title: Axon loss is an important determinant of weakness in multifocal motor neuropathy.
abstract: BACKGROUND
  Multifocal motor neuropathy (MMN) is characterised by asymmetrical weakness and muscle atrophy, in the arms more than the legs, without sensory loss. Despite a beneficial response to treatment with intravenous immunoglobulins (IVIg), weakness is slowly progressive. Histopathological studies in MMN revealed features of demyelination and axon loss. It is unknown to what extent demyelination and axon loss contribute to weakness. Unlike demyelination, axon loss has not been studied systematically in MMN. Aims/
  
  
  METHODS
  To assess the independent determinants of weakness in MMN, 20 patients with MMN on IVIg treatment were investigated. Using a standardised examination in each patient, muscle strength was determined in 10 muscles. In the innervating nerve of each muscle, axon loss was assessed by concentric needle electromyography, and conduction block or demyelinative slowing by motor nerve conduction studies. Multivariate analysis was used to assess independent determinants of weakness.
  
  
  RESULTS
  Needle electromyography abnormalities compatible with axon loss were found in 61% of all muscles. Axon loss, and not conduction block or demyelinative slowing, was the most significant independent determinant of weakness in corresponding muscles. Furthermore, axon loss and conduction block were independently associated with each other.
  
  
  CONCLUSIONS
  Axon loss occurs frequently in MMN and pathogenic mechanisms leading to axonal degeneration may play an important role in the outcome of the neurological deficit in patients with MMN. Therapeutic strategies aimed at prevention and reduction of axon loss, such as early initiation of treatment or additional (neuroprotective) agents, should be considered in the treatment of patients with MMN.
authors.affiliation: Department of Clinical Neurophysiology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: J T H
authors.initials: JT
authors.lastname: Van Asseldonk
authors.forename: L H
authors.initials: LH
authors.lastname: Van den Berg
authors.forename: S
authors.initials: S
authors.lastname: Kalmijn
authors.forename: R M
authors.initials: RM
authors.lastname: Van den Berg-Vos
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: J H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: H
authors.initials: H
authors.lastname: Franssen
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D003711:Demyelinating Diseases / Q000503:physiopathology; D004576:Electromyography; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D016472:Motor Neuron Disease / Q000188:drug therapy / Q000503:physiopathology*; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000503:physiopathology; D009431:Neural Conduction; D019636:Neurodegenerative Diseases / Q000503:physiopathology*
chemical_list: D016756:Immunoglobulins, Intravenous