MERRF Syndrome

Acronym for myoclonus epilepsy with ragged-red fibers. Belongs to a group of rare muscular disorders called mitochondrial encephalomyopathies. The most characteristic symptom is myoclonic seizures that are usually sudden, brief, jerking spasms that can affect the limbs or the entire body. Ataxia, lactic acidosis, dysarthria, optic atrophy, short stature, hearing loss, dementia, and nystagmus may occur.

Fukuhara Syndrome.

Mitochondrial; incidence of affected children is dependent upon maternal mutant load.

Defect of the respiratory chain enzymes, mainly complexes I and IV.

Clinical and laboratory confirmation of elevated pyruvate and lactate. Muscular biopsy shows ragged-red muscle fibers, and the biochemical defect is often segmental on histochemistry.

Clinical spectrum is proportional to the amount of normal and mutant DNA. Onset is in the neonatal period, with mental deterioration, intention tremor, myoclonic epilepsy, spasticity, ataxia, muscle weakness and atrophy, myopathy, and sensory neural hearing loss. The neuropathologic findings are (a) degeneration of dentate nucleus, red nucleus, globus pallidus, subthalamic nucleus, and pontine tegmentum; (b) degeneration of the Clarke column (the dorsal nucleus of the spinal cord), spinocerebellar tract, posterior column and corticospinal tract, and posterior spinal nerve root and sural nerve; and (c) degeneration of substantia nigra, locus caeruleus, cerebellar cortex, and inferior olivary nucleus.

Diagnosis of mitochondrial disease should be considered in any child with a multisystem neurologic disorder or who is being investigated for hypotonia. Anesthesia-related morbidity and mortality risk is essentially linked to the preoperative status of the child, that is, the number and extent of organ dysfunction. The presence of a mitochondrial disease is not considered a risk for malignant hyperthermia. Avoid any elective anesthesia/surgery in the presence of infection or temperature because cytokines (mainly tumor necrosis factor (TNF)), inhibit some complex of the respiratory chain. The following should be checked: central nervous system (seizures, myoclonus, strokes, swallowing problems); metabolic (usual venous or arterial concentration of lactates and glucose); muscles (hypotonia, contractures, scoliosis); cardiac (even if the child is asymptomatic, ECG and echocardiography to exclude conduction disorders and cardiomyopathy, respectively; check functioning of pacemaker, if present); pulmonary (frequent infections, chronic aspiration, pulse oximetry breathing room air, obstructive and/or central apnea; reduced ventilatory drive is common, and many patients have an abnormal response to both hypoxia and hypercarbia, and deaths have been reported following sedation with chloral hydrate or diazepam); hepatic and renal dysfunctions; nutritional status and diet (glucose and/or lipid rich; tolerance to fasting and treatment [carnitine, vitamin Q, antiepileptic drugs]).

Usual treatment until the morning of surgery. Preoperative fasting as short as possible; if fasting is usually poorly tolerated, a glucose-containing solution should be started when fasting period starts. A sedative premedication is best avoided because of the possible abnormal response to hypoxia/hypercarbia. Induction: No contraindication to choice of anesthetic; however, the dosage of sedative agents might require reduction; sevoflurane is the best choice for inhalation induction; propofol seems the best choice for IV induction, but a 2% solution should be used to lessen the lipid load. Opiates: Dose should be carefully titrated according to the patient's needs. Muscle Relaxant: Published data are often contradictory. Even in the absence of clinical myopathy, the patient's muscular response to nerve stimulation should be measured before administering a muscle relaxant. Atracurium and cis-atracurium are the best choice because of their spontaneous degradation. In case of myopathy, succinylcholine should not be used to avoid producing rhabdomyolysis. Intraoperative Fluids: Avoid infusion containing lactates, such as Ringer lactate or Hartmann solution, but the patient should receive a glucose solution (5 or 10% according to blood sugar level). Aim for normoglycemia because hyperglycemia can increase lactate production. Monitor (arterial or venous) blood gases and lactate levels; in case of severe lactic acidosis, use dichloroacetate 50 mg/kg IV over 30 minutes to stimulate pyruvate dehydrogenase to metabolize lactate in pyruvate. Perimedullar locoregional anesthesia can be used, but its cost-to-benefit ratio should be evaluated, taking into account the presence of severe scoliosis or degenerative lesions in the spinal cord. Some patients with mitochondrial disease also present with axonal neuropathy of peripheral nerves: the possible effects of local anesthetics on these nerves are unknown. Prevention of hypothermia is important to avoid shivering and increased oxygen consumption at awakening.

Patients with mitochondrial disease are very sensitive to the respiratory effects of sedatives. It also seems, according to BIS measurement, that children with an anomaly of complex I of the respiratory chain are much more sensitive to the hypnotic effects of sevoflurane. Most studies performed on isolated mitochondria use doses of anesthetic agents far in excess of those used in daily practice; thus their clinical relevance is often dubious.

Kearns-Sayre Syndrome: Neuromuscular disorder characterized by chronic progressive external ophthalmoplegia, atypical retinitis pigmentosa, cardiomyopathy, and conduction defects (e.g., heart block). Other findings may include muscle weakness, short stature, hearing loss, and ataxia.

MELAS Syndrome: Mitochondrial encephalomyopathy. The most characteristic presentation is recurring, stroke-like episodes associated with sudden headaches, vomiting, and seizures. Short stature, lactic acidosis, and seizures are typically present. Hemianopsia and cortical blindness may affect individuals with this medical entity.

Leigh Syndrome: Neurometabolic disorder characterized by progressive neurologic degeneration (i.e., brain, spinal cord, and optic nerve), generalized weakness, hypotonia, lactic acidosis, and impairment of respiratory and kidney function. It is inherited as an autosomal recessive pattern and usually begins between the ages of 3 months and 2 years. However, X-linked recessive and mitochondrial inheritance have also been suggested.