Properties of low-threshold motor axons in the human median nerve

This study investigated the excitability and accommodative properties of low-threshold human motor axons to test whether these motor axons have greater expression of the persistent Na(+) conductance, I(NaP). Computer-controlled threshold tracking was used to study 22 single motor units and the data were compared with compound motor potentials of various amplitudes recorded in the same experimental session. Detailed comparisons were made between the single units and compound potentials that were 40% or 5% of maximal amplitude, the former because this is the compound potential size used in most threshold tracking studies of axonal excitability, the latter because this is the compound potential most likely to be composed entirely of motor axons with low thresholds to electrical recruitment. Measurements were made of the strength-duration relationship, threshold electrotonus, current-voltage relationship, recovery cycle and latent addition. The findings did not support a difference in I(NaP). Instead they pointed to greater activity of the hyperpolarization-activated inwardly rectifying current (I(h)) as the basis for low threshold to electrical recruitment in human motor axons. Computer modelling confirmed this finding, with a doubling of the hyperpolarization-activated conductance proving the best single parameter adjustment to fit the experimental data. We suggest that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel(s) expressed on human motor axons may be active at rest and contribute to resting membrane potential.

Low-threshold monopolar motor mapping for resection of primary motor cortex tumors

Microsurgery within eloquent cortex is a controversial approach because of the high risk of permanent neurological deficit. Few data exist showing the relationship between the mapping stimulation intensity required for eliciting a muscle motor evoked potential and the distance to the motor neurons; furthermore, the motor threshold at which no deficit occurs remains to be defined.

Low-threshold monopolar motor mapping for resection of lesions in motor eloquent areas in children and adolescents

Object Resection of lesions close to the primary motor cortex (M1) and the corticospinal tract (CST) is generally regarded as high-risk surgery due to reported rates of postoperative severe deficits of up to 50%. The authors' objective was to determine the feasibility and safety of low-threshold motor mapping and its efficacy for increasing the extent of lesion resection in the proximity of M1 and the CST in children and adolescents. Methods The authors analyzed 8 consecutive pediatric patients in whom they performed 9 resections for lesions within or close (≤ 10 mm) to M1 and/or the CST. Monopolar high-frequency motor mapping with train-of-five stimuli (pulse duration 500 μsec, interstimulus interval 4.0 msec, frequency 250 Hz) was used. The motor threshold was defined as the minimal stimulation intensity that elicited motor evoked potentials (MEPs) from target muscles (amplitude > 30 μV). Resection was performed toward M1 and the CST at sites negative to 1- to 3-mA high-frequency train-of-five stimulation. Results The M1 was identified through high-frequency train-of-five via application of varying low intensities. The lowest motor thresholds after final resection ranged from 1 to 9 mA in 8 cases and up to 18 mA in 1 case, indicating proximity to motor neurons. Intraoperative electroencephalography documented an absence of seizures during all surgeries. Two transient neurological deficits were observed, but there were no permanent deficits. Postoperative imaging revealed complete resection in 8 patients and a very small remnant (< 0.175 cm(3)) in 1 patient. Conclusions High-frequency train-of-five with a minimal threshold of 1-3 mA is a feasible and safe procedure for resections in the proximity of the CST. Thus, low-threshold motor mapping might help to expand the area for safe resection in pediatric patients with lesions located within the precentral gyrus and close to the CST, and may be regarded as a functional navigational tool. The additional use of continuous MEP monitoring serves as a safety feedback for the functional integrity of the CST, especially because the true excitability threshold in children is unknown.

Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus

The thalamus integrates and transmits sensory information to the neocortex. The activity of thalamocortical relay (TC) cells is modulated by specific inhibitory circuits. Although this inhibition plays a crucial role in regulating thalamic activity, little is known about long-term changes in synaptic strength at these inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory inputs to TC cells in the posterior medial nucleus of the thalamus by combining patch-clamp recordings with two-photon fluorescence microscopy in rat brain slices. We found that specific activity patterns in the postsynaptic TC cell induced inhibitory long-term potentiation (iLTP). This iLTP was non-Hebbian because it did not depend on the timing between presynaptic and postsynaptic activity, but it could be induced by postsynaptic burst activity alone. iLTP required postsynaptic dendritic Ca2+ influx evoked by low-threshold Ca2+ spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane potential (−50 mV), which suppressed these low-threshold Ca2+ spikes, induced no plasticity. The postsynaptic dendritic Ca2+ increase triggered the synthesis of nitric oxide that retrogradely activated presynaptic guanylyl cyclase, resulting in the presynaptic expression of iLTP. The dependence of iLTP on the membrane potential and therefore on the postsynaptic discharge mode suggests that this form of iLTP might occur during sleep, when TC cells discharge in bursts. Therefore, iLTP might be involved in sleep state-dependent modulation of thalamic information processing and thalamic oscillations.

Internet-based individually versus group guided self-help treatment for social anxiety disorder: protocol of a randomized controlled trial

BACKGROUND: Social anxiety disorder (SAD) is one of the most common mental disorders and causes subjective suffering and economic burden worldwide. Although effective treatments are available, a lot of cases go untreated. Internet-based self-help is a low-threshold and flexible treatment alternative for SAD. Various studies have already shown that internet-based self-help can be effective to reduce social phobic symptoms significantly. Most of the interventions tested include therapist support, whereas the role of peer support within internet-based self-help has not yet been fully understood. There is evidence suggesting that patients' mutual exchange via integrated discussion forums can increase the efficacy of internet-based treatments. This study aims at investigating the added value of therapist-guided group support on the treatment outcome of internet-based self-help for SAD. METHODS/DESIGN: The study is conducted as a randomized controlled trial. A total of 150 adults with a diagnosis of SAD are randomly assigned to either a waiting-list control group or one of the active conditions. The participants in the two active conditions use the same internet-based self-help program, either with individual support by a psychologist or therapist-guided group support. In the group guided condition, participants can communicate with each other via an integrated, protected discussion forum. Subjects are recruited via topic related websites and links; diagnostic status will be assessed with a telephone interview. The primary outcome variables are symptoms of SAD and diagnostic status after the intervention. Secondary endpoints are general symptomology, depression, quality of life, as well as the primary outcome variables 6 months later. Furthermore, process variables such as group processes, the change in symptoms and working alliance will be studied. DISCUSSION: The results of this study should indicate whether group-guided support could enhance the efficacy of an internet-based self-help treatment for SAD. This novel treatment format, if shown effective, could represent a cost-effective option and could further be modified to treat other conditions, as well.

Internet-based stress management for women with preterm labour: a case-based experience report

Pregnant women with preterm labour (PTL) in pregnancy often experience increased distress and anxieties regarding both the pregnancy and the child's health. The pathogenesis of PTL is, among other causes, related to the stress-associated activation of the maternal-foetal stress system. In spite of these psychobiological associations, only a few research studies have investigated the potential of psychological stress-reducing interventions. The following paper will present an online anxiety and stress management self-help program for pregnant women with PTL. Structure and content of the program will be illustrated by a case-based experience report. L.B., 32 years (G3, P1), was recruited at gestational week 27 while hospitalized for PTL for 3 weeks. She worked independently through the program for 6 weeks and had regular written contact with a therapist. Processing the program had a positive impact on L.B.'s anxiety and stress levels, as well as on her experienced depressive symptoms and bonding to the foetus. As PTL and the risk of PTB are associated with distress, psychological stress-reducing interventions might be beneficial. This study examines the applicability of an online intervention for pregnant women with PTL. The case report illustrates how adequate low-threshold psychological support could be provided to these women.

Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis.

Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to different classes of assays, antibody specificities, thresholds, test variations, and manufacturers. We aimed to assess diagnostic accuracy measures of available immunoassays and to explore sources of heterogeneity. We performed comprehensive literature searches and applied strict inclusion criteria. Finally, 49 publications comprising 128 test evaluations in 15 199 patients were included in the analysis. Methodological quality according to the revised tool for quality assessment of diagnostic accuracy studies was moderate. Diagnostic accuracy measures were calculated with the unified model (comprising a bivariate random-effects model and a hierarchical summary receiver operating characteristics model). Important differences were observed between classes of immunoassays, type of antibody specificity, thresholds, application of confirmation step, and manufacturers. Combination of high sensitivity (>95%) and high specificity (>90%) was found in 5 tests only: polyspecific enzyme-linked immunosorbent assay (ELISA) with intermediate threshold (Genetic Testing Institute, Asserachrom), particle gel immunoassay, lateral flow immunoassay, polyspecific chemiluminescent immunoassay (CLIA) with a high threshold, and immunoglobulin G (IgG)-specific CLIA with low threshold. Borderline results (sensitivity, 99.6%; specificity, 89.9%) were observed for IgG-specific Genetic Testing Institute-ELISA with low threshold. Diagnostic accuracy appears to be inadequate in tests with high thresholds (ELISA; IgG-specific CLIA), combination of IgG specificity and intermediate thresholds (ELISA, CLIA), high-dose heparin confirmation step (ELISA), and particle immunofiltration assay. When making treatment decisions, clinicians should be a aware of diagnostic characteristics of the tests used and it is recommended they estimate posttest probabilities according to likelihood ratios as well as pretest probabilities using clinical scoring tools.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

OBJECTIVES: Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. METHODS: A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2-4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). RESULTS: There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). CONCLUSIONS: If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.

Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain

Recent studies have shown that the nociceptive withdrawal reflex threshold (NWR-T) and the electrical pain threshold (EP-T) are reliable measures in pain-free populations. However, it is necessary to investigate the reliability of these measures in patients with chronic pain in order to translate these techniques from laboratory to clinic. The aims of this study were to determine the test-retest reliability of the NWR-T and EP-T after single and repeated (temporal summation) electrical stimulation in a group of patients with chronic low back pain, and to investigate the association between the NWR-T and the EP-T. To this end, 25 patients with chronic pain participated in three identical sessions, separated by 1 week in average, in which the NWR-T and the EP-T to single and repeated stimulation were measured. Test-retest reliability was assessed using intra-class correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman analysis. The association between the thresholds was assessed using the coefficient of determination (r (2)). The results showed good-to-excellent reliability for both NWR-T and EP-T in all cases, with average ICC values ranging 0.76-0.90 and average CV values ranging 12.0-17.7%. The association between thresholds was better after repeated stimulation than after single stimulation, with average r (2) values of 0.83 and 0.56, respectively. In conclusion, the NWR-T and the EP-T are reliable assessment tools for assessing the sensitivity of spinal nociceptive pathways in patients with chronic pain.

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

Do Central Hypersensitivity and Altered Pain Modulation Predict the Course of Chronic Low Back and Neck Pain?

OBJECTIVES:: Widespread central hypersensitivity and altered conditioned pain modulation (CPM) have been documented in chronic pain conditions. Information on their prognostic values is limited. This study tested the hypothesis that widespread central hypersensitivity (WCH) and altered CPM, assessed during the chronic phase of low back and neck pain, predict poor outcome. METHODS:: A total of 169 consecutive patients with chronic low back or neck pain, referred to the pain clinic during 1 year, were analyzed. Pressure pain tolerance threshold at the second toe and tolerance time during cold pressor test at the hand assessed WCH. CPM was measured by the change in pressure pain tolerance threshold (test stimulus) after cold pressor test (conditioning stimulus). A structured telephone interview was performed 12 to 15 months after testing to record outcome parameters. Linear regression models were used, with average and maximum pain intensity of the last 24 hours at follow-up as endpoints. Multivariable analyses included sex, age, catastrophizing scale, Beck Depression Inventory, pain duration, intake of opioids, and type of pain syndrome. RESULTS:: Statistically significant reductions from baseline to follow-up were observed in pain intensity (P<0.001). No evidence for an association between the measures of WCH or CPM and intensity of chronic pain at follow-up was found. DISCUSSION:: A major predictive value of the measures that we used is unlikely. Future studies adopting other assessment modalities and possibly standardized treatments are needed to further elucidate the prognostic value of WCH and altered CPM in chronic pain.

Ranking of parameters of pain hypersensitivity according to their discriminative ability in chronic low back pain

Low back pain is associated with plasticity changes and central hypersensitivity in a subset of patients. We performed a case-control study to explore the discriminative ability of different quantitative sensory tests in distinguishing between 40 cases with chronic low back pain and 300 pain-free controls, and to rank these tests according to the extent of their association with chronic pain. Gender, age, height, weight, body mass index, and psychological measures were recorded as potential confounders. We used 26 quantitative sensory tests, including different modalities of pressure, heat, cold, and electrical stimulation. As measures of discrimination, we estimated receiver operating characteristics (ROC) and likelihood ratios. Six tests seemed useful (in order of their discriminative ability): (1) pressure pain detection threshold at the site of most severe pain (fitted area under the ROC, 0.87), (2) single electrical stimulation pain detection threshold (0.87), (3) single electrical stimulation reflex threshold (0.83), (4) pressure pain tolerance threshold at the site of most severe pain (0.81), (5) pressure pain detection threshold at suprascapular region (0.80), and (6) temporal summation pain threshold (0.80). Pressure and electrical pain modalities seemed most promising and may be used for diagnosis of pain hypersensitivity and potentially for identifying individuals at risk of developing chronic low back pain over time.

Suitability of low-dosage oxytocin treatment to induce milk ejection in dairy cows

Chronic use of high oxytocin (OT) dosages can cause a reduced response to endogenous OT. In this study the OT dosages used in the milking practice of 82 dairy cow farms were recorded. The OT dosages per cow used were high, especially when injected i.m. (23+/-2 IU) compared with i.v. (7+/-1 IU). In addition, the minimum OT dosages needed to obtain normal milk removal in cows with disturbed milk ejection were investigated. Seventeen cows routinely treated with OT during milking (group T) and 17 cows without previous OT treatment were used (group C). After cessation of spontaneous milk flow, both T and C groups were injected i.v. with a low dosage of OT (0.2 or 0.5 IU/cow). The time from injection until cessation of the OT-induced milk flow was recorded (response phase). The response phase and the amounts of removed milk by effect of the OT injection increased with increasing OT dosage. Values for 0.2 and 0.5 IU/cow of OT injected i.v. were (response phase and amount of milk removed) 198+/-27 and 302+/-18s and 3.4+/-0.7 kg and 6.5+/-1.3 kg, respectively, for the C group, and 157+/-15 and 221+/-16s and 3.2+/-0.5 and 5.5+/-1.0 kg, respectively, for the T group. Within 20 min of the OT injection, plasma concentrations returned to basal levels. The threshold OT concentration at cessation of milk flow after injection of 0.2 or 0.5 IU/cow of OT was calculated based on the OT plasma half-life. The threshold increased with increasing dosages of OT and was higher in group T (8+/-1 and 14+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively) than in group C (7+/-1 and 11+/-1 pg/mL for 0.2 and 0.5 IU/cow, respectively). In conclusion, desensitization of the udder toward OT occurs when the udder is exposed to elevated OT plasma concentrations, both short-term during the actual milking and long-term due to chronic high-dosage OT treatment. However, low-dosage OT treatments to induce normal milk removal can minimize the observed side effects.

Predictive value of the Acute Low Back Pain Screening Questionnaire and the Örebro Musculoskeletal Pain Screening Questionnaire for persisting problems

A small proportion of individuals with non-specific low back pain (NSLBP) develop persistent problems. Up to 80% of the total costs for NSLBP are owing to chronic NSLBP. Psychosocial factors have been described to be important in the transition from acute to chronic NSLBP. Guidelines recommend the use of the Acute Low Back Pain Screening Questionnaire (ALBPSQ) and the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) to identify individuals at risk of developing persistent problems, such as long-term absence of work, persistent restriction in function or persistent pain. These instruments can be used with a cutoff value, where patients with values above the threshold are further assessed with a more comprehensive examination.