Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies

Abstract

Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the central nervous system (CNS). Pain is highly prevalent and debilitating in NMOSD and MOGAD with a severe impact on quality of life, and there is a critical need for further studies to successfully treat and manage pain in these rare disorders. In NMOSD, pain has a prevalence of over 80%, and pain syndromes include neuropathic, nociceptive, and mixed pain, which can emerge in acute relapse or become chronic during the disease course. The impact of pain in MOGAD has only recently received increased attention, with an estimated prevalence of over 70%. These patients typically experience not only severe headache, retrobulbar pain, and/or pain on eye movement in optic neuritis but also neuropathic and nociceptive pain. Given the high relevance of pain in MOGAD and NMOSD, this article provides a systematic review of the current literature pertaining to pain in both disorders, focusing on the etiology of their respective pain syndromes and their pathophysiological background. Acknowledging the challenge and complexity of diagnosing pain, we also provide a mechanism-based classification of NMOSD- and MOGAD-related pain syndromes and summarize current treatment strategies.

Patient-reported burden of symptoms in neuromyelitis optica: A secondary analysis on pain and quality of life

“…While clinicians may prioritize relapse prevention [8], patients are often concerned about the relief of ongoing symptoms from previous relapses, including pain related to optic neuritis, headaches, neuropathic pain, tonic spasms, spasticity and back pain, which can affect quality of life (QoL) [9][10][11][12][13]. Pain severity and especially neuropathic character of pain are associated with depression [10].…”

“…Studies suggest that the number of relapses are not correlated with pain severity [15,20]. There is also conflicting evidence regarding the impact of AQP4-IgG serostatus on pain severity and pain-related disability [12,17,18], although it is hypothesized that the loss of AQP4 can result in elevated extracellular concentrations of neurotransmitters that contribute to chronic pain [13].…”

Neuroimaging findings in MOGAD -- MRI and OCT

“…Typical symptoms include motor and/or sensory deficits (numbness), bladder, bowel, and/or erectile dysfunction (41). Neuropathic pain has been implicated in NMOSD to be related to the level(s) at which spinal cord lesion(s) are located, which could be the case in MOGAD patients as well, since the 86% of MOGAD patients in one study reportedly suffered from chronic pain (42)(43)(44)(45). Clinical differences distinguishing myelitis in MOGAD vs. MS or AQP4-NMOSD are: a higher percentage of patients are male, frequency of bladder and erectile dysfunction, younger age, prodromal infection and concurrent ADEM.…”

Pain, depression, and quality of life in adults with MOG‐antibody–associated disease

“…In MOGAD, data on pain are scarce, and clinical case reports and series often ignore pain as a severe symptom. However, ON-related headache or periorbital pain, neuropathic pain, including radiculopathylike pain, and musculoskeletal pain have all been described anecdotally and can severely affect the patient's well-being [4,12,[14][15][16][17].…”