Skip to main content Accessibility help
×
Home
Hostname: page-component-5d6d958fb5-lm9t2 Total loading time: 0.449 Render date: 2022-11-28T06:15:18.963Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": false, "useSa": true } hasContentIssue true

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Myelitis Presenting with Headache

Published online by Cambridge University Press:  11 February 2021

Jonathan D. Krett*
Affiliation:
Division of Neurology, Department of Clinical Neurosciences, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
Scott E. Jarvis
Affiliation:
Division of Neurology, Department of Clinical Neurosciences, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
Katayoun Alikhani
Affiliation:
Division of Neurology, Department of Clinical Neurosciences, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
*
Correspondence to: Jonathan D. Krett, Department of Clinical Neurosciences, University of Calgary, Foothills Medical Centre, 1403 - 29 Street NW, 12th Floor, Calgary, AlbertaT2N 2T9, Canada. Email: jonathan.krett1@ucalgary.ca
Rights & Permissions[Opens in a new window]

Abstract

Type
Letter to the Editor
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Canadian Journal of Neurological Sciences Inc.

Previously thought to be variants of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSDs) are now well recognized as distinct autoimmune CNS gliopathies. Reference Flanagan1 Diagnostic criteria from 2015 center around the occurrence of inflammatory lesions at one or more core clinical sites (including the optic nerves, spinal cord, and others), along with the presence of aquaporin-4 (AQP4)-IgG antibodies in serum, which target primarily astrocytes and initiate immune-mediated CNS damage. Reference Wingerchuk, Banwell and Bennett2 AQP4-seronegative patients need to meet more stringent clinical criteria to be classified as NMOSD. Approximately 1/4 to 1/3 of AQP4-seronegative patients are seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies, which find their antigen on oligodendrocytes. Reference Reindl and Waters3 Overall, clinical manifestations of MOG antibody disease (MOGAD) may resemble AQP4-positive NMOSD, but MOGAD has emerged as an entity with its own distinguishing features. Reference Weber, Derfuss, Metz and Brück4 Patients with NMOSD and MOGAD commonly experience neuropathic pain and headache as part of their illness. Reference Asseyer, Schmidt and Chien5 An observational study found that greater than 80% of 49 patients with NMOSD/MOGAD suffered from pain, including 5 of 12 MOGAD patients who experienced headache. Reference Asseyer, Schmidt and Chien5 These symptoms can also be the patient’s presenting concern, as we report here.

A 69-year-old right-handed man presented with 3 weeks of new-onset progressive, atraumatic headache. He described 10/10 “electric-shock”-like shooting pain radiating intermittently from the lateral neck up to the occiput and crown of the head. It was exacerbated by movement, but not by postural changes or Valsalva. He reported no migrainous features, no cranial autonomic symptoms, and no infectious symptoms. For the preceding 2 weeks, he also experienced gait ataxia, urinary hesitancy, and constipation. He reported no visual disturbance, bulbar dysfunction, sensory loss, or weakness. His medical history was notable for elevated body mass index, gastroesophageal reflux, and chronic erectile dysfunction. His only regular medication was rabeprazole. He was a former smoker of 40 pack-years and had no other pertinent exposures.

On examination, the patient was afebrile and hemodynamically stable. There was no nuchal rigidity, and his systemic examination was otherwise unremarkable. Cognition was intact. Afferent visual system and ocular fundus examinations were normal, as were the remaining cranial nerves. Motor exam showed bilateral arm and leg spasticity with preserved strength. Deep tendon reflexes were symmetric, with 2+ throughout, and 3+ at the brachioradialis and patellae bilaterally. He had no clonus and Hoffmann’s sign was absent bilaterally. Plantar responses were flexor. He reported allodynia in bilateral C2–C3 dermatomes. Vibratory sensation was diminished in both legs, returning to normal at the hips, without evidence of spinothalamic tract involvement. He exhibited mild bilateral dysmetria with finger-nose-finger testing and ambulated with a wide base. Romberg sign was positive.

CT-CT angiogram of the head and neck revealed no vascular cause for the symptoms. MRI of the cervical spine with gadolinium showed a T2-hyperintense, intramedullary lesion in the high cervical spinal cord (Figure 1), enhancing on post-gadolinium images (not shown). Gadolinium-enhanced cranial MRI was normal. Unenhanced MRI of the thoracic spine and conus medullaris was also normal. Evaluation included serum, CSF, and body imaging studies (results in Figure 2). A serum cell-based immunofluorescence assay performed at Mitogen Advanced Diagnostic Laboratories (Calgary, Alberta, Canada) discovered a high-positive 1:1000 anti-MOG-IgG titer and was negative for anti-AQP4-IgG. This was confirmed by Mayo Clinic Laboratories (USA) serum flow cytometry cell-based testing with positive anti-MOG-IgG (titer 1:1000).

Figure 1: MRI C-spine axial images (A–B) demonstrate a T2-hyperintense, intramedullary cord lesion (arrow). On sagittal view (C) the lesion extends from C1–C2 interspace to the C3 vertebral body without evidence of spondylotic compression at these levels (upper arrows). Incidental posterior intervertebral disk bulge at C6–C7 without associated spinal cord signal change can also be appreciated (lower arrow).

Figure 2: Summary of investigations. Anti-MOG-IgG and anti-AQP4-IgG testing was sent on serum only. Paraneoplastic panel tests were sent on both serum and CSF. Abbreviations: PCR = polymerase chain reaction; VZV = varicella zoster virus; HSV = herpes simplex virus; EV = enterovirus; Cytopath. = cytopathology; OCB = oligoclonal bands; TB = tuberculosis; ANA = anti-nuclear antibodies; ENA = extractable nuclear antigens; SPEP = serum protein electrophoresis; ACE = angiotensin-converting enzyme; MOG = myelin oligodendrocyte glycoprotein; AQP4 = aquaporin-4. Paraneoplastic antibody panel at Mitogen Advanced Diagnostic Laboratories tests for the following: Amphiphysin, Ri (NOVA-1), Yo, Hu, PNMA2 (Ma2/Ta), CV2.1, Recoverin, SOX1, Titin.

Treatment was initiated with 5 days of methylprednisolone 1 g intravenously daily, which resulted in rapid clinical and radiologic improvement. A 2-week taper of oral prednisone was prescribed at discharge, starting at a dose of 60 mg, decreasing by 10 mg every 3 days. A headache associated with ear and scalp tenderness, hand numbness, and chest tightness occurred 3 weeks following discharge, heralding a relapse which was treated by restarting oral prednisone with gradual tapering. A third relapse featuring symptoms of myelitis occurred off therapy approximately 8 months into the illness. Serum anti-MOG-IgG remained positive at 1 year (medium-positive; titer 1:100). The patient began long-term immunosuppression with azathioprine due to his recurrent symptoms.

A comprehensive evaluation determined that our patient’s symptoms were likely the result of MOGAD cervical myelitis. Consistent with this etiology, his symptoms and radiologic findings were responsive to corticosteroid treatment, and relapses occurred when they were weaned. The patient’s clinical onset occurred at an uncommonly advanced age. Of 50 MOG-IgG-seropositive patients with optic neuritis or myelitis, only 3 presented between 61–80 years of age with the median age of onset found to be 31 years (range 6–70). Reference Jarius, Ruprecht and Kleiter6

We hypothesize that our patient’s headache is attributable to spinal cord and possibly meningeal inflammation due to MOGAD. The pain was entirely responsive to treatment with steroids. Phenotypically, the headache resembles occipital neuralgia, as has been reported in other patients with high cervical myelitis. Reference Kissoon, Watson, Boes and Kantarci7 Allodynia was present in bilateral C2–C3 dermatomes, but unlike idiopathic occipital neuralgia, our patient experienced a more progressive, constant discomfort which was not reproduced by palpation over the occiput. Raised intracranial pressure (ICP) and aseptic meningitis have been documented in other patients with MOGAD; Reference Narayan, Wang, Sguigna, Husari and Greenberg8 however, clinicoradiologic features which usually accompany these entities were largely absent in our patient. Specifically, there was no worsening of the headache with recumbency or Valsalva, and optic disk edema was absent. A limitation is that we did not measure opening pressure during lumbar puncture to definitively exclude raised ICP. Recently, prodromal headaches reminiscent of migraine were reported in 49.6% of 129 MOG-IgG-seropositive optic neuritis patients, suspected to be related to peri-optic meningeal inflammation. Reference Asseyer, Hamblin and Messina9 Active myelitis was not a selection criterion for this cohort, and the headaches described differ in comparison to our patient, who had no classical migrainous features. Nevertheless, meningeal inflammation remains a putative headache contributor in our patient even though no leptomeningeal enhancement was detected using MRI. We speculate that the degree of meningeal inflammation in MOGAD exists on a continuum ranging from mild, imaging-occult disease to fulminant aseptic meningitis with raised ICP in some patients.

Pain negatively affects quality of life in patients with NMOSD and MOGAD and can be challenging to treat. Reference Asseyer, Schmidt and Chien5,Reference Qian, Lancia, Alvarez, Klawiter, Cross and Naismith10 Potential localizations for pain in these disorders span the CNS, from optic nerves to hypothalamus through the spinal cord. In addition to aforementioned headache mechanisms, pain may relate to the disruption of ascending nociceptive and descending antinociceptive pathways, disturbed excitatory–inhibitory balance, and central sensitization. Reference Bradl, Kanamori and Nakashima11 Further prospective study of symptom management in NMOSD and MOGAD is needed, since not all patients will have resolution of their symptoms with immunosuppression.

Acknowledgments

We thank the patient for providing informed consent to publish this case report.

Conflict of Interest

No conflicts of interest are declared by the authors.

Statement of Authorship

JDK, SEJ, and KA were involved in clinical care of the patient. JDK wrote the first draft of the manuscript and prepared the figures. SEJ and KA participated in manuscript revision and production of the final draft.

References

Flanagan, EP. Neuromyelitis optica spectrum disorder and other non-multiple sclerosis central nervous system inflammatory diseases. Continuum (Minneap Minn). 2019;25(3):815–44.Google ScholarPubMed
Wingerchuk, DM, Banwell, B, Bennett, JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177–89.10.1212/WNL.0000000000001729CrossRefGoogle ScholarPubMed
Reindl, M, Waters, P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019;15:89102.10.1038/s41582-018-0112-xCrossRefGoogle ScholarPubMed
Weber, MS, Derfuss, T, Metz, I, Brück, W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disord. 2018;11:1756286418762083.10.1177/1756286418762083CrossRefGoogle ScholarPubMed
Asseyer, S, Schmidt, F, Chien, C, et al. Pain in AQP4-IgG-positive and MOG-IgG-positive neuromyelitis optica spectrum disorders. Mult Scler J Exp Transl Clin 2018;4(3):205521731879668–12.Google ScholarPubMed
Jarius, S, Ruprecht, K, Kleiter, I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016;13:280.10.1186/s12974-016-0718-0CrossRefGoogle ScholarPubMed
Kissoon, NR, Watson, JC, Boes, CJ, Kantarci, OH. Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease. Cephalalgia. 2018;39(1):21–8.10.1177/0333102418769953CrossRefGoogle ScholarPubMed
Narayan, RN, Wang, C, Sguigna, P, Husari, K, Greenberg, B. Atypical anti-MOG syndrome with aseptic meningoencephalitis and pseudotumor cerebri-like presentations. Mult Scler Relat Disord. 2019;27:30–3.10.1016/j.msard.2018.10.003CrossRefGoogle ScholarPubMed
Asseyer, S, Hamblin, J, Messina, S, et al. Prodromal headache in MOG-antibody positive optic neuritis. Mult Scler Relat Disord. 2020;40:101965.10.1016/j.msard.2020.101965CrossRefGoogle ScholarPubMed
Qian, P, Lancia, S, Alvarez, E, Klawiter, EC, Cross, AH, Naismith, RT. Association of neuromyelitis optica with severe and intractable pain. Arch Neurol. 2012;69(11):1482–6.10.1001/archneurol.2012.768CrossRefGoogle ScholarPubMed
Bradl, M, Kanamori, Y, Nakashima, I, et al. Pain in neuromyelitis optica—prevalence, pathogenesis and therapy. Nat Rev Neurol. 2014;10(9):529–36.10.1038/nrneurol.2014.129CrossRefGoogle ScholarPubMed
Figure 0

Figure 1: MRI C-spine axial images (A–B) demonstrate a T2-hyperintense, intramedullary cord lesion (arrow). On sagittal view (C) the lesion extends from C1–C2 interspace to the C3 vertebral body without evidence of spondylotic compression at these levels (upper arrows). Incidental posterior intervertebral disk bulge at C6–C7 without associated spinal cord signal change can also be appreciated (lower arrow).

Figure 1

Figure 2: Summary of investigations. Anti-MOG-IgG and anti-AQP4-IgG testing was sent on serum only. Paraneoplastic panel tests were sent on both serum and CSF. Abbreviations: PCR = polymerase chain reaction; VZV = varicella zoster virus; HSV = herpes simplex virus; EV = enterovirus; Cytopath. = cytopathology; OCB = oligoclonal bands; TB = tuberculosis; ANA = anti-nuclear antibodies; ENA = extractable nuclear antigens; SPEP = serum protein electrophoresis; ACE = angiotensin-converting enzyme; MOG = myelin oligodendrocyte glycoprotein; AQP4 = aquaporin-4. Paraneoplastic antibody panel at Mitogen Advanced Diagnostic Laboratories tests for the following: Amphiphysin, Ri (NOVA-1), Yo, Hu, PNMA2 (Ma2/Ta), CV2.1, Recoverin, SOX1, Titin.

You have Access

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Myelitis Presenting with Headache
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Myelitis Presenting with Headache
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Myelitis Presenting with Headache
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *