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Nodoparanodopathy is a recent concept in the field of peripheral neuropathy, corresponding to peripheral nerve disorders stemming from an autoimmune attack directed and limited to the nodal region. This concept was identified using modern techniques of electrophysiology, immunology, and pathology (including electron microscopy). We present here what we believe to be the earlier well-documented case of nodoparanodopathy in the medical literature, based on an article written by Samuel Gilbert Webber (1838-1926) in 1884., (© 2019 American Academy of Neurology.)

A wide range of neuroimmunological diseases, referred to as autoimmune neuropathies, affect the peripheral nervous systems (PNS). The PNS is structurally diverse with complex anatomical compartments enriched in many different myelin and neuronal glycolipids, notably gangliosides. Autoimmune neuropathies are a proportion of autoimmune neuropathies mediated by autoimmune attack due to antibodies reactive with these compartmentally localized gangliosides. Antiganglioside antibodies are principally associated with the acute paralytic disease, Guillain-Barré syndrome, and are also found in several chronic autoimmune neuropathy syndromes. These antibodies may arise spontaneously from the natural autoantibody repertoire, or be induced by infections that share structurally similar glycans to gangliosides, an immunological process often referred to as molecular mimicry. The principal infection exhibiting this structural similarity is Campylobacter jejuni, which displays mimics of GM1, GD1a, GT1a, and other gangliosides on its surface lipo-oligosaccharide. Autoantibodies thus induced bind glycan epitopes on peripheral nerve gangliosides where they activate complement and recruit macrophages, causing structural and functional disorganization of nerve conduction. Chronic autoimmune neuropathies are also associated with naturally arising IgM antibodies directed against ganglioside epitopes present on disialylated gangliosides, that induce a sensory neuropathy, and on GM1, that induce a motor neuropathy. In a third syndrome, the so-called "anti-MAG" neuropathy, the antibodies bind a sulfated glucuronic acid epitope present on myelin-associated glycoprotein and the glycolipid sulfated glucuronyl paragloboside. This review will describe the immunological, pathological, and clinical features of these disorders in the context of our broader knowledge of the ganglioside glycobiology of the peripheral nervous system., (Copyright © 2018. Published by Elsevier Inc.)

A 12-year-old girl developed acute erythromelalgia of distal extremities. Physical, imaging and laboratory examinations failed to find an infective, systemic autoimmune, metabolic, endocrine, and vascular origin. The severe pain and allodynia indicated small-fiber neuropathy but muscle weakness suggested an involvement of large myelinated nerve fibers. This was confirmed by electrophysiological testing. High-dose then slowly tapered methylprednisolone resulted in rapid remission of painful erythromelalgia and complete electrophysiological recovery. Our case may suggest an additional variant to recently described steroid-responsive erythromelalgia with small-fiber axonopathy and may denote a transitory variant to Guillain-Barré syndrome or chronic dysimmune neuropathies.

The IgG molecule is the main component of IVIg. Commercial preparations of IVIg are derived from a pool of donors and subsequently, IVIg products contain smaller amounts of IgA and IgM antibodies as well as Th2 cytokines and cytokine antagonists that may also contribute to therapeutic effects. Numerous targets for IVIg include: T-cells, cytokines, immune cell trafficking, B-cells, complement and Fc-receptors. IVIg has been demonstrated to inactivate auto-reactive T-cells by competing for and interrupting their interaction with antigen presenting cells. The balance of cytokines also appears to be restored by IVIg, with studies showing that IVIg contains antibodies and antagonists to pro-inflammatory cytokines. In addition, IVIg is thought to interfere with and prevent the passage of auto-immune T-cells into the blood-nerve barrier. The effects of exogenous antibodies on B-cells have been well studied; IVIg is thought to down-regulate antibody production by B-cells, interfere with B-cell proliferation via a blockade of cell surface receptors and prevent the activation of certain subtypes of B-cell. In addition, IVIg can affect innate immunity by interrupting the steps in the complement activation cascade and blocking Fc-receptor mediated activity, which results in down-regulation of macrophage activity. In conclusion, IVIg has numerous modes of action, which culminate in the down-regulation of the immune response; many of which may be relevant to neuromuscular disorders and immune neuropathies.

The usefulness of functional scales has become clear in the past few years, to evaluate patients with dysimmune peripheral neuropathies. Functional scales which measure the real impact of the disease process in our patients will probably be increasingly used in future therapeutic trials. By contrast with neurological disorders leading to pure motor involvement, peripheral neuropathies are difficult to evaluate, due to their clinical polymorphism. However, efforts have been made in the past ten years in order to validate functional scales that may be routinely used by neurologists for dysimmune neuropathies. New scales will probably arise in the next few years, to be used in neuropathies from other causes. These scales will have to be strictly validated to be used in the daily medical practice.

The authors report four patients with a syndrome of painless bilateral isolated phrenic neuropathy. Electrophysiologic testing demonstrated active denervation restricted to the diaphragm. Long-term recovery was poor. The authors conclude that bilateral isolated phrenic neuropathy is a cause of painless diaphragmatic paralysis distinguishable from immune brachial plexus neuropathy and other neuromuscular disorders with similar clinical presentation.

Purpose of Review: The physiological properties of nerve and muscle are influenced by pathological changes and the aim of this review is to discuss recent contributions of electrophysiological studies to the understanding and diagnosis of selected peripheral nerve disorders. The relationships between pathology and physiology emphasize the close interdependence between electrophysiological studies, clinical deficits and other laboratory information. Attention should be paid to the strengths and limitations of electrophysiological methods, considering their impact on diagnosis and treatment of patients., Recent Findings: Several studies have shown particular pathophysiological profiles associated with different antibody subtypes in autoimmune peripheral neuropathies and this association further supports the suggestion of pathological specificity in both acute and chronic neuropathy. The sensitivity and specificity of physiological profiles therefore become increasingly important since some of these neuropathies are accessible to treatment. On the other hand, the pathophysiological and clinical profiles may be heterogeneous in patients with some disorders. This could be related to a more indistinct division between different types of pathology with increased understanding of pathogenetic mechanisms. Moreover, new insights into disturbed axonal function have stimulated attempts to develop methods to explore normal and diseased human nerve function., Summary: The exploration of axonal membrane and ion-channel function has become accessible using studies of excitability and are of potential value where conventional studies only provide nonspecific evidence of the number of fibers and the integrity of myelin. These studies will presumably become increasingly important in the years ahead considering the lack of understanding of the functional disturbances in axonal neuropathies.