Peripheral neuropathy in patients with CPEO associated with single and multiple mtDNA deletions.
OBJECTIVE
To characterize peripheral nerve involvement in patients with chronic progressive external ophthalmoplegia (CPEO) with single and multiple mitochondrial DNA (mtDNA) deletions, based on clinical scores and detailed nerve conduction studies.


METHODS
Peripheral nerve involvement was prospectively investigated in 33 participants with CPEO (single deletions n = 18 and multiple deletions n = 15). Clinically, a modified Total Neuropathy Score (mTNS) and a modified International Cooperative Ataxia Rating Scale (mICARS) were used. Nerve conduction studies included Nn. suralis, superficialis radialis, tibialis, and peroneus mot. Early somatosensory evoked potentials were obtained by N. tibialis stimulation.


RESULTS
Participants with multiple deletions had higher mTNS and mICARS scores than those with single deletions. Electrophysiologically in both sensory nerves (N. suralis and N. radialis superficialis), compound action potential (CAP) amplitudes and nerve conduction velocities were lower and mostly abnormal in multiple deletions than those in single deletions. Early somatosensory evoked potentials of N. tibialis revealed increased P40 latencies and decreased N35-P40 amplitudes in multiple deletions. Both sensory nerves had higher areas under the receiver operating characteristic curves for the decreased CAP amplitudes than the 2 motor nerves. The N. suralis had the best Youden index, indicating a sensitivity of 93.3% and a specificity of 72.2% to detect multiple deletions.


CONCLUSIONS
Peripheral nerve involvement in participants with multiple mtDNA deletions is an axonal type of predominant sensory neuropathy. This is clinically consistent with higher mTNS and mICARS scores. Sensory nerve involvement in participants with multiple deletions was not correlated with age at onset and duration of disease.
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Diana
D
Lehmann
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Malte E
ME
Kornhuber
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Carolina
C
Clajus
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Charlotte L
CL
Alston
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Andreas
A
Wienke
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Marcus
M
Deschauer
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Robert W
RW
Taylor
Form the Department of Neurology (D.L., M.E.K., C.C., S.Z.), Institute of Medical Epidemiology, Biometrics and Informatics (A.W.), University of Halle-Wittenberg, Halle/Saale, Germany; Wellcome Trust Centre for Mitochondrial Research (C.L.A., R.W.T.), Institute of Neuroscience, The Medical School, Newcastle University, UK; and Department of Neurology (M.D.), Technical University Munich, Germany.
Stephan
S
Zierz