Fulminant and fatal onset of pan-aquaporinopathy

Area of Science:

• Neurology
• Immunology
• Pathology

Background:

• Neuromyelitis optica spectrum disease (NMOSD) is an autoimmune disorder targeting the central nervous system.
• Early high-dose steroids and plasma exchange (PE) are standard treatments for NMOSD attacks.
• Treatment resistance occurs in up to 20% of NMOSD patients.

Observation:

• A young female experienced a severe, monophasic NMOSD attack involving optic nerves, spinal cord, and circumventricular organs (CVOs), including the pineal gland.
• Despite receiving steroids and daily plasma exchange (PE), her condition rapidly deteriorated.
• The patient exhibited strongly positive AQP4-antibodies and extensive lesions across all AQP4-expressing sites.

Findings:

• This case represents the first documented instance of NMOSD with widespread lesions in all AQP4-expressing sites, including novel involvement of the pineal gland.
• The rapid progression and fatality despite optimal treatment, termed the "anti-Lazarus effect," underscore treatment resistance in severe NMOSD.
• Lesions in the periventricular ependyma and CVOs are exceptionally rare in NMOSD.

Implications:

• This case highlights the potential for devastating NMOSD attacks resistant to current therapies.
• Further research into the mechanisms of treatment resistance in NMOSD is crucial.
• Consideration of very early immunosuppressive therapy or novel salvage treatments may be warranted for severe NMOSD cases.