Understanding the Skull-Meninges-Brain Axis and Multifocal Meningoencephalitis

By SWA

Introduction

In early 2022, as I struggled with persistent headaches, partial memory lapses, confusion, neck pain, ringing in my left ear, and a loss of color vision in my left eye, a troubling question began to form in my mind: Could COVID-19 affect the brain? When I turned to medical professionals for answers about my symptoms, I was met with reassurances like, “That’s not possible—neither COVID-19 nor mRNA vaccines can cross the blood-brain barrier (BBB) to affect the brain.

Fast forward to today, and we now know that both COVID-19 and the mRNA vaccines can indeed interact with the brain, potentially breaching the BBB. Yet, despite this recognition, a clear understanding of how these neurological effects occur—and, more importantly, how to effectively address them—remains elusive.

The skull-meninges-brain axis refers to the intricate relationship between the skull, meninges (protective layers surrounding the brain and spinal cord), and the brain itself. These structures work together to protect the central nervous system (CNS), regulate the brain’s immune environment, and maintain neurological function. Disruption of this axis, such as through inflammation or infection of the meninges and brain tissue, can lead to severe conditions, including multifocal meningoencephalitis (MME).

MME is a serious neurological disorder characterized by simultaneous inflammation of the meninges (meningitis) and brain tissue (encephalitis) in multiple areas. It can arise from infections, autoimmune reactions, or other causes, posing life-threatening risks without timely treatment.

Symptoms of Multifocal Meningoencephalitis (MME)

Patients with MME can present with a diverse range of symptoms, depending on the areas of the brain involved and the severity of inflammation. Common clinical features include:

1. Generalized Symptoms:

  • Fever
  • Fatigue or malaise
  • Persistent and severe headache

2. Neurological Symptoms:

  • Seizures: These may be focal (affecting one part of the body) or generalized.
  • Altered mental status: Confusion, lethargy, or even coma in severe cases.
  • Focal neurological deficits: Such as muscle weakness, paralysis, or sensory deficits depending on the location of inflammation.
  • Ataxia: Difficulty with coordination and balance.
  • Behavioral changes: Irritability, mood disturbances, or personality shifts.

3. Meningeal Signs:

  • Neck stiffness: A hallmark of meningeal irritation.
  • Photophobia: Sensitivity to light.
  • Nausea and vomiting: Often caused by increased intracranial pressure.

4. Symptoms of Increased Intracranial Pressure (ICP):

  • Severe, unrelenting headache
  • Papilledema (optic disc swelling, observed on eye examination)
  • Decreased level of consciousness or drowsiness

Causes and Detection of MME

Causes:

MME can result from a variety of underlying conditions, including:

  • Infections: Bacterial, viral, fungal, or parasitic pathogens.
  • Autoimmune disorders: Such as autoimmune encephalitis.
  • Paraneoplastic syndromes: Neurological syndromes caused by cancer-associated antibodies.
  • Systemic inflammatory disorders: Such as lupus or vasculitis.

Detection:

Diagnosing MME requires a combination of clinical assessment, imaging, and laboratory tests:

1. Imaging Studies:

  • MRI of the brain: The gold standard for detecting multifocal lesions. MRI can reveal areas of inflammation, edema, or necrosis in the meninges and brain tissue.
  • CT scans: Useful in emergencies but less sensitive than MRI.

2. Cerebrospinal Fluid (CSF) Analysis:

  • A lumbar puncture is performed to collect CSF, which may show:
    • Elevated white blood cell count (pleocytosis)
    • Increased protein levels
    • Decreased glucose levels (in bacterial or fungal infections)
    • Pathogen-specific markers (e.g., PCR for viruses or bacterial cultures).

3. Electroencephalogram (EEG):

  • Detects abnormal electrical activity in the brain, particularly in patients experiencing seizures.

4. Blood Tests:

  • Infections: Elevated markers of inflammation (e.g., C-reactive protein, ESR).
  • Autoimmune disorders: Antibody testing (e.g., antinuclear antibodies).

Treatment of Multifocal Meningoencephalitis (MME)

Treatment depends on the underlying cause and severity of inflammation. MME is typically managed in an intensive care setting due to its potentially life-threatening nature.

1. Antimicrobial Therapy (for infectious causes):

  • Bacterial infections: High-dose intravenous antibiotics (e.g., ceftriaxone, vancomycin).
  • Viral infections: Antivirals like acyclovir for herpes simplex virus encephalitis.
  • Fungal infections: Amphotericin B or fluconazole.
  • Parasitic infections: Targeted antiparasitic medications.

2. Immunomodulatory Therapy (for autoimmune causes):

  • Corticosteroids: To reduce inflammation (e.g., dexamethasone).
  • Plasma exchange or intravenous immunoglobulin (IVIG): For autoimmune-mediated meningoencephalitis.
  • Immunosuppressants: Such as rituximab or cyclophosphamide.

3. Symptom Management:

  • Seizure control: Antiepileptic drugs (e.g., levetiracetam).
  • Management of ICP: Mannitol or hypertonic saline to reduce brain swelling.
  • Supportive care, including hydration, nutrition, and electrolyte monitoring.

4. Long-Term Rehabilitation:

  • Physical, occupational, and speech therapy may be required to address lingering neurological deficits.

Case Report: Multifocal Meningoencephalitis and COVID-19 Vaccine Implications

A recent case involving an 84-year-old male highlights the complex interaction between MME and immune responses to vaccination. The patient, who developed impaired consciousness and high fever about 10 weeks after his fourth COVID-19 vaccination, unfortunately passed away.

Key Findings from Autopsy:

  • Neurological findings:
    • Acute ischemic changes in the thalamus, pons, and cerebellum, with microhemorrhages and perivascular T-cell infiltration.
    • SARS-CoV-2 spike protein was detected in these brain regions, but nucleocapsid protein (a marker of active viral infection) was absent, suggesting the spike protein was vaccine-derived.
  • Cardiac findings:
    • The patient also exhibited right heart failure, with pleural effusion, ascites, and dilated right ventricle. Spike protein was detected in the pituitary and adrenal glands, potentially implicating endocrine dysfunction through disruption of the renin-angiotensin-aldosterone system (RAAS).

Discussion:

  • Spike Protein and Neuroinflammation:
    • The detection of spike protein in the CNS suggests a possible immune-mediated inflammatory response, with disruption of the blood-brain barrier (BBB) allowing immune cells and vaccine-related antigens to infiltrate the brain.
  • Endocrine Dysfunction:
    • Spike protein in the pituitary and adrenal glands may have contributed to fluid retention and heart failure via RAAS dysfunction.

This case raises critical questions about the potential role of vaccine-derived spike protein in rare but serious neurological complications. While vaccines are overwhelmingly safe, ongoing surveillance and research are needed to better understand these rare events.

SARS-CoV-2, Spike Protein, and the Skull-Meninges-Brain Axis

Emerging research underscores the role of SARS-CoV-2 spike protein in driving neuroinflammation and neurodegeneration. In both human patients and animal models:

  • Spike protein persistence in the skull-meninges-brain axis was observed long after viral clearance.
  • Injection of spike protein alone in mice triggered:
    • Neuroinflammation
    • Behavioral changes (e.g., anxiety-like behaviors)
    • Worsened outcomes in stroke and traumatic brain injury models.

Conclusion

Multifocal meningoencephalitis is a rare but severe neurological condition that requires prompt diagnosis and treatment. Recent findings on SARS-CoV-2 spike protein suggest potential immune and inflammatory effects that may disrupt the skull-meninges-brain axis. While vaccines remain critical in combating COVID-19, heightened awareness of rare adverse events and ongoing research into the mechanisms of spike protein persistence are essential to safeguard vulnerable populations.

Reference: Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19 https://www.sciencedirect.com/science/article/pii/S1931312824004384
Multifocal meningoencephalitis after vaccination against COVID-19
https://pubmed.ncbi.nlm.nih.gov/39570102/
 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742
ISBN: 0-9703195-0-9 

 

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