Background: Combined Central and Peripheral Demyelination (CCPD) is a rare yet a novel entity that is increasingly being recognized in clinical practice all over the world. The etiopathogenesis is largely unknown, but antibodies against paranodal proteins are usually incriminated.

Methods: A 28-year-old male patient presented with initial relapsing-remitting followed by progressive neurological deficits. MRI of the Brain and spine revealed lesions typical of MS with multiple cranial and peripheral nerve thickening and enhancement. Nerve conduction study revealed demyelinating sensorimotor polyneuropathy. Anti-Neurofascin antibody panel revealed positive anti-NF140 and anti-NF 186.

Conclusions: Cases presenting with features suggestive of CNS and PNS demyelination, should be worked up for the presence of anti-neurofascin antibodies along with MRI and electrophysiological studies.