DOI: https://doi.org/10.21203/rs.3.rs-2468988/v1
Background: With the availability of the COVID-19 vaccine, post-vaccination neurological complications have occasionally been reported.
Case presentation: We present a case of neuromyelitis optica spectrum disorder (NMOSD) that developed 1 month after the second dose of BIBP COVID-19 vaccine (SARS-CoV-2-Vaccine [Vero Cell] Inactived). The patient presented itching, numbness of the hand and right side of the face, associated with nausea, vomiting and hiccups. Brain MRI showed lesions in the area postrema, medulla, and bilateral hypothalamus, typical of NMOSD. Serum antibodies to anti-AQP4 and anti-MOG were negative.
Conclusions: The pathogenesis of NMOSD development and the vaccine is still unknown. The presentation of NMOSD is generally aggressive and disabling, it is important for the neurologist to be attentive to the highly variable clinical presentation after vaccination against COVID-9 for early diagnosis and effective treatment.
Neuromyelitis optica (NMO) is an inflammatory, autoimmune, and demyelinating disease that primarily affects the optic nerve and spinal cord. The recognition of incomplete forms of the disease and the inclusion of new syndromes associated with AQP4 antibodies has broadened the term to neuromyelitis optica spectrum disorder (NMOSD) (1).
NMOSD has recently been reported in certain vaccines. Most of these cases were positive for Aquaporin-4 (AQP4) antibodies (2). COVID-19 can present various neuroimmunological complications, including Guillain-Barré syndrome, NMOSD, Miller Fisher syndrome, cranial polyneuritis, myasthenia gravis, and myelitis. There are a few reported cases of NMOSD that developed during the recovery period from COVID-19 (3–5).
With the recent availability of the COVID-19 vaccine, reported cases of post-vaccination transverse myelitis have raised concerns about vaccine safety (6). We present a case of a previously healthy woman who developed NMOSD after receiving the second dose of inactivated virus vaccine against COVID-19 (BIBP COVID-19 vaccine).
A previously healthy 51-year-old woman, who after 1 month of receiving the second dose of BIBP COVID-19 vaccine (inactivated SARS-CoV-2-Vaccine - Vero Cell), a Sinopharm COVID-19 vaccine, insidiously and progressively she presented itching and numbness of her right hand and face, associated with excoriative lesions in the right nasolabial fold. She subsequently had nausea, uncontrollable vomiting and hiccups, for which she was admitted to our hospital emergency room.
During hospitalization, she developed diplopia, excessive yawning, hypersomnia, constipation, bladder retention, left-predominantly suspended paraparesis, and right palpebral ptosis.
Clinical examination upon admission revealed excoriative lesions in the right nasolabial fold, and 10 days after hospitalization, paraparesis with sensory level at T10, left internuclear ophthalmoplegia, predominantly right bilateral palpebral ptosis, right Babinski sign, patellar areflexia and Achilles hyporeflexia. Ishihara's test was normal. Days after hospitalization, she also presented with venous thrombosis of the lower left limb, most likely related to prostration.
Brain magnetic resonance MRi showed a lesion in the area postrema and bilateral hypothalamus without enhancement with Gadolinium (Fig. 1). After 2 weeks, an MRi of the cervical and dorsal spine was performed with sagittal T2-weighted images of the total spine, showing focal lesions of high signal intensity in the cervical segment of the medullary cord at the level of C3-C6 and the medullary-bulb junction. medullary. Additionally, the dorsal segment of the spinal cord showed several focal high signal intensity lesions on T2 and T2 STIR up to 40 mm. long at the level of D10 and D11, most of which compromised the central region of the medullary cord and without evidence of contrast enhancement, compatible with transverse myelitis (Fig. 2).
Cerebrospinal fluid: transparent, cells 19/uL with mononuclear predominance: 100%. Glucose: 64 mg/dL Proteins: 83.8 mg/dl. The electromyography was normal. The optic nerves were normal on MRi, but the visual-evoked potentials showed the P100 wave of both optic nerves with normal latency, but decreased amplitudes symmetrically.
Serum antibodies against aquaporin-4 (IgG-AQP4) and antibodies against myelin oligodendrocyte glycoprotein (IgG-MOG) were negative. Laboratory tests included routine blood, liver and kidney function, vitamin B12 levels, tumor markers, erythrocyte sedimentation rate, antinuclear antibody profiles, C-reactive protein, rheumatoid factor, antiphospholipid antibodies, ANA, SSA, SSB, and p -ANCA negative.
The pulmonary tomography revealed a non-obstructive hypodensity of 13x5 mm in the right branch of the pulmonary artery, which extends to the right inferior, middle and superior lobar arteries, reported as a probable tomographic sign of thrombosis, however the patient did not develop respiratory symptoms.
The patient met the diagnostic criteria for neuromyelitis optica spectrum disorder without AQP4-IgG, as he presented brainstem syndrome, area postrema syndrome, longitudinally extensive acute myelitis with cervical involvement of C3-C6, dissemination in space evidenced by MRi, having ruled out other pathologies.
After treatment with methylprednisolone (500 mg for 5 days), the patient presented with symptom improvement.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, demyelinating, inflammatory disease of the central nervous system, distinct from multiple sclerosis. NMOSD include optic nerve involvement as recurrent optic neuritis, and of the spinal cord as acute myelitis.
The relationship between vaccination and demyelination has not been fully described, furthermore, few reports are related to vaccines and NMOSD, this being rare, and its mechanism is poorly understood. However, it is generally attributed to an autoimmune overreaction of the body against the vaccine antigen. Previous case reports have emphasized that the most common demyelinating disease is acute demyelinating encephalitis, and it is most seen in children. (7).
A recent review of the literature from the past decade revealed that the most commonly reported vaccine-associated demyelinating diseases were diagnosed with ADEM and NMOSD, at 44% and 9%, respectively (8).
The most common reported side effects of COVID-19 vaccines have been localized pain at the injection site, low-grade fever, fatigue, myalgia, chills, and joint pain, and, rarely, anaphylactic shock (9).
The reported case is the first case in Peru of NMOSD that developed after the second dose of the attenuated COVID-19 vaccine. Some cases of NMOSD have already been reported worldwide, one case developing NMOSD after 2 months of the application of the attenuated virus vaccine against COVID-19 (10) and another case only after 10 days (11). Our patient developed NMOSD after 1 month. Regarding the type of vaccine, it has not only been reported with attenuated viruses but also with other types of vaccines (11, 12).
We were struck by the clinical presentation of acute brainstem syndrome, with pruritus being the first symptom, a presentation that has been previously described in NMOSD (13), and the following week, transverse myelitis was added, which delayed early diagnosis on admission. hospitable. The experience in Peru of cases of multiple sclerosis with initial symptoms of the brainstem could have been the reason for initially suspecting this pathology (14), however, the evolution and type of spinal cord lesions observed in magnetic resonance imaging after 2 weeks of the initial MRi clarified the diagnostic doubt.
NMOSD with positive AQP4 antibodies represents 80% of cases. Seronegative NMOSDs include other pathogenic antibodies against myelin oligodendrocyte glycoprotein (MOG). MOG is responsible for the stability of the myelin structure and has been postulated to be critical in relation to immune system interactions with the immune system, such as complement activation.
Although our case was negative for these 2 antibodies, the patient met the diagnostic criteria and it was decided to start treatment, as recommended in seronegative cases (15).
De novo cases following vaccination against different diseases appear more frequently IgG-AQP4 negative, while 75% relapsers are IgG-AQP4 antibody seropositive, and are primarily white women (16, 17).
NMOSD can coexist with other autoimmune disorders, such as Sjögren's syndrome (18), but we did not find any marker of associated autoimmune disease.
Likewise, our patient presented with venous thrombosis of the left lower limb, NMOSD is known to be a risk factor for venous thromboembolism (19). Additionally, she presented an alteration of the pulmonary tomography without clinical translation, an interstitial pulmonary lesion has been described since the Aquaporins4 are found in large quantities at the pulmonary level (20).
Further studies may be needed to clarify the possible connection between vaccination against COVID-19 and the development of NMOSD. However, both at the individual and population levels, the benefits of the COVID-19 vaccine far outweigh the risks of a neurological complication, although it would be important to consider the benefit-risk balance in patients with a diagnosis of NMOSD before vaccination.
The presented case of NMOSD produced after the administration of the inactivated vaccine against SARS-CoV-2 (Vero Cell) is relevant because it contributes to expanding the causes of NMOSD related to specific vaccines against COVID-19 and consequently achieving an early diagnosis. of a disease that can be catastrophic if timely intervention is not taken.
Contributions of authorship:
CG, SR, MT and AV participated in the conception, data collection, interpretation of results, critical review of the article and approval of the final version; WAQ has participated in interpretation of results, critical review and approval of the final version.
Corresponding author:
Wilfor Aguirre-Quispe,
Neurosciences, Clinical Effectiveness and Public Health Research Group. Universidad Científica del Sur, Lima, Perú.
Address: Panamericana Sur 19, Villa EL Salvador 15067
Phone: +51 941925104
E-mail: [email protected]
ORCID: 0000-0002-6677-0900
Funding: Self-financed.
Conflicts of interest: The authors declare that they have no conflict of interest.
Acknowledgements: We thank the internal medicine department of the Edgardo Rebagliati Martins National Hospital for the support provided.