Prevention of axonal loss after immediate dosage titration of immunoglobulin in multifocal motor neuropathy.

BACKGROUND: To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3-37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow-up. RESULTS: At follow-up, the Z-score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment-free period of 0.3 years (0.2-0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z-scores (0.9-17.0, p = 0.06) was observed in five patients with a treatment-free period of 4.0 years (0.9-9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow-up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss. CONCLUSION: Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.

Outcome in chronic inflammatory demyelinating polyneuropathy: A systematic review and meta-analysis.

INTRODUCTION/AIMS: Outcomes in chronic inflammatory demyelinating polyneuropathy (CIDP) have been reported in longitudinal and cross-sectional studies. A considerable variation in long-term disease outcome has appeared in those reports. To overcome this uncertainty, a systematic review and meta-analysis was conducted on CIDP outcomes, including the parameters of case fatality rate, ambulation, physical ability, and remission. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search was conducted in PubMed and EMBASE (OVID) for reports with at least 2 years of follow-up on patients with active or previously active CIDP that were published no later than May 12, 2022. Studies were appraised for quality using the Joanna Briggs Institute Critical Appraisal Checklist for studies reporting prevalence data. Pooled analyses were conducted and the results were visualized using forest plots. The study protocol was registered prospectively on PROSPERO (CRD42021266903). RESULTS: A total of 1290 titles were identified. Sixty-nine full-text articles were screened and 21 studies with 1199 patients were selected for the data analysis. The pooled case fatality rate was 3.3% (95% confidence interval [CI], 1.9% to 5.7%). The pooled fraction of nonambulatory patients was 8.2% (95% CI, 5.7% to 11.6%) and, overall, 47.1% (95% CI, 39.5% to 54.9%) of CIDP patients had a good outcome without disability. The pooled rate of remission was 40.8% (95% CI, 30.6% to 51.8%). DISCUSSION: Future research is warranted on how to prevent long-term impairment in CIDP. Care should be taken in developing clinical strategies to avoid immunomodulating therapy in the many patients in remission.

Axonal loss at time of diagnosis as biomarker for long-term disability in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIMS: We hypothesized that early, pretreatment axonal loss would predict long-term disability, supported by a pilot study of selected patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To further test this hypothesis, we examined a larger consecutive group of CIDP patients. METHODS: Needle electromyography and motor and sensory nerve conduction studies were carried out in 30 CIDP patients at pretreatment and follow-up 5 to 28 years later. Changes in amplitudes were expressed as axonal Z scores and changes in conduction as demyelination Z scores and correlated with findings of the Inflammatory Rasch-built Overall Disability Scale (I-RODS), the Neuropathy Impairment Score (NIS), and isokinetic dynamometry (IKS). RESULTS: At follow-up, the median I-RODS score was 73, the NIS was 23, and the IKS was 56%. The median axonal Z score was unchanged at follow-up. Conversely, the corresponding demyelination Z scores improved. The initial axonal loss was correlated with the clinical outcome and was an independent predictor of outcome by multivariate regression analysis. Axonal loss at follow-up was also correlated with the clinical outcome. Only the follow-up demyelination Z score was correlated with the clinical outcomes. Furthermore, the latency until treatment initiation was predictive of all three clinical outcome scores at follow-up, and of axonal loss and demyelination at follow-up. DISCUSSION: The present study findings indicate that pretreatment axonal loss at diagnosis in CIDP is predictive of long-term disability, neurological impairment, and strength. A delay in treatment is associated with more pronounced axonal loss and a worse clinical outcome.

Long-term follow-up of facilitated subcutaneous immunoglobulin therapy in multifocal motor neuropathy.

OBJECTIVE: To assess the feasibility, efficacy and patient satisfaction of long-term facilitated subcutaneous immunoglobulin therapy (fSCIG) in multifocal motor neuropathy (MMN). METHODS: Twelve patients previously participating in a randomized trial investigating the short-term efficacy of fSCIG were offered to switch to fSCIG maintenance therapy following a variable interval on conventional subcutaneous immunoglobulin. RESULTS: Eight patients were switched to fSCIG maintenance therapy, seven of whom were invited for a follow-up assessment after 18 months (range 13-23 months) of treatment. The age at follow-up was 57 years (range 45-70 years) and patients received a median weekly dose immunoglobulin G of 32.5 g (range 20.0-50.0 g), the dose being unaltered compared to baseline values following completion of the fSCIG trial. In five patients the infusion was biweekly, whereas two patients were infused weekly. The follow-up mean isometric strength normalized to pre-trial values was 107.7% (95% CI 86.4-129.0%) being non-inferior to baseline values (104.7%, 95% CI 97.6-111.8%, P = 0.015). The mean ODSS was 2.0 (95% CI 0.8-3.2) which is identical to the baseline score following completion of the fSCIG trial, the P-value for non-inferiority being <0.0001. The secondary variables of impairment, function and quality of life at follow-up all were non-inferior to baseline values (P ≤ 0.046). CONCLUSION: fSCIG seems feasible and effective for long-term maintenance treatment in patients with MMN.

Early axonal loss predicts long-term disability in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: To investigate early pre-treatment nerve fiber loss as a predictor of long-term clinical outcome in chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: In 14 patients, motor and sensory conduction studies of the median, fibular, and sural nerves were performed at pre-treatment and follow-up 11-28 years later. Z-scores of amplitudes were combined as biomarkers of axonal loss and Z-scores of conduction properties as demyelination scores. The axonal loss was further examined by electromyography (EMG) and motor unit number estimation. Axonal and demyelination scores were compared to clinical outcomes in the Inflammatory Rasch-built Overall Disability Scale, the Neuropathy Impairment Score, and dynamometry. RESULTS: At follow-up 12 patients walked independently, one needed support and one could not walk. The initial and follow-up axonal and demyelination scores were markedly abnormal. The initial axonal loss but not demyelination was strongly associated with both the follow-up axonal loss and the clinical measures. Moreover, delay of treatment initiation negatively influenced the axonal scores and clinical outcomes. CONCLUSION: In this hypothesis generating limited study, we found that axonal loss at early CIDP was highly predictive for long-term nerve fiber loss and disability. SIGNIFICANCE: The study indicates that prompt initiation of treatment to prevent nerve fiber loss is necessary for outcome in CIDP.

Quality of life in chronic inflammatory demyelinating polyneuropathy patients treated with subcutaneous immunoglobulin.

BACKGROUND: Subcutaneous immunoglobulin (SCIG) is effective treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). Quality of life (QoL) increases following switch from intravenous administration to SCIG, but its correlation with clinical functioning is sparsely studied. AIMS OF THE STUDY: The aim of this study is to evaluate the correlation between QoL and clinical functioning in CIDP patients treated with SCIG. METHODS: Danish patients with CIDP with a disease duration <10 years and currently treated with SCIG were eligible for inclusion. QoL was assessed with EQ-5D-5L and disability by the Overall Disability Sum Score (ODSS) and Rasch-built Overall Disability Scale (RODS). Gait performance was evaluated by a 40-meter-walk test (40-MWT) and a 6-spot-step test (6-SST) along with assessment of muscle strength (Medical Research Council score [MRC]). Correlations between QoL and the measured scores were calculated. RESULTS: Of 92 eligible patients, 44 were included. QoL on the visual analogue scale (VAS) was 65% (range: 15-90) of the level of healthy controls (P = .03) and correlated to impaired gait function by 40-MWT and 6-SST. QoL correlated to RODS and ODSS, whereas there was no correlation with the MRC score. CONCLUSIONS: In SCIG treated CIDP patients QoL is reduced and correlates to gait performance and disability.

A population-based study of long-term outcome in treated chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: The effect of long-lasting immune-modulating therapy was studied in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: A population-based, cross-sectional study of treated patients referred to the Danish health-care system between 1985 and 2006. RESULTS: The 51 participating patients had a median disease duration of 16 (interquartile range, 14-21) years. Twenty-seven patients (53%) had discontinued therapy and 46 walked independently. Disability and isokinetic strength were impaired by 17% and 20%, respectively, as compared with matched control subjects. For a few patients long-term CIDP was associated with severe morbidity (6%) and even mortality (1%). Prolongation of time until start of therapy was associated with an increased burden of long-term disability. DISCUSSION: Long-term prognosis in treated CIDP is characterized by limited disability in the majority of patients. Disability is related to delay of therapy. Therefore, more attention should be given to early treatment start in CIDP.

A population-based and cross-sectional study of the long-term prognosis in multifocal motor neuropathy.

A population-based, cross-sectional study of patients referred to the Danish hospital system between 1985 and 2006 was conducted to evaluate the long-term outcome in Danish patients treated for multifocal motor neuropathy (MMN). Thirty-four MMN patients were identified, three had died of unrelated diseases, 10 were excluded, one did not reply to study request and 20 were included. The median disease duration was 24 years (interquartile range: 18.5-31.0). Compared to 24 healthy matched control subjects, the Rasch-built Overall Disability Scale for Multifocal Motor Neuropathy was reduced by 9%, the Neuropathy Impairment Score showed a 3-fold increase, the isokinetic strength was reduced by 29%, the grip strength by 56%, the Timed 25-Foot Walk was prolonged by 13% and the EQ-5D-5 L-Index value was impaired by 20%. The isokinetic strength was significantly more impaired at the wrist and ankle as compared to the elbow and knee, and one patient had lost ambulation because of instability at the ankle. Patients were considerably more fatigued and had substantially impaired hand dexterity, while mood, aerobic capacity, social adjustment, and working capacity were not affected. Regression analysis showed that lag-time until start of initial therapy lead to impaired long-term outcome without any effect of disease duration. Long-term prognosis in treated MMN is characterized by moderate to severe impairment primarily affecting dexterity and stability at the ankle. Our observations support previous observations that the long-term impairment in MMN might be improved following earlier start of therapy and that an effect of disease duration cannot be demonstrated.

Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy.

BACKGROUND AND PURPOSE: For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy. METHODS: A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. RESULTS: Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity. CONCLUSION: Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels.