Chronic Progressive External Ophthalmoplegia (CPEO) Workup

Updated: Mar 06, 2023
  • Author: Michael Mercandetti, MD, MBA, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
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Laboratory Studies

Patients with Kearns-Sayre syndrome (KSS) have been reported to have the following:

  • Low magnesium

  • Low parathyroid hormone

  • Increased lactic acid

  • Increased pyruvic acid

  • Increased creatine phosphokinase (CPK)

  • Increased aldolase

  • Increased protein in CSF

Thyroid studies can confirm suspicion of Graves disease.

A positive acetylcholine receptor antibody test may establish the diagnosis of myasthenia gravis. A negative acetylcholine receptor antibody assay does not differentiate chronic progressive external ophthalmoplegia (CPEO) from myasthenia gravis. In addition, false-positive acetylcholine receptor antibodies have been reported in CPEO. [25]

Tensilon testing can be helpful in differentiating myasthenia gravis from CPEO. However, the clinician must remain wary of the effects of edrophonium in a patient harboring a possible cardiac conduction defect, that is, KSS.

Ultrastructural testing of skin biopsies has been used in cases in which muscle biopsy findings are negative. [26]


Imaging Studies

Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound may show thin, symmetrical extraocular muscles in CPEO, in contrast to enlarged extraocular muscles sometimes seen with Graves disease.

Patients with CPEO and KSS display a wide spectrum of MRI findings, to include the following:

  • Normal brain

  • Cortical and cerebellar atrophy

  • Increased T2 signal in subcortical cerebral white matter, cerebellar white matter, globi pallidi, thalami, and substantia nigra

A barium swallowing study would be useful to differentiate oculopharyngeal dystrophy. [27]


Other Tests

Electroretinography and visual-evoked potential testing may be abnormal with or without retinal pigmentary abnormalities. Electroretinography typically shows reduction of oscillatory potentials, scotopic b-wave amplitudes, and photopic b-wave amplitudes. Visual-evoked potential testing abnormalities include p100 latency.

Muscle biopsy is still the definitive test for mitochondrial disorders, but polymerase chain reaction (PCR) testing also has been shown to be conclusive. [28]


Histologic Findings

Biopsy of muscle in a patient with chronic progressive external upper plegia shows ragged-red fibers.This is due to the clumped or "ragged" structures that are aggregates of mitochondria. Mitochondria can also appear atypical including being fragmented or swollen. Additionally lipids can accumulate his droplet in the muscle fibers. Deficiency of Cytochrome C oxidase (COX ) enzyme or absence of Has also been found in muscle fibers.


Biopsy of muscle with oculopharyngeal dystrophy shows a marked reduction in muscle fibers without the characteristic ragged red fibers seen in mitochondrial disorders due to red-rimmed vacuoles and intranuclear inclusions.