Myopathic changes in patients with long-term fatigue after COVID-19.

OBJECTIVE: To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). METHODS: Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. RESULTS: qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. CONCLUSIONS: Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. SIGNIFICANCE: Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.

Specialized Outpatient Clinic vs Stroke Unit for TIA and Minor Stroke: A Cohort Study.

Objective: To evaluate the effects of an outpatient clinic set-up for minor stroke/TIA using subsequent admission of patients at 'high risk' of re-stroke.Methods: A cohort study of all patients with suspected minor stroke/TIA seen in an outpatient clinic at Aarhus University Hospital, Denmark, between September 2013 and August 2014. Stroke patients were compared to historic (same hospital) and contemporary (another comparable hospital) matched, hospitalized controls on the non-prioritized outcomes: Length-of-stay, re-admissions, care quality (10 process-performance measures) and mortality. TIA patients were compared to contemporary matched, hospitalized controls.Following complete diagnostic work-up, patients with stroke/TIA were classified into 'low'/high risk' of re-stroke ≤7 days. RESULTS: We analyzed 1,076 consecutive patients of whom 253 (23.5%) were subsequently admitted to the stroke ward. Stroke/TIA was diagnosed in 215/171 patients, respectively. Fifty-six percent (121/215) of the stroke patients were subsequently admitted to the stroke ward. Comparison with the historic stroke cohort (n=191) showed a shorter acute hospital stay for the strokes (median 1 vs 3 days); adjusted length-of-stay ratio 0.49 (95% CI 0.33-0.71). Furthermore, 30-day readmission rate was 3.2% vs 11.6%; adjusted hazard ratio 0.23 (0.09-0.59); and care quality was higher with a risk ratio of 1.30 (1.15-1.47). The comparison of stroke and TIAs to contemporary controls showed similar results. Only one patient in the 'low risk' category and not admitted experienced stroke within 7 days (0.6%). CONCLUSIONS: An outpatient clinic set-up for patients with minor stroke/TIA yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a neurovascular specialist driven outpatient clinic for minor stroke/TIA patients with the ability of subsequent admission is safe and yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units.

Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year in an open-label follow-up study. METHODS: Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT) and nine-hole peg test (9-HPT). Secondary end-points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS). RESULTS: The dose of SCIG was significantly unaltered during the follow-up period. Overall the isokinetic dynamometry value increased by 7.2% (P = 0.033) and after 3, 6 and 12 months by 5.7%, 8.2% and 6.8% (ns). The overall composite score at all time intervals and for each interval remained unchanged. Amongst the secondary parameters the MRC score increased significantly by 1.7% (P = 0.007), whereas grip strength, 40-MWT, 9-HPT and ODSS remained unchanged. CONCLUSION: SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long-term treatment of CIDP patients.

Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders.

BACKGROUND AND PURPOSE: High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship to the AB0 blood type system. METHODS: In a prospective study 34 de novo treated patients were given 2.0 g/kg bodyweight of Privigen and 50 patients received either Privigen [n = 28; 1.53 ± 0.4 g/kg (mean ± SD)] or Kiovig (n = 22; 1.7 ± 0.4 g/kg) as maintenance therapy. The de novo patients all had a post-polio syndrome, whereas the remaining patients received maintenance therapy for the neuromuscular disorders chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy. Blood sampling was performed before and 2 weeks after infusion of IVIG. RESULTS: Following IVIG treatment blood hemoglobin declined from 8.6 ± 0.9 to 8.0 ± 1.2 mM, P < 0.001. Reticulocyte counts and levels of bilirubin and lactate dehydrogenase were increased and haptoglobin levels decreased. The decline of hemoglobin was 0.9 ± 1.2 mM after de novo therapy versus 0.4 ± 0.8 mM after maintenance therapy with Privigen (P = 0.05) and 0.2 ± 0.3 mM after maintenance therapy with Kiovig (P = 0.47). In de novo patients compared with patients on maintenance therapy reticulocyte count and lactate dehydrogenase level increased whereas haptoglobin level decreased. Anemia correlated with the AB0 blood type system with a significant difference between type 0 (n = 17; +0.3 ± 0.4 mM) and type A, B and AB (n = 48; -1.0 ± 1.0 mM), anemia being most pronounced in type AB. CONCLUSION: Moderate hemolytic anemia is a concomitant complication of high dose IVIG in subjects with blood types A, B and AB.

Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18-80 years, were randomized either to SCIG at a dose corresponding to their pre-study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial as well as 2 weeks before (-2, 0, 10, 12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was measured. Also, an Overall Disability Sum Score (ODSS), 40-m-walking test (40-MWT), nine-hole-peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. RESULTS: SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group there was an increase of isokinetic muscle strength of 5.5 ± 9.5% (P < 0.05) as compared with a decline of 14.4 ± 20.3% (P < 0.05) in the placebo group; the difference between the two groups being significant (P < 0.01). ODSS, NIS, MRC, grip strength and 40-MWT improved following SCIG versus saline. CONCLUSIONS: SCIG treatment in CIDP is feasible, safe and effective, and seems an attractive alternative to IVIG.

The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: High-dose intravenous immunoglobulin (IVIg) is an established treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although Fc receptors on natural killer cells have been suggested as a target for IVIg, the pharmacological effects are not yet clarified. We hypothesize that IVIg therapy, dependent on the plasma IgG level, suppresses the cytotoxic capacity by a reduction in numbers of NK cells and their Fc receptor CD16. PATIENTS AND METHODS: Ten consecutive patients with CIDP in maintenance therapy with IVIg were studied before and immediately after the infusion of 0.7-2.0 g/kg IVIg. Peripheral blood mononuclear cell samples from these patients were analyzed immediately after isolation using flow cytometry and cytotoxicity assays. RESULTS: We found that following IVIg treatment, the cytotoxic activity of NK cells in CIDP patients was suppressed, partly caused by a dose-dependent decline in the number of circulating NK cells. In addition, a dose-dependent blockage of CD16 occurred. CONCLUSIONS: The study implies that IVIg infusion induces a substantial decline in the number of peripheral NK cells and a suppression of NK-cell-mediated cytotoxicity. We propose that these impairments of the NK cells contribute to the therapeutic effect of IVIg in CIDP.

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.