Laboratory Studies
The following studies are indicated in Kearns-Sayre syndrome (KSS):
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Urine measurements of pH, protein, glucose, and amino acid levels are indicated.
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Serum creatinine kinase level may be within the reference range or moderately elevated.
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Blood lactate and pyruvate are usually elevated. Cerebrospinal fluid (CSF) lactate levels are elevated even if blood lactate levels are within the reference range. [9] CSF protein levels are very frequently elevated.
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In young children, single large-scale deletions may be detectable in blood. Alternatively, diagnosis may be established by muscle biopsy with histochemistry and mtDNA analysis for major rearrangements. [10]
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Screening is recommended to exclude the endocrinologic abnormalities that occur in many patients. [11] Measure serum electrolyte, glucose, calcium, magnesium, and plasma cortisol levels, as well as thyroid function.
Imaging Studies
MRI of the brain may reveal subcortical white matter lesions (hyperintense on T2 and fluid attenuation inversion recovery [FLAIR], may be bilateral) along with involvement of thalamus, basal ganglia, and brainstem.
Cerebral and cerebellar atrophy may be present. [24, 25]
Spinal involvement on imaging may be underreported in Kearns-Sayre syndrome. One small study of 11 patients with the syndrome who underwent spinal cord imaging showed, in six individuals, involvement of gray matter, white matter, or both. [26]
Other Tests
See the list below:
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ECG reveals cardiac conduction defects; measurement of the PR interval is indicated. [27]
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Echocardiography is used to look for cardiomyopathy.
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Electroretinography helps assess retinal degeneration.
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Audiometry helps detect sensorineural deafness.
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Electroencephalography during period of encephalopathy reveals generalized slow wave activity.
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Electromyography and nerve conduction findings may be normal or may show mild myopathy with or without neuropathy.
Procedures
See the list below:
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Perform a lumbar puncture and measure protein and lactate levels in the CSF.
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Muscle biopsy may reveal ragged red fibers (as is shown in the image below).
Modified Gomori Trichrome stain showing ragged red fibres. These show red staining round the periphery as well as within the sarcoplasm, giving a speckled appearance. Of the two affected muscle fibres pictured here, the one on the right shows a more extreme degree of mitochondrial proliferation and also some degeneration/vacuolation than the one on the left.
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Muscle histochemistry (as is shown in the image below) reveals deficiency of cytochrome c oxidase.
Skeletal muscle stained for both cytochrome oxidase (COX) and succinic dehydrogenase (SDH), two mitochondrial respiratory chain enzymes. Fibers that stain only for SDH and are COX-negative appear blue. Original magnification X 50.
Histologic Findings
In patients with Kearns-Sayre syndrome, as with other mitochondrial encephalopathies, spongy degenerative changes occur in both the gray and white matter of the brain. White matter spongiosis is prominent in the cerebral hemispheres and brainstem fiber tracts in Kearns-Sayre syndrome. [28] Gray matter loss is also seen in the brainstem and Purkinje cell layer. Calcium deposits accumulate in the globus pallidus and thalamus.
Histologic studies of the heart show abnormalities of the conduction system. Large mitochondria with abnormal structure develop in both skeletal and heart muscles.
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Skeletal muscle stained for both cytochrome oxidase (COX) and succinic dehydrogenase (SDH), two mitochondrial respiratory chain enzymes. Fibers that stain only for SDH and are COX-negative appear blue. Original magnification X 50.
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Bilateral ptosis and external ophthalmoplegia. Top: patient looking straight ahead. Below: patient is being asked to look in the direction of the arrow in each case. Restriction of eye movements in each direction is demonstrated.
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Modified Gomori Trichrome stain showing ragged red fibres. These show red staining round the periphery as well as within the sarcoplasm, giving a speckled appearance. Of the two affected muscle fibres pictured here, the one on the right shows a more extreme degree of mitochondrial proliferation and also some degeneration/vacuolation than the one on the left.
