Report a case of Neuromyelitis Optica Spectrum Disorder (NMOSD) with comorbid Complex 1 Mitochondrial disorder, multifocal epilepsy, leukopenia and neutropenia leading to recurrent infections representing a challenge for treatment

AQP4 deficiency disrupts synaptic homeostasis and mitochondrial metabolism. We hypothesize that AQP4 antibodies can affect the mitochondrial respiratory chain exacerbating mitochondrial diseases

NA

A 23-year-old male presented with a focal onset seizure with impaired awareness at age 12. MRI showed a right temporal mass which was resected. Pathology revealed a low grade glioneuronal tumor. At age 18, he developed headaches, recurrent multifocal seizures and subclinical status epilepticus. Brain MRI showed extensive enhancing periventricular and corpus callosum T2 hyperintense lesions. MR spectroscopy demonstrated double lactate peak suggestive of mitochondrial disease. Gene testing showed a mutation in MT-ND4 gene encoding for NADH dehydrogenase 4 in mitochondrial complex 1. At age 19, he had left vision loss, serum aquaporin 4 antibody was positive 1:10000, hence diagnosed with NMOSD. At age 21, he had recurrence of left optic neuritis with vision loss treated with IV solumedrol, plasmapheresis and rituximab. Unfortunately, he developed mucormycotic pneumonia with cavitation requiring thoracotomy precluding further use of rituximab and other immunosuppressants. At age 22, he had right hemiparesis, a new left subcortical white matter hyperintensity with negative infectious workup. He developed multiple infections due to neutropenia and leukopenia prompting antiepileptic modification to clobazam and zonisamide. He started IVIG 2 grams monthly, filgrastim 300 mcg daily for 3 days montly and prednisone 20 mg every other day in addition to carnitine, riboflavin, thiamine and arginine to treat mitochondrial disorder and NMOSD, patient has been stable without relapses or infections ever since