The pathophysiological mechanisms for the occurrence of neurological symptoms after SARS-CoV-2 vaccination are not entirely clear. The origin of a para-infectious phenomenon, as suspected in case A, is thought to be autoimmune mediated and presumably based on molecular mimicry between epitopes of viral spike proteins and specific homologous self-proteins of the nervous system . Antibodies produced by the activated immune system will bind to viral epitopes and additionally, via a cross-reaction, damage specific parts of the nervous system. The modified RNA within the Pfizer/BioNTech vaccine will be anchored in the host cell membrane . After vaccination, cross-reactivity may occur again by renewed production of the auto-antibodies already known by the immune system . We hypothesize that the relative short timespan between the first and second vaccination with a still activated immune response might explain why symptoms did not worsen after the second vaccine in case A. A recent small (n = 15) post-mortem cohort-study showed, however, that patients with a SARS-CoV-2 infection—vaccination status unknown—have significantly more microglial activation (innate immune system) in the brainstem. This suggests that also other pathophysiological mechanisms might be involved .
The post-vaccination thunderclap headache, without a preceding SARS-CoV-2 infection, (case B and C) presumably, has a different cause. The onset of symptoms shortly after vaccination suggests a direct correlation with SARS-CoV-2 vaccination. Different hypotheses have been postulated.
First, headache is commonly seen in patients suffering from a respiratory virus and after a vaccination, including SARS-CoV-2-vaccines [3, 4]. Post-vaccination headache might be based on the same pathophysiological mechanism as described after a virus infection: although not fully understood, this might be ascribed to fever, activation of immunoinflammatory mediators, or a direct effect of specific microorganisms . This might also apply to post-vaccination thunderclap headache, supported by the concomitant signs of malaise and subfebrile temperature (case C).
Second, there might be reactivation of the immune system when patients have previously been infected with SARS-CoV-2 or a SARS-related infection. Medical history of patient B and C did not reveal this, but symptoms may have been subclinical.
Third, headache and encephalopathy have been reported as a neurological manifestation of SARS-CoV-2-infection due to virus induced systemic hyperinflammation by an extensive cytokine release . This could cause inflammation of multiple organ systems, including the central nervous system, and might lead to multi-organ failure . However, since the symptoms were relatively mild and the patients in case B and C were only vaccinated without a preceding infection, this cause is unlikely. Hypothetically, a milder version of this phenomenon could have occurred.
To date, there is no evidence for higher rates of neurological disease after COVID-19 vaccination  and it remains therefore unclear whether the episode of bradyphrenia and focal neurological symptoms could be related to the SARS-CoV-2 vaccine.
It remains essential to exclude other underlying conditions, including subarachnoid hemorrhage, stroke, cervical artery dissection, and cerebral venous sinus thrombosis.