Astrocytopathy in Wernicke Encephalopathy and Neuromyelitis Optica Spectrum Disorder. Pathogenic Differences With Occasional Clinical and Neuroimaging Overlap. A Review

There is an increasing number of single case reports describing patients with findings compatible with thiamine deficiency, in whom rapid replacement of thiamine fails to induce improvement. Further work-up identifies positive aquaporin-4 antibodies (AQP-4) leading to a final diagnosis of neuromyelitis optica spectrum disorder (NMOSD). Occasionally, NMOSD is the initial diagnosis, but it turns out that the patient has thiamine deficiency. Similarly, these two diagnoses may overlap, particularly with area postrema lesions and in other cases of protracted vomiting. We reviewed the literature to attempt further clarification for this clinical overlap. The common denominator is the astrocyte, as cytotoxic edema due to impaired mitochondrial dysfunction and lactic acidosis in instances of thiamine deficiency causes downregulation of the AQP-4 receptor leading to vasogenic edema and breakdown of the blood-brain-barrier (BBB). Similar dysfunction of the AQP-4 receptor occurs because of IgG binding antibodies in NMOSD. Impaired glutamate transport in the astrocytic podocytes regardless of the AQP4 receptor etiologic mechanism causes excitotoxicity. Awareness of this clinical overlap is critical to initiate timely treatment in thiamine deficiency states and NMOSD