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Modulatory Effects on Axonal Function After Intravenous Immunoglobulin Therapy in Chronic Inflammatory Demyelinating Polyneuropathy

Cindy Shin-Yi Lin, PhD; Arun V. Krishnan, PhD; Susanna B. Park, PhD; Matthew C. Kiernan, DSc
Arch Neurol. 2011;68(7):862-869. doi:10.1001/archneurol.2011.137.
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Objective  To investigate the immediate and longitudinal mechanisms of action of intravenous immunoglobulin (IVIg) on axonal function in chronic inflammatory demyelinating polyneuropathy (CIDP).

Design  Prospective single-center study.

Setting  Hospitals and outpatient clinics.

Participants  Clinical and functional assessment, nerve conduction studies, and 526 motor excitability studies were undertaken in 27 patients, matched before and immediately after infusion and followed up longitudinally.

Main Outcome Measures  Axonal excitability variables were measured before and immediately after infusion and compared with matched studies and findings in healthy controls.

Results  Immediately after infusion, patients demonstrated decreased threshold, with significant reduction in strength-duration time constant (P = .003), reduction in accommodation to depolarization (P = .04), and reduced threshold change during hyperpolarization (P = .003), accompanied by significant decreases in superexcitability (P = .03) and subexcitability (P = .02). In contrast, changes were absent in disease controls, confirming a specific IVIg action in CIDP patients. Longitudinally, changes correlated with clinical improvement (mean [SE] increase in the Medical Research Council sum score, 2.7 [0.7]; P = .005). Increased compound muscle action potential amplitude was associated with reduction in terminal latency (correlation coefficient, −0.65; P = .02). In addition, these changes translated into improvement in functional assessment with the adjusted Inflammatory Neuropathy Cause and Treatment score, which demonstrated a significant correlation with nerve excitability variables longitudinally (P = .01).

Conclusions  Findings from the present series establish a modulatory effect of IVIg on axonal function in CIDP patients, suggesting that IVIg stabilizes axonal membrane potential and promotes axonal recovery.

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Figures

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Figure 1. Patterns of modulation of motor excitability with intravenous immunoglobulin (IVIg) treatment in a single representative patient. Motor excitability recordings were obtained at preinfusion (open), 1 week postinfusion (solid) and 2 weeks postinfusion (gray). Strength-duration time constant (SDTC) (A), threshold electrotonus (B), recovery cycle (C), and changes in SDTC within the same infusion and longitudinally (22 months) in a single patient (D) are depicted. TEh indicates hyperpolarizing threshold electrotonus.

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Figure 2. Changes in motor excitability with intravenous immunoglobulin (IVIg) treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Motor excitability variables are reported as mean (SE) before and after a single IVIg infusion in CIDP patients. The threshold to elicit a 50% maximum response decreased after the infusion (A), and reductions were observed in the strength-duration time constant (SDTC) (B), S2 accommodation (C), and hyperpolarizing threshold electrotonus (TEh) (90-100 ms) (D). The recovery cycle demonstrated a significant decrease in superexcitability (E) and in subexcitability (F). NS indicates not significant (P = .15). * P < .01. † P < .05.

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Figure 3. Longitudinal changes with intravenous immunoglobulin (IVIg) treatment in patients with chronic inflammatory demyelinating polyneuropathy. Longitudinal changes in motor axons with IVIg treatment are depicted in strength-duration time constant (SDTC) (A), stimulus for 50% maximum response (B), depolarizing threshold electrotonus (TEd) (90-100 ms) (C), hyperpolarizing TE (TEh) (90-100 ms) (D), superexcitability (E), and Medical Research Council (MRC) sum score (F). * P < .05. † P < .01.

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Figure 4. Normalization of motor excitability longitudinally with intravenous immunoglobulin (IVIg) treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Histograms (mean [SE]) of significant nerve excitability variable changes before and after longitudinal IVIg treatment in motor axons were compared with values in healthy control participants (HC). Strength-duration time constant (SDTC) was significantly shortened in CIDP patients initially compared with HCs (A). Rheobase was significantly reduced with long-term IVIg treatment (B). Reduced accommodation to depolarizing currents (TEd) (90-100 ms) in CIDP patients initially compared with HCs (C). Reduced accommodation to hyperpolarizing currents (TEh) (90-100 ms) in CIDP patients initially compared with HCs (D). Normalized superexcitability in CIDP patients with long-term IVIg treatment (E), and a trend toward normalized subexcitability in CIDP patients with long-term IVIg treatment (F). NS indicates not significant. * P < .01. † P < .001.

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