Craniofacial Muscles

5 Extraocular Muscle Response to Neuromuscular Diseases…
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The EOMs and the levator palpebrae are typically the fi rst muscles to be affected
in MG, 50–80% of the patients presenting with double vision (diplopia) and ptosis,
that get worse along the day or with fatigue (Kaminski et al. 1990 ; Elrod and
Weinberg 2004 ; Romi et al. 2005 ) . A classical sign is the worsening of the ptosis
following sustained upgaze, a sign that helps in the differential diagnosis of other
pupil-sparing disorders affecting ocular motility. The disease may be limited to the
EOMs and levator palpebrae, the so-called ocular myasthenia, or it may spread to
the other muscles, the so-called generalized form. The most feared complication
with time is a myasthenic crisis, an acute exacerbation of muscle weakness, e.g.,
after an infection, leading to respiratory failure. However, adequately treated with
acetylcholine inhibitors and different regimens of immunosuppression, the vast
majority of patients lives a normal life and has no major complications (Drachman
2008 ; Drachman et al. 2008 ) .
The pathological hallmark of MG is the loss of synaptic folds and their acetylcholine
receptors, which apparently result from a complement-mediated autoantibody
lesion localized to the NMJ. It has been proposed (Kaminski et al. 2002 ) that
differences in gene expression levels of elements of the complement cascade (Porter
et al. 2001 ) make the EOMs more susceptible to MG. However, a difference in the
levels of gene expression of the elements of the complement cascade could not be
con fi rmed on the human EOMs vs. limb muscles (Fischer et al. 2005 ) . Furthermore,
it remains unknown whether the levator palpebrae differs from the other muscles
regarding the complement cascade. The EOMs differ from the other muscles by
having very high fi ring frequencies and a low so-called safety-factor, a measure of
the overcapacity of the endplate potential. These two features may partly be the
reason why the EOMs are functionally affected earlier by the loss of acetylcholine
receptors. Further studies are needed to shed light on the triggering factors and on
the causes of the wide heterogeneity of the disease.
5.4 Mitochondrial Disorders and Chronic Progressive
External Ophthalmoplegia
The EOMs are typically affected in mitochondrial disorders with a myopathy
component, the most common of them being chronic progressive external ophthalmoplegia
(CPEO). A wide spectrum of clinical conditions resulting from anomalies
of the respiratory chain and leading to impaired oxidative phosphorylation is collectively
referred to as mitochondrial disorders (Zeviani and Di Donato 2004 ) .
These disorders have very diverse clinical implications and may show high phenotypic
variability between generations and complex patterns of inheritance, as both
nuclear and mitochondrial DNA (mtDNA) encode the elements of the respiratory
chain and the key enzymes needed for mtDNA replication and expression as well as
RNA translation within the mitochondria (Oldfors and Tulinius 2003 ; Zeviani and
Di Donato 2004 ) . The frequency of pathogenic mtDNA mutations that potentially
can cause disease in the offspring of female carriers has been estimated to be
approximately 1:200 in an unselected European population (Elliott et al. 2008 ) .