Validation of the Serbian version of inflammatory Rasch‐built overall disability scale in patients with chronic inflammatory demyelinating polyradiculoneuropathy

Inflammatory Rasch‐built overall disability scale (I‐RODS) seems to be a valid activity measure for use in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our aim was to translate and validate the I‐RODS for use in CIDP patients from Serbia. Study comprised 83 patients diagnosed with CIDP. I‐RODS was translated and cross‐culturally validated using the standard guidelines. Following scales were also administered: Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Krupp's Fatigue Severity Scale, Beck Depression Inventory, Visual Analogue Scale for pain, and health survey‐36 (SF‐36) as a quality of life measure. According to the I‐RODS, significant proportion of our patients reported that “running” (51%), “dancing” (41%), and “standing for hours” (40%) were impossible tasks to perform, while “teeth brushing” (94%), “eating” (88%), and “reading a newspaper/book” (82%) were noted as the easiest items. Patients with more muscle weakness (lower MRC sum score) and more severe INCAT sensory score had lower I‐RODS score (P < .01). Also, patients with fatigue, depression and pain had lower I‐RODS scores (P < .01). I‐RODS score correlated with the INCAT disability score (P < 0.01) was 78 ± 19 compared to 51 ± 30 in patients with INCAT >1 (P < .01). I‐RODS score correlated with the total SF‐36 score (rho = +0.73, P < .01), as well as with all SF‐36 domain scores. Serbian version of the I‐RODS seems to be a valid activity measure for use in CIDP patients. I‐RODS was able to assess different levels of disability, it was in association with impairment measures, INCAT disability scale and quality of life. Further studies are needed to assess its responsiveness.     

Psychometric evaluation of a new sensory scale in immune-mediated polyneuropathies. Inflammatory Neuropathy Cause and Treatment (INCAT) Group

OBJECTIVE: To perform a psychometric evaluation of the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore (ISS) in sensory-motor immune-mediated polyneuropathies. This new sensory scale was evaluated to strive for uniformity in assessing sensory deficit in these disorders. METHODS: The ISS comprises vibration and pinprick sense plus a two-point discrimination value and ranges from 0 (normal sensation) to 20 (maximum sensory deficit). Before its clinical use, a panel of expert neurologists concluded that the ISS has face and content validity. The construct validity of the ISS was investigated by correlation and regression studies with additional scales (Nine-Hole Peg Test, 10-Meter Walking Test, a disability sumscore). All scales were applied in 113 patients with a stable neurologic condition (83 patients who experienced Guillain-Barre syndrome [GBS] in the past, 22 with chronic inflammatory demyelinating polyneuropathy [CIDP], 8 patients with a monoclonal gammopathy associated polyneuropathy), and 10 patients with recently diagnosed GBS or CIDP with changing clinical conditions. Reliability of the ISS was evaluated in the stable patients. Its responsiveness was investigated in the patients examined longitudinally. RESULTS: A moderate to good validity was obtained for the ISS (stable group: r = 0.38 to 0.56, p < or = 0.006; longitudinal group: R = 0.60 to 0.82, p < or = 0.007, except for the association with the 10-Meter Walking Test [p = 0.08]). Acceptable internal consistency, and inter- and intraobserver reliability were demonstrated for the ISS (alpha = 0.68 to 0.87; R = 0.85 to 0.89, p < 0.0001). Standardized response mean scores for the ISS were high (> or =0.8), indicating good responsiveness. CONCLUSIONS: All psychometric requirements are provided for the the inflammatory neuropathy cause and treatment sensory sumscore. The use of this scale is therefore suggested for bedside evaluation of sensory deficit in the individual patient with a sensory-motor immune-mediated polyneuropathy as well as in clinical trials.     

Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies

OBJECTIVES: To determine the validity, reliability, and responsiveness of a new overall disability sum score in immune mediated polyneuropathies. METHODS: Three impairment measures (MRC sum score, sensory sum score, grip strength (Vigorimeter)) and three disability scales (an overall disability sum score (ODSS), Hughes' functional scale (f score), Rankin scale) were assessed in a cross sectional group of 113 clinically stable patients (83 with Guillain-Barré syndrome, 22 with chronic inflammatory demyelinating polyneuropathy (CIDP), eight with a gammopathy related polyneuropathy). The ODSS was also used serially in 20 patients with recently diagnosed Guillain-Barré syndrome (n = 7) or CIDP (n = 13) and changing clinical conditions. Multiple regression studies were performed to compare the impact of impairment disturbances (independent variables) on the various disability scales (dependent variable). RESULTS: Moderate to good construct validity (stable group: Spearman's rank test (absolute values), r = 0.41-0.79; longitudinal group: multiple correlation coefficient, R = 0.69-0.89; p < 0.006 for all associations) and reliability (intraclass correlation coefficient, R = 0.90-0.95; p < 0.0001) were demonstrated for the ODSS. Its SRM values were high (> 0.8), indicating good responsiveness. Impairment measures accounted for a higher variance proportion of the ODSS compared with the f score and Rankin (R = 0.64 v 0.56 and 0.45, respectively). CONCLUSIONS: All clinimetric requirements were met by the overall (arm and leg) disability sum score in immune mediated polyneuropathies. Its use is therefore suggested in evaluating immune mediated polyneuropathies.     

Getting closer to patients: the INCAT Overall Disability Sum Score relates better to patients' own clinical judgement in immune-mediated polyneuropathies

Objective

To determine which widely used disability measure in Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) shows the strongest association with patients'' rating scores.

Methods

Five disability scales and the Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36) were assessed serially in 20 patients with newly diagnosed GBS (n = 7) or CIDP (n = 13). Also at each visit, the patient''s condition was self‐assessed as being worse, unchanged or better. Longitudinal regressions were carried out to determine the association between disability scales (independent variables) and SF‐36 and patients'' rating scores (dependent variables).

Results

Higher associations with the SF‐36 were found in the Overall Disability Sum Score (ODSS) than other disability measures. A higher correlation with ODSS changes was also found in the rating scores of the patients.

Conclusion

In addition to literature findings, higher associations were found between Inflammatory Neuropathy Cause and Treatment Group ODSS and outcome assessed from patients'' perceptions in immune‐related polyneuropathies than in other commonly used disability scales.During the past 8 years the Rotterdam Inflammatory Neuropathy Cause and Treatment (INCAT) Group published various papers considering outcome measures in patients with Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), focusing primarily on their scientific properties such as being simple and easily applicable, valid, reliable and responsive.^1,2,3 By consensus among the INCAT group, the disability level was proposed as the main level of measuring therapeutic response and the INCAT Overall Disability Sum Score (ODSS) was proposed as a preferential outcome measure for treatment trials of these conditions for the following reasons. The ODSS

• covers not only mobility disturbances but also upper limb dysfunction;
• has good clinimetric properties, especially greater responsiveness; and
• captures a higher proportion of variance of disability explained by impairment qualities.^4,5

During these investigations, we questioned whether the ODSS, an instrument applied by clinicians, would have the best correlation with patients'' own judgement of their clinical condition, when compared with other disability scales. Therefore, in patients with GBS and CIDP, we investigated the possible association between selected disability measures and patients'' own clinical judgement using (1) the Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36) status and (2) a self‐assessed rating score of being worse, unchanged or better at each visit.⁶ The INCAT group''s hypothesis was that the ODSS would be more strongly related to patients'' perception than would other measures.     

Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies

Aim of the study: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. Materials and Methods: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. Results: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. Conclusions: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.     

Chronic Acquired Polyneuropathy Patient Reported Index (CAPPRI) in chronic inflammatory demyelinating polyradiculoneuropathy

To date there are only two validations on the Chronic Acquired Polyneuropathy Patient‐Reported Index (CAPPRI) questionnaire, both originated from the North America. We sought to translate and validate CAPPRI for use in Serbian patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We included 109 CIDP patients. CAPPRI, short form (36) health survey (SF‐36), Medical Research Council Sum Score (MRC‐SS), Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used. Serbian CAPPRI questionnaire was understandable and the language was appropriate and simple. Calculation demonstrated good person (0.9) and item (0.9) reliability with adequate item (4.1), and person (2.9) separation indices. There was a minor floor effect (13.8%), and no ceiling effect. All items had good fit, except items 2 (pain), 5 (sleeping), and 14 (eating) to some degree. Category responses were well ordered and organized, except item 14 (eating). The CAPPRI score did not vary regarding gender, age, or education. Patients with worse scores on MRC‐SS, INCAT sensory score, INCAT disability score, FSS, and BDI had worse scores on CAPPRI (P < .01). The CAPPRI score showed strong correlation with the SF‐36 score (rho = ?0.76, P < .01). The Serbian version of the CAPPRI is reliable and valid patient‐reported index for patients with CIDP, able to differentiate between levels of impairment and disability in this disease.     

One‐year follow‐up study of neuropathic pain in chronic inflammatory demyelinating polyradiculoneuropathy

We sought to gather information about frequency and features of neuropathic pain (NeP) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients and to investigate course of NeP during 1‐year follow‐up. Study included 105 patients diagnosed with CIDP. Patients with diabetes (N = 26) were excluded. NeP was diagnosed by the official guidelines and painDETECT questionnaire (PD‐Q). Medical Research Council Sum Score (MRC‐SS), INCAT disability and sensory scores, and Beck Depression Inventory were also measured. PD‐Q showed presence of NeP in 16 (20%) of 79 CIDP patients and their mean pain was moderate (5.1 ± 3.0 of 10). Diagnostic delay in CIDP patients with NeP was prolonged compared to CIDP patients without NeP (21 ± 28 vs 9 ± 12 months, P < .05). Slowly progressive course of the disease was more frequent in patients with NeP (81% vs 52%, P < .05). Patients with NeP had worse INCAT sensory score (P < .01), INCAT disability score (P < .05), MRC‐SS, as well as worse disease outcome at time of testing (P < .05). Depression was more common in patients with NeP (69% vs 17%, P < .01). During 1‐year follow‐up, majority of our CIDP patients had good control of NeP with gabapentinoids or amitriptyline. NeP was common in our cohort of non‐diabetic CIDP patients. It was associated with worse functional disability, worse sensory deficit, and depression. Special attention should be paid to CIDP patients with NeP because they request additional symptomatic therapy that appeared efficacious in our cohort.     

Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M

We evaluated the efficacy and safety of rituximab in an open-label, uncontrolled study of 13 patients with polyneuropathy associated with antibodies to myelin-associated glycoprotein (MAG) and correlated the response to therapy with clinical and laboratory features. One year after rituximab therapy, anti-MAG immunoglobulin M (IgM) titers were significantly reduced. At that time, eight patients (62%) had improved in both the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore and the Medical Research Council sumscore for muscle strength and seven of them also in the INCAT disability score. The improvement in the mean INCAT sensory sumscore was significant at 12 months and correlated with lower anti-MAG antibody at entry and at follow-up. This study suggests that rituximab may be efficacious in patients with anti-MAG associated neuropathy and particularly on sensory impairment and in those with moderately elevated antibody titers. These findings suggest that antibody reduction below a critical level may be necessary to achieve clinical improvement.     

Connecting impairment,disability, and handicap in immune mediated polyneuropathies

BACKGROUND: In the World Health Organisation (WHO) International Classification of Impairments, Disabilities, and Handicaps (ICIDH), it is suggested that various levels of outcome are associated with one another. However, the ICIDH has been criticised on the grounds that it only represents a general, non-specific relation between its entities. OBJECTIVE: To examine the significance of the ICIDH in immune mediated polyneuropathies. METHODS: Four impairment measures (fatigue severity scale, MRC sum score, "INCAT" sensory sum score, grip strength with the Vigorimeter), five disability scales (nine hole peg test, 10 metres walking test, an overall disability sum score (ODSS), Hughes functional grading scale, Rankin scale), and a handicap scale (Rotterdam nine items handicap scale (RIHS9)) were assessed in 113 clinically stable patients (83 with Guillain-Barré syndrome, 22 with chronic inflammatory demyelinating polyneuropathy, eight with a gammopathy related polyneuropathy). Regression analyses with backward and forward stepwise strategies were undertaken to determine the correlation between the various levels of outcome (impairment on disability, impairment on handicap, disability leading to handicap, and impairment plus disability on handicap). RESULTS: Impairment measures explained a substantial part of disability (R(2) = 0.64) and about half of the variance in handicap (R(2) = 0.52). Disability measures showed a stronger association with handicap (R(2) = 0.76). Combining impairment and disability scales accounted for 77% of the variance in handicap (RIHS9) scores. CONCLUSIONS: In contrast to some suggestions, support for the ICIDH model is found in the current study because significant associations were shown between its various levels in patients with immune mediated polyneuropathies. Further studies are required to examine other possible contributors to deficits in daily life and social functioning in these conditions.     

Chronic polyneuropathies in Vest-Agder, Norway

Epidemiological data on chronic polyneuropathies, especially inflammatory types, is limited. The purpose of this study was to examine the spectrum of causes and estimated prevalence of various polyneuropathy types in Vest‐Agder, and to examine the clinical features of the Vest‐Agder population of chronic inflammatory demyelinating polyneuropathy (CIDP). In Vest‐Agder county (population of 155 464), polyneuropathy patients are registered in a database and followed prospectively. We did a measure of the database on October 31 1999. A total of 192 patients were registered. The prevalence for chronic inflammatory demyelinating polyneuropathy (CIDP) was 7.7 per 100 000 population. The course was relapsing in five of fifteen patients, progressive in four patients and slowly progressive in six of fifteen patients. Two of the fifteen patients had pure sensory symptoms. The mean Rankin disability score was 3.4 at maximal deficit and 2.1 at last follow‐up. The prevalence of paraproteinemic polyneuropathy was 5.1 per 100 000 population. None of the patients with paraproteinemic polyneuropathy were worse than slightly disabled (disability score ≤ 2). The prevalences for other polyneuropathies were as follows: polyneuropathy and RA, 1.3; polyneuropathy and Sjögren's syndrome or sicca complex, 4.5 (polyneuropathy was the presenting symptom in five of seven patients); sarcoidosis 1.9; polyneuropathy and chronic Lyme, 0.6; paraneoplastic polyneuropathy, 1.9; diabetic polyneuropathy 23.2; vitamin deficiency, 5.1; alcoholic and toxic polyneuropathy, 19.9; hereditary polyneuropathy, 14.8. Cryptogenic polyneuropathies made up 26% of all polyneuropathies. The mean disability score was 2.0 (SD 1.1). In conclusion, prevalence of CIDP was significantly higher than previously reported, and the prognosis was good in the majority of patients. Patients with paraproteinemic polyneuropathy were not severely disabled. Polyneuropathy was the presenting symptom in the majority of patients with Sjögren's syndrome or sicca complex.     

Impairment and disability in 20 CIDP patients according to disease activity status

Twenty patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) meeting the EFNS/PNS criteria were examined in order to assess differences/similarities between the various grading systems according to CIDP disease activity status (CDAS). A principal component (PC) analysis and the correlations between the following scores were performed: Neurological Symptom Score; MRC sum score; Neurological Impairment Score; Hammersmith Functional Motor Scale; Inflammatory Neuropathy Cause and Treatment (INCAT) Sensory Sum Score; Overall Disability Sum Score; INCAT Disability Score; Rasch‐built Overall Disability Scale. Our analysis outlined two main sets of scales, with high influence in the top two PCs. The first PC that best explained the variability within the cohort consisted of CDAS, general disability scores and motor scores; these parameters were also strongly correlated amongst each other. The second PC explained less the variability and consisted mainly of sensory scores and disease duration; these parameters did not correlate with the scores of the first PC or with the CDAS. Our findings suggest separating screening for motor and sensory deficits when evaluating CIDP patients, as only the motor scores correlate with CDAS.     

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.].     

Efficacy and safety of Privigen® in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective,single‐arm,open‐label Phase III study (the PRIMA study)

This prospective, multicenter, single‐arm, open‐label Phase III study aimed to evaluate the efficacy and safety of Privigen^® (10% liquid human intravenous immunoglobulin [IVIG], stabilized with l ‐proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2 g/kg body weight [bw]) and up to seven maintenance doses (1 g/kg bw) at 3‐week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of ≥1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being ≥35%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG‐pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%–76.43%). IVIG‐pretreated patients demonstrated a higher responder rate than IVIG‐naïve patients (76.9% vs. 46.7%). The median (25%–75% quantile) INCAT score improved from 3.5 (3.0–4.5) points at baseline to 2.5 (1.0–3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5–72.0] points vs. 75.5 [71.5–79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well‐tolerated induction and maintenance treatment in patients with CIDP.     

Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

BACKGROUND: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. METHODS: 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740. FINDINGS: During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension. INTERPRETATION: This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP.     

Understanding the consequences of chronic inflammatory demyelinating polyradiculoneuropathy from impairments to activity and participation restrictions and reduced quality of life: the ICE study

A randomized trial (ICE trial) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) demonstrated significantly more improvement with intravenous immunoglobulin (Gamunex^®, Talecris Biotherapeutics, Inc., Research Triangle Park, NC) than placebo. To understand the relationship between CIDP impairments, activity and participation restrictions, and quality of life (QoL) in this trial, we investigated the association between scales representing these outcome levels. Gamunex or placebo was given every 3 weeks for up to 24 weeks to 117 patients in an initial treatment period after which treatment failures were crossed over (alternative treatment). We assessed impairments, activity and participation, and SF‐36 component mental (MCS) and physical summaries (PCS). Regression analyses of baseline data were performed (all subjects) and change from baseline to endpoint (Gamunex‐treated group only) to determine correlations between outcomes. Grip strength, medical research council (MRC) sum score, and inflammatory neuropathy cause and treatment (INCAT) sensory sum score were the strongest explanatory variables of disability (at baseline: r² = 0.46; change from baseline: r² = 0.66). Only up to half of the variance in QoL scores (PCS at baseline: r² = 0.30; change from baseline: r² = 0.41; MCS: at baseline: r² = 0.10; change from baseline: r² = 0.24) was explained by impairment and activity and participation measures. Future studies are required to elucidate the impact of CIDP on disability and QoL changes, because the obtained correlations provide only partial explanation.     

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.     

Rasch‐built Overall Disability Scale for Multifocal motor neuropathy (MMN‐RODS©)

Clinical trials in multifocal motor neuropathy (MMN) have often used ordinal‐based measures that may not accurately capture changes. We aimed to construct a disability interval outcome measure specifically for MMN using the Rasch model and to examine its clinimetric properties. A total of 146 preliminary activity and participation items were assessed twice (reliability studies) in 96 clinically stable MMN patients. These patients also assessed the ordinal‐based overall disability sum score (construct, sample‐dependent validity). The final Rasch‐built overall disability scale for MMN (MMN‐RODS^©) was serially applied in 26 patients with newly diagnosed or relapsing MMN, treated with intravenous immunoglobulin (IVIg) (1‐year follow‐up; responsiveness study). The magnitude of change for each patient was calculated using the minimum clinically important difference technique related to the individually obtained standard errors. A total of 121 items not fulfilling Rasch requirements were removed. The final 25‐item MMN‐RODS^© fulfilled all Rasch model's expectations and showed acceptable reliability and validity including good discriminatory capacity. Most serially examined patients improved, but its magnitude was low, reflecting poor responsiveness. The constructed MMN‐RODS^© is a disease‐specific, interval measure to detect activity limitations in patients with MMN and overcomes the shortcomings of ordinal scales. However, future clinimetric studies are needed to improve the MMN‐RODS^©'s responsiveness by longer observations and/or more rigorous treatment regimens.     

Electrophysiological assessment of polyneuropathic involvement in rheumatoid arthritis: relationships among demographic,clinical and laboratory findings

Abstract

Objectives: The aims of this study were to electrophysiologically evaluate polyneuropathy in rheumatoid arthritis (RA) patients and to examine the relationships among polyneuropathy and demographic, clinical and laboratory findings.

Patients and methods: Sixty consecutive patients (51 women and nine men) with a clinical diagnosis of RA were examined electrophysiologically for the evidence of polyneuropathy. Parameters including age, gender, subcutaneous nodules, erosions, joint deformities, laboratory parameters, duration of RA, as well as dose, duration and type of disease modifying anti-rheumatic drug (DMARD) and steroid usage were recorded. RA activity was assessed using a 28-joint disease activity score (DAS28). The functional status of patients was measured using the health assessment questionnaire (HAQ). The symptoms and signs of polyneuropathy were quantified using the neuropathy symptoms score (NSS) and the neuropathy disability score (NDS), respectively.

Results: Ten patients (17%, eight women and two men) had polyneuropathic involvement as defined by nerve conduction studies (NCS). Two patients had mild symmetric sensory neuropathy and eight patients had mild symmetric sensorimotor axonal polyneuropathy. There was no significant difference in age, gender, subcutaneous nodules, erosions, joint deformities, rheumatoid factor, as well as dose, duration and type of DMARD and steroid therapy administered. We found a significant relationship among polyneuropathy and duration of RA, DAS28, HAQ, as well as abnormal NSS and NDS values. The durations of RA and DAS28 were also associated with a four- and three-fold increase in the risk of polyneuropathy, respectively.

Conclusion: Mild symmetric sensory or sensorimotor axonal polyneuropathies are common in RA patients and it is difficult to distinguish the symptoms of polyneuropathy from those of arthritis. An electrophysiological examination should be routinely carried out especially when patients have had a long disease duration and high scores for DAS28, HAQ, NSS and NDS.     

Long-term neurophysiological and clinical response in patients with chronic inflammatory demyelinating polyradiculoneuropathy treated with subcutaneous immunoglobulin

Objective

To assess the long-term effects of subcutaneous immunoglobulin (SCIg) on neurophysiological and clinical parameters in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

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.