A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy

Intravenous immunoglobulin (IVIG) has become the standard treatment for multifocal motor neuropathy (MMN) based on limited data. To critically assess the efficacy, safety, and tolerability of 10% liquid IVIG (IVIG), 44 adults with MMN were randomized 1 : 1 to either double‐blind treatment of IVIG followed by placebo for 12 weeks each or the reverse. Open‐label IVIG was administered for 12 weeks at the beginning and end of the study for clinical stabilization, and between double‐blinded periods to prevent a carry‐over effect. To avoid potential worsening, switching to open‐label IVIG was permitted if deterioration occurred during blinded treatment. Mean maximal grip strength of the more affected hand declined 31.38% during placebo and increased 3.75% during IVIG (p = 0.005). In 35.7% of participants, Guy's Neurological Disability scores for upper limbs worsened during placebo and not during IVIG, whereas the converse was true in 11.9% (p = 0.021). Sixty‐nine percent (69.0%) switched prematurely from placebo to open‐label IVIG and 2.4% switched from blinded to open‐label IVIG (p < 0.001). One serious adverse reaction (pulmonary embolism) and 100 non‐serious reactions (69 mild, 20 moderate, and 11 severe) to IVIG occurred. IVIG was effective in improving disability and muscle strength, and was safe and well tolerated in adults with MMN.     

Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial

Background and purpose:  For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better quality of life.
Methods:  In a randomized single-blinded cross-over study, nine IVIG responsive patients were allocated to receive either SCIG or IVIG for a period equivalent to three IVIG treatment intervals and, subsequently, crossed over to the other treatment. Primary end-points were (i) dynamometric strength of affected muscles and (ii) the SF-36 quality of life questionnaire.
Results:  The two treatments were equally effective, the mean change in muscle strength after SCIG being 3.6% (95% CI −3.6% to 10.9%) vs. 4.3% (−1.3% to 10.0%) after IVIG ( P  = 0.86). One patient had sustained erythema and oedema at the injection sites for a few weeks. All other adverse effects during SCIG were mild and transient. No differences between treatments of health-related quality of life occurred.
Conclusion:  In MMN, short-term subcutaneous infusion of immunoglobulin is feasible, safe and as effective as intravenous infusion. Subcutaneous administration is an alternative option that adds flexibility to the treatment schedule.     

Long-term follow-up of Lambert-Eaton syndrome treated with intravenous immunoglobulin

Recent reports have shown that patients with Lambert-Eaton myasthenic syndrome (LEMS) improve transiently after high-dose intravenous immunoglobulin (IVIG) administration. Information about the usefulness of IVIG for long-term treatment is rather scanty. Our findings demonstrate the efficacy of monthly IVIG courses at a dose of 0.4 g/kg/day for 5 days, in a 41-year-old patient with LEMS without detectable malignancy. Improvement in limb strength, peak expiratory flow rate, and electrophysiological parameters, as well as clinical signs following IVIG, was evident as early as 7 days after the first course and is still maintained at 24-months follow-up. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 674–678, 1997.     

Serum tumour necrosis factor-alpha and soluble tumour necrosis factor receptors levels in patients with Guillain-Barre syndrome

OBJECTIVES: To estimate the serum concentrations of Tumour Necrosis Factor alpha (TNF-alpha) and soluble TNF receptors (s TNF-RI and TNF-RII) in patients with Guillain-Barre syndrome (GBS), before and after treatment. MATERIAL AND METHODS: The serum TNF-alpha and the soluble TNF receptors concentrations were measured by a sandwich enzyme-linked immunosorbent assay (ELISA) in 47 patients with GBS before and after the treatment - IVI therapy (n=26); Plasma Exchange (n=21). RESULTS: At the time of admission, the serum TNF-alpha concentrations were elevated (32.5-182.5 pg/ml) in 41/47 GBS patients (87.2%). Following the treatment (IVIG or PE), there was a significant decrease in the serum TNF-alpha concentrations (8.5-58.5 pg/ml) in these 41 GBS patients. The soluble TNF receptors, particularly sTNF-RII concentrations were significantly increased in GBS patients treated by IVIG therapy. CONCLUSIONS: The results of this indicated that (a) Elevated serum concentrations of TNF-alpha showed a positive correlation with the disease severity in patients with GBS. (b) The decrease in the serum TNF-alpha and increase in the serum soluble TNF receptors, particularly sTNF-RII showed a positive correlation with the neurological recovery in GBB patients following treatment.     

Bright light treatment for high-anxious young adults: a randomized controlled pilot study

Background: Available treatments for anxiety have limitations and/or side effects. The aim of this study was to examine the influence of bright light exposure as a treatment in high‐anxious young adults. Methods: In an acute exposure study, participants (n = 33) were randomly assigned to 45 min of (1) bright light or (2) placebo. Participants then performed a 5‐week study (n = 29). Following a 1‐week baseline, participants were randomly assigned to 4 weeks of daily exposure to either (1) bright light (45 min/day) or (2) placebo treatment, initiated ≤1 hr after awakening. Before and after the experiment, clinical ratings were conducted with the Hamilton Anxiety Scale (HAM‐A), Hamilton Depression Scale, and Clinical Global Impressions scale. Following each week, blood pressure, anxiety (Spielberger State–Trait Anxiety Inventory Y1), depression, mood, sleep, and side effects were assessed. Results: No significant treatment effect was found in the acute exposure study. Likewise, in the 5‐week study, no significant treatment effect was found. However, bright light elicited marginally greater reductions in psychic symptoms of the HAM‐A (P = .06) and other measures. Conclusions: This pilot study provides little compelling evidence for an anxiolytic effect of bright light in high‐anxious young adults. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Competence feedback improves CBT competence in trainee therapists: A randomized controlled pilot study

Objective: The development and improvement of therapeutic competencies are central aims in psychotherapy training; however, little is known about which training interventions are suitable for the improvement of competencies. Method: In the current pilot study, the efficacy of feedback regarding therapeutic competencies was investigated in cognitive behavioural therapy (CBT). Totally 19 trainee therapists and 19 patients were allocated randomly to a competence feedback group (CFG) or control group (CG). Two experienced clinicians and feedback providers who were blind to the treatment conditions independently evaluated therapeutic competencies on the Cognitive Therapy Scale at five treatment times (i.e., at Sessions 1, 5, 9, 13, and 17). Whereas CFG and CG included regular supervision, only therapists in the CFG additionally received written qualitative and quantitative feedback regarding their demonstrated competencies in conducting CBT during treatment. Results: We found a significant Time × Group interaction effect (η²?=?.09), which indicates a larger competence increase in the CFG in comparison to the CG. Conclusions: Competence feedback was demonstrated to be suitable for the improvement of therapeutic competencies in CBT. These findings may have important implications for psychotherapy training, clinical practice, and psychotherapy research. However, further research is necessary to ensure the replicability and generalizability of the findings.     

Electroacupuncture for patients with refractory functional dyspepsia: A randomized controlled trial

Background

To test the efficacy of electroacupuncture for patients with refractory functional dyspepsia (FD).

Methods

A 24‐week, 2‐arm, single‐blind, randomized controlled trial was conducted at three hospitals in China. Patients with refractory FD were randomly assigned to receive 20 sessions of authentic or sham electroacupuncture in a treatment duration of 4 weeks. The primary outcome was complete absence of dyspeptic symptoms at 16 weeks after initiation of acupuncture (week 16). The secondary outcomes included adequate relief of dyspeptic symptoms, Leeds Dyspepsia Questionnaire (LDQ ), Nepean Dyspepsia Index (NDI ), and adverse events. Intention‐to‐treat analysis was performed.

Key Results

Two hundred patients were included, of which 196 (98%) completed follow‐up data at week 24. At week 16, 17 (17%) patients in the authentic electroacupuncture group vs 6 (6%) patients in the sham group achieved the primary outcome (P  = .014). Sixty‐two (62%) patients had adequate relief in the authentic electroacupuncture group, as compared to 22 (22%) in the sham group (P  = .001). The scores of LDQ and NDI were significantly improved in both groups at week 16, and patients in the authentic electroacupuncture group have more improvements (LDQ , mean difference, ?2.2, 95% confidence interval, ?2.3 to ?2.1, P  < .001; NDI , ?7.3, ?10.5 to ?4.2, P  < .001). Results were similar for all the outcomes assessed at week 24. No serious adverse events were reported in both groups.

Conclusion

Acupuncture efficaciously improves dyspeptic symptoms in patients with refractory FD.

     

Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial.

The objective of this study was to investigate the long-term efficacy of ropinirole in patients with restless legs syndrome (RLS) and to assess the potential for relapse after the discontinuation of active treatment. Patients with primary RLS (n = 202) received single-blind ropinirole for 24 weeks. Patients meeting treatment continuation criteria were randomized to double-blind treatment with ropinirole or placebo for a further 12 weeks. The primary efficacy variable was the proportion of patients relapsing during double-blind treatment. Additional efficacy measures included time to relapse, withdrawals due to lack of efficacy, improvement on the Clinical Global Impression-Improvement (CGI-I) scale, change in International Restless Legs Scale (IRLS) score during double-blind treatment, and changes in sleep and quality of life (QoL) parameters. Significantly fewer patients relapsed on ropinirole than on placebo (32.6% vs. 57.8%; P = 0.0156). Time to relapse was longer with ropinirole and more patients withdrew due to lack of efficacy with placebo. Patients showed improvements in IRLS and CGI-I scores, sleep and QoL parameters with single-blind ropinirole, which were better maintained when ropinirole was continued during the double-blind phase, but reduced with placebo. Ropinirole was well tolerated; adverse events were typical for dopamine agonists. Ropinirole was highly effective and well tolerated in the long-term management of RLS, with pharmacological effect over 36 weeks.     

A randomised,multi‐centre phase III study of 3 different doses of intravenous immunoglobulin 10% in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ProCID trial): Study design and protocol

Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) show varying degrees of response to intravenous immunoglobulin (IVIg) therapy. This randomised phase III study in patients with CIDP (ProCID trial) will compare the efficacy and safety of 3 different doses (0.5, 1.0, and 2.0 g/kg) of IVIg 10% (panzyga) administered every 3 weeks for 24 weeks. The primary efficacy endpoint is the rate of treatment response, defined as a decrease in adjusted inflammatory neuropathy cause and treatment disability score of ≥1 point, in the IVIg 1.0 g/kg arm at week 24. Patients with definite or probable CIDP according to European Federation of Neurological Sciences/Peripheral Nerve Society criteria with IVIg or corticosteroid dependency and active disease are eligible. All potentially eligible patients will undergo IVIg or corticosteroid dose reduction (washout phase) over ≤12 weeks or until deterioration of CIDP (active disease). Patients with deterioration during the washout phase will be randomised to receive study treatment during a dose‐evaluation phase starting with a loading dose of IVIg 2.0 g/kg followed by maintenance treatment with IVIg 0.5, 1.0, or 2.0 g/kg every 3 weeks. Rescue medication (2 doses of IVIg 2.0 g/kg given 3 weeks apart) will be administered to patients in the IVIg 0.5 and 1.0 g/kg groups who deteriorate after week 3 and before week 18 or who do not improve at week 6. Safety, tolerability and quality of life will be assessed. The ProCID study will provide new information on the best maintenance dose of IVIg for patients with CIDP.     

Ecopipam,a D1 receptor antagonist,for treatment of tourette syndrome in children: A randomized,placebo‐controlled crossover study

Background : Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4‐week randomized, double‐blind, placebo‐controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome. Methods : Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale – total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2‐week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic‐suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales. Results : Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, ‐3.7; 95% CI, ‐6.5 to ‐0.9; P = 0.011) and 30 days (mean difference, ‐3.2; 95% CI, ‐6.1 to ‐0.3; P = 0.033). There were no weight gain, drug‐induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo). Conclusions : Ecopipam reduced tics and was well tolerated. This placebo‐controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society     

Double-blind randomized controlled trial of low-level laser therapy in carpal tunnel syndrome

Several studies have suggested that low-level laser therapy (LLLT) is effective in patients with carpal tunnel syndrome (CTS). In a double-blind randomized controlled trial of LLLT, 15 CTS patients, 34 to 67 years of age, were randomly assigned to either the control group (n = 8) or treatment group (n =7). Both groups were treated three times per week for 5 weeks. Those in the treatment group received 860 nm galium/aluminum/arsenide laser at a dosage of 6 J/cm2 over the carpal tunnel, whereas those in the control group were treated with sham laser. The primary outcome measure was the Levine Carpal Tunnel Syndrome Questionnaire, and the secondary outcome measures were electrophysiological data and the Purdue pegboard test. All patients completed the study without adverse effects. There was a significant symptomatic improvement in both the control (P = 0.034) and treatment (P =0.043) groups. However, there was no significant difference in any of the outcome measures between the two groups. Thus, LLLT is no more effective in the reduction of symptoms of CTS than is sham treatment.     

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial

Background and Aims

ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse.

Methods

ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0–7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints.

Results

Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: −21.8% [−34.5%, −7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common.

Interpretation

fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.     

Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial

The aim of the study was to assess the safety and feasibility of a clinical trial on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute ischaemic stroke. Thirty consecutive patients with computed tomography verified diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h of stroke onset, were enrolled. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. Poor outcome was defined as being dead or having a Barthel index of < 70 or a Rankin score of 3--5. Intention-to-treat analysis was applied. One-tenth of all hospitalized patients with acute ischaemic stroke were eligible for the trial. Thirty eligible patients were treated with either low-molecular weight dextran alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable with respect to major prognostic variables. A relative risk (RR) reduction of poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval [CI] 0.1--3.4), as defined by the modified Barthel Index, and 60% as defined by the modified Ranking score (RR = 0.4, 95% CI: 0.1--1.7). The National Institute of Health (NIH--NINDS) Stroke Scale score was marginally significantly better in the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No significant adverse effects were seen. This pilot study shows that a full-scale randomized double-blind, placebo-controlled trial of vinpocetine treatment in acute ischaemic stroke is feasible and warranted.     

Corticosteroid iontophoresis to treat carpal tunnel syndrome: A double‐blind randomized controlled trial

Even though injection of corticosteroids into the carpal tunnel alleviates the symptoms of mild to moderately severe carpal tunnel syndrome (CTS), it has not gained universal popularity due to its invasiveness. This study was designed to investigate the effectiveness of dexamethasone iontophoresis as a noninvasive method of treating CTS. We carried out a double‐blind randomized controlled trial comparing six sessions of iontophoresis with 0.4% dexamethasone sodium phosphate with distilled water in 17 patients. Outcome measures including nerve conduction studies, the Levine Self‐Assessment Questionnaire, and the Semmes–Weinstein Monofilaments were done monthly for 6 months after intervention. Most of the outcome measures did not show any significant change following treatment. Although there was subjective improvement of symptom severity scores in the treatment group as quantified by the Levine Self‐Assessment Questionnaire, similar improvement was also observed in the control group (P < 0.05). Although corticosteroid iontophoresis is feasible in clinical settings and is well‐tolerated by patients, iontophoresis of 0.4% dexamethasone was not effective in the treatment of mild to moderate CTS. Muscle Nerve 39: 627–633, 2009