In this chapter, we describe the pathophysiology, clinical presentation, laboratory findings, and treatment of the nondystrophic myotonias and periodic paralyses (Table 31-1).
There are several inherited myopathic disorders associated with clinical or electrical myotonia in which muscle is not dystrophic.1–5 These disorders are caused by mutations in various ion channels, and are thus referred to here as muscle channelopathies. Mutations in the chloride channel cause myotonia congenita (MC). The sodium channelopathies include potassium-sensitive (hyperkalemic) periodic paralysis (HyperKPP), paramyotonia congenita (PMC), potassium-aggravated myotonias (PAM) (e.g., myotonia fluctuans, myotonia permanens, and acetazolamide-responsive myotonia), and familial hypokalemic periodic paralysis type 2 (HypoKPP2). HyperKPP and PMC are usually associated with episodes of transient generalized or focal weakness. Hypokalemic periodic paralysis type 1 (HypoKPP1) is not associated with myotonia clinically or electrically and is caused by mutations of muscle dihydropyridine (DHP) receptor (a type of calcium channel). Andersen–Tawil syndrome (ATS) is another rare form of hereditary periodic paralysis of which some forms are due to mutations in a potassium channel.
Electrophysiological studies, in particular the short- and long-exercise tests (SETs and LETs), also described in Chapter 2, can be useful in distinguishing subtypes of muscle channelopathy and thus deserve special comment (Tables 32-1,32-2).1–9 The SET is performed by having the patient isometrically exercise a muscle (e.g., abductor digiti minimi) for 10 seconds, followed by measurement of compound muscle action potential (CMAP) amplitudes immediately after exercise and every 10 seconds thereafter up to 60 seconds. Fournier et al. modified the test by having the SET repeated twice more with a rest period of 60 seconds between trials. In addition, the SET should be done at room temperature and then with cooling of the muscle. In normal individuals, immediately after short exercise, there is a mild increase in the CMAP amplitudes compared to baseline (mean 4–5%, range −28% to +27%) with the amplitudes returning to baseline within 10 seconds.8,9 If the SET is performed after cooling the limb (e.g., with an ice pack), the CMAP amplitudes decrease (−25% to −65%), but the durations of the CMAPs increase.
TABLE 32-1.NONDYSTROPHIC MYOTONIAS AND HEREDITARY PERIODIC PARALYSIS ||Download (.pdf) TABLE 32-1.NONDYSTROPHIC MYOTONIAS AND HEREDITARY PERIODIC PARALYSIS
|Disorder ||Inheritance ||Gene (Location) ||Clinical or EMG Myotonia ||Short Exercise Test ||Long Exercise Test ||Fournier Electro-physiologic Pattern |
Myotonia congenita (MC)
|CLCN-1 (7q35) ||Yes ||±PEMPs; transient decrease in CMAP amplitudes after the first trial in AR-MC but less common with AD MC; reduction in amplitudes is less in the second and third trials. No change with cold in AR-MC, but reduction in amplitudes occurs after the first trial in AD-MC that improves with subsequent trials ||Slight or no decrease in amplitudes immediately after exercise with no change over time ||Pattern II |
|Hyperkalemic periodic paralysis (HyperKPP) ||AD...|