Effects of lamotrigine on human motor cortex plasticity

ObjectiveBesides its use in epilepsy, lamotrigine (LTG) is also effective as mood stabilizer. The pathophysiology of mood disorders may incorporate a dysfunction of neuronal plasticity and animal experiments suggest that mood stabilizers influence induction of long-term potentiation (LTP) and –depression (LTD), two major forms of synaptic plasticity. However, the exact modes of action of LTG and its impact on neuronal plasticity in humans remain unclear.MethodsHere, we tested the effects of a single oral dose of LTG (300 mg) on motor cortical plasticity induced by paired associative stimulation (PAS₂₅), a protocol that typically induces LTP-like plasticity, in 26 young healthy adults in a placebo-controlled, randomized, double-blind crossover design. We stratified analysis of the LTG effects according to the individual PAS₂₅ response in the placebo session (14 LTP-responders vs. 12 LTD-responders). Plasticity was indexed by motor evoked potential (MEP) amplitudes recorded before and for 60 min after PAS₂₅.ResultsLTG resulted in a significant reduction of the LTP-like MEP increase in the LTP-responders and a reduction of the LTD-like MEP decrease in the LTD-responders, with the majority of LTD-responders even showing an MEP increase.ConclusionsIn summary, LTG differentially modulated cortical plasticity induced by non-invasive brain stimulation in human subjects depending on their individual intrinsic propensity for expressing LTP-like or LTD-like plasticity.SignificanceFindings contribute to our understanding of the anticonvulsant and antidepressant clinical effects of LTG, which have been suggested to occur, at least in part, through downregulation of LTP (epilepsy) and LTD (depressive disorders).     

A comparison of relative-frequency and threshold-hunting methods to determine stimulus intensity in transcranial magnetic stimulation

ObjectiveStimulation intensity (SI) in transcranial magnetic stimulation is commonly set in relation to motor threshold (MT), or to achieve a motor-evoked potential (MEP) of predefined amplitude (usually 1 mV). Recently, IFCN recommended adaptive threshold-hunting over the previously endorsed relative-frequency method. We compared the Rossini–Rothwell (R–R) relative-frequency method to an adaptive threshold-hunting method based on parameter estimation by sequential testing (PEST) for determining MT and the SI to target a MEP amplitude of 1 mV (I_1 mV).MethodsIn 10 healthy controls we determined MT and I_1 mV with R–R and PEST using a blinded crossover design, and performed within-session serial PEST measurements of MT.ResultsThere was no significant difference between methods for MT (52.6 ± 2.6% vs. 53.7 ± 3.1%; p = 0.302; % maximum stimulator output; R–R vs. PEST, respectively) or I_1 mV (66.7 ± 3.0% vs. 68.8 ± 3.8%; p = 0.146). There was strong correlation between R–R and PEST estimates for both MT and I_1 mV. R–R required significantly more stimuli than PEST. Serial measurements of MT with PEST were reproducible.ConclusionsPEST has the advantage of speed without sacrificing precision when compared to the R–R method, and is adaptable to other SI targets.SignificanceOur results in healthy controls add to increasing evidence in favour of adaptive threshold-hunting methods for determining SI.     

A new temporal window for inducing depressant associative plasticity in human primary motor cortex

ObjectiveSpike-timing dependent plasticity (STDP) usually refers to synaptic plasticity induced by near-synchronous activation of neuronal input and neuronal firing. However, some models of STDP predict effects that deviate from this tight temporal synchrony. We aimed to characterise the induction of STDP using paired associative stimulation (PAS) when the pre-synaptic input arrives in primary motor cortex (M1) at (i) intermediate intervals (50–80 ms; PAS₅₀,..PAS₈₀) before the post-synaptic neuron is activated and (ii) long intervals (100–450 ms; PAS_?100,..PAS_?450) after the post-synaptic neuron is activated. PAS at near-synchronicity (PAS₂₅) was applied for comparison.MethodsTo characterise the physiological effects of the different PAS protocols, we examined short- and long-interval intra-cortical inhibition; intra-cortical facilitation and short- and long-latency afferent inhibition, in addition to recording MEPs in 45 healthy individuals.ResultsMEP amplitude was reduced at PAS intervals between ?250 and ?450 ms, increased with PAS₂₅, and unaltered at the remaining intervals. There was no change in intra-cortical inhibitory or facilitatory circuits following any PAS protocol.ConclusionsThese findings provide evidence of a previously unreported temporal window in which PAS induces a depression of corticospinal excitability in human M1.SignificanceEstablishing new temporal rules for STDP broadens its applicability for therapeutic usage in future.     

Effects of persistent Mal de debarquement syndrome on balance,psychological traits,and motor cortex exctiability

Mal de debarquement syndrome (MdDS) is a poorly characterized and understood disorder of perceived motion. We sought to characterize postural control and the psychological impact of MdDS. Additionally, we explored whether patients with MdDS exhibit altered corticospinal and intracortical excitability. In a case-control study we compared patients with MdDS to age- and sex-matched controls (n = 8/group). Postural stability (σ_r) was quantified from plane phase plots based on center or pressure, and psychological indices of depression, fatigue and kinesiophobia were obtained. Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability by quantifying the motor evoked potential (MEP) amplitude of the flexor carpi radialis, and intracortical excitability was assessed by quantifying indices of intracortical facilitation (ICF), and short-interval and long-interval intracortical inhibition using a paired-pulse TMS paradigm. The patients with MdDS exhibited greater mean (±standard error of the mean) σ_r during semi-tandem stance (10.9 ± 1.5 compared to 7.1 ± 0.7, p = 0.04), higher levels of kinesiophobia (41.6 ± 2.8 compared to 27.3 ± 2.2), and higher levels of fatigue (27.0 ± 4.1 compared to 48.4 ± 1.0). Patients with MdDS exhibited a higher mean motor threshold (MT) (58.1 ± 2.5 compared to 47.4 ± 2.7% of stimulator output), and larger MEP (13.1 ± 3.1 compared to 5.1 ± 1.2% of maximal compound muscle action potential) but there was no difference in measures of intracortical excitability. These findings suggest that patients with MdDS exhibit impaired postural stability, and high levels of kinesiophobia and fatigue. Additionally, we observed that patients with MdDS exhibit higher MT and large MEP amplitudes, but do not exhibit differences in measures of intracortical excitability, compared to controls. These findings help characterize MdDS, and provide insight into the physiology of MdDS.     

Reduced motor cortex plasticity following inhibitory rTMS in older adults

ObjectiveAgeing is accompanied by diminished practice-dependent plasticity. We investigated the effect of age on another plasticity inducing paradigm, repetitive transcranial magnetic stimulation (rTMS).MethodsHealthy young (n = 15; 25 ± 4 years) and old (n = 15; 67 ± 5 years) adults participated in two experiments. Motor evoked potentials (MEPs) were measured in the target muscle (first dorsal interosseus, FDI) and a remote muscle (abductor digiti minimi) during a set of single stimuli. Subjects then received real or sham inhibitory rTMS (intermittent subthreshold trains of 6 Hz stimulation for 10 min). MEPs were measured for 30 min after rTMS.ResultsIn young adults, MEPs in the target FDI muscle were ∼15% smaller in the real rTMS experiment than in the sham rTMS experiment (P < 0.026). In old adults, FDI MEP size did not differ between experiments.ConclusionsAdvancing age is associated with reduced efficacy of inhibitory rTMS.SignificanceThis work has important implications for the potential therapeutic use of rTMS in stroke and neurological disease.     

Modulating motor cortical neuroplasticity with priming paired associative stimulation in young and old adults

Objective

To examine the effect of priming paired associative stimulation (PAS) on the modulation of motor cortex (M1) plasticity in young and old adults.

Nocturnal autonomic function in preschool children with sleep-disordered breathing

BackgroundObstructive sleep apnea (OSA) is associated with autonomic dysfunction in adults and school-aged children; however, this association has not been investigated in preschool children. We aimed to analyze heart rate variability (HRV) and catecholamine levels in preschool children with OSA.MethodsOne hundred and forty-two snoring children aged 3–5 years and 38 nonsnoring control group children underwent overnight polysomnography (PSG). Nocturnal urinary catecholamines were measured in 120 children. Children were grouped according to their obstructive apnea–hypopnea index (OAHI) (control [no snoring], OAHI ⩽ 1 event/h; primary snoring, OAHI ⩽ 1 event/h; mild OSA OAHI > 1 ⩽ 5 events/h; moderate to severe [MS] OSA, OAHI > 5 events/h). The HRV parameters for each child were averaged during rapid eye movement (REM) and non-REM (NREM) sleep.ResultsDuring stable sleep, low-frequency (LF) HRV was similar between groups. High-frequency (HF) HRV was higher in the MS OSA group compared with the control group during all sleep stages (NREM sleep stages 1 and 2 [NREM1/2], 4234 ± 523 ms² vs 2604 ± 457 ms²; NREM sleep stages 3 and 4 [NREM3/4], 4152 ± 741 ms² vs 3035 ± 647 ms²; REM, 1836 ± 255 ms² vs 1456 ± 292 ms²; P < .01 for all). The LF/HF ratio was lower in the MS OSA group compared with the control group (NREM1/2, 0.4 ± 0.06 vs 0.7 ± 0.05; NREM3/4, 0.3 ± 0.06 vs 0.4 ± 0.05; REM, 0.8 ± 0.1 vs 1.3 ± 0.1; P < .01 for all). Catecholamine levels were not different between groups.ConclusionsIn preschool children, OSA is associated with altered HRV, largely due to the HF fluctuations in heart rate (HR) which occur during respiratory events and are still evident during stable sleep. The preschool age may represent a window of opportunity for treatment of OSA before the onset of the severe autonomic dysfunction associated with OSA in adults and older children.     

The role of altered tissue osmolality on the characteristics and propagation of seizure activity in the intact isolated mouse hippocampus

ObjectivesTo study the role of altered tissue osmolality on the characteristics and propagation dynamics of seizure activity and on interictal activity, in a low-Mg⁺² artificial cerebrospinal fluid (ACSF) model of recurrent seizures, using the immature (P8–P25) intact isolated mouse hippocampus.MethodsRecordings were obtained extracellularly from a single site in the CA1 region and from multiple sites along the septotemporal axis measuring spontaneous epileptiform field activity in ACSFs of different osmolalities.ResultsIn normal osmolar ACSF (310 mOsmol), the average duration of recorded seizures was 90 ± 10 s and the average peak amplitude was 0.9 ± 0.1 mV. In a hypoosmolar ACSF (270 mOsmol), the seizures were significantly prolonged at 165 ± 20 s (p < 0.05) with a peak amplitude of 1.2 ± 0.3 mV, whereas interictal activity was suppressed. Hyperosmolar ACSF (340 mOsmol) reduced the duration (65 ± 15 s) and peak amplitude (0.6 ± 0.1 mV, p < 0.05) from control, but interictal activity was not affected. No differences in seizure recurrence rate were noted in all three osmolar states.ConclusionThe present study, the first to assess of the role of altered tissue osmolality in an intact in vitro preparation, demonstrates that changes in perfusate osmolality play a significant role on the amplitude, duration, and propagation velocity of seizure-like events, and the characteristics of interictal activity, without affecting seizure recurrence rate.SignificanceIncreasing tissue osmolality should be considered as a valid target for anticonvulsant treatment.     

Reduced plastic brain responses to repetitive transcranial magnetic stimulation in severe obstructive sleep apnea syndrome

ObjectivesAbnormalities in cortical excitability have been proposed to underlie the pathophysiology of various neurocognitive manifestations of obstructive sleep apnea syndrome (OSAS). Transcranial magnetic stimulation (TMS) provides a noninvasive method for study and modulation of cortical excitability in the human brain, and repetitive TMS (rTMS) has been proven useful for neurophysiologic investigation in various neurologic conditions. We aimed to investigate cortical excitability in patients with OSAS during wakefulness and to determine if rTMS would change the abnormal excitability patterns.MethodsMeasures of motor cortical and corticospinal excitability (resting motor threshold [RMT], motor-evoked potential [MEP] amplitude, and cortical silent period [CSP]) were taken before and after a session of 10-Hz rTMS applied to the motor cortex in 13 individuals with untreated severe OSAS (apnea–hypopnea index [AHI] > 30) and 12 age- and sex-matched healthy controls (HC).ResultsOSAS subjects had a significantly higher RMT (P < .003) and a longer CSP duration (P < .002) compared to HC. No difference was observed between MEP values of OSAS subjects and HC (P > .05). In response to rTMS, the HC group had a significant increase in CSP and MEP values from baseline, which were absent in OSAS subjects.ConclusionsIndividuals with OSAS demonstrated increased motor cortex inhibition, which did not respond to 10-Hz rTMS. As rTMS-induced changes in MEP and CSP involve a separate neurotransmitter system (N-methyl-d-aspartate [NMDA] and gamma-aminobutyric acid [GABA], respectively), these findings suggest a widespread alteration in cortical neurophysiology in severe OSAS subjects that requires clarification with further exploration.     

Serum nitrite and nitrate levels in children with obstructive sleep-disordered breathing

BackgroundDiminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB).ObjectivesTo assess levels of serum NO metabolites in children with SDB and to explore the effects of NO metabolites, SDB and their interaction on blood pressure.MethodsMorning nitrite, the sum of nitrite and nitrate (NO_x), and the average of evening and morning blood pressure were assessed in children with SDB referred for polysomnography and in controls without SDB.ResultsForty-three children with SDB (age: 5.8 ± 2.1 years) had moderate-to-severe nocturnal hypoxemia (SpO₂ nadir: 85.6 ± 4%), 54 subjects (6.6 ± 2.7 years) had mild hypoxemia (SpO₂ nadir: 91.4 ± 1.3%) and 20 subjects were controls free of SDB (6.7 ± 3.7 years). Subjects with moderate-to-severe hypoxemia had significantly lower ln-transformed NO metabolites (1.4 ± 0.7, nitrites; 2.6 ± 0.5, NO_x) compared to those with mild hypoxemia (1.9 ± 0.8, nitrites; 3 ± 0.6, NO_x) and controls (2.2 ± 0.7, nitrite; 3 ± 0.6, NO_x; p < 0.05). The effects of NO metabolites and SDB or their interaction on blood pressure were not significant (p > 0.05).ConclusionsModerate-to-severe hypoxemia accompanying SDB is associated with reduced concentrations of morning serum NO metabolites, but NO levels do not seem to affect blood pressure.     

Ocular vestibular evoked myogenic potentials to head tap and cervical vestibular evoked myogenic potentials to air-conducted sounds in isolated internuclear ophthalmoplegia

ObjectiveThe central pathways responsible for ocular vestibular evoked myogenic potentials (VEMPs) to forehead tapping remain to be determined. This study aimed to determine whether the medial longitudinal fasciculus (MLF) carries the signals for ocular VEMPs (oVEMPs) in response to this mode of stimulation.MethodsTwelve patients with isolated unilateral internuclear ophthalmoplegia (INO) due to brainstem infarction underwent evaluation of the ocular tilt reaction (ocular torsion and skew deviation), tilt of the subjective visual vertical (SVV), cervical VEMPs (cVEMPs) in response to tone burst sound, and oVEMPs induced by tapping the forehead.ResultsEight (67%) patients showed abnormal oVEMPs that included no wave formation (n = 4) and decreased amplitude (n = 3) in the lesion side, and bilaterally absent responses in the remaining patient. Furthermore, the patients showed diminished oVEMPs responses in the lesion side compared with normal side (6.0 ± 5.6 vs. 11.7 ± 5.5 μV, paired t-test, p = 0.001) and increased IAD_amp(%) of the oVEMPs compared with normal controls (43.6 ± 41.2 vs. 9.1 ± 6.2, t-test, p = 0.018). In contrast, cVEMPs were abnormal in only three (25%) patients, decreased (n = 2) or no response in the lesion side. Eleven (92%) patients showed contraversive ocular tilt reaction or SVV tilt.ConclusionPatients with INO frequently show impaired formation of ipsilesional oVEMPs in response to forehead tapping. The occasional abnormality and decreased amplitude of ipsilesional cVEMPs also suggest a modulatory pathway for the inhibitory sacculocollic reflex descending in the MLF.SignificanceThis study suggests that the MLF contains the fibers for the otolith-ocular reflex from the contralateral ear.     

The effect of modafinil on cortical excitability in patients with narcolepsy: A randomized,placebo-controlled,crossover study

ObjectiveTo investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).MethodsNineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400 mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3 h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.ResultsNarcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P < 0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.ConclusionsNarcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.     

Prognostic impact of sleep duration and sleep efficiency on mortality in patients with chronic heart failure

BackgroundBoth short and long self-reported sleep duration (SD_SR) has been linked to increased mortality. Our analysis tested the hypothesis that long SD_SR is paralleled by impaired objective sleep efficiency (SE_PSG) measured by polysomnography (PSG) and that impaired SE_PSG is a risk factor for death in patients with chronic heart failure (CHF).MethodsSD_SR and SE_PSG were assessed by standardized questionnaire and PSG in 188 consecutive CHF patients (age range, 63 ± 10 year; left ventricular ejection fraction, 34 ± 10%) admitted to the Sleep Center of the University Hospital Regensburg between 1/2002 and 12/2009. The mean follow-up period was 44 ± 26 months.ResultsSE_PSG in CHF patients from the highest quintile of SD_SR (⩾9 h) was significantly lower compared with the middle quintile (7.25–8 h; 71 ± 15% vs 77% ± 11%; p = 0.032) and similar to the lowest quintile (⩽5.75 h; 71 ± 15% vs 71 ± 16%, p = 0.950). SE_PSG is an independent predictor for death in the multivariable model after accounting for the significant confounders age, left ventricular ejection fraction, cause of CHF, and NYHA class (hazard ratio [HR] per 5% increase, 0.85; 95% confidence interval [CI], 0.77–0.93; p < 0.001).ConclusionsData indicate that subjective long sleepers with CHF have poor sleep efficiency. Objectively measured SE_PSG strongly predicts mortality in CHF patients, underscoring the importance of objective assessment of sleep.     

Plasticity of motor threshold and motor-evoked potential amplitude – A model of intrinsic and synaptic plasticity in human motor cortex?

BackgroundNeuronal plasticity is the physiological correlate of learning and memory. In animal experiments, synaptic (i.e. long-term potentiation (LTP) and depression (LTD)) and intrinsic plasticity are distinguished. In human motor cortex, cortical plasticity can be demonstrated using transcranial magnetic stimulation (TMS). Changes in motor-evoked potential (MEP) amplitudes most likely represent synaptic plasticity and are thus termed LTP-like and LTD-like plasticity.Objective/hypothesisWe investigated the role of changes of motor threshold and their relation to changes of MEP amplitudes.MethodsWe induced plasticity by paired associative stimulation (PAS) with 25 ms or 10 ms inter-stimulus interval or by motor practice (MP) in 64 healthy subjects aged 18–31 years (median 24.0).ResultsWe observed changes of MEP amplitudes and motor threshold after PAS[25], PAS[10] and MP. In all three protocols, long-term individual changes in MEP amplitude were inversely correlated to changes in motor threshold (PAS[25]: P = .003, n = 36; PAS[10]: P = .038, n = 19; MP: P = .041, n = 19).ConclusionWe conclude that changes of MEP amplitudes and MT represent two indices of motor cortex plasticity. Whereas increases and decreases in MEP amplitude are assumed to represent LTP-like or LTD-like synaptic plasticity of motor cortex output neurons, changes of MT may be considered as a correlate of intrinsic plasticity.     

Unilateral strength training increases voluntary activation of the opposite untrained limb

ObjectiveWe investigated whether an increase in neural drive from the motor cortex contributes to the cross-limb transfer of strength that can occur after unilateral strength training.MethodsTwitch interpolation was performed with transcranial magnetic stimulation to assess changes in strength and cortical voluntary activation in the untrained left wrist, before and after 4 weeks of unilateral strength-training involving maximal voluntary isometric wrist extension contractions (MVCs) for the right wrist (n = 10, control group = 10).ResultsWrist extension MVC force increased in both the trained (31.5 ± 18%, mean ± SD, p < 0.001) and untrained wrist (8.2 ± 9.7%, p = 0.02), whereas wrist abduction MVC did not change significantly. The amplitude of the superimposed twitches evoked during extension MVCs decreased by 35% (±20%, p < 0.01), which contributed to a significant increase in voluntary activation (2.9 ± 3.5%, p < 0.01). Electromyographic responses to cortical and peripheral stimulation were unchanged by training. There were no significant changes for the control group which did not train.ConclusionUnilateral strength training increased the capacity of the motor cortex to drive the homogolous untrained muscles.SignificanceThe data show for the first time that an increase in cortical drive contributes to the contralateral strength training effect.     

Long-term changes in blood pressure control in elementary school-aged children with sleep-disordered breathing

ObjectiveIn adults sleep-disordered breathing (SDB) has been associated with impaired baroreflex control of blood pressure (BP), which has been linked to increased cardiovascular morbidity. In children, the long-term effects of SDB on baroreflex sensitivity (BRS) and BP variability (BPV) are unknown.MethodsChildren previously diagnosed with SDB (n = 40) and 20 nonsnoring controls aged 11–16 y underwent overnight polysomnography with continuous BP measurement, four years after the original diagnosis. At follow-up, SDB was categorized as resolved (absence of snoring and obstructive apnea hypopnea index (OAHI) ⩽ 1) or unresolved (continued to snore or had an OAHI > 1). BRS and BPV were calculated using cross-spectral analysis and power spectral analysis, respectively.ResultsOnly children with resolved obstructive sleep apnea (OSA) at follow-up demonstrated an increase in BRS from 9.7 ± 3 (ms mmHg⁻¹) at baseline to 11.8 ± 4 (ms mmHg⁻¹) at follow-up (P = .03). However, children with all severities of both resolved and unresolved SDB showed a significant decrease in BPV from baseline to follow-up (a decrease in total power BPV (P < .05) and a shift in BPV spectra away from respiratory-related frequencies (increased low-frequency/high-frequency [LF/HF] ratio, P < .01). The change in OAHI was the sole determinant of change in BRS, HF power, and LF/HF ratio.ConclusionsImprovement in SDB was associated with improved BP control, regardless if SDB was treated or spontaneously resolved four years after initial diagnosis. Our findings highlight the importance of monitoring children to ensure improvement of SDB and reduce the risk for cardiovascular morbidity in the future.     

The effect of cigarette smoking on vitamin D level and depression in male patients with acute ischemic stroke

ObjectiveThe association between low vitamin D levels and depression has been well documented in nonstroke subjects. Accumulating evidence shows that low vitamin D levels may be also associated with depression post stroke. Cigarette smoking was associated with lower vitamin D levels. The purposes of this study were to compare vitamin D levels in smokers to nonsmokers and examine the association between vitamin D levels and depression symptoms in patients with acute ischemic stroke.Materials and methodsSerum levels of 25-hydroxyvitamin D [25(OH)D] were measured in 194 males within 24 h after admission: 116 smokers and 78 nonsmokers. Depression symptoms were assessed with the 17-item Hamilton Depression Scale (HAMD-17). Patients with the HAMD-17 score >7 were identified to have depression symptoms.ResultsThe chi-square test showed that the frequency of depression in the smoker group was 23.3% (27/116), which was significantly higher than that in the nonsmoker group (11.5% = 9/78), with an odds ratios (OR) of 2.33 (95% CI: 1.03–5.27; χ² = 4.25, df = 1, p = 0.039, φ = 0.15). Vitamin D levels were significantly lower in smokers than in nonsmokers (52.4 ± 20.8 vs 61.7 ± 19.2; F = 9.88, p = 0.002), with an effect size of 0.05 (η_p²). Patients with depression symptoms showed lower vitamin D levels than those with no depression symptoms (49.2 ± 19.6 vs 57.7 ± 20.6; F = 5.03, p = 0.03), with an effect size of 0.03 (η_p²).ConclusionHigher rates of depression in smokers with acute ischemic stroke may be associated with lower vitamin D levels induced by smoking.     

Influence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing's syndrome

BackgroundAsymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing's syndrome (CS).ObjectiveTo assess the influence of IPS drainage patterns on detection of an adenoma in CS.MethodsRetrospective single-center cohort analysis reviewing records of patients with CS and negative MRI findings who subsequently underwent BIPSS.ResultsBIPSS was performed in 38 patients with a mean age of 45 ± 15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing's disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6 ± 2.7 versus 16.4 ± 6.0; P = 0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0 ± 2.5 versus 35.7 ± 22.5; P = 0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P = 0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS.ConclusionsBearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome.     

Individuals with intellectual disability have lower voluntary muscle activation level

The aim of this study was to explore the voluntary activation level during maximal voluntary contraction (MVC) in individuals with intellectual disability (ID) versus individuals without ID using the twitch interpolation technique. Ten individuals with mild ID (ID group) and 10 sedentary men without ID (control group) participated in this study. The evaluation of neuromuscular function consisted in three brief MVCs (3 s) of the knee extension superimposed with electrical nerve stimulation (NES) to measure voluntary activation. Muscle activity levels were also measured with surface EMG. The root mean square (RMS) was extracted from the EMG signal. The RMS/Mmax ratio and the neuromuscular efficiency (NME) were calculated. Our results reported that individuals with ID present lower muscle strength (p < 0.001), lower voluntary activation level (p < 0.001), lower RMS values of vastus lateralis (p < 0.05), vastus medialis (p < 0.05), and rectus femoris (p < 0.001) muscles. In addition, our results showed lower RMS/Mmax values in the ID group than in the control group for the VM (0.05 ± 0.01 mV vs. 0.04 ± 0.01 mV; p < 0.05) and the RF (0.06 ± 0.02 mV vs. 0.05 ± 0.02 mV; p < 0.05) muscles. However, no significant difference was reported for the VL muscle (0.05 ± 0.02 mV vs. 0.05 ± 0.02 mV; p = 0.463). Moreover, Individuals with ID present smaller potentiated twitch (p < 0.001). However, no significant difference was reported in the NME ratio. These results suggest that the lower muscle strength known in individuals with ID is related to a central nervous system failure to activate motor units and to some abnormal intrinsic muscle properties. It seems that the inactive lifestyle adopted by individuals with ID is one of the most important factors of their lower voluntary activation levels. Therefore, physical activities should be introduced in life style of individuals with ID to improve their neuromuscular function.     

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.