Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune‐mediated neuropathies

High‐dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25–60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg.     

Subcutaneous versus intravenous immunoglobulin for chronic autoimmune neuropathies: A meta‐analysis

Introduction: High‐dose intravenous immunoglobulin (IVIg) is an evidence‐based treatment for multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). Recently, subcutaneous immunoglobulin (SC‐Ig) has received increasing attention. Methods: We performed a meta‐analysis of reports of efficacy and safety of SC‐Ig versus IVIg for inflammatory demyelinating polyneuropathies. Results: A total of 8 studies comprising 138 patients (50 with MMN and 88 with chronic CIDP) were included in the meta‐analysis. There were no significant differences in muscle strength outcomes in MMN and CIDP with Sc‐Ig (MMN: effect size [ES] = 0.65, 95% confidence interval [CI] = ‐0.31‐1.61; CIDP: ES = 0.84, 95% CI = ‐0.01‐1.69). Additionally SC‐Ig had a 28% reduction in relative risk (RR) of moderate and/or systemic adverse effects (95% CI = 0.11‐0.76). Conclusions: The efficacy of SC‐Ig is similar to IVIg for CIDP and MMN and has a significant safety profile. Muscle Nerve 55 : 802–809, 2017     

Treatment of immune neuropathies

PURPOSE OF THE REVIEW: Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating poly(radiculo)neuropathy (CIDP) and multifocal motor neuropathy (MMN) are potentially treatable disorders. The use of appropriate assessment scales to evaluate the effects of treatment is essential. Recent therapeutic trials and the question of whether patients with mild disease or other variants of these disorders need to be treated are discussed. RECENT FINDINGS: Recent clinical trials and Cochrane reviews give new information on the effect of various treatments in patients with GBS, CIDP and MMN. Intravenous immunoglobulin remains the only treatment proven to be effective in MMN. Combinations of treatment may be even more effective in GBS. Studies on prognostic factors related to improvement have been reported. Whether patients with Miller-Fisher syndrome or those with mild GBS should also be treated is still debated. New assessment scales at the disability and handicap level have now been evaluated for GBS and CIDP, and are ready for use. Results of studies in experimental models contribute to our understanding of the mechanism of action of intravenous immunoglobulin. SUMMARY: Recent new information on the use of intravenous immunoglobulin and steroids indicates that the former should remain the cornerstone of treatment for GBS and MMN, and probably also for CIDP. Whether steroids not only suppress disease activity in CIDP but also eradicate the disease remains to be established. Some GBS patients have secondary deterioration or finally turn out to have CIDP; additional information in this group of patients may lead to more appropriate disease management. Most patients with CIDP and those with MMN need long-term treatment. New treatment strategies should now focus also on the effect and the costs of treatment over long-term follow up.     

Quality of life predictors in patients with chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic disease which can lead to many functional impairments, and like most other chronic disorders it might significantly affect quality of life (QoL). Information about QoL in patients with CIDP from developing countries is still lacking. We, therefore, sought to complete these data mosaic by investigating QoL in patients with CIDP from Serbia and surrounding countries. Our study comprised 106 patients diagnosed with CIDP. QoL was investigated using the Serbian version of the SF-36 questionnaire. The Medical Research Council 0–5 point scale, INCAT motor and sensory scores, Krupp’s Fatigue Severity Scale, and Beck Depression Inventory were also used. Factors that significantly correlated with SF-36 total score in univariate analysis were included in the multiple linear regression analysis. Physical domains of the SF-36 were more affected than mental, and the overall score was 56.6 ± 25.4. Significant predictors of worse SF-36 score in our patients with CIDP were severe fatigue (β = ? 0.331, p < 0.01), higher INCAT motor score (β = ? 0.301, p < 0.01), depression (β = ? 0.281, p < 0.01), being unemployed/retired (β = ? 0.188, p < 0.05), and shorter duration of CIDP (β = + 0.133, p < 0.01). QoL was reduced in CIDP patients, especially in physical domains. Patients with presence of fatigue and depression, with more severe motor disability, unemployed/retired ones, and those with shorter duration of the disease need special attention of clinicians since they could be at higher risk to have worse QoL.     

Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy

Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS‐weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response‐based immunotherapy (R‐IRx) of CIDP. Using efficacious R‐IRx, a large early and late therapeutic response (≥ one‐fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non‐significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons). Muscle Nerve 52: 488–497, 2015     

Motor unit number index (MUNIX) in chronic inflammatory demyelinating polyneuropathy: A potential role in monitoring response to intravenous immunoglobulins

ObjectiveTo compare motor unit number index (MUNIX) values in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and healthy controls, to assess correlations between MUNIX and clinical assessments used in CIDP and to assess short-term changes in MUNIX in CIDP following intravenous immunoglobulins (IVIg).MethodsMUNIX sum scores were calculated from three muscles in patients and healthy controls. CIDP patients also underwent a series of clinical assessments and completed the Overall Neuropathy Limitations Scale (ONLS) and the Rasch-built Overall-Disability Scale (R-ODS). Repeat assessments were performed in CIDP patients receiving IVIg and CIDP patients not on active treatment.ResultsMUNIX sum scores were significantly lower in CIDP patients than healthy controls (mean values 214.0 vs 516.9, respectively; p < 0.001). MUNIX sum scores correlated with clinical assessment of motor and sensory function and ONLS and R-ODS scores in CIDP patients. Significant short-term improvements were seen in MUNIX values on repeat testing following IVIg (188.3–226.4, p = 0.001), but not in CIDP patients not receiving IVIg.ConclusionsMUNIX values show stronger correlation with commonly-used clinical assessments and disability scores than other routinely used electrophysiological parameters. Rapid improvements in MUNIX sum scores are seen following IVIg.SignificanceMUNIX sum score may provide an objective marker of response to IVIg.     

Neuromuscular disease‐specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy

To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease‐specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (β = 0.35, p < 0.01), higher INCAT disability score at time of testing (β = 0.29, p < 0.01), and being unemployed/retired (β = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.     

Chronic inflammatory neuropathies and their impact on activities and participation

Background

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are inflammatory neuropathies that can lead to considerable limitations in daily activities and in social participation. However, systematic evaluation of these self-reported limitations is lacking in the currently available studies. Understanding the impact of these diagnoses on patients' life is important to optimize management strategies.

Aim

To systematically assess the self-reported limitations in activities and participation and determine associated factors.

Methods

A survey study was conducted in 2021 in a cohort of patients with CIDP (n = 257) and MMN (n = 148) from a university hospital. The survey included the Rasch-built Overall Disability Scale and the Utrecht Scale for Evaluation of Rehabilitation-Participation, questions addressing personal and disease-related factors and treatment. Multivariate linear regression analysis was used to determine associations with disease-related and personal factors.

Results

A total of 147 CIDP and 103 MMN patients responded. Limitations in activities were reported by 70.7% CIDP and 52.2% MMN patients with moderate to severe limitations in 22.4% and 5.9% patients, respectively. Participation restrictions were reported by 50% of CIDP and 40% of MMN patients, nevertheless satisfaction with participation was high. Fatigue, pain and resilience were independently associated with limitations in activities and satisfaction with participation in CIDP patients.

Conclusions

Activity limitations and restrictions in participation are common in CIDP patients and to a lesser extent in MMN patients. Fatigue, pain and resilience independently contributed to perceived limitations in CIDP patients. Referral to a rehabilitation physician is warranted to address these limitations appropriately.     

Chronic inflammatory demyelinating polyradiculoneuropathy and anesthesia: a case series

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired autoimmune demyelinating polyneuropathy characterized by symmetrical diffuse weakness that also can rarely affect bulbar and respiratory muscles. The study objective was to describe perioperative outcomes of patients with CIDP who received general anesthesia. This retrospective observational study evaluated patients with active (diagnosed or treated within the previous year) CIDP who underwent general anesthesia at our institution between January 1, 2010, and December 31, 2015. Medical records were reviewed for perioperative outcomes with emphasis on respiratory complications or unexpected reactions to muscle relaxants. Seventeen patients with CIDP underwent general anesthesia, of whom 16 had muscle weakness. Succinylcholine was used in 5 cases (29.4%) and nondepolarizing muscle relaxants in 11 cases (64.7%). Two patients required postoperative mechanical ventilation; one was critically ill and the other had open heart surgery. One patient had aspiration on the second postoperative day and required endotracheal intubation and mechanical ventilation for 3 days. Three patients had worsening CIDP symptoms: 1 acutely after surgery; 1 several months later; and 1 who died in the hospital. The patient who died underwent lengthy abdominal exploration, had acute worsening of neurologic symptoms, and died after 46 days of malnutrition. Anesthetic concerns of patients with CIDP include frailty, bulbar dysfunction, and the effects of immunosuppressive therapy. Although our patients tolerated neuromuscular drugs, substantial theoretical concerns with these medications in patients with demyelinating neuropathies preclude safety in this population without further study.     

Outcome measures in MMN revisited: further improvement needed

The objectives of this study were to provide an overview of the outcome measures (OMs) applied in clinical trials in multifocal motor neuropathy (MMN) and to determine the responsiveness of a core set of selected OMs as part of the peripheral neuropathy outcome measures standardization (PeriNomS) study. The following OMs were serially applied in 26 patients with newly diagnosed or relapsing MMN, receiving intravenous immunoglobulin (assessments: T0/T3/T12 months): 14 muscle pairs MRC (Medical Research Council) scale, the Neuropathy Impairment Scale motor‐subset, a self‐evaluation scale, grip strength, and MMN‐RODS© (Rasch‐built overall disability scale). All data, except the grip strength, were subjected to Rasch analyses before determining responsiveness. For grip strength, responsiveness was examined using a combined anchor‐ (SF‐36 question‐2) and distribution‐based (½ × SD) minimum clinically important difference (MCID) techniques, determining the proportion of patients exceeding both the identified cut‐offs. For the remaining scales, the magnitude of change for each patient on each scale was determined using the MCID related to the individual SE (responder definition: MCID‐SE ≥ 1.96). Overall, a great assortment of measures has been used in MMN trials with different responsiveness definitions. For the selected OMs, responsiveness was poor and only seen in one fourth to one third of the patients, the grip strength being more responsive. Despite the efforts taken to standardize outcome assessment, further clinimetric responsiveness studies are needed in MMN.     

Comparison of monoclonal gammopathy of undetermined significance-associated neuropathy and chronic inflammatory demyelinating polyneuropathy patients

Objectives

There are varying reports on whether monoclonal gammopathy of undetermined significance-associated neuropathy (MGUSN) patients are distinguishable from those with chronic inflammatory demyelinating polyneuropathy (CIDP) and whether specific MGUSN subclasses are associated with specific clinical phenotypes.

Methods

We performed a retrospective chart review of MGUSN (n = 56) and CIDP (n = 67) patients. Data extracted included: demographics, neurological examination, and nerve conduction studies (NCS) at baseline and last visit. Clinical status was rated as 0 = worse, 1 = unchanged, 2 = stabilized after a declining course, or 3 = improved. The electrophysiology data were rated as 0 = worse, 1 = stable, or 2 = improved. Statistical analyses were performed using JMP (version 9.0.2 for Macintosh, from SAS).

Results

Seventy percent were males, aged 68.1 ± 12.6 years with neuropathy for 9.8 ± 6.8 years and follow-up of 4.0 ± 3.2 years. CIDP patients had more severe neuropathy, and were more likely to receive treatment and to respond. The clinical neuropathy status remained unchanged in 52.8 % of the MGUSN and 24.2 % of the CIDP patients, and stabilized in 7.6 % of MGUSN and 30.3 % of CIDP patients. IgM-MGUSN patients did not differ from other immunoglobulin subclasses in response to treatment. The clinical severity and the number of abnormal NCS parameters were greater in the demyelinating MGUSN in comparison to the axonal group.

Conclusion

MGUSN patients have less severe neuropathy than CIDP patients, but among the MGUSN patients the severity is greater in the demyelinating and the IgM groups. MGUSN patients may do well without treatment and exposure to potential adverse effects.     

Treatment of chronic inflammatory demyelinating polyneuropathy

The management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the main topic of this review. A few comments will also be made about treatment of the demyelinating form of paraproteinaemic demyelinating polyneuropathy (PDN) and of multifocal motor neuropathy (MMN). The review briefly describes the main characteristics of these neuropathies, and examines case series and trials which evaluated the principal therapeutic strategies for CIDP, PDN and MMN, such as intravenous immunoglobulin (IVIg) therapy, steroid treatment, plasma exchange and immunosuppressor administration. Controlled trials demonstrated that IVIg, steroid treatment and plasma exchange are effective in CIDP. For PDN the therapeutic strategies are the same as for idiopathic CIDP, but usually the clinical response is poorer. For MMN, IVIg therapy is definitely the first choice treatment.

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Sommario Lo scopo principale di questa review è di esaminare le strategie terapeutiche nella neuropatia infiammatoria cronica demielineizzante (CIDP). Alcuni commenti vengono fatti anche riguardo il trattamento della forma demielinizzante della neuropatia demielinizzante paraproteinemica (PDN) e della neuropatia motoria multifocale (MMN). La review delinea le principali caratteristiche cliniche delle diverse forme di neuropatia demielinizzante ed esamina i principali studi clinici, controllati e non controllati, che hanno valutato il trattamento deila CIDP e della PDN e MMN con immunoglobuline endovena (IVIg), con la terapia steroidea, la plasmaferesi e farmaci immunosoppressori. Studi controllati hanno dimostrato che le IVIg, to steroide e la plasmaferesi sono efficaci nella CIDP. Per quanto riguarda la PDN le strategic terapeutiche sono analoghe a quelle adottate nella CIDP anche se la risposta clinica è solitamente meno evidente. Infine, nella MMN le IVIg sono sicuramente il trattamento di prima scelta.

     

Concurrence of Multifocal Motor Neuropathy and Hashimoto's Thyroiditis

Background

Multifocal motor neuropathy (MMN) is an immune-mediated disorder that is characterized by slowly progressive and asymmetrical weakness, but its pathophysiological mechanism is uncertain. The hypothesis that MMN is an immunological disease has been supported by the proven therapeutic effects of intravenous immunoglobulin and the detection of antiganglioside antibodies in MMN patients. The coexistence of MMN with other immune diseases has been rarely reported.

Case Report

A 37-year-old woman visited our hospital complaining of weakness in both hands. The clinical manifestations coincided well with MMN: predominantly distal upper-limb weakness, asymmetric involvement, a progressive course, absence of sensory symptoms, absence of pyramidal signs, and sparing of the cranial muscles. The electrophysiological findings also supported a diagnosis of MMN, with motor nerve conduction block in the median, ulnar, and radial nerves, without sensory nerve involvement. The patient was simultaneously diagnosed as having Hashimoto''s thyroiditis, which is a well-known immune-mediated disease.

Conclusions

The concurrence of MMN and Hashimoto''s thyroiditis in our patient is significant for understanding the immunological characteristics of the two diseases.     

Ultrasound of inherited vs. acquired demyelinating polyneuropathies

We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited [Charcot–Marie–Tooth-1 (CMT-1) (n = 35)] and acquired [chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 55), Guillaine–Barre syndrome (GBS) (n = 21) and multifocal motor neuropathy (MMN) (n = 17)] demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none, no enlargement; mild, nerves enlarged but never more than twice normal; regional, nerves normal in at least one region and enlarged more than twice normal in at least one region; diffuse, nerves enlarged at all four regions with at least one region more than twice normal size. Nerve enlargement was commonly diffuse (89 %) and generally more than twice normal size in CMT-1, but not (p < 0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement [CIDP (64 %), GBS (95 %), and MMN (100 %)]. In CIDP, subjects treated within 3 months of disease onset had less nerve enlargement than those treated later. Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement.     

Systematic reviews of treatment for chronic inflammatory demyelinating neuropathy

Chronic inflammatory demyelinating polyradiculoneuropathies include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraprotein-associated demyelinating neuropathy. This review summarises the evidence from randomised controlled trials (RCTs) for the treatment of these conditions. It leads to the conclusions that: 1) steroids are beneficial in CIDP but not MMN and their efficacy in paraproteinaemic demyelinating neuropathy (PDN) is uncertain; 2) intravenous immunoglobulin (IVIg) produces short-term benefit in CIDP, MMN and IgM PDN. Its effect in IgG or IgA PDN has not been tested in RCTs; 3) plasma exchange (PE) also produces short-term benefit in CIDP and IgG or IgA PDN but probably not in MMN; 4) there is almost no information from RCTs concerning the possible benefits of immunosuppressive agents; and 5) volunteers are needed to write Cochrane systematic reviews of IVIg for MMN and of interventions for PDN associated with IgG and IgA.     

The effect of telestroke systems among neighboring hospitals: more and better? The Madrid Telestroke Project

A telestroke system was established between a community hospital lacking an on-call neurologist and a comprehensive stroke center only 13 km away. Our goal was to analyze the impact of telestroke on the number of intravenous thrombolysis (IVT), door-to-needle times and stroke outcomes. An observational before-and-after study of patients with acute ischemic stroke (IS) who were attended in a community hospital during the 2 years before the telestroke system was implemented (pre-telestroke group) and the first 2 years after telestroke was established (telestroke group). The number of IVT, the door-to-needle time (min), the outcomes [modified Rankin Scale (mRS)] and the safety (mortality and hemorrhagic transformations) were compared between groups. During the pre-telestroke years, 259 patients with IS were attended (28 phone activations), 12 of whom received IVT (4.7 %). During the telestroke years, 225 patients with IS were attended (42 telestroke activations), of whom 18 (8 %) received IVT. The door-to-needle times were lower in the telestroke group [median interquartile range: 66 (54) vs. 143.5 (48) min, P < 0.0001]. The safety was similar in both groups; however, the 3-month mRS scores were lower in the telestroke group (P = 0.049). The multiple linear regression analysis showed a negative association between telestroke and door-to-needle time [β-coefficient (SE) = ?59.089 (14.461)], adjusted for confounders. In conclusion, telestroke systems are effective, even between nearby hospitals, shortening door-to-needle time and improving stroke outcomes.     

Current treatments of chronic immune‐mediated demyelinating polyneuropathies

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti–myelin‐associated glycoprotein (anti‐MAG) neuropathy are three demyelinating acquired neuropathies, with distinct responses to immunotherapy. In placebo‐controlled, double‐blind, randomized trials, intravenous immunoglobulin (IVIg) has been effective for CIDP and MMN, and plasmapheresis has been effective for CIDP. Corticosteroids have been beneficial in controlled trials for CIDP. Other agents, including cyclophosphamide, rituximab, azathioprine, cyclosporine, interferons, fludarabine, mycophenolate mofetil, and etanercept, have been reported to benefit some patients with inflammatory demyelinating neuropathies in case series and case reports. This review examines the use and toxicity associated with these immunotherapy medications in treating patients with chronic immune‐mediated demyelinating neuropathies. Muscle Nerve, 2009     

Clinical trials in CIDP and chronic autoimmune demyelinating polyneuropathies

The main chronic autoimmune neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy. On the basis of randomized controlled studies, corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis provide short-term benefits in CIDP. MMN responds only to IVIg. Because in MMN and CIDP, IVIg infusions are required every 3-6 weeks to sustain benefits or long-term remissions, there is a need for "IVIg-sparing" agents. In CIDP, immunosuppressive drugs, such as azathioprine, cyclosporine, methotrexate, mycophenolate, and cyclophosphamide, are used, but controlled trials have not shown that they are effective. Controlled trials have also not shown benefit to any agents in anti-MAG neuropathy. However, clinicians use many immunosuppressive drugs in both settings, but all have potentially serious side effects and are only effective in some patients. Thus, there is a need for new therapies in the inflammatory and paraproteinemic neuropathies. New agents targeting T cells, B cells, and transmigration and transduction molecules are discussed as potential treatment options for new trials. The need for biomarkers that predict therapeutic responses or identify patients with active disease is emphasized, and the search for better scoring tools that capture meaningful changes after response to therapies is highlighted.     

Long-term therapy with high-dose intravenous immunoglobulins (IVIG) in inflammatory neuropathies

Clinical data about the course of long-term IVIG treatment in chronic inflammatory demyelinating polyneuropathy (CIDP) and in multifocal motor neuropathy (MMN) are sparse. Twenty patients with CIDP or MMN were investigated during up to 65 months of high-dose intravenous immunoglobulin (IVIG) therapy in an open and prospective study. In all therapy-responders (18/20), amelioration of symptoms was evident within the first 3 weeks of treatment. Dosage was reduced slowly according to the clinical symptoms. All 18 patients now show very few or no symptoms. The mean value of the Rankin disability scale changed from 2.5 to 1.1 during therapy. Ten patients are still regularly given IVIG. In eight patients no further therapy has been necessary for 7–63 months. Treatment could even be stopped in one patient after 46 months of therapy. No marked clinical side-effects were observed during 529 months of IVIG therapy. IVIG therapy is safe, and remains effective in the long-term treatment of CIDP and MMN.     

A new treatment regimen with high-dose and fractioned immunoglobulin in a special subgroup of severe and dependent CIDP patients

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is treated with intravenous immunoglobulins (IVIg), corticosteroids or plasma exchange (PE). IVIg dosage is not universal and markers for treatment management are needed. Methods: We report the response to high-dose and fractioned IVIg in a subgroup of definite CIDP patients, resistant to corticosteroids and PE, responders to IVIg but with an efficacy window <15 d. Results: Four patients were included with similar predominantly clinical motor form and conduction abnormalities. Treatment management consisted of fractioning IVIg and increasing the monthly cumulated dose (mean: 3 g/kg/month). Serum IgG concentration was measured and correlated to the clinical state. Monitoring of serum IgG helped to guide IVIg administration dosage and frequency. A mean of 10 months was required to improve symptoms; therapy was then switched to subcutaneous (SC) route (maintenance dose: 3.5 g/kg/month). The mean Overall Neuropathy Limitations Scale was improved from 11 to 3.2 and the mean Medical Research Council scale from 26 to 90. Conclusion: It is important to distinguish patients with short IVIg efficacy window from those with classical resistance since the former may benefit from fractioning and increasing the IVIg dose. The monitoring of serum IgG level and its correlation to the clinical response could be of help in monitoring each individual's dosage.