Case Studies Show IVIG May Improve Neurological Symptoms in Pediatric Multisystem Inflammatory Syndrome


Relapses of MIS-C occurred in 2 patients due to rapid tapering of corticosteroids at 2 weeks instead of the standard protocol of 4 to 6 weeks.

Findings from a recent case series and previous studies show that children with multisystem inflammatory syndrome (MIS-C) may present signs of acute neurological symptoms, and immunomodulatory agents such as intravenous immunoglobulin (IVIG) and corticosteroids provide a relatively good prognosis.

Image credit: Dr_Microbe -

Image credit: Dr_Microbe -

MIS-C emerged as a concern early in the COVID-19 pandemic and can have severe clinical manifestations. Various neurological issues, including Guillain-Barre syndrome, transverse myelitis, reversible cerebral vasoconstriction syndrome, and acute encephalitis, have been reported in patients with either COVID-19 or MIS-C.

Between March 1, 2020, and December 28, 2021, 12 children were diagnosed with acute neurological symptoms and MIS-C in 2 hospitals in the Isfahan province in Iran. Diagnosis of MIS-C was made according to World Health Organization criteria and recommendations from the American College of Rheumatology, in addition to prior detection of SARS-CoV-2.

The median age of the patients was 4.5 years, and 3 patients were aged 1 year or younger. Underlying diseases included chronic neurological disorders (neurodegenerative disease and seizure disorder), cardiac disease, and malignancy. Immunodeficiency was not observed in any patient.

Standard treatment protocol was performed for all patients, based on the Iranian treatment protocol for children with MIS-C. Two patients were admitted to the intensive care unit during their hospitalization and 1 patient experienced myocarditis and vegetation-like lesions in the endocardium. Eleven patients were ultimately discharged in good condition, and in 4-week follow-ups 10 of them showed no complaints. One patient suffered from short-term memory loss.

Notably, relapses of MIS-C occurred in 2 patients due to rapid tapering of corticosteroids at 2 weeks instead of the standard protocol of 4 to 6 weeks. One patient who suffered from cobalamin deficiency died after full recovery from acute neurological symptoms, attributed to irreversible shock due to cobalamin deficiency.

Based on their observations, the investigators said central nervous system involvement is a non-rare associating condition with MIS-C. Acute neurological symptoms are life-threatening, although the epidemiology, pathophysiology, and prognosis of acute neurological symptoms in children with MIS-C are still unclear.

Cerebrospinal fluid (CSF) analysis of the cases was almost insignificant. However, one case had pleocytosis in their CSF analysis, which has been noted previously in other patients with COVID-19. Importantly, however, lumbar puncture of cases was performed within 24 hours of admission, which may not be enough time for white blood cells to migrate to the CSF.

Additionally, polymerase chain reaction (PCR) testing of SARS-CoV-2 particles, immunoglobulin M (IgM), and immunoglobulin G (IgG) antibodies of SARS-CoV-2 were negative in the CSF of all cases. Negative serology of CSF diminished the role of humoral immunity because it was suggested that immune-mediated pathophysiological mechanisms triggered by previous SARS-CoV-2 infection play an important role in the pathophysiology of acute neurological symptoms in MIS-C and COVID-19.

The investigators did note some limitations. Firstly, the retrospective nature of the study meant that investigations of patients were dissimilar and dependent on the current guidelines at the time, although neurologic evaluation was performed for all patients in the same way. Second, because MIS-C is a clinical diagnosis and diagnostic tests are lacking, it is not possible to distinguish between acute neurological symptoms as part of MIS-C and as a coincidence.

Despite these limitations and the remaining gaps in knowledge about MIS-C, the investigators concluded that immunomodulatory agents such as IVIG and corticosteroids can significantly improve patients’ prognosis.


Dehghan A, Saleh R, Rahimi H, Pourmoghaddas Z, et al. Acute neurological symptoms in multisystem inflammatory syndrome in children: A case series. Heliyon. 2023;9(8):e18566. doi:10.1016/j.heliyon.2023.e18566

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