Does polyethylene glycol, used as an excipient at mRNA-based (Moderna, Pfizer) vaccines, cause an increase in the frequency of epilepsy in PWE?
Authors: Ahmed Amr 
Published: September 2022

PEGs, also known as polyethylene glycol, are hydrophilic polymers of various diameters made up of repeated (-CH2-CH2-O-) units and are frequently used in commercial and medical applications like cosmetics, and pharmaceutical preparations and now increase in drug development but the concern about antibodies against PEGs is producing (1) PEGs (PEGs2000) are used as excipients in mRNA-based vaccines like Moderna and Pfizer (2) it is utilized in these vaccines to encapsulate the SLNPs, polyethylene glycol (PEG), which has been identified as the main culprit for this anaphylactic reactions4,5. PEG is used in a wide variety of additional products6, including cosmetics, meals, and pharmaceutical preparations. Its action is essential for preserving the colloidal stability of nanoparticles in biological fluids as well as for lowering the amount of uptake by filter organs, which increases the effectiveness and safety of the particles after vaccination. (3).One of the most prevalent neurological conditions, epilepsy is linked to higher morbidity and mortality rates. PWE who aspirate during seizures have a higher chance of developing pneumonia, and infections can make their PWE's seizure symptoms worse. Patients with particular epilepsy syndromes who take immunosuppressive medications (such as those with tuberous sclerosis complex or autoimmune encephalitis) must also be regarded as "at risk." PWE is also more likely to have comorbid conditions, which increases their chance of developing a severe SARS-CoV-2 infection. (4).In a study for colonoscopic screening using PEG as safe more than sodium, the study reported 2 cases of increased frequency of epilepsy attacks on two women who were admitted with generalized tonic-clonic seizures induced by precolonoscopic PEG preparation because of PEG effect on fluids and hyponatremia-induced epilepsy, Electrolyte solutions containing PEG have been linked to seizure activity and/or unconsciousness. Low serum osmolality and irregular electrolytes were linked to the seizure cases. Patients having a history of seizures or a tendency toward them, as well as those with known or suspected hyponatremia, should receive therapy with these drugs with caution (5)Numerous research and evaluations found no evidence linking vaccines to afebrile seizures, and they concluded that immunizations do not cause the beginning of epilepsy [6]. In patients in our cohort who grew more prone to seizures post vaccination but did not have a simultaneous fever, this finding raises doubts about the direct impact of immunization, even though these patients had more serious epilepsy with less control than our multivariate analysis did confirm that seizures frequency is only influenced by one component. The frequency pattern of pre-vaccine seizures was getting worse consequently, it is conceivable to imagine that immunization was an immediate contributing factor in altering seizure frequency, in actuality, the patients who deteriorated were affected by epilepsy that is more severe and poorly controlled. (7) According to several observational studies, individuals with epilepsy (PWE) experienced worsening seizure control during the COVID-19 pandemic. (8-13) An observational study by Isabel Martinez-Fernandez shows Seizure frequency increased after vaccination in 6.2% of people with epilepsy. 6.2% of PWE saw a meaningful increase in seizure frequency after receiving the covid-19 vaccine and in 61.5% of these cases, other probable causes were also present, the causes of worsening seizures are distinct from immunization were identifiable, and patients with a higher risk of seizures and those who had an aggravation after receiving the covid-19 immunization monthly epilepsy. (14) Understanding that PEG is immunogenic and antigenic is important. More thorough investigations are necessary to thoroughly assess the effect of anti-PEG antibodies on PEG conjugates. The chance of experiencing potential adverse effects is increased by the growing usage of PEG and PEGylated therapeutic proteins. First off, side products created during polymer production can indirectly cause hypersensitivity. Second, the pharmacokinetic behavior of the PEGylated medicines exhibits some undesirable modifications. Furthermore, there are certain unanticipated impacts of the leftovers because PEG is not biodegradable. (15) Finally, this letter to the editor gives alarming about the immune response in form of anti-PEGs antibodies as a concern in the future as PEGs are included in drug development as nanoparticles and protein bindings to decrease the clearance of these compounds. And many cases of epilepsy were reported as increasing the frequency after covid-19 vaccinations.