Atypical inflammatory demyelinating syndrome with central and peripheral nerve involvement

Abstract We report a patient who has peripheral demyelination in the form of chronic inflammatory demyelinating polyneuropathy (CIDP) with central demyelination following a relapsing-remitting disease course. The patient developed bilateral sequential optic neuritis predating the diagnosis of CIPD, then developed a profound brainstem syndrome with ataxia, dysarthria, a complex eye movement disorder, visual disturbance and urinary incontinence. Interval imaging fulfilled McDonald criteria for multiple sclerosis (MS) with a right parieto-occipital tumefactive lesion with new enhancing lesions in the right temporal white matter and midbrain tegmentum. Oligoclonal bands (OCBs) were matched and serum antibodies against aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) were negative. Genetic sequence analysis and deletion/duplication testing revealed variants of uncertain significance with compound heterozygosity for point mutations in two genes, DYNC1H1 and SH3TC2, which are associated with Charcot-Marie-Tooth (CMT) disease though the patient was negative for known CMT mutations. The patient responded poorly to steroids and regular intravenous immunoglobulin (IVIg) but clinically improved following aggressive immunomodulatory therapy with pulsed steroids and plasmapheresis, followed by Rituximab. Combined central and peripheral demyelination (CCPD) is rare. Autoimmune mechanisms are postulated in the pathogenesis. Whether overlap of central and peripheral demyelination is coincidental or caused by a shared epitope in both the peripheral and central nervous systems still remains to be elucidated. There is no clear therapeutic consensus in the treatment of both central and peripheral demyelination, though immunomodulating treatment strategies may minimise disability and improve prognosis.