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Background: The aim of this study was to investigate if the supplementation with Opuntia ficus-indica (OFI) juice may affect plasma redox balance and heart rate variability (HRV) parameters following a maximal effort test, in young physically active women. Methods: A randomized, double blind, placebo controlled and crossover study comprising eight women (23.25 ± 2.95 years, 54.13 ± 9.05 kg, 157.75 ± 0.66 cm and BMI of 21.69 ± 0.66 kg/m2) was carried out. A juice containing OFI diluted in water and a Placebo solution were supplied (170 ml; OFI = 50 ml of OFI juice + 120 ml of water; Placebo = 170 ml beverage without Vitamin C and indicaxanthin). Participants consumed the OFI juice or Placebo beverage every day for 3 days, before performing a maximal cycle ergometer test, and for 2 consecutive days after the test. Plasma hydroperoxides and total antioxidant capacity (PAT), Skin Carotenoid Score (SCS) and HRV variables (LF, HF, LF/HF and rMSSD) were recorded at different time points. Results: The OFI group showed significantly lower levels of hydroperoxides compared to the Placebo group in pretest, post-test and 48-h post-test. PAT values of the OFI group significantly increased compared to those of the Placebo group in pre-test and 48-h post-test. SCS did not differ between groups. LF was significantly lower in the OFI group 24-h after the end of the test, whereas rMSSD was significantly higher in the OFI group 48-h post-test. Conclusion: OFI supplementation decreased the oxidative stress induced by intense exercise and improved autonomic balance in physically active women. more...

Background: Eryptosis is a physiological, apoptosis-like death of injured erythrocytes crucial to prevent premature haemolysis and the pathological sequalae generated by cell-free haemoglobin. When dysregulated, the process is associated to several inflammatory-based pathologies. 4-Hydroxy-trans-2-nonenal (HNE) is an endogenous signalling molecule at physiological levels and, at higher concentrations, is involved in the pathogenesis of several inflammatory-based diseases. This work evaluated whether HNE could induce eryptosis in human erythrocytes. Methods: Measurements of phosphatidylserine, cell volume, intracellular oxidants, Ca++, glutathione, ICAM-1, and ceramide were assessed by flow cytometry. Scanning electron microscopy evaluated morphological alterations of erythrocytes. Western blotting assessed caspases. PGE2 was measured by ELISA. Adhesion of erythrocytes on endothelial cells was evaluated by gravity adherence assay. Results: HNE in the concentration range between 10&ndash, 100 &micro, M induces eryptosis, morphological alterations correlated to caspase-3 activation, and increased Ca++ levels. The process is not mediated by redox-dependent mechanisms, rather, it strongly depends on PGE2 and ceramide. Interestingly, HNE induces significant increase of erythrocytes adhesion to endothelial cells (ECs) that are in turn dysfunctionated as evident by overexpression of ICAM-1. Conclusions: Our results unveil a new physiopathological role for HNE, provide mechanistic details of the HNE-induced eryptosis, and suggest a novel mechanism through which HNE could exert pro-inflammatory effects. more...

Cigarette smoking has been linked with oxidative stress and inflammation. In turn, eryptosis, the suicidal erythrocyte death similar to apoptosis that can be triggered by oxidative stress, has been associated with chronic inflammatory diseases including atherosclerosis. However, the link between smoking and eryptosis has not been explored so far. The aim of the present study was to determine the level of eryptotic erythrocytes in healthy male smokers (n = 21) compared to non-smokers (n = 21) and assess its relationship with systemic inflammation (CRP) as well as with antioxidant defense (GSH) and their resistance to ex-vivo induced hemolysis. Smoking caused an increase in phosphatidylserine translocation outside the erythrocyte membrane (hallmark of eryptosis), significantly correlated to the plasma level of CRP (r = 0.546) and GSH concentration in erythrocytes (r=−0.475). With respect to non-smokers, smokers show a marginal increase of total leucocytes and erythrocyte volume, no modifications of the RBC resistance to oxidative stress-induced hemolysis and hematological and lipid parameters unvaried. We conclude that the inflammatory status (high CRP levels) and RBC oxidative stress (low GSH levels) caused by cigarette smoking are associated with an increase of eryptotic erythrocytes, a yet unknown relationship potentially involved with atherosclerosis and cardiovascular disease in smokers. more...

Objective To assess body distribution and timing of appearance of rest tremor in Parkinson's disease. Methods Information was obtained by a computerized database containing historical information collected at the first visit and data collected during the subsequent follow-up visits. Information on rest tremor developed during the follow-up could be therefore obtained by our own observation in a proportion of patients. Results Among 289 patients, rest tremor was reported at disease onset in 65.4% of cases and detected at last follow-up examination in 74.4% of patients. Analysis of patients who did not report rest tremor at disease onset indicated that 26% of such patients (9% in the overall population) manifested rest tremor over the disease course. Rest tremor spread to new sites in 39% of patients who manifested rest tremor at disease onset. Regardless of tremor presentation at disease onset or during the follow-up, upper limb was the most frequent tremor localization. Over the follow-up, rest tremor developed faster in the upper limb than in other body sites. The risk of developing rest tremor during the follow-up was not affected by sex, side of motor symptom onset and site of tremor presentation. However, age of disease onset > 63 years was associated with an increased risk of rest tremor spread. Conclusions This study provides new information about body distribution and timing of rest tremor appearance during the course of early stages of Parkinson's disease that may help clinicians in patients' counselling. more...

Objective: Although there has been contrasting evidence for a causative role of parathyroid hormone (PTH) in sleep disorders in patients on maintenance hemodialysis, a recent study disclosed the possibility that this role might exist at least in patients requiring parathyroidectomy because of failure of medical therapy. The present study was devised to assess a possible difference in sleep disorders of patients on hemodialysis needing parathyroidectomy and those in whom medical therapy controlled hyperparathyroidism. Design and Patients: To this end, a group of 22 patients requiring parathyroidectomy were studied by means of a sleep questionnaire, along with a group of 44 patients matched for age, gender, body weight, and duration of dialytic treatment. Results: Patients requiring parathyroidectomy slept fewer hours (P < .001), had a higher prevalence of sleep disorders (P < .001), and were more often insomniac (P < .001). Conclusions: This study indicates that patients on hemodialysis requiring parathyroidectomy for intractable hyperparathyroidism comprise a good model for investigating the causative role of PTH on disordered sleep, and that these patients have very poor sleep. These data support recent findings on the prevalence of sleep disorders in dialyzed patients with insuppressible hyperparathyroidism. © 2008 National Kidney Foundation, Inc. more...

Background Adult-onset primary dystonia is thought to be a purely motor disorder. Nevertheless, several studies provided evidence that sensory and psychiatric disturbances may contribute to the clinical spectrum of of dystonia, whereas evidence supporting cognitive impairment is still limited. Methods A set of neuropsychological tests was administered to non depressed, non demented patients with cranial-cervical dystonia and healthy control subjects. The test battery included n -Back Task, Wechsler Memory Scale, Trail Making Test version A and B, and Wisconsin Card Sorting Test. Results As compared with healthy control subjects of similar age, sex and socio-economic status, patients with cranial-cervical dystonia showed deficit on working memory functions revealed by n -Back task, impairment of mental control and visual reproduction subtests of Wechsler memory scale, deficit on information processing speed and set-shifting capacity revealed by Trail Making Test A and B. Conclusion Patients with cranial-cervical dystonia may have impairment in specific cognitive domains relative to working memory, processing speed, visual motor ability and short term memory. Probably, these deficits are not dependent on the clinical expression of dystonia but might rather reflect the cortical and subcortical changes highlighted by functional and VBM imaging studies in patients with different forms of dystonia. more...

The aim of our study was to analyze morphological and functional aspects of cerebral veins by means of ecocolor-Doppler in young (i.e., ≤ 30 years old) and older (i.e.,30 years old) patients suffering from multiple sclerosis. 552 multiple sclerosis patients were evaluated by means of a dedicated Echo-Color-Doppler support (MyLab Vinco echocolor Doppler System, Esaote), in both supine and sitting positions. 458 (83%) showed alterations in their morphological and functional structures of cerebral veins and were divided in two different groups: 1) ≤ 30 (110 patients) and 2)30 years old (348 patients). Young patients showed a statistically significant higher number of both hemodynamically (44% vs. 35%, p0.01) and non-hemodynamically (51% vs. 45%, p0.05) significant stenosis in the internal jugular veins as compared to older patients. A lower percentage of young patients showed blocked outflow in the cervical veins (50% vs. 65%, p0.01) as compared to older ones. Patients30 years old outlined a significantly higher disability degree (Expanded Disability Status Scale score: 5 vs. 3, p0.01) as well as higher disease duration (12 vs. 5 months, p0.01) than younger. No differences could be outlined about multiple sclerosis clinical form of the disease. It was evidenced that young and adult groups are different kind of patients, the former showing much more cerebral veins stenosis and blocked flow in internal jugular veins and vertebral veins than the latter. Duration of disease could explain such differences: the higher the diseases duration, the higher the degree of vascular alterations and, therefore, the disability degree. This could be due to the complex venous hemodynamic impairments induced by alterations in vascular walls: the blocked or difficult blood flow through stenosis could increase the hydrostatic pressure in the skull and this could induce damages to cerebral cells leading to the genesis of more advanced morphological abnormalities. Furthermore, the vessels' alterations could impair venous endothelial functions which could turn in a possible alteration of the controls of cerebral vein return which could worsen the cerebral vascular outflow. It may be possible that early clinical, pharmacological and/or invasive vascular interventions could exert a possible role in the natural history of multiple sclerosis. Nevertheless, further trials are needed in order to confirm such considerations. more...

Background and purpose In medication-overuse headache (MOH) patients, the presence of psychopathological disturbances may be a predictor of relapse and poor response to treatment. This multicentre study aimed to assess the occurrence of psychopathological disorders in MOH patients by comparing the incidence of psychopathological disturbances with episodic migraine (EM) patients and healthy controls (HC). Methods The psychopathological assessment of patients and HC involved the administrations of the Beck Depression Inventory, the Beck Anxiety Inventory, the Modified Mini International Neuropsychiatric Interview (M-MINI), the Yale−Brown Obsessive Compulsive Scale (Y-BOCS) and the Leeds Dependence Questionnaire. Results The MOH, EM and HC groups (88, 129 and 102 subjects, respectively) differed significantly from each other for the presence of moderate/severe anxiety, whereas mood disorder and depression were revealed in similar proportions for both MOH and EM patients. By stratifying the M-MINI questionnaire results according to the number of psychiatric disorders, it was found that MOH patients had a more complex profile of psychiatric comorbidity. Furthermore, clinically relevant obsessive−compulsive disturbances for abused drugs assessed by Y-BOCS appeared to be more represented in the MOH group, whilst the prevalence of this trait in the EM group was comparable to that of HC (12.5%, 0.8% and 0%, respectively). Conclusions Our study indicates the multiple presence of psychopathological comorbidities in patients with MOH. In light of this, it is recommended that the assessment of the psychopathological profile be included in an evaluation of MOH patients, allowing the clinician to more rapidly start an appropriate behavioural treatment, which would greatly improve MOH management. more...

Dermal carotenoids are a good indicator of antioxidant status in the body. This study aimed to determine whether regular consumption of orange juice could increase dermal carotenoids. Two types of orange juice, obtained from regularly (CI) and partially (PRD) irrigated trees, were tested to reveal any possible association between juice and dermal carotenoids. Soluble solids, titratable acidity, and total carotenoids were quantified in the juice; skin carotenoid score (SCS) was assessed by Raman spectroscopy. Carotenoid content was 7.3% higher in PRD than in CI juice, inducing no difference in SCS. In a first trial with daily juice intakes for 25 days, SCS increased linearly (10%) in the individual with higher initial SCS, and exponentially (15%) in the individual with lower initial SCS. In a second trial, SCS showed a 6.5% increase after 18 days of drinking juice every other day, but returned to initial values three days after last intake. Skin carotenoids can be increased by regular consumption of fresh orange juice, while their persistence may depend on the accumulation level, environmental conditions or living habits. more...

Background: To assess Guillain-Barré syndrome (GBS) incidence we relied on the Italian Network for the study of GBS (ITANG) established in 2010 in 7 Italian regions to analyse the association between influenza vaccination and GBS. Methods: All individuals aged ≥18 years, presenting with clinical manifestations that suggested GBS according to the universally accepted Asbury's diagnostic criteria (1990) were prospectively notified to a centralised database by ITANG neurologists over the period October 1, 2010-September 30, 2011. Through a telephone survey, 9 trained interviewers followed up the cases to diagnosis and then for 1 year since hospital discharge. Validation of case reporting was performed with the support of administrative data in 5 regions. Results: We found 365 cases fulfilling the definition for GBS or one of its variants over 19,846,068 population ≥18 years of age, yielding an annual incidence rate of 1.84 per 100,000 (95% CI 1.65-2.03), 2.30 (95% CI 1.99-2.60) in men and 1.41 (95% CI 1.18-1.64) in women. A highly significant peak of incidence was observed in February 2011 as compared to reference month (September 2011, rate ratio 3.3:1, p < 0.01). Conclusions: In Italy, GBS incidence was among the highest reported in Europe and higher than previously observed in Italian studies. more...

Background Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The visual line-bisection task administered to normally cycling women showed different patterns of the interhemispheric interactions during menses and the midluteal cycle phase. However, the contribution of estrogens and progestins hormones to this phenomenon is still unclear. Study Design The aim of our study was to show a variation of FCAs in women administered oral contraceptives (OCs) using the visual line-bisection task. Visual line-bisection task with three horizontal lines was administered to 36 healthy women taking a 21-day OC. Twenty-nine patients were right handed. The task was administered during OC intake (day 10) and at the end of the pill-free period. Results The right-handed women showed a significant leftward bias of veridical center on the first and third lines during OC intake compared with an opposite rightward bias during the pill-free period. The same phenomenon of contralateral deviation was observed in left-handed women on day 10 of OC intake. Conclusions The results of this study confirm a hormonal modulation on interhemispheric interaction and suggest that OCs may improve the interhemispheric interaction reducing FCAs compared with the low hormone level period. This opens new insights in OC prescription and choice of administration schedule in order to improve cognitive performances. more...

Background Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain. Methods One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM). Results Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration. Conclusion Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development. more...

Background: There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs. Objective: To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFN beta) treatment response in a cohort of relapsing (RR) MS patients. Methods: A cohort of 2570 IFN beta-treated RRMS was prospectively followed for Lip to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by I point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique. Results: The multivariate Cox Regression analyses showed that male patients had a significant (p = 0.0097) lower risk for 1st relapse and a trend (p = 0.0897) for a higher risk to reach I point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR = 0.86; 95% Cl = 0.76-0.98; p = 0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for I point EDSS progression (HR = 1.33; 95% Cl: 1.00-1.76; p more...

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression. more...

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS. more...

Background: The purpose of our study was to evaluate the impact of laparoscopic adrenalectomy on patients with incidentalomas. We analyzed the results of a multi-centre trial that was performed to evaluate the effectiveness of imaging (computed tomography and magnetic resonance imaging) to obtain a correct preoperative diagnosis. Methods: We obtained our data from the results of a questionnaire that was distrib-uted by mail or email in May 2005 to several surgical units operating in the Campania Region, Italy. Lap Club, a collaborative laparoscopic surgery study group founded in Naples in 1995, distributed the questionnaire. Thirteen centres participated in the audit. In all, we analyzed 255 adrenalectomies performed on 250 patients. We per-formed statistical analysis using SPSS software. Results: The distribution of pathologic findings demonstrates that the number of lesions caused by cancer discovered from a preoperative indication of incidentaloma has been even smaller (1/114, 0.8%) than the previous numbers reported in the litera-ture. Moreover, whereas most patients with adrenal cancer had lesions larger than 6 cm (7/8, 87.5%), the majority of patients with adrenal metastases had lesions 6 cm or smaller (10/12, 83.3%). Different indications for adrenalectomy emerged on com-parison of endocrine surgery units with general surgery units. This difference appears to be significant (p < 0.001), especially on evaluation of the number of nonfunctioning adenomas and the number of endocrine lesions that were observed and treated. Conclusion: Laparoscopy remains the gold standard method for adrenalectomy, but its availability must not obligate physicians to treat with surgery when an inciden-taloma is detected through imaging. Adrenal malignancies when metastatic are often 6 cm or smaller. If they are single and they originated from a non–small lung cancer, they must be removed. The endocrine surgery unit remains the best setting to evalu-ate and treat adrenal gland surgical pathology. more...

Background β-Site amyloid precursor protein (APP)–cleaving enzyme 1 (BACE1) activity determines the rate of APP cleavage and is therefore the main driver of amyloid β production, which is a pathological hallmark of Alzheimer's disease (AD). Methods The present study explored the correlation between BACE1 activity and cerebrospinal fluid (CSF) markers of APP metabolism and axonal degeneration in 63 patients with mild AD and 12 healthy control subjects. Results In the AD group, positive correlations between BACE1 activity and soluble APP β, the APP sorting receptor sortilin-related receptor with A-type repeats (also known as SorLA or LR11), and tau were detected. BACE1 activity was not associated with amyloid β 1–42 or soluble APP α concentrations in the AD group, and no associations between BACE1 activity and any of the protein concentrations were found in the control group. Conclusion Our results confirm the relevance of BACE1 and sortilin-related receptor with A-type repeats within the amyloid cascade and also provide a further piece of evidence for the link between amyloid and tau pathology in AD. more...

Elevated homocysteine (Hcy) levels exert several neurotoxic actions and vascular dysfunctions that may be involved in pathogenesis and progression of multiple sclerosis (MS). The effective role of Hcy in MS however remains to be determined. The aim of this work was to compare plasma Hcy levels in MS patients and neurological disease controls (NDC) and to evaluate their relationships with clinical and demographic variables. In this cross-sectional study, we examined plasma Hcy levels in 217 patients with MS [53 clinically isolated syndromes (CIS) suggestive of MS, 134 relapsing remitting (RR), 23 secondary progressive (SP) and seven primary progressive (PP) MS], recruited among patients attending a tertiary clinical center in southern Italy and in 219 age/sex-matched controls. Median Hcy levels were slightly higher in MS patients compared to NDC (9.1 μmol/l; range, 3.4–35.9 vs. 8.6, range 3.5–27.4; p = 0.02). Median Hcy concentrations were increased in males more than in females in the MS population (10.4 vs. 8.4; p < 0.0001), whereas no differences across genders were found in NDC (9.1 vs. 8.5). Hcy levels were higher in male MS patients compared to the male NDC patients (p = 0.001). Patients with CIS had lower Hcy (7.5 μmol/l; p = 0.004) compared to patients with RR (9.5 μmol/l), SP (10.1 μmol/l) and PP (9.9 μmol/l). Median Hcy concentration was higher in patients with disease duration longer than 22 months (9.7 vs. 8.6 μmol/l; p = 0.02). Plasma Hcy levels are increased in patients with definite MS. Higher Hcy levels are associated with male sex, suggesting a role of Hcy in neurodegenerative processes of MS, which are prominent in male patients. more...

Adult-onset dystonia (AOD) may manifest in focal forms (as blepharospasm, oromandibular dystonia, cervical dystonia, laryngeal dystonia, and hand dystonia) or in segmental forms. Time from onset of dystonia to diagnosis can be an indicator of the quality of care received during the diagnosis of AOD, likely reflecting factors associated with both the patient and their health system. Three previously reported single-center studies showed that diagnosis of AOD may be delayed for several years. Here, we examined the time lapse between onset and diagnosis in patients with different forms of AOD from an Italian movement disorder center. We found the time lapse between dystonia onset and diagnosis was very long for patients who developed AOD before 1980; and even in the most recent years reaching a correct diagnosis required more than year in almost half of cases. Our results suggest that the delay in diagnosis of adult-onset focal and segmental dystonia has improved over time, but remains unacceptable. The findings are a promising indicator of improvements in care of this uncommon disorder. However, education of patients and doctors is still needed. more...

BACKGROUND/AIMS: Laparoscopic cholecystectomy is characterized by a higher incidence of iatrogenic biliary lesions. The Authors evaluate the role of hepaticojejunostomy in the treatment of iatrogenic biliary lesions following laparoscopic cholecystectomy in 51 patients observed in the Campania region, Italy from 1991 to 2003. METHODOLOGY: The Authors report the data of a retrospective multicentric study of 51 patients -39 women (76.47%), 12 men (13.53%)-reoperated on for major biliary lesions following laparoscopic cholecystectomy. Hepaticojejunostomy in 20 cases (39.21%) and T-Tube plasty in 20 cases (39.21%) were performed. RESULTS: The mean follow-up was 25.01 months. The mean hospital stay was 25.7 days. 1/51 patients (1.9%) died from intraoperative incontrollable hemorrhage while cumulative postoperative mortality was 9.8% (5/51 patients). Therapeutic success rate of hepaticojejunostomy was 70% with a T-Tube plasty success rate of 65%. 9/51 patients (17.64%) were reoperated while in 4/51 (7.84%) a biliary stent was positioned. In 1/51 patients (1.9%) a biliary cirrhosis and in 3/51 (5.7%) a bioumoral cholestasis was observed. CONCLUSIONS: Laparoscopic cholecystectomy causes a higher incidence of iatrogenic biliary lesions. Hepaticojejunostomy gives better long-term results and lower morbidity compared to T-Tube plasty. Management of septic complications in patients with iatrogenic biliary lesions represents the first therapeutic step. more...

Background According to a widely accepted hypothesis, the amyloid precursor protein (APP) is processed by two competing pathways: the amyloidogenic β-secretase–mediated pathway or the nonamyloidogenic α-secretase–mediated pathway. APP is cleaved preferentially through the nonamyloidogenic pathway in normal brain, whereas the balance shifts to the amyloidogenic pathway in Alzheimer's disease (AD). The levels of the α-secretase–cleaved soluble APP (sAPPα) and β-secretase–cleaved soluble APP (sAPPβ) in cerebrospinal fluid (CSF) are likely to reflect these competing mechanisms. Methods We investigated the levels and the relationship between sAPPα and sAPPβ in the CSF of 64 patients with mild AD, 76 patients with mild cognitive impairment, and 12 cognitively healthy control subjects, as well as the effect of apolipoprotein E genotype and sex on soluble APP levels. Results There was a significant positive correlation between sAPPα and sAPPβ levels in all three groups. sAPPα and sAPPβ concentrations were higher in patients with mild cognitive impairment compared with patients with AD. In the AD group, females exhibited higher sAPPα and sAPPβ levels than males. No influence of the apolipoprotein E genotype on soluble APP concentrations was detected. Discussion The positive correlation between sAPPα and sAPPβ challenges the hypothesis that AD is caused by an imbalance of the α- and β-secretase APP proteolysis through competing mechanisms. Moreover, the differences in CSF levels of sAPPα and sAPPβ between male and female patients with AD may reflect a "sexual dimorphism" in the activity of the two APP processing pathways in AD. more...

Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p more...

Abnormalities of central pain processing play an important role in the pathophysiology of fibromyalgia (FM). The aims of the present study were to: 1) evaluate habituation of laser-evoked potentials (LEP) to repeated painful stimulation of 1 tender and 2 nontender points; and 2) determine correlations between LEP abnormalities and major clinical features of FM. Fourteen consecutive FM outpatients and 13 normal controls were included. LEP were recorded from scalp designations Fz, Cz, Pz, T3, and T4. The dorsum of the right hand, the right supra-orbital zone, and the right knee (a tender point in all patients) were subjected to repeated CO2 laser stimuli. For each stimulation site, recordings were obtained for 3 consecutive series of 20 stimuli. The 3 main findings in FM patients were: 1) an increased amplitude of vertex LEP and subjective laser pain; 2) decreased habituation of vertex LEP and subjective laser pain; and 3) a correlation between reduced N2 wave habituation and the severity of self-reported depressive symptoms. As with other chronic pain syndromes, the pathophysiology of FM may involve a generalized increase in the perception of painful stimuli and reduced habituation of the sensory cortex. Perspective Reduced habituation of cortical responses to laser stimuli in FM patients suggests alterations in the pattern of cortical excitability. This is facilitated by depressive symptoms and abnormalities in central neurotransmission. These findings provide further support for the use of medications with effects on the central nervous system in the management of FM. more...

Introduction The mechanisms underlying functional movement disorders are poorly known. We examined whether experience of a movement disorder model in the family and/or the friendships contributes to functional movement disorders. Methods The hypothesis was tested in a case–control study including 33 patients with functional movement disorders and 66 age- and sex-matched patients with organic movement disorders and using a conditional logistic multivariable analysis (adjusted by age, education, disease duration, chronic medical illnesses and clinical phenotype). Results Case-control comparison yielded a significant association between functional movement disorders and exposure to phenotypically congruent movement disorder models (Odds ratio, 3.9, p = 0.01), mainly when disease model came from friendships (Odds ratio, 5.9, p = 0.04). By contrast no association was found between functional movement disorders and phenotypically different neurological or non neurological disease models. A significant inverse relationship between exposure to a phenotypically concordant movement disorder model and age of disease onset was also observed. Conclusions These findings support disease modeling as a factor contributing to the phenomenology of functional movement disorders. more...

Background Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. Objective To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. Methods We studied 222 relapsing remitting MS patients with low disability (scores ≤ 2 at the Kurtzke Expanded Disability Status Scale). Lesion load, WM and GM were measured by fully automated, operator-independent, multi-parametric segmentation method. T1 and T2 lesion volume were also measured by a semi-automated method. Fatigue was assessed by the Fatigue Severity Scale (FSS), and patients divided in high-fatigue (FSS ≥ 5; n = 197) and low-fatigue groups (FSS ≤ 4; n = 25). Results High-fatigue patients showed significantly higher abnormal white matter fraction (AWM-f), T1 and T2 lesion loads, and significant lower WM-f, and GM-f. Multivariate analysis showed that high FSS was significantly associated with lower WM-f, and GM-f. Females and highly educated patients were significantly less fatigued. Conclusion These results suggest that among MS patients with low disability those with high-fatigue show higher WM and GM atrophy and higher lesion load, and that female sex and higher levels of education may play a protective role towards fatigue. Furthermore, they suggest that in MS, independent of disability, WM and GM atrophy is a risk factor to have fatigue. more...

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNβ)ina 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 IFNβ 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 IFNβ 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 IFNβ treatment was lower ( P more...

Objectives The aim of this study was to evaluate the function of Aδ fibers at the hand level in patients with clinical symptoms of Carpal Tunnel Syndrome (CTS) using CO 2 laser evoked potentials (LEPs), in light of the intensity and distribution of sensory symptoms and pain. Methods Thirty-four CTS outpatients (62 hands) were compared to 23 sex- and age-matched control subjects (46 hands). The periungueal skin of the first, second, third and fifth fingers, and the dorsum of the hands were stimulated in random order. The latency and amplitude of the N2, P2 and N1 components were evaluated with respect to the Nerve Conduction Study (NCS) data, clinical scales, pain intensity and glove-like symptoms distribution. Results The amplitude of the N2–P2 complex was significantly reduced in CTS hands compared to normal hands after stimulation of the second and third fingers, even in patients with mild nerve conduction impairment. No significant fifth finger LEP abnormalities were found in patients with glove-like distribution symptoms. The N2–P2 amplitude at the second and third fingers was positively correlated with the severity of sensory symptoms. Conclusions The involvement of median nerve Aδ fibers in CTS seems to be an early phenomenon, which concurs with the impairment of large motor and sensory afferents and is linked to the severity of the disease. Significance The finding of reduced sensory symptoms in patients with severe thin afferents damage, may suggest a slight expression of central sensitisation phenomena in the advanced stage of CTS syndrome. more...

The authors evaluated the role of a laparoscopic approach on a complete resection of an omental cyst. A young female patient (25 years of age) underwent a complete resection of a 12-cm omental cyst via a laparoscopic approach. The patient presented with vomiting, nausea, and pain in the periduodenal area. The lesion was diagnosed via CT and MRI. The authors used four trocars (2 × 10 mm, 2 × 5 mm). After complete resection and aspiration, the cyst was removed in a bag. The postoperative period was uneventful, and the patient was discharged after 48 hours. There was no sign of relapse after 30 months of follow-up. Mesenteric and omental cysts are congenital abdominal lesions. Therefore, a complete resection is mandatory because of the high incidence of relapse. A laparoscopic operation proves a suitable approach because of the advantages of lower costs and comparable results to open surgery. more...

Objective: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. Methods: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). Results: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. Conclusions: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability. more...

BACKGROUND Hypertension and diabetes are significantly associated with insulin resistance (IR), which could affect the vasodilatory capacity and microcirculation. The aim of the study was to verify whether IR is associated with a reduced microvascular blood flow in normoglycemic mild hypertensives. METHODS Eighty-four untreated grade-1 hypertensives were equally divided, according to the IR homeostasis model assessment (HOMA) index, into three groups: IR-Low = 2.16 +/- 0.09 vs. IR-Medium = 3.77 +/- 0.09 vs. IR-High = 7.08 +/- 0.68 (P < 0.001) with similar sex distribution, office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and history of hypertension. They underwent ambulatory blood pressure monitoring (ABPM) and a laboratory stress session, during which blood pressure (BP), heart rate (HR), and skin blood flow (Laser Doppler) were taken on the forehead (LDF) and the hand (LDH), where the neuroadrenergic control of the microvascular blood flow is higher. Reactivity was calculated as "area-under-the-curve" (AUC) during arithmetic and cold pressor tests. Postischemic LDH served as the index of endothelial microcirculatory damage. RESULTS ABPM confirmed the diagnosis of hypertension, but IR-High patients showed a reduced nighttime BP fall. They also demonstrated reduced LDH-AUC and LDF-AUC although BP-AUC and HR-AUC reactivity were similar. Postischemic LDH was lower in the IR-High group (P < 0.05), and the postischemic LDH change was progressively impaired in both IR-Medium and IR-High patients (P < 0.001). LDH-AUC (-0.305, P = 0.007) and postischemic LDH at 30 s (-0.217, P = 0.059) and 60 s (-0.248, P = 0.030) during hyperemia were associated with HOMA. Multiple regression analysis, with HOMA as the dependent variable, showed that BMI (beta = 0.336, P < 0.001) and LDH (beta = -0.239, P < 0.001), LDH-AUC (beta = -0.296, P < 0.01) and postischemic LDH change (beta = -0.321, P < 0.001) entered the equation. CONCLUSIONS The findings suggest that IR is associated with functional microvascular constrictive impairment in normoglycemic mild hypertensives. more...

In fibromyalgia (FM), reduced habituation of laser-evoked potentials (LEPs) suggests a dysfunction of pain processing at a central level. In this study, we aimed to further examine the nociceptive pathways at the peripheral to the central level in a large group of FM patients by means of LEPs and skin biopsy, in light of healthy controls findings and main clinical features. One hundred and ninety-nine FM patients and 109 age- and sex-matched controls were submitted to LEPs by the dorsum of the right hand and the skin over the right chest and knee tender point stimulation. Skin biopsy was performed in 21 randomly selected FM patients and 60 age- and sex-matched controls. The mean N2-P2 amplitude was reduced in the whole FM group, with normal or even increased values in patients with migraine as comorbidity and reduced values in other patients including those presenting with distal sensory deficits. All patients had reduced N2-P2 habituation in respect to controls. In the FM group, LEPs habituation was correlated with pain at tender points and bad quality of life. Epidermal fiber density was significantly reduced in FM patients versus controls, and correlated with N2-P2 amplitude by the hand and chest tender-point stimulation. Dysfunction in the nociceptive system at both the central and peripheral levels may concur to explain phenotypical eterogeneity and clinical symptom complexity in fibromyalgia. more...

The present study aimed to evaluate heat pain thresholds and evoked potentials following CO(2) laser thermal stimulation (laser-evoked potentials, LEPs), during remote application of capsaicin, in migraine patients vs. non-migraine healthy controls. Twelve outpatients suffering from migraine without aura were compared with 10 healthy controls. The LEPs were recorded by 6 scalp electrodes, stimulating the dorsum of the right hand and the right supraorbital zone in basal condition, during the application of 3% capsaicin on the dorsum of the left hand and after capsaicin removal. In normal subjects, the laser pain and the N2-P2 vertex complex obtained by the hand and face stimulation were significantly reduced during remote capsaicin application, with respect to pre-and post-capsaicin conditions, while in migraine LEPs and laser pain were not significantly modified during remote painful stimulation. In migraine a defective brainstem inhibiting control may coexist with cognitive factors of focalised attention to facial pain, less sensitive to distraction by a second pain. more...

Objective To investigate the impact of interferon-beta (IFNβ) on disease progression in relapsing-remitting multiple sclerosis patients. Methods A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFNβ–treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables. Results The IFNβ–treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24–0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23–0.56 for time from date of birth; p < 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53–0.94 for time from first visit; HR, 0.69, 95% CI, 0.52–0.93 for time from date of birth; p < 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38–0.95 for time from first visit; HR, 0.54, 95% CI, 0.34–0.86 for time from date of birth; p ≤ 0.03) when compared with untreated patients. SP and EDSS scores of 4 and 6 were reached with significant delays estimated by times from first visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years) in favor of treated patients. Sensitivity analysis confirmed findings. Interpretation IFN-β slows progression in relapsing-remitting multiple sclerosis patients. Ann Neurol 2007;61:300–306 more...

The contingent negative variation (CNV) is a neurophysiological pattern related to planning of external — paced, voluntary movements. The aim of the study, was to examine the CNV in a cohort of mild demented and non-medicated HD patients, evaluating the CNV amplitude modifications in the light of clinical features and performing Low Resolution Brain Electromagnetic Tomography (LORETA) analysis in order to show the CNV multiple generators. Fourteen HD patients and 25 sex and age-matched controls were studied. All subjects were evaluated by the motor section of UHDRS, MMSE and WAIS. The CNV was recorded by 19 scalp electrodes, with a red light flash as visual warning stimulus (S1), followed by a blue light flash (S2) after a fixed interval of 3 s. The amplitude of early CNV was significantly reduced in HD, compared to controls: the amplitude reduction was significantly correlated with the bradikinesia score. LORETA analysis of early CNV significantly discriminated patients from controls, for a prevalent activation of the posterior part of anterior cingulate cortex in HD. An abnormal activation of the associative cortex devoted to the processing of attention preceding voluntary movement may be supposed in HD, probably mediated by the altered basal ganglia modulation. more...

Influenza vaccination has been implicated in Guillain Barre Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations. more...

Objective: Levetiracetam (LEV) is a novel antiepileptic drug characterized by a wide spectrum of action; no pharmacologic interaction and poor adverse events are reported. In animal models, effects of LEV are observed in basal ganglia. The aim of this study was to evaluate the efficacy of LEV in reducing involuntary movements in subjects affected by Huntington disease (HD). Methods: This was a single-center, short-term, open-label, controlled study. Patients had LEV as add-on therapy for 6 months. In the first visit patients were rated according to the Unified Huntington Disease Rating Scale. Every 2 months they were submitted to all these tests. LEV was added at the dose of 500 mg twice daily for the first 2 months and then the dosage was increased until 1000 mg twice daily for the next 4 more months. The authors enrolled 22 patients: 15 were assigned to the LEV group and 7 were enrolled as control subjects. Results: No serious adverse events were experienced by the treated patients. After 6 months of treatment patients on LEV showed a significant reduction of involuntary movements, with a slight improvement of functional capacity compared with the control group. Conclusion: Results of this short-term, prospective, controlled study indicates that in HD patients, LEV is effective in reducing involuntary movements, thus improving the quality of life. more...

Apoptotic deletion of autoreactive T–cells is defective in patients with multiple sclerosis (MS). Glatiramer acetate (GA) treatment seems to restore apoptosis of detrimental T–cells. We analyzed the mitochondria membrane pro– (Bax) and anti–apoptotic (Bcl– 2) and cytosolic pro–apoptotic (Cyt–c, APAF–1) proteins expression in peripheral lymphocytes from relapsing–remitting (RR) MS patients during GA treatment. Blood samples were collected from 8 healthy controls (HCs) and from 8 RR MS patients prior to and every three months during the 9 months of GA treatment. Peripheral blood mononuclear cells (PBMNCs) Bcl–2, Bax, Cyt–c and APAF–1 were quantified by western blot followed by densitometric scanning and Bax/Bcl–2, cytosolic Cyt–c/Bcl–2 and APAF–1/Bcl–2 ratios were calculated. T–cells were in vitro tested for oxygen consumption by a respirometric analysis. Bax/Bcl–2, cytosolic Cyt–c/Bcl–2 and APAF–1/Bcl–2 ratios in untreated MS patients were significantly (p < 0.05) lower than in HCs. Bax/Bcl–2 ratio increased (p = 0.03) and Cyt–c/Bcl–2 ratio showed a trend to increase during the 9 months of GA treatment in MS patients. A reduction of 58% and 59% in oxygen consumption by PBMNCs was evident after GA treatment in vitro or when GA treated patients' cells were compared with those from HCs, respectively. Our findings suggest that GA exerts a regulatory effect on peripheral T lymphocytes through pro–apoptosis mechanisms involving mitochondria and cytosolic proteins. more...

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. more...

To investigate the immune-mediated response in TS, and its relationship with streptococcal infection, we measured serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with TS, compared to healthy and diseased controls. Soluble VCAM-1 and sE-selectin were significantly elevated in children and adults with TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive adults with TS. No correlation of adhesion molecule levels to clinical severity or anti-streptococcal antibodies was observed. Children with Sydenham's chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not sVCAM-1 and sE-selectin. These results provide initial evidence for a role of adhesion molecules and systemic inflammation in TS, and support the hypothesis of an ongoing immune-mediated process in this condition. more...

The aim of this study is to investigate the expression of P2X7R, IL-1beta and the ATP activity modulating ecto-apyrase CD39 on peripheral blood monocytes of MS patients and to observe the possible effects of Glatiramer Acetate (GA) on such expression. Twelve RR treatment-free MS patients were selected and peripheral blood monocytes were obtained. The expression of P2X7R, IL-1beta and CD39 on monocytes was investigated by qrt-PCR. The in vitro effects of GA on the expression of monocytes stimulated with BzATP (a potent P2X7R agonist)-were evaluated. Ten healthy donors (HDs) were similarly studied. Finally, 5 MS patients were given GA therapy and the monocytes obtained before treatment, after 3 and 12 months of GA treatment were similarly investigated. No differences were found in P2X7R, IL-1beta and CD39 expression between patients and controls. In MS Bz-ATP stimulated monocytes, GA pre-conditioning clearly downregulated P2X7R (p=0.003) but IL-1beta expression also showed a decreasing trend (p=0.07). Conversely, CD39 showed an increasing trend (p=0.07). Similar evidence was found in HDs. GA in vivo treatment induced a reduction in the expression that was clear for P2X7R and CD39 (p0.05) but only not significant for IL-1beta after 12 months of treatment. Monocytes from both MS and control subjects express P2X7R, IL-1beta and CD39, and GA seems to interfere with such expression. more...

Background. Subtotal parathyroidectomy (SP) and total parathyroidectomy (TP) with autotransplantation (TPai) are the most commonly adopted operations for the treatment of secondary hyperparathyroidism (2HPT). TP without autotransplantation had previously been confined to patients with advanced dialytic vintage, not eligible for kidney transplantation. Over the years, the procedure has gained more widespread use, but there is no precise knowledge on the immediate and long-term effects. Methods. The Authors analysed the immediate and long-term results of TP without autotransplantation, that is after the systematic removal of at least four glands in 20 patients operated for 2HPT, which were compared with results from TPai in an equal number of cases. Results. An improvement of the typical clinical symptoms was found in every patient undergoing surgery, and a significant reduction in intact parathyroid hormone (iPTH) serum levels was achieved. Immediate normalisation of iPTH level was observed in 11/20 TP cases, hypoparathyroidism in 4/20 and persistent HPT in five cases. One year of follow-up showed a slight increase in hypoparathyroidism, with 1/20 (5 %) recurrence of the disease. One year TPai results showed a similar percentage of euparathyroidism, as well as a higher long-term recurrence rate (4/20, 20 %), although values do not reach statistical significance. Conclusions. TP may still be considered the operation of choice in patients with aggressive forms of 2HPT or of advanced dialytic vintage, with no access to renal transplantation, because of its low recurrence rate (5%). Postoperative aparathyroidism is rare, while hypoparathyroidism and hypocalcaemia can be well controlled by medical treatment. Background: Subtotal parathyroidectomy (SP) and total parathyroidectomy (TP) with autotransplantation (TPai) are the most commonly adopted operations for the treatment of secondary hyperparathyroidism (2HPT). TP without autotransplantation had previously been confined to patients with advanced dialytic vintage, not eligible for kidney transplantation. Over the years, the procedure has gained more widespread use, but there is no precise knowledge on the immediate and long-term effects. Methods: The authors analyzed the immediate and long-term results of TP without autotransplantation, that is after the systematic removal of at least four glands in 20 patients operated for 2HPT, which were compared with results from TPai in an equal number of cases. Results: An improvement of the typical clinical symptoms was found in every patient undergoing surgery, and a significant reduction in intact PTH (iPTH) serum levels was achieved. Immediate normalization of iPTH level was observed in 11/20 TP cases, hypoparathyroidism in 4/20 and persistent HPT in 5/20 cases. One year of follow-up showed a slight increase in hypoparathyroidism, with 1/20 (5%) recurrence of the disease. One-year TPai results showed a similar percentage of euparathyroidism, as well as a higher longterm recurrence rate (4/20, 20%), although values do not reach statistical significance. Conclusions: TP may still be considered the operation of choice in patients with aggressive forms of 2HPT or of advanced dialytic vintage, with no access to renal transplantation, because of its low recurrence rate (5%). Post-operative aparathyroidism is rare, while hypoparathyroidism and hypocalcemia can be well controled by medical treatment. ©2012, Editrice Kurtis. more...

Background The identification of biomarkers able to improve the differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica (NMO) is challenging because of a different prognosis and response to treatment. Growing evidence indicates that brain and CSF N-acetyl aspartate (NAA) concentration is a useful marker for characterising different phases of axonal pathology in demyelinating diseases, and preliminary studies suggest that increased serum NAA levels may be a telltale sign of acute neuronal damage or defective NAA metabolism in oligodendrocytes. Objective To evaluate whether serum and CSF NAA concentration differs in patients with MS and NMO. Design Observational, multicentre, prospective, cross sectional study. Methods Serum samples were collected from 48 relapsingeremitting MS, 32 NMO and 76 age matched healthy controls. Coeval CSF samples were available for all MS and for 8/32 NMO patients. NAA was measured in serum and CSF by liquid chromatography-mass spectrometry. Results MS patients showed higher serum and CSF NAA levels than NMO patients, and higher serum NAA levels than healthy controls (p more...

In multiple sclerosis (MS), matrix metalloproteinase (MMP) activity in tissues is the result of a balance between MMPs and their tissue inhibitors (TIMPs). MMP-9 predominates in acute MS lesions and is inhibited by TIMP-1, while MMP-2 may participate in the remodeling of the extracellular matrix (ECM) such as in chronic disease and is inhibited by TIMP-2. These differences may be reflected in serum and cerebrospinal fluid (CSF). We have tried to characterize MMP-2 and MMP-9 activities, in relation to their respective TIMPs, 2 and 1, as a factor of different types of the disease, as this information was not previously clearly stated. We found the MMP-2/TIMP-2 ratio in serum to show higher values in secondary progressive (SP, p=0.02) and primary progressive (PP, p=0.01) MS than short disease duration (SDD) relapsing-remitting (RR) MS, but not different from the healthy control (HC) group. Whereas the MMP-9/TIMP-1 ratio in serum showed higher (p=0.04) values in SDD RR MS than PP but also in active patients, evaluated either clinically (p=0.006) or from the magnetic resonance imaging (MRI, p0.05), compared to inactive disease. CSF MMP to TIMP ratios did not differ between MS subtypes, suggesting systemic rather CNS-restricted changes. These results show that an increase in MMP-2/TIMP-2 ratio marks chronic progression in MS, but it is as high as in HC, and also confirm that high MMP-9 activity characterizes short duration relapsing and active forms of the disease. more...

The aim of this study was to examine the effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on subjective pain and evoked responses induced by laser stimulation (LEPs) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter-critical phase, and to compare the effects with those of non-migraine healthy controls. Thirteen migraine patients and 12 sex- and age-matched controls were evaluated. Each rTMS session consisted of 1,800 stimuli at a frequency of 5 Hz and 90% motor threshold intensity. Sham (control) rTMS was performed at the same stimulation position. The vertex LEP amplitude was reduced at the trigeminal and hand levels in the sham-placebo condition and after rTMS to a greater extent in the migraine patients than in healthy controls, while the laser pain rating was unaffected. These results suggest that HF rTMS of motor cortex and the sham procedure can both modulate pain-related evoked responses in migraine patients. more...

Background The management of Medication overuse headache (MOH) represents a difficult challenge for clinicians and headache experts, particularly for the responder rate after a successful withdrawal treatment. The purpose of this study was to investigate the role of demographic and clinical characteristics as well as the score of Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Disability Questionnaire and Leeds Dependence Questionnaire in predicting a response after a successful withdrawal treatment in patients with MOH. Methods This ancillary study is part of a randomized trial that demonstrated the safety and the efficacy of a 3-month treatment with sodium valproate (VPA) (800 mg/day vs placebo) in MOH. Demographic and clinical characteristics and questionnaire results were obtained from the entire sample. Results A significant correlation was found only between MOH relapse and the total MSQ score, the Role Preventive sub-scale and the Emotional Function sub-scale, suggesting a poorer quality of life in non responders. Conclusion A high MSQ score could be associated with a poor short-term outcome in MOH patients after a successful treatment with detoxification followed by a new treatment. more...

To establish the prognostic role of clinical and demographic factors in a hospital-based cohort of MS patients categorized by age at clinical onset and clinical course.Eighty-three patients with MS had a clinical onset of the disease in childhood (age16 years; early-onset MS [EOMS]) and 710 in adult age (between 16 and 65 years; adult-onset MS [AOMS]). Patients were followed for a mean period of observation of 5 years. Univariate and multivariate analyses of clinical and demographic predictors for rapid progression and disability were performed using a stepwise Cox regression model with time-dependent covariates.In EOMS, the Expanded Disability Status Scale (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a longer disease duration. The probability to reach growth disability and progression was significantly lower in EOMS than in AOMS. Median times to reach EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but the age at both endpoints was significantly lower in EOMS. In EOMS and AOMS, an irreversible disability was related to a secondary progressive course, a sphincteric system involvement at onset, and an older age at onset (in EOMS only for the group14 years); in AOMS, other unfavorable factors were a pyramidal involvement at onset and a high relapse frequency in the first 2 years. The risk of entering secondary progression was significantly influenced by a high number of relapses in EOMS and by a higher age at onset and a short interattack interval in AOMS.A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor. more...

Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics.About 195 cognitively unimpaired MS patients (150 relapsing-remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients' anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance.Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients.The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex. more...

Fifteen beta-thalassemia intermedia patients, not requiring chronic transfusional therapy, were monitored in order to check their antioxidant status, and the lipid oxidation products in plasma, LDL, and erythrocytes before and during a 9-month oral treatment with 600 mg/day vitamin E. The low level of vitamin E, and high level of malondialdehyde in plasma clearly tended to normalize after three months (P < .001), and were quite similar to control after six months. The abnormally low level of vitamin E in LDL and the four times higher than control basal level of conjugated dienes (LDL-CD), were not modified after three months of treatment. Significant changes of LDL-VE (P < .05) and of the basal LDL-CD (P < .001) were evident after six months. LDL-VE was within the normal range after nine months, whereas LDL-CD still appeared twice as higher than control. Plasma vitamin A, ascorbate, beta-carotene, and lycopene increased markedly at the end of the trial (P < .005). The level of vitamin E in red blood cells was normalized after six months of supplementation. A decrease of the baseline value of conjugated dienes was observed after nine months, although it remained 1.4-fold higher than control. The RBC count and hematocrit appeared higher at the end of the trial (P < .05 and P < .001, respectively). The hemoglobin value did not show variations. A shift to normal of the resistance of erythrocytes to osmotic lysis was observed. Our findings provide evidence that an oral treatment with vitamin E improves the antioxidant/oxidant balance in plasma, LDL particles, and red blood cells, and counteracts lipid peroxidation processes in beta-thalassemia intermedia patients. more...

The purpose of this study was to compare magnetic resonance imaging (MRI) features and proton MR spectroscopy (1H-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesion subtypes. Combined MRI and single-voxel 1H-MRS investigation was performed in 54 MS patients (47 relapsing remitting (RR) and seven secondary progressive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions were Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-contrast T(1)-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypointense on pre- and post-contrast T(1)-weighted scans). Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in 1H spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurological controls. MS lesions of RR patients were characterized by a significant increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No significant metabolite changes were found in lesions of SP patients. Gd enhancing plaques showed lactate signal with higher frequency (37.8%) than Gd unenhancing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p0.01), and to Gd unenhancing lesions (p0.05). In particular, there was evidence of a significant increase of Cho/Cr in pre-contrast T(1) hypointense Gd enhancing lesions (p0.01 vs. controls). The Gd unenhancing lesions (p0.01), in particular the T(1) hypointense group (p0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates key pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T(1) hypointense lesions, may reflect increased membrane cell turnover. The T(1) hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/Cr. Nevertheless, the lack of statistical differences in NAA/Cr between plaque subgroups suggests that axonal impairment might occur even in the early stages. more...