Regarding the past, what is the trial you have always been dreaming of in CIDP?

Chronic inflammatory demyelinating polyradiculoneuropathy is an orphan disease of poorly understood cause. While first line treatments with corticosteroids, intravenous immunoglobulin and plasma exchange have at least short-term efficacy, no trial has shown that immunosuppressants work. In our dream, we will take advantage of the recently improved EU regulations to launch a Europe wide trial which will investigate the cause of the disease. It will compare three parallel groups, the anti-B cell agent rituximab, the anti-T cell agent abatacept and usual care. The trial will not be blinded and the design will be very simple. The primary outcome measure will be improvement from baseline of the overall neuropathy limitations scale (ONLS) score by 1 or more grades at 12 weeks without increase in concomitant corticosteroids or IVIg or use of plasma exchange. There will be an option to substitute improvement in the Rasch-built overall disability scale depending on future experience with that scale as the primary outcome measure. The trial will require 3 groups of 60 participants to detect an increase from 20% in the usual care group to 30% with one of the other agents with a power of 90% and P-value of 5%. It will be larger than any trial of an immunosuppressant agent so far performed in CIDP. However, recruitment will be easier because inclusion criteria will be broad and allow randomisation of any patient in whom their neurologist wishes to introduce an immunosuppressant. Avoidance of blinding and use of simple monitoring with facetime will simplify running the trial and reduce expense. The trial will follow participants and measure outcomes at 12 months. Other outcomes will consist only of grip strength, time to walk 10 m and Euroqol, the last allowing us to estimate the cost per QALY of rituximab or abatacept. Even including central analysis of key biomarkers, the trial will only cost 3 million euros, a fraction of the cost of the usual phase III pharmaceutical company trial.

Nerve conduction velocity in CMT1A: what else can we tell?

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A. METHODS: Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot-Marie-Tooth Examination Score (CMTES). RESULTS: NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES. CONCLUSIONS: This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length-dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.

Comparison of imputation variance estimators.

Appropriate imputation inference requires both an unbiased imputation estimator and an unbiased variance estimator. The commonly used variance estimator, proposed by Rubin, can be biased when the imputation and analysis models are misspecified and/or incompatible. Robins and Wang proposed an alternative approach, which allows for such misspecification and incompatibility, but it is considerably more complex. It is unknown whether in practice Robins and Wang's multiple imputation procedure is an improvement over Rubin's multiple imputation. We conducted a critical review of these two multiple imputation approaches, a re-sampling method called full mechanism bootstrapping and our modified Rubin's multiple imputation procedure via simulations and an application to data. We explored four common scenarios of misspecification and incompatibility. In general, for a moderate sample size (n = 1000), Robins and Wang's multiple imputation produced the narrowest confidence intervals, with acceptable coverage. For a small sample size (n = 100) Rubin's multiple imputation, overall, outperformed the other methods. Full mechanism bootstrapping was inefficient relative to the other methods and required modelling of the missing data mechanism under the missing at random assumption. Our proposed modification showed an improvement over Rubin's multiple imputation in the presence of misspecification. Overall, Rubin's multiple imputation variance estimator can fail in the presence of incompatibility and/or misspecification. For unavoidable incompatibility and/or misspecification, Robins and Wang's multiple imputation could provide more robust inferences.

Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. METHODS: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). RESULTS: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). CONCLUSIONS: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.

Transformation of truncated gold octahedrons into triangular nanoprisms through the heterogeneous nucleation of silver.

Described is a straightforward procedure for forming organized substrate-immobilized nanoprisms which are single crystalline, surfactant-free and which form a heteroepitaxial relationship with the underlying substrate. The devised route utilizes truncated Au octahedrons formed through solid state dewetting techniques as high temperature heterogeneous nucleation sites for Ag adatoms which are arriving to the substrate surface in the vapour phase. Observed is a morphological and compositional transformation of the Au structures to triangular nanoprisms comprised of a homogeneous AuAg alloy. During this transformation, the localized surface plasmon resonance red-shifts, broadens and increases in strength. The shape transformation, which cannot be rationalized using thermodynamic arguments dependent on the surface energy minimization, is described in terms of a kinetically driven growth mode, previously predicted by molecular dynamic simulations. The so-formed structures, when coated with a thin layer of Pd, are demonstrated as plasmonic sensing elements for hydrogen detection.

Is overwork weakness relevant in Charcot-Marie-Tooth disease?

BACKGROUND: In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot-Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles. METHODS: We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity. RESULTS: We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity. DISCUSSION: Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients.

Epidemiology of chronic inflammatory neuropathies in southeast England.

BACKGROUND AND PURPOSE: There is little information about the prevalence and disease burden of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN). METHODS: Multiple sources were used to study the prevalence and clinical features of these diseases in a southeast England population of 3,557,352 people. RESULTS: The crude prevalences were as follows: CIDP, 2.84 (95% CI 2.31-3.45); MMN, 0.53 (95% CI 0.32-0.83); and PDN, 1.04 (95% CI 0.73-1.43) per 100,000 population. All three diseases were more common in men than in women. The peak decade of onset was older in those with CIDP (70-79 years) and PDN (70-79 years) than in those with MMN (50-59 years). Disability was greater in CIDP and PDN, with median (range) overall neuropathy limitations scores of 4 (0-8) and 4 (1-6), respectively, than in MMN, with a score of 2 (1-5). CONCLUSION: The common forms of chronic inflammatory neuropathy cause a considerable disease burden in the community.

Economic costs and quality of life in chronic inflammatory neuropathies in southeast England.

BACKGROUND AND PURPOSE: Cost-of-illness studies and health-related quality of life (HRQoL) measurements are needed to assess the effects of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinaemic demyelinating neuropathy (PDN) on society. METHODS: This study was conducted in 2008 in a southeast England population of 3,557,352 people. Data on service use and treatment were collected with a client service receipt inventory and service costs were calculated by combining these data with national unit costs. The EuroQol was used to calculate utility scores, a measurement of HRQoL. RESULTS: The total annual cost-of-illness per patient was £22,085 for CIDP, £22,812 for MMN and £7566 for PDN. The annual total cost per patient was £49,430 for individuals on intravenous immunoglobulin (IVIg) and £9046 for those not on IVIg (P < 0.01). The mean (SD) utility scores were 0.62 (0.23) for CIDP, 0.63 (0.22) for PDN and 0.72 (0.14) for MMN (P = 0.52). The mean (SD) utility score for those on IVIg was 0.65 (0.16) and those not on IVIg 0.63 (0.23) (P = 0.77). CONCLUSION: The use of IVIg was the most important determinant of cost in all three diseases and the higher frequency of its use in CIDP and MMN accounted for the much greater average cost per patient in these diseases. There was no significant difference in HRQoL amongst the three diseases or between those receiving or not receiving IVIg.

Effect of pig breed and dietary protein level on selected fatty acids and stearoyl-coenzyme A desaturase protein expression in longissimus muscle and subcutaneous fat.

The aims of the study were 1) to investigate effects of a low protein diet on fatty acids content and composition of the LM and subcutaneous adipose tissue in 3 genetically diverse breeds, Large White × Landrace, Alentejano, and Bizaro, and 2) to determine whether the effect of the low protein diet of fatty acid composition is associated with dietary modulation of stearoyl-CoA desaturase (SCD) protein expression. The experiments were conducted on 12 Large White × Landrace, 12 Alentejano, and 10 Bízaro female and male pigs. The average animal BW at the beginning of experiments was 40.8, 40.7, and 38.3 kg for Large White × Landrace, Alentejano, and Bízaro, respectively, and the BW of animals at slaughter was 90 kg. The diets contained 202 or 169 g/kg DM of CP (high and low protein diets, respectively) and were balanced in essential AA. The diets were fed until the animals reached 90 kg BW (approximately 73 d). It was established that Large White × Landrace pigs had a less (P = 0.001) total fatty acid content in subcutaneous adipose tissue when compared with Alentejano and Bízaro and less (P < 0.001) intramuscular fat (IMF) content when compared with Alentejano. There was a positive relationship between SCD protein expression in the LM and MUFA content (r = 0.627, P = 0.029) and SCD protein expression and total muscle fatty acids content (r = 0.725, P = 0.008) in Large White × Landrace but not in Alentejano and Bizaro breeds. It has been suggested that SCD protein expression is associated with regulation of fat deposition only in breeds with genetic predisposition to a low IMF content.

Vigorimeter grip strength in CIDP: a responsive tool that rapidly measures the effect of IVIG--the ICE study.

BACKGROUND AND PURPOSE: In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV-C) intravenously than in those receiving placebo. METHODS: We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP. RESULTS: A randomized double-blind trial was undertaken in 117 CIDP patients who received IGIV-C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut-off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV-C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV-C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV-C group (37.5%-50.9%) than in the placebo group (21.1%-25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1-point deterioration) findings. CONCLUSIONS: Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.

Altering the dewetting characteristics of ultrathin gold and silver films using a sacrificial antimony layer.

Solid state dewetting of ultrathin films is the most straightforward means of fabricating substrate-supported noble metal nanostructures. This assembly process is, however, quite inflexible, yielding either densely packed smaller structures or widely spaced larger structures. Here, we demonstrate the utility of introducing a sacrificial antimony layer between the substrate and noble metal overlayer. We observe an agglomeration process which is radically altered by the concurrent sublimation of antimony. In stark contrast with conventional dewetting, where the thickness of the deposited metal film determines the characteristic length scales of the assembly process, it is the thickness of the sacrificial antimony layer which dictates both the nanoparticle size and interparticle spacing. The result is a far more flexible self-assembly process where the nanoparticle size and areal density can be varied widely. Demonstrations show nanoparticle areal densities which are varied over four orders of magnitude assembled from the identical gold layer thickness, where the accompanying changes to nanostructure size see a systematic shift in the wavelength of the localized surface plasmon resonance. As a pliable self-assembly process, it offers the opportunity to tailor the properties of an ensemble of nanostructures to meet the needs of specific applications.

[Guillain-Barré syndrome after exposure to influenza]. / Guillain-Barré-Syndrom nach Exposition mit Influenza.

Guillain-Barré Syndrome (GBS) is an acquired, monophasic inflammatory polyradiculoneuritis of autoimmune origin, which occurs after infection and occasionally also after vaccination. Seasonal and pandemic influenza vaccines have in particular been implicated as triggers for GBS. However, a number of recent studies indicate that infection with influenza virus may also cause GBS. This review summarizes the epidemiological and experimental data of the association of GBS with exposure to influenza antigens by immunization (including vaccines against A/H1N1/2009) and infection. Vaccination against influenza is associated with a very low risk for the occurrence of GBS. In contrast infection with influenza may play a more important role as a triggering factor for GBS than previously assumed.

Long-term trends in CD4 cell counts and impact of viral failure in individuals starting antiretroviral therapy: UK Collaborative HIV Cohort (CHIC) study.

OBJECTIVE: The aim of the study was to describe trends in CD4 cell counts in HIV-infected patients after initiation of combination antiretroviral therapy (cART), according to CD4 cell count at initiation (baseline), and to quantify the implications of virological failure for these trends. METHODS: Eligible participants from the UK Collaborative HIV Cohort (CHIC) were antiretroviralnaïve and started cART after 1997. Random effects were used to model CD4 cell count trends, accounting for multiple measurements within participants. We assessed whether CD4 cell count trends varied according to baseline CD4 cell count and separately in participants with and without post-cART virological failure. Effects of post-cART virological failure (>1000 HIV-1 RNA copies/mL) on subsequent CD4 cell counts were evaluated. FINDINGS: A total of 7069 participants were included in the analysis (median follow-up in all baseline CD4 cell count groups was ≥ 35 months). Among participants without virological failure ≥ 6 months after the start of cART, CD4 cell counts continued to increase up to 8 years, with little evidence that differences between baseline CD4 cell count groups diminished over time. Virological failure ≥ 6 months after the start of cART was associated with lower subsequent CD4 cell counts, with greater CD4 cell count reduction for more recent virological failure and higher viral load. CONCLUSIONS: Post-cART CD4 cell counts are strongly related to pre-cART CD4 cell counts. CD4 cell count recovery is greatest in individuals who can avoid viral loads >1000 copies/mL while on cART.

Variable phenotypes are associated with PMP22 missense mutations.

Charcot-Marie-Tooth disease (CMT) is the commonest hereditary neuropathy encompassing a large group of clinically and genetically heterogeneous disorders. The commonest form of CMT, CMT1A, is usually caused by a 1.4 megabase duplication of chromosome 17 containing the PMP22 gene. Mutations of PMP22 are a less common cause of CMT. We describe clinical, electrophysiological and molecular findings of 10 patients carrying PMP22 missense mutations. The phenotype varied from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe CMT1. We identified six different point mutations, including two novel mutations. Three families were also found to harbour a Thr118Met mutation. Although PMP22 point mutations are not common, our findings highlight the importance of sequencing the PMP22 gene in patients with variable CMT phenotypes and also confirm that the PMP22 Thr118Met mutation is associated with a neuropathy albeit with reduced penetrance.

Confirming the efficacy of intravenous immunoglobulin in CIDP through minimum clinically important differences: shifting from statistical significance to clinical relevance.

BACKGROUND: The ICE trial demonstrated the efficacy of immune globulin intravenous (IGIV-C) over placebo in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, improving the interpretability of the results by analysing the minimum clinically important difference (MCID) had not been considered. OBJECTIVES: To identify MCID thresholds of various outcome measures using different methods and to test treatment differences (IGIV-C vs placebo) using these thresholds. METHODS: One anchor-based (Short Form-36 question 2) and three distribution-based (½ SD, 1 SE of measurement, and effect size) techniques were employed to identify MCID cut-offs for various impairments (electromyographic parameters, Medical Research Council (MRC) sum score, grip strength, inflammatory neuropathy cause and treatment (INCAT) sensory sum score), disability (INCAT scale score, Rotterdam handicap scale (RHS) score) and quality of life (SF-36). IGIV-C or placebo was administered every 3 weeks for up to 24 weeks to 117 CIDP patients. Patients who did not improve by ≥1 point on the INCAT scale received alternate treatment. The proportion of patients with results exceeding identified MCID thresholds was compared. Results MCID cut-offs for outcomes were determined using each method. For the INCAT disability scale (primary ICE-trial outcome), all MCID methods identified significantly more responders with IGIV-C than placebo. Significant differences favouring IGIV-C were also demonstrated for various nerve conduction parameters, MRC sum score, grip strength, RHS score and SF-36 physical component summary score. CONCLUSION: In addition to being statistically significant, all MCID analyses showed that CIDP improvements with IGIV-C are clinically meaningful. Consideration of MCID is recommended in future therapeutic trials. Trial Registration Number NCT00220740 (http://ClinicalTrials.gov).

Intramuscular interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) shares immunologic features with multiple sclerosis (MS). Because IM interferon beta-1a (IM IFNbeta-1a) is an effective and safe treatment for MS, we conducted a dose-ranging efficacy study of IFNbeta-1a in patients with CIDP. METHODS: Adults with IV immunoglobulin (IVIg)-dependent CIDP (n = 67) were enrolled in this 32-week double-blind trial and randomized to IM IFNbeta-1a. Patients received 30 microg once weekly plus placebo (n = 12), IM IFNbeta-1a 60 microg once weekly plus placebo (n = 11), IM IFNbeta-1a 30 microg twice weekly (n = 11), IM IFNbeta-1a 60 microg twice weekly (n = 11), or placebo twice weekly (n = 22). Participants were maintained on IVIg through week 16, when IVIg was discontinued. Patients who worsened were restarted on IVIg. The primary outcome was total IVIg dose (g/kg) administered from week 16 to 32. RESULTS: There was no difference in total IVIg dose administered after week 16 for patients treated with IFNbeta-1a (1.20 g/kg) compared with placebo (1.34 g/kg; p = 0.75). However, exploratory analyses suggested IFNbeta-1a significantly reduced total dose of IVIg compared with placebo for participants who required either high-dose IVIg (>0.95 g/kg per month) or had greater weakness at baseline (Medical Research Council sum score <51). Adverse events included flu-like symptoms, headache, and fatigue in the IFNbeta-1a groups. CONCLUSIONS: Interferon beta-1a (IFNbeta-1a) therapy did not provide significant benefit over IV immunoglobulin (IVIg) therapy alone for patients with chronic inflammatory demyelinating polyradiculoneuropathy. However, IFNbeta-1a might be beneficial for patients with more severe disability or those needing high doses of IVIg. LEVEL OF EVIDENCE: This study was designed to provide Class I evidence for the safety and efficacy of IM IFNbeta-1a in the treatment of CIDP but has been subsequently classified as Class II due to a >20% patient dropout rate. Thus, this randomized, controlled clinical trial provides Class II evidence of no effect on primary and secondary endpoints of 4 dosage regimens of IM IFNbeta-1a added to IVIg in persons with CIDP.

Clinical applications of intravenous immunoglobulins in neurology.

Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.

Health-related quality-of-life improvements in CIDP with immune globulin IV 10%: the ICE Study.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy trials have demonstrated the efficacy of IV immunoglobulin vs placebo. However, these trails have not addressed the long-term impact on health-related quality of life (HRQoL). METHODS: One hundred seventeen patients in a randomized, double-blind, response-conditional crossover trial received immune globulin IV, 10% caprylate/chromatography purified (IGIV-C [Gamunex(R)]), or placebo every 3 weeks for up to 24 weeks in the first period (FP). Participants whose inflammatory neuropathy cause and treatment disability score did not improve by >/=1 point received alternate treatment in a 24-week crossover period (CP). In either period, participants who improved and completed treatment were eligible to be randomly reassigned to a blinded 24-week extension phase (EP). HRQoL analyses were conducted using the Short Form-36(R) (SF-36) and the Rotterdam Handicap Scale (RHS). RESULTS: In the FP, greater improvements in both SF-36 physical and mental component scores were observed with IGIV-C vs placebo, with a significant improvement in the physical component score (difference 4.4 points; 95% confidence interval [CI] 0.7-8.0). Improvements in all SF-36 domains favored IGIV-C vs placebo, with physical functioning, role-physical, social functioning, and mental health reaching significance. Participants receiving IGIV-C experienced a larger improvement in RHS vs those receiving placebo (difference 3.4 points; 95% CI 1.4-5.5; p = 0.001). In the CP, similar general trends were observed. In the EP, mean SF-36 improvements were generally improved or maintained in participants who continued IGIV-C therapy; however, worsening was observed in participants re-randomized to placebo. CONCLUSIONS: Long-term therapy with immune globulin IV, 10% caprylate/chromatography purified, improves and maintains health-related quality of life in chronic inflammatory demyelinating polyradiculoneuropathy.