The growth arresting effect of human immunoglobulin for intravenous use is mediated by antibodies recognizing membrane glycolipids

Intravenous human IgG (IVIg) given to patients with autoimmune disorders can result in significant clinical improvement in some patients. The mechanism(s) by which IVIg induces these improvements is(are) not known. We have previously shown that IVIg inhibited the proliferation of peripheral blood lymphocytes in allogeneic mixed lymphocyte reactions and of autonomously growing human and mouse cell lines. In an effort to identify the antigen(s) to which the human IgG binds, the human B cell line JY, whose proliferation was inhibited by IVIg, was incubated with IVIg, washed extensively with PBS, and lysed. Human IgG from these lysates was purified by protein A-Sepharose (IVIgJY). IVIgJY binds to and inhibits the proliferation of JY cells and of peripheral blood lymphocytes stimulated in a MLR at a 1000- to 10,000-fold lower concentration compared to IVIg. IVIgJY was analyzed on a 5-15% gradient SDS/PAGE and only immunoglobulin heavy- and light-chain (run under reducing conditions) proteins were detected. Immunoprecipitation experiments from JY cell lysates with IVIgJY indicated that this IgG did not bind to a protein epitope. Thin-layer immunoblot experiments showed that the IVIgJY binds to glycolipids expressed by JY cells and lymphocytes. Furthermore, evidence is presented indicating that antiglycolipid antibodies are involved in IVIg-induced growth inhibitio

Monitoring disease progression using high-density motor unit number estimation in amyotrophic lateral sclerosis

Contains fulltext : 89158.pdf (publisher's version ) (Closed access)In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated high-density motor unit number estimation (MUNE), as compared with the ALS Functional Rating Scale (ALSFRS) and maximal compound muscle action potential (CMAP) amplitude, for monitoring and classifying disease progression. MUNE showed good reproducibility (intraclass correlation coefficient = 0.86). MUNE showed a significantly greater decrease than the ALSFRS, the Medical Research Council (MRC) scale, and CMAP amplitude. Patients could be stratified into groups with rapidly or slowly progressive disease based on a decrement in MUNE at 4 months from baseline; ALSFRS score at 8 months was significantly lower in the rapidly progressive group. MUNE was sensitive to motor neuron loss early in the disease course when compared to other clinical measures. Stratification of patients based on a decrease in MUNE seems feasible.1 augustus 201

Motor unit number estimation using high-density surface electromyography

Contains fulltext : 70622.pdf (publisher's version ) (Closed access)OBJECTIVE: To present a motor unit number estimation (MUNE) technique that resolves alternation by means of high-density surface EMG. METHODS: High-density surface EMG, using 120 EMG channels simultaneously, is combined with elements of the increment counting technique (ICT) and the multiple-point stimulation technique. Alternation is a major drawback in the ICT. The spatial and temporal information provided by high-density surface EMG support identification and elimination of the effects of alternation. We determined the MUNE and its reproducibility in 14 healthy subjects, using a grid of 8 x 15 small electrodes on the thenar muscles. RESULTS: Mean MUNE was 271+/-103 (retest: 290+/-109), with a coefficient of variation of 22% and an intra-class correlation of 0.88. On average, 22 motor unit potentials (MUPs) were collected per subject. The representativity of this MUP sample was quantitatively assessed using the spatiotemporal information provided by high-density recordings. CONCLUSIONS: MUNE values are relatively high, because we were able to detect many small MUPs. Reproducibility was similar to that of other MUNE techniques. SIGNIFICANCE: Our technique allows collection of a large MUP sample non-invasively by resolving alternation to a large extent and provides insight into the representativity of this sample. The large sample size is expected to increase MUNE accuracy

Motor axon loss is associated with hand dysfunction in Charcot-Marie-Tooth disease 1a.

Contains fulltext : 70597.pdf (publisher's version ) (Closed access)BACKGROUND: Charcot Marie Tooth type 1a (CMT1a) is a primarily demyelinating neuropathy, characterized by slowly progressive muscle weakness, atrophy, and sensory loss, and is most pronounced in both feet and hands. There is increasing evidence that muscle weakness is determined by motor axonal dysfunction. OBJECTIVE: To investigate in patients with CMT1a whether motor axon loss, as estimated with motor unit number estimation (MUNE) and compound muscle action potential (CMAP), is related to hand function and manual dexterity. METHODS: Hand function, manual dexterity, and axon loss were studied in 48 patients with proven CMT1a. Using high-density surface EMG on the thenar muscles, MUNE was determined and CMAPs were measured. RESULTS: Pinch strength, clawing of the fingers, and manual dexterity correlated significantly with MUNE and CMAP (amplitude and area), while sensory impairments did not. Grip strength correlated significantly with CMAP amplitude but did not become significant with MUNE and CMAP area. Neurophysiologic variables were particularly associated with fine motor function of the hand. CONCLUSIONS: Motor axon loss is likely to be the major cause of hand dysfunction and impaired manual dexterity in Charcot Marie Tooth type 1a (CMT1a). In a clinical setting, the evaluation of the hands of patients with CMT1a should thus be mainly directed toward the evaluation of fine motor functions

How incremental video training did not guarantee implementation due to fluctuating population prevalence

Contains fulltext : 208509.pdf (publisher's version ) (Open Access)Patients with stroke admitted at the neurology/neurosurgery ward of the Academic Medical Centre in Amsterdam, The Netherlands, may experience problems in communication, such as aphasia, severe confusion/delirium or severe language barriers. This may prevent self-reported pain assessment; therefore, pain behaviour observation scales are needed. In this project, we therefore aimed to implement the Rotterdam Elderly Pain Observation Scale (REPOS) by video training. We used a stepped-wedge cluster design with clusters of four to five nurses with intervals of 2 weeks, for a total study duration of 34 weeks. Primary endpoint was the proportion of shifts in which nurses used the REPOS when caring for an eligible patient. A questionnaire was send biweekly to assess self-perceived competence and attitude on pain measurement in patients able or unable to self-report pain intensity. No other strategies were used to promote the use of the REPOS. Though the proportion of shifts in which trained nurses cared for eligible patients increased from 0% at baseline to 83% at the end of the study, the proportion of cumulative shifts where the REPOS was used decreased from 14% to 6%, respectively. Process evaluation suggests that this decrease can (in part) be attributed to low and varying prevalence of eligible patients and opportunities for practice. In total, 24 (45.3%) nurses had used the REPOS at least once after 34 weeks, with a median of two times (1-33). Nurses perceived themselves 'competent' to 'very competent' in pain behaviour observation. There was no negative attitude towards pain measurement. This study shows that education alone may not be effective when implementing a pain behaviour observation scale for non-communicative patients with Acquired Brain Injury. Individual motivation of health professionals and individual patient factors may be of influence for the use of the REPOS

Assessing deterioration using impairment and functional outcome measures in chronic inflammatory demyelinating polyneuropathy: A post-hoc analysis of the immunoglobulin overtreatment in CIDP trial

It is unclear whether frequently used cutoff values for outcome measures defining minimal clinically important differences (MCIDs) can accurately identify meaningful deterioration in chronic inflammatory demyelinating polyneuropathy (CIDP). We used data from the immunoglobulin overtreatment in CIDP (IOC) trial, in which 60 clinically stable patients with CIDP were randomized to intravenous immunoglobulin (IVIg) withdrawal or continuation. We calculated change scores of the Inflammatory Rasch-Built Overall Disability Scale (I-RODS), grip strength, and Medical Research Council-sum score (MRC-SS) and classified visits based on a treatment anchor (ie, decision to restart/increase treatment after reaching a predefined early endpoint of deterioration). The variability of scores in patients without deterioration was calculated using the limits of agreement. We defined optimized MCIDs for deterioration and specific combinations of MCIDs from different outcome measures, and subsequently calculated the accuracies of the (combined) MCIDs. Substantial variability was found in scores of the I-RODS, grip strength and MRC-SS in patients without deterioration over time, and most MCIDs were within the limits of the variability observed in patients without deterioration. Some MCID cut-offs were insensitive but highly specific for detecting deterioration, for example, the MCID-SE of -1.96 of the I-RODS and -2 point on the MRC-SS. Others were sensitive, but less specific, for example, -4 centiles of the I-RODS. Some combined MCIDs resulted in high specificities and moderate sensitivities. Our results suggest that clinically important deterioration cannot be distinguished from variability over time with currently used MCIDs on the individual level. Combinations of MCIDs might improve the accuracy of determining deterioration, but this needs validation

Quality of life in inflammatory neuropathies: the IN-QoL

Item does not contain fulltextBACKGROUND: No consensus exists which quality of life (QoL) measure should be used in patients with inflammatory neuropathies. Moreover, most QoL measures are ordinal-based scales with their known deficiencies. OBJECTIVES: To establish a new disease-specific interval-based QoL questionnaire in inflammatory neuropathies (IN-QoL) using the Rasch model and evaluate its scientific properties (validity, reliability and responsiveness). METHODS: 264 patients with inflammatory neuropathies completed six commonly used QoL questionnaires. The obtained data were stacked and subjected to Rasch analysis. Responsiveness was determined by using the concept of minimum clinically important differences related to varying individually obtained SEs (responsiveness definition: MCID-SE>/=1.96 after 1-year follow-up compared with baseline). RESULTS: The IN-QoL fulfilled all Rasch's model requirements with high internal reliability values (patient separation index of 0.94), except being multidimensional. Additional factor analysis resulted in two (functional and mental) subsets that were unidimensional on their own. The IN-QoL showed good correlation with the EuroQol-health quality visual analogue scale (EQ-VAS) (Spearman's rho 0.72). It demonstrated acceptable responsiveness in patients with Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as did the EQ-VAS. In patients with monoclonal gammopathy-related neuropathy and multifocal motor neuropathy, hardly any changes were seen over time. CONCLUSION: The IN-QoL questionnaire fulfils modern clinimetric requirements and correlates strongly with a patient's self-assessment of their own quality of health, while also showing responsiveness in patients with GBS and CIDP. We propose using the IN-QoL and the EQ-VAS for assessing the QoL of patients with inflammatory neuropathies in future studies