Tratamiento anestésico en el síndrome de Kearns-Sayre. Descripción de un caso / Anesthetic management of Kearns-Sayre syndrome. Case report

El síndrome de Kearns-Sayre constituye una miopatía mitocondrial que cursa con oftalmoplejia, retinopatía pigmentaria y alteraciones de la conducción cardiaca. Presentamos el caso de un paciente de 50 años de edad con síndrome de Kearns-Sayre intervenido de una fractura de fémur con anestesia subaracnoidea.(AU)

Kearns-Sayre syndrome is a mitochondrial myopathy characterized by ophthalmoplegia, pigmentary retinopathy and cardiac conduction abnormalities. This article describes the clinical management of a 50-year-old patient with Kearns-Sayre syndrome who underwent subarachnoid anesthesia for a traumatic femoral fracture surgery.(AU)

El ácido folínico no es eficaz en el tratamiento del síndrome de Kearns-Sayre / Folinic acid is ineffective for treating kearns-sayre síndrome

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A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review.

Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial DNA. Here, we report an unusual case of Kearns-Sayre syndrome accompanied by hypopituitarism (deficiencies in reproductive and growth hormones). A 20-year-old male presented with growth retardation for the last 8 years, as well as the following findings: short stature, delayed puberty, myasthenia, an extraocular movement deficit, drooping eyelids, pectus carinatum and scoliosis. Cerebral enhanced magnetic resonance imaging revealed dysplasias of the pituitary, white matter and cerebellum. Laboratory work-up showed subnormal testosterone and growth hormone levels, a subnormal testicular volume, sensorineural deafness, pigmentary retinopathy, complete right bundle branch block and left anterior bundle branch block. Pathological examination revealed ragged red muscle fibres. Thus, this rare case involved the coexistence of Kearns-Sayre syndrome and hypopituitarism in a patient. Administration of coenzyme Q10 for the KSS and hormone replacement therapy for the endocrinopathies were performed for treatment of this patient.

Efficacy of growth hormone therapy in Kearns-Sayre syndrome: the KIGS experience.

Kearns-Sayre syndrome (KSS) is characterized by external ophthalmoplegia, retinal pigmentation and cardiac conduction defects due to mitochondrial DNA (mtDNA) deletions. Short stature and growth hormone (GH) deficiency have been reported in KSS, but data on GH treatment is limited. We describe the clinical presentation, phenotype evolution, and response to GH in a patient with KSS and report data on eight additional KSS patients from the KIGS database. Our patient with KSS and GH deficiency achieved a final adult height at -0.8 SDS. In the KIGS database GH treatment resulted in mean improvement in height from -3.9 to -2.9 SDS in patients with KSS. Two patients did not show growth improvement. Our data shows improvement in height SDS in our patient and mixed results in eight additional patients from the KIGS database after treatment with GH. Heterogeneity in responsiveness may relate to presence of GH deficiency or severity of underlying mitochondrial dysfunction.

Coenzyme Q10 in the Treatment of Corneal Edema in Kearns-Sayre: Is There an Application in Fuchs Endothelial Corneal Dystrophy?

PURPOSE: Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway. METHODS: A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea". RESULTS: There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation. CONCLUSIONS: The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.

Therapeutic approach in a case of Pearson's syndrome.

Mitochondrial cytopathy is a multisystemic disease that requires different pharmacological and specialist approaches; although most therapies are usually of scarce effectiveness. We describe a clinical management of a very young girl with Pearson's syndrome that developed the symptoms of Kearns-Sayre syndrome. Many of symptoms were temporarily improved by the replacement therapy with hydrocortisone introduced to treat the partial adrenal insufficiency. During her life, she showed an ample clinical spectrum of symptoms because of multiple organs involvements: firstly bone marrow and, thereafter, brain, retina, inner ear, and kidney. Partial adrenal insufficiency, rarely described in mitochondrial disorders, was a distinctive characteristic of this case. When our patient was treated with hydrocortisone, in addition to ubiquinone and carnitine, the episodes of decompensation regressed and an improvement of the adrenal insufficiency, but only temporary reversion of the weakness of muscle, ophthalmoplegia and of the fatigue, were testified. Nevertheless, after a brief period of recovery, she developed the de Toni-Debré-Fanconi syndrome and the reappearance of the neurological symptoms.

Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells.

Impairment of mitochondrial energy metabolism has been associated with a wide range of human disorders. Large-scale partial deletions of mitochondrial DNA (mtDNA) cause sporadic Kearns-Sayre syndrome, a fatal multisystem disorder, in which the majority of mtDNAs in affected tissues have deletions (Delta-mtDNAs). Since most mtDNA-related diseases, including Kearns-Sayre syndrome, are recessive, only a few wild-type mtDNAs can compensate for the deleterious effects of many Delta-mtDNAs. We have developed a pharmacological approach to reduce the proportion of Delta-mtDNAs in vitro, in which we grow cells in medium containing ketone bodies, replacing glucose as the carbon source. Cells containing 100% Delta-mtDNA died after 5 days of treatment, whereas those containing 100% wild-type mtDNA survived. Furthermore, in a cloned heteroplasmic cell line, the proportion of wild-type mtDNA increased from 13% initially to approximately 22% after 5 days in ketogenic medium and was accompanied by a dramatic improvement in mitochondrial protein synthesis. We also present evidence that treatment with ketone bodies caused "heteroplasmic shifting" not only among cells (ie, intercellular selection) but also within cells (ie, intracellular selection). The demonstration that ketone bodies can distinguish between normal and respiratorily compromised cells points to the potential use of a ketogenic diet to treat patients with heteroplasmic mtDNA disorders.

Transient improvement of pyruvate metabolism after coenzyme Q therapy in Kearns-Sayre syndrome: MRS study.

Coenzyme Q therapy has been used to support metabolic derangements in patients with mitochondrial encephalomyopathies. Biochemical analysis of the living human brain can be performed by magnetic resonance spectroscopy (MRS). We report upon a KSS patient who was serially imaged with localized proton MRS to monitor the efficacy of CoQ treatment. A 17-year-old girl with KSS was serially imaged with localized proton MRS performed on a GE 1.5 T SIGNA MRI/MRS system. The elevated lactate contents of lesions decreased after one month of CoQ therapy but were re-elevated 10 months after treatment. We conclude that MRS presents us with a powerful tool for monitoring the effects of therapeutic trials in mitochondrial encephalomyopathies.

Transient improvement of pyruvate metabolism after coenzyme Q therapy in Kearns-Sayre syndrome: MRS study

Coenzyme Q therapy has been used to support metabolic derangements in patients with mitochondrial encephalomyopathies. Biochemical analysis of the living human brain can be performed by magnetic resonance spectroscopy (MRS). We report upon a KSS patient who was serially imaged with localized proton MRS to monitor the efficacy of CoQ treatment. A 17-year-old girl with KSS was serially imaged with localized proton MRS performed on a GE 1.5 T SIGNA MRI/MRS system. The elevated lactate contents of lesions decreased after one month of CoQ therapy but were re-elevated 10 months after treatment. We conclude that MRS presents us with a powerful tool for monitoring the effects of therapeutic trials in mitochondrial encephalomyopathies.

Treatment of mitochondrial encephalomyopathy with a combination of cytochrome C and vitamins B1 and B2.

The therapeutic efficacy of a regimen consisting of intravenous injection of Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate for mitochondrial encephalomyopathy (MEM) was examined. This combined therapy was applied to nine patients with MEM, including four with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. For the standard regimen, Cardiocrome was first injected daily, usually for 4 weeks, and later by means of intermittent injections for maintenance treatment. Clinical improvement was obtained in eight of the patients. Improvement was observed in the muscle symptoms of easy fatigability, motor disability and severity of stroke-like episodes, as well as in various other symptoms such as phosphate, tinnitus, headache, corneal edema, chilblains, thalamic pain, respiratory failure, and nystagmus. This clinical improvement was maintained for more than 1 year by additional intermittent injections. In conclusion, this therapy was fairly effective for the management of patients with MEM.

The influence of Coenzyme Q10 on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism.

Two patients with Kearns-Sayre Syndrome and hypoparathyroidism were treated with alfacalcidol (1a-OH D3) and total serum calcium concentration remained within normal range for a long period. After two months of combined therapy with Coenzyme Q10 (CoQ10), hypercalcemia was noticed and as a result, 1a-OHD3 was gradually discontinued. Normal total serum calcium concentration was obtained with CoQ10 monotherapy while the replacement of CoQ10 with placebo led to hypocalcemia. The mechanism of action of CoQ10 is difficult to explain. Since the parathormone level remained unchanged during CoQ10 or placebo therapy, we speculate that the capacity of producing an active form of vitamin D in mitochondria of proximal tubules was restored by CoQ10 therapy.

Abnormal evoked potentials of Kearns-Sayre syndrome.

We examined eight patients with Kearns-Sayre syndrome (KSS) to investigate a dysfunction in the central nervous system (CNS) using PTN-SEP, MN-SEP and BAEP. We found a significant increase in the P37 latency of PTN-SEPs and the central conduction time of MN-SEPs, and interpeak latencies of BAEPs. Delayed SEPs or BAEPs were caused by a dysfunction of the somatosensory or lateral lemniscus pathways which could be related to mitochondrial abnormalities in the CNS. Long-term therapy with CoQ showed an improvement of the latencies of SEPs after about half a year from the start of CoQ therapy in our patients. The improvement of the latencies of SEPs were preserved during CoQ therapy. It could be demonstrated that CoQ therapy had the beneficial effects on abnormal functions of the CNS in patients with KSS.

The treatment of mitochondrial myopathies and encephalomyopathies.

This paper briefly summarizes the results of a long-term, open pharmacotherapy trial in 16 patients with well-characterized mitochondrial disease. Outcome measures included repeated clinical evaluation, 31P-NMR spectroscopy and near-infrared spectroscopy. Treated patients appeared to survive longer with less functional disability and medical complications than typically seen in clinical practice.

[Treatment with ubiquinone in Kearns-Sayre syndrome. Improvement in ocular motility and visual evoked potentials]. / Tratamiento con ubiquinona en el síndrome de Kearns-Sayre. Mejoría de la motilidad ocular y los potenciales evocados visuales.

In 1985 Ogasahara observed that treatment with ubiquinone produced improvement in the cardiac conduction and the metabolism of the lactic and pyruvic acids in the Kearns-Sayre syndrome. The results of the administration of 150 mg/day of ubiquinone for 3 years in a patient diagnosed with the Kearns-Sayre syndrome is described. The patient improved notably in strength, ocular movement, visual evoked potentials and in the metabolism of lactic and pyruvic acids. Other beneficial effects reported in the literature have been improvement of ataxia and the somato-sensitive evoked potentials. No side effects have been described.

Clinical and biochemical correlations in mitochondrial myopathies treated with coenzyme Q10.

We tested the efficacy of coenzyme Q10 (ubidecarenone, CoQ10) therapy in patients with Kearns-Sayre syndrome and other mitochondrial myopathies with chronic progressive external ophthalmoplegia (CPEO). We treated seven patients for 1 year with daily oral administration of 120 mg of CoQ10. Throughout the treatment most of our patients showed a progressive reduction of serum lactate and pyruvate levels following standard muscle exercise and generally improved neurologic functions. The ECG and echocardiogram showed no significant changes in our patients. None of our patients showed any improvement in ptosis and CPEO.

Fatal metabolic acidosis, hyperglycemia, and coma after steroid therapy for Kearns-Sayre syndrome.

Two adolescent boys with Kearns-Sayre syndrome (progressive external ophthalmoplegia, heart block, elevated CSF protein, and ragged-red muscle fibers) developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria after a brief course of steroid therapy. Both had hyperglycemia and acidosis. Nonketotic, lactic acidosis was present in one and ketosis in the other. Severe respiratory failure developed, and both patients died. Postmortem revealed fatty infiltration of the pancreas in addition to a diffuse spongiform encephalopathy.

Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome.

This paper presents the clinical and metabolic findings in two young boys with long-standing Kearns-Sayre syndrome. Following short exposure to oral prednisone, both boys developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria. Both presented in the emergency room with profound coma, hypotension, severe hyperglycemia, and acidosis. Nonketotic lactic acidosis was present in one and ketosis without a known serum lactate level was present in the other. Respiratory failure rapidly ensued and both patients expired in spite of efforts at resuscitation. We believe these two cases represent a newly described and catastrophic metabolic-endocrine failure in the Kearns-Sayre syndrome.