Research Article| Volume 319, ISSUE 1-2, P81-85, August 15, 2012

Is peripheral neuron degeneration involved in multiple system atrophy? A clinical and electrophysiological study


      Lower motor neuron lesions are not among the characteristic features of multiple system atrophy (MSA), although electromyography (EMG) and autopsy studies revealed peripheral neuron abnormalities in some cases of MSA.
      The aim of the study was to evaluate subclinical involvement of the peripheral neuron in MSA using EMG and electroneurography (ENG).


      48 patients with clinically probable MSA (mean age 60.6 years; 67% males) were included in the study and divided into subgroups, with predominant cerebellar (MSA-C) and parkinsonian signs (MSA-P).


      ENG in ulnar, peroneal and sural nerves and EMG of the first interosseus dorsal and tibial anterior muscles were performed.


      Abnormal ENG in one nerve was recorded in 20.8% of patients, and in two nerves in another 20.8% of patients. The most frequent and significant findings were decreased compound motor action potential amplitudes in the ulnar nerve in the overall MSA group as well as in the MSA-P type as compared to controls. Abnormalities suggesting reinnervation was observed in 43 of 96 examined muscles (44.7%). In individual cases, neurogenic features were recorded in one muscle in 31.2% of patients and in two muscles in 29.1% of patients.


      Subclinical axonopathy in MSA is not frequent and is more pronounced in MSA with predominant parkinsonian signs. In MSA, neurogenic EMG abnormalities in muscles are more frequent than peripheral nerve lesions and as evidenced by increased motor unit potential amplitudes, could be considered a sign of anterior horn cell involvement and a hallmark of the “continuum” of neurodegeneration in MSA.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Gilman S.
        • Low P.A.
        • Quinn N.
        • Albanese A.
        • Ben-Schlomo Y.
        • Fowler C.
        • et al.
        Consensus statement on the diagnosis of multiple system atrophy.
        J Auton Nerv Syst. 1998; 74: 189-192
        • Gilman S.
        • Wenning G.K.
        • Low P.A.
        • Brooks D.J.
        • Mathias C.J.
        • Trojanowski J.Q.
        Second consensus statement on the diagnosis of multiple system atrophy.
        Neurology. 2008; 26: 670-676
        • Ozawa T.
        • Paviour D.
        • Quinn N.P.
        • Josephs K.A.
        • Sangha H.
        • Kilford L.
        The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multisystem atrophy: clinicopathological correlations.
        Brain. 2004; 127: 2657-2671
        • Trojanowski J.Q.
        • Revesz T.
        Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy.
        Neuropathol Appl Neurobiol. 2007; 33: 615-620
        • Papp M.I.
        • Kahn J.E.
        • Lantos P.L.
        Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy–Drager syndrome).
        J Neurol Sci. 1989; 94: 79-100
        • Yoshida M.
        Multiple system atrophy: α-synuclein and neuronal degeneration.
        Neuropathology. 2007; 27: 484-493
        • Da Rocha A.J.
        • Maia A.C.M.
        • da Siva C.J.
        • Ferreira N.P.D.F.
        • Barsottini O.G.P.
        • Ferraz H.B.
        Pyramidal Tract degeneration in Multiple System Atrophy: The Relevance of Magnetization Transfer Imaging.
        Mov Disord. 2007; 22: 238-244
        • Su M.
        • Yoshida Y.
        • Hirata Y.
        • Watahiki Y.
        • Negata K.
        Primary involvement of the motor area in association with the nigrostriatal pathway in multiple system atrophy: neuropathological and morphometric evaluations.
        Acta Neuropathol. 2001; 101: 57-64
        • Wennig G.
        • Tison F.
        • Ben-Schlomo Y.
        • Daniel S.
        • Quinn N.
        Multiple system atrophy: a review of 203 pathological cases.
        Mov Disord. 1997; 12: 133-147
        • Pramstaller P.
        • Wennig G.
        • Smith S.
        • Beck R.
        • Quinn N.
        • Fowler C.
        Nerve conduction studies, skeletal muscle EMG in multiple system atrophy.
        J Neurol Neurosurg Psychiatry. 1995; 5: 618-621
        • Rodolico C.
        • Toscano A.
        • De Luca G.
        • Mazzeo A.
        • Di Leo R.
        • Baldari S.
        • et al.
        Peripheral neuropathy as a presenting feature in multisystem atrophy.
        Clin Auton Res. 2001; 11: 119-121
        • Wu Y.R.
        • Chen C.M.
        • Ro L.S.
        Sensory neuropathy as the initial manifestation of multiple system atrophy.
        J Formos Med Assoc. 2004; 103: 727-730
        • Abele M.
        • Schulz J.B.
        • Bürk K.
        • Topka H.
        • Dickgans J.
        • Klockgether T.
        Nerve conduction studies in multiple system atrophy.
        Eur Neurol. 2000; 43: 221-223
        • Kanda T.
        • Tsukagoshi H.
        • Oda M.
        • Miyamoto K.
        • Tanabe H.
        Changes of unmyelinated nerve fibers in sural nerve in amyotrophic lateral sclerosis, Parkinson's disease and multiple system atrophy.
        Acta Neuropathol. 1996; 91: 145-154
        • Mori F.
        • Inenaga C.
        • Yoshimoto M.
        • Umezu H.
        • Tanaka R.
        • Takahashi H.
        • et al.
        Alpha-synuclein immunoreactivity in normal and neoplastic Schwann cells.
        Acta Neuropathol. 2002; 103: 145-151
        • Müller T.
        • Muhlack S.
        Peripheral COMT inhibition prevents levodopa associated homocysteine increase.
        J Neural Transm. 2009; 116: 1253-1256
        • Müller T.
        • Muhlack S.
        Acute homocysteine rise after repeated levodopa application in patients with Parkinson's disease.
        Parkinsonism Relat Disord. 2010 Dec; 16: 688-689
        • Müller T.
        • Jugel C.
        • Ehret R.
        • Ebersbach G.
        • Bengel G.
        • Muhlack S.
        • et al.
        Elevation of total homocysteine levels in patients with Parkinson's disease treated with duodenal levodopa/carbidopa gel.
        J Neural Transm. 2011; 118: 1329-1333
        • Toth C.
        • Breithaupt K.
        • Ge S.
        • Duan Y.
        • Terris J.M.
        • Thiessen A.
        • et al.
        Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease.
        Ann Neurol. 2010; 68: 28-36
        • Sonoo M.
        • Stålberg E.
        The ability of MUP parameters to discriminate between normal and neurogenic MUPs in concentric EMG: analysis of the MUP “thickness” and the proposals of “size index”.
        Electroencephalogr Clin Neurophysiol. 1993; 89: 291-303
        • Bischoff C.
        • Stålberg E.
        • Falck B.
        • Eeg-Olofsson K.
        Reference values of motor unit action potentials obtained with multi-MUAP analysis.
        Muscle Nerve. 1994; 17: 842-851
        • Galassi G.
        • Nemni R.
        • Baraldi A.
        • Gibertoni M.
        • Colombo A.
        Peripheral neuropathy in multisystem atrophy with autonomic failure.
        Neurology. 1982; 32: 1116-1121
        • Kuwabara S.
        • Sonoo M.
        • Komori T.
        • Shimizu T.
        • Hirashima F.
        • Inaba A.
        • et al.
        Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent and specificity.
        Muscle Nerve. 2008; 37: 426-430
        • Konno H.
        • Yamamoto T.
        • Iwasaki Y.
        • Iizuka H.
        Shy–Drager syndrome and amyotrophic lateral sclerosis. Cytoarchitectonic and morphometric studies of sacral autonomic neurons.
        J Neurol Sci. 1986; 73: 193-204
        • Montagna P.
        • Martinelli P.
        • Rizutto N.
        • Salviati A.
        • Rasi F.
        • Lugaresi E.
        Amyotrophy in Shy–Drager syndrome.
        Acta Neurol Belg. 1983; 83: 142-157
        • Rodi Z.
        • Denislic M.
        • Vodusek D.B.
        External anal sphincter electromyography in the differential diagnosis of parkinsonism.
        J Neurol Neurosurg Psychiatry. 1986; 49: 554-562
        • Palace J.
        • Chandiramani V.A.
        • Fowler C.J.
        Value of sphincter electromyography in the diagnosis of multiple system atrophy.
        Muscle Nerve. 1997; 20: 1396-1403
        • Gilad R.
        • Giladi N.
        • Korczyn A.D.
        • Gurevich T.
        • Sadeh M.
        Quantitative anal sphincter EMG in multisystem atrophy and 100 controls.
        J Neurol Neurosurg Psychiatry. 2001; 71: 596-599
        • Libelius R.
        • Johansson F.
        Quantitative electromyography of the external anal sphincter in Parkinson's disease and multiple system atrophy.
        Muscle Nerve. 2000; 23: 1250-1256
        • Chovancova Z.
        • Kanovsky P.
        • Dufek J.
        • Nevrly M.
        • Otruba P.
        Peripheral nerve involvement and severity of motor disorder in Parkinson's disease: a correlational study.
        Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009; 153: 59-62