Myotonic Muscle Disorders and Periodic Paralysis Syndromes

Clinical

Patients with DM1 generally present in their late teens with mild distal weakness and delayed muscle relaxation, such as difficulty releasing their hand grip. This disorder is distinguished from other muscle disorders by the distal rather than proximal predominance of weakness, as well as the myotonia. The myotonia is less marked than in the myotonia congenitas. In classic myotonic dystrophy, patients experience stiffness that improves with repeated contractions. Thus, patients often report that repeated opening and closing of the hand results in a faster relaxation time with each grip. As the weakness progresses over years, the myotonic symptoms generally recede.

There is a distinctive clinical appearance characterized by bifacial weakness, temporal wasting, and frontal balding, resulting in a narrow, elongated face and horizontal smile, with ptosis, and distal muscle wasting and weakness ( Fig. 39.4 ). Patients with a smaller CTG trinucleotide repeat may not have the typical facial appearance. Weakness of neck flexion is also an early sign, and patients may notice difficulty lifting their head off the pillow or a tendency for the head to fall backwards during acceleration. DM1 is distinguished from many of the other myotonic disorders by the progressive distal weakness as well as involvement of several organ systems outside of skeletal muscle resulting in cataracts, cardiac conduction and pulmonary defects, endocrine dysfunction, testicular atrophy, hypersomnia, gynecologic problems, and, in some patients, mild to moderate cognitive impairment. As in the other myotonic and periodic paralysis syndromes, patients with myotonic dystrophy should be warned against potential anesthetic complications of succinylcholine and anticholinesterase agents.

The clinical examination in a patient suspected of having myotonic dystrophy is directed at recognition of the typical facies; demonstration of bifacial, neck flexor, and distal wasting and weakness; and demonstration of grip and percussion myotonia. Percussion myotonia can generally be elicited most easily over the thenar muscles and long finger extensors. Eyelid myotonia is not seen. Deep tendon reflexes often are reduced or absent in the lower extremities as the disease progresses. Slit lamp examination reveals posterior capsular cataracts, which early on have a characteristic multicolored pattern. Approximately 10% of cases are congenital, characterized by severe weakness and hypotonia at birth and intellectual disability. Children with the congenital form are floppy at birth, have a typical tented upper lip with poor sucking and swallowing, and often have contractures. Surprisingly, clinical myotonia is not present the first year of life. The congenital form nearly always is maternally inherited. In many cases, the mother may be so minimally affected that her diagnosis is not made until the infant is born with severe hypotonia and a myopathic facies.

Creatine kinase (CK) levels may be mildly to moderately elevated. Muscle biopsy typically reveals a mild increase in connective tissue, increased variation in fiber size, predominant atrophy of type I muscle fibers, an increase in central nuclei, ring fibers, and occasional small angulated fibers.

The clinical severity of DM1 is directly related to the number of CTG repeats. In normals, the number varies between 5 and 37, whereas in patients with DM1, the number of CTG repeats may range into the thousands. In individuals with a very small increase in the number of repeats (50–100), fewer than half of these people are symptomatic, and most have cataracts only. Symptoms and signs of DM1 are more typically present in individuals with over 100 repeats.

Electrophysiologic Evaluation

The electrophysiologic evaluation of DM1 ( Table 39.2 ) consists of routine nerve conduction studies, EMG, muscle cooling, and exercise testing.

• 1.

  Routine motor and sensory nerve conduction studies are normal as a rule. Generally, one motor and sensory nerve conduction study and F responses in an upper and lower extremity will suffice. A mild neuropathy has been described, perhaps secondary to the accompanying endocrine changes. Low CMAP amplitudes may be noted secondary to the distal myopathy in patients with severe disease.

• 2.

  Concentric needle EMG of at least one upper and one lower extremity should be performed, in addition to sampling facial and paraspinal muscles. Most but not all patients with DM1 will demonstrate myotonic discharges on EMG. In very mild cases (e.g., in patients with a small increase in the number of repeats), myotonic discharges may be difficult to find. Otherwise, myotonic discharges are generally most prominent in the distal hand, forearm extensor, foot dorsiflexor (tibialis anterior), and facial muscles but usually are not found in proximal muscles. The distribution of myotonic discharges follows the same pattern as the weakness. Myotonic discharges in DM1 consist of the classic waxing and waning muscle fiber action potentials ( Fig. 39.5A ). MUAP analysis may be difficult because of the myotonic discharges provoked by needle insertion or muscle contraction. However, careful examination reveals myopathic (low amplitude, short duration, polyphasic) MUAPs with early recruitment, which are generally noted in the forearm extensor and tibialis anterior muscles, consistent with the distal predominant weakness on clinical examination. Late in the course of DM1, MUAPs may become large and long.

  

• 3.

  Muscle cooling to 20°C has no appreciable effect on the EMG examination.

• 4.

  The short exercise test produces a drop in the CMAP amplitude immediately after exercise. If the CMAP then is recorded every 10 seconds up to 2 minutes, it recovers to baseline. If short exercise is repeated, the decremental response habituates after one or two cycles, with no further decrement in the CMAP occurring immediately after exercise.

• 5.

  RNS at 10 Hz produces a decrement similar to the short exercise test.

When electrophysiologic testing is completed, one has established the presence of myotonia with myopathic MUAPs on the needle examination, with a distal and facial muscle predominance. There is no effect of muscle cooling. The short exercise test demonstrates a decrement that recovers over 1–2 minutes and habituates with further cycles. This pattern of abnormalities strongly suggests the diagnosis of DM1. Note that when a patient presents with typical signs and symptoms of myotonic muscular dystrophy, muscle cooling, exercise testing, and RNS are not necessarily done on a routine basis but may be helpful in some clinical situations, when the diagnosis is still in question after standard nerve conduction studies and EMG needle examination are completed.

Clinical

DM2 has many features in common with DM1. Like DM1, it is an autosomal dominant inherited muscle disorder recognized by a constellation of signs, including bifacial weakness, ptosis, progressive weakness, myotonia, and involvement of several organ systems outside of skeletal muscle. Patients typically present after the age of 40 with progressive weakness. Unlike myotonic dystrophy, however, the weakness involves predominantly proximal, as opposed to distal, muscles. The pattern of weakness typically involves the hip flexors and extensors, neck flexors, elbow extensors, and finger and thumb flexors. Anticipation is generally not seen between generations of affected family members. Like DM1, the multisystem involvement may include posterior capsular cataracts, frontal balding, testicular atrophy, and cardiac conduction defects. However, central nervous system involvement does not occur or is much less common.

Patients are recognized by their presentation of proximal greater than distal weakness, with mild bifacial weakness and ptosis in the setting of grip and percussion myotonia. Many patients have a peculiar intermittent pain syndrome in the thighs, arms, or back. CK may be mildly to moderately elevated, and the muscle biopsy reveals a nonspecific myopathic pattern, including increased variation in fiber size, small angulated fibers, pyknotic nuclear clumps, predominant atrophy of type II muscle fibers, and increased central nuclei. Rare cases of isolated elevated CK (“hyper-CKemia”) without other clinical or electrical abnormalities have been reported in DM2.

Electrophysiologic Evaluation

See Table 39.2 .

• 1.

  Routine motor and sensory nerve conduction studies are normal as a rule. Generally, one motor and sensory nerve conduction study and F responses in an upper and lower extremity will suffice.

• 2.

  Concentric needle EMG of at least one upper and one lower extremity and paraspinal muscles should be performed. In contrast to DM1, the myotonic discharges seen in DM2 tend to be predominantly waning potentials ( Fig. 39.5B ). These potentials are less specific than the classic waxing and waning discharges typically associated with myotonia. The distribution of the myotonic discharges in the upper extremities in DM2 is surprisingly more predominant in the distal than in the proximal muscles, similar to DM1. In the lower extremities, however, the pattern is different. Although myotonic discharges are present in distal muscles (e.g., the tibialis anterior), the number of myotonic discharges is approximately the same in distal and proximal muscles (e.g., tensor fascia lata). Thus the presence of myotonic discharges in the proximal lower extremity muscles is much more common in DM2 than DM1. Similar to DM1, the absence of myotonic discharges does not exclude the diagnosis of DM2. Complex repetitive discharges are noted occasionally. MUAP analysis reveals myopathic (low amplitude, short duration, polyphasic) MUAPs with early recruitment, which are generally noted in the proximal lower extremity muscles.

• Once the nerve conduction studies and EMG are completed, the presence of myotonia with myopathic MUAPs has been established on needle examination, present primarily in proximal muscles of the lower extremity, and distal muscles of both the upper and lower extremities. Few disorders associated with myotonia have a proximal predominance with myopathic MUAPs. Rarely, prominent myotonic discharges, complex repetitive discharges, and myopathic MUAPs are noted in the very proximal muscles of patients with adult-onset acid maltase deficiency. In this disorder, however, the myotonic discharges are generally restricted to the paraspinal muscles. Myotonic discharges also may be seen in some patients with polymyositis, in whom abnormal spontaneous activity and MUAP changes are more prominent proximally. However, myotonic discharges are only infrequently seen in polymyositis. In the myotonia congenitas, myotonic discharges are noted mostly in proximal muscles as well, but with rare exception (i.e., some cases of recessive generalized myotonia congenita), there are no myopathic MUAP changes.

• 3.

  The effects of muscle cooling and the short and prolonged exercise tests have not been well described for this disorder. Short exercise testing in one patient personally examined by the authors revealed no drop in the CMAP amplitude recording from a distal hand muscle. This negative finding may reflect the proximal predominance of weakness.