Neonatal Cortical Auditory Evoked Potentials Are Affected by Clinical Conditions Occurring in Early Prematurity

Purpose: Cortical auditory evoked potentials may serve as an early indicator of developmental problems in the auditory cortex. The aim of the study was to determine the effect on neonatal cortical auditory processing of clinical conditions occurring in early prematurity. Methods: Sixty-seven preterm infants born at 29 weeks mean gestational age (range, 23\u201334 weeks) were recorded at a mean postconception age of 35 weeks, before discharge from the third level neonatal intensive care unit. The average of 330 responses to standard 1000 Hz pure tones delivered in an oddball paradigm was recorded at frontal location. Data of 45 of 67 recruited premature infants were available for analysis. Mean amplitudes calculated from the data points of 30 milliseconds centered on P1 and N2 peaks in the waveforms of each subject were measured. The effect of perinatal clinical factors on cortical auditory evoked responses was evaluated. Results: The amplitude of P1 component was significantly lower in infants with bronco-pulmonary dysplasia (P \ubc 0.004) and retinopathy of prematurity (P \ubc 0.03). The multivariate analysis, done to evaluate the relative weight of gestational age and bronco-pulmonary dysplasia and/or retinopathy of prematurity on cortical auditory evoked potentials components, showed an effect of clinical factors on P1 (P \ubc 0.005) and of gestational age on N2 (P \ubc 0.02). Conclusions: Cortical auditory processing seems to be influenced by clinical conditions complicating extremely preterm birth

The Impact of Age and Duration of Cochlear Implant in a Congenital Deaf Population: An ERP Study

Objective: It is well known that patients with Cochlear Implant (CI) have a large inter-individual variability in linguistic and auditory performances. This can be related to individual auditory processing abilities and integrity of auditory system from auditory nerve to cerebral cortex. P300 can be used for the evaluation of central auditory functions in people with hearing loss and CI. No studies considered the P300 in the population of prelingually deafened adults that underwent CI in old age. The aim of this study is to assess Event Related Potential (ERP) in patients with congenital profound hearing loss with early or late implantation and evaluate these results respect to an age-matched normal hearing group. Methods: ERPs (N100, N200 and P300) and auditory benefit testing (pure tone average and speech audiometric test) and auditory perception testing (Categories of Auditory Performance\u2014CAP) were evaluated in all subjects with their device. Results: All mean latencies (N100, N200 and P300) were found greater in patients group compared to control group. When analyzing all measures in patient group, we did not find any significant differences according to age of implant while significant difference (p > 0.05) in N100 amplitude (p = 0.045) and P300 latency (p = 0.035) were found according to time of CI use. A linear correlation between N200 and P300 latency in control and patients groups was found. Conclusion: In summary, ERPs analysis in the evaluation of CI showed a great importance of long use of the device in addiction to an early time of implant

Primary stroke prevention for sickle cell disease in north-east Italy: the role of ethnic issues in establishing a Transcranial Doppler screening program

<p>Abstract</p> <p>Background</p> <p>Stroke is a serious complication of sickle cell disease (SCD) in children. Transcranic Doppler (TCD) is a well-established predictor of future cerebrovascular symptoms: a blood flow velocity >200 cm/sec in the Middle Cerebral Artery (MCA) correlates with a high risk of stroke in cohorts of African-american HbS/HbS patients. In North-East Italy the recent increase in SCD patients is mainly due to immigration from Africa. A comprehensive care program for children with SCD was established in our Center since 2004, but a wide and routine screening for Primary stroke prevention needs to be developed.</p> <p>Methods</p> <p>In order to verify the feasibility of TCD and Transcranial color coded Sonography (TCCS) screening in our setting and the applicability of international reference values of blood velocities to our population of African immigrants with HbS/HbS SCD, we performed TCD and TCCD in 12 HbS/HbS African children and two groups of age-matched controls of Caucasian and African origin respectively. TCD and TCCS were performed on the same day of the scheduled routine hematologic visit after parental education.</p> <p>Results</p> <p>All parents accepted to perform the sonography to their children. TCD and TCCD were performed in all patients and an adequate temporal window could be obtained in all of them. Pulsatility index and depth values in both the MCA and the Basilar Artery (BA) were similar at TCD and TCCS evaluation in the three groups while time-average maximum velocities (TAMM), peak systolic velocity and diastolic velocity in the MCA and BA were higher in the patients' group on both TCD and TCCS evaluation. African and Caucasian healthy controls had similar lower values.</p> <p>Conclusion</p> <p>Our preliminary data set the base to further evaluate the implementation of a primary stroke prevention program in our setting of HbS/HbS African immigrants and HbS/beta thalassemia Italians. Parental education-preferably in the native language- on stroke risk and prevention in SCD increases compliance and should be a necessary part of the program. Ethnic background does not seem to influence TCD velocity and internationally accepted reference values already validated in African-American SCD pediatric patients can be used, but long prospective trials are needed to verify their efficacy in defining stroke risk in our setting.</p

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study

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Early and long-term outcomes of carotid endarterectomy in the very elderly: An 18-year single-center study

ObjectiveTo evaluate the perioperative (30-day) and long-term outcomes of carotid endarterectomy (CEA) in elderly patients with severe symptomatic and asymptomatic carotid disease. Although the efficacy of CEA in preventing stroke in selected patients has been clearly demonstrated, concern has been expressed about the role of CEA in people over 80 years old.MethodsAn analysis was conducted on a prospectively compiled computerized database of all primary CEAs performed at our institution from 1990 to 2007. Descriptive demographic data, risk factors, surgical details, perioperative strokes and deaths, and other complications were recorded. All patients underwent postoperative duplex ultrasound scanning and clinical follow-up at one, six, and 12 months, and yearly thereafter. Survival analyses were performed using Kaplan-Meier life-tables. Long-term relative survival after CEA was assessed against age- and gender-matched controls.ResultsIn all, 1769 CEAs were performed in 1562 patients, 193 of them (207 CEAs; group I) were ≥ 80 years old and 1371 were younger (1562 CEAs; group II). All CEA procedures were performed with patients under deep general anesthesia with continuous perioperative EEG monitoring for selective shunting. No strokes or deaths occurred in group I, whereas there were 11 perioperative strokes and three deaths in group II (1%). A complete follow-up (median, 5.2 years) was obtained in 185 elderly patients: no late occlusions or restenoses were detected, while the seven-year freedom from stroke and death were 96.6% and 52.4%, respectively. The relative seven-year survival rate was 99.8%.ConclusionsCEA in elderly patients proved safe and effective, with an excellent long-term durability. The long-term relative survival after CEA in elderly patients was better than in an age-and gender-matched population, so the likelihood of living long enough to benefit from CEA is not jeopardized by being very elderly

Short-wave diathermy in the clinical management of musculoskeletal disorders: a pilot observational study

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D-KEFS ST Failure Identifies Multiple Sclerosis Patients With Worse Objective and Self-Perceived Physical and Cognitive Disability

Background and Objectives: The Brief Repeatable Battery of Neuropsychological Test (BRB-NT) does not explore the executive functions. We combined BRB-NT and Delis-Kaplan Executive Function System Sorting Test (D-KEFS ST) to obtain a more comprehensive evaluation of cognitive impairment in Multiple Sclerosis (MS) patients.Methods: 137 Relapsing Remitting MS (RRMS) patients underwent a detailed neuropsychological assessment including BRB-NT, D-KEFS ST and self-administrated questionnaires, namely the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), the Fatigue Severity Scale (FSS) and the Beck Depression Inventory-Second Edition (BDI-II).Results: Fifty-four patients (39.4%) had normal scores in each item of both batteries (cognitive normal), while 64 patients (46.7%) failed in at least one test of BRB-NT but not of D-KEFS ST (BRB-NT impaired) and 18 (13.1%) failed in at least one test of both batteries (BRB-NT+D-KEFS ST impaired). Only one patient (0.7%) failed in D-KEFS ST, but not in BRB-NT and was excluded from further analysis. BRB-NT+D-KEFS ST impaired patients had a significant higher mean disease duration and median EDSS score (15.5 ± 13.6 years and 3.5, respectively) compared to those with only BRB-NT impaired (7.9 ± 9.2, p &lt; 0.01 and 2.5, p &lt; 0.05) and with cognitive normal patients (6.7 ± 9.4, p &lt; 0.005 and 2.0, p &lt; 0.01). SDMT was more frequently impaired in BRB-NT+D-KEFS ST impaired patients (77.8%) compared to only BRB-NT impaired ones (20.0%, p &lt; 0.001). The failure in D-KEFS ST was associated with the number of failed BRB-NT items (OR 1.46, IC95% 1.07–1.99, p &lt; 0.05) and with pathological SDMT z-value (OR 10.56, IC95% 2.50–44.66, p &lt; 0.005). Compared to BRB-NT impaired patients and the cognitive normal ones, BRB-NT+D-KEFS ST impaired patients had significant higher MSNQ (p &lt; 0.01) and BDI-II (p &lt; 0.05) values.Conclusion: D-KEFS ST did not increase the number of cognitively impaired MS patients identified by BRB-NT, but provided a more comprehensive evaluation of cognitive decline. D-KEFS ST identified a subgroup of patients with increased self-perception of cognitive decline, depression and higher physical disability

Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

Non-neural phenotype of spinal and bulbar muscular atrophy: Results from a large cohort of Italian patients

Objective: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). Methods: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. Results: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. Conclusions: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients. \ua9 2016 Published by the BMJ Publishing Group Limited

Promoter methylation analysis of O6-methylguanine-DNA methyltransferase in glioblastoma: detection by locked nucleic acid based quantitative PCR using an imprinted gene (SNURF) as a reference

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of the <it>MGMT </it>gene by promoter methylation is associated with loss of <it>MGMT </it>expression, diminished DNA-repair activity and longer overall survival in patients with glioblastoma who, in addition to radiotherapy, received alkylating chemotherapy with carmustine or temozolomide. We describe and validate a rapid methylation sensitive quantitative PCR assay (MS-qLNAPCR) using Locked Nucleic Acid (LNA) modified primers and an imprinted gene as a reference.</p> <p>Methods</p> <p>An analysis was made of a database of 159 GBM patients followed between April 2004 and October 2008. After bisulfite treatment, methylated and unmethylated CpGs were recognized by LNA primers and molecular beacon probes. The <it>SNURF </it>promoter of an imprinted gene mapped on 15q12, was used as a reference. This approach was used because imprinted genes have a balanced copy number of methylated and unmethylated alleles, and this feature allows an easy and a precise normalization.</p> <p>Results</p> <p>Concordance between already described nested MS-PCR and MS-qLNAPCR was found in 158 of 159 samples (99.4%). The MS-qLNAPCR assay showed a PCR efficiency of 102% and a sensitivity of 0.01% for LNA modified primers, while unmodified primers revealed lower efficiency (69%) and lower sensitivity (0.1%). <it>MGMT </it>promoter was found to be methylated using MS-qLNAPCR in 70 patients (44.02%), and completely unmethylated in 89 samples (55.97%). Median overall survival was of 24 months, being 20 months and 36 months, in patients with <it>MGMT </it>unmethylated and methylated, respectively. Considering <it>MGMT </it>methylation data provided by MS-qLNAPCR as a binary variable, overall survival was different between patients with GBM samples harboring <it>MGMT </it>promoter unmethylated and other patients with any percentage of <it>MGMT </it>methylation (p = 0.003). This difference was retained using other cut off values for <it>MGMT </it>methylation rate (i.e. 10% and 20% of methylated allele), while the difference was lost when 50% of <it>MGMT </it>methylated allele was used as cut-off.</p> <p>Conclusions</p> <p>We report and clinically validate an accurate, robust, and cost effective MS-qLNAPCR protocol for the detection and quantification of methylated <it>MGMT </it>alleles in GBM samples. Using MS-qLNAPCR we demonstrate that even low levels of <it>MGMT </it>promoter methylation have to be taken into account to predict response to temozolomide-chemotherapy.</p