Search

Beckground: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. The studys aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment. Patients and methods: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analysed. Sural nerve SAP amplitude reduction ⩾40% was the criteria for discontinuing therapy. Results: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction ⩾50% and 2 <50%). One patient showed no changes in SAP amplitude. Five patients complained of paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients. At detection of reduction in sural nerve SAP amplitude, the median thalidomide cumulative dose was 21.4 g. The threshold neurotoxic dosage is lower than previously reported. Conclusions: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of degeneration and recovery of sensory fibres. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms. [ABSTRACT FROM AUTHOR]

The aims of this study were (1) to analyze whether correlations exist between lumbar spine (LS) bone mineral density (BMD) and the main preoperative biochemical parameters in a large population of patients with primary hyperparathyroidism (HPT); and (2) to evaluate the LS-BMD changes after parathyroidectomy (PTx) at long-term follow-up. Sixty-two patients (median age 57 years, range 23-82 years) with confirmed primary HPT underwent LS osteodensitometry by dual-energy X-ray absorptiometry with BMD measurements at the L2-L4 region before surgery and at 1 year and 2 years after successful PTx. Three groups of patients were considered: Group A (men, n = 14, 22.6%), Group B (premenopausal women, n = 12, 19.3%), and Group C (postmenopausal women, n = 36, 58.1%). There were no linear correlations (P = NS) among the main biochemical parameters, the age of the patients, and their baseline LS-BMD values that were significantly (P < 0.01) lower in Group C patients. At 2-year follow-up the LS-BMD improved by 13.0%, 11.5%, and 11.7% in Groups A, B, and C, respectively (P = NS). In order to compare groups with the same linear relationship between age and LS-BMD, a subgroup of postmenopausal patients aged < or = 60 years (Group C2) was considered. ANOVA showed that the improvement of the LS-BMD at 1- and 2-year follow-up was higher (P = 0.002) in Group B than in Group C2 patients. The result was confirmed by using the Mann-Whitney U-test (P = 0.0078). Improvement of LS-BMD after successful PTx was significantly (P < 0.01) higher in premenopausal women, suggesting a possible role of estrogen hormone in complete bone remodeling. [ABSTRACT FROM AUTHOR]

Several risk factors for breast cancer (BC) have been investigated in different reports, but none has been really useful in preventing BC development. The aim of this study was to evaluate the risk of BC in self-selected symptomatic women in comparison with the healthy population residing in an urban area of Italy. A group of 404 women (median age 59 years, range 26–89 years) with confirmed BC (cases) were age-matched with 389 healthy women (Group A), and 391 (Group B) symptomatic non-screened patients without BC, who were referred to our Breast unit. The results of univariate analysis showed a significant (P < 0.01) difference between cases and controls in (1) age at menarche, (2) number of birth and age at first births, (3) lactation and months of lactation, and (4) estrogen replacement therapy (ERT) and duration of ERT. Multivariate analysis using a logistic regression model adjusted for age showed that five independent parameters (no pregnancy, age at first birth > 30 years, no lactation, use of ERT, ERT > 40 months) significantly (P < 0.01) correlated with BC onset. The relative odds ratios (ORs) at 95% confidence interval (95% CI) were 5.25, 2.47, 2.82, 2.80, and 5.56, respectively. The cumulative OR (95% CI) calculated from the observed vs. predicted values was 7.15. No differences (P = NS) were found between groups A and B. In conclusion, in our study population, the prolonged use (> 40 months) of ETR in menopausal women resulted in an increased risk of BC, and represented the only risk factor that could be removed. [Copyright &y& Elsevier]

The aim of this study was to provide information about risk of breast cancer (BC) in women with breast complaints undergoing spontaneously clinical examination. The records of 2,879 self-selected symptomatic new patients observed consecutively were reviewed, and the chief breast complaint such as pain, lump and nipple discharge had been recorded. Patients were divided in three groups: Group A, 1,186 (41.2%) patients aged < 41 years; Group B, 809 (28.1%) patients aged 41–55 years; and Group C, 884 (30.7%) patients aged > 55 years. Pain was most common (P < 0.01) in Group A (60.8%), and lump in Groups B (53.3%) and C (89.7%).A total of 318 (11.0%) women had histologically confirmed BC (Group A = 3.5%, Group B = 30.5%, Group C = 66.0%), accounting for 3.2, 16.4 and 12.0% of patients with pain, lump and nipple discharge, respectively. Breast complaints were equally (P = NS) distributed between patients with and without BC. The relative risk (RR) of BC developing ranged between 0.5–1.4, 0.5–1.9, and 0.6–3.0 in Groups A, B, and C, respectively. It ranged between 0.3 and 0.7 in patients with breast pain, and was significantly higher (RR = 1.9–3.0) only in patients with breast lump aged > 40 years. In conclusion, in symptomatic patients BC risk is strictly related to age, and independent of the referred symptoms. Therefore, further investigations have to be warranted only when risk factors different from breast complaints are present. [Copyright &y& Elsevier]

Objective: The aim of our study was to validate the Myasthenia Gravis TeleScore (MGTS), a scale for the evaluation of MG patients in telemedicine. Introduction: COVID-19 pandemic has boosted telemedicine in clinical practice. It could be crucial in the care of neurological patients with chronic disease. However, there is a lack of validated disease-specific tools to evaluate MG patients in telemedicine. Methods: The MGTS included ten items divided in four districts: ocular, generalized muscular strength, bulbar, and respiratory. Patients were assessed with two different scales: the MGTS and the INCB-MG chosen as a reference from which MGTS was partially derived. Visit in presence with INCB-MG and televisit with MGTS were performed consecutively. Televisit was conducted by another neurologist between two rooms. A blind method was adopted. The strength of correlation was determined by the correlation coefficient (r); analysis of covariance (ANOVA—Kruskal–Wallis test) was used to compare subgroups. Significance was set to p < 0.05. Results: One hundred thirty-one patients were included in the study, 71 females and 60 males. The Spearman correlation coefficient between the INCB-MG scale and the MGTS was 0.825 (p < 0.001), indicating a very strong correlation between them. Different items showed different correlations from low to high (0.32 to 0.80). As expected, correlation was lower between items with different evaluation modality (anamnestic vs clinical). Discussion: The MGTS demonstrated a good correlation with INCB-MG, reliability and construct validity. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Methods: Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48months after the first treatment. Results: There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. Conclusions: In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Significance: Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. [Copyright &y& Elsevier]

Background: Steroid administration is beneficial in Duchenne muscular dystrophy (DMD), but the response, incidence, and the severity of side effects ore variable. Aims: To investigate whether glucocorticoid receptor (GRL) gene polymorphisms may be responsible for glucocorticoid sensitivity in DMD. Methods: Forty eight DMD patients treated either with prednisone or deflazacort were subjected to genetic analyses of the GRL gene. Results: Mutation studies revealed an heterozygous A to G mutation at GRL cDNA position 1220 in three DMD patients resulting in an asparagine to serine amino acid change at amino acid position 363 (N363S). The N363S carrier DMD patients showed a trend towards a later age at loss of ambulation in comparison with non-carrier patients. Conclusions: These data suggest that the N363S GRL polymorphism may be implicated in the long term response to glucocorticoids. [ABSTRACT FROM AUTHOR]

Background and purpose Anti-sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme-linked immunosorbent assay testing compared to sulfatide alone was assessed. Methods Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti-myelin-associated glycoprotein (anti-MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control. Results Thirty-three patients showed increased titers of anti-sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy ( P < 0.0001). When evaluating the reactivity for the combination Sulf/GalC, 57/229 patients were found to be positive, including 36/73 (49%) with IgM paraproteinemic neuropathy ( P < 0.0001). Patients with known anti-sulfatide antibodies also showed anti-Sulf/GalC reactivity, with increased titers in 48.5% of the cases. Testing for anti-Sulf/GalC antibodies allowed 24 additional patients to be detected (eight with IgM paraproteinemic neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti- MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside. Conclusions Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti-sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy. [ABSTRACT FROM AUTHOR]

Objective In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography ( US), US-guided fine-needle aspiration cytology ( FNAC) and flow cytometry phenotyping ( FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. Design Retrospective cohort study with stepwise forward logistic regression analysis of results. Setting Tertiary referral centre. Participants A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. Methods On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. Results Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results ( P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). Conclusion This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded. [ABSTRACT FROM AUTHOR]

Background: B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS.Methods: Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh).Results: Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes (p < 0.01), lower values of BAFF Index (11.9 ± 6.1 vs 17.5 ± 5.2, p < 0.01), and higher CSF CXCL13 levels (27.7 ± 33.5 vs 0.9 ± 1.5, p < 0.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis (r > 0.5 and p < 0.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB- (p < 0.05) and HC (p < 0.01), and correlated to CSF CXCL13 concentrations (r 0.77, p < 0.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41 ± 0.1 vs 2.49 ± 0.1 mm, p < 0.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB-.Conclusions: The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by higher leukocyte counts in the CSF and early evidence of cortical thinning, further suggesting a role for this chemokine as a possible marker of disease severity. [ABSTRACT FROM AUTHOR]

Background and purpose Transcranial sonography ( TCS) of the brain parenchyma is used to visualize alterations in the substantia nigra ( SN) and it is applied for early diagnosis of Parkinson's disease. Our aim was to explore specific echogenic alterations of the SN in dementia with Lewy bodies ( DLB) compared to Alzheimer's disease ( AD). Methods Seventy-one subjects underwent TCS: 22 DLB, 28 AD and 21 healthy elderly controls. Cognitive impairment, extrapyramidal signs, visual hallucinations, fluctuations and rapid eye movement sleep behaviour symptoms were investigated. TCS assessed SN hyperechogenicity and symmetry. Results Transcranial sonography revealed SN hyperechogenicity in 100% of DLB compared to 50% of AD and 30% of controls. Mean SN echogenic area (cm2) was 0.22 ± 0.03 in DLB, 0.15 ± 0.03 in AD and 0.14 ± 0.03 in controls ( P < 0.0001). More than 50% of DLB presented a marked hyperechogenicity (cutoff value >0.22 cm2) compared to only 10% of AD ( P < 0.0003). DLB had symmetrical SN enlargement, whereas AD were mostly asymmetrical ( P = 0.015). A combination of SN echogenic area and asymmetry index had a sensitivity of 88.9% and a specificity of 81.2% in discriminating DLB from AD (positive predictive value 85.7%, negative predictive value 85.7%). No association was found between SN hyperechogenicity and Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination or the presence of visual hallucinations. Conclusions Transcranial sonography may be a valid supportive tool in the diagnostic workup of neurodegenerative dementia helping clinicians to distinguish DLB from AD even at the early stages. [ABSTRACT FROM AUTHOR]

Summary Objective To evaluate whether wearing a wool cap, a routine practice used to prevent heat loss in premature infants, affects interpretation of electroencephalogram spectral analysis. Methods Eighteen premature infants (median gestational age 28 weeks, range 23–32) without neurological complications were randomized to two channel (C3, C4 referred to Cz) digital electroencephalogram recordings with (90 min) and without (90 min) wearing wool cap, at 4 days of life. Electroencephalogram was analyzed automatically by measurement of burst suppression ratio and asymmetry index and by Fast Fourier Transform to calculate total absolute spectral power; relative spectral power in the δ (0.5–3.5 Hz), θ (4–7.5 Hz), α (8–12.5 Hz), and β (13–30 Hz) frequency bands; spectral edge frequency; and mean dominant frequency. Results The use of wool cap had no effect on all electroencephalogram parameters considered. Gestational age showed an effect on relative spectral power of all considered bands, spectral edge frequency and mean dominant frequency, while no effect was seen on burst suppression ratio and asymmetry index. Neonates born at gestational weeks lower than 28 had significantly higher relative power in the δ band and lower relative power in the α and β bands. Conclusions Heat loss prevention using wool cap does not affect interpretation of spectral electroencephalogram. Spectral values in our group of very premature infants without neurological complications correspond to normal data reported in the literature. Maturation changes consist of reduction of relative power of the δ band, spectral edge frequency and mean dominant frequency. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia, the most frequent respiratory sequelae of prematurity, usually occurs as part of the multiorgan foetal inflammatory response syndrome. The underlying mechanism is thought to be the same cytokine mediated leukemoid reaction associated with periventricular leukomalacia of premature infants. Event-related potentials have been shown to serve as early indicators of problems in cortical development. Our aim was to determine the effect of bronchopulmonary dysplasia on neonatal cortical auditory processing. Forty-five premature infants (23–34weeks) were recorded at 35 post-conceptional weeks. Infants with genetic syndromes, clinical evidence of neonatal encephalopathy, intra-ventricular haemorrhage or periventricular leukomalacia were not recruited. The average of 330 responses to 1000Hz pure tones (inter-stimulus interval 1250–1850ms), were recorded at frontal location. Mean amplitudes calculated from the data points of 30ms centered on P1 and N2 peaks in the waveforms of each subject were measured. The amplitude of P1 component resulted lower in infants with bronchopulmonary dysplasia (p =.004). Results show an association between bronchopulmonary dysplasia and alterations in brain auditory processing, even in absence of major neurological risk factors. This further support the hypothesis of an interference with brain development mediated by the foetal inflammatory response syndrome. [Copyright &y& Elsevier]

Objective: The aim of this study was to determine whether a failure of neonatal hearing screening affected the anxiety level of parents of high-risk infants. Methods: Two hundred and eighty-eight parents of infants included in the neonatal hearing screening protocol of our Institution were tested with the Spielberger State-Trait Anxiety Inventory and with an open-question questionnaire investigating parents' attitude to hearing problems in their child, done at the time of audiological follow-up. 105 were parents of high-risk infants who had been discharged from neonatal intensive care unit (NICU) and 183 of low-risk infants discharged from well-baby nursery. Results: No differences in anxiety levels were seen between parents of high-risk infants passing and failing neonatal hearing screening using homogeneous case-control pairs. Additionally, no differences in the level of anxiety were found between parents of high- and low-risk infants failing neonatal auditory screening. Conclusions: Failure of neonatal auditory screening does not affect the anxiety levels of parents of high-risk infants at post discharge from NICU. This finding is a key factor to be considered when evaluating the costs and benefits of tests for universal neonatal hearing screening. [ABSTRACT FROM AUTHOR]

Background and purpose: Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. Patients and methods: Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37-75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. Results: Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. Discussion: Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings. [ABSTRACT FROM AUTHOR]

The aim was to study brain involvement in myotonic dystrophy type 1 by single photon emission tomography (SPECT) and positron emission tomography (PET). 58 DM1 patients were subjected to SPECT; 17 to both SPECT and PET. SPECT patients were grouped as 'normally perfused' and 'abnormally perfused'; PET patients as 'normal performers' and 'abnormal performers'. To quantify hypoperfusion and/or hypometabolism, we used a semi-quantitative scale. To localize focal hypoperfusion/hypometabolism, nine cerebral areas of involvement were identified. The Chi-square, Wilcoxon, McNemar tests were used for statistics. SPECT showed abnormalities in 52/58 patients. PET showed an abnormal glucidic uptake in 15/17. Hypoperfusion was mild/moderate in 50/58 patients, mostly involving the left supratentorial areas. Abnormal glucidic uptake was mainly observed in the left frontal lobe. Abnormalities in blood perfusion and/or glucose metabolism are frequent in DM1. These abnormalities involve the left more often than the right hemisphere, the frontal lobe more than other lobes. Such abnormalities are more often cortical than subcortical. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the degree of brain involvement in a cohort of myotonic dystrophy type 1 and type 2 (DM1, DM2) patients by brain studies and functional tests and to compare the results of the two groups. DM1, DM2 are multisystemic disorders due to polynucleotide expansions. Previous studies on brain involvement by neuroimaging and functional methods have led to contradictory results. Fifty molecularly defined DM1 patients and 14 DM2 patients, were recruited for the study. Age at recruitment, age at disease onset, disease duration and educational level were recorded. Neuromuscular assessment was done by MIRS. An extensive neuropsychological battery was performed in 48/50 DM1 and in a control group of 44 healthy matched subjects. Forty six of 50 DM1 and 12/14 DM2 underwent brain MRI; 21/50 DM1 and 9/14 DM2 underwent brain perfusion SPECT, with semiquantitative analysis of the results. MRI images were classified by ARWMC (age-related white matter changes) score, in order to quantify recurrence, localization and patterns of distribution of white matter hyperintense lesions (WMHLs) in our two cohorts. MRI results were matched to SPECT and to neuropsychological results. Thirty-seven of 46 DM1 and 10/12 DM2 had abnormal MRI imaging, showing scattered supratentorial, bilateral, symmetrical focal or diffuse WMHLs. A typical temporo-insular diffuse subcortical pattern was seen in DM1 subjects only, with no correlation with cognitive involvement. Major cognitive involvement was seen in the case of diffuse frontal lesions. A relationship with CTG expansion size was documented for DM1 subjects. SPECT showed minimal hypoperfusion in the posterior cortex planes in DM1 and, to a lesser extent, in DM2. Very mild degrees of involvement in the DM2 cohort were seen. Neuroimaging and functional investigations confirmed a more severe involvement of the brain in DM1 compared to DM2. A temporo-insular diffuse lesional pattern, specific for DM1, was found on MRI. This confirms greater expansion size as a risk factor for more extensive brain involvement in DM1. [ABSTRACT FROM AUTHOR]

Abstract: Bilateral loss of cortical somatosensory evoked potential (SEP) is considered the single best indicator of adverse outcome in acute encephalopathy of adult patients and older children. This study determines whether the presence or absence of the neonatal cortical SEP can predict cerebral palsy at two years in survivors of neonatal encephalopathy scored according to Sarnat criteria. We also compare SEPs with visual evoked potentials (VEPs), the EEG and neonatal neurological status. Fifty-nine neonates admitted to the neonatal intensive care unit had SEP, VEP and EEG recordings analysed according to the presence (n =37, 63%) or absence (n =22, 37%) of neonatal encephalopathy (score ≥1). Cortical SEP was always present in the perinatal period in those surviving without major neurological disability, while it was bilaterally absent in all but one patient with a subsequent diagnosis of cerebral palsy. Multivariate analysis using the logistic regression model showed that bilateral loss of cortical SEP and Sarnat Score correctly classified the neurological outcome in all patients. Bilateral absence of cortical SEP indicates early identification of neonates at risk of cerebral palsy indicating that EPs have a clinical role in the workup of neonatal encephalopathy. [Copyright &y& Elsevier]

Background and purpose Disease severity varies considerably among patients with Spinal and Bulbar Muscular Atrophy ( SBMA). Our aim was to investigate the role of androgen receptor ( AR) polymorphic repeats in SBMA phenotype. Methods We analyzed the length of AR polyQ and polyG tracts in 159 SBMA patients. Results No relationship between polyG size or polyG/polyQ haplotypes and clinical phenotype was found. An independent negative correlation between polyQ-length and onset of weakness was confirmed ( P < 0.001). Conclusions The negative results of our study prompt to continue the search for potential disease modifiers in SBMA outside the AR gene. [ABSTRACT FROM AUTHOR]

Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100–75 mg m2) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m2) every 3 weeks for ≤1 year. Forty-three patients (29 M, 14 F; median age 51 years, range 34–68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9–33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5–7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients ( P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide. [ABSTRACT FROM AUTHOR]

Background: A recent randomized study conducted on newly diagnosed glioblastoma (GBM) patients demonstrated that concomitant and adjuvant temozolomide added to standard radiotherapy had a survival advantage compared with radiotherapy alone. The overall survival benefit of this aggressive treatment, however, was attenuated in older or poor performance status patients. The aim of the present study was to verify the activity and the toxicity of temozolomide administration concurrent and adjuvant to radiotherapy as first-line treatment for elderly GBM patients, and to explore correlations between clinical outcome and O6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status.Methods: Newly diagnosed GBM patients>or=65 years were considered eligible. Treatment comprised radiotherapy (60 Gy in 30 fractions over 6 weeks) plus continuous daily temozolomide (75 mg/m2/day), followed by 12 maintenance temozolomide cycles (150 mg/m2 once a day for 5 consecutive days every 28 days) if MRI showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression.Results: A total of 58 patients (34 males; median age, 68 years; range, 65-82 years) were enrolled. Sixteen patients (43%) presented MGMT promoter methylated and 21 unmethylated (57%) status. The median progression-free survival and median survival time (MST) were 9.5 months (95% confidence interval [CI], 8.6-10.5) and 13.7 months (95% CI, 10-17.3 months), respectively. Mental status deterioration grade 3-4 was detected in 25% of patients. Leukoencephalopathy was diagnosed in 10% of patients.Conclusions: The overall and progression-free survival of patients given concomitant and adjuvant temozolomide are greater than in those given radiotherapy alone; however, this regimen incurs a greater deterioration in mental status. Further randomized trials should, therefore, be conducted to investigate the efficacy and against the toxicity of this regimen as first-line therapy in patients with GBM. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Serum IgG antibodies (Abs) to phosphorylated ribosomal (P ribosomal) proteins have been inconsistently associated with neuropsychiatric manifestations in systemic lupus erythematosus (SLE). Our aim was to assess whether serum IgG Abs to ribosomal P proteins are associated with neuropsychiatric SLE. Patients and methods: We examined an inception cohort of 219 SLE patients. Neuropsychiatric SLE manifestations were characterized using the American College of Rheumatology (ACR) definition. Serum Abs to P ribosomal proteins were searched for by immunoblotting. In a subgroup of patients, Abs were investigated also in cerebrospinal fluid (CSF). Results: Abs to P ribosomal proteins were detected in 45 (21%) patients, 23 of whom (51%) with neuropsychiatric involvement. Abs to P ribosomal protein were present both in serum and CSF. Abs to P ribosomal proteins significantly correlated with psychosis (p =0.017), mononeuropathy multiplex (p =0.040), malar rash (p =0.004), serum anti-Sm Abs (p =0.042), and lupus anticoagulant (p =0.036). SLE onset age was significantly younger in patients with Abs to P ribosomal proteins. Logistic regression analysis confirmed the relationship between Abs to P ribosomal proteins and psychosis, malar rash, SLE onset age and lupus anticoagulant. Conclusions: Abs to ribosomal P proteins are associated with psychosis and might be associated with peripheral nervous system complications. [Copyright &y& Elsevier]

Abstract: Objective: To compare the diagnostic reliability of automated transient evoked otoacoustic emissions (a-TEOAE), automated auditory brainstem response (a-ABR) and conventional brainstem auditory evoked potential (BAEP/ABR) for identification of hearing loss in high-risk neonates. Methods: Two hundred and six neonatal intensive care unit (NICU) admitted neonates were tested pre-discharge. Follow-up included a-TEOAE in all children, repetition of a-ABR or BAEP if failed in NICU. Sensitivity and specificity were compared and correlated with auditory risk factors. Results: BAEP had the highest sensitivity (100%) and specificity (90.8%), a-ABR the lowest (88.9% and 70.6%). A statistically significant difference in risk factors for temporary hearing loss was observed between normal and false positive a-TEOAE and BAEP, but not a-ABR outcome. Differences in specificity between a-ABR and a-TEOAE explain the pattern of ‘absent a-ABR/present a-TEOAE’ in 13.8% of ears. Conclusions: The BAEP appears the more reliable test for hearing screening of high-risk neonates because of highest sensitivity and specificity and should be used to confirm the diagnosis of ‘auditory neuropathy’ in high-risk neonates. The reliability of a-ABR devices in critically ill neonates needs further investigation. Significance: This is, to our knowledge, the first attempt to compare the diagnostic reliability of a-TEOAE, a-ABR and BAEP in high-risk neonates. [Copyright &y& Elsevier]

The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m(2)/daily for 21 days every 28 days until disease progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31-71) with a median KPS of 90 (range 60-100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen. [ABSTRACT FROM AUTHOR]

Background: Thalidomide is used in cutaneous lupus erythematosus (CLE) refractory to conventional therapies. Peripheral neuropathy (PN) is the most severe side effect, but the incidence of PN and its relation to thalidomide dose are still unclear. Objective: To prospectively evaluate the efficacy as well as the occurrence of PN in CLE patients treated with thalidomide, and to assess whether PN, when occurs, correlates with thalidomide dose and/or length of treatment. Methods: Fourteen female patients with CLE in low-dose thalidomide therapy were followed for up to 24 months. Prior to, and regularly during treatment patients underwent rheumatological, dermatological, neurological and electrophysiological evaluations. A decline in sural SNAP of 50% or more from baseline value was considered as criterion of sensory axonal PN. Results: All patients showed a dramatic improvement of skin manifestations. Ten patients (71.4%) developed a sensory axonal PN. The median time free from this complication was 14 months. No correlations were found between age of the patients nor thalidomide cumulative dose and occurrence of PN (Mann-Whitney U Test; p >0.16). Other adverse effects were: tremor, paresthesias, somnolence, amenhorrea, constipation and thoracic pain. Conclusions: Low does thalidomide is efficacious in treating CLE, but PN is a common complication whose occurrence does not seem to correlate with total thalidomide dose, whereas with the duration of therapy. A closer electrophysiological follow-up is therefore recommended in the long-term treatment. [ABSTRACT FROM AUTHOR]

Abstract: The shortage of organ donations is a major limiting factor in transplant programs. Since a favorable attitude of health professionals to organ donation can positively influence the decision of families of potential donors, educating physicians early in their careers may become crucial in this setting. The aim of this study was to compare medical student opinions on organ donation and transplantation at different stages in their undergraduate career. Methods: Medical students were prospectively surveyed in their first and fourth years by an anonymous 10-item questionnaire. Results: The 100 of 195 (51.3%) students completed both questionnaires including 29 men, of an overall cohort mean age 23.7 (range, 22¿32 years). 91% of the students had attended classical or scientific high school and 83% were Catholic. Their attitude to transplantation remained strongly positive (96% vs 92%, fourth vs first year). 96% of the fourth year students would accept an human donor organ or an artificial organ (vs 95% of first year) and 91% would accept an animal organ (vs 84%). The students showed a positive attitude to organ donation (96% vs 91%, fourth vs first year). Most of them were prepared to donate their organs after death (88% vs 87%). 63% of the fourth year students signed a donor card. In conclusion, medical student attitudes to organ donation and transplantation are highly positive, but do not improve during the first 3 years of Medical School. An educational program is therefore needed. [Copyright &y& Elsevier]

: Emerging evidence points to humoural mechanisms in neurological complications of coeliac disease. Immunoglobulin G anti-ganglioside antibodies have been reported in coeliac disease patients with neuropathy, suggesting an immune response to peripheral nerve antigens. No data are so far available on anti-ganglioside antibodies in coeliac disease children or on antibody modifications after gluten-free diet. : To evaluate the presence of antibodies to ganglioside antigens in children with coeliac disease, their modification after gluten-free diet, and possible correlations with neurological manifestations. : Sera from 42 coeliac disease children, before and after gluten-free diet, were tested by enzyme-linked immunosorbent assay for the presence of antibodies (immunoglobulin M, immunoglobulin A, immunoglobulin G) to gangliosides. Thirty-five sera of age-matched children with dyspepsia were used as control. : High anti-ganglioside antibodies titres were present in two patients. In one patient, antibody titre reversed after gluten-free diet, whereas in the other one the titre increased after diet. Neither one complained of neurological symptoms. : Anti-ganglioside antibodies do not seem to correlate with gluten ingestion or with neurological manifestations in children with coeliac disease. Mechanisms different from gluten exposure may be implicated in the antibody production. An ongoing prospective study will help clarify the role, if any, of these antibodies in coeliac disease. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence and prevalence rates of multiple sclerosis (MS) and their temporal profiles over the last 30 years in the province of Padova (northeast Italy). Background: In the early 1970s an epidemiological survey in the province of Padova showed a MS prevalence and incidence of 16/100 000 and 0.9/100000 population, respectively; these figures are much lower than current estimates in other regions of Italy and Central Europe. Methods: The population of the study area was approximately 820000 (422 028 women, 398290 men) in the 1991 census. All possible sources of case collection were used, but only clinically definite/probable and laboratory-supported definite/probable MS were considered in the analysis of incidence and prevalence trends from 1971 to 1999. Results: On 31 December 1999, the crude prevalence rate was 80.5/100 000 (95% CI 70.3-90.7); prevalence was higher in women (111.1/100 000; 95% CI 99.0-123.1) than in men (49.7/100 000; 95% CI 41.3-58.1). This difference was significant (F/M = 2.43; z = 10.1, P <0,00001); a rate adjusted for the European population was 81.4/100 000. On 31 December 1980 and on 31 December 1990 the estimated prevalence rates were 18/100 000 and 45.7/100 000, respectively. Thus, a fivefold increase in prevalence was observed from the 1970s. The mean annual incidence was 2.2/100000 in the period 1980-89, 3.9 in the period 1990-94 and 4.2 in the period 1995-99. Thus, incidence increased more than fourfold from the 1970s through 1994 and remained quite stable in the last several years. Mean age at onset was 31.3±9.88 years. Mean diagnostic latency decreased significantly from 49.2±44.5 months in 1985 to 23.0±30.3 months in 1990, 12.9±15.61 in 1995 and 5.3±4.7 in 1999. Conclusions: The actual prevalence (80.5/100000) and incidence (4.2/100000) of MS in the province of Padova agree with the most recent epidemiological estimates/trends observed in other Italian and European areas, except for Sardinia and Scotland. The increase in both incidence and prevalence rates observed in much of this region over the last 30 years parallels the introduction of more sensitive diagnostic techniques and a highly significant decrease in diagnostic latency. These findings probably do not support a real increase in the frequency of MS in northeast Italy because recent estimates of incidence have increased only slightly (3.9 to 4.2, which is <10% in five years) and increase in the prevalence rate was almost completely due to the accumulation of new incidence cases. [ABSTRACT FROM AUTHOR]

Objective: To assess whether pegylated interferons (PEG-IFNs) treatment is associated with occurrence, worsening or improvement of peripheral neuropathy in HCV patients. Background: Alpha-IFN is associated with central nervous system side effects. There are reports of both improvement and worsening of neuropathy during alpha-IFN treatment, but the possible alpha-IFN peripheral neurotoxicity has never been consistently investigated. Patients and Methods: Twenty-six HCV patients (19 male, 7 females, median age 41.5 ± 9.6 years) have been treated with PEG-IFNs (alpha-2a 180 mcg weekly or alpha-2b 1.5 mcg, weekly) and ribavirin for 6–12 months. Eleven patients had neuropathy at recruitment (two diabetic, nine HCV-related neuropathy, one with cryoglobulins). Before therapy (T0) all patients underwent quantitative viral RNA determination, HCV genotype analysis, liver biopsy, neurological and electrophysiological evaluation. Response amplitude and conduction velocities of median, ulnar, sural, and peroneal nerves were recorded. During therapy (T1)(mean follow-up 7,8 ± 4.0 months), patients were neurologically and electrophysiologically re-evaluated. Eighteen HCV patients (11 males, 7 females, median age 47.4 ± 9.6) with comparable viral load, not in IFN treatment, were studied as controls. Results: During PEG-IFNs therapy, no significant differences of all electrophysiological parameters were detected between T0 and T1 evaluations (repeated measures ANOVA) in all 44 treated and non-treated patients, also in those with neuropathy at recruitment. No correlations were found between electrophysiological parameters and length of therapy (Spearman's Rho). Conclusions: Peripheral neuropathy seems not to complicate PEG-IFNs therapy in HCV patients. An ongoing follow-up study on a larger group of patients will help confirm these results. [ABSTRACT FROM AUTHOR]

Parkinson's disease is characterized by heterogeneity of clinical presentations, association of signs and symptoms, rate of progression, and response to therapy. The aim of this prospective 5-year study was to evaluate whether clinical features at onset were predictive of the subsequent progression. Two courses were identified which differed in the characteristics at onset. Slow course was characterized by earlier age at onset, lateralization of motor signs, rest tremor, and absence of gait disturbance. Rapid course presented older age, less evident lateralization of signs, predominance of bradykinesia-rigidity and gait disturbance. Our results confirmed that PD is clinically heterogeneous and specific patterns of onset seem to be associated with different rates of disease progression. Predictive models based on these clinical characteristics have a good sensitivity in indicating a slow disease progression but are not reliable in indicating a rapid evolution. [ABSTRACT FROM AUTHOR]

This study was proposed to compare two different equipment: TCD (trans-cranial doppler) and TCCS (transcranial color-coded sonography) with or without using the angular correction, in a group of patients with the sickle cell anemia in order to identify the most suitable technique for the sampling of blood velocity (TAMM). 35 pediatric patients without previus history of neurological disease or transfusion were enrolled. Arteries examined were the middle cerebral artery, the anterior cerebral artery, the posterior cerebral and the basilar arteries. TAMM values greater than 200cm/s identify patients at high risk of stroke who are candidates for transfusion therapy. Our study demonstrated that there was a good correlation between TCCS and TCD. In addition, we found that if applied the angular correction to the TCCS increases the number of false-positive doppler examination. According to our study, we recommend to perform an initial assessment of the intracranial circulation with a method that allows to have morphological information, without the application of the angular correction. Indeed, the study of sickle cell anemia is complicated by the peculiar small diameter of the arteries and numerous variant of the circle of Willis. [Copyright &y& Elsevier]

Sickle Cell Disease (SCD) is a congenital familial pathology of the haemoglobin and it is classified as the most common genetic disease in the world. Neurological complications are very frequent: symptomatic stroke occurs in 11% of the SCD patients before they reach 20years of age, while 35% of the patients shows silent damages at the RMN with cognitive impairments and learning disabilities. The aim of this study is to verify the hypothesis that a different cerebral maturation between children with SCD and healthy controls exists. This has been achieved with the spectral analysis of electroencephalographic (EEG) rhythms and with the LORETA program that estimates the cortical sources of these rhythms. The study demonstrates that, according to both spectral and source analysis, the control group shows a consistent pattern while SCD patients show a great variability: some SCD children show a similar pattern as controls whereas others have a form which is compatible with a delayed degree of maturation. For these reasons, prompt cognitive and pharmacological treatments are advisable in SCD children that show impairments in neuropsychological tests. To this purpose, prospective studies on the effects of the hydroxyurea in the prevention of haemodynamics alterations would be useful. [Copyright &y& Elsevier]