Axon loss is an important determinant of weakness in multifocal motor neuropathy.
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.
Van Asseldonk
J T H
JT
Department of Clinical Neurophysiology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
Van den Berg
L H
LH
Kalmijn
S
S
Van den Berg-Vos
R M
RM
Polman
C H
CH
Wokke
J H J
JH
Franssen
H
H
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*
D016756:Immunoglobulins, Intravenous