Central core disease
Incidence
The incidence of central core disease is unknown, but the disease is thought to be rare. CCD is usually transmitted in an autosomal dominant fashion with variable expression and incomplete penetrance (rare autosomal recessive and sporadic cases) and is almost always due to a mutation in the ryanodine receptor 1 (RYR1).
Clinical Characteristics
Central Core Disease is transmitted as an autosomal dominant trait and is marked by diffuse muscle weakness predominating in shoulders and pelvis, late acquisition of walking, difficulties to run and climb the stairs, and scoliosis. The affection is non-progressive and usually moderately invalidating. It is often associated with a susceptibility to malignant hyperthermia. The most common presentation is at birth or in early childhood with weakness and hypotonia. A history of decreased fetal movement or breech presentation is typical. Progression is slow, but motor milestones are delayed. Occasionally, facial weakness and cramps are present. Skeletal abnormalities are common, including congenital hip dislocation, kyphoscoliosis, and foot deformities. The disease can also present in adolescence as a slowly progressive limb-girdle syndrome. A severe variant that has an onset in infancy has been noted in a few families with autosomal recessive inheritance. Asymptomatic individuals may also present with a high creatine kinase (CK) level or malignant hyperthermia. About 25% of patients with CCD are susceptible to malignant hyperthermia. Central core disease is generally thought to be non- progressive or very slowly progressive. Sometimes progression is seen in adulthood, but some people actually show an improvement over time, with reduced weakness and increased mobility.
Precipitants
Patients with CCD are inclined to develop malignant hyperthermia. However, since the precise diagnosis may not be known, precautions should be taken in all patients with a presumed diagnosis of congenital myopathy. General anesthesia usually triggers a full-blown episode, but excessive heat, neuroleptic drugs, alcohol, or infections may trigger milder episodes. If surgery is required, these patients (and their relatives) should avoid inhaled anesthetics (except nitrous oxide) and succinylcholine. Signs and symptoms of malignant hyperthermia include the following: Elevated pCO2, muscle rigidity, tachycardia, hemodynamic instability, hyperventilation, cyanosis, lactic acidosis, fever, hyperkalemia, hypercalcemia, myoglobinuria. Death may result from pulmonary edema, coagulopathy, ventricular fibrillation, cerebral edema, or renal failure.
Provocation Tests
Many patients with central core disease are at risk of developing malignant hyperthermia during a general anesthetic. As the first exposure to trigger substances elicits an event in only 50% of malignant hyperthermia susceptible patients, a previous history of tolerance of halogenated anesthetic agents or depolarizing muscle relaxants does not guarantee that these agents can be used safely in the future anaesthetics. Anesthetists and surgeons responsible for the care of such patients should be made aware of the risk of malignant hyperthermia, and appropriate anesthetic precautions should be taken in all instances.
Diagnostic Procedures
The diagnosis is established with certainty on muscle biopsy, in which oxidative enzyme histochemistry, performed on frozen sections of skeletal muscle, demonstrates the presence of cores. The diagnosis of central core disease requires a muscle biopsy. The pathological hallmark of central cord disease is the presence, within type 1 muscle fibers, of well demarcated cores (round or oval shaped regions within a muscle fiber that lack oxidative enzyme activity on histochemical stains). There is usually type 1 fiber predominance. Cores usually extend along most or all of the length of the fiber. There may be 1 or more cores within a fiber. Although the biopsy may show other myopathic features such as fiber size variability, increased internal nuclei, and fiber splitting, the presence of cores as the predominant pathological feature in the biopsy establishes the diagnosis of central core disease.