In a recent “Letter to the Editor” published in the English edition of the journal Neurologandiacute, researchers reported the rare occurrence of Hashimoto’s encephalopathy in a recipient of the (COVID-19) Spikevax vaccine. Spikevax, research name mRNA-1273, is a COVID-19 vaccine based on messenger ribonucleic acid (mRNA) technology.
Letter to the Editor – Hashimoto’s 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 an autoimmune encephalopathy, known as Hashimoto’s encephalopathy. The underlying pathophysiology of this disease is unclear, particularly the pathogenicity of antithyroid antibodies.
Studies have suggested that some vaccines worsen immune-mediated neurological diseases. For example, vaccines against influenza, measles, mumps, rubella, and hepatitis B resulted in 708 cases of autoimmune encephalitis in the United States between 1990 and 2010. Yet its association with vaccines remains controversial. and has no 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) after vaccination, it is possible that vaccination against COVID-19 triggers it. Additionally, several cases of post-vaccination encephalitis have been reported in recipients of COVID-19 vaccines, based on mRNA and viral vectors.
Additionally, studies have reported neurological complications following vaccination after post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For example, the United States Centers for Disease Control and Prevention (US-CDC) has reported cases of Guillain-Barré syndrome in recipients of the Ad26.COV2.S adenoviral vector-based vaccine. The European Medicines Agency (EMA) has reported cases of acute disseminated encephalomyelitis and encephalitis in ChAdOx1 recipients. These neurological complications seem less frequent with mRNA vaccines than with adenovirus vaccines.
In the current study, researchers presented one of the first cases of Hashimoto’s encephalopathy as a likely complication of SARS-CoV-2 vaccination. A 36-year-old man met the Graus criteria, that is, he had antithyroid antibodies in the cerebrospinal fluid (CSF). In addition, he presented the typical manifestations of encephalopathy.
The patient had a history of autoimmune hypothyroidism but no psychiatric disorders. He received the first dose of Spikevax vaccine in July 2021 and his second dose 28 days later. Within 24 hours of receiving the second vaccine, he presented with a self-limited febrile syndrome and mild postural tremors. Six days later, he presented with a first focal seizure in the left hemisphere, progressing to a bilateral tonic-clonic seizure and convulsive status epilepticus. He was immediately admitted to the intensive care unit (ICU).
Computed tomography (CT) 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 alterations in postictal signaling.
Polymerase chain reaction (PCR) tests for neurotropic viruses gave negative results. CSF analysis showed slightly elevated protein levels (98 mg/dL) but cell counts within the normal range. Initially, the serum did not contain antineuronal antibodies; PCR for SARS-CoV-2 was negative at baseline and in all subsequent tests. Additionally, the researchers noted no pathological issues in the blood test, including biochemistry, complete blood count, kidney and liver function, etc.
The patient suffered a second episode of toniclonic seizure in November 2021 and was again admitted to intensive care. In addition to increased postural tremors, gait disturbances and memory deficit (Montreal Cognitive Assessment [MoCA] rating of 21/30). The doctors prescribed a short course of methylprednisolone.
After partial improvement, although the ultrasound study revealed normal morphology of the thyroid gland, the patient had ATG and TPO antibody levels of 4.2 IU/l and 60.9 IU/l in the CSF. Previous CSF analysis had shown normal levels of IgG and ADA antibodies, and results for antineuronal antibodies were negative.
Additionally, 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 antithyroidase peroxidase (TPO) antibody levels of 986 IU/L and 538 IU/L, respectively. Fortunately, the patient also had no malignancy in CT scans of the chest, abdomen, or pelvis. Doctors gave him the second course of methylprednisolone, which reduced the tremors and improved his gait. He continued with the prescribed maintenance treatment with prednisone upon discharge. Within six months he was seizure free and able to walk independently, showing a MoCA score of 27/30.
An underlying molecular mimicry with the SARS-CoV-2 spike protein that results in the loss of this protein’s transmembrane anchorage most likely triggers adverse events, such as Hashimoto’s encephalopathy. However, the incidence of Hashimoto encephalopathy is nearly 617 times lower than that caused by natural viral infection. Thus, the benefits of the COVID-19 vaccine or any other vaccine clearly outweigh the risks of not vaccinating.