|Ahead of print publication
COVID-19 associated myelitis: A case series
Pravin Naphade, Sravya Kotharu, Shalesh Rohatgi, Satish Nirhale, Prajwal Rao
Department of Neurology, Dr. DY Patil Medical College, Hospital & Research Center - DPU, Pune, Maharashtra, India
|Date of Submission||10-Feb-2022|
|Date of Decision||10-Mar-2022|
|Date of Acceptance||08-May-2022|
Department of Neurology, Dr. D.Y. Patil Medical College, Hospital & Research Centre, Pune - 18, Maharashtra
Source of Support: None, Conflict of Interest: None
Spinal cord involvement in COVID-19 infections can be varied and may present as acute transverse myelitis, acute necrotizing myelitis, neuromyelitis optica spectrum disorder, Myelin oligodendrocyte-associated glycoprotein (MOG) antibody myelitis, and SARS-CoV-2 myelitis. We retrospectively analyzed eight cases of COVID-19-associated myelitis. All patients had only mild antecedent symptoms of COVID-19 infection and were admitted with clinical features of acute transverse myelitis confirmed on neuroimaging. Seven patients had longitudinally extensive transverse myelitis (LETM). Serum Aquaporin-4 antibodies (NMO), cerebrospinal fluid (CSF) oligoclonal bands, and RT PCR for COVID-19 were negative. Serum MOG antibodies were positive in three patients; out of this two had CSF pleocytosis. All patients were treated with steroids followed by plasmapheresis. Five cases showed good improvement (increase in power by grade 2 or more), while three cases that were MOG positive had poor outcomes with either minimal or no improvement. The severity of COVID-19 infection was not related to the development of myelitis. Seven cases had LETM. Response to therapy was not uniform and the presence of MOG antibodies and CSF pleocytosis was associated with poor outcomes.
Keywords: Acute transverse myelitis, covid-19, myelin associated glycoprotein
| Introduction|| |
The incidence of SARS-CoV-2-associated Acute transverse myelitis (ATM) is found to be 20.1.2% of all neurological complications. Out of the total 46 million COVID-19 cases as of October 31, 2020, the incidence of myelitis was 0.83 per million.
Angiotensin-converting enzyme 2 has been identified as the functional receptor for the SARS-CoV-2 virus, which is present in the nervous system. The neurological complications of viral infections can be either due to direct viral invasion or post-infectious, resulting from immune-mediated inflammatory reactions against the virus. The proposed mechanisms of post-infectious neurological disorders include molecular mimicry, epitope spreading, bystander activation, and polyclonal B Cell activation.
| Materials and Methods|| |
We retrospectively analyzed all eight cases of COVID-19-associated myelitis over 1 year from May 1, 2020, to April 30, 2021. All patients had three mild antecedent COVID symptoms. RT-PCR for COVID was done upon admission. MRI for the brain and spinal cord were performed in all cases. Other relevant investigations like cerebrospinal fluid analysis for protein, sugar, cells, culture and sensitivity, viral encephalitis panel, anti-aquaporin-4 antibodies, myelin oligodendrocytes glycoprotein antibodies (MOG), antinuclear antibodies (ANA), Venereal disease Research Lab (VDRL), anti-phospholipid antibodies, anti-angiotensin converting enzyme level (ACE), CSF for Oligoclonal bands, and RT-PCR for COVID-19 were done. Visual-evoked potentials were done in three cases that were MOG positive.
| Results|| |
The clinical, radiological, and CSF profiles are summarized in [Table 1].
CSF viral encephalitis panel, serum ANA, VDRL, antiphospholipid antibodies, ACE 4, and HIV were all negative. RT-PCR was positive for COVID-19 in all patients. MRI brain did not reveal the involvement of the brain or optic nerves.
The time of onset of ATM varied from 3 to 20 days after onset of COVID-19 symptoms. All cases had mild COVID symptoms which did not necessitate hospital admission. RT-PCR for COVID-19 was positive on admission in all cases. The presentation was with acute onset flaccid quadriparesis (4 cases) or paraparesis (4 cases) which developed over a few hours. All had urinary retention and sensory level. The anatomical distribution of the spinal cord lesions by MRI imaging showed LETM in seven cases [Figure 1] in which the cervicothoracic cord was the most common site of involvement (5 out of 8). All patients had raised proteins in CSF with normal sugar, and two patients had increased cells (lymphocytes) in CSF. Serum MOG antibodies were positive in three patients. Serum anti-aquaporin-4 antibodies, ANA, vasculitis profile, APLA, ANA, anti-angiotensin-converting enzyme were negative in all patients. CSF RT-PCR for COVID was negative in all. VEP in three patients who were MOG antibody-positive was normal.
|Figure 1: T2-weighted MRI sagittal view showing T2 hyperintensities from T1 to T5 (1), from T2 to T6 (2), from T2 to T4 (3), from C2 to T10 (4), from C2 to C7 (5), from C5 to T4 (6), from C6 to T3 (7), and from T1 to T7 (8)|
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All the patients were given intravenous steroids (methylprednisolone 1 gm/day) for 5 days followed by oral prednisolone 1 mg/kg/day. Seven cycles of plasmapheresis were done in all patients following which only five (62.5%) patients had marked improvement of the symptoms (increase in power by grade 2) and three (38%) patients who were MOG positive and had CSF pleocytosis in two patients showed only minimal or no improvement.
| Discussion|| |
About 80% of the hospitalized COVID-19 patients exhibit at least one new neurological symptom, sign, or syndrome during the course and 55% have at least one neurological sign or syndrome on clinical evaluation. The incidence of SARS-CoV-2-associated ATM is found to be at least 1.2% of all neurological complications. Out of the total 46 million COVID-19 cases as of October 31, 2020, the incidence of myelitis was 0.83 per million.
Some authors have implicated “cytokine storm” in severe cases which could trigger an indirect immune response that affects the central nervous system. But in these cases, there was multisystem involvement suggestive of severe COVID-19 infection. None of our patients had multisystem involvement.
MOG-associated diseases (MOG-AD) is an antibody-mediated inflammatory demyelinating disorder of the CNS. Viral infection can play an important role in the pathophysiology of MOG-AD. The possible mechanism identified is viral antigens triggering a humoral immune response directed toward endogenous CNS myelin proteins, such as MOG.,
There have been many case reports of SARS-CoV-2 MOG-associated central nervous system manifestations.,,, The most common neurological manifestation of COVID-19-associated MOG-AD is optic neuritis, whereas in our case series, none of the patients had optic neuritis.
COVID-19-associated myelitis can also appear in mild COVID-19 patients as seen in our case series. The majority of patients had LETM; the cervicothoracic region being the most common anatomical site which is consistent with previously reported cases.,
After treatment with methylprednisolone and plasmapheresis, five (62.5%) showed improvement. Previously reported cases of COVID-associated MOG had significant improvement with immunotherapy., However, in our series, those with MOG antibodies and CSF pleocytosis had poor outcomes.
| Conclusion|| |
The presence of MOG antibodies and CSF pleocytosis was associated with poor outcomes. Optic neuritis was not seen in any case.
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Conflicts of interest
There are no conflicts of interest.
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