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Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency
  1. Sean W Taylor1,2,
  2. Ruple S Laughlin1,
  3. Neeraj Kumar1,
  4. Brent Goodman3,
  5. Christopher J Klein1,
  6. Peter J Dyck1,
  7. P. James B. Dyck1
  1. 1Department of Neurology, Mayo Clinic Rochester, Minnesota, USA
  2. 2Department of Neurology, Queens University, Kingston, Ontario, Canada
  3. 3Department of Neurology, Mayo Clinic Scottsdale Arizona, Minnesota, USA
  1. Correspondence to Dr P. James B. Dyck, Department of Neurology, Mayo Clinic, Rochester MN, 55905; dyck.pjames{at}mayo.edu

Abstract

Introduction Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised.

Objectives To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy.

Methods Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified.

Results 34 patients were identified (median age 55 years, range 36–78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0–0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation.

Conclusions An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance.

  • Copper
  • sensory neuropathy
  • peripheral neuropathy
  • copper myelopathy

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Footnotes

  • Contributors SWT and RSL contributed equally to this work. SWT, RSL, NK, BG, CJK, PJD and PJBD designed the study and reviewed the manuscript. RSL, NK, CJK, PJD and JBD clinically assessed subjects. SWT, RSL and PJBD wrote and revised the manuscript. SWT, RSL and PJBD performed the analyses.

  • Competing interests No, there are no competing interests.

  • Patient consent Obtained.

  • Ethics approval Mayo Clinic Institutional Review Board approved the research protocol and patients gave written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement SWT takes full responsibility for the data, the analyses and interpretation, the conduct of the research, has full access to all of the data, and has the right to publish any and all data separate and apart from any sponsor.

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