Comparisons in fluctuation of muscle strength and function in patients with immune-mediated neuropathy treated with intravenous versus subcutaneous immunoglobulin.

INTRODUCTION: Variations in muscle strength and function have not been studied in patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy whose treatment regimen has been changed from intravenous to subcutaneous immunoglobulin (IVIg to SCIg). METHODS: In a prospective, open-label study, patients were changed from monthly IVIg to weekly SCIg. The primary endpoint was variation in isokinetic muscle strength (cIKS). Secondary endpoints were variations in Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), and 40-meter-walk test (40-MWT). RESULTS: The coefficient of variance of cIKS during the IVIg and SCIg treatment periods was unchanged (mean ± SD: 6.97 ± 4.83% vs. 5.50 ± 3.13%, P = 0.21). The variations in the 9-HPT and 40-MWT were significantly lower in the SCIg group (P = 0.01 and P = 0.005, respectively). DISCUSSION: When therapy was changed from IVIg to SCIg, fluctuation of muscle strength was unchanged, but performance fluctuations were diminished. Muscle Nerve 57: 610-614, 2018.

Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We investigated the effects of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Eighteen CIDP patients treated with subcutaneous immunoglobulin performed 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run-in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO2 -max) and maximal combined isokinetic muscle strength (cIKS) of knee and elbow flexion/extension. RESULTS: VO2 -max and muscle strength were unchanged during run-in (-4.9% ± 10.3%, P = 0.80 and -3.7% ± 10.1%, P = 0.17, respectively). Aerobic exercise increased VO2 -max by 11.0% ± 14.7% (P = 0.02). Resistance exercise resulted in an increase of 13.8% ± 16.0% (P = 0.0004) in cIKS. DISCUSSION: Aerobic exercise training and resistance exercise training improve fitness and strength in CIDP patients. Muscle Nerve 57: 70-76, 2018.

The six-spot-step test - a new method for monitoring walking ability in patients with chronic inflammatory polyneuropathy.

The aim of this study was to evaluate whether the six-spot-step test (SSST) is more suitable for monitoring walking ability in patients with chronic inflammatory polyneuropathy than the timed 25-foot-walking test (T25FW). In the SSST, participants have to walk as quickly as possible across a field measuring 1 × 5 m, while kicking blocks out of five circles on the floor. Sixty-two patients and 61 controls performed the SSST and T25FW. Patients also performed the overall disability sumscore, INCAT sensory sumscore, Medical Research Council sumscore, and 9-hole-peg-test. Twenty-one patients treated with intravenous immunoglobulin (IVIG) every 4-6 weeks were tested prior to and 2-3 weeks after treatment and judged change in their own clinical condition using the patient global impression of change (PGIC) scale. In patients, SSST ranged from 5.7 to 26.8 s and T25FW ranged from 3.6 to 12.9 s. Intra-class correlation between repeated tests was 0.97 for SSST and 0.95 for T25FW. Correlation with the additional tests was stronger for SSST than T25FW. In IVIG-treated patients, the mean change in walking time was -2.3 s for SSST and -0.6 s for T25FW. The SSST showed larger responsiveness in terms of effect size, standardized response means, and relative efficiency. Both ambulation tests correlated moderately to PGIC. The SSST may be superior to the T25FW in terms of dynamic range, floor effect, and responsiveness which makes the SSST a possible alternative for monitoring walking ability in patients with chronic inflammatory polyneuropathy.

Diffusion tensor imaging can be used to detect lesions in peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy treated with subcutaneous immunoglobulin.

INTRODUCTION: Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) has shown that fractional anisotropy (FA) is lower in peripheral nerves in chronic inflammatory demyelinating polyneuropathy (CIDP). We examined whether DTI correlates to muscle strength or impairment. METHODS: MRI of sciatic and tibial nerves was performed on 3-T MR scanner by obtaining T2- and DTI-weighted sequences with fat saturation. On each slice of T2-weighted (T2w) and DTI, the tibial and sciatic nerves were segmented and served for calculation of signal intensity. On DTI images, pixel-by-pixel calculation of FA and apparent diffusion coefficient (ADC) was done. Muscle strength at knee and ankle was determined by isokinetic dynamometry and severity of CIDP by neuropathy impairment score (NIS). RESULTS: Fourteen CIDP patients treated with subcutaneous immunoglobulin were compared to gender- and age-matched controls. T2w values expressed as a nerve/muscle ratio (nT2w) were unchanged in CIDP versus controls 0.93 ± 0.21 versus 1.02 ± 0.21 (P = 0.10). FA values were lower in CIDP compared to controls 0.38 ± 0.07 versus 0.45 ± 0.05 (P < 0.0001), and ADC values were higher in CIDP versus controls 1735 ± 232 versus 1593 ± 116 × 10(-6) mm(2)/s (P = 0.005). In CIDP, FA values correlated to clinical impairment (NIS) (r = -0.57, P = 0.03), but not to muscle strength. FA value in the sciatic nerve distinguishes CIDP from controls with a sensitivity and a specificity of 92.9 %. CONCLUSION: CIDP patients have unchanged nT2w values, lower FA values, and higher ADC values of sciatic and tibial nerves compared to controls. FA values correlated to NIS but were unrelated to muscle strength. DTI of sciatic nerves seems promising to differentiate CIDP from controls.

Subcutaneous immunoglobulin treatment in CIDP and MMN. Efficacy, treatment satisfaction and costs.

Subcutaneous administration of immunoglobulin (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) has been reported in several case reports and in a few randomized trials during the last decade. In this review we present the studies on SCIG in CIDP and MMN with special focus on the clinical effects. Moreover, the effect on quality of life, side effects to SCIG and the health economic perspectives are reviewed. Nine case studies, three randomized trials and six long-term, follow-up studies were identified. Most of the studies are conducted in patients switched from regular IVIG to SCIG treatment; one study involves treatment-naïve patients. The review shows that none of the studies have been powered to demonstrate an effect on disability. SCIG can maintain muscle strength for a period of 1 to 2years and ability seems preserved for a similar period. Quality of life is generally unchanged or improved after switch to SCIG and generalized side-effects seem fewer, whereas local reactions at the injection site occur. Health economic analyses favour SCIG at the doses used in the reviewed studies.

Headache and Nausea after Treatment with High-Dose Subcutaneous versus Intravenous Immunoglobulin.

Treatment with intravenous immunoglobulin (IVIG) leads to transient side effects such as headache and nausea during and after the infusion. We hypothesized that subcutaneous administration of smaller doses of immunoglobulin (SCIG) given more frequently leads to less severe headache and nausea and could be an alternative in patients experiencing side effects. Fifty-nine patients diagnosed with neurological disorders (chronic inflammatory demyelinating polyneuropathy (CIDP), multi-focal motor neuropathy (MMN) or post-polio syndrome) were treated with IVIG, and 27 CIDP or MMN patients with SCIG. For two consecutive weeks daily, registration of the severity of headache and nausea was registered on a visual analogue scale (VAS) from 0 to 100 mm. In the SCIG group, headache reached a peak value of 1 (0-13) mm at day 6 versus 11 (0-96) mm in the IVIG group at day 4 (p < 0.0001). For nausea, the SCIG group had a stable value of 0 (0-21) mm at all days, whereas a peak value of 3 (0-90) mm was reached at day 4 in the IVIG group (p < 0.0001). SCIG leads to less severe headache and nausea than IVIG without fluctuations of side effects in relation to the injections.

Pressure load: the main factor for altered gene expression in right ventricular hypertrophy in chronic hypoxic rats.

BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure.