A Vaccine, A Brain Attack, and A Medical Mystery
The Story of Reversible Splenial Lesion Syndrome
The Patient Who Vanished and Returned
Imagine receiving a routine COVID-19 vaccination, then days later your personality begins to change. You become agitated, confused, and experience seizures. Your family doesn't recognize you anymore. Brain scans reveal something bizarre—a tiny, mysterious lesion in the very center of your brain that appears like a ghost on MRI, only to vanish without a trace weeks later.
This isn't science fiction; it's the perplexing reality of a newly recognized neurological condition that combines metabotropic glutamate receptor 5 (mGluR5) autoimmune encephalitis with reversible splenial lesion syndrome (RESLES) following SARS-CoV-2 vaccination.
Key Facts
- Extraordinarily rare condition
- Combines autoimmune encephalitis with reversible brain lesion
- Most patients make full recovery with treatment
- Temporal association with COVID-19 vaccination
When Defense Turns to Attack: Understanding mGluR5 Autoimmune Encephalitis
What is mGluR5 and Why Does It Matter?
Think of your brain as an incredibly complex communication network, with neurotransmitters as messengers and receptors as specialized receiving stations. mGluR5 is one such receiving station for glutamate, the brain's most common excitatory neurotransmitter1 .
In autoimmune encephalitis, the body's immune system mistakenly produces antibodies that target these essential receptors. Research has demonstrated that patients' antibodies cause "a significant and specific decrease of cell-surface synaptic and extrasynaptic mGluR5"1 , effectively reducing the number of functional communication stations in the brain.
mGluR5 Function
Crucial for learning, memory, mood regulation, and cognitive functions
The Clinical Picture: How mGluR5 Encephalitis Manifests
The Ghost in the Machine: Reversible Splenial Lesion Syndrome
What is RESLES?
Reversible splenial lesion syndrome (RESLES) refers to a temporary abnormality in the splenium, the posterior part of the corpus callosum—the thick bundle of nerve fibers that connects the brain's two hemispheres2 7 .
This lesion appears on MRI as a bright spot indicating cytotoxic edema—essentially, swollen brain cells due to fluid imbalance7 9 . The most remarkable characteristic is its complete reversibility—within days to weeks, this ghost-like lesion vanishes without a trace2 .
Brain Anatomy
The corpus callosum connects the brain's hemispheres
Causes and Symptoms of RESLES
Both viral and bacterial
Or antiepileptic drug changes
Hypoglycemia, hyponatremia
The Vaccination Connection: Temporal Association vs. Causation
The Emerging Evidence
A comprehensive systematic review analyzed 65 cases of encephalitis occurring after COVID-19 vaccination3 . The findings revealed several important patterns:
- Cases occurred after various vaccine types, including AstraZeneca (38.5%), Pfizer (33.8%), and Moderna (16.9%)
- Most cases (66.1%) occurred after the first vaccine dose
- The average time between vaccination and symptom onset was approximately 10 days3
Distribution of encephalitis cases by vaccine type3
Putting Risk in Perspective
A massive South Korean study involving nearly 130 million vaccine doses found a small but statistically significant increased risk of encephalitis after COVID-19 vaccination (1.26-fold increase)8 .
However, the absolute risk remained extremely small—approximately 1.9 cases per million doses8 .
Important Note
The scientific consensus strongly supports that the benefits of COVID-19 vaccination far outweigh the risks, even considering these rare neurological events.
The Smoking Gun: Experimental Evidence of Antibody Pathogenicity
Setting Up the Critical Experiment
Researchers designed a study to answer a fundamental question: What happens to mGluR5 receptors when exposed to patients' antibodies?1
Antibody Purification
IgG antibodies isolated from a patient with confirmed mGluR5 encephalitis
Neuronal Culture
Rat hippocampal neurons grown in culture
Antibody Exposure
Neurons incubated with patient antibodies or control antibodies for 24 hours
Measurement
Confocal microscopy quantified mGluR5 cluster density1
Striking Results and Their Meaning
The findings were both clear and remarkable:
| Experimental Component | Finding | Significance |
|---|---|---|
| mGluR5 cluster density | Significant decrease after antibody exposure | Explains neurological symptoms |
| PSD95 levels | Unchanged | Demonstrates antibody specificity |
| Reversibility | Gradual recovery after antibody removal | Explains potential for recovery |
The Diagnostic Toolkit: Essential Tools for Identification
Diagnostic Process Flow
Combining clinical presentation, antibody testing, and imaging leads to diagnosis
Treatment and Outcomes: The Path to Recovery
Treatment Approaches
First-line Immunotherapy
Second-line Options
Symptomatic Management
Cancer-directed Therapy
Conclusion: A Story of Medical Detectiveism and Hope
The rare intersection of mGluR5 autoimmune encephalitis and reversible splenial lesion syndrome following COVID-19 vaccination represents a fascinating narrative in modern medicine. It showcases both the unexpected ways our immune systems can occasionally malfunction and the remarkable capacity for recovery when appropriate treatments are administered.
For the handful of individuals affected worldwide, the journey typically begins with terrifying neurological and psychiatric symptoms but often ends with dramatic recovery—a testament to both the resilience of the human brain and the importance of medical recognition of this condition.