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.

Treatment & Management

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Media Gallery

This table outlines the differential diagnoses of chronic progressive external ophthalmoplegia.

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Author

Michael Mercandetti, MD, MBA, FACS Private Practice

Michael Mercandetti, MD, MBA, FACS is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, Sarasota County Medical Society, American Academy of Ophthalmology, American College of Surgeons, American Society for Laser Medicine and Surgery, American Society of Ophthalmic Plastic and Reconstructive Surgery, The Society of Federal Health Professionals (AMSUS)

Disclosure: Nothing to disclose.

Coauthor(s)

Adam J Cohen, MD Physician/CEO, Eyelid and Facial Plastic Surgery and MediSpa; Assistant Professor, Director of Oculoplastic and Reconstructive Surgery, Department of Ophthalmology, Rush University Medical Center

Adam J Cohen, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Triad Inc.<br/>Serve(d) as a speaker or a member of a speakers bureau for: Mimedx; InMode.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Edsel B Ing, MD, PhD, MBA, MEd, MPH, MA, FRCSC Professor, Department of Ophthalmology and Vision Sciences, Sunnybrook Hospital, University of Toronto Faculty of Medicine; Incoming Chair of Ophthalmology, University of Alberta Faculty of Medicine and Dentistry, Canada

Edsel B Ing, MD, PhD, MBA, MEd, MPH, MA, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Society of Ophthalmic Plastic and Reconstructive Surgery, Canadian Medical Association, Canadian Ophthalmological Society, Canadian Society of Oculoplastic Surgery, Chinese Canadian Medical Society, European Society of Ophthalmic Plastic and Reconstructive Surgery, North American Neuro-Ophthalmology Society, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, Statistical Society of Canada

Disclosure: Nothing to disclose.