Co-Existent Central and Peripheral Demyelination: Related or Coincidental?

Background: Hereditary Sensory Motor Neuropathy (HSMN) 1A and Multiple Sclerosis (MS) are distinct demyelinating disorders affecting the peripheral and central nervous systems, respectively. We present a case of simultaneous occurrence of both conditions, exploring the clinical presentation, diagnostic workup, and potential interplay between these diseases. Case presentation and clinical approach: A 49-year-old male with a history of optic neuritis presented with progressive numbness, weakness, and sensory loss in all extremities over four years. Neurological examination revealed distal weakness, sensory deficits in a stocking-glove distribution, pes cavus, and hammer toes. Nerve conduction studies and electromyography confirmed sensory motor demyelinating polyneuropathy. The patient's lack of response to intravenous immunoglobulin therapy suggested hereditary neuropathy as an etiology. Genetic testing identified a PMP22 gene duplication, confirming HSMN 1A. Elevated cerebrospinal fluid protein level and oligoclonal bands, combined with magnetic resonance of the brain showing multiple T2 hyperintense lesions in the brain and spinal cord, fulfilled the diagnostic criteria for MS.

Discussion: This case of co-existing HSMN 1A and MS highlights a rare overlap of peripheral and central demyelination. While HSMN 1A results from PMP22 gene duplication, primarily affecting peripheral myelin, MS is driven by immune-mediated central myelin attacks. The co-existence of these disorders suggests potential shared mechanisms, such as immune dysregulation. Some evidence suggests that overexpression of PMP22 in HSMN 1A may disturb immune tolerance, possibly triggering autoimmune responses linked to MS. Further research is needed to explore the genetic and autoimmune interplay between these two diseases, expanding our understanding of demyelinating disorders.