This case presented substantial challenges for the treating medical team, not least due to the patient’s distress during her illness and the diagnostic conundrum presented. Neurology opinion was sought locally with input from the regional referral centre. Extensive involvement of Psychiatry colleagues was also paramount in management.
The presentation was of a limbic encephalitis. Neuroborreliosis was considered, but with absence of epidemiological risk such as travel to endemic areas within the UK or abroad, negative serum serology, normal brain imaging, and resolution of the CSF pleiocytosis, it was felt that this was unlikely; and there was an extensive workup for common known viruses. The variety of investigations outlined above aimed to identify autoimmune and paraneoplastic causes. Shin et al. provide further discussion of aetiology and management [2].
Isolated reports exist of anti-NMDA receptor–associated encephalitis following Japanese encephalitis, H1N1, and diphtheria, tetanus, pertussis and polio vaccinations, with plausible biochemical evidence of causality [3].
It is known that psychiatric illness, delirium, encephalopathy and encephalitis may complicate COVID-19 [4, 5], and potential biomarkers exist to support these diagnoses alongside imaging changes [6]. In this patient, however, multiple negative SARS-CoV-2 PCR tests made this diagnosis less likely, although an asymptomatic COVID-19infection around the time of vaccination cannot be excluded.
To our knowledge, there have not yet been any published case reports of encephalopathy, encephalitis, or neuropsychiatric syndromes following vaccination against COVID-19. Data from clinical trials until early in the global vaccination campaign was incomplete but overall reassuring [7]. The initial ChAdOx1 nCoV-19 Oxford vaccine trial was paused following a case of transverse myelitis that later was confirmed to be multiple sclerosis (MS), but there were no documented cases of encephalitis or psychosis in 12,408 participants vaccinated between April and December 2020 [8]. Yellow Card adverse incident reports to the UK Medicines & Healthcare Regulatory Agency (MHRA) from 4 January 2021 to 16 June 2021 list 32 cases of ‘encephalitis’, 4 cases of ‘noninfective encephalitis’, and 3 cases of ‘autoimmune encephalopathy’ temporally associated with ChAdOx1 nCoV-19 administration [9]. Various psychiatric conditions are also listed. It is not yet possible to analyse comprehensively the reports presented.
Whilst temporal relationship is not indicative of causation, the clinical syndrome, coupled with evidence of inflammatory changes in cerebrospinal fluid, and lack of evidence of an infective or immune-mediated cause, would plausibly fit with vaccine-induced encephalitis and encephalopathy. Determination of causality in this relationship is not currently possible as no specific test yet exists [10]. On this basis, a claim for litigation for a case of ‘acute encephalopathy’ reported in a ChAdOx1 nCoV-19 trial participant in India was dismissed as no evidence could be found of a causal link [11].
There is an association of psychosis and neurological complications after COVID-19, including high rates of stroke (such as in the study by Taquet et al. [12]), but overwhelming evidence suggests that vaccination is safe and effective, and that such risks are minimal compared to COVID-19 infection in the unvaccinated.
In summary, we believe that the patient presented in this case may have experienced a rare side-effect of COVID-19 vaccination, in the absence of another identifiable cause. Uncertainty remains, and there is no current definitive proof of causality for the patient’s symptoms and signs. Further work is urgently required to clarify this association and compare data with pre-pandemic disease incidence, to determine the mechanism involved, and to formulate appropriate treatment strategies. Encephalitis is a recognised complication of COVID-19 and at far greater rates than our sole case of uncertain causation with vaccination.
Patient perspective
My illness started as a headache, slowly becoming throbbing and waking me at night. Nineteen days after receiving my second vaccine dose, I started to hallucinate right after feeling euphoric. I then hallucinated silhouettes running past me in slow motion. We initially thought it could be cerebral venous thrombosis. The CT scan turned out to be normal. The first two weeks I spent at the hospital were very difficult: I only remember my hallucinations and don’t recall anything else (including the staff). I also remember being convinced that I had schizophrenia and was very distraught.
However, I was beginning to recover towards the third week of my stay and was no longer hallucinating frightening things. The last two weeks I spent at the hospital were wonderful; I remember the staff and they took excellent care of me. My recovery would’ve taken longer if it wasn’t for the staff and their caring and considerate attitude. The time I spent with the nurses allowed me to gain an insight into what it takes to be a nurse, and I hope to apply for further study next year. Overall, my experience at the hospital was very positive and that was made possible by the staff.
