Case Report: Anti-LGI1 Encephalitis Following COVID-19 Vaccination

Abstract

Anti-leucine rich glioma inactivated 1 (LGI1) autoimmune encephalitis (AE) is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, faciobrachial dystonic seizures (FBDS) and refractory hyponatremia. Since December 2020, millions of people worldwide have been vaccinated against COVID-19. Several soft neurological symptoms like pain, headache, dizziness, or muscle spasms are common and self-limited adverse effects after receiving the COVID-19 vaccine. However, several major neurological complications, despite the unproven causality, have been reported since the introduction of the COVID-19 vaccine. Herein, we describe a 48 years old man presenting with rapidly progressive cognitive decline and hyponatremia diagnosed with anti LGI1 AE, occurring shortly after the second dose of mRNA COVID -19 vaccine and possibly representing a severe adverse event related to the vaccination. Response to high dose steroid therapy was favorable. As millions of people worldwide are currently receiving COVID-19 vaccinations, this case should serve to increase the awareness for possible rare autoimmune reactions following this novel vaccination in general, and particularly of anti-LGI1 AE.

Anti-LGI1 encephalitis following COVID-19 vaccination: a case series

“…We described four patients who developed anti-LGI1 encephalitis with classic clinical features following different COVID-19 vaccinations. The mean time from vaccination to disease onset was approximately 2 weeks, as in the only previously reported case [ 4 ]. Anti-LGI1 encephalitis represents an extremely rare disease, with a reported annual incidence ranging from 0.4/million (95% CI 0.3–0.5) in a French study [ 5 ] to 0.83/million (95% CI 0.45–1.40) in a nationwide Dutch study [ 1 ].…”

“…The most frequently employed vaccines are based on mRNA (BNT122b2 and CX-024414) or viral vectors (ChAdOx1-S and Ad26.COV2.S). A few patients presenting with autoimmune encephalitis following COVID-19 vaccinations were reported, including a case diagnosed with anti-LGI1 encephalitis [ 2 – 4 ].…”

“…Even though this epidemiological data should be considered cautiously, the presence of a strict temporal relationship between disease onset and vaccination lets us hypothesize that anti-LGI1 encephalitis may represent a rare complication of COVID-19 vaccination. Four patients developed anti-LGI1 encephalitis after the vaccination with two different mRNA vaccines (three cases from this report, one previously reported [ 4 ]), while case 1 was administered a viral vector vaccine; therefore, should this association be confirmed, the trigger would not be a specific COVID-19 vaccine, but rather the immune response generated by the encoded SARS-CoV-2 spike protein or by shared adjuvants [ 6 ]. This might speculatively happen due to molecular mimicry and immune cross reaction, a process by which several other vaccines have been suspected to trigger autoimmunity, likely in genetically predisposed subjects [ 7 ].…”

“…This might speculatively happen due to molecular mimicry and immune cross reaction, a process by which several other vaccines have been suspected to trigger autoimmunity, likely in genetically predisposed subjects [ 7 ]. However, as for other reported neurological and systemic autoimmune manifestations, whether the association of anti-LGI1 encephalitis with COVID-19 vaccines is coincidental or causal remains to be definitely determined [ 2 – 4 , 6 ]. Additionally, the extraordinary benefits of mass COVID-19 vaccination in preventing disease morbidity and mortality surely outweigh the risk of developing autoimmune disorders in general and anti-LGI1 encephalitis specifically, especially considering the good clinical response of this condition to immunotherapies [ 1 ].…”

LGI-1 encephalopathy following ChAdOx1 nCov-19 vaccination

“…Equally worthy of consideration are the critical remarks regarding the possibility of the causal connection, so that the debate about a coincidental or causal connection continues [ 2 ]. Furthermore, we were alerted to reports of post-COVID-19 opsoclonus-myoclonus syndrome and encephalopathy associated with leucine-rich glioma-inactivated 1 (LGI-1) antibodies [ 3 ] and anti-LGI1 encephalitis following COVID-19 vaccination [ 4 ]. We would like to contribute to this issue with a case of LGI-1 encephalopathy following vaccination with the ChAdOx1 nCov-19 vaccine in which we discuss a possible connection to vaccination.…”