Craniofacial Muscles

5 Extraocular Muscle Response to Neuromuscular Diseases…
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Fig. 5.3 Notice the impact of ALS on the limb muscles (( a ) control, ( b ) ALS) with fi brosis and
muscle fi ber atrophy on the left side of ( b ) and extremely hypertrophic muscle fi bers with internal
nuclei ( right side ) as well as fatty replacement ( white areas on the left ). In contrast, in the same
patient, the EOMs are notably less affected at the end-stage of ALS. Notice however the wider
variation in muscle fi ber size and the increased space between muscle fi bers in ( d ). ( a – b ): eosin
staining; ( c – d ): NADH-activity staining
denervation and muscle fi ber overuse, with a wider range of muscle fi ber area and
altered composition of contractile and extracellular matrix (ECM) proteins (Ahmadi
et al. 2010 ; Liu et al. 2011 ) . Wide variation in the extent of pathological changes
was seen between different donors and also between the EOMs of the same donor.
In all cases, the changes present in the EOMs were very mild when compared to the
devastating impact of ALS on the skeletal muscles of the same individuals at the
time of death (Fig. 5.3 ). We have therefore suggested that the EOMs are more resistant
to the pathophysiological process underlying ALS. However, our understanding
of the pathophysiology of ALS is rather limited, in spite of intensive research in
the fi eld (Boillée et al. 2006 ) . Approximately 90% of the cases of ALS are so-called
sporadic and of unknown pathogenesis. In the remaining cases, a familial pattern of
inheritance may be present or become apparent later on, and in 10–20% of these
patients, mutations in the SOD1 gene are present. Mutated SOD1 is thought to
cause ALS by a gain of toxic function, as the absence of SOD1 activity in animal
models does not cause ALS. The interplay of genetics, environment, and aging in
the pathophysiology of ALS is gaining increasing importance (Andersen 2006 ) .
Furthermore, recent data indicate that metabolic changes in skeletal muscle likely
play an important role in the early pathogenesis of ALS (Dupuis and Loef fl er 2009 ) .
Defects in energy metabolism such as hypermetabolism and hyperlipidemia are
regarded as negative factors contributing to the pathogenesis of ALS. Convincing
data show that motor neuron death starts at the NMJ and proceeds towards the
spinal cord (Fischer et al. 2004 ) . In two elegant proof of concept papers, it has been