Journal of Neurology

, Volume 262, Issue 4, pp 870–880 | Cite as

Nerve ultrasound for differentiation between amyotrophic lateral sclerosis and multifocal motor neuropathy

  • Alexander Grimm
  • Bernhard F. Décard
  • Ioanna Athanasopoulou
  • Kathi Schweikert
  • Michael Sinnreich
  • Hubertus Axer
Original Communication


Ultrasound is useful for non-invasive visualization of focal nerve pathologies probably resulting from demyelination, remyelination, edema or inflammation. In patients with progressive muscle weakness, differentiation between multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) is essential regarding therapy and prognosis. Therefore, the objective of this study was to investigate whether nerve ultrasound can differentiate between ALS and MMN. Systematic ultrasound measurements of peripheral nerves and the 6th cervical nerve root (C6) were performed in 17 patients with ALS, in 8 patients with MMN and in 28 healthy controls. Nerve conduction studies of corresponding nerves were undertaken in MMN and ALS patients. Electromyography was performed in ALS patients according to revised El-Escorial criteria. ANOVA and unpaired t test with Bonferroni correction revealed significant differences in cross-sectional areas (CSA) of different nerves and C6 diameter between the groups. Nerve enlargement was found significantly more frequently in MMN than in other groups (p < 0.001). Receiver operating characteristics analysis revealed detection of enlarged nerves/roots in at least four measurement points to serve as a good marker to differentiate MMN from ALS with a sensitivity of 87.5 % and a specificity of 94.1 %. Ultrasonic focal nerve enlargement in MMN was often not colocalized with areas of conduction blocks found in nerve conduction studies. Systematic ultrasound measurements in different nerves and nerve roots are valuable for detecting focal nerve enlargement in MMN, generally not found in ALS and thus could serve as a diagnostic marker to differentiate between both entities in addition to electrodiagnostic studies.


Nerve ultrasound MMN Polyneuropathy Cross-sectional area ALS 



Amyotrophic lateral sclerosis


Area under the curve


Chronic inflammatory demyelinating polyradiculoneuropathy


Compound muscle action potential


Charcot Marie Tooth


Cross-sectional area


Conduction velocity


Cervical nerve root 6


European Federation of Neurological Societies/Peripheral Nerve Society


Guillain-Barré syndrome


Intraclass correlation coefficient


Intranerve CSA variability


Lower motor neuron




Multifocal motor neuropathy


Nerve conduction studies




Peripheral nerve ultrasound


Positive sharp waves


Receiver operating characteristics


Sensory nerve action potential


Upper motor neuron



The research was supported by the German Center for Sepsis Control and Care (CSCC, funded by the Ministry of Education and Research (BMBF), Grant No 01 E0 1002. The authors thank Nasim Kroegel for her help in language editing.

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS0005253) and approved by the local ethics committee (No. 3663-01/13 and EKZN 2014-230). Informed consent was obtained from all patients and controls.


  1. 1.
    Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(Suppl):96–107CrossRefPubMedGoogle Scholar
  2. 2.
    Hardiman O, van den Berg LH, Kiernan MC (2011) Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol 7:639–649CrossRefPubMedGoogle Scholar
  3. 3.
    Kraemer M, Buerger M, Berlit P (2010) Diagnostic problems and delay of diagnosis inn amyotrophic lateral sclerosis. Clin Neurol Neurosurg 112:103–105CrossRefPubMedGoogle Scholar
  4. 4.
    Brooks BR, Miller RG, Swash M et al (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 1:293–299CrossRefGoogle Scholar
  5. 5.
    de Carvalho M, Dengler R, Eisen A et al (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119:497–503CrossRefPubMedGoogle Scholar
  6. 6.
    Grimm A, Prell T, Décard BF, et al. (2014) Muscle ultrasonography as an additional diagnostic tool for the diagnosis of amyotrophic lateral sclerosis. Clin Neurophysiol. doi: 10.1016/j.clinph.2014.06.052 [Epub ahead of print]
  7. 7.
    Pestronk A, Cornblath DR, Ilyas AA et al (1988) A treatable multifocal motor neuropathy with antibodies to GM1ganglioside. Ann Neurol 24:73–78CrossRefPubMedGoogle Scholar
  8. 8.
    Nobile-Orazio E (2001) Multifocal motor neuropathy. J Neuroimmunol 115:4–18CrossRefPubMedGoogle Scholar
  9. 9.
    Cornblath DR, Sumner AJ, Daube J et al (1991) Conduction block in clinical practice. Muscle Nerv 14:869–871CrossRefGoogle Scholar
  10. 10.
    Nobile-Orazio E, Gallia F (2013) Multifocal motor neuropathy: current therapies and novel strategies. Drugs 73(5):397–406CrossRefPubMedGoogle Scholar
  11. 11.
    Grimm A, Heiling B, Schumacher U et al (2014) Ultrasound differentiation of axonal and demyelinating neuropathies. Muscle Nerv 50:976–983CrossRefGoogle Scholar
  12. 12.
    Hobson-Webb LD (2013) Neuromuscular ultrasound in polyneuropathies and motor neuron disease. Muscle Nerv 47:790–804CrossRefGoogle Scholar
  13. 13.
    Kerasnoudis A (2013) Nerve ultrasound in a case of chronic inflammatory demyelinating neuropathy. Muscle Nerv 47:443–446CrossRefGoogle Scholar
  14. 14.
    Kerasnoudis A, Pitarokoili K, Behrendt V et al (2013) Correlation of nerve ultrasound, electrophysiological, and clinical findings in post Guillain-Barré syndrome. J Peripher Nerv Syst 18:232–240CrossRefPubMedGoogle Scholar
  15. 15.
    Kerasnoudis A, Pitarokoili K, Behrendt V et al (2013) Cross sectional reference values for sonography of peripheral nerves and brachial plexus. Clin Neurophysiol 124:1881–1888CrossRefPubMedGoogle Scholar
  16. 16.
    Kerasnoudis A, Pitarokoili K, Behrendt V, et al. (2014) Correlation of nerve ultrasound, electrophysiological and clinical findings in chronic inflammatory demyelinating polyneuropathy. J Neuroimaging. doi: 10.1111/jon.12079 [Epub ahead of print]
  17. 17.
    Matsuda M, Ikeda S, Sakurai S et al (1996) Hypertrophic neuritis due to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): a postmortem pathological study. Muscle Nerv 19:163–169CrossRefGoogle Scholar
  18. 18.
    Padua L, Granata G, Sabatelli M et al (2014) Heterogeneity of root and nerve ultrasound pattern in CIDP patients. Clin Neurophysiol 125:160–165CrossRefPubMedGoogle Scholar
  19. 19.
    Zaidman CM, Al-Lozi M, Pestronk A (2009) Peripheral nerve size in normal and patients with polyneuropathy: an ultrasound study. Muscle Nerv 40:960–966CrossRefGoogle Scholar
  20. 20.
    Zaidman CM, Harms MB, Pestronk A (2013) Ultrasound of inherited vs. acquired demyelinating polyneuropathies. J Neurol 260:3115–3121PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Schreiber S, Oldag A, Kornblum C et al (2013) Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP. Muscle Nerv 47:385–395CrossRefGoogle Scholar
  22. 22.
    Ito T, Kijima M, Watanabe T et al (2007) Ultrasonography of the tibial nerve in vasculitic neuropathy. Muscle Nerve 35:379–382CrossRefPubMedGoogle Scholar
  23. 23.
    Grimm A, Décard BF, Bischof A, et al. (2014) Ultrasound of the peripheral nerves in systemic vasculitic neuropathies. J Neurol Sci. doi: 10.1016/j.jns.2014.09.017 [Epub ahead of print]
  24. 24.
    Kerasnoudis A, Pitarokoili K, Behrendt V, et al. (2014) Multifocal motor neuropathy: correlation of nerve ultrasound, electrophysiological and clinical findings. J Peripher Nerv Syst 19:165–174CrossRefPubMedGoogle Scholar
  25. 25.
    Beekman R, van den Berg LH, Franssen H et al (2005) Ultrasonography shows extensive nerve enlargements in multifocal motor neuropathy. Neurology 65:305–307CrossRefPubMedGoogle Scholar
  26. 26.
    Cartwright MS, Walker FO, Griffin LP et al (2011) Peripheral nerve and muscle ultrasound in amyotrophic lateral sclerosis. Muscle Nerve 44:346–351PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Nodera H, Takamatsu N, Shimatani Y et al (2014) Thinning of cervical nerve roots and peripheral nerves in ALS as measured by sonography. Clin Neurophysiol 125:1906–1911CrossRefPubMedGoogle Scholar
  28. 28.
    Schreiber S, Abdulla S, Debska-Vielhaber G, et al. (2014) Peripheral nerve ultrasound in ALS phenotypes. Muscle Nerve. doi: 10.1002/mus.24431 [Epub ahead of print]
  29. 29.
    Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 15(4):295–301CrossRefGoogle Scholar
  30. 30.
    Boehm J, Scheidl E, Bereczki D et al (2014) High-resolution ultrasonography of peripheral nerves: measurements on 14 nerve segments in 56 healthy subjects and reliability assessments. Ultraschall Med 35:459–467CrossRefPubMedGoogle Scholar
  31. 31.
    Padua L, Martinoli C, Pazzaglia C et al (2012) Intra- and internerve cross-sectional area variability: new ultrasound measures. Muscle Nerve 45:730–733CrossRefPubMedGoogle Scholar
  32. 32.
    Nodera H, Bostock H, Izumi Y et al (2006) Activity-dependent conduction block in multifocal motor neuropathy: magnetic fatigue test. Neurology 67:280–287CrossRefPubMedGoogle Scholar
  33. 33.
    Van Schaik IN, Bossuyt PMM, Brand A et al (1995) The diagnostic value of GM1 antibodies in motor neuron disorders and neuropathies: a meta-analysis. Neurology 45:1570–1577CrossRefPubMedGoogle Scholar
  34. 34.
    Hooper DR, Lawson W, Smith L et al (2011) Sonographic features in hereditary neuropathy with liability to pressure palsies. Muscle Nerve 44:862–867CrossRefPubMedGoogle Scholar
  35. 35.
    Beekman R, Visser LH (2002) Sonographic detection of diffuse peripheral nerve enlargement in hereditary neuropathy with liability to pressure palsies. J Clin Ultrasound 30:433–436CrossRefPubMedGoogle Scholar
  36. 36.
    Martinoli C, Schenone A, Bianchi S et al (2002) Sonography of the median nerve in Charcot- Marie-Tooth disease. AJR Am J Roentgenol 178:1553–1556CrossRefPubMedGoogle Scholar
  37. 37.
    Scheidl E, Böhm J, Simó M et al (2012) Ultrasonography of MADSAM neuropathy: focal nerve enlargements at sites of existing and resolved conduction blocks. Neuromuscul Disord 22:627–631CrossRefPubMedGoogle Scholar
  38. 38.
    Van Es HW, Van den Berg LH, Franssen H et al (1997) Magnetic resonance imaging of the brachial plexus in patients with multifocal motor neuropathy. Neurology 48:1218–1224CrossRefPubMedGoogle Scholar
  39. 39.
    Grimm A, Décard BF, Axer H (2014) Ultrasonography of the peripheral nervous system in the early stage of Guillain-Barré syndrome. J Peripher Nerv Syst. doi: 10.1111/jns.12091 PubMedGoogle Scholar
  40. 40.
    Grimm A, Thomaser AL, Peters N, et al. (2014) Vagal hypertrophy in immune-mediated neuropathy visualised with high-resolution ultrasound (HR-US). J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp-2014-308271 [Epub ahead of print]
  41. 41.
    Cartwright MS, Brown ME, Eulitt P et al (2009) Diagnostic nerve ultrasound in Charcot-Marie-Tooth disease type 1B. Muscle Nerv 40:98–102CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Alexander Grimm
    • 1
  • Bernhard F. Décard
    • 1
  • Ioanna Athanasopoulou
    • 1
  • Kathi Schweikert
    • 1
  • Michael Sinnreich
    • 1
  • Hubertus Axer
    • 2
    • 3
  1. 1.Department of Neurology, Neuromuscular Center, Basel University HospitalUniversity BaselBaselSwitzerland
  2. 2.Hans Berger Department of NeurologyJena University HospitalJenaGermany
  3. 3.Center for Sepsis Control and Care (CSCC)Jena University HospitalJenaGermany

Personalised recommendations