Epilepsy may cause increased pain sensitivity: Evidence from absence epileptic WAG/Rij rats

ObjectiveThe comorbidity of epilepsy and pain disorders as well as effectiveness of certain therapeutic approaches in both conditions attracted attention to epilepsy–pain interactions. This lead to the discovery of significantly shared pathophysiological mechanisms although many aspects remain largely unknown. To test the hypothesis that epilepsy may be associated with altered pain sensitivity, we analyzed interictal pain sensitivity using epilepsy prone WAG/Rij rats, a genetic model exhibiting age-related-onset absence epilepsy.MethodsTwo series of experiments were conducted. In experiment I, pain sensitivity of symptomatic WAG/Rij rats were compared with age-matched control Wistar rats. In experiment II, pain sensitivity of WAG/Rij rats were monitored longitudinally when they were presymptomatic (at 2 months) and symptomatic (after maturation, at 8 months), and compared with age-matched control Wistar rats. Pain sensitivity was assessed by applying heat stimuli to hind paws and measuring the paw-withdrawal latency using thermal plantar analgesia meter in awake and freely moving animals. All pain measurements were made during the interictal period, confirmed by simultaneous electroencephalography through intracranially implanted electrodes.ResultsIn experiment I, the interictal pain withdrawal latency of symptomatic WAG/Rij rats was significantly shorter than control Wistar rats (P < 0.01).In experiment II, WAG/Rij rats had significantly shorter latency of withdrawal response than control Wistar rats, both at presymptomatic (P < 0.05) and symptomatic stage (P < 0.0001). Matured (8 months old) control Wistar rats demonstrated significantly increased withdrawal latency compared to the 2 months animals (P < 0.01), but the WAG/Rij rats did not (P > 0.5).ConclusionEpileptic WAG/Rij rats present significantly increased pain sensitivity when compared to control Wistar rats, suggesting comorbidity of epilepsy and pain.     

Polyneuropathy induced by HIV disease and antiretroviral therapy

ObjectiveTo investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs.MethodsWe tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining.ResultsSeverity of the disease (CD4 + count) correlated to conduction velocities of peroneal (p < 0.01, Spearmans rank correlation), sural (p < 0.01) and median nerves (p < 0.05/p < 0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p > 0.3) but correlated to reduced IENFD in the ankle (r = ?0.24, p < 0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4 + count.ConclusionsNeurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers.SignificanceThese findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment.     

Ectonucleotidase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of streptozotocin-induced diabetic rats and treated with resveratrol

The aim of the present study was to investigate the effects of resveratrol (RV), an important neuroprotective compound on NTPDase, 5′-nucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes of streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n = 8): control/saline; control/RV 10 mg/kg; control/RV 20 mg/kg; diabetic/saline; diabetic/RV 10 mg/kg; diabetic/RV 20 mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results demonstrated that NTPDase and 5′-nucleotidase activities were significantly increased in the diabetic/saline group (p < 0.05) compared to control/saline group. Treatment with resveratrol significantly increased NTPDase, 5′-nucleotidase activities in the diabetic/RV10 and diabetic/RV20 groups (p < 0.05) compared to diabetic/saline group. When resveratrol was administered per se there was also an increase in the activities of these enzymes in the control/RV10 and control/RV20 groups (p < 0.05) compared to control/saline group. AChE activity was significantly increased in the diabetic/saline group (p < 0.05) compared to control/saline group. The treatment with resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups. In conclusion, this study demonstrated that the resveratrol interfere with the purinergic and cholinergic neurotransmission by altering NTPDase, 5′-nucleotidase and AChE activities in cerebral cortex synaptosomes of diabetic rats. In this context, we can suggest that resveratrol should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with the diabetes.     

Trends in the presentation,surgical treatment,and outcomes of tethered cord syndrome: A nationwide study from 2001 to 2010

ObjectiveThis is a nationwide query into surgical management techniques for tethered cord syndrome, focusing on patient demographic, hospital characteristics, and treatment outcomes. Our hypothesis is that detethering vs. fusion for TCS results in different in-hospital complications.Materials and methodsRetrospective review of the Nationwide Inpatient Sample 2001–2010. Inclusion: TCS discharges undergoing detethering or fusion. Sub-analysis compared TCS cases by age (pediatric [≤9 years] vs. adolescent [10–18 year]). Independent t-tests identified differences between fusion and detethering for hospital-related and surgical factors; multivariate analysis investigated procedure as a risk factor for complications/mortality.Results6457 TCS discharges: 5844 detetherings, 613 fusions. Fusion TCS had higher baseline Deyo Index (0.16 vs. 0.06), procedure-related complications (21.3% vs. 7.63%), and mortality (0.33% vs. 0.09%) than detethering, all p < 0.001. Detethering for TCS was a significant factor for reducing mortality (OR 0.195, p < 0.001), cardiac (OR 0.27, p < 0.001), respiratory (OR 0.26, p < 0.001), digestive system (OR 0.32, p < 0.001), puncture nerve/vessel (OR 0.56, p = 0.009), wound (OR 0.25, p < 0.001), infection (OR 0.29, p < 0.001), posthemorrhagic anemia (OR 0.04, p = 0.002), ARDS (OR 0.13, p < 0.001), and venous thrombotic (OR 0.53, p = 0.043) complications. Detethering increased nervous system (OR 1.34, p = 0.049) and urinary (OR 2.60, p < 0.001) complications. Adolescent TCS had higher Deyo score (0.08 vs. 0.03, p < 0.001), LOS (5.77 vs. 4.13 days, p < 0.001), and charges ($54,592.28 vs. $33,043.83, p < 0.001), but similar mortality. Adolescent TCS discharges had increased prevalence of all procedure-related complications, and higher overall complication rate (11.10% vs. 5.08%, p < 0.001) than pediatric.ConclusionsWith fusion identified as a significant risk factor for mortality and multiple procedure-related complications in TCS surgical patients, this study could aid surgeons in counseling TCS patients to optimize outcomes.     

Adult separation anxiety disorder in complicated grief: an exploratory study on frequency and correlates

IntroductionComplicated grief (CG) has been the subject of increasing attention in the past decades but its relationship with separation anxiety disorder (SEPAD) is still controversial. The aim of the current study was to explore the prevalence and clinical significance of adult SEPAD in a sample of help-seeking individuals with CG.Methods151 adults with CG, enrolled in a randomized controlled trial comparing the effectiveness of (CG) treatment to that of interpersonal therapy, were assessed by means of the Inventory of Complicated Grief (ICG), the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression (HAM-D), the Work and Social Adjustment Scale (WSAS), the Adult Separation Anxiety Questionnaire (ASA-27), the Grief Related Avoidance Questionnaire (GRAQ), the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), and the Impact of Events Scale (IES).Results104 (68.9%) individuals with CG were considered to have SEPAD (ASA-27 score ≥22). Individuals with SEPAD were more likely to have reported a CG related to the loss of another close relative or friend (than a parent, spouse/partner or a child) (p = .02), as well as greater scores on the ICG (p = <.001), PDEQ (p = .004), GRAQ (p < .001), intrusion (p < .001) and avoidance (p = <.001) IES subscales, HAM-D (p < .001) and WSAS (p = .006). ASA-27 total scores correlated with ICG (p < .0001), PDEQ (p < .001) GRAQ (p < .0001) scores and both the IES intrusion (p < .0001) and IES avoidance (p < .0001) subscale scores. People with SEPAD had higher rates of lifetime post-traumatic stress disorder (PTSD) (p = .04) and panic disorder (PD) (p = .01).ConclusionsSEPAD is highly prevalent among patients with CG and is associated with greater symptom severity and impairment and greater comorbidity with PTSD and PD. Further studies will help to confirm and generalize our results and to determine whether adult SEPAD responds to CG treatment and/or moderates CG treatment response.     

Central nervous system abnormalities in vaginismus

ObjectiveTo investigate possible altered CNS excitability in vaginismus.MethodsIn 10 patients with primary idiopathic lifelong vaginismus, 10 with vulvar vestibulitis syndrome accompanied by vaginismus and healthy controls we recorded EMG activity from the levator ani (LA) and external anal sphincter (EAS) muscles and tested bulbocavernosus reflex (BCR). Pudendal-nerve somatosensory evoked potentials (SEPs) were tested after a single stimulus. Pudendal-nerve SEP recovery functions were assessed using a paired conditioning-test paradigm at interstimulus intervals (ISIs) of 5, 20 and 40 ms.ResultsEMG in patients showed muscular hyperactivity at rest and reduced inhibition during straining. The BCR polysynaptic R2 had larger amplitude (p < 0.01) and longer duration (p < 0.01) in patients from both groups than in controls. In controls, paired-pulse SEPs were suppressed at the 5 ms ISI for N35–P40 (p < 0.05) and P40–N50 ms (p < 0.001) and facilitated at the 20 ms ISI for N35–P40 (p < 0.05) and P40–N50 (p < 0.05). No significant differences were found in the paired-pulse N35–P40 in patients and controls but the cortical P40–N50 at 20 ISI was facilitated in patients (p < 0.05).ConclusionsEMG activity is enhanced and the cortical SEP recovery cycle and BCR are hyperexcitable in vaginismus.SignificanceThe neurophysiological abnormalities in patients with vaginismus indicate concomitant CNS changes in this disorder.     

Sexual performance and precontact 50-kHz ultrasonic vocalizations in WAG/Rij rats: Effects of opioid receptor treatment

WAG/Rij rats are genetically selected animals that model absence epilepsy in rats. Ultrasonic vocalizations and sexual behavior – both ethologically relevant markers of reward system functioning – are poorly described in this strain. The aim of our experiment was to investigate reward-dependent precontact 50-kHz vocalizations (PVs) and copulatory behavior as well as the effects of opioid receptor treatment on such behaviors in sexually experienced WAG/Rij males and rats from two control strains: Sprague–Dawley and Crl: Han Wistar. We analyzed the effects of the opioid receptor antagonist naltrexone (3 mg/kg) and the agonist morphine (1 mg/kg) administration. Additionally, we analyzed the initiation of copulation in sexually naïve males before drug treatment. A significantly lower number of sexually naïve WAG/Rij rats initiated copulation. Sexually experienced WAG/Rij males differed at the control session (after physiological saline treatment) compared with Sprague–Dawley rats: WAG/Rij rats displayed more 50-kHz precontact vocalizations and had longer mount and intromission latencies, longer ejaculation latency, longer postejaculatory latency to exploration, longer 22-kHz vocalization duration after ejaculation, and longer postejaculatory intromission latency. Compared with Crl: Han Wistar rats, WAG/Rij males displayed longer mount latency and shorter 22-kHz vocalization duration. Neither naltrexone nor morphine affected PVs in all groups. On the other hand, opioid receptor treatment differently influenced the number of intromissions required to achieve ejaculation and 22-kHz postejaculatory vocalization duration in WAG/Rij rats than in both control groups. This suggests functional differences in the opioid system in this strain. As a result of the number of males that initiated copulation as well as the number of intromissions to ejaculation and 22-kHz postejaculatory vocalizations which all depend on D1 receptor activation, we suggest that the proportion of opioid receptor to D1 receptors in WAG/Rij rats is different when compared with the control strains. The reward system of Wag/Rij rats with absence epilepsy is sensitive to social rewards (high level of precontact 50-kHz ultrasounds) although this strain displays a lower level of sexual motivation (longer mount latency) compared with other control strains. A lower number of sexually naïve rats initiating copulation and longer mount latency in sexually experienced males could suggest a moderate depressive-like syndrome in this strain of rats.     

Sensorimotor function in preschool-aged children with expressive language disorder

AimThe aim of the study was to evaluate functional motor performance and haptic object recognition in 5-year-old children with mild expressive language disorder (ELD) in comparison with age- and gender-matched healthy children.MethodsThe subjects were classified by speech-language pathologist using The Reynell Developmental Language Scales III and Boehm Test of Basic Concepts: Preschool as children with mild ELD (n = 29, incl. 23 boys and 6 girls) and children with typical language development as controls (n = 29, incl. 23 boys and 6 girls). The children were examined for manual dexterity, ball skills, static and dynamic balance by Movement-ABC, haptic object recognition (HOR), hand-grip strength (HGS) and vertical jumping performance.ResultsChildren with mild ELD demonstrated significantly higher scores (i.e., inferior performance) in all subtests of M-ABC (all p values <0.05), in haptic object recognition (p < 0.01) and vertical jumping height (p < 0.05) compared to controls. However, no statistically significant differences (p > 0.05) emerged from HGS. Boys with mild ELD demonstrated higher results in impairment score (p < 0.001), ball skills (p < 0.01) and balance (p < 0.01) of M-ABC, as well as in HOR (p < 0.05). Girls with mild ELD showed higher impairment score (p < 0.05) with lower percentile (p < 0.05) in M-ABC, indicating inferior motor performance, and lower HGS for the non-dominant hand (p < 0.05). Seven out of 29 (24.1%) children with mild ELD had definite or borderline motor difficulties, while only one child in control group (3.4%) demonstrated borderline motor difficulties.ConclusionsChildren with mild expressive language disorder do not perform as well as controls in tests of functional motor skills, but their results in tests demanding maximal muscle force generation are in level with typically developing children. Boys and girls with mild ELD demonstrated higher impairment scores in M-ABC, indicating the need to follow their overall development more closely.     

Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities

BackgroundDespite being frequently described in patients with end-stage renal disease (ESRD), clinical characteristics and comorbidities in association with restless legs syndrome (RLS) are still to be confirmed.ObjectivesThe aim of this study was to investigate clinical factors associated with RLS in ESRD patients in hemodialysis.MethodsThis is a cross-sectional study of 400 patients on hemodialysis, evaluating RLS, clinical features and other sleep abnormalities.ResultsOut of 400, 86 patients presented RLS (21.5%; mean age 48.8 ± 13.8 y), being more frequent in females (p < 0.005). Forty-eight individuals (12% mean age 50.7 ± 13.1 y) had moderate/severe RLS, 14 reported symptoms prior to hemodialysis, 13 described family history of RLS, and eight described symptoms as disturbing during dialysis. RLS cases showed lower hemoglobin (p < 0.005), poorer quality of sleep (Pittsburgh Sleep Quality Index >5, p = 0.002), higher scores on the Beck Depression Inventory Scale (p < 0.005), greater scores on the Charlson Comorbidity Index (p = 0.01) and the Epworth Sleepiness Scale (p = 0.001) and higher risk of obstructive sleep apnea (OSA; Berlin questionnaire, p = 0.01). Hypertension was more frequent in cases with moderate/severe RLS (p = 0.01) and remained after controlling for the risk of OSA (p = 0.02).ConclusionIn ESRD patients in hemodialysis, RLS is present in 21.5%; 16% report symptoms prior to hemodialysis and a family history of RLS. Symptoms are disturbing during hemodialysis in 9% of cases. RLS is associated with lower hemoglobin, worse sleep quality, excessive daytime sleepiness, depressive symptoms and higher risk of OSA. Hypertension is associated with moderate/severe RLS.     

Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

ObjectiveHigher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr).MethodsPlasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4⁺ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin.ResultsBefore ART, phe/tyr was mean ± S.D.: 0.99 ± 0.57 μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs = 0.434, and rs = 0.392; both p < 0.001) and less strongly with HIV-RNA levels (rs = 0.173) and CD4⁺ counts (rs = ?0.182, both p < 0.05). After ART, phe/tyr dropped to 0.72 ± 0.16 (=?27%; U = 5.21, p = 0.01) which was due to an average decline of ?14% of phe concentrations from 73.1 ± 34.0 μmol/L at baseline to 62.9 ± 17.8 μmol/L after ART (U = 2.51, p = 0.01) and a concomitant increase of tyr concentrations (+13%, U = 2.46, p = 0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART.ConclusionsIncreased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients.     

Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults

BackgroundDysfunctional neutrophils with advanced age are a hallmark of immunosenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age. Physical activity and structured exercise have been suggested to improve immune function in the elderly. The aim of this study was to assess a comprehensive range of neutrophil functions and determine their association with habitual physical activity.MethodPhysical activity levels were determined in 211 elderly (67 ± 5 years) individuals by 7-days of accelerometry wear. Twenty of the most physically active men and women were matched for age and gender to twenty of the least physically active individuals. Groups were compared for neutrophil migration, phagocytosis, oxidative burst, cell surface receptor expression, metabolic health parameters and systemic inflammation. Groups were also compared against ten young participants (23 ± 4 years).ResultsThe most active group completed over twice as many steps/day as the least active group (p < 0.001), had lower BMI’s (p = 0.007) and body fat percentages (p = 0.029). Neutrophils migrated towards IL-8 better in the most active group compared to the least active (p < 0.05) and was comparable to that of the young (p > 0.05). These differences remained after adjusting for BMI, body fat and plasma metabolic markers which were different between groups. Correlations revealed that steps/day, higher adiponectin and lower insulin were positively associated with migratory ability (p < 0.05). There was no difference in expression of the chemokine receptors CXCR1 or CXCR2 (p > 0.05 for both). CD11b was higher in the most active group compared to the least active (p = 0.048). No differences between activity groups or young controls were observed for neutrophil phagocytosis or oxidative burst in response to Escherichia coli (p > 0.05). The young group had lower concentrations of IL-6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p < 0.05 for all) with no differences between the two older groups.ConclusionThese data suggest that impaired neutrophil migration, but not bactericidal function, in older adults may be, in part, the result of reduced physical activity. A 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people. As a consequence increasing habitual physical activity may be beneficial for neutrophil mediated immunity.     

Levetiracetam but not valproate inhibits function of CD8+ T lymphocytes

PurposeTo further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8⁺ T lymphocytes in humans.MethodsIn 15 healthy subjects (9 female (60%), 35.7 ± 12.1 years), apoptosis and cytotoxic function of CD8⁺ T lymphocytes were measured using flow cytometry following in vitro exposure to LEV (5 mg/L and 50 mg/L) and VPA (10 mg/L and 100 mg/L). Apoptosis rates were determined after incubation with LEV or VPA for 1 h or 24 h. Cytotoxic function was assessed following 2 h stimulation with mixed virus peptides, using perforin release, CD107a/b expression and proliferation. The presence of synaptic vesicle protein 2A (SV2A) was investigated in human CD8⁺ T lymphocytes by flow cytometry analysis, Western blot and real time polymerase chain reaction (rtPCR).ResultsHigh concentration of LEV decreased perforin release of CD8⁺ T lymphocytes (LEV 50 mg/L vs. CEF only: 21.4% (interquartile range (IQR) 16.5–35.9%) vs. 16.6% (IQR 12–24.9%), p = 0.002). LEV had no influence on apoptosis and proliferation (p > 0.05). VPA (100 mg/L) slowed apoptosis of CD8⁺ T lymphocytes after 24 h (VPA 100 mg/L vs. control: 7.3% (IQR 5.4–9.5%) vs. 11.3% (IQR 8.2–15.1%), p < 0.001), but had no effects on perforin release (p > 0.05). SV2A protein was detected in CD8⁺ T lymphocytes.ConclusionLEV decreased degranulation of CD8⁺ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. Inhibition of SV2A may be responsible for this effect.     

Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy

ObjectiveIdentify factors that predict improvement versus persistence of insomnia symptoms following treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy.MethodsArchival data from 68 PAP-treated sleep apnea patients aged 25–83 were analyzed using nonparametric tests and stepwise regression to assess the relationships between insomnia symptoms, multiple OSA variables, and PAP use over time.ResultsPretreatment insomnia symptom severity (ISS; b = −0.72, p < 0.001), PAP average use (b = −0.01, p = 0.01) and respiratory disturbance index (RDI; b = −0.02, p = 0.03) predict change in insomnia following PAP therapy. Forty-five percent (24/53) of the subjects with moderate to severe insomnia at pretreatment reported no/mild symptoms after PAP therapy and were considered improved. Improved subjects had lower pretreatment ISS (p < 0.001), higher RDI (p = 0.01), and higher average PAP use (p < 0.035) than subjects with persistent insomnia. Number of medications and comorbidities were similar between improved and persistent groups. New onset of insomnia symptoms occurred in 13% (2/15) of the patients with no/mild pretreatment insomnia.ConclusionsAlthough ISS declines following PAP treatment, 55% of OSA patients have persistent moderate to severe symptoms despite treatment. More severe OSA is linked to higher likelihood of insomnia improvement and the effect of PAP therapy on insomnia may be mediated by OSA severity. Persistent insomnia is unrelated to medication use or comorbidities and may represent an independent, self-sustaining disorder requiring targeted intervention.     

Efficacy and safety of doxepin 6 mg in a model of transient insomnia

IntroductionThe efficacy and safety of doxepin (DXP) 6 mg tablets were evaluated in healthy adults in a model of transient insomnia.MethodsThis was a randomized, double-blind, parallel-group, placebo-controlled study in healthy adults using a model of transient insomnia. A first-night effect combined with a 3-h phase advance was implemented to induce transient insomnia in healthy adults. Subjects received a single night time dose of placebo (PBO; N = 282) or DXP 6 mg (N = 283) in a sleep laboratory. Efficacy was evaluated objectively (polysomnography; PSG) and subjectively (morning questionnaire). Consistent with the model utilized, the primary endpoint was latency to persistent sleep (LPS); secondary PSG endpoints included wake after sleep onset (WASO; key secondary endpoint), total sleep time (TST), wake time after sleep (WTAS) and sleep efficiency (SE; overall, by quarter of the night and hourly); secondary subjective endpoints included latency to sleep onset (LSO), subjective WASO (sWASO), subjective TST (sTST) and sleep quality.ResultsDXP 6 mg demonstrated statistically significant improvements in LPS (13 min decrease versus PBO; p < 0.0001), WASO (39 min less than PBO; p < 0.0001), TST (51 min more than PBO; p < 0.0001), WTAS (p < 0.0001), overall SE (p < 0.0001), SE in each quarter of the night (p < 0.0001) and SE in each of the 8 h (p ? 0.0003), all versus PBO. Additionally, DXP 6 mg significantly improved subjective variables including LSO (p < 0.0001), sWASO (p = 0.0063), sTST (p < 0.0001), and sleep quality (p = 0.0004), versus PBO. There was no consistent evidence of next-day residual sedation and also minor sleep stages alterations. The incidence of adverse events was comparable to placebo.ConclusionsIn this model of transient insomnia, DXP 6 mg demonstrated significant improvements in sleep onset, sleep maintenance, sleep duration and sleep quality, and also appeared to reduce early morning awakenings. These data suggest that DXP 6 mg may be effective and well tolerated in adults experiencing transient insomnia.     

Afferent control of walking: Are there distinct deficits associated to loss of fibres of different diameter?

ObjectivesTo compare the gait pattern in patients affected by different types of neuropathy.MethodsWe recruited healthy subjects (HS, n = 38), patients with Charcot–Marie–Tooth disease type 1A (CMT1A) (n = 10) and patients with diabetic neuropathy (DNP) (n = 12). Neuropathy impairment score and neuropathy score were assessed. Body sway during quiet stance, and spatio-temporal gait parameters were recorded.ResultsMost patients had reduced or absent tendon-tap reflexes. Strength of foot dorsiflexor muscles (p < 0.05) and conduction velocity (CV) of leg nerves (p < 0.0001) were more impaired in CMT1A than DNP, whereas joint-position sense was more affected (p < 0.05) in DNP. Body sway while standing was larger in DNP compared to CMT1A and HS (p < 0.01 and p < 0.0001 respectively). During gait, the distribution of foot sole contact pressure was abnormal in CMT1A (p < 0.05) but not in DNP. Velocity and step length were decreased, and foot yaw angle at foot flat increased, in DNP with respect to CMT1A and HS (both variables, p < 0.001). Gait velocity and step length were decreased (p < 0.005) also in CMT1A, but to a smaller extent than in DNP, so that the difference between patient groups was significant (p < 0.0005). Duration of the double support was protracted in DNP compared to CMT1A and HS (p < 0.0005). For DNP only, velocity of gait and duration of single support were correlated (p < 0.05) both to sway path and lower limb muscle strength.ConclusionsChanges in both body sway and stance phase of gait were larger in DNP than CMT1A, indicating more impaired static and dynamic control of balance when neuropathy affects the small in addition to the large afferent fibres. Diminished somatosensory input from the smaller fibres rather than muscle weakness or foot deformity plays a critical role in the modulation of the support phase of gait.SignificanceThe analysis of balance and gait in patients with neuropathy can offer a tool for understanding the nature and functional impact of the neuropathy and should be included in their functional evaluation.     

Variation des fonctions cognitives et de la glycémie lors de l’exercice physique durant le jeûne du mois de Ramadan

IntroductionDuring the month of Ramadan, Muslims fast every day from dawn to sunset. Several studies have shown that Ramadan fasting affects biochemical parameters, sleep/wake cycle, behaviour and food habits.The purpose of the study was to evaluate the effect of Ramadan fasting (RF) and physical exercise on cognitive functions, blood glucose.MethodsEleven healthy male volunteers aged 20.45 ± 1.65 years were assessed before RF (B.RF), during the 1st week (wk), 3th wk and 1 wk B.RF, in blood sugar, work memory (WM), visual perception (VP), before exercise (B. Ex) and after exercise (A. Ex) exercise of 1000 m.ResultsCompared to control days (B.RF), there were no significant changes in body mass index. Physical performance declined significantly during 1st wk (p < 0.001), 3th wk (p < 0.013) and before (p < 0.046) of RF.At the level of the glycemia, the results show a significant effect of Ramadan by increasing gradually during Ramadan but nevertheless, the values remain lower of 100 mg/dl. No significant change was observed between B. Ex and A. Ex value in WM during RF. However, the WM A. Ex value increase significantly during and after RF (respectively 1st wk (p < 0.013), 3th wk (p < 0.005) and before (p < 0.003). The VP was significantly affected by fasting effect (F = 16.84, p < 0.001) and exercise effect (F = 14.01, p < 0.0001), and was progressively increased 15.56% in the 1st wk, 25.69%, the 3th wk during RF, and 27.07% A.RF, but no significant change was found in errors performances of VP during and after RF.ConclusionThese results showed that the intermittent fasting imply differently effects on cognitive functions and physiological.     

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery

IntroductionOlder patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery.AimTo determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors.MethodsWe prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery.ResultsPatients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p < 0.01), history of smoking (p < 0.01), arterial hypertension (p = 0.022), diabetes mellitus (p = 0.024), heart failure (p = 0.036) and preoperative cognitive dysfunction (p < 0.01), and surgery-associated aspects such as EuroSCORE (p < 0.01) and operation time (p < 0.01) were identified as related risk factors.ConclusionsOlder patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.     

Neuropeptide Y associated with asthma in young adults

ObjectiveNeuropeptide Y, a widely circulating neurotransmitter, plays a pivotal role in energy balance, immunomodulation and asthma, and several NPY polymorphisms are promising genetic risk factors for asthma and obesity. We explored the associations of candidate NPY gene polymorphisms with prevalent asthma and its relationship with obesity in young adult asthma patients free of other chronic medical morbidity.MethodsFive common gene variants of NPY (rs16147 (− 399T/C), rs17149106 (− 602G/T), rs16140 (+ 1000C/G), rs5573 (+ 1201A/G), rs5574 (+ 5327C/T)) previously validated to account for most of the NPY expression in vitro and in vivo were investigated in 126 physician-diagnosed asthma patients without other chronic medical morbidity and 182 healthy controls (21–35 years). Plasma levels of NPY, adiponectin, and CRP were determined using ELISA, and IL-6 was measured by Luminex in a subgroup of 70 patients and 69 age- and sex-matched healthy controls.ResultsIn logistic regression models controlling for gender and obesity, the CT genotype of rs5574 (OR = 0.54, 95%CI: 0.30–0.89) and the GT genotype of rs17149106 (OR = 5.58, 95%CI: 1.09–28.54) were significantly associated with asthma. No significant interaction between NPY SNP polymorphisms and obesity were detected. Plasma NPY level was correlated with adiponectin levels (p < 0.05). Compared with the healthy controls, patients with asthma had higher BMI (p < 0.001), adiponectin (p < 0.05), IL-6 (p = 0.001) and CRP (p < 0.001), and lower NPY levels (p < 0.01).ConclusionsThe CT genotype of rs5574 and the GT genotype of rs17149106 are significantly associated with prevalent asthma.     

Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans

PurposeThere is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters.Methods36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54 ± 27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45 ± 19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3⁺CD4⁺-, CD3⁺CD8⁺- and CD4⁺CD25⁺-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs.ResultsValproate intake resulted in a significant decrease of the total white blood count (6.96 ± 1.23/nl vs. 6.13 ± 1.57/nl, p = 0.026) and of absolute count and percentage of neutrophils (4.60 ± 1.05/nl vs. 3.69 ± 1.30/nl, p = 0.01; 65.4 ± 7.9% vs. 59.5 ± 11.5%, p = 0.01, respectively). The percentage of CD3⁺CD4⁺-lymphocytes dropped significantly (50.4 ± 10.9% vs. 45.3 ± 12.3%, p = 0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4⁺CD25⁺-lymphocytes (26.1 ± 8.0% vs. 21.5 ± 9.2%, p = 0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines.ConclusionValproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam.     

Lifetime presence of psychotic symptoms in bipolar disorder is associated with less favorable socio-demographic and certain clinical features

BackgroundThe presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the “with psychotic features” specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area.MethodsThe present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N = 360), with (BDPs, N = 207) and without a lifetime history of psychosis (BDNPs, N = 153).ResultsAn overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7 ± 10.5 vs 30.1 ± 12.3 years; p = 0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p < 0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p < 0.001) and most recent episode (69.8% vs 35.6%; p < 0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p = 0.002), more lifetime hospitalizations (3.8 ± 6.1 vs 2 ± 3; p = 0.002) and involuntary commitments (1 ± 1.9 vs 0.1 ± 0.4; p < 0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p = 0.001), more current antipsychotic use (90.1% vs 70.9%; p < 0.001), and lower GAF (62.3 ± 14.2 vs 69.3 ± 12.5; p < 0.001), but shorter duration of most recent episode (34.1 ± 45.4 vs 50.3 ± 65.7 days; p = 0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p = 0.005), and antidepressant use (19.4% vs 56.6%; p < 0.001).ConclusionsThe present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.