The COVID-19, which has spread rapidly since the beginning of the pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Knowledge about neurological manifestations associated with the infection continues to be updated. The commonly reported symptoms are headache, dizziness, olfactory or tactile disturbances, and impaired consciousness. Rare but more serious complications include acute cerebrovascular conditions, seizures, Guillain-Barré, and Miller-Fisher syndromes, polyneuritis cranialis, oculomotor nerve palsies, meningitis, and encephalitis (1).

Encephalitis is an inflammatory disease that can have various etiologies. Several cases of autoimmune encephalitis (AE) associated with the previous COVID-19 infection have been reported (2–4). Possibly molecular mimicry in response to the virus is thought to lead to the activation of host antibodies that damage the central nervous system (CNS). Several antibodies have been found to attack CNS of patients infected with SARS-CoV-2. The commonly described are anti-NMDAR and others, such as: anti-GAD, anti-CASPR2, anti-amphiphysin, and anti-GD1a/GD1b (5, 6). These also include anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (4, 6), which occur in other demyelinating diseases such as optic neuritis (ON), transverse myelitis or acute disseminated encephalomyelitis (ADEM). The entire spectrum of anti-MOG positive diseases is defined as MOG antibody-associated disease (MOGAD) and affects people of all ages. The incidence is estimated at 1.6–3.4 per million people per year and the prevalence at 20 per million (7).

Although the knowledge about MOGAD is increasing, its association with COVID-19 infection is still insufficient. Therefore, the aim of this study was to present a case of MOG antibody associated encephalitis (MOGAE) following SARS-CoV-2 infection and to review the literature on other MOGADs with similar clinical presentation.

On October 10, 2022, a 60-year-old patient was admitted to our General Neurology Department with a rapidly progressive deterioration of cognitive functions which lasted for 3 months. Previously, on July 4, 2022, he had suffered a myocardial infarction and was admitted to the Cardiology Department, where he underwent stenting using the percutaneous coronary intervention. On July 20, 2022, SARS-CoV-2 virus was detected by Polymerase Chain Reaction (PCR) method. The only signs of COVID-19 were mild upper respiratory tract infection with fever, so isolation at home was recommended. Three weeks after, initial neurological deficits in the form of memory loss and poor concentration were noted during his stay in the Cardiac Rehabilitation Ward. The chronology of symptoms is presented in Figure 1. Other comorbidities included: arterial hypertension, prostatic hypertrophy, dyslipidemia, chronic heart failure, and permanent blindness of the right eye after toxoplasmosis infection 15 years earlier.

On admission, the patient was in simple verbal contact, self-oriented and disoriented in time and space, Mini-Mental State Examination (MMSE) = 17 points. He presented focal signs: the right VIIth nerve central paresis and right side pyramidal hemiparesis. During hospitalization, the patient’s condition worsened in terms of cognitive functions and he also developed complete aphasia. The score of the MMSE decreased to 13 points. On extended psychological examination (the Clock Drawing Test, Five Words Test, Digit Repetition Test, Trace Drawing Test, and Rey Complex Figure Copying Test), significant deficits were found in executive functions, short-term and episodic memory bordering moderate to severe dementia.

Numerous laboratory tests were performed showing: mild megaloblastic anemia (HGB 12.5 g/dL, MCV 98.2 fl), decreased folic acid level (2.57 ng/mL), slightly increased D-dimmers (821 ng/mL) and lactates (2.72 mmoL/L). Homocysteine and vitamin B12 levels were normal. A head CT revealed numerous hypodense foci up to 11 mm in the periventricular and subcortical white matter. The brain MRI in T2-weighted and FLAIR images showed bands of confluent hyperintense lesions in the white matter of both cerebral hemispheres, periventricularly, in the frontal, parietal, and to a lesser extent in the temporal lobes and corpus callosum, with clear Virchow-Robin spaces on both sides (Figure 2). The described changes were not enhanced by the gadolinium contrast, nor did they exhibit diffusion restriction properties. In addition, numerous vascular changes were noted in the lenticular nuclei. The MRI of cervical spinal cord revealed no abnormalities. The EEG showed generalized slowing of the recording with baseline activity in most leads with an average frequency of 7.5–9.5 Hz, consisting of mixed alpha and theta waves of 6–7 Hz and an amplitude of up to 50 μV. A CSF examination was performed, showing an elevated total protein level (608 mg/L) with a normal cell count (3 cells/μl). The presence of oligoclonal bands (OCBs) was not detected. A comprehensive diagnostic work-up for autoimmune diseases, including a-NMDAR, a-AQ4, auto-antibodies (pANCA, cANCA, a-β2 glycoprotein, ANA, a-dsDNA, lupus anticoagulant 1 and 2), onco- and antineuronal antibodies (a-AMPA1, a-AMPA2, a-GABABR1, a-LGI, a-CASPR2, a-Ri, a-Yo, a-Hu, a-Ma2/Ta, a-Ma1, a-CV2, a-amphizin, a-PCA2, a-Tr, a-SOX1), infectious diseases (Borrelia, HIV, HBS, HCV, M. pneumoniae, V. zoster, VDRL), and genetic diseases (CADASIL, MTHFR gene polymorphism) was performed. A common mutation in the MTHFR gene was found: a heterozygous polymorphism c 677C > T and c 1298A > C. The study of CSF biomarkers revealed an increased total τ- protein level (931 pg/mL), a normal level of hyperphosphorylated τ- protein (41.4 pg/mL), and a normal level of amyloid β-42 (917 pg/mL). In addition, a positive result of anti-MOG antibodies in serum was obtained (titre ≥1:10), by indirect immunofluorescence in duplicate. The presence of anti-MOG antibodies in the CSF was not detected. The results of other autoimmune diseases and paraneoplastic syndromes were negative.

Considering the patient’s overall clinical picture and excluding other possible explanations, the diagnosis of AE was made, according to the Graus criteria (8). Positivity of anti-MOG antibodies determined the MOGAE diagnosis, which was supported by the subsequently published MOGAD diagnostic panel criteria of Banwell et al. (7). Treatment with methylprednisolone at a dose of 1 g i.v. for 5 consecutive days was applied, after which no clinical improvement was observed. It was decided to administer intravenously immunoglobulin infusions (IVIG) in dose of 160 grams (0.4 grams per kg for 5 days). On the 27th day of hospitalization, complete resolution of focal symptoms was observed, the patient was discharged home in a good condition. After 8 months of repeated IVIG treatment (160 grams every 6 weeks), the patient showed inhibition of symptoms progression and a slow improvement of cognitive functions. On the last evaluation, the patient was in full verbal contact with improvement in cognitive testing (MMSE 23 pts). Controlled brain MRI showed neither new findings, nor regression. We believe that the IVIG treatment is effective and it was decided to continue the treatment, so that the full 12 months cycle is completed.

MOGAD is an increasingly recognized disease, and its association with COVID-19 has been documented (17). The heightened immune response following COVID-19 infection may provide a potential explanation for this phenomenon (2, 6, 18). In our case, we present a patient who developed MOGAE preceded by COVID-19 infection. Rapidly progressive cognitive dysfunction was the prominent symptom, which has been observed in only a few cases according to literature search (4, 14). However, the mental status and/or consciousness disturbances were observed in five other cases (11–13, 15, 16). These findings are consistent with a recent study by Orozco et al. (19), which demonstrated that cognitive and psychiatric symptoms were prevalent in the majority of patients with AE. Moreover, the presence of focal symptoms has also been reported in patients with encephalitis (20). The brain MRI played a crucial role in establishing the diagnosis. In our patient and in the other cases reviewed, extensive cortical and subcortical changes were observed, which are not typical of other diseases such as Alzheimer’s disease (AD), multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), or ADEM (20, 21). Additionally, measuring the concentration of total τ-protein proved helpful, as elevated levels indicate rapid brain tissue damage. Notably, normal concentrations of hyperphosphorylated τ-protein and amyloid β-42 helped exclude AD. Mutations in the MTHFR gene and associated high homocysteine levels have been implicated in the increased cardiovascular risk and various neurological complications, including a higher risk of developing AD (22, 23). However, in our patient, despite the presence of the mutation, homocysteine levels were within the normal range, suggesting that its impact on the clinical picture was negligible.

The presented case was positive for anti-MOG antibodies in serum, but negative in CSF. Following the Graus criteria (8), the antibody assay was repeated, yielding the same result. Additional CSF changes, such as increased protein levels and pleocytosis, were observed in most of the described patients, further supporting the diagnosis (20). The EEG is not included in the diagnostic criteria, since there are no specific changes in the recording. However, a generalized slowing of the recording, as in our case as well as in two other cases (11, 12), or the presence of epileptic discharges were described (4, 14).

Our patient met the criteria for definite AE according to Graus et al. (8). The recently published diagnostic criteria for MOGAD by Banwell et al. (7) provided detailed guidance for the management of patients with positive anti-MOG antibodies. Thereafter, the following criteria were met in this case: the presence of cerebral polyfocal deficits (criterion A), a low positive titre of anti-MOG combined with a negative result for anti-AQP4-IgG and MRI findings expressed as T2 FLAIR supratentorial hyperintensities (criterion B), and the exclusion of other more likely explanations (criterion C).

The treatment administered in our case proved to be effective, as demonstrated by the disappearance of the focal symptoms shortly after the start of treatment and the gradual improvement of cognitive function after several months of IVIG infusions. However, a full evaluation of the patient’s recovery will only be possible after a longer period of time. We are aware that it might be difficult to achieve a complete recovery in our case, because of the patient’s age, coexisting chronic vascular changes, and a long-time distance between the onset of symptoms and the start of treatment. The review found that in 8 out of 9 patients, immunosuppressive treatment with steroids or IVIG proved beneficial and resulted in complete remission of symptoms, further supporting the autoimmune nature of the disease and its hyperinflammatory response after infection by possible molecular mimicry, as previously reported (5).

Herein, we report a case demonstrating a rare occurrence of MOGAE following COVID-19 infection, suggesting a potential overlap between these conditions. The manifestation of rapidly progressive cognitive dysfunction in our patient is an uncommon phenotype in MOGADs, but is consistent with literature findings. The absence of anti-MOG antibodies in the CSF, although consistent with the Graus and Banwell criteria, has been noted in other cases. Distinct MRI findings, not typically observed in other neurological disorders, as well as unique laboratory findings, further support the thesis and suggest a strong association.

The limited number of reported cases of MOGAE following COVID-19 infection suggests a potential emerging problem. Our case, along with a comprehensive literature review, offers evidence that supports the association between COVID-19 and MOGAE. Such cases, including the one presented, can create diagnostic challenges as they straddle the line between AE and MOGAD. The recent standardization of diagnostic criteria for MOGAD by Banwell et al. (7) may aid in classifying and diagnosing such patients more efficiently.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.

MB was responsible for the patient case description, discussion, and overall manuscript preparation. JW contributed to the introduction and conducted the literature review on MOGAD. AB conducted the systematic literature review to identify similar cases. JS conceived the study, supervised the project, and provided critical revisions for intellectual content. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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