CK serum levels on most muscle disorders in paediatric population. (serum CK expressed in IU/L)
EDX evaluation for muscle disorders in the pediatric population can be challenging and is usually used to differentiate between primary muscle disorders and mimics such as NMJ diseases. The EMG diagnostic yield for neurogenic diseases and NMJ disorders is high in young children. A recent large retrospective study of myopathies (age range 6 months to 18 years) showed that EMG is similarly highly sensitive for detecting abnormalities in documented myopathies (91% sensitive), but less specific in terms of distinct diagnoses (67%) . However, different cohorts, particularly those that include infants being evaluated for neonatal hypotonia, have shown that the yield for diagnosis of myopathy with only EMG may be low, with a high frequency of false-negative results. The reason for such a low diagnostic yield is unclear. Possible explanations include technical issues, patchy distribution of myopathic findings, the lower number of muscles often sampled in infants and young children versus adults, and the difficulty of distinguishing between expected small MUAPs in infants versus MUAPs that are truly myopathic [10, 19, 20].
The usual protocol for myopathy should include one sensory and one motor nerve conduction study with an accompanying F response in one upper and one lower limb. For needle EMG, it is ideal to study at least two distal and two proximal muscles in the upper and lower extremities and at least one paraspinal muscle or the genioglossus. However, in practice the number of muscles studied in children is generally fewer, depending on circumstances such as the tolerance of the individual child. The use of sedatives like propofol can improve the quality and tolerability of some aspects of the study, however this must be balanced with the loss of active patient recruitment and reduced or absent visualization of MUAPs in a sedated or anesthetised patient . Thus, it is generally recommended to perform the majority of studies in children without sedation or general anesthesia, as explained in greater detail in Chap. 3.
One has to keep in mind that there can be a transient mild elevation of CK after an EMG study. Therefore, measuring the CK right after the EMG is not recommended if it is possible to have blood drawn for the test another day, though the elevation typically doesn’t exceed 1.5× of baseline. Another precaution is to avoid performing a muscle biopsy in a muscle where a needle EMG was recently performed since the needle can generate a mild inflammation at the site of the recording.
EDX findings can be divided into 6 different groups that can assist with generating a differential diagnosis (Fig. 22.2).
Combined myopathies with neuropathies
Myopathic pattern with no spontaneous activity
Myopathic pattern with predominant fibrillation discharges
Myopathic pattern with myotonia
Myopathic pattern with complex repetitive discharges
Myopathies with normal EDX
Diagnostic algorithm by most prevalent electrophysiological findings in muscle disorders
Nerve Conduction Studies
Nerve conduction studies should be normal in myopathies, except in cases with severe muscle wasting where decreased compound muscle action potential (CMAP) amplitude may be observed. In the setting where there is a low CMAP amplitude and normal sensory nerve action potential (SNAP) amplitudes, one should also consider a disorder of neuromuscular transmission (especially presynaptic NMJ disorders such as Lambert-Eaton syndrome) as well as disorders of motor neurons and/or motor nerves. Lambert-Eaton myasthenic syndrome (LEMS) is rare in the paediatric population but it has been reported in a handful of cases associated with paraneoplastic or autoimmune disorders [22–25]. Testing should include a single supramaximal stimulation delivered before and after short (10-second) exercise. Presynaptic NMJ disorders such as LEMS will classically demonstrate a dramatic post-exercise facilitation, namely a > 60–100% increase in CMAP amplitude above baseline values [26, 27]. When such a diagnosis is under consideration, it is helpful to perform a repetitive nerve stimulation study (RNS) (see Chap. 6) with a proper protocol that includes the evaluation of the presynaptic NMJ disorders (see Chap. 21).
The existence of both a neuropathy and myopathy should suggest a more limited differential diagnosis that includes mitochondrial disorders, congenital muscular dystrophies such as those associated with mutations in LAMA2 (which can produce a demyelinating peripheral neuropathy), and more rarely LMNA (which rarely is also associated with a type 2 form of Charcot-Marie-Tooth disease) and COL6 (where some cases of subclinical neuropathy have been observed), rare cases of glycogenosis type 3, Marinesco-Sjögren syndrome, myofibrillar myopathies, or injuries due to toxins (Fig. 22.2) [28–32].
Increased insertional activity in myopathies results from of muscle fiber irritability. Fiber necrosis, inflammation and/or fiber splitting can produce a “functional denervation” which is a partial detachment of a segment of the myofiber from its motor endplate. This represents the muscle-fiber equivalent of what is seen in denervation. In advanced stages of the disease with severe fatty replacement of the muscle, the insertional activity may appear more normal. However, increased insertional activity in isolation without other abnormalities is of unclear significance, and care should be taken not to base a neurophysiologic diagnosis entirely on increased insertional activity alone.
Fibrillation potentials and positive sharp waves (PSW) are the usual findings in neurogenic processes producing denervation. However, for the reason noted above, they can be frequently present in different muscle disorders and thus should not be relied on to distinguish between neurogenic and myopathic diseases.
Fibrillation potentials are usually up to 2 ms in duration and less than 100 μV in amplitude, with bi or triphasic morphology and an initial positive deflection. They have a regular frequency and the sound is usually described as “raindrops on a tin roof”. Positive sharp waves (PSWs) are biphasic waves with an initial sharp positive deflection followed by a slow negative wave. The amplitude can be from 50 μV up to 1 mV. As with fibrillation potentials, they are regular in frequency and the sounds emanating from loudspeakers are described as dull pops, given their longer durations. The frequency of fibrillation potentials or PSWs is usually between 0.5 and 10 Hz and rarely up to 30 Hz. In muscle disorders, they result from segmental necrosis of the myofiber splitting in at least two fragments, one of which is separated from the motor plate. Therefore in those myopathies where the inflammation and necrosis is a typical finding in the muscle biopsy (inflammatory myopathies, dystrophies), it is common to observe fibrillation potentials and PSWs at the time of the EMG (Fig. 22.3a).
(a) Fibrillation potentials and positive sharp waves in myopathies are caused by a partial detachment of the nerve terminal from the motor endplate due to segmental necrosis of the myofiber, producing a “denervated” healthy fragment. On EMG, they are biphasic or triphasic with an initial positive wave and a regular rhythm with a frequency up to 30 Hz. (b) Complex repetitive discharges are secondary to ephaptic firing of a group of myofibers. The MUAPs are regular and stable with an acute onset and stop. (c) Myotonia is caused by spontaneous rhythmic firing of one fiber. It has a characteristic waxing and waning morphology in amplitude and frequency and it produces a typical sound on the loudspeakers reminiscent of a “dive bomber” or “motorcycle”
Another common finding is the presence of complex repetitive discharges (CRDs) due to irritability of the fibers (Fig. 22.3b). They are caused by ephaptic activation of a group of myofibers that will provoke an abrupt onset and abrupt end of the electrophysiological phenomenon. They have uniform frequency (5–100 Hz), morphology and amplitude and are stable in configuration. They are also known as pseudomyotonic discharges given their resemblance to myotonic discharges, however, we avoid the use of this term due to potential confusion that can result. Unlike myotonic discharges, CRDs do not have a waxing and waning configuration. The sounds produced by CRDs have been likened to machine or machine gun noises. This finding can be seen in both myopathic and neurogenic disorders and usually indicates a long standing process with associated atrophy of large groups of muscle fibers that are in close proximity to one another. CRDs by themselves do not indicate a specific diagnosis or class of diagnoses.
A third common finding in myopathies is myotonia (Fig. 22.3c). It is important to differentiate between those disorders that produce clinical and electrophysiological myotonia (i.e., DM1, myotonia congenita and some forms of periodic paralysis) with the ones that produce only electrophysiological myotonia (i.e., some centronuclear myopathies and metabolic disorders such as Pompe disease)  (Fig. 22.2).
Finally, cramps can be associated with underlying metabolic myopathies such as glycogen storage disorders (e.g., McArdle disease) or disorders of fatty acid oxidation (e.g., carnitine palmitoyltransferase II deficiency). Cramps in these cases result from sustained contraction or impaired relaxation resulting from energy failure and/or ion channel dysfunction. Whereas physiological cramping will be associated with high frequency firing of one or more MUAPs (20–150 Hz), patients with metabolic myopathy or channelopathies may demonstrate electrical silence during needle EMG. Hence, as this specific muscle symptom does not actually correspond to an electrophysiologic cramp, some have advocated that it be referred to as a contracture .
The motor unit potential in myopathies is characterized by a smaller morphology and early recruitment due to a dropout of muscle fibers from a motor unit, hence the need to recruit more motor units to generate a specific amount of muscle force. In general the recruitment pattern is appropriate for the firing frequency or activation (defined as the ability of a motor unit to increase the firing rate), but increased for the amount of force being generated. In general, the ratio is 1:5; that means, at a firing rate of 5 Hz only one motor unit should be recruited, at 30 Hz there should be at least 6 different motor units on the screen (Fig. 22.4a). In myopathies, since there are fewer contractile myofibers per motor unit, to generate a given amount of force, it requires a higher amount of active motor units. So, with a slight contraction of the muscle, there will be an inappropriately high number of firing MUAPs, corresponding to a higher number of active motor units (Fig. 22.4b). Traditionally, this finding could only be assessed by the neurophysiologist performing the study who can feel the amount of force generated by a muscle. Accordingly, with the loss of fibers for each motor unit, the amplitudes and durations of the MUAPs will be small, with frequent polyphasia and unstable morphologies (Fig. 22.5), due to loss of synchronicity of activation of the myofibers within a motor unit .
Recruitment pattern. (a) Normal Motor Unit (MU) recruitment. The ratio of firing frequency (activation) to the number of different muscle action potentials (MUAPs) (recruitment) is approximately 5:1. When the firing rate of the first MUAP (I) is 10 Hz, a second MU is recruited (II). By 15 Hz, a third MU starts firing (III), and so forth. (b) Myopathic MU recruitment pattern. The loss of myofibers causes that under a mild muscle contraction there is an inappropriate higher number of activated MU, seen in the screen by different MUAPs at early stages of muscle activation. This is defined as early recruitment. However, the firing ratio is still appropriate at 5:1 producing an interference pattern but with reduced amplitude secondary to small MUs. (c) Neuropathic MU recruitment pattern. Since there is a loss of MU (II) the recruitment is reduced and the remaining MU are forced to fire at a higher frequency. At maximal contraction at approximately 30 Hz there are only 2 MU activated. This produces an abnormal ratio of 15:1. Also observe the nerve sprouting by MU I and III to reinnervate the muscle fibers of MU II. This produces a polyphasic, long duration, high amplitude MUAP. (d) Central MU recruitment pattern. Central involvement will produce an abnormal activation. The recruitment ratio will still be normal at 5:1, however there is an impaired ability to increase the firing rate. (UMN, upper motor unit)
Motor unit action potentials. (a) Normal MUAP. (b) Myopathic MUAP, due to the loss of myofibers the MUAPs are small and of short duration. Unstable and polyphasic potentials are secondary to malfunction of remaining myofibers. (c) Neuropathic MUAP. Nerve sprouting to denervated muscle fibers. This leads to a bigger MUAP of longer duration and polyphasic pattern due to lack of synchronicity with the newly incorporated myofibers
Although the findings in minimal voluntary contraction in the setting of a muscle disease is what is traditionally termed a “myopathic pattern”, small MUAPs may also be found in neuromuscular junction disorders such as botulism, or during early re-innervation after severe neurogenic process [12, 34]. However, the early recruitment pattern is present only in true myopathies , and thus assessment of recruitment pattern is often crucial to the interpretation of a study in which small motor units are observed.
Clinical and Electrophysiological Description of Selected Muscle Disorders
As the overall goal of the present book is to describe EMG patterns specifically in the pediatric population, the childhood myopathies discussed below were selected as examples of electrodiagnostic patterns, and are not meant to comprise a comprehensive discussion of all muscle disorders.
Myopathic Pattern With Fibrillations
As mentioned earlier, fibrillation potentials in myopathies are mainly due to inflammation and necrosis of the myofibers. In children, this is mainly due to inflammatory myopathies and dystrophies.
While in adults there is a higher proportion of patients with polymyositis than dermatomyositis, in children the converse is true, with dermatomyositis being by far the most common inflammatory myopathy in childhood [35, 36]. Juvenile dermatomyositis is a chronic autoimmune disease characterized by limb girdle weakness, with involvement of neck flexors and extensors muscles and pathognomonic skin rashes. It is a multisystem disorder affecting primarily the muscle and skin due to a capillary vasculopathy. There is a predominance in females that ranges from 2:1 to 5:1 [21, 35, 37].
The diagnostic criteria include symmetrical limb girdle weakness, heliotrope dermatitis and/or Gottron’s papules, increased CK (though it is important to note that some patients may have normal values), muscle biopsy consistent with diagnosis (the characteristic finding is the perimysial atrophy of muscle fibers) and an abnormal EMG . In acute-subacute stages EMG shows prominent presence of fibrillation potentials and or positive sharp waves, with short small MUAPs and early recruitment. In long standing forms it is possible to find CRDs. These findings are more evident in proximal and paraspinal muscles. This last muscle group is the most sensitive and should be evaluated when there is no abnormal finding in other muscles . In more chronic cases the MUAPs may have long durations and increased amplitudes, mimicking a neurogenic disorder. The NCVs are normal unless there is severe muscle atrophy in which case decreased CMAP amplitudes will be observed in conjunction with normal sensory responses.
Currently, EMG and muscle biopsy are not used as frequently for diagnosis of dermatomyositis as in the past, as they are considered invasive studies . Muscle MRI has proven to be a useful method for the diagnosis of dermatomyositis and as a biomarker for treatment response, usually revealing increased T2 signals in affected muscles and subcutaneous tissues .
The main therapy is immunosuppressive medications such as corticosteroids, methotrexate or cyclosporine. In some patients who require prolonged corticosteroid use, a secondary proximal muscle weakness may develop, reflecting a steroid myopathy that is associated with selective type 2 fiber atrophy. EMG can be used in such cases to help differentiate among a relapse, refractory dermatomyositis, or a steroid myopathy since dermatomyositis is associated with increased spontaneous activity whereas steroid myopathy is not (see normal EDX group Fig. 22.2) .
Duchenne Muscular Dystrophy (DMD)
DMD is the most common form of muscular dystrophy in childhood . Since it is an X-linked disorder it typically affects males, with heterozygous female carriers sometimes showing mild cardiac and muscle symptoms in adulthood; exceptionally, females will have more dramatic phenotypes such as in the setting of concomitant Turner syndrome, unfavorable X-linked inactivation, or relevant chromosomal translocation . DMD most commonly results from an out-of-frame deletion or duplication within the DMD gene, or less commonly, a frameshift or nonsense mutation. Patients exhibit progressive proximal muscle weakness and contractures, eventually losing independent ambulation, developing cardiomyopathy and later death from cardiorespiratory complications . The diagnosis is confirmed with genetic testing. When DNA testing is negative, muscle biopsy may be required to evaluate for the possibility of a mimicking disorder . Typical muscle biopsy findings include absent dystrophin staining with characteristic dystrophic changes (e.g., split fibers, increased internalized nuclei, regenerating fibers, and replacement of muscle by fat and connective tissue). In some cases, it may be necessary to extract RNA to find direct evidence for cryptic splicing defects . Published databases can also guide clinicians as to whether specific mutations are or are not known to be pathogenic, and clinical genetic test reports increasingly make use of such databases to reduce the reporting of the dreaded “variants of unknown significance”. High serum CK levels (typically >20–150 × the upper limit of normal) should trigger the suspicion for this diagnosis, particularly when there is clinical onset after 1.5 years of age, toe-walking, pseudohypertrophy of the calves, and/or a positive Gowers sign . EDX is rarely used in the diagnostic evaluation for Duchenne muscular dystrophy. In those rare instances when it is performed, nerve conduction studies will be normal, while needle EMG may reveal abnormal insertional activity, fibrillation potentials and PSW, with myopathic motor units and an early recruitment pattern, especially in proximal symptomatic muscles. With advancing disease, the CMAP amplitude will decrease, insertional activity will diminish, and the myopathic findings will become more apparent due to progressive muscle atrophy. In endstage muscle it may be difficult to find areas where motor units can be consistently recruited and evaluated.
Becker muscular dystrophy (BMD) also results from dystrophin mutations. However, unlike DMD, patients with BMD show some residual protein expression and activity, due to the association in most cases with in-frame deletions, duplications, and point mutations . Consequently, patients have a milder symptomatology with a later onset compared to DMD.
DMD management requires a multidisciplinary approach. Corticosteroids have been used to slow disease progression, improving and preserving muscle strength and function, prolonging independent ambulation, and delaying the onset of complications such as scoliosis, respiratory decline and cardiomyopathy [45, 47]. Other therapies are emerging with the goal of improving the expression of dystrophin through novel molecular mechanisms. Such novel therapies include ones that transform an out-of-frame to an in-frame mutation via exon skipping induced by an antisense oligonucleotide that was recently provisionally approved by the US Food and Drug Administration; other novel therapies are in development [47–50].
Glycogen storage disease type II, also known as Pompe disease or acid maltase deficiency, is an autosomal recessive lysosomal glycogen storage disorder. It has two main phenotypes, an early onset form presenting during infancy and characterized by generalized hypotonia, weakness, macroglossia, cardiomegaly, hepatosplenomegaly, failure to thrive, and respiratory insufficiency . The late onset form presents with progressive muscle weakness in both pediatric and adult populations that often mimics the phenotype of limb-girdle muscular dystrophy with frequent respiratory complications but usually without heart involvement . The late onset patients are more difficult to recognize since the presentation can include a limb girdle muscular dystrophy pattern, an asymmetric scapular winging, ptosis, and/or asymptomatic hyperCKemia . The muscle biopsy usually shows vacuoles positive for glycogen with PAS staining, but there are also atypical cases without glycogen accumulation [54, 55]. The serum CK is usually elevated, particularly in the infantile form of the disease (<10× upper limit of normal). Due to the phenotypic variability of this disease, particularly in the later onset form, EDX studies can provide important clues for the diagnosis. NCS are normal except in advanced cases with severe muscle atrophy. Needle EMG may demonstrate fibrillation potentials and PSW as well as myotonic discharges. This is seen in paraspinal muscles in half of the children and two-thirds of adults with this disease. The examination of this group of muscles is important since it may be the only site revealing abnormalities in the EDX . It is important also to mention that this group of patients has electrophysiological myotonia but no clinical signs of it. The diagnosis is usually confirmed by analyzing the enzyme activity in the blood using a dried blood spot testing, followed by genetic testing . The advent of enzyme replacement therapy (ERT) has changed the outcome of the infantile onset patients. Without ERT the early onset has a high mortality with death by the age of 1 year . ERT has also improved symptomatology for patients with late onset Pompe .
Myopathic Pattern with no Spontaneous Activity
Congenital Muscular Dystrophies
The congenital muscular dystrophies (CMD) are a heterogeneous group of disorders. The diagnosis is usually made by the clinical exam, CK levels, which can range from normal to 6–10× high, brain MRI, and immunohistochemical staining in the muscle biopsy. An abnormal brain MRI may be seen in a subset of CMD patients, especially the dystroglycanopathies and merosinopathies. Muscle biopsy shows dystrophic features and may show abnormalities on immunohistochemical staining for merosin and or alpha-dystroglycan (aDG). It is the second most common reason for requests for EMG studies in floppy infants admitted to the NICU for suspected primary muscle disorders, after congenital myopathies . The most common CMD subtype is MDC1A (primary merosin deficiency) . The findings include generalized weakness, early contractures and respiratory insufficiency, high serum CK, diffuse white matter changes on brain MRI and deficient merosin on muscle biopsy [43, 59]. Partial merosin deficiency can be seen in some patients with LAMA2 mutations and also in the alpha-dystroglycanopathies due to abnormalities in protein glycosylation of aDG. The findings include increased CK and frequent eye and brain malformations that range from abnormalities in the posterior fossa to lissencephaly. The most severe classic phenotypes are muscle-brain-eye disease, Walker-Warburg syndrome and Fukuyama CMD . Other CMDs include the rigid spine syndrome due to mutations in SEPN1 and the collagen VI related myopathies (Bethlem myopathy and Ullrich CMD). The latter is characterized by congenital hip dislocation, congenital torticollis, and joint hyperlaxity with development of early contractures and scoliosis and generalized muscle weakness .
Nerve conduction studies are usually normal except for patients with primary merosin deficiency. In this group there is a slowing in the conduction velocities of the motor nerves with normal amplitude and normal sensory studies . Motor neuropathy is often associated with severe form of MDC1A. Also there has been a report of borderline low NCVs in a young patient with Ullrich CMD (due to mutations in COL6) . EMG does not demonstrate the abnormal spontaneous activity that can be seen in other primary myopathies and more significantly in neuropathies. The typical “myopathic” potentials when demonstrated are usually present in more proximal muscles. One report describes brief repetitive decreasing discharges in distal muscles post-electrical stimulation. These were of high frequency (90–300 Hz) and short duration (median 61.5 ms) with the shape of single motor response. They were not elicited by muscle percussion and were different from myotonia due to the lack of the waxing and waning feature .
Congenital myopathies are a heterogeneous group of inherited muscle diseases that vary in age of onset, clinical features, morbidity and mortality. Although the classical description is of patients with onset in infancy, they can present in a wide range of ages. Signs that can help to establish the diagnosis include: lack of antigravity movements, ophthalmoplegia, ptosis, high arched palate, arthrogryposis, hip dysplasia, and lower facial muscle weakness with open tented mouth. The serum CK is typically within the normal range but can be slightly elevated. The diagnosis has been historically established by muscle biopsy, as the different types are classified according to pathological findings. As genetic testing has become more widely available there is a trend to classify them by gene, since numerous genes are now associated with multiple phenotypes and histopathological findings . The different histological subtypes include:
Core myopathy. The muscle biopsy reveals areas lacking enzyme activity with oxidative stains such as SDH and NADH, hence, devoid of mitochondria. This category may further be subdivided into central core disease due to dominant mutations in the RYR1 gene (90% of cases), minicore myopathy without ophthalmoplegia due to mutations in SEPN1 and minicores with ophthalmoplegia due to recessive mutations in RYR1 . Other rare causes of core myopathy including mutations in MYH7, ACTA1, and CCDC78.
Congenital fiber-type disproportion. This term refers to the presence of significantly smaller type I fibers compared with type II without features suggestive of other subtypes of congenital myopathy. A pure CFTD is associated with mutations in RYR1, SEPN1, ACTA1, TPM2 and TPM3. Clinically, CFTD overlaps with other types of congenital myopathies, but the phenotype is typically milder than the other subtypes .
Nemaline myopathy (NM) is diagnosed when the classic nemaline rods are observed on Gomori trichrome stain and on electron microscopy of a muscle biopsy specimen. Clinically, there is severe congenital NM, intermediate congenital NM, typical congenital NM, childhood/juvenile onset NM and adult-onset NM. There are at least 11 genes within this group. The most common are those in NEB causing a recessive disease and in ACTA1 causing a dominantly inherited NM, typically due to de novo mutations. The characteristic features in this group include bulbar muscle involvement, a myopathic face (open mouth, tented lips, excessive drooling), and a high arched palate, with preservation of extraocular movements .
Centronuclear myopathy (including myotubular myopathy) can be caused by mutations in six genes identified to date (MTM1, DNM2, BIN1, SPEG, TTN, and RYR1). Muscle biopsy is characterized by centralized nuclei in at least 25% of the fibers with abnormal central oxidative aggregate staining with SDH and NADH. Certain genes are associated with particular features on muscle biopsy. With DNM2 mutations there is often a “spoke on wheel” appearance with oxidative stains. BIN1 mutations tend to present with clusters of central nuclei. Necklace fibers have been related to mutations in MTM1 and correspond with internalised nuclei within a desmin positive stain ring .
EDX in congenital myopathies has a sensitivity of 36% in infants (<2 years of age) with a false negative rate of 25%. The presence of a “myopathic pattern” in a newborn is extremely low [20, 65]. The use of EMG in this age group has been largely replaced by muscle biopsy and genetic studies, but in some cases EMG may still yield useful diagnostic information. In patients >2 years of age there are no characteristics findings for most of the congenital myopathies. The NCS are normal with normal F-responses. The needle EMG will show MUAPs of small amplitude, short duration and polyphasic potentials with an early recruitment and no spontaneous activity . Centronuclear myopathies can represent an exception since fibrillations, positive sharp waves, and more rarely complex repetitive discharges can be seen on needle EMG [13, 66]. The association of myopathic and myotonic findings have been reported in nemaline myopathy . Abnormal repetitive nerve stimulation testing and other features of a NMJ disorder have been observed in cases of congenital myopathy, including those due to mutations in DNM2, MTM1, RYR1, TPM2, TPM3 and KLHL40 [67–72].
Clinical myotonia is a symptom and sign found in a subgroup of neuromuscular disorders. It is caused by muscle ion channel abnormalities and presents with stiffness or cramping in involved muscles. Myotonia may be detected clinically after forced eye closure, leading to delay in eye opening or by making a fist followed by difficulty releasing the grip. Percussion myotonia can be elicited by tapping the thenar muscle, as well as the quadriceps, gastrocnemius or tongue. Myotonia usually decreases with repeated muscle contractions (positive “warm-up” phenomenon) in contrast to paramyotonia (“paradoxical myotonia”) in which muscle relaxation becomes progressively delayed with repetitive contractions. This is an important clinical distinction that can help to differentiate these two types of myotonic disorders.
Historically, myotonias were classified accordingly to their clinical features and inheritance patterns. More recently, genetic testing has further defined the different types (Table 22.1).
Common genetic causes of myotonia
Clinical myotonia and electrical myotonia
Myotonic dystrophy type 1
Myotonic dystrophy type 2 (proximal myotonic myopathy)
Clinical paramyotonia and electrical myotonia
Hyperkalemic periodic paralysis
Electrical myotonia without clinical myotonia
Acid maltase deficiency
Needle EMG in the detection of myotonia plays a very important role as electrical myotonia is quite often more easily detected than clinical myotonia. Myotonic potentials are recorded after insertion or movement of the EMG recording electrode in relaxed muscle or on percussion next to the needle. It presents as trains of rhythmic firing of grouped motor unit potentials in the form of positive waves or fibrillation potentials with waxing and waning frequency and amplitude with firing ranges of 20 to 80 Hz and amplitudes from 10 to 1000 μV . Audio profile of the discharges has been characterized as that of dive bomber airplane, motorcycle, or chain saw engine .
The most common is myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) and they both share prominent clinical and electrical myotonia.
DM1 is an autosomal dominant disease caused by a CTG trinucleotide expansion in the untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene on chromosome 19q13.3 [75–77]. Anticipation is characteristic in this disease with an increasing number of CTG repeats in subsequent generations, especially with maternal inheritance, with large CTG repeats of 1000–4000 typically occurring in the congenital form of DM1. Although cranial muscle weakness and wasting and predominantly distal muscles weakness and wasting are the main features of this disease along with myotonia, other systems can be involved leading to cognitive dysfunction, hypersomnia, dysphagia, cardiac arrhythmias, muscle pain, cataracts, respiratory insufficiency, insulin resistance and diabetes, and cancer [78, 79]. The childhood-onset form of DM1 can present as early as the neonatal period with muscle weakness and respiratory insufficiency and although these children improve with time, they have long term global developmental delays.