IqYmune® is an effective maintenance treatment for multifocal motor neuropathy: A randomised, double-blind, multi-center cross-over non-inferiority study vs Kiovig®-The LIME Study.

Intravenous immunoglobulin (IVIg) is the gold-standard for maintenance treatment of multifocal motor neuropathy (MMN). This phase III, randomised, double-blind, multi-centre, active-control, crossover study, aimed to evaluate the non-inferiority of IqYmune® relative to Kiovig®, primarily based on efficacy criteria. Twenty-two adult MMN patients, treated with any brand of IVIg (except Kiovig® or IqYmune®) at a stable maintenance dose within the range of 1 to 2 g/kg every 4 to 8 weeks, were randomised to receive either Kiovig® followed by IqYmune®, or IqYmune® followed by Kiovig®. Each product was administered for 24 weeks. The primary endpoint was the difference between IqYmune® and Kiovig® in mean assessments of modified Medical Research Council (MMRC) 10 sum score (strength of 5 upper-limb and 5 lower-limb muscle groups, on both sides, giving a score from 0 to 100) during the evaluation period (non-inferiority margin of Δ = 2). A linear mixed model analysis demonstrated the non-inferiority of IqYmune® relative to Kiovig®, independently of the covariates (value at baseline, treatment period, and treatment sequence). The estimated "IqYmune® - Kiovig®" difference was -0.01, with a 95% confidence interval (CI) -0.51 to 0.48. The number of adverse reactions (ARs) and the percentage of patients affected were similar for the two products: 39 ARs in 10 patients with IqYmune® vs 32 ARs in 11 patients with Kiovig®. No thromboembolic events nor haemolysis nor renal impairment were observed. In this first clinical trial comparing two IVIg brands for maintenance treatment of MMN, efficacy and tolerability of both brands were similar.

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies.

Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open-label, single-arm study of IVIG in immunoglobulin (Ig)-naïve or IVIG pre-treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double-blind, randomized study including an open-label, single-arm IVIG phase in IVIG pre-treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7% in all PRIMA subjects at Week 25 (76.9% in IVIG pre-treated subjects) and 72.9% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was -1.0 (interquartile range -2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA-approved IVIG for CIDP, in a population of mainly pre-treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].

Multifocal motor neuropathy.

PURPOSE OF REVIEW: Multifocal motor neuropathy (MMN) has specific clinical and electrophysiologic features but can be difficult to diagnose if cases are not typical. Intravenous immunoglobulin (IVIg) remains the core initial and long-term treatment. In this review, recent advances in the diagnosis, monitoring and treatment of MMN are discussed. RECENT FINDINGS: The pathology of MMN likely depends on immune-mediated attack of the nodes of Ranvier and paranodal regions leading to conduction block. Antiganglioside antibodies are present in over 50% of patients. The sensitivity of antibody detection can be improved by testing for GM1/galactocerebroside (GM1/GalC) complexes. Complement activation plays a key role in the pathophysiology of MMN. Subcutaneous immunoglobulins are an efficacious alternative to IVIg for maintenance therapy in MMN. Complement inhibitor eculizumab may be a potential future treatment, but further studies are necessary. SUMMARY: The European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) guidelines for the diagnosis of MMN are currently widely used but probably need revision. Nerve ultrasound and plexus/nerve MRI can be helpful in diagnostic dilemmas. Monitoring of disease and response to treatment may improve using disease-specific evaluation scales such as MMN-Rasch-built overall disability scale. Further research into the pathophysiology of MMN is necessary to direct future treatment strategies.

Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features.

OBJECTIVE: To assess the clinicopathological and therapeutic features of patients with low (≥1000 to <10 000 Bühlmann Titre Units) (BTU), medium (10 000-70 000) or high (≥70 000) anti-myelin-associated glycoprotein (anti-MAG) antibody titres. METHODS: We retrospectively and prospectively analysed standardised report forms and medical records of 202 patients from 14 neuromuscular centres. RESULTS: Mean age at onset and mean time between symptom onset to last follow-up were respectively 62.6 years (25-91.4) and 8.4 years (0.3-33.3). Anti-MAG antibody titres at diagnosis were low, medium or high in 11%, 51% and 38% of patients. Patients presented with monoclonal gammopathy of undetermined significance in 68% of cases. About 17% of patients presented with 'atypical' clinical phenotype independently of anti-MAG titres, including acute or chronic sensorimotor polyradiculoneuropathies (12.4%), and asymmetric or multifocal neuropathy (3%). At the most severe disease stage, 22.4% of patients were significantly disabled. Seventy-eight per cent of patients received immunotherapies. Transient clinical worsening was observed in 12% of patients treated with rituximab (11/92). Stabilisation after rituximab treatment during the 7-12-month follow-up period was observed in 29% of patients. Clinical response to rituximab during the 6-month and/or 7-12-month follow-up period was observed in 31.5% of patients and correlated with anti-MAG titre ≥10 000 BTU. CONCLUSION: Our study highlights the extended clinical spectrum of patients with anti-MAG neuropathy, which appears unrelated to antibody titre. Besides, it may also suggest beneficial use of rituximab in the early phase of anti-MAG neuropathy.

N-hexane exposure: a cause of small fiber neuropathy.

A 59-year-old woman presented with progressive paresthesias of all of her limbs for 4 years, associated with neuropathic pain, tingling in the tongue and allodynia, consistent with small fiber neuropathy (SFN). Several systemic symptoms and signs were found on clinical examination and laboratory work-up. Neurological investigations including neurophysiologic test and skin biopsy supported the diagnosis of SFN. Chronic exposure to N-hexane was then disclosed and suspected to be the cause of the disease. Following the discontinuation of chronic N-hexane exposure, the patient had a progressive improvement of all signs and symptoms, reinforcing the correlation between exposure to N-hexane, and development of SFN. Exposure to N-hexane may be considered as a novel reversible cause of SFN, which underlines the need to look for toxic etiologies in the diagnosis of SFN.

Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN.

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.

Long-term efficacy of rituximab in IgM anti-myelin-associated glycoprotein neuropathy: RIMAG follow-up study.

The Rituximab vs. Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy (RIMAG) study showed no improvement using the inflammatory neuropathy cause and treatment sensory score (ISS) as primary outcome in patients with IgM anti-myelin-associated glycoprotein neuropathy (IgM anti-MAG neuropathy) treated with rituximab, when compared with placebo. However, some secondary outcomes seemed to improve in the per protocol analysis. Patients from one participating center in the RIMAG study underwent a new evaluation after a median follow-up of 6 (interquartile range (IQR) 4.9; 6.5) years, using the same outcome measures used in the original study. Data were recorded in seven rituximab patients (group 1) and in eight placebo patients (group 2). In group 2, six of eight patients received immunotherapy during follow-up, while only two of seven did in group 1. No significant change was observed in either the ISS or the secondary outcomes in both groups, with the exception of worsening in the 10-m walk time in group 2 (p = 0.016). The RIMAG follow-up study failed to find any significant change in most outcome measures in patients from the RIMAG study, some of them having received new immunotherapies. This study stresses the lack of useful clinical scales sensitive enough to capture small, even meaningful, improvement in IgM anti-MAG neuropathy.

Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature.

In patients with infectious cryoglobulinemia vasculitis (CryoVas) in the absence of hepatitis C virus infection, data on presentation, therapeutic management and outcome are lacking. We conducted a nationwide survey that included patients with HCV-negative CryoVas. We describe here the presentation, therapeutic management and outcome of 18 patients with non-HCV infectious CryoVas and 27 additional patients identified form a systematic review of the literature. We included 18 patients, mean age 57.9±13.5 years. Infectious causes were viral infections in 8 patients [hepatitis B virus (HBV) in 4, and cytomegalovirus, Epstein Barr virus, parvovirus B19 and human immunodeficiency virus in one case each], pyogenic bacterial infection in 6 patients, parasitic infection in 2 patients, and leprosy and candidiasis in one case each. Baseline manifestations were purpura (78%), glomerulonephritis (28%), arthralgia (28%), peripheral neuropathy (22%), skin necrosis (22%), cutaneous ulcers (17%), and myalgia (11%). Cryoglobulinemia was type II in 2/3 of cases. Most cases received specific anti-infectious therapy as first-line therapy, sometimes associated with corticosteroids, achieving sustained remission in the majority of cases. Refractory or relapsing patients, frequently related to HBV infection, showed a complete remission after rituximab in addition to antiviral therapy. In contrast, corticosteroids and/or immunosuppressive agents used in the absence of anti-infectious agents were frequently associated with refractory CryoVas. Viral and pyogenic bacterial infections represent the main causes of non-HCV infectious CryoVas. Antimicrobial therapy is commonly associated with sustained remission. Immunosuppressive agents should be considered only as a second-line option in patients with refractory vasculitis.

Long-term outcome of infliximab in severe chronic and refractory systemic sarcoidosis: a report of 16 cases.

OBJECTIVES: Infliximab (IFX) appears to be effective in refractory sarcoidosis. However, data are lacking regarding its efficacy in severe sarcoidosis (i.e. with cardiac and/or neurological involvement). METHODS: Retrospective single-centre study including 16 unselected consecutive patients with biopsy proven, severe, and resistant sarcoidosis, who were treated by infliximab (3 or 5 mg /kg at 0, 2 and 6 weeks, then every 8 weeks) between 2005 and 2013. RESULTS: Following IFX therapy we observed an improvement in 92% of cases, with a marked decrease of the severity score [median score 6 (3-12) vs. 2 (1-8), p<0.0001] and trend toward steroid sparing effect [12.5 (0-40) vs. 8.5 mg/d (0-30), p=0.11] between baseline and the end of follow-up, respectively. Regarding the index organ response, we observed a remission of cardiac and central nervous system involvements in 4 out of 4 and 11 out 12 cases, respectively. Thirty-eight percent of patients experienced a relapse. After a median follow-up of 57 months (2 to 91), we observed 7 (44%) infectious complications, 1 paradoxical cutaneous granuloma and 1 leucoencephalopathy. Infectious complications were mostly observed in male [6/7 (86%), p=0.06], with a longer duration of steroids (108 vs. 39 months, p=0.11) and immunosuppressant use prior IFX (42 vs. 24 months, p=0.08) compared to their negative counterpart, respectively. CONCLUSIONS: IFX was efficient in severe and refractory sarcoidosis. Infectious complications were frequent and occurred mainly in male patients with longer duration of steroids and immunosuppressant use prior to IFX.

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.

Impairment measures versus inflammatory RODS in GBS and CIDP: a responsiveness comparison.

This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP.

Grip strength comparison in immune-mediated neuropathies: Vigorimeter vs. Jamar.

The Jamar dynamometer and Vigorimeter have been used to assess grip strength in immune-mediated neuropathies, but have never been compared to each other. Therefore, we performed a comparison study between these two devices in patients with immune-mediated neuropathies. Grip strength data were collected in 102 cross-sectional stable and 163 longitudinal (new diagnoses or changing condition) patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), gammopathy-related polyneuropathy (MGUSP), and multifocal motor neuropathy (MMN). Stable patients were assessed twice (validity/reliability studies). Longitudinal patients were assessed 3-5 times during 1 year. Responsiveness comparison between the two tools was examined using combined anchor-/distribution-based minimum clinically important difference (MCID) techniques. Patients were asked to indicate their preference for the Jamar or Vigorimeter. Both tools correlated highly with each other (ρ = 0.86, p < 0.0001) and showed good intra-class correlation coefficients (Jamar [Right/Left hands]: ICC 0.997/0.96; Vigori: ICC 0.95/0.98). Meaningful changes were comparable between the two instruments, being higher in GBS compared to CIDP patients. In MGUSP/MMN poor responsiveness was seen. Significant more patients preferred the Vigorimeter. In conclusion, validity, reliability, and responsiveness aspects were comparable between the Jamar dynamometer and Vigorimeter. However, based on patients' preference, the Vigorimeter is recommended in future studies in immune-mediated neuropathies.

Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses.

We performed a comparison between Neuropathy Impairment Scale-sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed (RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12 months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients.

Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy.

BACKGROUND: Multifocal motor neuropathy (MMN) is characterised by progressive, predominantly distal, asymmetrical limb weakness and usually multiple partial motor nerve conduction blocks. Intravenous immunoglobulin (IVIg) is beneficial but the role of immunosuppressive agents is uncertain. This is an update of a review first published in 2002 and previously updated in 2003, 2005, 2008 and 2011. OBJECTIVES: To assess the effects of immunosuppressive agents for the treatment of multifocal motor neuropathy. SEARCH METHODS: On 22 September 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE and LILACS for trials of MMN. We also searched two trials registers for ongoing studies. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs. We considered prospective and retrospective case series and case reports in the Discussion. DATA COLLECTION AND ANALYSIS: Two review authors searched the titles and abstracts of the articles identified and extracted the data independently. MAIN RESULTS: Only one RCT of an immunosuppressive or immunomodulatory agent has been performed in MMN. This study randomised 28 participants and showed that mycophenolate mofetil, when used with IVIg, did not significantly improve strength, function or reduce the need for IVIg. No serious adverse events were observed. The study was deemed at low risk of bias. We summarised the results of retrospective and prospective case series in the discussion. AUTHORS' CONCLUSIONS: According to moderate quality evidence, mycophenolate mofetil did not produce significant benefit in terms of reducing need for IVIg or improving muscle strength in MMN. Trials of other immunosuppressants should be undertaken.

Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey.

Data on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials.

Sensitivity and predictive value of anti-GM1/galactocerebroside IgM antibodies in multifocal motor neuropathy.

BACKGROUND: Increased titres of serum IgM antibodies to GM1 ganglioside are often associated with multifocal motor neuropathy (MMN). Testing for IgM antibodies to other antigens including GM2, the mixture of GM1 and galactocerebroside (GM1/GalC) and the disulfated heparin disaccharide NS6S were reported to increase the sensitivity of antibody testing in MMN even if it is unclear whether the specificity and positive (PPV) or negative predictive value (NPV) for MMN were also affected. METHODS: We measured IgM antibodies to GM1, GM2, galactocerebroside, GM1/GalC and NS6S in 40 consecutive patients with MMN and 142 controls with other neuropathies or related diseases and compared their sensitivity, specificity and PPV for MMN. RESULTS: With the only exception of anti-GM2 and, partially, anti-NS6S antibodies, IgM antibodies to the antigens tested were more frequent in MMN than in controls. Increased titres of anti-GM1 IgM were found in 48% of MMN patients with a specificity of 93% and PPV for MMN of 66%. Anti-GM1/GalC antibodies were present in all anti-GM1 positive MMN patients and in 11 additional patients (28%) with MMN raising the sensitivity of antibody testing to 75%. The specificity (85%) and PPV (59%) for MMN was, however, moderately reduced compared to anti-GM1 IgM, even if they rose with increasing anti-GM1/GalC titres. IgM antibodies to GM2, NS6S and galactocerebroside were found in 8%, 23% and 60% of MMN patients but had a low specificity and PPV for MMN. CONCLUSIONS: Testing for anti-GM1/GalC IgM significantly increased the sensitivity of antibody testing in MMN compared to anti-GM1 alone (p=0.021) and may represent a preferred option for GM1 reactivity testing in MMN.

Chronic inflammatory demyelinating polyradiculoneuropathy: search for factors associated with treatment dependence or successful withdrawal.

BACKGROUND: About 40% of responders to treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remain treatment dependent and have a relapse if treatment is interrupted. OBJECTIVE: To look for factors associated with treatment dependence or successful withdrawal in CIDP patients. METHODS: We retrospectively studied 70 responder CIDP patients comprising 34 patients who remained treatment dependent (treatment-dependent group) and 36 patients whose treatment could be discontinued (treatment withdrawal group). Clinical, biological, electrophysiological and therapeutic features were compared between these groups. RESULTS: A multifocal deficit was more frequent in the treatment-dependent group (35%) than in the treatment withdrawal group (8%) (p<0.01). The most frequent effective treatment was intravenous immunoglobulin (IVIG) for the treatment-dependent group (79%). In this group, more patients were resistant to corticosteroids in first-line therapy (93%) than in the treatment withdrawal group (40%) (p=0.002). The delay to effective treatment was significantly shorter for the treatment withdrawal group than for the treatment-dependent group (mean 11.1 vs 31.2 months; p<0.01). The rate of successful withdrawal was lower with IVIG (29%) than with corticosteroids (83%) (p<0.001). CONCLUSIONS: When compared with the treatment withdrawal group, the treatment-dependent group was more frequently responsive to IVIG, more frequently resistant to corticosteroids in first-line treatment, had a longer delay to effective treatment and was more likely to present a multifocal deficit. The rate of successful withdrawal seems to be higher with corticosteroids, but a prospective study with a long-term follow-up is needed to confirm these features.

Multifocal motor neuropathy.

PURPOSE OF REVIEW: Multifocal motor neuropathy (MMN) remains a difficult issue for neurologists, as its clinical and electrophysiological presentation may be atypical, and because no alternative treatment to periodic immunoglobulin infusions has been assessed in its long-term management. This review intends to summarize the most recent advances in the diagnosis and treatment of MMN. RECENT FINDINGS: Recent reports have focused on atypical onset and unusual clinical presentation. Several sophisticated electrophysiological techniques, as triple stimulation, may help establish the presence of conduction blocks, as well as MRI findings. A recent immunological study focused on the detection of serum IgM binding to NS6S heparin disaccharide. In another research article, it was proposed that the use of combinatorial glycoarray or ELISA may increase the diagnostic sensitivity of antiglycolipid antibody testing. Subcutaneous immunoglobulin may represent an interesting alternative option to intravenous immunoglobulin. Lastly, recently reported open-label clinical trials with complement inhibitors and anti-CD20 monoclonal antibody may constitute a first step for further developments. SUMMARY: Diagnostic criteria for MMN are well established, but challenging situations still occur. Progresses in neurophysiologic and other laboratory tests may help in clarifying doubtful diagnoses. Current research into the pathophysiology of MMN is required to determine the future treatment targets.

Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey.

BACKGROUND: Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. METHODS: The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. RESULTS: After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate <60 ml/min and age >65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p<0.0001). The area under the curve for the CVS was 0.74 compared with 0.67 for the FFS, indicating a better performance of the CVS (p=0.052). CONCLUSIONS: In patients with non-infectious mixed CryoVas, the main prognostic factors are age >65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.