Adverse Events of Special Interest (AESI) and Related Risks: Acute myelitis

Acute myelitis falls within the neurological category of adverse events of special interest (AESI), and has a proven association with immunization with several different vaccines (1). There are numerous underlying causes of acute myelitis, including infectious, toxic, neoplastic, autoimmune, and metabolic etiologies (2).   

Definition: There are three important levels of certainty, based on clinical and laboratory characteristics. The characteristic findings of spinal cord biopsy for myelitis are sufficient to establish level 1, but this is considered rare. In order to establish level 2 or 3, it is essential to document at least one feature of myelopathy in addition to evidence of spinal cord inflammation (fever, CSF pleocytosis, CT/MRI findings characteristic of myelitis), and the absence of alternative diagnoses. If features of encephalitis or ADEM (acute disseminated encephalomyelitis) are present, in addition to myelitis, the level of certainty for myelitis should be determined, and should include an evaluation of the tools used in the particular case to diagnose encephalitis/ADEM. Myelitis can occur in combination with encephalitis. If this is the case, and if there is the same level of certainty for both, the diagnosis is encephalomyelitis.  

Diseases and other factors: Autoimmune/connective tissue disease, Bechet’s disease, Sjogren's syndrome, neoplastic, thyroid, mixed connective tissue disease; systemic lupus erythematosus;

antiphospholipid antibody syndrome; systemic sclerosis; urticarian vasculitis; systemic vasculitis; perinuclear ANCA (anti-neutrophil cytoplasmic antibodies); nutritional deficiency: vitamin B12, vitamin E, copper; conditions causing spinal cord compression; spinal cord tumors; abscesses or post-transplant conditions ; graft-versus-host disease; common variable immunodeficiency; conditions that resulted in spinal cord radiation therapy, which would be important in assessing causality.

Bacterial infections caused by the mycobacterium tuberculosis bacterium; Borrelia burgdorferi (Lyme disease); Treponema pallidum (neurosyphilis); Mycoplasma pneumoniae, Campylobacter jejuni, Chlamydia species, Legionella pneumoniae, brucellosis, groups A and B beta hemolytic streptococcus, Salmonella paratyphi B, Acinetobacter baumanii, orientia tsutsugamushi (scrub typhus).

Parasitic infections: Toxocara species; species of Schistosoma, Gnasthostoma spinigerum, Echinococcus granulosus, Toxoplasma gondii, species of Acanthamoeba, Trypanosoma brucei, Taenia solium, Gnasthostoma spinigerum, Paragonimus westermani, Neurocysticercosis.

Fungal infections: Actinomyces species, Blastomyces species, Coccidioides immitis, Aspergillus species, Cryptococcus species, Cladophialophora bantiana vaccine (3).

Medications: TNF-alpha inhibitors, sulfasalazine, epidural anesthesia, chemotherapeutic agents, heroin, benzene, brown recluse spider toxin (3).  

Vaccines in general: Evidence for the link between MMR, VZV, influenza, hepatitis A/B, HPV, DTaP, meningococcal vaccines, and ADEM has been reviewed, and the overall evidence was insufficient to either accept or reject a causal relationship. It should be noted that immune-mediated mechanisms include autoantibodies, T cells, and molecular mimicry.

Window of risk for myelitis as a vaccine-related reaction:

• Inactivated or subunit vaccines: Immune-mediated mechanism for myelitis, probably as ADEM, where the recommended window of risk for people is 2 to 42 days, and for epidemiological studies, 5 to 28 days for primary analysis and 2 to 42 days for secondary analysis.
• Live attenuated vaccines: This should be based on the incubation period of the vaccine strain, adding, as stated above, 5 to 28 days after the end of the incubation period for primary analysis, and 2 to 42 days after the end of the incubation period for secondary analysis (3).

 Sources:

1. Safety Platform for Emergency Vaccines (SPEAC) - D2.3 Priority List of Adverse Events of Special Interest:
   COVID-19 - Authors: Barbara Law, Miriam Sturkenboom,V2.0, Date: May 25, 2020.
2. SPEAC - Work Package: WP2 Standards and tools, V1.0 – February 15, 2021, Author: Barbara Law. Nature: Report | Diss. level: Public https://brightoncollaboration.us/wp-content/uploads/2021/03/SPEAC_D2.5.2.1_Generalised-Convulsion-Case-Definition-Companion-GuideV1.0_format12068-1.pdf
3. Barbara Law. Safety Platform for Emergency Vaccines SO2- D2.5.2.1 - AESI Case Definition Companion Guide for 1st Tier AESI. Acute Myelitis Work Package: WP2 Standards and tools, V3.0,  February 13, 2021, Nature: Report | Diss. level: Public. https://brightoncollaboration.us/wpcontent/uploads/2021/03/SPEAC_D2.5.2.1_Myelitis-Case-Definition-CompanionGuide_V3.0_13Feb2021_format12066-1.pdf