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.