Myotonia congenita - A successful response to carbamazepine
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《美国医学杂志》
1 Department of Pediatrics, Government Medical College, Mysore, India
2 Department of Studies in Zoology, University of Mysore, India
Abstract
Myotonia congenita is a rare disease of skeletal muscle characterized by painless myotonia, generalized muscular hypertrophy and a non-progressive course. We report a 10-year-old girl with myotonia, "Herculean appearance" and electromyographic confirmation of myotonic discharges. There was a dramatic response to carbamazepine. The aim of this report is to make the readers aware of this entity which can be easily controlled with medication and also prevented by genetic counseling.
Keywords: Myotonia; Myotonia congenita; Carbamazepine
Myotonia implies continued active contraction of a muscle after cessation of voluntary effort or stimulation.[1] Myotonia congenita is a non-progressive disorder characterized by myotonia and muscular hypertrophy.[2] World wide prevalence is between 0.2 to 7.3 per 1,00,000.[3] However, incidence among Asians is not well established.[3] Here, we report a case of myotonia congenita with a dramatic response to carbamazepine.
Case Report
A 10-year-old female child presented with difficulty in standing up from sitting posture, initiating walking after sitting for sometime, and difficulty in climbing stairs from past 2 years. Mother stated that this painless "stiffness of muscles" resolved as she walked about 15 - 20 steps, after which her gait was normal. There was no history of progression or fluctuation in severity or exacerbation in cold weather. This child was born to a second degree consanguineously wedded couple and had normal developmental milestones. There was no family history of similar complaints. There was no feeding difficulty or difficulty in opening the eyes after crying, in early childhood.
On examination, getting up from sitting posture was difficult and initiation of movement was slow, which improved as she continued to walk. She had marked hypertrophy of calf muscles, thighs, gluteal muscles and biceps giving a 'Herculean appearance". There was a prominent percussion myotonia of the tongue Figure1. There was no evidence of handgrip or eyelid myotonia. Muscle tone, power and tendon reflexes were normal with bilateral ankle contractures. There was no muscle wasting, abnormal facies, short stature or restriction in movements of multiple joints. Rest of clinical examination was normal. Clinical examination of both the parents and her sibling was normal.
Serum creatinine phosphokinase (CPK), serum potassium and electrocardiogram were normal, muscle biopsy was normal, except for few angulated fibers. Electromyography (EMG) revealed typical repetitive discharges of varying amplitude and frequency along with the classical "dive bomber's sound" indicating myotonia Figure2.
A diagnosis of myotonia congenita was done based on - non progressive painless myotonia, with "Herculean appearance", percussion myotonia of tongue and EMG confirmation of myotonic discharges.
She was started on carbamazepine at a dose of 15 mg/ Kg/day. After one month of treatment, there was total relief of all her symptoms. Now, with seven months of follow up, she is totally free of all her symptoms and continuing the drug without any undesirable effect. The clinical response was assessed as follows- the child was asked to sit for 10 minutes. Then, she was asked to climb five steps of the hospital. Before treatment, she was taking approximately 15 seconds to finish the task. After treatment she took 5 seconds to finish the task and she had no evidence of muscle stiffness. However post treatment EMG did not show any significant improvement Figure3.
Discussion
Myotonia congenita is a non-progressive disorder,[4] wherein the patient has painless, muscle stiffness with difficulty in starting to run or walk briskly. The movements resemble a "slow motion film". However, with continued activity the patient can "work off" the slowness.[1] Another characteristic feature is the generalized muscular hypertrophy leading to the classic description of a "Herculean appearance''.[5] This hypertrophy is principally seen in the lower limbs, probably as a result of work hypertrophy, since the quadriceps and other muscles are in a continued state of contraction.[6] Thomsen's disease (autosomal dominant) occurs in infancy. However, Becker's disease (autosomal recessive) occurs later, is more severe, manifests transient weakness during muscle exertion after rest and may have contractures.[2] As our patient is born to a second degree consanguineously wedded couple presenting at 8 years of age with marked generalized muscular hypertrophy and myotonia with bilateral ankle contractures, probably she has a Becker variant of myotonia congenita. However, without family history, distinguishing type is difficult.
Diagnosis is established by EMG. On muscle biopsy, histology is normal, but type 2B fibers are absent.[7],[8] However, histologically some were unable to discern any significant morphologic changes.[2] CPK level is often normal.[1] Genetic defect has been localized to CLCN1 gene on chromosome 7q35. Other myotonic disorders are- myotonic dystrophy, where patients have facial and distal muscle weakness and wasting.[7],[9] Paramyotonia congenita is characterized by increasing muscle stiffness with sustained activity (paradoxical myotonia) and cold induced exacerbation of myotonia.[1] Patients with chondrodystrophic myotonia (Schwartz Jampel syndrome) have typical dysmorphic facies, dwarfism, with progressive limitation of joint movements.[1], [9] myotonia fluctuans has fluctuating severity of myotonia from day to day.[2] Hyperkalemic periodic paralysis presents with hyperkalemia during an attack of myotonia.[2]
Treatment of myotonia is aimed at electrical stabilization of muscle membrane.[3] Mexilitine, acetazolamide and dantrolene have been tried. In a study comparing phenytoin to carbamazepine, there was a good response to both the drugs, but phenytoin showed decreased efficiency at higher doses.[10] In our patient, even though there is a good clinical response there was no significant EMG improvement with treatment. Although some studies, have found an EMG response along with clinical response in myotonia,[11],[12] some are of the opinion that electromyographic measurement utilizing either surface or intramuscular needle electrodes for evaluation of drug therapy has been disappointing.[13] Spontaneous muscle discharge in myotonia is frequent and obliterates a clear beginning and end point during muscle contraction.[13] Leyburn and Walton concluded that myotonia also could be equally effectively measured by merely timing relaxation with a stopwatch.[13],[14] Also, the EMG measurement of the relaxation time after maximal voluntary effort requires perfect co-operation from the patient and even so, results are sometimes difficult to read.[14],[15]
Myotonia congenita being a non progressive disorder carries a better prognosis and subjects may live up to adult life.[6]
Conclusion
Myotonia congenita should be suspected in a child presenting with painless myotonia, generalized hypertrophy of skeletal muscles with a non-progressive course. Electromyography is confirmatory. The disability can be fully controlled with drugs. All the members of the family of an affected child should undergo detailed screening for diagnosis and genetic counselling.
References
1. Brett EM, Lake BD. Neuromuscular disorders: I Primary muscle disease and anterior horn cell disorders. In: Pediatric Neurology, 3rd edn. eds Brett EM. Churchill Livingstone, New York 1997:pp70-77.
2. Victor M, Ropper AH: The Hereditary myotonias and periodic paralyses (The Channelopathies). In Adams and Victor's Principles of Neurology, 7th edition. eds Victor M, Ropper AH. McGraw Hill (Medical publishing division) USA, 2001; pp1553-1564.
3. Chew KTL, Wong YS, Teoh HL, Lim ECH. Myotonia congenita in a young active man-symptoms and physique tip the diagnosis. The Physician and Sports Medicine 2004: vol 32(7) : 26-29
4. Sarnat HB. Neuromuscular disorders. In Nelson Textbook of Pediatrics, 17th edition . Eds Behrman RE, Kligeman RM, Jenson HB. Saunders, Philadelphia 2004; pp2066.
5. Sheela S.R. Myotonia Congenita: Response to Carbamazepine. Indian Pediatrics 2000; 37 : 1122-1125.
6. Bhattacharya KB, Sengupta P, Basu S, Bhattacharya NP. Becker's variant of myotonia congenita in two siblings-A clinicogenetic study. Neurology India 2004:52(3)363-364
7. Menkes JH. Diseases of the motor unit. In Textbook of Child Neurology. 5th edition. eds Menkes JH. Williams and Winkins USA, 1995, pp836-841
8. Crews J, Kaiser KK, Brooke MH. Muscle Pathology of Myotonia congenita. J Neurol Sci. 1976. Aug; 28(4) : 449-457.
9. Moxley III RT, Tawil, Thornton CA. Channelopathies: Myotonic disorders and periodic paralysis. In Pediatric Neurology. Principles and Practice. 3rd edition. Eds Swaiman KF, Ashwal S. Mosbs. Missouri. 1999. pp1299-1310
10. Sechi GP, Traccis S, Durelli L, Monaco F, Mutan R. Carbamazepine versus diphenylhydantoin in the treatment of Myotonia. Eur Neurol 1983; 22 : 113-118.
11. Streib EW .Successful treatment with Tocainide of recessive generalized congenital myotonia. Annals of Neurol May 1986: 19 : 501-504.
12. Kwiecinski H, Ryniewicz B, Ostrzycki A. Treatment of myotonia with antiarrhythmic drugs. Acta Neurol Scand 1992: 86 : 371-375.
13. Munsat TL. Therapy of myotonia. Neurology 1967; 17: 359-366.
14. Leyburn P, Walton JN. The treatment of myotonia : A controlled clinical trial. Brain 1959; 81-91.
15. Durelli L, Multani R, Piredda S, Fassio F, Delsedime M. The quantification of myotonia - A problem in the evaluation of new anti myotonic drugs. J Neurological Sciences 1983; 59 : 167-173.(Savitha MR, Krishnamurthy)
2 Department of Studies in Zoology, University of Mysore, India
Abstract
Myotonia congenita is a rare disease of skeletal muscle characterized by painless myotonia, generalized muscular hypertrophy and a non-progressive course. We report a 10-year-old girl with myotonia, "Herculean appearance" and electromyographic confirmation of myotonic discharges. There was a dramatic response to carbamazepine. The aim of this report is to make the readers aware of this entity which can be easily controlled with medication and also prevented by genetic counseling.
Keywords: Myotonia; Myotonia congenita; Carbamazepine
Myotonia implies continued active contraction of a muscle after cessation of voluntary effort or stimulation.[1] Myotonia congenita is a non-progressive disorder characterized by myotonia and muscular hypertrophy.[2] World wide prevalence is between 0.2 to 7.3 per 1,00,000.[3] However, incidence among Asians is not well established.[3] Here, we report a case of myotonia congenita with a dramatic response to carbamazepine.
Case Report
A 10-year-old female child presented with difficulty in standing up from sitting posture, initiating walking after sitting for sometime, and difficulty in climbing stairs from past 2 years. Mother stated that this painless "stiffness of muscles" resolved as she walked about 15 - 20 steps, after which her gait was normal. There was no history of progression or fluctuation in severity or exacerbation in cold weather. This child was born to a second degree consanguineously wedded couple and had normal developmental milestones. There was no family history of similar complaints. There was no feeding difficulty or difficulty in opening the eyes after crying, in early childhood.
On examination, getting up from sitting posture was difficult and initiation of movement was slow, which improved as she continued to walk. She had marked hypertrophy of calf muscles, thighs, gluteal muscles and biceps giving a 'Herculean appearance". There was a prominent percussion myotonia of the tongue Figure1. There was no evidence of handgrip or eyelid myotonia. Muscle tone, power and tendon reflexes were normal with bilateral ankle contractures. There was no muscle wasting, abnormal facies, short stature or restriction in movements of multiple joints. Rest of clinical examination was normal. Clinical examination of both the parents and her sibling was normal.
Serum creatinine phosphokinase (CPK), serum potassium and electrocardiogram were normal, muscle biopsy was normal, except for few angulated fibers. Electromyography (EMG) revealed typical repetitive discharges of varying amplitude and frequency along with the classical "dive bomber's sound" indicating myotonia Figure2.
A diagnosis of myotonia congenita was done based on - non progressive painless myotonia, with "Herculean appearance", percussion myotonia of tongue and EMG confirmation of myotonic discharges.
She was started on carbamazepine at a dose of 15 mg/ Kg/day. After one month of treatment, there was total relief of all her symptoms. Now, with seven months of follow up, she is totally free of all her symptoms and continuing the drug without any undesirable effect. The clinical response was assessed as follows- the child was asked to sit for 10 minutes. Then, she was asked to climb five steps of the hospital. Before treatment, she was taking approximately 15 seconds to finish the task. After treatment she took 5 seconds to finish the task and she had no evidence of muscle stiffness. However post treatment EMG did not show any significant improvement Figure3.
Discussion
Myotonia congenita is a non-progressive disorder,[4] wherein the patient has painless, muscle stiffness with difficulty in starting to run or walk briskly. The movements resemble a "slow motion film". However, with continued activity the patient can "work off" the slowness.[1] Another characteristic feature is the generalized muscular hypertrophy leading to the classic description of a "Herculean appearance''.[5] This hypertrophy is principally seen in the lower limbs, probably as a result of work hypertrophy, since the quadriceps and other muscles are in a continued state of contraction.[6] Thomsen's disease (autosomal dominant) occurs in infancy. However, Becker's disease (autosomal recessive) occurs later, is more severe, manifests transient weakness during muscle exertion after rest and may have contractures.[2] As our patient is born to a second degree consanguineously wedded couple presenting at 8 years of age with marked generalized muscular hypertrophy and myotonia with bilateral ankle contractures, probably she has a Becker variant of myotonia congenita. However, without family history, distinguishing type is difficult.
Diagnosis is established by EMG. On muscle biopsy, histology is normal, but type 2B fibers are absent.[7],[8] However, histologically some were unable to discern any significant morphologic changes.[2] CPK level is often normal.[1] Genetic defect has been localized to CLCN1 gene on chromosome 7q35. Other myotonic disorders are- myotonic dystrophy, where patients have facial and distal muscle weakness and wasting.[7],[9] Paramyotonia congenita is characterized by increasing muscle stiffness with sustained activity (paradoxical myotonia) and cold induced exacerbation of myotonia.[1] Patients with chondrodystrophic myotonia (Schwartz Jampel syndrome) have typical dysmorphic facies, dwarfism, with progressive limitation of joint movements.[1], [9] myotonia fluctuans has fluctuating severity of myotonia from day to day.[2] Hyperkalemic periodic paralysis presents with hyperkalemia during an attack of myotonia.[2]
Treatment of myotonia is aimed at electrical stabilization of muscle membrane.[3] Mexilitine, acetazolamide and dantrolene have been tried. In a study comparing phenytoin to carbamazepine, there was a good response to both the drugs, but phenytoin showed decreased efficiency at higher doses.[10] In our patient, even though there is a good clinical response there was no significant EMG improvement with treatment. Although some studies, have found an EMG response along with clinical response in myotonia,[11],[12] some are of the opinion that electromyographic measurement utilizing either surface or intramuscular needle electrodes for evaluation of drug therapy has been disappointing.[13] Spontaneous muscle discharge in myotonia is frequent and obliterates a clear beginning and end point during muscle contraction.[13] Leyburn and Walton concluded that myotonia also could be equally effectively measured by merely timing relaxation with a stopwatch.[13],[14] Also, the EMG measurement of the relaxation time after maximal voluntary effort requires perfect co-operation from the patient and even so, results are sometimes difficult to read.[14],[15]
Myotonia congenita being a non progressive disorder carries a better prognosis and subjects may live up to adult life.[6]
Conclusion
Myotonia congenita should be suspected in a child presenting with painless myotonia, generalized hypertrophy of skeletal muscles with a non-progressive course. Electromyography is confirmatory. The disability can be fully controlled with drugs. All the members of the family of an affected child should undergo detailed screening for diagnosis and genetic counselling.
References
1. Brett EM, Lake BD. Neuromuscular disorders: I Primary muscle disease and anterior horn cell disorders. In: Pediatric Neurology, 3rd edn. eds Brett EM. Churchill Livingstone, New York 1997:pp70-77.
2. Victor M, Ropper AH: The Hereditary myotonias and periodic paralyses (The Channelopathies). In Adams and Victor's Principles of Neurology, 7th edition. eds Victor M, Ropper AH. McGraw Hill (Medical publishing division) USA, 2001; pp1553-1564.
3. Chew KTL, Wong YS, Teoh HL, Lim ECH. Myotonia congenita in a young active man-symptoms and physique tip the diagnosis. The Physician and Sports Medicine 2004: vol 32(7) : 26-29
4. Sarnat HB. Neuromuscular disorders. In Nelson Textbook of Pediatrics, 17th edition . Eds Behrman RE, Kligeman RM, Jenson HB. Saunders, Philadelphia 2004; pp2066.
5. Sheela S.R. Myotonia Congenita: Response to Carbamazepine. Indian Pediatrics 2000; 37 : 1122-1125.
6. Bhattacharya KB, Sengupta P, Basu S, Bhattacharya NP. Becker's variant of myotonia congenita in two siblings-A clinicogenetic study. Neurology India 2004:52(3)363-364
7. Menkes JH. Diseases of the motor unit. In Textbook of Child Neurology. 5th edition. eds Menkes JH. Williams and Winkins USA, 1995, pp836-841
8. Crews J, Kaiser KK, Brooke MH. Muscle Pathology of Myotonia congenita. J Neurol Sci. 1976. Aug; 28(4) : 449-457.
9. Moxley III RT, Tawil, Thornton CA. Channelopathies: Myotonic disorders and periodic paralysis. In Pediatric Neurology. Principles and Practice. 3rd edition. Eds Swaiman KF, Ashwal S. Mosbs. Missouri. 1999. pp1299-1310
10. Sechi GP, Traccis S, Durelli L, Monaco F, Mutan R. Carbamazepine versus diphenylhydantoin in the treatment of Myotonia. Eur Neurol 1983; 22 : 113-118.
11. Streib EW .Successful treatment with Tocainide of recessive generalized congenital myotonia. Annals of Neurol May 1986: 19 : 501-504.
12. Kwiecinski H, Ryniewicz B, Ostrzycki A. Treatment of myotonia with antiarrhythmic drugs. Acta Neurol Scand 1992: 86 : 371-375.
13. Munsat TL. Therapy of myotonia. Neurology 1967; 17: 359-366.
14. Leyburn P, Walton JN. The treatment of myotonia : A controlled clinical trial. Brain 1959; 81-91.
15. Durelli L, Multani R, Piredda S, Fassio F, Delsedime M. The quantification of myotonia - A problem in the evaluation of new anti myotonic drugs. J Neurological Sciences 1983; 59 : 167-173.(Savitha MR, Krishnamurthy)