketamine at increasing doses produced a progressive reduction in the mean resting motor threshold (RMT) (F(3, 18) = 22.33, P < 0.001) and active motor threshold (AMT) (F(3, 18) = 12.17, P < 0.001). Before ketamine administration, mean RMT +/- S.D. was 49 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 42.6 +/- 2.6 % (P < 0.001). Before ketamine administration, AMT +/- S.D. was 38 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 33 +/- 4.4 % (P < 0.002). Ketamine also led to an increase in the amplitude of EMG responses evoked by magnetic stimulation at rest; this increase was a function of ketamine dosage (F(3, 18) = 5.29, P = 0.009). In contrast to responses evoked by magnetic stimulation, responses evoked by electric stimulation were not modified by ketamine. The differential effect of ketamine on responses evoked by magnetic and electric stimulation demonstrates that subanaesthetic doses of ketamine enhance the recruitment of excitatory cortical networks in motor cortex. Transcranial magnetic stimulation produces a high-frequency repetitive discharge of pyramidal neurones and for this reason probably depends mostly on short-lasting AMPA transmission. An increase in this transmission might facilitate the repetitive discharge of pyramidal cells after transcranial magnetic stimulation which, in turn, results in larger motor responses and lower thresholds. We suggest that the enhancement of human motor cortex excitability to transcranial magnetic stimulation is the effect of an increase in glutamatergic transmission at non-NMDA receptors similar to that described in experimental studies.

Adult↗

Prescription practices of diagnostic imaging in dementia: a survey of 47 Alzheimer's Centres in Northern Italy.

BACKGROUND: To date, there are no data at the national or European level on the prescription practices of imaging (CT, MR, and SPET) in the diagnosis of cognitively impaired elderly patients. METHODS: We addressed prescription practices of diagnostic imaging in 47 Alzheimer's Centres in Northern Italy, with an ad-hoc questionnaire. RESULTS: The use of imaging in new cases was relatively intensive: 62% of the Alzheimer's Centres prescribed CT to more than 95% of cases, 24% prescribed MR to more than 33% of cases, and 33% prescribed SPET to more than 5% of cases. A minority of Alzheimer's Centres (n = 3, 6%) prescribed imaging to less than 100% of new cases. The association between onsite scanner availability and frequency of prescription increased from CT (Odds ratio (OR) = 1.8) through MR (OR = 2.4) to SPET (OR = 4.6), although only the latter was significant (95% confidence interval (CI) 1.2-17.7, p = 0.003). Patient-related factors (age, severity of cognitive impairment, and clinical suspicion of cerebrovascular disease) influenced prescription of structural imaging in 30-53% of Alzheimer's Centres and organizational factors (onsite scanner availability, and waiting list) in a similar proportion (32 and 43% respectively). CONCLUSIONS: Organizational factors play a relevant role in the prescription of imaging exams in patients with cognitive impairment and, at least for CT, the perceived diagnostic added value is rather low, suggesting a high degree of uncertainty in the clinical use of imaging techniques.

Dementia↗

Carpal tunnel syndrome in pregnancy: multiperspective follow-up of untreated cases.

In a follow-up of carpal tunnel syndrome (CTS) after pregnancy, the Italian CTS Study Group prospectively studied 63 pregnant women with multiple measurements of CTS symptoms. Fifty-four percent of women with CTS symptoms during pregnancy had symptoms 1 year later. Patients with onset of CTS symptoms early during pregnancy are less likely to improve after delivery.

Adult↗