Massive enlargement of all peripheral nerves

Abstract

A 29 year old woman presented with three months of intermittent but increasing bifacial paraesthesia. On close questioning she reported five years of mild intermittent paraesthesiae in both hands and very mild proximal upper limb weakness. Examination revealed a small area of pinprick loss over the left cheek as the only abnormality. Nerve conduction study of both upper limbs demonstrated symmetric distal sensory and motor abnormalities strongly suggestive of demyelination (small or absent sensory potentials and markedly prolonged distal motor latencies). The remainder of extensive neurophysiologic assessment was normal. MRI brain and whole spine revealed massive symmetric enlargement of multiple cranial nerves, nerve roots, brachial and lumbosacral plexuses (Fig. 1A–F), without contrast enhancement. CSF showed albuminocytologic dissociation (protein 1.48 g/L) and extensive blood tests and whole body PET scan were normal. The most likely diagnosis isA.SarcoidosisB.Charcot Marie Tooth (CMT)C.Chronic Inflammatory Demyelinating Polyradiculopathy (CIDP)D.Leprosy CIDP was diagnosed based on these neurophysiologic, CSF and MRI findings and intravenous immunoglobulin (ivIg) was eventually commenced due to increasing symptoms. One year following presentation the patient was largely asymptomatic on maintenance monthly ivIg, with significant improvement in neurophysiologic parameters but no change in MRI features. The striking feature of this case was the extreme discordance between a mild clinical presentation of CIDP and the MRI findings of widespread and massive hypertrophy of multiple cranial nerves, nerve roots and plexuses. This point is highlighted by noting that the dramatic lumbar root and plexus MRI abnormalities were associated with absolutely no symptoms, signs or neurophysiological abnormalities. Massive peripheral nerve enlargement has a relatively limited differential diagnosis. Congenital causes, such as Charcot-Marie-Tooth or Neurofibromatosis; and acquired pathology, in particular leparomatous disease or an infiltrative process such as systemic amyloidosis, seemed unlikely given demyelinating neurophysiology that was clearly reversible with ivIg. Massive nerve root thickening on MRI has been reported in inflammatory conditions. The most common of these being CIDP, but to our knowledge this is the first report of massive cranial nerve enlargement in the condition [1Duggins A.J. McLeod J.G. Pollard J.D. et al.Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy.Brain. 1999; 122: 1383-1390Crossref PubMed Scopus (193) Google Scholar, 2Adachi Y. Sato N. Okamoto T. et al.Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient.Neuroradiology. 2010; 53 ([published Online First: Epub Date]): 3-11https://doi.org/10.1007/s00234-010-0684-7Crossref PubMed Scopus (69) Google Scholar, 3Shibuya K. Sugiyama A. S-i Ito et al.Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.Ann Neurol. 2015; 77 ([published Online First: Epub Date]): 333-337https://doi.org/10.1002/ana.24314Crossref PubMed Scopus (85) Google Scholar]. The initial report correlated massive root hypertrophy with a long and disabling disease course [[1]Duggins A.J. McLeod J.G. Pollard J.D. et al.Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy.Brain. 1999; 122: 1383-1390Crossref PubMed Scopus (193) Google Scholar]. However subsequent case series have not found any definite correlation between nerve hypertrophy and disease severity or duration [2Adachi Y. Sato N. Okamoto T. et al.Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient.Neuroradiology. 2010; 53 ([published Online First: Epub Date]): 3-11https://doi.org/10.1007/s00234-010-0684-7Crossref PubMed Scopus (69) Google Scholar, 3Shibuya K. Sugiyama A. S-i Ito et al.Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.Ann Neurol. 2015; 77 ([published Online First: Epub Date]): 333-337https://doi.org/10.1002/ana.24314Crossref PubMed Scopus (85) Google Scholar]. It is possible that MRI features differ between the various subtypes of CIDP and focal demyelination on neurophysiological testing of peripheral nerves has been associated with focal reversible contrast enhancement [3Shibuya K. Sugiyama A. S-i Ito et al.Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.Ann Neurol. 2015; 77 ([published Online First: Epub Date]): 333-337https://doi.org/10.1002/ana.24314Crossref PubMed Scopus (85) Google Scholar, 4Kuwabara S. Nakajima M. Matsuda S. Hattori T. Magnetic resonance imaging at the demyelinative foci in chronic inflammatory demyelinating polyneuropathy.Neurology. 1997; 48 ([published Online First: Epub Date]): 874-877https://doi.org/10.1212/wnl.48.4.874Crossref PubMed Google Scholar]. However in routine practice MRI abnormalities simply provide supportive evidence of CIDP without specific management implications. The remarkable findings in our case suggest that massive hypertrophy can occur with very mild clinical disease. We propose that recurrent or chronic subclinical inflammation, demyelination and repair can lead to massive hypertrophy, almost as an oyster lays down layers of a pearl. Dr Fong was involved in the management and care of the patient and preparation and drafting of the manuscript. No disclosures relevant to this study are reported. Dr Masters was involved in the management and care of the patient and preparation and drafting of the manuscript and figures. No disclosures relevant to this study are reported. Dr Watson was involved in the management and care of the patient and preparation and drafting of the manuscript. No disclosures relevant to this study are reported.