In a recent ‘Letter to the Editor’ published in the English edition of the journal Neurologandiacute, researchers reported the rare occurrence of Hashimoto encephalopathy in a recipient of the (COVID-19) vaccine Spikevax. Spikevax, research name mRNA-1273, is a COVID-19 vaccine based on the messenger ribonucleic acid (mRNA) technology.
Letter to the Editor - Hashimoto encephalopathy after vaccination against SARS-CoV-2. Image Credit: DOERS / Shutterstock
Antithyroid antibodies are present in 13% of healthy individuals. In rare cases, it triggers autoimmune encephalopathy, popularly known as Hashimoto encephalopathy. The underlying pathophysiology of this disease is unclear, especially the pathogenicity of antithyroid antibodies.
Studies have suggested that some vaccines worsen immune-mediated neurological diseases. For instance, influenza, measles, mumps, rubella, and hepatitis B vaccines resulted in 708 cases of autoimmune encephalitis in the United States between 1990-2010. Yet, its association with vaccines remains controversial and lacks a causal relationship.
Under their emergency use authorization (EUA), 11 billion doses of COVID-19 vaccines have been administered worldwide. Although the occurrence of Hashimoto encephalopathy is rare (less than one case per million patients) post-vaccination, there is a possibility that the COVID-19 vaccination triggers it. In addition, several post-vaccination encephalitis cases have been reported in recipients of COVID-19 vaccines, both mRNA and viral vector-based.
Furthermore, studies have reported neurological complications after vaccination after post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For instance, the United States Centers for Disease Control and Prevention (US-CDC) have reported cases of Guillain-Barré syndrome in the recipients of the adenoviral vector-based vaccine Ad26.COV2.S. The European Medicines Agency (EMA) has reported cases of acute disseminated encephalomyelitis and encephalitis in the recipients of ChAdOx1. These neurological complications seem less frequent with mRNA vaccines than with adenovirus vaccines.
In the present study, researchers presented one of the first cases of Hashimoto encephalopathy as a probable complication of SARS-CoV-2 vaccination. A 36-year-old male patient met the Graus criteria, i.e., he had antithyroid antibodies in cerebrospinal fluid (CSF). Also, he presented the typical encephalopathy manifestations.
The patient had a history of autoimmune hypothyroidism but no psychiatric disorder. He received the first Spikevax vaccine dose in July 2021 and its second dose 28 days later. Within 24 hours of receiving the second vaccine, he experienced self-limited febrile syndrome and mild postural tremors. Six days later, he presented a first focal seizure in the left hemisphere, progressing to bilateral tonic-clonic seizure and convulsive status epilepticus. He was admitted to the intensive care unit (ICU) immediately.
A computed tomography (CT) scan and CT angiography study did not show vascular or neoplastic etiology. However, an electroencephalogram (EEG) showed symmetrical diffuse slowing. In the brain magnetic resonance imaging (MRI) study, diffusion sequences revealed cortical hyperintensity in the left temporal pole, attributed to postictal signal alterations.
Polymerase chain reaction (PCR) testing for neurotropic viruses fetched negative results. The CSF analysis showed mildly elevated protein levels (98 mg/dL) but a cell count within the normal range. Initially, the serum had no antineuronal antibodies; PCR for SARS-CoV-2 was negative at baseline and in all subsequent testings. Further, the researchers noted no pathological issues in the blood analysis, including biochemistry, complete blood count, kidney and liver function, etc. At discharge, the patient presented naming difficulties, impaired memory, and postural tremors with mild gait instability.
The patient suffered from a second episode of toni-clonic seizure in November 2021 and was again admitted to the ICU. Apart from increased postural tremor, gait impairment, and memory deficit (Montreal Cognitive Assessment [MoCA] score of 21/30). The doctors prescribed a short course of methylprednisolone.
After partial improvement, although the ultrasound study revealed normal thyroid gland morphology, the patient had ATG and TPO antibody levels of 4.2 IU/l and 60.9 IU/l in the CSF. An earlier CSF analysis had shown normal levels of IgG and ADA antibodies, and results for antineuronal antibodies were negative.
Further, his thyroid-stimulating hormone, T4, and T3 levels were 4.4 mIU/L, 1.0 nmol/L, and 2.7 nmol/L, respectively. Serum analysis revealed antithyroglobulin (ATG) antibody and antithyroid peroxidase (TPO) antibody levels of 986 IU/L, and 538 IU/L, respectively. Thankfully, the patient also had no malignancy in the chest, abdomen, or pelvis CT scans. The doctors administered the second course of methylprednisolone, which decreased tremors and improved his gait. He continued with prescribed maintenance treatment with prednisone at discharge. Within six months, he was seizure-free and able to walk independently, presenting a MoCA score of 27/30.
An underlying molecular mimicry with the SARS-CoV-2 spike protein that results in the loss of the transmembrane anchor of that protein most likely trigger adverse events, such as Hashimoto encephalopathy. However, the incidence of Hashimoto encephalopathy is nearly 617 times lower than those caused by a natural viral infection. Thus, the benefits of the COVID-19 vaccine or any other vaccine clearly outweigh the risks of not vaccinating.