Case Presentation: 62-year-old man with recent hospitalization for septic shock due to toe osteomyelitis,complicated by severe C. difficile infection requiring fecal transplant 3 weeks prior to admission,presenting with confusion,right-sided weakness,and ataxia.Symptoms were first noted 2 weeks after the fecal transplant and consisted of depressed mood and right shoulder weakness.Neurological exam was notable for neglect of right visual field,sensory neglect of the right side,2/5 motor strength in right upper and lower extremities.Magnetic resonance imaging of the brain showed multiple ring-enhancing lesions throughout the white matter of both cerebral hemispheres,basal ganglia,and bilateral cerebral peduncles,with no edema or mass-effect.Cerebrospinal fluid analysis was unrevealing,with no oligoclonal bands or malignant cells.An echocardiogram didn’t reveal vegetations.An extensive infectious workup including serum and CSF testing for toxoplasmosis,HIV,tuberculosis,cryptococcus were negative.CT scan of the chest and abdomen revealed no infection or malignancy.Brain biopsy was consistent with active demyelination.He received IV steroids followed by an oral taper.His mental status and weakness improved slightly, however, subsequent MRI showed multiple new small enhancing white matter lesions,requiring 2 further admission for plasmapheresis and Rituxan.A repeat MRI 2 months later showed decrease in size of most of the lesions with no evidence of new or enhancing lesions and improvement of cognition.
Discussion: ADEM is a monophasic inflammatory demyelinating disorder,more common in pediatrics.Due to its rarity in adults,there is limited understanding of its triggers,clinical course,or management.Mounting evidence indicates that gut microbiota can influence the immune and nervous system via a bidirectional relationship termed the microbiota-gut-brain axis.This influences the pathogenesis of a number of disorders in which inflammation is implicated,such as mood and demyelinating disorders.In addition,acute stress increases GI and BBB permeability through activation of mast cells,that further induce a strong auto-inflammatory response,leading to inflammation and neuronal damage.We postulate that in our case, ADEM was triggered by severe C. difficile infection.Our patient’s symptoms were refractory to steroids and plasmapheresis,which have been previously used for treatment,subsequently requiring 2 doses of Rituxan before clinical and radiological improvement were noted.
Conclusions: Increasing evidence indicates that a delicate balance of gut microorganisms is necessary for health, disruption of which is associated especially with neuropsychiatric disorders.We present the case of a middle aged adult with refractory ADEM triggered by combination of systemic infection and severe C difficile requiring fecal transplant who improved dramatically after combination of immunotherapies,including IV steroids,plasmapheresis,and Rituxan.