INCREASED CSF PROTEINS IN CMT1A: ROLE OF ROOT HYPERTROPHY OR SUPERIMPOSED CIDP?

Abstract

A 45‐year‐old male patient came to our observation with a clinical picture of slowly progressive wasting and weakness of distal limb muscles, mild distal sensory to all modalities, with pes cavus and hammer toes. His parents were consanguineous and both were affected by Charcot‐Marie‐Tooth disease (CMT). In the patient, disease onset occurred at age 11. Disease course was slowly progressive, but a somewhat sudden worsening had occurred three years before; muscle wasting and weakness were slightly asymmetrical. A previous spinal tap had demonstrated very high levels of CSF proteins (about 300 mg/dl). When admitted to our hospital, a repeat CSF examination revealed even higher protein content (380 mg/dl), raising the hypothesis of CIDP (chronic inflammatory demyelinating polyradiculoneuropathy) superimposed on CMT. Nerve conduction studies showed a diffuse and uniform nerve conduction slowing (10–12 m/s in limb nerves). Molecular analyses demonstrated the common 17p11.2 duplication of CMT1A. We performed nerve biopsy looking for signs of nerve inflammation, and MR scan of lumbar roots searching for evidence of blood‐root barrier disruption and root inflammation (root enhancement). We administered to the patient two courses of high dose intravenous immunoglobulin (IVIg), followed by steroid treatment for some weeks: there was a questionable clinical improvement and CSF protein content slightly decreased (288 mg/dl). Nerve biopsy showed the typical features of CMT1A with diffuse onion‐bulb formations, but neither focal abnormality nor inflammatory infiltrates were observed. MR scan demonstrated very mild enhancement of lumbar nerve roots after gadolinium administration, but the most impressive finding was a striking hypertrophy of the lumbar roots, which were overall much thicker than the cord itself and filled almost completely the spinal canal. Although superimposition of CIDP cannot be excluded, root hypertrophy causing leakage of the blood‐root barrier or even block of the CSF circulation appears the most likely explanation of the incredible rise of CSF protein content in this case.Partly supported by a grant from the Italian Ministry of Health.