慢性炎症性脱髄性多発神経炎／多巣性運動ニューロパチー

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nerves and nerve roots. It typically presents with symmetrical weakness of both proximal and distal muscles. Although cranial nerve involvement is rare, it can occasionally occur before the typical peripheral neuropathy develops. We report an unusual case of a 37-year-old woman in whom cranial neuropathy preceded peripheral demyelinating neuropathy. She initially presented with painful vision loss caused by compressive optic neuropathy due to trigeminal nerve hypertrophy. She later developed lower limb weakness, and characteristic MRI findings of cranial nerve hypertrophy together with persistent demyelinating changes on nerve conduction studies over a 2-year follow-up confirmed the diagnosis of CIDP. This case highlights the importance of considering CIDP in patients with painful ophthalmoplegia and cranial nerve hypertrophy. Early recognition of these atypical presentations may lead to earlier diagnosis, timely treatment, and better outcomes.

The immunobiology of Guillain-Barré syndrome (GBS) has long been organized around a dichotomy: acute motor axonal neuropathy (AMAN) is an antibody-mediated nodal disorder, whereas acute inflammatory demyelinating polyneuropathy (AIDP) has been interpreted mainly through T-cell-mediated models of compact-myelin injury. Four successive findings challenge this separation. Intraneural injection of GBS sera produced demyelination without transfer of immune cells; pathological studies in AIDP localized complement activation to the Schwann-cell surface before macrophage-associated myelin stripping. Serum IgG from a substantial subset of patients with AIDP bound nodal or paranodal surface domains; and identification of gelsolin-3 defined an AIDP subset in which patient IgG, together with active complement, produced nodal disruption before internodal demyelination. Peripheral-myelin-reactive T cells further indicate that T-cell-mediated and antibody-mediated immunity may coexist. Within this evidence hierarchy, AMAN and a subset of AIDP have distinct initiating targets but converge on nodal dysfunction. CD55 and CD59 are membrane-bound complement regulators: CD55 limits complement amplification, whereas CD59 prevents assembly of the membrane attack complex. Both are detectable in compact myelin but not at human nodes of Ranvier, revealing a localized discontinuity in complement control. This local absence of complement regulators may influence whether antibody binding progresses to conduction failure, axonal degeneration, or internodal demyelination, but should be regarded as a permissive substrate for injury rather than as evidence of lesion localization. Observations in chronic inflammatory demyelinating polyneuropathy (CIDP) suggest that antibody-mediated functional injury may precede structural demyelination. This Review proposes complement-regulated nodal vulnerability to integrate evidence across AMAN and subsets of AIDP and CIDP while preserving differences in targets, tempo, and mechanistic strength.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy characterized by progressive or relapsing weakness and sensory loss because of demyelination of peripheral nerves. CIDP has a higher prevalence in men and older adults. Immunopathogenesis involves both cellular and humoral mechanisms, including autoreactive T cells and macrophage-mediated demyelination. Typical CIDP presents with symmetric sensorimotor deficits, whereas atypical variants such as distal acquired demyelinating symmetric neuropathy, Lewis-Sumner syndrome, and motor- or sensory-predominant forms pose diagnostic challenges. Corticosteroids, intravenous immunoglobulin, and plasma exchange remain first-line treatments, although antibody-mediated subtypes often respond better to B-cell-directed therapy. The newly FDA-approved FcRn antagonist, efgartigimod alfa, provides a targeted option for adults with refractory CIDP. Accurate recognition of atypical and antibody-associated forms is essential for optimizing individualized management and improving outcomes.

INTRODUCTION: Efgartigimod is a human immunoglobulin G1 (IgG) antibody Fc fragment that reduces levels of circulating IgG, including pathogenic autoantibodies, by blocking neonatal Fc receptor. The original 1000-mg fixed-dose formulation of efgartigimod coformulated with recombinant human hyaluronidase PH20 for subcutaneous injection (PH20 SC) is supplied in a single-dose vial and administered with a separate syringe (V + S). To increase patient convenience, a 5-ml prefilled syringe (PFS) of efgartigimod PH20 SC has been developed. These studies examined the pharmacokinetics, injection speed, and usability of the efgartigimod PH20 SC PFS. METHODS: Bioequivalence of efgartigimod PH20 SC administered via PFS or V + S was assessed in an open-label study in healthy participants. Feasibility, safety, and tolerability of injecting efgartigimod PH20 SC at different injection speeds ranging from 20 to 60 s was examined in a separate open-label study in healthy participants. Finally, two human factor (HF) validation studies investigated usability of the efgartigimod PH20 SC PFS by participants with generalized myasthenia gravis (gMG) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and lay caregivers in a simulated at-home environment. RESULTS: Pharmacokinetic bioequivalence was established between efgartigimod PH20 SC administered by PFS and V + S. No meaningful differences were observed between mean fluid leakage/backflow volume at the injection site between the injection speed groups, and no meaningful differences in tolerability across injection speeds occurred. All participants in the HF studies successfully used the efgartigimod PH20 SC PFS and associated instructional materials without training to deliver the full injection volume in an average of 30 s. CONCLUSION: These studies support the bioequivalence, safety, and feasibility of an efgartigimod PH20 SC PFS. Both participants with gMG or CIDP and lay caregivers successfully administered the full dose of the efgartigimod PH20 SC PFS. Rapid-administration efgartigimod PH20 SC PFS is safe and feasible for both patients with autoimmune diseases and lay caregivers. TRIAL IDENTIFICATION NUMBER: ClinicalTrials.gov identifier: NCT05817435.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy typically characterized by a monophasic course and rapid progression of weakness. However, in a subset of patients, the clinical evolution may deviate from this expected pattern, creating important diagnostic challenges. Recurrence of symptoms, progression beyond eight weeks, or an atypical treatment response may suggest alternative diagnoses such as acute-onset chronic inflammatory demyelinating polyneuropathy or autoimmune nodopathies. Distinguishing these entities is essential because they differ in pathophysiology, clinical course, prognosis, and therapeutic strategies. Whereas GBS usually responds well to short-course immunotherapy, chronic inflammatory demyelinating polyneuropathy (CIDP), often requires maintenance immunomodulatory treatment, and IgG4 antibody-associated nodopathies may show limited response to intravenous immunoglobulin. In this manuscript, we review the clinical, electrophysiological, and temporal features that help distinguish recurrent GBS, acute-onset CIDP, and autoimmune nodopathies. We also discuss the importance of longitudinal clinical follow-up and serial electrophysiological studies for establishing an accurate diagnosis and guiding appropriate therapeutic management.