Discussion:
The main clinical manifestation of COVID-19 is respiratory involvement. However, there also have been reports of neurological manifestations besides pulmonary involvement(6). Acute cerebellitis is a rare disease, characterized by cerebellar dysfunction. Acute cerebellitis has been attributed to infectious, parainfectious, paraneoplastic, ischemic, and systemic autoimmune diseases(7). Acute cerebellitis caused by viral agents such as varicella-zoster, herpes simplex, Epstein-Barr, rotavirus, echovirus, coxsackie, mumps, measles, and rubella(8) happens most commonly in children(9) but it could be seen in adults as well. To the best of our knowledge, COVID-19 vaccination has not yet been reported as a cause of acute cerebellitis with positive CSF COVID PCR along with no associated respiratory symptoms and negative oropharyngeal swab test for COVID-19.
There have been various reports on extrapulmonary involvements of COVID-19 vaccines, like stroke, GBS, Bell’s palsy and TM(3-5). The underlying etiology is still unknown. As the Sinopharm vaccine contains inactivated virus, one possible neuroinvasive mechanism that can lead to neurologic manifestations could be a direct viral injury to the central nervous system (CNS) via blood circulation(10). In this mechanism, multiorgan spread of the virus occurs as a result of the wide distribution of the human angiotensin-converting enzyme-2 (hACE2) receptors (11). Another possible explanation could be a stimulation of the immune response following administration of vaccine. When distinguishing between foreign antigens and host antigens becomes difficult for the immune system, it triggers autoimmunity which results in destruction of host cells(12, 13), an immune response similar to those observed for various infections mentioned above. One of the most common mechanisms attributed to this process is molecular mimicry between infectious antigens and self-antigens(14).
To diagnose cerebellitis, brain MRI and lumbar puncture are used which rule out other differential diagnoses(9). Brain MRI in acute cerebellitis demonstrated bilateral or unilateral diffuse cerebellar hemispheric abnormalities in T2-weighted images and pial enhancement in contrast enhanced T1-weighted images(15). The diagnosis of multiple sclerosis was unlikely due to the absence of multiple sclerosis-like lesion in brain and oligoclonal bands in CSF. The imaging studies were also negative for acute disseminated encephalomyelitis and vascular lesions. Laboratory evidence of vasculitis and connective tissue disease was also absent. As most of the possible causes were eliminated, the abovementioned feature was attributed to post vaccination cerebellitis following SARS-CoV-2 vaccination. The case shows close temporal association to a positive CSF COVID-19 PCR as a result of COVID-19 vaccination. The patient did not have any signs of previous COVID-19 infection, neither were COVID-19 antibodies detected in the serum. The acute attack of cerebellitis appeared within 2 weeks of COVID-19 vaccination. To our knowledge, no similar case has been reported yet. Specifically, we only found three reports of postvaccination cerebellitis which were secondary to influenza vaccine. The first case was a 16-year-old girl 12days after receiving H1N1 vaccine with cortical foci of hyperintensity on FLAIR in the cerebellar hemispheres with significant mass effect on the 4th ventricle(16). The second one was a 66-year-old woman presented with limb and gait ataxia and a history of H1N1 vaccination 3weaks prior to her symptoms. Her brain MRI had no abnormality but Technetium-99m hexamethyl propylene amine oxime-single photon emission computed tomography (HMPAO-SPECT) showed markedly cerebellar asymmetry, suggesting hypoperfusion in the right cerebellum(17). The third one was a 5 year-old girl with acute cerebellar ataxia after Influenza vaccination with marked Cerebellar Atrophy(7).
These reports may not be able to identify causality as no distinction can be made between infectious and other etiology. Our study lacks laboratory data analysis on autoimmune and paraneoplastic causes of acute cerebellitis. However, the close temporal association along with positive CSF COVID-19 PCR in our case, makes it very likely. More studies have to be done to determine the causal relationship and as of now, vaccination seem to outweigh the risks.
As the number of vaccinated people worldwide are growing, vaccine-related disorders are coming to our notice. Certainly, accurate reporting is needed for finding of the actual relevance and potential risk. In this regard, we reported a case of post-vaccination acute cerebellitis with positive CSF COVID-19 PCR and no pulmonary symptoms for the first time.