Longitudinally extensive transverse myelitis following ChAdOx1 nCoV-19 vaccineAJ Shetty, A Rastogi, V Jha, A Sudhayakumar
Department of Endocrinology and Metabolism, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_1047_21
Source of Support: None, Conflict of Interest: None
Keywords: Adverse event, corticosteroids, COVID-19 vaccine, SARS-CoV-2, transverse myelitis
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has claimed countless lives all over the world, but 2020 also has seen 58 vaccines against SARS-CoV-2 being developed including some in clinical trials. Widespread vaccination against novel COVID 19 has been implemented globally for breaking the chain of transmission. Although vaccination has been associated with autoimmune sequelae, relatively few of these complications have been reported in association with the vaccine to date, despite its extensive use. Herein, we report a rare case of longitudinally extensive (LE) transverse myelitis (TM), that occurred shortly after vaccination with the COVISHIELD vaccine.
A 59-year-old female presented with acute urinary retention with intact bladder sensation and constipation for 15 days, followed by numbness and gradually progressive weakness involving bilateral lower limbs for 10 days. Numbness of the legs gradually extended up to the costal margin and was associated with band like sensation. She reported no prior neurological symptoms, respiratory, gastrointestinal illness, or fever preceding the onset of symptoms. She had received the first dose of ChAdOxx1 nCoV-19 (recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein, COVISHIELD) vaccine intramuscular 5 days prior to the onset of symptoms. There was no prior history of testing positive for COVID or history of any other vaccinations including hepatitis B in the past 1 year.
On neurological examination, she had paraplegia (Medical Research Council Muscle Scale 3/5) involving proximal and distal muscle groups with hypotonia and diffuse hyperreflexia but normal power and tone in the upper limbs. Plantar response was extensor. Abdominal reflexes were absent. All modalities of sensations were diminished below the sixth thoracic segmental level. Higher mental functions and cranial nerve examination revealed no abnormality. A provisional diagnosis of transverse myelitis and neuromyelitis optica was considered. Other differentials that were considered were multiple sclerosis and vasculitis with multi-system involvement.
On the day of admission, haemogram, renal, liver, and thyroid function tests were within normal limits. Viral serology for hepatitis B, hepatitis C, and Human immunodeficiency virus I and II were negative. Her chest X-ray was normal. Antinuclear antibodies, Anti-neutrophil cytoplasmic antibodies, aquaporin-4 antibodies & Anti myelin oligodendrocyte glycoproteins antibodies were undetectable. Nasopharyngeal swab for Reverse Transcription-polymerase chain reaction test to detect SARS-CoV-2 was negative on admission. Lumbar puncture was performed for cerebrospinal fluid (CSF) study which revealed lymphocytic pleocytosis with 207 cells (98% lymphocytes) and elevated protein levels (71 mg/dL); gram stain was negative. CSF evaluation for tuberculosis was negative. Contrast-Enhanced Magnetic Resonance Imaging of the brain was normal. On Day-2 of admission, T2-weighted MRI imaging of the dorsal spine revealed hyperintensity in the spinal cord involving the cervical cord and lower thoracolumbar cord (D7 – L1), suggestive of longitudinally extensive transverse myelitis (LETM) [Figure 1]. Subsequent nerve conduction studies of sural, median, and ulnar nerves (D-3 of admission) were normal. A diagnosis of LETM was corroborated secondary to vaccination considering the temporal correlation with ChAdOxx1 nCoV-19 vaccine.
Daily intravenous methylprednisolone at a dose of 1 g/day (pulse therapy) was started following a lumbar puncture on the day of admission with a clinical diagnosis (provisional) of transverse myelitis. MRI done on the second day of admission was consistent with the diagnosis of myelitis and steroid was continued. After three doses of pulse steroid, subjective improvement in the power of the lower limb in the form of raising her legs against resistance was noticed. The patient was able to feel all forms of sensations up to the medial aspect of the bilateral ankle. After five days of pulse therapy (D-6), she was switched over to oral prednisolone (1 mg/kg). Her symptoms significantly improved (end of first week) with steroids and she was able to walk with no difficulty, able to void, and pass stool on her own. She was discharged after one week of admission and followed weekly (telephonically), that confirmed remission. Subsequently, steroids were tapered off over 6 weeks.
Herein, we describe the first case of LETM as a serious adverse event (SAE) following COVID vaccination from India. Though some cases of transverse myelitis have been described in the past following hepatitis B virus, measles-mumps-rubella, diphtheria-tetanus-pertussis, and others, it is still not a common complication following vaccination., A systemic review identified only 37 cases of transverse myelitis following vaccination other than COVID. Transverse myelitis as an adverse event to COVID vaccine was first identified during Astra Zeneca's COVID-19 vaccine trial as an association with vaccine. However, the causal relationship of vaccination with TM has not yet been well established. The concept of molecular mimicry has been postulated whereby in genetically predisposed individuals the offending agent triggers an autoimmune response to the myelin sheath of the central tracts of the spinal cord. Similarly, the suggested association in the present case is based on temporal events lacking confirmatory evidence (WHO AEFI causality level “consistent causal association” or demonstration of rising COVID antibody titer.
LETM is defined as the involvement of more than three consecutive vertebral segments. The response to treatment for LETM is variable, with one study showing complete recovery in 41.2% of patients treated with methylprednisolone. Following the introduction of Covid-19 vaccines, reports of transverse myelitis following COVID vaccination have emerged, with very few being longitudinally extensive lesions.,,,,,,, The response to steroids,,,,, or plasmapheresis, has been favorable in general with complete or near-complete recovery, although Nakano et al. reported a case of an 85-year-old man who did not respond to immunosuppression. Similarly, in our case, the lady responded dramatically to intravenous steroids. This seems to suggest that although the myelitis associated with the COVID vaccine tends to involve multiple segments, the prognosis seems to be favorable as the response to treatment is robust.
To our knowledge, this is the first report of extensive transverse myelitis following ChAdOxx1 nCoV-19 vaccination from India. Transverse myelitis is an uncommon complication following COVID vaccination, which can be longitudinally extensive but shows a good response to immunosuppression.
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