Myotonic dystrophy type 2 with focal asymmetric muscle weakness and no electrical myotonia

Genetically proven myotonic dystrophy type 2 (DM2) was found in a 61‐year‐old woman with creatine kinase (CK) elevation and only isolated weakness of one triceps. There was no clinical or electrical myotonia. Electromyography (EMG) showed only scattered fibrillation potentials and short duration motor unit potentials. Muscle biopsy showed nonspecific myopathic features and highly atrophic fibers with nuclear clumps. DM2 should be considered in patients with focal proximal weakness and abnormal EMG without myotonic discharges. Muscle Nerve 39: 383–385, 2009     

Proximal myotonic myopathy: clinical, electrophysiological and pathological findings in a family

Proximal myotonic myopathy (PROMM) is an autosomal dominant muscle disorder characterized by proximal weakness, myotonia, muscle pain and cataract. It resembles Steinert myotonic dystrophy (MD), but weakness is proximal, without facial muscle involvement, and the chromosome 19 CTG trinucleotide repeat expansion characteristic of MD is not present. We describe a further family with PROMM. Affected members complained of weakness of lower limbs or of myotonia. EMG revealed diffuse myotonic discharges. Muscle histology showed dystrophic abnormalities. The PROMM phenotype varies, even in the same pedigree, and may mimic MD or limb-girdle muscle dystrophy. EMG is particularly useful, since it may disclose myotonic discharges even in the absence of overt myotonia. Thus far it is not known whether PROMM is a single entity, or if it represents a heterogeneous group of disorders. This question will probably soon be settled through genetic analysis.     

Proximal myotonial myopathy (PROMM): clinical and histology study

We report 13 French patients with proximal myotonic myopathy. PROMM is a recently delineated multisystem disorder with dystrophic myopathy, myotonia and cataracts. This syndrome is genetically distinct from myotonic dystrophy (DM) by the absence of abnormal CTG repeat expansion. The geographical origin varies but 4 families originated from Poland. Of late onset, muscle weakness is diffuse and predominantly affected proximal and axial muscles. Facial involvement and myotonia were moderate or absent, but in all cases myotonic discharges were detected on EMG. 6 patients suffered from myalgia. Cataracts occurred in 11 patients, mainly indistinguishable from those in DM. Cardiac arrythmia occurred in 7 patients. Muscle biopsy revealed rare structural changes of the muscle fibers and selective type I atrophy, common in DM, could not be found on morphometric analysis. PROMM has a distinct clinical spectrum from DM which includes a predominantly proximal muscle weakness, with troubling pain, a more favourable prognosis and a different histopathological pattern.     

The spectrum of myotonic and myopathic disorders in a pediatric electromyography laboratory over 12 years

This study assessed the spectrum of disorders associated with electrophysiologic myotonia in a pediatric electromyography laboratory. Records of 2234 patients observed in the Electromyography Laboratory at Boston Children's Hospital from 2000-2011 were screened retrospectively for electrophysiologic diagnoses of myotonia and myopathy. Based on electromyography, 11 patients manifested myotonic discharges alone, eight exhibited both myotonic discharges and myopathic motor unit potentials, and 54 demonstrated myopathic motor unit potentials alone. The final diagnoses of patients with myotonic discharges alone included myotonia congenita, paramyotonia congenita, congenital myopathy, and Pompe disease (acid maltase deficiency). The diagnoses of patients with both myotonic discharges and myopathic motor unit potentials included congenital myopathy and non-Pompe glycogen storage diseases. Myotonic discharges are rarely observed in a pediatric electromyography laboratory, but constitute useful findings when present. The presence or absence of concurrent myopathic motor unit potentials may help narrow the differential diagnosis further.     

The clinical and myopathological features of oculopharyngodistal myopathy in a Chinese family

Oculopharyngodistal myopathy is a rare type of hereditary myopathy characterised pathologically by the changes of muscular dystrophy with rimmed vacuoles and intra‐muscular tubulofilamentous inclusions. Here we report the clinical and myopathological changes in a Chinese family with oculopharyngodistal myopathy. The proband showed external ophthalmoplegia, dysphagia, distal weakness and atrophy in all extremities. Serum creatine kinase level was mildly elevated and a myopathic pattern with myotonic discharge was demonstrated by electromyography (EMG). Molecular genetic analysis showed that the number of trinucleotide repeat expansions in the polyadenylate‐binding protein nuclear 1 gene was within the normal limit. No mutations were indentified in the GNE gene. Five other persons with similar symptoms were found in the same generation. Muscle biopsy was performed on the tibialis anterior muscle in the proband. Muscular dystrophy changes with rimmed vacuoles were the main histopathological changes. Ultrastructural examination revealed numerous tubulofilamentous inclusions in both sarcoplasm and nucleus. EMG showed myotonic discharges in oculopharyngodistal myopathy. In addition to the sarcoplasm inclusions, we confirmed that tubulofilamentous inclusions appeared also in the nucleus.     

Myotonia in colchicine myoneuropathy

Colchicine may induce a myoneuropathy in patients with renal insufficiency. To date, myotonia has not been described in this disorder. We recently studied 4 patients treated with routine doses of colchicine who, in the setting of renal insufficiency, developed a severe myoneuropathy characterized by prominent myotonic discharges on electromyography. In addition, 1 of the 4 patients had profound clinical myotonia. In the 3 patients in whom biopsies were performed, marked myopathic change with intracytoplasmic vacuolization was identified. All 4 patients improved rapidly with discontinuation of the medication. The patient in whom electrophysiologic studies were repeated had a complete resolution of the myotonic discharges. Colchicine myoneuropathy can present with prominent clinical and electrophysiologic myotonia that resolves completely with discontinuation of the medication. © 1996 John Wiley & Sons, Inc.     

A case of Isaac's syndrome--continuous muscle fiber activity syndrome

A 34-year-old woman noted difficulty of gait initiation, then dilated finger opening and hyperhidrosis appeared. Her stature was a muscular habitus, and muscle stiffness and myokymia were found in all muscles of the extremities. Her stiffness persisted during sleep. Her calf muscles were large and a contracture was noticed in ankle joints. There was no evidence of wasting and weakness. A remarkable delay in voluntary relaxation of the contracted muscles without percussion myotonia was recognized. Tendon reflexes of lower extremities were absent. Laboratory examination revealed elevation of CPK, LDH, myoglobulin, aldolase and basal metabolic rate (BMR). An extraband of CPK isoenzyme between MB and MM fraction was observed. The thin layer gel filtration technique and immunofixation technique showed that this extraband was complexes of CPK and IgA, and light chain of the CPK linked IgA was lambda type. All other laboratory tests were normal for the following: urinalysis, ESR, a blood count, liver function, kidney function, glucose, rheumatoid factor, CRP, thyroid function, parathyroid function, serum electrolytes, ECG, EEG, cranial CT, without slight elevation of IgA, and CSF protein. In needle EMG and surface EMG spontaneous discharges were recorded at rest. These discharges consist of normal motor unit potentials, doublets, and triplets in needle EMG. The discharges were markedly reduced after the median nerve block with xylocaine. In needle EMG, myotonic discharge was not observed. Nerve conduction velocities were within normal ranges. According to these data, she was diagnosed as having Issacs' syndrome (continuous muscle fiber activity syndrome). Carbamazepine, 200 mg daily was administrated and showed a dramatic reversal of the symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proximal myotonic myopathy

Three Swedish patients with proximal muscle weakness, myotonia and lack of CTG expansion on genetical analysis are presented. Clinical neurological and neurophysiological examination and muscle biopsy were performed. There was an indication of autosomal dominant inheritance in 2 of the 3 patients. The main symptoms and clinical findings in the 3 patients were weakness of the proximal muscles, myotonia, muscle stiffness, muscle pain and muscle atrophy. Neurophysiological examination showed myotonic bursts and muscle biopsy snowed a variation of fibre sizes, an increased number of muscle fibres with centralized nuclei and scattered atrophic muscle fibres. Laboratory data showed elevated CK, GT and LD in 1 patient. Before genetical analysis was performed, all 3 patients had been diagnosed as atypical cases of myotonic dystrophy. However, the symptoms, clinical signs, laboratory data, electrophysiological and muscle biopsy findings were compatible with proximal myotonic myopathy (PROMM).     

Equine muscular dystrophy with myotonia.

OBJECTIVES: To describe a case of equine muscular dystrophy with myotonia. METHODS: A 5-year-old horse presented with hypertrophy and delayed relaxation of the muscles of the hindlimbs from age 2 months. Testicular atrophy developed from 2 years of age. Action and percussion myotonia was associated with weakness in these muscles, and EMG showed diffuse myotonic discharges and myopathic features. Biopsy of the gluteal muscle showed adipose and connective tissue infiltration, marked variation in muscle fibre size, and moth-eaten, ring and whorled fibres. RESULTS: Injection of apamin, a peptide blocker of calcium-activated potassium channels, which inhibits myotonia in human myotonic dystrophy, was ineffective in blocking myotonic discharges. Discharges promptly abated with 2% lidocaine injection. CONCLUSIONS: Myotonia in this horse is associated with dystrophic changes similar to human myotonic dystrophy, though there are some pharmacological differences.     

Diagnostic impact of myotonic discharges in myofibrillar myopathies

Introduction: In patients with myofibrillar myopathies (MFM), myotonic discharges have occasionally been detected by needle electromyography (EMG). Nevertheless, this peculiar type of spontaneous repetitive discharge has not attracted special interest in the genetically heterogeneous MFMs. Methods: EMG features were analyzed in 6 patients with genetically confirmed MFM (n = 1 MYOT, n = 1 DES, n = 2 ZASP, n = 2 FLNC). Results: Fibrillation potentials, positive sharp waves, and myotonic discharges were found in all 6 patients, and complex repetitive discharges were found in 5. Myotonic discharges were detected in approximately 50% of the analyzed muscles independent of the site, including distal (3/6), proximal limb (4/6), and paravertebral muscles (3/6). Clinical myotonia could not be elicited in any patient. Conclusions: Myotonic discharges appear to be part of the electrodiagnostic characteristics of myofibrillar myopathy. Along with other appropriate clinical and histological findings, the presence of myotonic discharges supports the diagnosis of myofibrillar myopathy. Muscle Nerve 47: 845–848, 2013     

The influence of skeletal muscle reinnervation on experimentally induced myotonia

Earlier studies have shown that prior denervation of muscle prevents myotonia induced by 2,4-dichlorophenoxy acetic acid (2,4-D) both in vivo and in vitro. This work studied the effect of reinnervation on 2,4-D myotonia. Twenty Sprague-Dawley rats were injected with 2,4-D at specific intervals following unilateral sciatic nerve crushing; the gastrocnemius muscle on both sides was studied electromyographically to assess myotonia and to document denervation and reinnervation. All the rats gradually became amyotonic following denervation; myotonia reappeared during reinnervation. Myotonic discharges were no longer detectable 1 week after nerve crushing, but returned completely within 3 weeks. Blocking axoplasmic transport with colchicine had essentially the same effect on myotonia. A reciprocal temporal relationship was noted between the occurrence of fibrillations and myotonic discharges. These findings substantiate the view that innervation is essential to maintain the muscle membrane in a state that will support myotonic discharges.     

A case of Beh?et's disease associated with myopathy during cyclosporin treatment]

A 46-year-old male was admitted to the Department of Neurology complaining of gait disturbance. He was given a diagnosis of Beh?et's disease and placed on colchicine (0.5-1.0 mg/day) for 7 months without improvement. Subsequently cyclosporin (290 mg/day) was added this regimen. However, 7 months after initiation of combined colchicine/cyclosporin therapy serum creatine kinase (CK) rose to 1,255 U/l. On admission, neurological examination revealed generalized muscle atrophy with predominant proximal muscle weakness and decreased deep tendon reflexes. No myalgia was noted. Laboratory tests demonstrated anemia, liver dysfunction, chronic renal failure and an elevated serum CK level. The plasma cyclosporin concentration was 220 ng/dl, which is within therapeutic limits. Motor unit potentials in electromyography of bilateral quadriceps muscles were generally of short duration and reduced amplitude. A biopsy of quadriceps muscle showed variability in the size of type 2 fibers and scattered small vacuoles. Some of the vacuoles resembled rimmed vacuoles. These vacuoles were stained positively for acid phosphatase. Electronmicroscopy revealed that these vacuoles contained dense bodies, myeloid bodies, and glycogen particles. Collectively suggesting that these structures are autophagic vacuoles. Cyclosporin was reduced to 200 mg/day with unchanged colchicine dose and bromocriptine, which potentiates cyclosporin effects, was started. Gradual recovery from muscle weakness ensued. These findings suggest that cyclosporin contributed to the pathogenesis of this myopathy. On increase in use of cyclosporin, one should consider the possibility of myopathy as one of its side effects especially in combination therapy with myotoxic drugs such as colchicine.     

Lysosomal glycogen storage disease with normal acid maltase (Danon) without apparent cardiomyopathy and mental retardation]

A 29-year-old male who had a past history of mild ECG abnormality of arrhythmia at the age of 14 years, was referred to our hospital because of elevated serum creatine kinase (CK) level. He had never been aware of muscular weakness nor cardiac symptoms. Neurological examination revealed normal muscle strength of all extremities except marked back muscle weakness. He had normal intelligence. On laboratory examination, serum AST, ALT, LDH, aldolase, CK and myoglobin levels were elevated. Both lactate and pyruvate levels were normally responded after an ischemic exercises test. Acid maltase activity was normal in white blood cells. A muscle biopsy obtained from rectus femoris muscle revealed vacuolar myopathy with mildly increased PAS positive material. On electron microscopy, there were autophagic vacuoles scavenging glycogen particles and cytoplasmic debris, and sarcolemmal indentation, compatible with the findings of lysosomal glycogen storage disease with normal acid maltase. This patient had unusual clinical features of absent mental retardation and no apparent cardiomyopathy. Accordingly, mental retardation is probably not necessary to see later onset of cardiac muscle involvement.     

A patient with proximal myotonic myopathy and parkinsonism

INTRODUCTION: There are two case reports of patients who had proximal myotonic myopathy (PROMM)/myotonic dystrophy (DM) Type 1 and parkinsonism. The combination of myotonic myopathy and parkinsonism is so rare that it may appear to be just a coincidence. However, previous neuropathological examinations of patients who had myotonic dystrophy showed that there were intracytoplasmic inclusion bodies in the nigra and striatum, which raises the possibility that myotonic myopathy may be associated with parkinsonism. In this report we describe a patient with PROMM and a clinically definite parkinsonism to highlight this possibility. CASE REPORT: A 65-year-old man developed proximal muscle weakness, myotonia and atrophy around the age of 55 and was diagnosed as having PROMM at the age of 62. Needle electromyography and muscle biopsy supported the diagnosis. A gene study of the DM Type 1 showed a normal CTG repeat length. At age 63, he developed rest tremor, bradykinesia, hypomimia, stooped posture, and gait disturbance. The postural instability worsened rapidly. The tremor and rigidity were much worse in his right side, where myotonia was more severe. Levodopa therapy was only partially effective. CONCLUSION: This is a case report of a patient with PROMM that shows an association with a rapidly progressive form of parkinsonism. We suggest that this may be a novel form of a neurodegenerative disorder, which we name 'Parkinsonism-Myotonic Myopathy-Complex'.     

A case of myotonic dystrophy showing proximal dominant muscle involvement but not myotonia]

A 45-year-old female had progressive difficulty in climbing stairs and standing from a chair for 10 years. She had binocular cataracts which were operated at the age of 42 years. On examination, she had marked muscle wasting in the proximal limbs, scapular and sternomastoid muscles. She presented as marked muscle weakness in the proximal portion of the lower extremities and moderate in the upper extremities and the legs. Deep tendon reflexes were absent in all limbs. There was no grip myotonia, or percussion myotonia of the thenar muscle and tongue. Myotonia was not elucidated even after the hands were exposed to cold water. Moreover, none of the examined muscles revealed insertion myotonic discharge on electromyography. Serum CK level was normal and IgG value decreased to 546 mg/dl. Muscle biopsy of the left biceps muscle showed the variation in fiber size, increased central nuclei and many fiber with pyknotic nuclear clumps on HE staining. Sarcoplasmic mass and ring fibers were also found on HE staining. There were a few percents of ragged-red fibers on Gomori-trichrome staining, and type 1 fiber atrophy was found on pH 4.5 ATP-ase staining. The expansion of lymphocyte CTG trinucleotide repeats in the myotonin protein kinase gene was about 733, so that she was diagnosed as having myotonic dystrophy (MD). MRI of skeletal muscles exhibited marked atrophy especially in the femoral region and the biceps muscle. This patient had the proximal dominant muscle weakness, and absent myotonia even on electromyographic examination, which are unusual clinical features of adult onset MD.     

Evaluation of enzymes in serum and cerebrospinal fluid in cases of stroke

Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) were estimated in serum and cerebrospinal fluid of 25 patients of stroke, and were correlated with severity of disease. 21 (84%) patients had ischemic stroke and four (16%) had hemorrhagic stroke. Serum and CSF AST levels were significantly elevated in the study group. The rise in CSF AST was more in the hemorrhagic subtype than in the ischemic subtype. Serum ALT and CSF LDH levels were also significantly elevated in patients with ischemic stroke. None of the enzyme levels were related to the severity of disease as assessed by the Glasgow coma scale.     

Unclassified familial myopathy resembling Steinert disease, without myotonia

A familial myopathy with predominantly proximal muscle atrophy is described. Although several clinical features such as sternomastoid and brachioradialis muscle involvement suggested Steinert disease, myotonia was not demonstrated by clinical examination or EMG. Histological data were consistent with myotonic dystrophy.     

Experimental simvastatin-induced myopathy in rabbits.

We induced experimental myopathy in rabbits by giving simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. After oral administration of simvastatin (50 mg/kg/day) for 2 weeks, serum CK was elevated in 5 of 7 rabbits; degenerating or necrotic fibers were seen in 3 rabbits. Using electromyography, myotonic discharges were found in the 2 rabbits examined. The combination of myotonic discharges, necrosis and raised serum CK levels suggests that the myopathy was induced by lesions of the muscle surface membrane.     

Asymptomatic hyper-CK-emia: an electrophysiologic and histopathologic study

Since the popularization of routine creatine kinase (CK) measurement, an increasing number of patients with unexplained CK elevation ("asymptomatic hyper-CK-emia") are being identified. We studied 19 patients with persistent CK elevation of unknown etiology with electromyography (EMG) and muscle biopsy. Needle EMG was abnormal in 14 patients. Muscle biopsy was positive in all individuals with abnormal EMG and in one patient with normal EMG. Diagnoses included polymyositis in five patients, morphologically nonspecific myopathy in three, mitochondrial myopathy in two, and sarcoid myopathy, central core disease, multicore disease, inclusion body myopathy, and McArdle's disease in one case, respectively. Five patients with abnormal biopsies developed weakness within 1 year of presentation. We conclude that persistent asymptomatic CK elevation represents mild or early myopathy in a majority of cases.     

Differential diagnosis of myotonic disorders

The presence of myotonia and paramyotonia on clinical examination and of myotonic discharges during electrodiagnostic (EDX) studies are important for the diagnosis of certain neuromuscular conditions. The increased muscle activity of myotonia produces muscle stiffness that improves with repeated activity. Paramyotonia produces a similar symptom, but the stiffness paradoxically increases with activity. Myotonic discharges are easily recognized on EDX testing because of the waxing and waning discharges. Myotonic dystrophy and myotonia congenita share both clinical and electrodiagnostic myotonia. Paramyotonia congenita and hyperkalemic periodic paralysis are associated with clinical paramyotonia and electrical myotonia. Acid maltase deficiency often produces myotonic potentials without clinical evidence of myotonia or paramyotonia. The differential diagnosis of these myotonic disorders is discussed.