Neurological complications of influenza vaccination: navigating the spectrum with a focus on acute disseminated encephalomyelitis (ADEM)
Authors: Mashkoor Yusra , Nadeem Abdullah , Fatima Tehreem , Aamir Minahil , Vohra Laiba I. , Habib Ashna , Khan Afsheen , Raufi Nahid , Habte Alexander 
Published: January 2024

Introduction:
Acute disseminated encephalomyelitis (ADEM) is a rare neurological disorder characterized by inflammation in the brain and spinal cord. This systematic review aims to investigate the potential association between ADEM and influenza vaccination by analyzing relevant case reports. ADEM is traditionally thought to be a monophasic condition, predominantly affecting children, often following viral illnesses or immunizations. Recent attention has focused on a possible link between ADEM and influenza vaccination, prompting the need for a thorough investigation.

Methods:
The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the AMSTAR2 (A MeaSurement Tool to Assess systematic Reviews 2) guidelines. Electronic searches were conducted on PubMed, Cochrane Library, and clinicaltrials.gov databases, spanning up to August 2023. Inclusion criteria encompassed full-text articles in English, observational studies, case reports, and case series providing comprehensive details for confirming clinical diagnoses of ADEM following influenza vaccination. Data were extracted, including demographic information, vaccination details, clinical symptoms, diagnostic evaluations, treatment modalities, and outcomes. Quality assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal tool.

Results:
A total of 23 cases of ADEM following influenza vaccination were identified from 19 included articles. The mean age of affected individuals was 40.2 years (±25.7) with 60.8% being male. Common presenting symptoms included muscle weakness (52.1%), urinary abnormalities (30.4%), altered consciousness (26%), and sensory disturbances (26%). Neurological examination revealed findings such as extensor plantar reflex (positive Babinski sign) in 26%, hyperreflexia in 30.4%, and generalized hyporeflexia in 13% of the cases. Diagnostic evaluations involved MRI, showing multiple hyperintense lesions in cerebral hemispheres (43.4%), subcortex (60.8%), and spinal cord (39.1%). Cerebrospinal fluid analysis indicated elevated white blood cell count in 69.5% of cases, with lymphocytic pleocytosis in 52.1%. Oligoclonal bands were reported positively in 8.6% of cases. Treatment approaches varied, with intravenous methylprednisolone being the most common (39.1%). Out of the 23 cases, two (8.6%) patients had a fatal outcome, while the rest showed clinical improvement with complete or partial resolution of symptoms. Persisting symptoms included numbness in the lower extremities (8.6%) and impaired ability to walk after 10 months (4.3%).

Conclusion:
While the association between ADEM and influenza vaccination is rare, healthcare professionals should remain vigilant and consider patients’ vaccination history, particularly following an influenza immunization. This systematic review highlights the clinical manifestations, diagnostic tools, treatment approaches, and outcomes of ADEM cases post-influenza vaccination. Further research is essential to understand this association and improve clinical decision-making, ensuring the safety and efficacy of immunization programs.