Kearns-Sayre Syndrome

Kearns-Sayre Syndrome (KSS) is a mitochondrial encephalomyopathy characterized by progressive external ophthalmoplegia, atypical retinitis pigmentosa, and cardiomyopathy.

Chronic Progressive External Ophthalmoplegia (CPEO) with Myopathy; CPEO with Ragged-Red Fibers; Progressive External Ophthalmoplegia with Ragged-Red Fibers; Kearns Syndrome; Kearns-Sayre Mitochondrial Cytopathy; Kearns-Sayre-Shy-Daroff Syndrome; Ophthalmoplegia Pigmentary Degeneration of Retina and Cardiomyopathy Syndrome; Oculo-Cranio-Somatic Syndrome; Ophthalmoplegia Plus Syndrome; Barnard-Scholz Syndrome.

The combination of ophthalmoplegia and retinal degeneration was first described by the two American ophthalmologists R.I. Barnard and R.O. Scholz in 1944; however, the syndrome now bears the names of the two Americans Thomas P. Kearns, a neuroophthalmologist, and George P. Sayre, an ophthalmologist, who published their findings in two patients in 1958.

Approximately 300 cases have been reported. No sex or race predilection.

Mitochondrial (deletions in mitochondrial DNA). Incidence of affected children is dependent upon maternal mutant load. Mitochondrial DNA encodes proteins that are part of the respiratory chain complexes.

In vitro studies of mitochondrial metabolism have identified defects in the respiratory chain and in the oxidative phosphorylation system. These defects are responsible for the elevated levels of serum lactate found during and after exercise.

Clinical and laboratory confirmation of elevated pyruvate and lactate. Light microscopy reveals “ragged-red muscle fibers,” which are caused by the presence of abnormal mitochondria. Electron microscopy demonstrates clusters of cells filled with abnormally enlarged mitochondria (paracrystalline inclusions). The biochemical defect often appears segmental on histochemistry.

KSS is a multiorgan disease characterized by the clinical triad of a chronic, progressive, external ophthalmoplegia, retinal pigment degeneration (with progressive loss of vision), and onset before the age of 20 years. Significant other clinical findings may include increased levels of protein in the cerebrospinal fluid, dementia, encephalopathy, cerebellar ataxia, bulbar weakness (dysphagia, which may also be related to cricopharyngeal achalasia), electroencephalographic anomalies (including seizures), sensorineural hearing loss, corneal anomalies (with increased risk of spontaneous perforation), but also cardiac anomalies (e.g., high-degree atrioventricular heart blocks, QT prolongation with the risk of sudden death, dilated cardiomyopathy, mitral valve prolapse, congestive heart failure), endocrine anomalies (hypogonadism, short stature due to growth hormone deficiency, hyperaldosteronism, diabetes mellitus, hypoparathyroidism, hypothyroidism), renal tubular acidosis, and myopathy with weakness. The clinical spectrum is related to the proportion of normal and mutant DNA.

Due to the fact that KSS may affect many organ systems, a thorough review of the patient history and the actual clinical findings is necessary. Special attention has to focus on the cardiac, endocrine, and renal issues (check electrolytes and acid-base balance). Also assess the degree of muscle weakness to decide if postoperative mechanical ventilation may be required.

Mental retardation, loss of vision and hearing may affect patient cooperation. Sedative premedication and/or the presence of the primary caregiver for induction of anesthesia may be helpful.

The major anesthetic complication is sudden third-degree atrioventricular block. The patient should therefore be closely monitored at all times and a transcutaneous cardiac pacemaker should be easily available throughout the perioperative period. Avoid profound sedation with spontaneous ventilation. Meticulous care should be paid to temperature control (shivering may significantly increase lactate production and result in metabolic acidosis), glucose homeostasis, and ventilation with proper airway management and oxygenation. Avoid hypocarbia since it inhibits the pyruvate decarboxylase, which may further increase the serum lactate levels. Regular blood gas analyses (including lactate and glucose measurements) are recommended. A rapid-sequence induction may be necessary in the presence of dysphagia. Postoperative respiratory failure is a known risk in these patients and, depending on the surgical procedure, an intensive care unit bed with the possibility of mechanical ventilation should be available. A stress-free anesthesia technique reduces not only the metabolic response to surgery, but also lactate production.

Patients are extremely sensitive to induction agents. Caution with benzodiazepines in view of myopathy. Extreme caution with opioids in spontaneously breathing patients. Careful inhalation anesthesia with isoflurane has been found to be safe. Local anesthetic techniques may be used. In order of preference, these agents are chloroprocaine, procaine, prilocaine, lignocaine, mepivacaine, etidocaine, bupivacaine, tetracaine, dibucaine, and cocaine. However, articaine administration for a tooth extraction resulted in transient exacerbation of neuromuscular symptoms in one patient. Because of muscle wasting, neuromuscular blockers should be used with a nerve stimulator only. Although the pathways of malignant hyperthermia and mitochondrial myopathy are different, the potential for malignant hyperthermia has been suggested after succinylcholine; consequently, it might be wise to avoid this agent. No reports of malignant hyperthermia with use of volatile anesthetic in these patients, but caution should be used. Avoid proepileptic drugs. Large doses of propofol should be avoided because of its blocking effects on mitochondrial complex 1.

Other mitochondrial myopathies, especially the following:

MELAS Syndrome: Progressive neurodegenerative disorder with lactic acidosis, stroke-like episodes. Deafness and diabetes mellitus are frequent.

MERRF Syndrome: Mitochondrial encephalopathy characterized by myoclonic epilepsy, muscle weakness, and progressive external ophthalmoplegia.

Pearson Syndrome: A mitochondrial disease presenting in infancy with sideroblastic anemia or pancytopenia, defective oxidative phosphorylation, exocrine pancreatic insufficiency and variable degrees of hepatic, renal, and endocrine failure.