Highlights ► Abnormal 5 Hz-rTMS responses in AD patients, indicate altered synaptic plasticity. ► These responses remain abnormal even after chronic treatment with rivastigmine. ► Our results might ...explain why rivastigmine yields a poor clinical benefit in AD. ► AD patients might fare better with drugs improving cortical plasticity.
Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic ...determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (
) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (
) rs58542926, membrane bound O-acyltransferase domain containing 7 (
) rs641738, and cluster of differentiation 14 (
) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption.
A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and
,
,
, and
variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves.
We found that
,
, and
were associated with alcoholic cirrhosis prevalence.
and
were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of
allele T) + (number of
allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity.
We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors.
We aimed at seeking more precise diagnostic information on the sensory nervous system involvement described in patients with amyotrophic lateral sclerosis (ALS). We investigated large myelinated ...nerve fibers with nerve conduction study and small-nerve fibers with Quantitative Sensory Testing (QST) (assessing thermal-pain perceptive thresholds) and skin biopsy (assessing intraepidermal nerve fiber density) in 24 consecutive patients with ALS, 11 with bulbar-onset and 13 with spinal-onset. In 23 of the 24 patients, regardless of ALS onset, nerve conduction study invariably showed large myelinated fiber sparing. In patients with bulbar-onset ALS, QST found normal thermal-pain perceptive thresholds and skin biopsy disclosed normal intraepidermal nerve fiber density. Conversely, in patients with spinal-onset, thermal-pain thresholds were abnormal and distal intraepidermal nerve fiber density was reduced. Sensory nervous system involvement in ALS differs according to disease onset. Patients with spinal-onset but not those with bulbar-onset ALS have concomitant distal small-fiber neuropathy. Neurologists should therefore seek this ALS-related non-motor feature to improve its diagnosis and treatment.
Anxiety symptoms in depression result often in treatment resistance, residual symptoms, and persistent functional impairment.
To assess the effectiveness and safety of adjunctive pregabalin to ...antidepressants for residual anxiety in patients with major depressive disorder (MDD).
A retrospective chart review was conducted to identify partial responders among patients with MDD with residual anxiety. Twenty such patients (age, 58.4 ± 11.2 years; 15 women; baseline Hamilton Depression Rating Scale HDRS, 17.1 ± 3.5) who received adjunctive pregabalin for residual anxiety were included. Antidepressants augmented were the selective serotonin reuptake inhibitors (n = 12), mirtazapine (n = 2), and selective serotonin-norepinephrine reuptake inhibitors (n = 6).
Twenty patients received at least 4 weeks of pregabalin treatment after 8 weeks of antidepressant therapy. At week 1 (9 weeks after initiating treatment), pregabalin was prescribed at a mean ± SD dose of 71.2 ± 31.7 mg, and the mean maximum pregabalin dose prescribed was 156.2 ± 76.5 mg (range, 75-300 mg). At week 8, there were 13 responders (13/20 65%), and 7 of these 13 patients achieved remission (HDRS17 < 8). There were significant decreases in HDRS scores (13.5 ± 3.1 vs 9.1 ± 2.9, P < 0.000), and HDRS anxiety/somatization subscale scores (6.3 ± 2 to 3.6 ± 1.7, P < 0.000). Adverse effects included somnolence (n = 7), weight gain (n = 3), dizziness (n = 4), dry mouth (n = 6), edema (n = 3), blurred vision (n = 3), difficulty with concentration/attention (n = 8), headache (n = 6), and diarrhea (n = 5).
The results suggest a possible augmentation role for pregabalin when used in conjunction with conventional antidepressants for residual anxiety in MDD.
To examine the extent to which a effect does exist between Positivity (POS), smoking and socio-demographic factors in determining quitting smoking in subjects participating in a Group Counselling ...Program (GCP) for smoking cessation.
481 subjects were contacted through a telephone call. A logistic regression analysis was carried out. Possible interaction between sociodemographic variables and POS level was tested using the Synergism Index (SI).
For individuals with a POS level over or equal to 3.4 the odds of being smoker was significantly higher among females (OR = 1.55), who smoked at home (OR = 2.16) and lower if there had children at home (OR = 0.53). For individuals with a POS level under 3.4, the only significant variable associated with smoking was beinga female (OR = 2.58). As far concerns the synergistic effect between the variables considered does exist between POS levels and having children at home (SI=1.13) and female gender (SI = 2.8).
The synergistic effect between POS and sociodemographic factors adds evidence on the use of POS as possible determinants of individual happiness.
EMG, blink reflex and nerve conduction studies in Bell’s palsy can help to determine the site of nerve injury and the lesion characterization: neurapraxia, axonotmesis and neurotmesis. Aim of this ...study was to determine electrophysiology role in predicting clinical outcome. We recruited 92 patients in a longitudinal prospective study. Three neurophysiological evaluations were performed 10–14 days, 17–21 days and 3 months after palsy onset. Clinical evaluation used the House-Brackmann scale, in a 6 months follow-up period. Reinnervation ( p < 0.05; R = 0.49) and maximum contraction trace measured from orbicularis oculi ( p < 0.05; R = 0.48) and oris ( p < 0.05; R = 0.49) at baseline correlated with HB clinical scale. The presence of denervation at baseline significantly related with HB scale at second evaluation (orbicularis oculi: p < 0.05; R = 0.30; orbicularis oris: p < 0.05; R = 0.29). Combination of blink reflex and ENG demonstrated 2%-increased risk of not reaching the main outcome (HB scale ⩽2) for each additional point of degeneration index in patients who had absence of blink reflex. Regarding synkinesis, at first neurophysiological evaluation only the presence of orbicularis oculi denervation (HR = 3.31, p = 0.041) was associated with a poor prognosis. Baseline ENG/EMG and 17–21 days after palsy onset ENG and blink reflex are related to clinical outcomes in Bell’s palsy.
Our aim was to investigate whether rapid changes in visual input or prolonged visual deafferentation modify primary motor cortex (M1) excitability in healthy subjects. rTMS, consisting of 10 stimuli ...delivered at 5 Hz, at 120% of resting motor threshold was delivered over M1 in 13 healthy volunteers. They were instructed to relax under eyes-opened (EO) and eyes-closed (EC) resting conditions. Two experimental sessions were performed. In the first session, subjects were tested in both EO and EC conditions in order to see whether short visual deprivation affected the M1 excitability, through the possible changes in the motor evoked potential (MEP) amplitude during the rTMS. In the second session, rTMS was delivered both under EO with room lights on and after 30 min of blindfolding in order to evaluate the effects of prolonged visual deprivation on the M1 excitability. A short-term visual deprivation left the MEP facilitation unchanged during 5 Hz-rTMS trains, whilst 30 min of blindfolding significantly decreased the MEP facilitation. The short-term visual deprivation condition did not significantly influence the M1 excitability, whereas prolonged visual deafferentation decreased rTMS-induced MEP facilitation. Prolonged visual deafferentation can significantly modulate motor cortical synaptic plasticity.
Abstract Objective We designed this study to find out whether 5 Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and ...in patients with chronic alcohol consumption. Methods Ten stimuli-5 Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3 ms) and intracortical facilitation (10 ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. Results In healthy subjects before and after acute ethanol intake, 5 Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5 Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. Conclusions Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5 Hz-rTMS. Significance This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.
Background
: Chronic alcohol abuse is a risk factor for osteoporosis and fractures, whose pathogenesis is still unclear. We investigated the influence of alcoholism and other risk factors on calcium ...and skeletal metabolism, bone mineral density (BMD), and fractures.
Materials and methods
: In 51 chronic male alcoholics without liver failure and 31 healthy controls, serum total and ionised calcium, phosphate, creatinine, 25-hydroxy vitamin D (25OHD), PTH, total (ALP) and bone-specific (BALP) alkaline phosphatase, osteocalcin (BGP), carboxy-terminal telopeptide of type I collagen (β-CTx), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were assessed. In patients only, we also measured serum testosterone, 17-β estradiol, LH, and IGF-I. BMD was measured by dual energy x-ray absorptiometry at lumbar spine (LS-) and femur neck (FN-) and total hip (TF-). Vertebral fractures were identified by a semiquantitative method on thoraco-lumbar spine x-ray, non-vertebral fractures (as life-style factors) by history.
Results
: Alcoholics were leaner, had significantly higher ALP and BALP, and lower BGP and 25OHD levels than controls. No significant difference in other calcium and bone metabolism parameters was found. OPG/RANKL ratio was significantly higher in alcoholics. Beta-CTx negatively correlated with abuse duration. OPG positively correlated with daily alcohol assumption and with indexes of liver cytolysis. Though LS-, FN-and TF-BMD of alcoholics and controls did not significantly differ, patients had a much higher prevalence of vertebral fractures. The same was found considering both vertebral and non-vertebral fractures.
Conclusions
: Ethanol-induced skeletal damage seems mainly dependent on negative effects on bone formation. Lifestyle factors and traumas likely contribute to the high fracture incidence of alcohol abusers, independently of BMD.
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