Quality of life complements traditional outcome measures in immune-mediated polyneuropathies

Participants.

A cross-sectional group of 114 Dutch patients (83 with GBS, 23 with CIDP, 8 with MGUSP) with a stable clinical condition were recruited from the Rotterdam immune-mediated polyneuropathy databank and the Dutch GBS study group (stable group). These patients came from all Dutch districts and were treated in various hospitals throughout The Netherlands. The patients did not have any known concomitant disease that might influence quality of life. These patients still had residual symptoms or signs due to their illness, representing a broad range of disability: functional grading scale (F-score) ranging from 1 to 4 (see also assessment scales).12 Nine patients with CIDP required interval treatment ranging from weeks to months, with IV immunoglobulins (IVIg). With this therapy their clinical condition has been stable for >6 months. Six patients with MGUSP had an associated demyelinating polyneuropathy, with minor concurrent axonal damage in three. An axonal polyneuropathy was diagnosed in the remaining two patients with MGUSP.

Twenty consecutive patients at the University Hospital Rotterdam with newly diagnosed GBS (n = 7) or CIDP (n = 13) and changing clinical conditions were enrolled to investigate whether the SF-36 captured longitudinal changes in these disorders (longitudinal group). These patients were also free from concomitant disease. The baseline F-score values in these patients ranged from 1 to 5 (see also assessment scales).12 During the recruitment period, no patients with newly diagnosed MGUSP were seen at our department. All patients with GBS and CIDP met the international criteria for their illness.13,14⇓ The diagnosis of MGUSP was established after excluding all possible causes for the gammopathy and polyneuropathy.15

The reported mean (SD) SF-36 domain scores and summary values for a random, nationwide sample of 1,742 healthy individuals in The Netherlands were used. There were 976 men and 766 women with a mean age of 47.6 years (18.0 years) (range, 16 to 94 years) used for the comparison studies with the SF-36 values in the selected patient groups.10,11⇓

Assessment scales.

The SF-36, a generic health status questionnaire, consists of 36 items, assigned to the domains of physical functioning (10 items), role functioning–physical (4), role functioning–emotional (3), social functioning (2), body pain (2), mental health (5), vitality (4), general health perception (5), and change in health, which is scored separately.8 The numbers of response categories per item range from two to six. Each domain has a scoring range from 0 to 100. A high score indicates better health or less body pain. The Dutch version of the SF-36 was used.10 The corresponding physical component summary (PCS) and mental component summary (MCS) values were also calculated using the reported means, standard deviations, and factor score coefficients that came from the general Dutch population.9-11⇓⇓ A linear T-score transformation method was used so that the PCS had a mean of 49.7 (SD 9.3) and the MCS had a mean of 52.1 (SD 9.6), as reported for the general Dutch population.9-11⇓⇓

The Medical Research Council (MRC) sumscore is a summation of the MRC grades given in full numbers of the following muscle pairs: upper arm abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and foot dorsal flexors.12 The MRC sumscore ranges from 0 (total paralysis) to 60 (normal strength).12

The Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (ISS) was applied to measure general sensory deficit.16 The ISS comprises vibration and pinprick sense plus a two-point discrimination value and ranges from 0 (normal sensation) to 20 (most severe sensory deficit).16

The Hughes functional grading scale (F-score) assesses the functional ability of the patients.12 The F-score of the patients included in this study ranged from 0 to 5. An F-score of 0 indicates normal health (no symptoms or signs); 1 denotes having minor neurologic symptoms or signs and being able to run; 2 denotes able to walk at least 10 m, but unable to run; 3 denotes able to walk 10 m with a walker or support; 4 denotes bedridden or chair bound (unable to walk 10 m with a walker or support); 5 denotes requiring artificial ventilation for at least part of the day.12 Good psychometric properties were demonstrated for all selected scales.9-12,16⇓⇓⇓⇓ However, SF-36 has not been evaluated in terms of its validity, reliability, and responsiveness in immune-mediated polyneuropathies.

Test procedures and treatment.

All participants gave informed consent before the study. All measures were obtained at our clinic. The patients received instructions on how to fill in the SF-36. The time to complete the SF-36 was recorded in 50 participants. The assessments were performed in a random order. For the assessment of strength, a predefined standardized joint and limb position as well as the point at which counter force was administered were taken for each muscle group. Sensory modalities were examined in triplicate according to the recently described standard procedures.16 In the stable group of patients, all measures were examined once. Before leaving, all SF-36 items were checked for possible missing values, and if necessary patients were asked to complete the missing questions.

The longitudinal group of patients was examined by the same clinician (I.M.) and the MRC sumscore, ISS, and F-score were assessed randomly at the weeks 0, 2, 4, 8, 12, 16, 21, 26, 32, 40, and 52 of follow-up in each patient. If necessary, additional clinical investigations were performed. The SF-36 was concurrently assessed at the weeks 0, 4, 12, 26, 32, 40, and 52. All SF-36 domains and summary measures were scored as recommended by the SF-36 developers.8,9⇓ Patients were also allowed to contact us between clinical visits for any question possibly related to their illness. Family members of the patients were also stimulated to participate in the whole process of dealing with the consequences of the illness.

All but one mildly affected patient was initially treated with IVIg. IVIg demonstrated to be efficacious in GBS and CIDP.17-20⇓⇓⇓ One IVIg-nonresponsive patient with CIDP received additional treatment with prednisone.21 The study took place between March 1997 and December 1999 and was part of a more comprehensive outcome assessment research in patients with immune-mediated polyneuropathies on behalf of the INCAT group, a collaborating force of European neurologists with special interest in neuroimmunologic illnesses.

Statistics.

Patient characteristics and general aspects.

The basic characteristics of all patients are presented in table 1. In the stable group, 14 patients required assistance or a device to walk short distances (F-score = 3) and eight patients were bed bound (F-score = 4) (22/114 = 19%; 17 GBS, 3 CIDP, 2 MGUSP). The remaining 92 patients (81%) could walk independently (F-score ≤ 2; 66 GBS, 20 CIDP, 6 MGUSP; see table 1). At study entry, 13 longitudinally examined patients were unable to walk independently (4 GBS, 5 CIDP) or were bed bound (2 GBS, 2 CIDP), one requiring artificial ventilation. The remaining seven patients (1 GBS, 6 CIDP) could walk independently.

According to all patients, the SF-36 was easily administered and took 9 (SD 2) minutes for completion. All SF-36 items were completed. The longitudinally examined patients contacted us with questions (usually once a week by telephone), especially within the first 3 months of their illness. All patients reported having the opportunity to contact us as a big support in managing the consequences of their illness.

SF-36 scores in stable patients.

The mean SF-36 subscale values with corresponding mean PCS and MCS scores for the stable group of 114 patients were notably lower compared with the reported mean normal values (figure 1, A and B; t-test: p < 0.0001). Differences between independent ambulatory patients (n = 92; F-scores ≤ 2) and patients who needed support to walk or could not walk (n = 22; F-scores = 3 and 4) are presented in figure 1, C and D. These differences were primarily reflected in the more physically focused domains (“physical functioning” and “role functioning–physical”; t-test: p ≤ 0.002; for the dimension “role functioning–emotional”: p = 0.02; for the remaining subscales: p ≥ 0.1). The PCS scores clearly distinguished between the two disability subgroups, demonstrating a lower mean PCS value for the more disabled subgroup (see figure 1D; t-test: p = 0.0007). No differences between these subgroups were seen for the MCS values (see figure 1D; t-test: p = 0.5).

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Figure 1. Comparison of mean Medical Outcome Study 36-item short-form health status profile (SF-36) in a stable group of patients with immune-mediated polyneuropathies vs mean values for the healthy Dutch community. (A) Mean domain values for the whole stable group. (B) Mean component summary scores for the whole stable group. Mean dimensions and summary measures were notably lower compared with corresponding values in healthy control subjects (t-test: p < 0.0001 for all comparisons). (C) Mean domain values for the two disability subgroups (F-score ≤ 2: able to walk independent v F-scores 3 + 4: able to walk with support or bed bound). (D) Mean component summary scores for the two disability subgroups. Differences between these two subgroups were especially reflected in the more physically focused domains (“physical functioning” and “role functioning–physical”; t-test: p ≤ 0.002; for the domain “role functioning–emotional”: p = 0.02; for the remaining dimensions: p ≥ 0.1). The reported mean (SD) SF-36 domain scores with corresponding summary values for a nationwide sample of 1,742 healthy individuals in the Netherlands were used for the comparison studies.10,11⇓ PhF = physical functioning; RFPh = role functioning–physical; RFE = role functioning–emotional; SF = social functioning; BP = body pain; MH = mental health; Vit = vitality; GHP = general health perception; PCS = physical component summary score; MCS = mental component summary score.

SF-36 values in longitudinally examined patients.

Eight women and 12 men were examined longitudinally. A total of 201 visits were completed in these patients. SF-36 was concurrently assessed on 147 occasions of these 201 visits (five to 10 visits in each patient). The follow-up period ranged from 40 to 58 weeks (mean 52 weeks). Nineteen patients completed a 1-year follow-up. All patients experienced general loss of strength, sensory disturbances, and reported functional deficit. Good clinical improvement was noted during follow-up in all patients. The GBS patients (n = 7; six were treated with IVIg; one patient received no treatment) did not show any deterioration during follow-up. Twelve IVIg-responsive patients with CIDP needed interval therapy with IVIg (1 to 2 days 0.4 g/kg/d; intervals: 3 to 21 weeks) to maintain the achieved improvement. One patient with CIDP did not respond on IVIg therapy and was treated with prednisone (initial dose 100 mg/d for 4 weeks, tapered down over 5 months to 30 mg every other day). Eventually, all patients demonstrated during follow-up a general increase in quality of life as shown in figures 2 and 3⇓. As can be seen, the SF-36 adequately captured improvement in these patients, demonstrating a gradual shift of all scores in the whole group toward normal values (see figures 2 and 3⇓). At entry, all dimensions and summary measures were substantially lower compared with the corresponding normal values (t-test: p < 0.0001 for all comparisons). All SF-36 entities, except for the domains “physical functioning” and “role functioning–physical,” and PCS score, reached within normal values at 6 and 12 months of follow-up (t-test; p < 0.04 for comparison between “physical functioning,” “role functioning–physical,” and PCS score vs corresponding normal values; p > 0.07 for the remaining comparisons; see figures 2 and 3⇓). The MRC sumscore and ISS also captured improvement over time (table 2). Moreover, lower F-score values were seen in most patients during follow-up, hence representing a better functional status (see table 2).

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Figure 2. Mean Medical Outcome Study 36-item short-form health status (SF-36) changes in a longitudinal group of patients with immune-mediated polyneuropathies (I) receiving maintenance therapy vs mean normal values for the general Dutch community (II). PhF = physical functioning; RFPh = role functioning–physical; RFE = role functioning–emotional; SF = social functioning; BP = body pain; MH = mental health; Vit = vitality; GHP = general health perception. Twenty patients were examined longitudinally. A total of 147 SF-36 measures were completed. There was a gradual shift of all SF-36 domains and summary measures toward normal values. The reported mean (SD) SF-36 domain scores and summary measures for a random sample of 1,742 healthy individuals in the Netherlands were used for the comparison studies.10,11⇓

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Figure 3. Mean Medical Outcome Study 36-item short-form health status (SF-36) component summary scores in a longitudinal group of patients with immune-mediated polyneuropathies receiving maintenance therapy vs mean normal values for the general Dutch community. Twenty patients were examined longitudinally. A total of 147 SF-36 measures were completed. There was a gradual shift of all SF-36 domains and summary measures toward normal values. The reported mean (SD) SF-36 domain scores and summary measures for a random sample of 1,742 healthy individuals in the Netherlands were used for the comparison studies.10,11⇓ PCS = physical component summary score; MCS = mental component summary score.

Clinical variables and their impact on SF-36 physical component summary and mental component summary scores in the stable group.

Age was not significantly related to the PCS and MCS values. Also, duration of symptoms was not significantly correlated with the summary values in this group. General strength and sensory disturbances partially explained the obtained PCS values (MRC sumscore: fraction explained variation: R² = 0.12; ISS: R² = 0.16; p < 0.0001 for all regressions). MRC sumscore and ISS values were not significantly related to the MCS scores in the stable group.

Validity, reliability, and responsiveness of the SF-36.

The psychometric requirements for the SF-36 are presented in tables 3 and 4⇓. Poor to good correlation values were obtained between the SF-36 and other clinical measures. The highest associations were seen between the physically oriented SF-36 entities and the MRC sumscore and F-score values (see table 3). Good internal consistency values were obtained for all SF-36 dimensions and summary measures (see table 3). All dimensions and summary measures, except “body pain” and “general health perception,” had standardized response mean and effect size values ≥ 0.8, indicating high responsiveness. Moderate standardized response mean and effect size values (0.4 to 0.7) were obtained for “body pain” and “general health perception” (see table 4).