Generalized or Multifocal Disorders Occasionally Mimicking Focal Neuropathies

  • Thomas Schelle


A couple of generalized or multifocal disorders affecting peripheral nerves, plexus and motor-neurons may occasionally mimic focal neuropathies. Despite the fact that most of them are rather uncommon or rare, an erroneous diagnosis may mean that patients will undergo non-indicated surgical interventions or other therapies without benefit or even that they are harmed in a worst case scenario. Therefore, knowledge of these diseases will help to avoid misleading diagnoses. Moreover, after the first failed surgery this should always kept in mind as a part of an extensive differential diagnostic approach. The following chapter highlights some essential facts about motor neuron diseases, diseases of brachial and lumbosacral plexus, hereditary neuropathies, autoimmune neuropathies and vasculitic neuropathies so that physicians can differentiate generalized multifocal from focal neuropathies clinically, and furthermore understand the essential diagnostic pathways, such as different imaging techniques and nerve conduction studies.


Amyotrophic Lateral Sclerosis Carpal Tunnel Syndrome Brachial Plexus Motor Neuron Disease Multifocal Motor Neuropathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Charcot JM. Sclérose des cordons latéraux de la moelle epinierè chez une femme hysterique, atteinte de contracture permanente des quatre membres. Bull Soc Med Hopit Paris. 1865;2:24–35.Google Scholar
  2. 2.
    Murros K, Fogelholm R. Amyotrophic lateral sclerosis in Middle-Finland: an epidemiological study. Acta Neurol Scand. 1983;67:41–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Leigh PN, Ray-Chaudhuri K. Motor neuron disease. J Neurol Neurosurg Psychiatry. 1994;57:886–96.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Logroscino G, Traynor BJ, Hardiman O, et al. Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry. 2008;79:6–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Traub R, Mitsumoto H, Rowland LP. Research advances in amyotrophic lateral sclerosis, 2009 to 2010. Curr Neurol Neurosci Rep. 2009;11:67–77.CrossRefGoogle Scholar
  6. 6.
    Norris F, Shepherd R, Denys E, et al. Onset, natural history and outcome in idiopathic adult onset motor neuron disease. J Neurol Sci. 1993;118:48–55.PubMedCrossRefGoogle Scholar
  7. 7.
    Ravits J, Paul P, Jorg C. Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. Neurology. 2007;68:1571–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Yoshor D, Klugh 3rd A, Appel SH, et al. Incidence and characteristics of spinal decompression surgery after the onset of symptoms of amyotrophic lateral sclerosis. Neurosurgery. 2005;57:984–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Vincent AM, Sakowski SA, Schuyler A, et al. Strategic approaches to developing drugtreatments for ALS. Drug Discov Today. 2008;13:67–72.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Rowland LP. Diagnosis of amyotrophic lateral sclerosis. J Neurol Sci. 1998;160 Suppl 1:S6–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Mills KR. Neurophysiological investigations of motor neuron disorders. In: Shaw PJ, Strong MJ, editors. Motor neuron disorders. Philadelphia: Butterworth-Heinemann; 2003. p. 51–2.CrossRefGoogle Scholar
  12. 12.
    Kuncl RW, Cornblath DR, Griffin JW. Assessment of thoracic paraspinal muscles in the diagnosis of ALS. Muscle Nerve. 1988;11:484–92.PubMedCrossRefGoogle Scholar
  13. 13.
    Taylor BV, Wright RA, Harper CM, et al. Natural history of 46 patients with multifocal motor neuropathy with conduction block. Muscle Nerve. 2000;23:900–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Pillen S, van Alfen N. Skeletal muscle ultrasound. Neurol Res. 2011;33(10):1016–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Parsonage M, Turner J. Neuralgic amyotrophy: the shoulder-girdle syndrome. Lancet. 1948;1:973–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Kuhlenbaumer G, Hannibal MC, Nelis E, et al. Mutations in SEPT9 cause hereditary neuralgic amyotrophy. Nat Genet. 2005;37:1044–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Suarez GA. Immune brachial plexus neuropathy. In: Dyck PJ, Thomas PK, editors. Peripheral neuropathy. Philadelphia: Elsevier Saunders; 2005. p. 2299–308.CrossRefGoogle Scholar
  18. 18.
    MacDonald BK, Cockerell OC, Sander JW, et al. The incidence and lifetime prevalence of neurological disorders in a prospective communitybased study in the UK. Brain. 2000;123:665–76.PubMedCrossRefGoogle Scholar
  19. 19.
    van Alfen N, van Engelen BGM. The clinical spectrum of neuralgic amyotrophy in 246 cases. Brain. 2006;129:438–50.PubMedCrossRefGoogle Scholar
  20. 20.
    Pham M, Bäumer P, Meinck HM, Schiefer J, Weiler M, Bendszus M, Kele H. Anterior interosseous nerve syndrome: fascicular motor lesions of median nerve trunk. Neurology. 2014;82(7):598–606. doi:0.1212/WNL.0000000000000128. Epub 2014 Jan 10.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Pan Y, Wang S, Zheng D, Tian W, Tian G, Ho PC, Cheng HS, Zhong Y. Hourglass-like constrictions of peripheral nerve in upper extremity: a clinical review and pathological study. Neurosurgery. 2014 Mar 21. [Epub ahead of print].Google Scholar
  22. 22.
    Charcot J, Marie P. Sue une forme particulaire d’atrophie musculaire progressive souvent familial debutant par les pieds et les jamber et atteingnant plus tard les mains. Rev Med. 1886;6:97–138.Google Scholar
  23. 23.
    Tooth H. The peroneal type of progressive muscular atrophy. London: Lewis; 1886.Google Scholar
  24. 24.
    Dyck PJ, Lambert EH. Lower motor and primary sensory neuron diseases withperoneal muscular atrophy. II. Neurologic, genetic, and electrophysiologic findings in various neuronal degenerations. Arch Neurol. 1968;18(6):619.PubMedCrossRefGoogle Scholar
  25. 25.
    Lupski JR, de Oca-Luna RM, Slaugenhaupt S, et al. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 1991;66(2):219–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhao C, Takita J, Tanaka Y, et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell. 2001;105(5):587–97.PubMedCrossRefGoogle Scholar
  27. 27.
    Jani-Acsadi A, Krajewski K, Michael ES. Charcot-Marie-Tooth neuropathies: diagnosis and management. Semin Neurol. 2008;28(2):185–94.PubMedCrossRefGoogle Scholar
  28. 28.
    Krajewski KM, Lewis RA, Fuerst DR, et al. Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. Brain. 2000;123(Pt7):1516–27.PubMedCrossRefGoogle Scholar
  29. 29.
    Thomas PK, Marques Jr W, Davis MB, et al. The phenotypic manifestations of chromosome 17p11.2 duplication. Brain. 1997;120(Pt3):465–78.PubMedCrossRefGoogle Scholar
  30. 30.
    Lewis RA, Sumner AJ. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology. 1982;32(6):592.PubMedCrossRefGoogle Scholar
  31. 31.
    Goedee HS, Brekelmans GJ, van Asseldonk JT, et al. High resolution sonography in the evaluation of the peripheral nervous system in polyneuropathy – a review of the literature. Eur J Neurol. 2013. doi: 10.1111/ene.12182.PubMedGoogle Scholar
  32. 32.
    Krajewski KM, Shy ME. Genetic testing in neuromuscular disease. Neurol Clin. 2004;22:481–508.PubMedCrossRefGoogle Scholar
  33. 33.
    Koehler PJ. Hereditary neuropathy with liability to pressure palsies: the first publication (1947). Neurology. 2003;60(7):1211–3.PubMedCrossRefGoogle Scholar
  34. 34.
    Chance PF, Alderson MK, Leppig KA, et al. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. 1993;72:143–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Chance PF. Overview of hereditary neuropathy with liability to pressure palsies. Ann N Y Acad Sci. 1999;883:14–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Meier C, Moll C. Hereditary neuropathy with liability to pressure palsies. Report of two families and review of the literature. J Neurol. 1982;228:73–95.PubMedCrossRefGoogle Scholar
  37. 37.
    Mouton P, Tardieu S, Goider R, et al. Spectrum of clinical and electrophysiologic features in HNPP patients with the 17p11.2 deletion. Neurology. 1999;52:1440–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Li J, Krajewski K, Shy ME, et al. Hereditary neuropathy with liability to pressure palsy. The electrophysiology fits the name. Neurology. 2002;58:1769–73.PubMedCrossRefGoogle Scholar
  39. 39.
    Verhagen WI, Gabreëls-Festen AA, van Wensen PJ, et al. Hereditary neuropathy with liability to pressure palsies: a clinical, electrophysiological and morphological study. J Neurol Sci. 1993;116:176–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Taggart TF, Allen TR. Surgical treatment of a tomaculous neuropathy. J R Coll Surg Edinb. 2001;46(4):240–1.PubMedGoogle Scholar
  41. 41.
    Tsai YT, Kuo HC, Chu CC, et al. Hereditary neuropathy with liability to pressure palsies: a clinical and genetic study of a Taiwanese family. Chang Gung Med J. 2005;28(1):56–63.PubMedGoogle Scholar
  42. 42.
    Köller H, Kieseier BC, Jander S, et al. Chronic inflammatory demyelinating polyneuropathy. N Engl J Med. 2005;352(13):1343–56.PubMedCrossRefGoogle Scholar
  43. 43.
    Bouchard C, Lacroix C, Planté V, et al. Clinicopathologic findings and prognosis of chronic inflammatory demyelinating polyneuropathy. Neurology. 1999;52(3):498–503.PubMedCrossRefGoogle Scholar
  44. 44.
    Mygland A, Monstad P. Chronic polyneuropathies in Vest-Agder, Norway. Eur J Neurol. 2001;8(2):157–65.PubMedCrossRefGoogle Scholar
  45. 45.
    Dyck PJ, Oviatt KF, Lambert EH. Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann Neurol. 1981;10(3):222–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Cornblath DR. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Neurology. 1991;41(5):617–8.CrossRefGoogle Scholar
  47. 47.
    Saperstein DS, Katz JS, Amato AA, et al. Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve. 2001;24(3):311–24.PubMedCrossRefGoogle Scholar
  48. 48.
    Hughes R, Bensa S, Willison H, et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001;50(2):195–201.PubMedCrossRefGoogle Scholar
  49. 49.
    Bromberg MB. Comparison of electrodiagnostic criteria for primary demyelination in chronic polyneuropathy. Muscle Nerve. 1991;14(10):968–76.PubMedCrossRefGoogle Scholar
  50. 50.
    Yan WX, Archelos JJ, Hartung HP, et al. P0 protein is a target antigen in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001;50(3):286–92.PubMedCrossRefGoogle Scholar
  51. 51.
    Niino M, Tsuji S, Tashiro K. Chronic inflammatory demyelinating polyneuropathy with multiple hypertrophic nerves in intracranial, and intra- and extra-spinal segments. Intern Med. 1999;38(5):445–9.PubMedCrossRefGoogle Scholar
  52. 52.
    De Smet K, De Maeseneer M, Talebian Yazdi A, et al. MRI in hypertrophic mono- and polyneuropathies. Clin Radiol. 2013;68(3):317–22.PubMedCrossRefGoogle Scholar
  53. 53.
    Zaidman CM, Pestronk A. Nerve Size in CIDP Varies with Disease Activity and Therapy Response Over Time: A Retrospective Ultrasound Study. Muscle Nerve. 2014 Feb 25. doi: 10.1002/mus.24227. [Epub ahead of print].
  54. 54.
    Granata G, Pazzaglia C, Calandro P et al.: Ultrasound visualization of nerve morphological alteration at the site of conduction block. Muscle Nerve. 2009;40:1068–1070Google Scholar
  55. 55.
    Mendell JR, Barohn RJ, Freimer ML, et al. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 2001;56(4):445–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Dyck PJ, Obrien PC, Oviatt KF, et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol. 1982;11(2):136–41.PubMedCrossRefGoogle Scholar
  57. 57.
    Lewis RA, Sumner AJ, Brown MJ, et al. Multifocal demyelinating neuropathy with persistent conduction block. Neurology. 1982;32(9):958–64.PubMedCrossRefGoogle Scholar
  58. 58.
    Saperstein DS, Amato AA, Wolfe GI, et al. Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome. Muscle Nerve. 1999;22(5):560–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Nobileorazio E, Latov N, Hays AP, et al. Neuropathy and anti-MAG antibodies without detectable serum M-protein. Neurology. 1984;34(2):218–21.CrossRefGoogle Scholar
  60. 60.
    Latov N, Hays AP, Sherman WH. Peripheral neuropathy and anti-MAG antibodies. Crit Rev Neurobiol. 1988;3(4):301–32.PubMedGoogle Scholar
  61. 61.
    Pedersen SF, Pullman SL, Latov N, et al. Physiological tremor analysis of patients with anti-myelin-associated glycoprotein associated neuropathy and tremor. Muscle Nerve. 1997;20(1):38–44.PubMedCrossRefGoogle Scholar
  62. 62.
    Trojaborg W, Hays AP, Vandenberg L, et al. Motor conduction parameters in neuropathies associated with anti-MAG antibodies and other types of demyelinating and axonal neuropathies. Muscle Nerve. 1995;18(7):730–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Parry GJ, Clarke S. Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease. Muscle Nerve. 1988;11(2):103–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Lange DJ, Trojaborg W, Latov N, et al. Multifocal motor neuropathy with conduction block – is it a distinct clinical entity. Neurology. 1992;42(3):497–505.PubMedCrossRefGoogle Scholar
  65. 65.
    Azulay JP, Blin O, Pouget J, et al. Intravenous immunoglobulin treatment in patients with motor-neuron syndromes associated with anti-Gm1 antibodies – a double-blind. Placebo-controlled study. Neurology. 1994;44(3):429–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Beydoun SR, Copeland D. Bilateral phrenic neuropathy as a presenting feature of multifocal motor neuropathy with conduction block. Muscle Nerve. 2000;23(4):556–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Brannagan TH, Latov N. Motor neuropathy and monoclonal gammopathy. In: Younger DS, editor. Motor disorders. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 235–41.Google Scholar
  68. 68.
    Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Multifocal motor neuropathy: correlation of nerve ultrasound, electrophysiological and clinical findings. J Peripher Nerv Syst. 2014 May 23. doi: 10.1111/jns5.12067. [Epub ahead of print] (B)
  69. 69.
    Beekman R, van den Berg LH, Franssen H, et al. Ultrasonography shows extensive nerve enlargements in multifocal motor neuropathy. Neurology. 2005;65:305–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Levine TD, Pestronk A. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using Rituximab. Neurology. 1999;52(8):1701–4.PubMedCrossRefGoogle Scholar
  71. 71.
    vanden Berg LH, Kerkhoff H, Oey PL, et al. Treatment of multifocal motor neuropathy with high-dose intravenous immunoglobulins – a double-blind, placebo-controlled study. J Neurol Neurosurg Psychiatry. 1995;59(3):248–52.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Hufschmidt A, Lücking CH. NeurologieCompact. 4. Auflage. Thieme, Stuttgard: New York. 2006;S:102. ISBN 3-13-117194-4.Google Scholar
  73. 73.
    Said G. Vasculitic neuropathy. ACNR. 2010;10(4):10–2.Google Scholar
  74. 74.
    Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994;37(2):187–92.CrossRefGoogle Scholar
  75. 75.
    Gorson KC. Vasculitic neuropathies, an update. Neurologist. 2007;13:12–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Sampaio L, Silva LG, Terroso G, et al. Vasculitic neuropathy. Acta Reumatol Port. 2011;36(2):102–9.PubMedGoogle Scholar
  77. 77.
    Olney RK. Neuropathies associated with connective tissue disease. Semin Neurol. 1998;18:63–72.PubMedCrossRefGoogle Scholar
  78. 78.
    Bouche P, Leger JM, Travers MA, et al. Peripheral neuropathy in systemic vasculitis: clinical and electrophysiologic study of 22 patients. Neurology. 1986;36:1598–602.PubMedCrossRefGoogle Scholar
  79. 79.
    McCluskey L, Feinberg D, Cantor C, et al. “Pseudo-conduction block” in vasculitic neuropathy. Muscle Nerve. 1999;22:1361–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Nodera H, Sato K, Terasawa Y, et al. High-resolution sonography detects inflammatory changes in vasculitic neuropathy. Muscle Nerve. 2006;34:380–1.PubMedCrossRefGoogle Scholar
  81. 81.
    Ito T, Kijima M, Watanabe T, et al. Ultrasonography of the tibial nerve in vasculitic neuropathy. Muscle Nerve. 2007;35:379–82.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Thomas Schelle
    • 1
  1. 1.Neurological DepartmentMunicipal Hospital DessauDessau-RosslauGermany

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