Myotonic Muscle Disorders and Periodic Paralysis Syndromes

The myotonic muscle disorders and periodic paralysis syndromes compose a group of disorders characterized by muscle stiffness, pain, and sometimes weakness, which may be intermittent or constant. Evaluation of these disorders in the electromyography (EMG) laboratory is particularly gratifying, as the EMG accompaniment of myotonia is easily recognized by the experienced electromyographer. Clinically, myotonia is characterized by delayed muscle contraction after activation. Myotonia can also be demonstrated after percussion of the muscle. On EMG, myotonic discharges produce a distinctive revving engine sound. This results from the spontaneous firing of muscle fibers that wax and wane in frequency and amplitude, producing this unmistakable sound ( Figure 36–1 ). The myotonic potential may take the form of either a positive wave or a brief spike potential, thus identifying the source generator as a muscle fiber. Myotonia can be induced by mechanical stimulation, such as percussion of the muscle or movement of the EMG needle, or may follow voluntary muscle contraction. Clinically, myotonia is noted most frequently in the myotonic muscle disorders and in some of the periodic paralysis syndromes ( Box 36–1 ). Patients describe an inability to relax their muscles after contraction, such as during hand grip. In addition, myotonia may be experienced by the patient as muscle stiffness.

Box 36–1

Classification of Myotonic and Periodic Paralysis Disorders

I

Inherited myotonic muscle/periodic paralysis disorders
- A
  
  Dystrophic myotonic muscle disorders
  - 1
    
    Myotonic dystrophy, types 1 and 2
- B
  
  Nondystrophic myotonic muscle disorders/periodic paralysis syndromes
  - 1
    
    Chloride channel disorders
    - a
      
      Autosomal dominant myotonia congenita (Thomsen)
    - b
      
      Autosomal recessive myotonia congenita (Becker)
  - 2
    
    Sodium channel disorders
    - a
      
      Paramyotonia congenita (Eulenburg)
    - b
      
      Hyperkalemic periodic paralysis (±myotonia)
    - c
      
      Sodium channel myotonia congenita
    - d
      
      Hypokalemic periodic paralysis type 2 (rare form)
- C
  
  Andersen–Tawil syndrome (no myotonia)
- D
  
  Hypokalemic periodic paralysis, type 1 (calcium channel, no myotonia)
- E
  
  Schwartz–Jampel syndrome (note: there is evidence that the abnormal discharges on EMG are more likely neuromyotonic and not myotonic)
II

Acquired periodic paralysis disorders
- A
  
  Secondary hyperkalemic periodic paralysis (may be associated with myotonia) may be seen in association with the following:
  - 1
    
    Renal failure
  - 2
    
    Adrenal failure
  - 3
    
    Hypoaldosteronism
  - 4
    
    Metabolic acidosis
- B
  
  Secondary hypokalemic periodic paralysis (not associated with myotonia) may be seen in association with:
  - 1
    
    Hyperthyroidism, especially in Asian adults
  - 2
    
    Primary hyperaldosteronism
  - 3
    
    Diuretics
  - 4
    
    Inadequate potassium intake
  - 5
    
    Chronic licorice ingestion
  - 6
    
    Excessive potassium loss through sweat
  - 7
    
    Gastrointestinal or renal potassium wasting
  - 8
    
    Steroid use
III

Muscle disorders associated with electromyographic myotonia
- A
  
  Metabolic: acid maltase deficiency
- B
  
  Inflammatory: polymyositis
- C
  
  Congenital: myotubular myopathy
- D
  
  Associated with systemic disorders: malignant hyperpyrexia
- E
  
  Drug-induced hypothyroidism
IV

Drugs that unmask or precipitate myotonia either clinically or on electromyographic examination
- A
  
  Clofibrate
- B
  
  Propranolol
- C
  
  Fenoterol
- D
  
  Terbutaline
- E
  
  Colchicine
- F
  
  Penicillamine
- G
  
  Cyclosporin
- H
  
  Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (lipid-lowering agents)

Traditionally, the myotonic muscle disorders have been classified into those with dystrophic changes on muscle biopsy, such as the myotonic dystrophies, resulting in weakness, and those without dystrophic changes, such as myotonia congenita and paramyotonia congenita, where weakness is generally not a feature. Myotonia also occurs in several of the periodic paralysis syndromes, both inherited and acquired, as well as on the EMG examination in some metabolic, inflammatory, congenital, and toxic myopathies, although clinical myotonia is generally not apparent. Myotonia can be unmasked or precipitated by various drugs. Very rarely, myotonic discharges are noted on EMG examination in disorders of nerve associated with severe denervation. Although a single, brief run of myotonia may be seen in denervating disorders, it is never the predominant waveform. Neuromyotonia, a rare phenomenon associated with peripheral nerve as opposed to muscle disorders, may result in a delay in muscle relaxation. However, this can be distinguished from myotonia in the EMG laboratory by the spontaneous firing of motor unit action potentials (MUAPs) as opposed to muscle fiber action potentials .

Genetic linkage and mutational analyses have identified the molecular basis for several of the myotonic muscle disorders and periodic paralysis syndromes, resulting in the classification of these disorders based on a specific ion channel or protein kinase defect. Classification of these disorders now can be accomplished based on clinical, electrophysiologic, and molecular findings ( Table 36–1 ). Once myotonia is identified on clinical or needle EMG examination, the electrophysiologic evaluation is directed toward answering several key questions to arrive at the correct diagnosis. To answer these questions, a variety of tests can be performed in the EMG laboratory to distinguish among the dystrophic and nondystrophic myotonic muscle disorders, the periodic paralysis syndromes, and other disorders of muscle with accompanying EMG myotonia. In addition to routine nerve conduction studies and needle EMG, muscle cooling, exercise testing, and repetitive nerve stimulation often are very helpful in differentiating among these disorders ( Box 36–2 ).

Table 36–1

Clinical Features of Myotonic and Periodic Paralysis Disorders

	Myotonic Dystrophy, Type 1	Myotonic Dystrophy, Type 2	Myotonia Congenita: Dominant	Myotonia Congenita: Recessive	Sodium Channel Myotonia	Paramyotonia Congenita	Hyperkalemic Periodic Paralysis	Hypokalemic Periodic Paralysis	Andersen–Tawil Syndrome
Age at onset	Teens to early adult	Teens to mid-adult	Infancy	Early childhood	Childhood to early teens	Infancy	Infancy to early childhood	Early teens	Childhood or early teens
Inheritance	Autosomal dominant	Autosomal dominant	Autosomal dominant	Autosomal recessive	Autosomal dominant	Autosomal dominant	Autosomal dominant	Autosomal dominant	Autosomal dominant
Gene defect	Protein kinase, chromosome 19q ( DMPK gene)	Zinc finger protein-9, chromosome 3q ( ZNF9 gene)	Chloride channel, chromosome 7q ( CLCN gene)	Chloride channel, chromosome 7q ( CLCN gene)	Sodium channel, chromosome 17q ( SCN4A gene)	Sodium channel, chromosome 17q ( SCN4A gene)	Sodium channel, chromosome 17q ( SCN4A gene)	Calcium channel, chromosome 1q (type 1) ( CACNA1S gene) Sodium channel chromosome 17q (type 2) ( SCN4A gene)	Potassium channel, chromosome 17q ( KCNJ2 gene)
Myotonia	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	No
Distribution of myotonia	Distal more than proximal	Proximal and distal	Generalized	Generalized	Proximal more than distal	Face, hands, thighs	Generalized, if present	None	None
Periodic weakness	No	No	No	Yes, in some patients	No	Yes	Yes	Yes	Yes, in some patients
Duration of weakness	N/A	N/A	N/A	N/A	N/A	Minutes to days	Minutes to days	Hours to days
Progressive weakness	Yes	Yes	No	Rarely	No	No	Variable	Yes	Yes
Extramuscular involvement	Yes	Yes	No	No	No	No	No	No	Yes
Provocative factors	None	None	Cold	Cold	Potassium, delay after exercise	Cold, exercise, fasting	Cold, rest after exercise, emotional stress, fasting, potassium loading	Cold, rest after exercise, emotional stress, carbohydrates, alcohol	Rest after exercise, alcohol
Alleviating factors	None	None	Exercise	Exercise	Unknown	Warming	Carbohydrates, mild exercise	Potassium, mild exercise	Mild exercise

Box 36–2

Protocol for Evaluation of Myotonic and Periodic Paralysis Disorders

1

Routine motor and sensory nerve conduction studies should be done first. Generally one or two motor and sensory conduction studies and corresponding F responses in an upper and lower extremity should be performed. Distal CMAPs may be low in the dystrophic myopathies. Proceed to needle EMG.
2

Needle EMG study is carried out after standard conduction studies are completed. The study should include proximal and distal muscles of one upper and lower extremity, as well as facial and paraspinal muscles. Careful note should be made of abnormal spontaneous activity, including myotonic discharges, complex repetitive discharges, fibrillation potentials and positive waves, and MUAP potential configuration and recruitment pattern.
3

Muscle cooling is carried out if there is a clinical suspicion of paramyotonia congenita.
- A
  
  Wrap the limb in a plastic bag, submerge in ice water for about 10 to 20 minutes to bring skin temperature to 20°C. Remove the patient’s hand from water. The hand should always be removed from the ice water if weakness develops.
- B
  
  Needle EMG of a distal forearm or hand muscle is performed, noting the presence of abnormal spontaneous activity (e.g., fibrillation potentials, myotonic bursts) and MUAPs with voluntary contraction.
- C
  
  Allow muscle to rewarm to precooling temperature and continue to record EMG activity (may take >1 hour).
4

Short exercise test is performed if steps 1, 2, and 3 do not yield a definitive diagnosis.
- A
  
  Immobilize hand. Record supramaximal CMAP at abductor digiti minimi stimulating ulnar nerve at the wrist.
- B
  
  Record the CMAP once per minute for 5 minutes with muscle at rest to ensure no decrease in the baseline CMAP.
- C
  
  Have the patient perform maximum voluntary contraction for 5 to 10 seconds.
- D
  
  Record the CMAP immediately. If a decrement in amplitude is seen, continue to record the CMAP every 10 seconds until it recovers to baseline (typically 1–2 minutes).
- E
  
  In cases where a decrement is seen after exercise, repeat the same procedure several times to see if a decrement in the CMAP continues to occur or habituates.
5

Prolonged exercise test is performed if steps 1, 2, 3, and 4 do not yield a definitive diagnosis.
- A
  
  Immobilize hand. Record supramaximal CMAP at abductor digiti minimi, stimulating ulnar nerve at the wrist.
- B
  
  Record the CMAP once per minute for 5 minutes with muscle at rest to ensure a stable baseline.
- C
  
  Have the patient perform maximal voluntary muscle contraction for 2 to 5 minutes, resting every 15 seconds for 3 to 4 seconds.
- D
  
  After the 5 minutes of exercise are complete, have the patient relax completely.
- E
  
  Record the CMAP immediately, then every 1 to 2 minutes for 40 to 60 minutes afterward or until there is no further decline observed in the CMAP (this can go on for >1 hour). Decrement is calculated as follows: (Highest CMAP amplitude after exercise − Smallest CMAP amplitude after exercise)/(Highest CMAP amplitude after exercise × 100). Any decrement >40% definitely is abnormal.
- F
  
  Note that immediately after exercise, the CMAP may be larger, before the slow decline in amplitude takes place. This finding is more common when the pre-exercise rest produces a drop in CMAP, as seen in the periodic paralyses.
6

Repetitive nerve stimulation at 10 Hz.

CMAP, compound muscle action potential; EMG, electromyography; MUAP, motor unit action potential.

Muscle Cooling

In some of the myotonic disorders, muscle cooling can be used to enhance myotonic discharges or bring out other characteristic abnormalities (see sections on Myotonia Congenita and Paramyotonia Congenita). Muscle cooling is best accomplished by wrapping the limb in a plastic bag and submerging it in ice water for 10 to 20 minutes. After the skin temperature is brought down to 20°C, needle EMG of the extremity is performed, with the electromyographer looking for abnormalities. Note that the limb should always be removed from the ice water if weakness develops.

Exercise Testing

Exercise testing can play an important role in the periodic paralysis and myotonic syndromes. Both short and prolonged exercise tests can be performed. In both, a routine distal compound muscle action potential (CMAP) is evoked with supramaximal stimulation (e.g., stimulating the ulnar nerve at the wrist, recording the abductor digiti minimi [ADM]). The nerve then is stimulated at 1-minute intervals for several minutes to ensure a stable baseline, before exercise is begun.

Short Exercise Test

For the short exercise test, the patient is asked to rest for about 5 minutes while a CMAP is recorded every minute, to ensure that the baseline is stable and does not decrease at rest. The patient is then asked to perform maximal voluntary contraction for 5 to 10 seconds. Immediately afterward, a CMAP is recorded. If a decrement in amplitude is seen, then a CMAP is recorded every 10 seconds until the CMAP recovers to baseline (typically 1–2 minutes) ( Figure 36–2 ). If a decrement occurs after brief exercise and then recovers, the same procedure is repeated several times to see if the decrement continues to occur or habituates, which can help differentiate among some of the myotonic syndromes (discussed later).

Prolonged Exercise Test

For the prolonged exercise test, the recording procedure is the same. The patient is asked to rest for about 5 minutes while a CMAP is recorded every minute, to ensure the baseline is stable and does not decrease at rest. After ensuring a stable baseline, the patient is asked to voluntarily contract his or her muscle maximally for 5 minutes, resting every 15 seconds for a few seconds. After the 5 minutes of exercise are complete, the patient relaxes completely. A CMAP is recorded immediately and then every 1 to 2 minutes for the next 40 to 60 minutes. In the periodic paralysis syndromes, both inherited and acquired, the CMAP amplitude may be unchanged or slightly larger immediately after prolonged exercise and then decline substantially over the next 20 to 60 minutes ( Figure 36–3 ).

Repetitive Nerve Stimulation

Many of the same findings on exercise testing can also be found with repetitive nerve stimulation (RNS). Decrements are not uncommon with RNS in the myotonic syndromes. Although decrements may be seen with slow repetitive stimulation (3 Hz), they are more common with faster frequencies, typically 10 Hz. Abnormalities are not seen in all patients; when present, they are not specific to any individual syndrome.

When all the available electrophysiologic techniques are used, the correct diagnosis usually can be determined by answering several key questions ( Table 36–2 ):

1

Are routine nerve conduction studies normal?
2

On concentric needle EMG:
- A
  
  Are myotonic discharges present on needle EMG, and, if present, are they widespread or focal? If focal, what is the distribution, proximal or distal?
- B
  
  Are the MUAPs and recruitment pattern on EMG examination normal or abnormal? If the MUAPs and recruitment pattern are abnormal, are they myopathic or neurogenic?
3

Is there an effect of muscle cooling on the needle examination?
4

What does the short exercise testing show?
5

What does the prolonged exercise testing show?
6

What does the repetitive nerve stimulation show?

Table 36–2

Electrophysiologic Testing in Myotonic and Periodic Paralysis Disorders

Test	Myotonic Dystrophy, Type 1	Myotonic Dystrophy, Type 2	Myotonia Congenita: Dominant	Myotonia Congenita: Recessive	Sodium Channel Myotonia	Paramyotonia Congenita	Hyperkalemic Periodic Paralysis	Hypokalemic Periodic Paralysis	Andersen–Tawil Syndrome
Nerve conduction studies	Normal or decreased distal CMAPs	Normal	Normal	Normal	Normal	Normal	Normal between attacks; decreased CMAP amplitude during attack of weakness	Normal between attacks; decreased CMAP amplitude during attack of weakness	Normal
EMG Myotonia MUAPs	++D >P Myopathic D	++D >P (upper extremity); D = P (lower extremity) Occasional CRDs Myopathic P	+++P and D Normal	+++P and D Usually NL, ±Myopathic	++P and D Normal	++P and D Normal	++P and D, especially during attack Myopathic late in course	No myotonia Myopathic late in course	No myotonia Normal
Muscle cooling (20°C) on electromyography	No effect	Unknown	May lead to increased duration of myotonic bursts; easier to elicit	No effect	Unknown	Transient dense fibrillation potentials that disappear below 28°C; myotonic bursts disappear below 20°C electrical silence, long lasting muscle contracture at 20°C	No effect	No effect	No effect
Short exercise	Drop in CMAP amplitude; quick recovery over 2 minutes; drop is smaller or does not persist on subsequent trials	Not well documented	Variable drop in CMAP amplitude; quick recovery over 2 minutes	Large drop in CMAP amplitude; delay in recovery may become progressive over time	Unknown	Normal or small increment in a warm muscle; marked drop in CMAP amplitude and very slow recovery over 1 hour in cooled muscle	No effect or transient increase in CMAP amplitude during an attack of weakness	No effect or transient increase in CMAP amplitude during an attack of weakness	No effect
Prolonged exercise	Small decrement immediately after exercise, with recovery over 3 minutes	Unknown	Unknown	Small decrement immediately after exercise, with recovery over 3 minutes	Unknown	Moderate decrement immediately after exercise, maximal at 3 minutes, with slow recovery over 1 hour in cooled muscle	Most with initial increase in CMAP amplitude (∼35%); progressive drop in CMAP amplitude (∼50%) over 20 to 40 minutes with slow recovery over 1 hour	Most with initial increase in CMAP amplitude (∼35%); progressive drop in CMAP amplitude (∼50%) over 20 to 40 minutes with slow recovery over 1 hour	Most with initial increase in CMAP amplitude (∼35%); progressive drop in CMAP amplitude (∼50%) over 20 to 40 minutes with slow recovery over 1 hour
10 Hz RNS	Decrement	Not well documented	Decrement	Large decrement	Not documented	Normal	Normal	Normal	Normal

CMAP, compound muscle action potential; CRD, complex repetitive discharge; D, distal; EMG, electromyogram; MUAP, motor unit action potential; NL, normal; P, proximal; RNS, repetitive nerve stimulation.

Dystrophic Myotonic Muscle Disorders

Myotonic Dystrophy

The myotonic dystrophies are among the most common of the myotonic muscle disorders. They are an autosomal dominant inherited, multisystem disorder characterized by progressive facial and limb muscle weakness, myotonia, and involvement of several organ systems outside of skeletal muscle. Myotonic dystrophy type 1 (DM1) is the most common; it is due to a defect in the protein kinase myotonin [dystrophia myotonica-protein kinase ( DMPK )] gene on chromosome 19q. The gene defect itself is an unstable expansion of a CTG trinucleotide repeat in the untranslated region of the myotonin gene. Age of onset and severity of symptoms are variable and proportional to the size of the abnormal CTG trinucleotide repeats, which expands over subsequent generations. This phenomenon of “anticipation” results in an earlier onset and more severe course in subsequent generations. Myotonic dystrophy type 2 (DM2), also known as proximal myotonic myopathy (PROMM syndrome) and proximal myotonic dystrophy (PDM), is due to a defect in the zinc-finger protein-9 ( ZNF9 ) gene on chromosome 3q. The gene defect itself is an unstable expansion of a CCTG repeat in intron 1 of the zinc-finger protein-9 gene.

Myotonic Dystrophy Type 1

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 ( Figure 36–4 ). Patients with a smaller CTG 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, i.e., 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 mental retardation. 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, atrophy of type I muscle fibers, 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 patients with a very small increase in the number of repeats (50–100), less than a half of these patients are symptomatic, and most of these patients have cataracts only. More typically symptoms and signs of DM1 are present in patients with over 100 repeats.

Electrophysiologic Evaluation

The electrophysiologic evaluation of DM1 ( Table 36–2 ) consists of routine nerve conduction studies, electromyography, 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 are the classic waxing and waning muscle fiber action potentials ( Figure 36–5A ). 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.

FIGURE 36–5

Myotonic discharges.

A: Two-second myotonic discharge in a patient with DM1 showing typical waxing and waning frequency and amplitude; maximal frequency about 60 Hz, minimal frequency about 8 Hz. B: Four-second myotonic discharge (two successive oscilloscope sweeps) in a patient with DM2 in which frequency and amplitude gradually decline with no waxing component; maximal frequency toward onset about 23 Hz, minimal frequency toward termination about 19 Hz.

(With permission from Logigian, E.L., Ciafaloni, E., Quinn, L.C., et al., 2007. Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy. Muscle Nerve 35, 479–485.)
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

Repetitive nerve stimulation 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 to 2 minutes and habituates with further cycles. This pattern of abnormalities strongly suggests the diagnosis of myotonic dystrophy type 1. Note that when a patient presents with typical signs and symptoms of myotonic muscular dystrophy, muscle cooling, exercise testing, and repetitive nerve stimulation 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.

Myotonic Dystrophy Type 2

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, CNS 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 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 36–2 .

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 tend to be predominantly waning potentials ( Figure 36–5B ). 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 prominent in the distal than in the proximal muscles, similar to DM1. The leg, however, is different. Although myotonic discharges are present in distal muscles (e.g., the tibialis anterior), the number of myotonic discharges is not significantly greater in distal than in 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 in the very proximal muscles are noted in 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 cases of polymyositis, where 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.