Neuroinflammation, Neuroautoimmunity and Functional Disorders

This article is worth reading:

Neuroinflammation, Neuroautoimmunity, and the Co-Morbidities of Complex Regional Pain Syndrome

Quotes:
"Complex Regional Pain Syndrome (CRPS) is associated with non-dermatomal patterns of pain, unusual
movement disorders, and somatovisceral dysfunctions. These symptoms are viewed by some neurologists and psychiatrists as being psychogenic in origin. Recent evidence, however, suggests that an autoimmune attack on self antigens found in the peripheral and central nervous system may underlie a number of CRPS symptoms."

“For a substantial fraction of adult CRPS cases initiation of CRPS may lie in a breakdown of immunologic self-tolerance, and the development of autoantibodies to the β2AR and M2R neurotransmitter receptors. Once autoantibodies have been generated to these neuroantigens in a given individual, an ongoing progression of stereotyped autoimmune-mediated neuroinflammatory responses might become initiated.”

“In CRPS patients, features of central sensitization appear to involve a complex set of neuroinflammatory responses involving NMDA receptors, glial cell activation in the spinal cord as well as the release of pro-inflammatory cytokines from neurons, glia, and leukocytes. Extravasation of leukocytes and exudation of autoantibodies into the parenchyma of the nervous system are key features of central sensitization during a neuroautoimmune attack of the CNS. The autoimmune attack is focused on sites where autoantibodies bind. Autoimmune attack can potentially lead to the loss of GABAergic inhibitory interneurons.”

“Instead of autoimmune-mediated neuroinflammation, the term “medically unexplained symptoms” has often been used to describe sensory, autonomic, and motor symptoms of CRPS patients, even though there is an extensive literature describing neurophysiological pathologies and mechanisms in these patients. There are several inherent difficulties with the psychogenic hypothesis. However, absence of evidence is not evidence of absence. In addition, characteristics such as the speed of onset and remission have also been used to assign symptoms to neurological vs. psychogenic causes, with the assumption that neurological disease processes have a longer timecourse than psychogenic ones. In this regard, rapid onset and rapid remission have often been used as criteria for diagnosing psychogenic movement disorders, even though autoimmune disorders are well know for their cyclic character of remission and relapse.”

“Conclusion
In clinical practice, when an organic explanation cannot be found for functional disorders, psychogenic etiologies are often asserted. However, as the understanding of functional disorders improves, it appears that neuroimmune and neuroinflammatory disorders are much more common than previously thought. Neuroautoimmunity combined with neuroinflammation together provide a viable etiology for the relapsing-remitting chronicity, atypical presentation and intensity of neurological and psychiatric symptoms. When faced with medically unexplained symptoms, health practitioners and patients should actively seek physiological hypotheses, as an alternative to diagnoses of somatoform or conversion disorders. Neuroinflammatory lesions, along with their functional consequences, should always be considered in the differential diagnosis of medically unexplained symptoms, even when commonly used clinical neuroimaging protocols fail to reveal positive evidence of neuroinflammation. When viewing the symptoms of an individual patient, health practitioners should anticipate that a given patient might have a complex, multifocal pattern of neuroinflammation and associated functional symptoms. The presentation of symptoms may be idiosyncratic to that patient, depending on the topographic pattern and severity of neuroinflammation and other variables, often yet undiscovered. However, key mechanistic elements of spreading neuroinflammation could be common to a wide spectrum of patients and disorders. By integrating neuroinflammation and neuroautoimmune concepts into the differential diagnosis of neurological and neuropsychiatric symptoms, a number of functional sensory and motor disorders may become less medically unexplainable than was previously thought. As diagnostic methods continue to improve, it may someday be possible for neuroautoimmuity and neuroinflammation to be commonly assessed as a part of a differential diagnosis of chronic pain syndromes such as CRPS.”