This consists of discontinuation of anesthesia at the first hint of masseter spasm or rise of temperature. The intravenous administration of dantrolene, which inhibits the release of calcium from the sarcoplasmic reticulum, may be lifesaving. An infusion of 1 mg/kg is given initially and increased slowly until symptoms subside, the total dosage not exceeding 10 mg/kg. Other measures should include body cooling, intravenous hydration, sodium bicarbonate infusion to correct acidosis, and mechanical hyperventilation to decrease acidosis. Thereafter, halothane and other volatile anesthetic agents and succinylcholine should be avoided in such individuals and surgical procedures, if necessary, should be done with other agents, such as propofol, nitrous oxide, fentanyl, thiopental (or other barbiturate), or local anesthesia. Intravenous dantrolene (2.5 mg/kg given slowly 1 h prior to anesthesia) prevents the syndrome, but this is not a preferred option in patients with the disorder.
This state, in which hyperthermia occurs as an idiosyncratic reaction to neuroleptic drugs, is also accompanied by widespread myonecrosis. It shares some features with malignant hyperthermia but is a distinct entity, as discussed in Chap. 41.
The discovery of several types of seizure disorders based on inherited defects of the potassium channel has elicited considerable interest and only recently was it appreciated that one form of periodic paralysis, Andersen disease, is associated with the voltage-gated potassium channel.
Andersen and coworkers first drew attention to a distinct form of potassium-sensitive periodic paralysis characterized by the triad of periodic potassium-sensitive weakness, ventricular dysrhythmias with long QT syndrome, and dysmorphic features (micrognathia, short stature, scaphocephaly, hypertelorism, broad nose, low-set ears, and short index fingers). Sometimes called “Andersen disease,” it is not to be mistaken for the glycogen storage disease of the same name, which is discussed in Chap. 45.
From a study of 5 kindreds, Sansone and colleagues have pointed out that attacks of paralysis can be associated with hypo-, normo-, or hyperkalemia, and that a prolonged QT interval is an integral feature of the disease (and sometimes the only sign in a given family). Plaster and colleagues demonstrated that most cases of Andersen disease are a consequence of dominant-negative mutations in the gene KCNJ2 that encodes a type of K channel. In vitro studies indicate that the mutation impairs the ability of preformed channels to migrate to the membrane surface and also impedes the current-carrying capacity of the potassium channel system. This defect would be expected to impair repolarization of the muscle membrane, thereby making both skeletal and cardiac muscle hyperexcitable.
This oddly named disease is included in this chapter because an abnormality of voltage-gated potassium channels (VGKC) or circulating antibodies against the channel has been discovered in many patients (anti-VGKC). Some of the latter have the disorder as a result of a paraneoplastic reaction to thymoma and that is the context in which we have encountered it approximately 10 times over a 40 year span. It is characterized by continuous muscle fiber activity sometimes referred to as “neuromyotonia” and therefore may also be considered among similar disorders of constant muscle activity that are discussed further in the chapter. Hyperhidrosis, weight loss, insomnia, and hallucinations may occur, and most cases so far described have ended fatally in a matter of months (Serratrice and Azulay). Other antibodies may accompany the anti-VGKC, including against CASPR2 (mainly with an associated thymoma) and LGI1 and each binds to numerous brain regions as indicated in the series by Irani and colleagues.