Aim/Background: We report a case of Acute Combined Central and Peripheral Demyelination (ACCPD). This rare disease presents with features of both peripheral and central demyelination. Methods: Case Report Results: A 24 year-old Iraqi female presented with acute onset of ascending paralysis, numbness and areflexia over the course of a few days. Systemic examination was negative. She responded to IVIG. She suffered two severe relapses over the next three months, which resolved rapidly with PLEX/corticosteroid. CSF was normal after first and second relapses. Brain and cord MRI revealed multiple T2/FLAIR hyperintensities consistent with multiple sclerosis. There were no longitudinally extensive cord lesions. Aquaporin 4 antibody assay is pending. ANA was strongly positive; anti-DSDNA and SS antibodies were negative; complement4 was low and serum cyroglobulins were positive. Hepatitis C was negative. Ganglioside antibody assay was negative. Anti-neurofascin is pending. Neurophysiology confirmed features of an acquired demyelinating neuropathy with profound secondary axonal denervation. Conclusions: The underlying etiology of ACCPD is presumed autoimmune likely secondary to auto-antibody targeting of central and peripheral myelin epitopes. Low complement component 4 and cryoglobulinemia in this patient supports an autoimmune pathogenesis. Neurofascin has been previously reported as one such auto-antibody in ACCPD.