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Peer Reviewed

Photoclinic

Longitudinally Extensive Transverse Myelitis: A Rare Neuromyelitis Optica Spectrum Disorder

Volume 61 - Issue 3 - March 2021

AUTHORS:
Aman Deep, MD • Andrew N. Wilner, MD

AFFILIATIONS:
Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee

CITATION:
Deep A, Wilner AN. Longitudinally extensive transverse myelitis: a rare neuromyelitis optica spectrum disorder. Consultant. 2021;61(3):e22-e23. doi:10.25270/con.2020.09.00013

Received May 10, 2020. Accepted August 29, 2020. Published online September 22, 2020.

DISCLOSURES:
The authors report no relevant financial relationships.

CORRESPONDENCE:
Aman Deep, MD, Department of Neurology, University of Tennessee Health Science Center, 920 Madison Ave, Memphis, TN 38163 (mintusm2000@gmail.com)

 

A 57-year-old woman with a history of hypertension and polysubstance abuse presented with 2 weeks of progressive bilateral lower-extremity weakness.

Motor examination findings were normal in the upper extremities, but she had 2/5 strength in the bilateral lower extremities in both the proximal and distal musculature. Deep tendon reflexes were normal in the bilateral upper extremities but brisk bilaterally in the patellae and ankles. Babinski test results were equivocal.

Lumbar puncture revealed pleocytosis, with total white blood cell count of 700 with 84% lymphocytes. The cerebrospinal fluid protein level was increased to 105 mg/dL. The serum neuromyelitis optica (NMO) immunoglobulin G (IgG) antibody titer result was extremely high at 270.1 U/mL, confirming the diagnosis of NMO spectrum disorder (NMOSD).

Magnetic resonance imaging (MRI) of the cervical, thoracic, and lumbar spine with and without contrast showed extensive cord edema involving the cervical (Figures 1 and 2) and thoracic cord segments (Figure 3). This extensive inflammation extending over 3 or more vertebral spinal cord sections further characterized the diagnosis as longitudinally extensive transverse myelitis (LETM). Results of MRI of the brain were unremarkable.

Fig 1
Figure 1. Axial T2-weighted MRI of the cervical spine showing central cord edema sparing the spinal cord periphery.

Fig 2
Figure 2. Sagittal T2-weighted MRI of the cervical showing cord edema beginning at C2 and extending through C7. Edema is wide and spares the periphery.

Fig 3
Figure 3. Sagittal T2-weighed MRI showing cord edema throughout the thoracic spine.

The patient was administered intravenous methylprednisolone, 1 g/day for 5 days, followed by azathioprine maintenance therapy. Over the next 2 weeks, the patient’s weakness improved significantly, and she was discharged to a rehabilitation facility.

Discussion. Longitudinally extensive transverse myelitis (LETM) is defined as inflammation that extends over 3 or more vertebral spinal cord sections.1 It is a rare presentation of neuromyelitis optica spectrum disorder (NMOSD) and rarely is associated with multiple sclerosis and Sjögren syndrome. NMOSD is an umbrella term used for a syndrome that presents with a wide variety of neurologic symptoms that may involve sensory, motor, and autonomic pathways. NMOSD is associated with NMO IgG antibodies that bind selectively to the aquaporin-4 protein (AQP4).

NMOSD can manifest as a single event or with multiple relapses. These events include LETM symptoms, which vary from sensory loss, paraparesis, and quadriparesis to bladder/bowel function disturbances.2 LETM can also present with an acute brainstem syndrome with nystagmus, diplopia, and various other cranial nerve palsies. Another presentation is area postrema syndrome, which includes intractable nausea, vomiting, and/or hiccups. Narcolepsy may also develop, possibly due to impaired release of hypocretin from bilateral hypothalamic regions in which AQP4 is highly expressed.3,4 Various vascular, infectious, neoplastic, traumatic brain injury, and nutritional deficiencies have also been reported in association with LETM.5

The presence of NMO IgG antibodies confirms the diagnosis of NMOSD and is also a risk factor for further relapses. There is no clear single etiology of NMOSD, but its association with autoimmune, infectious, metabolic, and ischemic disorders has been described.

Acute treatment relies on high-dose corticosteroids (1 g/day for 3-5 days) and/or plasmapheresis (plasma exchange). For maintenance therapy, azathioprine, rituximab, and mycophenolate are often used. Intravenous immunoglobulin (IVIG) and other immunosuppressive agents are additional options.6

In 2019, the Food and Drug Administration approved eculizumab for NMOSD relapse prevention. Eculizumab is a monoclonal antibody that, by binding to complement component 5 (C5), inhibits the cleavage and release of C5a and C5b, which prevents the formation of the membrane attack complex C5b-9. Phase 3 trials of inebilizumab and satralizumab were also completed in 2019 with promising results.7 Bevacizumab, which selectively binds and inhibits vascular endothelial growth factor A and stabilizes the blood-brain barrier, has shown good response as an adjunctive therapy with corticosteroids. C1 esterase inhibitor showed good tolerance when combined with intravenous corticosteroids in AQP4 IgG-positive NMOSD patients. Ublituximab, which targets CD20-positive B cells, is also under investigation as an adjunctive therapy with corticosteroids for NMOSD.8

Our patient showed good response to therapy with corticosteroids and azathioprine. This case is notable for the patient’s classic symptoms, extreme lesion length, the high NMO titer, and the patient’s impressive response to treatment despite extensive spinal cord involvement.

REFERENCES:

  1. Chee CG, Park KS, Lee JW, et al. MRI features of aquaporin-4 antibody-positive longitudinally extensive transverse myelitis: insights into the diagnosis of neuromyelitis optica spectrum disorders. AJNR Am J Neuroradiol. 2018;39(4):782-787. doi:10.3174/ajnr.A5551
  2. Nightingale H, Witherick J, Wilkins A. Diagnosis of longitudinally extensive transverse myelitis. BMJ Case Rep. 2011;2011:bcr1020103444. doi:10.1136/bcr.10.2010.3444
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  5. Trebst C, Raab P, Voss EV, et al. Longitudinal extensive transverse myelitis—it’s not all neuromyelitis optica. Nat Rev Neurol. 2011;7(12):688-698. doi:10.1038/nrneurol.2011.176
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  7. Pardo S, Giovannoni G, Hawkes C, Lechner-Scott J, Waubant E, Levy M. Editorial on: Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2019;33:A1-A2. doi:10.1016/j.msard.2019.07.001
  8. Romeo AR, Segal BM. Treatment of neuromyelitis optica spectrum disorders. Curr Opin Rheumatol. 2019;31(3):250-255. doi:10.1097/BOR.0000000000000603