In the wide spectrum of diseases affecting the peripheral nervous system, antibody-associated disorders of the peripheral nerves, neuromuscular junction, and muscles are attracting a lot of attention in the past decade. One of the reasons is due to the advances in the understanding of autoantibodies which imitate the cascade of pathological changes in the peripheral nervous system, in the context of inflammatory neuropathies (acute or chronic), secondary neuropathies, disorders of the neuromuscular junction and anterior horn cells, and myopathies.
Inflammatory neuropathies are autoimmune-mediated disorders affecting the peripheral nervous system, including the large nerve fibers and the small nerve fibers. The pathophysiology of this disorder has gained increasing understanding over the years. Inflammatory neuropathies occur when an immune response to an antecedent infection or other event cross-reacts with shared epitopes on peripheral nerves, causing peripheral nerve inflammation and damage. Guillain-Barre syndrome (GBS) is the prototypic acute inflammatory neuropathy presenting with rapidly progressive, symmetrical, often ascending weakness of all extremities with variable sensory deficits that can develop in 4 weeks, while chronic inflammatory demyelinating polyradiculopathy (CIDP) is the commonest chronic inflammatory neuropathy, presenting with similar symptoms over two or more months and the course can be either chronically progressive or relapsing with stepwise progression. While autoantibodies that bind components of the axonal membranes, ion channels and neuronal receptors are implicated in various cases of GBS, the cellular structure or defined antigen of the target remains largely unknown. Similarly, autoantibodies against different nerve components, CD8+ T cells and various chemokines and cytokines have been implicated in the immunopathogenesis of CIDP, but further studies are required for elucidation of this complex milieu of immunological interactions. Small fiber neuropathy (SFN) is a condition that affects the small nerve fibers exclusively, which are in charge of temperature sensation, neuropathic pain, and autonomic dysfunction. By definition, the large nerve fibers are not involved. Autoantibodies have also been found to be associated with, or pathogenic for apparently idiopathic SFN.
Myasthenia gravis is an autoimmune-mediated disorder of the neuromuscular junction. Autoantibodies are directed against various receptors in the neuromuscular junction, affecting the synaptic transmission with subsequent muscle weakness and fatigue. The commonest autoantibody is directed against acetylcholine receptor, followed by muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane.
Many patients suffering from rheumatological disorders are commonly presented with polyneuropathies and myopathies. The presence of autoantibodies or sequelae of vasculitis can lead to various forms of polyneuropathies with severe disability. Severe pain, loss of proprioception and ataxia are common presentations.
Inflammatory myopathies (IIMs) include dermatomyositis (DM), polymyositis (PM), myositis as part of a rheumatic disease overlap syndrome, myositis of the antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). With the exception of IBM, these diseases share the clinical manifestation of progressive muscle weakness and the histopathologic finding of inflammatory infiltrate in muscle tissue.
Paraneoplastic disorders have an incidence that varies with the neurologic syndrome and type of tumor, and are found to be due to antibodies created by the tumor targeting components of the nervous system. Paraneoplastic syndromes affecting the peripheral nervous system can be organized by anatomically:
?Sensory neuronopathy – Paraneoplastic involvement of the dorsal root ganglia results in subacute sensory neuronopathy, with loss of vibratory sensation and joint position sense, sensory ataxia, and impaired pain and temperature sensation.
?Peripheral neuropathies – A variety of peripheral neuropathies have been described as paraneoplastic syndromes, including an acute sensorimotor radiculoneuropathy that is clinically identical to Guillain-Barré syndrome, chronic sensorimotor neuropathy, neuropathies associated with lymphoproliferative disorders, autonomic neuropathy (usually in combination with other areas of nervous system involvement), and multifocal mononeuropathy due to vasculitic neuropathy. Of note, recurrent gastrointestinal pseudo-obstruction (enteric neuropathy) can represent a paraneoplastic autonomic neuropathy related to myenteric plexus dysfunction, typically associated with anti-Hu antibodies.
?Neuromuscular junction disorders – Antibodies directed against voltage-gated calcium channels in presynaptic nerve terminals result in Lambert-Eaton myasthenic syndrome (LEMS). Myasthenia gravis (MG), is a paraneoplastic manifestation of a thymic tumor in approximately 10 percent of cases.
?Muscle syndromes – Paraneoplastic syndromes involving muscle include dermatomyositis, acute necrotizing myopathy, and neuromyotonia (peripheral nerve hyperexcitability, or Isaacs syndrome). Nerve hyperexcitability in combination with encephalopathy and sleep disorders (Morvan syndrome) can also be seen.
Despite the new advances in the field of antibody-associated peripheral nervous system, in many cases, epidemiological and diagnostic criteria may still be obscure, and pathogenic targets and mechanisms are still unknown, leading to ineffective therapies and vague prognoses. This research topic focuses on the spectrum of disorders affecting the peripheral nervous system which are associated with autoantibodies, and their epidemiological, diagnostic, pathophysiological and therapeutic advances originating from both clinical and experimental studies. By doing so, we hope to present the most recent, high-quality evidence in antibody-associated disorders of the peripheral nervous system.
We encourage the submission of original research reports, methods articles, perspectives, reviews, and mini-reviews on the above (but not limited to) topics.
In the wide spectrum of diseases affecting the peripheral nervous system, antibody-associated disorders of the peripheral nerves, neuromuscular junction, and muscles are attracting a lot of attention in the past decade. One of the reasons is due to the advances in the understanding of autoantibodies which imitate the cascade of pathological changes in the peripheral nervous system, in the context of inflammatory neuropathies (acute or chronic), secondary neuropathies, disorders of the neuromuscular junction and anterior horn cells, and myopathies.
Inflammatory neuropathies are autoimmune-mediated disorders affecting the peripheral nervous system, including the large nerve fibers and the small nerve fibers. The pathophysiology of this disorder has gained increasing understanding over the years. Inflammatory neuropathies occur when an immune response to an antecedent infection or other event cross-reacts with shared epitopes on peripheral nerves, causing peripheral nerve inflammation and damage. Guillain-Barre syndrome (GBS) is the prototypic acute inflammatory neuropathy presenting with rapidly progressive, symmetrical, often ascending weakness of all extremities with variable sensory deficits that can develop in 4 weeks, while chronic inflammatory demyelinating polyradiculopathy (CIDP) is the commonest chronic inflammatory neuropathy, presenting with similar symptoms over two or more months and the course can be either chronically progressive or relapsing with stepwise progression. While autoantibodies that bind components of the axonal membranes, ion channels and neuronal receptors are implicated in various cases of GBS, the cellular structure or defined antigen of the target remains largely unknown. Similarly, autoantibodies against different nerve components, CD8+ T cells and various chemokines and cytokines have been implicated in the immunopathogenesis of CIDP, but further studies are required for elucidation of this complex milieu of immunological interactions. Small fiber neuropathy (SFN) is a condition that affects the small nerve fibers exclusively, which are in charge of temperature sensation, neuropathic pain, and autonomic dysfunction. By definition, the large nerve fibers are not involved. Autoantibodies have also been found to be associated with, or pathogenic for apparently idiopathic SFN.
Myasthenia gravis is an autoimmune-mediated disorder of the neuromuscular junction. Autoantibodies are directed against various receptors in the neuromuscular junction, affecting the synaptic transmission with subsequent muscle weakness and fatigue. The commonest autoantibody is directed against acetylcholine receptor, followed by muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane.
Many patients suffering from rheumatological disorders are commonly presented with polyneuropathies and myopathies. The presence of autoantibodies or sequelae of vasculitis can lead to various forms of polyneuropathies with severe disability. Severe pain, loss of proprioception and ataxia are common presentations.
Inflammatory myopathies (IIMs) include dermatomyositis (DM), polymyositis (PM), myositis as part of a rheumatic disease overlap syndrome, myositis of the antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). With the exception of IBM, these diseases share the clinical manifestation of progressive muscle weakness and the histopathologic finding of inflammatory infiltrate in muscle tissue.
Paraneoplastic disorders have an incidence that varies with the neurologic syndrome and type of tumor, and are found to be due to antibodies created by the tumor targeting components of the nervous system. Paraneoplastic syndromes affecting the peripheral nervous system can be organized by anatomically:
?Sensory neuronopathy – Paraneoplastic involvement of the dorsal root ganglia results in subacute sensory neuronopathy, with loss of vibratory sensation and joint position sense, sensory ataxia, and impaired pain and temperature sensation.
?Peripheral neuropathies – A variety of peripheral neuropathies have been described as paraneoplastic syndromes, including an acute sensorimotor radiculoneuropathy that is clinically identical to Guillain-Barré syndrome, chronic sensorimotor neuropathy, neuropathies associated with lymphoproliferative disorders, autonomic neuropathy (usually in combination with other areas of nervous system involvement), and multifocal mononeuropathy due to vasculitic neuropathy. Of note, recurrent gastrointestinal pseudo-obstruction (enteric neuropathy) can represent a paraneoplastic autonomic neuropathy related to myenteric plexus dysfunction, typically associated with anti-Hu antibodies.
?Neuromuscular junction disorders – Antibodies directed against voltage-gated calcium channels in presynaptic nerve terminals result in Lambert-Eaton myasthenic syndrome (LEMS). Myasthenia gravis (MG), is a paraneoplastic manifestation of a thymic tumor in approximately 10 percent of cases.
?Muscle syndromes – Paraneoplastic syndromes involving muscle include dermatomyositis, acute necrotizing myopathy, and neuromyotonia (peripheral nerve hyperexcitability, or Isaacs syndrome). Nerve hyperexcitability in combination with encephalopathy and sleep disorders (Morvan syndrome) can also be seen.
Despite the new advances in the field of antibody-associated peripheral nervous system, in many cases, epidemiological and diagnostic criteria may still be obscure, and pathogenic targets and mechanisms are still unknown, leading to ineffective therapies and vague prognoses. This research topic focuses on the spectrum of disorders affecting the peripheral nervous system which are associated with autoantibodies, and their epidemiological, diagnostic, pathophysiological and therapeutic advances originating from both clinical and experimental studies. By doing so, we hope to present the most recent, high-quality evidence in antibody-associated disorders of the peripheral nervous system.
We encourage the submission of original research reports, methods articles, perspectives, reviews, and mini-reviews on the above (but not limited to) topics.
