69.: Neuropathological, imaging and clinical features of a patient with neurofibromatosis type 1 and multiple sclerosis

Abstract

We present detailed histopathological and clinical characterisation of a young male patient with neurofibromatosis type 1 (NF1) and primary progressive multiple sclerosis (MS) and discuss the putative basis for association between these diseases. A young man with typical cutaneous stigmata of NF1 presented in his late 20s with a progressive myelopathy and pancerebellar disturbance. MRI demonstrated multifocal T2-weighted hyperintensities in the hemispheres, brainstem and spinal cord. Investigations revealed cerebrospinal fluid oligoclonal immunoglobulin G bands, and absent visual evoked responses. Clinical progression was rapid and non-remitting. Within 4 years he was wheelchair-bound. He died following an aspiration event 6 years after presentation. Histopathologically, extensive multifocal, and sometimes confluent, areas of demyelination were seen with perivascular inflammation and astrogliosis in the hemispheres and spinal cord. Abundant corpora amylacea deposition in areas of white matter degeneration was present. NF1 is an autosomal dominant neurocutaneous disorder caused by mutation in the Neurofibronin gene. It is unclear if the concurrence of MS and NF1 occurs by chance but early hypotheses of causal associations followed the discovery that the oligodendrocyte myelin glycoprotein gene is embedded within the NF1 gene. Approximately 27 patients with MS and NF1 have been described but none with detailed neuropathologic data, to our knowledge. In this patient, the rapidly progressive phenotype, severity of tissue injury histopathologically and extensive presence of corpora amylacea are of interest. Clinicians should be vigilant for the development of central nervous system demyelinating disease in patients with NF1.