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Case Reports  |   November 1997
An Adult with Inherited Mitochondrial Encephalomyopathy  : Report of A Case
Author Notes
  • (Ciccotelli) Anesthesiology Resident.
  • (Prak) Medical Student.
  • (Muravchick) Professor of Anesthesia.
  • Received from the Department of Anesthesia, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Submitted for publication February 18, 1997. Accepted for publication June 9, 1997.
  • Address reprint requests to Dr. Muravchick: Ravdin Courtyard #402, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104–4283. Address electronic mail to: smuravch@mail.med.upenn.edu.
Article Information
Case Reports
Case Reports   |   November 1997
An Adult with Inherited Mitochondrial Encephalomyopathy  : Report of A Case
Anesthesiology 11 1997, Vol.87, 1240-1242. doi:
Anesthesiology 11 1997, Vol.87, 1240-1242. doi:
The terms mitochondrial myopathy or inherited mitochondrial encephalomyopathy encompass a grouping of neurologic syndromes produced by genetic defects that disrupt mitochondrial energy production. Most have been described in detail only recently. [1,2 ] Many of these disorders are clinically apparent during infancy, but others first appear during the young or middle adult years and then eventually progress to incapacitation and premature death. It is uncertain whether these are truly rare disorders or whether they are relatively common but remain undiagnosed because they are insidious in onset and phenotypically pleiotropic. This report describes the anesthetic management of one such affected adult patient and discusses some of the anesthetic implications of inherited mitochondrial disease.
Case Report 
A 41-yr-old man (height, 175 cm; weight, 84 kg), American Society of Anesthesiologists physical status III, with hiatal hernia and severe gastroesophageal reflux disease and cholelithiasis was scheduled for Nissen fundoplication with parietal cell vagotomy and cholecystectomy. He had been diagnosed by a neurologist several years earlier as having “NARP syndrome” because he exhibited the fundamental stigmata of that disorder: sensory Neuropathy, Ataxia, and Retinitis Pigmentosa. In addition, physical examination revealed mild mental retardation, progressive deafness, generalized limb weakness, and dysarthria. He had worked as a delivery man and drove a truck until his eyesight deteriorated significantly by age 28 years. Two years later, he had been given a general anesthetic consisting of thiopental, pancuronium, fentanyl, droperidol, and nitrous oxide in oxygen, apparently without complications, for open reduction and fixation of a hip that was fractured when he was struck by an automobile. He now lived alone but was visually assisted by a guide dog. Regular medications included omeprazole, alprazolam, amitriptyline, dicyclomine, coenzyme Q10, and ferrous sulfate. He was known to be allergic to iodinated contrast dye.
During this hospitalization, preoperative laboratory data were within the normal range. An epidural catheter for postoperative analgesia was offered but refused by the patient. Because of an anticipated difficult intubation (Mallampati class 3) and severe gastroesophageal reflux, his trachea was intubated using fiberoptic guidance with topical lidocaine anesthesia of the oropharynx and transmucosal block of the superior laryngeal nerves after the patient had been sedated with midazolam, fentanyl, and droperidol. He then underwent an uneventful general anesthetic with thiopental, fentanyl, rocuronium, and nitrous oxide 70% in oxygen. At the end of surgery, neuromuscular blockade was reversed easily within 5 min with neostigmine and glycopyrrolate. Extubated promptly on resumption of spontaneous ventilation and responsiveness to verbal commands, the patient was transported to the surgical intensive care unit for overnight monitoring and observation. He had no evidence of gastric aspiration or ventilatory insufficiency, and he was transferred to a regular surgical nursing unit on the first postoperative day.
Discussion 
The molecular components of the five major enzyme-protein complexes needed for mitochondrial oxidative phosphorylation (ox/phos) are encoded in a complementary manner by the nuclear genome of the host cell and by a small circular genome found within the mitochondrion itself. Loss of mitochondrial bioenergetic capacity is a possible explanation for the ubiquitous and insidious deterioration of organ system functional reserve of normal aging and perhaps for much age-related disease. [3,4,5 ] There are genetically transmitted mitochondrial disorders mediated by mutations of nuclear deoxyribonucleic acid that usually involve primary carnitine deficiencies and follow Mendelian (dominant-recessive) patterns of inheritance." [6 ] Less well known are syndromes such as NARP that result from maternally transmitted mutations of mitochondrial DNA (mtDNA). [7 ] In those with NARP, a point mutation at base-pair position 8993 of mtDNA produces defects in adenosine triphosphatase (ATPase). Reduced ATPase activity and lower rates of ATP production are found in mitochondrial isolates of lymphoblastoid cell lines obtained from NARP patients, [8 ] and there are increased brain levels of phosphocreatine and inorganic phosphate in NARP patients compared with age- and sex-matched control subjects. [9 ]
Progressive decrease in cardiac, muscle, and nervous system functional reserve probably begins long before the appearance of overt signs or symptoms of NARP in young adulthood (Figure 1). The diversity of organ systems that are involved in this and other syndromes of inherited mitochondrial encephalomyopathy are a result of the markedly different metabolic demands of various tissues and of “heteroplasmy,” the uneven distribution of mutant mitochondrial genomes to different tissues during the early phases of embryogenesis. [10 ] There are few case reports that describe the anesthetic treatment of adults with mitochondrial encephalomyopathy, and there are none of those with NARP syndrome. We chose a “nontriggering” anesthetic regimen for our patient because he had received this type of anesthesia uneventfully in the past and because we were not well versed in the likelihood of malignant hyperthermia (MH) in patients with NARP. However, susceptibility to MH and enhanced sensitivity to neuromuscular blockade, issues typically considered for patients with the more familiar muscular dystrophies and neurogenic myopathies, are probably not important for those with most forms of inherited mitochondrial encephalopathy and myopathy. Only the rare myopathies with “multicore” or “minicore” histology may be actually be associated with MH. [11 ]
Figure 1. There is a decrease in maximal oxidative phosphorylation (ox/phos) capacity (solid line) in visual, motor, muscle, and renal tissues throughout the adult years. However, in patients with inherited mitochondrial disorders (interrupted line), capacity may decrease below the minimum values needed for normal functioning (dotted lines) during early or middle adulthood. Redrawn from Wallace. [7 ]
Figure 1. There is a decrease in maximal oxidative phosphorylation (ox/phos) capacity (solid line) in visual, motor, muscle, and renal tissues throughout the adult years. However, in patients with inherited mitochondrial disorders (interrupted line), capacity may decrease below the minimum values needed for normal functioning (dotted lines) during early or middle adulthood. Redrawn from Wallace. [7]
Figure 1. There is a decrease in maximal oxidative phosphorylation (ox/phos) capacity (solid line) in visual, motor, muscle, and renal tissues throughout the adult years. However, in patients with inherited mitochondrial disorders (interrupted line), capacity may decrease below the minimum values needed for normal functioning (dotted lines) during early or middle adulthood. Redrawn from Wallace. [7 ]
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Local anesthetics disrupt ox/phos [12 ] in mitochondrial isolates, but clinical reports suggest that patients with mitochondrial disorders do well with regional anesthetics. [13,14 ] Similarly, propofol and the potent inhalational agents interfere in vitro with mitochondrial energy production, [15 ] although patients with inherited mitochondrial encephalomyopathies have been exposed to various general anesthetic regimens with and without neuromuscular blockade without apparent adverse consequences. [16–18 ] It appears that these patients require preoperative assessment of functional organ system reserve rather than simple screening for the presence of disease. Other unique concerns include reduced anesthetic requirement and susceptibility to prolonged nervous system depression, intrinsic skeletal muscle hypotonia and decreased aerobic work capacity, and cardiomyopathy with increased risk of sudden death from conduction abnormalities. [19,20 ] Overt encephalopathy may be present, and subclinical hepatic and renal involvement is always possible, predisposing the patient to prolonged drug effects and delayed recovery of neurology function.
References 
References 
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Figure 1. There is a decrease in maximal oxidative phosphorylation (ox/phos) capacity (solid line) in visual, motor, muscle, and renal tissues throughout the adult years. However, in patients with inherited mitochondrial disorders (interrupted line), capacity may decrease below the minimum values needed for normal functioning (dotted lines) during early or middle adulthood. Redrawn from Wallace. [7 ]
Figure 1. There is a decrease in maximal oxidative phosphorylation (ox/phos) capacity (solid line) in visual, motor, muscle, and renal tissues throughout the adult years. However, in patients with inherited mitochondrial disorders (interrupted line), capacity may decrease below the minimum values needed for normal functioning (dotted lines) during early or middle adulthood. Redrawn from Wallace. [7]
Figure 1. There is a decrease in maximal oxidative phosphorylation (ox/phos) capacity (solid line) in visual, motor, muscle, and renal tissues throughout the adult years. However, in patients with inherited mitochondrial disorders (interrupted line), capacity may decrease below the minimum values needed for normal functioning (dotted lines) during early or middle adulthood. Redrawn from Wallace. [7 ]
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