Case Report: Multiple sclerosis and Neurofibromatosis type 1: a rare comorbidity

Neurofibromatosis type 1 (NF1) and Multiple Sclerosis (MS) are distinct neurological conditions with different underlying pathogenetic mechanisms. Their co-occurrence is exceedingly rare, with approximately 40 cases reported in the literature. Due to overlapping clinical and neuroimaging features, diagnosis is often challenging. We describe two cases of NF1-MS comorbidity highlighting the importance of a careful neuro-ophthalmological and neuroradiological evaluation for this rare association.

A 33-year-old female presented with acute bilateral visual loss and bladder dysfunction. Brain and spinal cord Magnetic Resonance Imaging (MRI) showed multiple demyelinating lesions and a right globus pallidus Focal Area of Signal intensity (FASI); CSF exam showed oligoclonal bands, supporting a diagnosis of MS. Moreover, the identification of café-au-lait macules, optic pathway glioma (OPG) and Lisch nodules led to the discovery of a pathogenic NF1 variant.

A 49-year-old male with left eye visual blurring, right optic nerve glioma, café-au-lait macules and subcutaneous neurofibromas was diagnosed with NF1. Initial brain and spine MRI identified a cervical neurofibroma and a dorsal intramedullary lesion, originally interpreted as a FASI. The patient developed new-onset genitourinary and sensory deficits. Follow-up brain MRI revealed new periventricular and subcortical demyelinating lesions, including a contrast enhancing one. Given its specific localization within the dorsolateral columns, the spinal lesion was redefined as a demyelinating plaque, supporting the diagnosis of definite MS.

Our cases highlight two distinct diagnostic trajectories of NF1 and MS coexistence: MS as the presenting condition (Patient 1) and MS diagnosed during NF1 surveillance (Patient 2). The diagnostic challenge involves differentiating MS-related optic neuritis from OPG-associated visual symptoms and demyelinating plaques from FASIs. Furthermore, the management of MS co-occurring with NF1 is further complicated by the absence of established therapeutic guidelines. These cases highlight the importance of rigorous neuroimaging and neuro-ophthalmological evaluation in NF1 patients presenting new-onset symptoms or atypical MRI evolution.