Brief Communication
Early Surgical Treatment in a Case of Myoclonus Dystonia Syndrome
Journal of Child Neurology 1-2 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813513071 jcn.sagepub.com
Andrea A. Ku¨hn, MD1, Patricia Krause, MD1, Katharina Lauritsch1, Christian Zentner2, Christof Bru¨cke, PhD1, and Gerd-Helge Schneider, MD3
Abstract Myoclonus dystonia syndrome is often misdiagnosed in young children and appropriate treatment is delayed, which has a negative impact on motor development, participation, and emotional well-being. In severely affected patients, deep brain stimulation of the globus pallidus internus has been used successfully to treat both dystonia and myoclonus. Here, the authors present a case of early successful treatment of myoclonus dystonia syndrome by pallidal deep brain stimulation in a patient at the age of 17 years leading to 83% reduction in dystonia score and 89% reduction in myoclonus. The patient gained significant improvement in motor function as well as increased participation and reduced stigma. Keywords myoclonus, dystonia, deep brain stimulation, quality of life, pallidal Received September 23, 2013. Accepted for publication October 22, 2013.
Myoclonus dystonia syndrome is a rare disabling movement disorder with disease onset in early childhood.1 The definite diagnosis is often delayed in these children, resulting in unnecessary investigations or inappropriate therapy.1 In severely affected patients, deep brain stimulation of the globus pallidus internus has been used successfully to treat both dystonia and myoclonus.2 A recent meta-analysis suggested that a shorter disease duration and younger age at surgery may be related to improved outcome,3 similar to recent findings in idiopathic dystonia.4,5 Thus, early surgery is recommended in patients with myoclonus dystonia syndrome. However, data on pediatric patients who underwent deep brain stimulation for myoclonus dystonia syndrome are very limited.1,6 The mean age at surgery of the patients described so far was 39.5 years.3 Here, the authors describe another case of early successful treatment of myoclonus dystonia syndrome by pallidal deep brain stimulation in a patient at the age of 17 years that underscores the need for increased awareness of this condition among pediatric neurologists.
with standing and walking; and moderate jerks in both arms. He had developed tonic spasms of his right upper limb and myoclonic jerks at the age of 3 years that worsened over time. At the age of 7 years, dystonic posturing and jerks obviated writing. He relearned writing with his left hand but needed to change to a school for physically disabled children at the age of 13 years due to his motor impairment. At this time, the jerks of the neck and trunk became more significant. He became stigmatized and avoided joining friends in public. All neurological examinations and cranial magnetic resonance imaging (MRI) were unremarkable. He had no signs of psychiatric comorbidity. He was prescribed trihexyphenidyl, clonazepam, valproate, propranolol, tiapride, levodopa, and levetiracetam without any effect. Later, Psychological assessment suggested a learning disability and functional origin of jerks. In 2010 the diagnoses of myoclonus dystonia syndrome was made and was confirmed by genetic testing, and he received botulinum toxin treatment with moderate effect on dystonic symptoms for about 1 year.
Case Summary The authors report on an adolescent of European descent with genetically proven mutation in the gene that encodes epsilonsarcoglycan (SGCE; DYT-11).1 He was referred to the authors’ movement disorder center for further treatment options at the age of 16 years. He presented with moderate multifocal dystonia involving the neck, trunk, and both arms; severe myoclonic jerks of the upper trunk and neck with retropulsion interfering
1
Department of Neurology, Charite´-University Medicine, Berlin, Germany Department of Neurology, Martha Maria Hospital, Halle/Saale, Germany 3 Department of Neurosurgery, Charite´-University Medicine, Berlin, Germany 2
Corresponding Author: Andrea A. Ku¨hn, MD, Department of Neurology, Campus Virchow, Charite´University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Email: [email protected]
Downloaded from jcn.sagepub.com at TEXAS SOUTHERN UNIVERSITY on December 11, 2014
2
Journal of Child Neurology
Table 1. Progressive Improvement in Motor Symptoms During Continuous Pallidal Deep Brain Stimulation. Burke-Fahn-Marsden Dystonia Rating Scale Motor Score
Disability Score
Unified Myoclonus Rating Scalea
Global Clinical Impression
26 11 10.5 4.5
10 — 2 2
101 28 16 11
5 — — 1
Before surgery 3-mo follow-up 6-mo follow-up 9-mo follow-up a
Sum of scores for myoclonus at rest, with action, functional tests, Global Disability Score.
Results Pallidal deep brain stimulation was performed in early 2012 leading to a reduction of dystonia and severity of myoclonic jerks within days to weeks. Parameters used for bilateral deep brain stimulation were the following: monopolar (1–; case þ); 3.4 V; 90 ms; 130 Hz. Further improvement occurred up to the last follow-up (9 months after surgery) leading to an 83% reduction in dystonia score and an 89% reduction in myoclonus (Table 1). The patient reports easy, fast, and legible handwriting with his right hand and only residual mild myoclonic jerks of the trunk that occur during emotional stress. He further reports a significant gain in quality of life and self-confidence as he is now entirely independent. He started to join friends in public and pursue his hobbies, which he had given up before deep brain stimulation. He also reports improved concentration while at vocational training and even feels confident to switch training courses according to his personal choice, no longer restricted due to motor disability.
clinical scores, videos, and deep brain stimulation programming. CZ made the diagnosis and initiated deep brain stimulation therapy. GHS performed deep brain stimulation surgery.
Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AAK has received honoraria from Medtronic, St. Jude Medical, Boston Scientific, Novartis, and Bayer AG and support for travel to conferences by Ipsen Pharma. GHS has received honoraria from Medtronic and St. Jude Medical. PK and CB have received honoraria or support for travel to conferences by UCB and Medtronic.
Funding The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The project was supported by the DFG grant KFO 247.
Ethical Approval
Discussion Here, the authors report a case of an adolescent patient with myoclonus dystonia syndrome who experienced tremendous improvement after pallidal deep brain stimulation not only in motor symptoms but especially in quality of life and psychological well-being. Myoclonus dystonia syndrome usually affects young children, and the motor disability can also influence their emotional development and can even limit their access to secondary and higher education. The significant functional improvement after deep brain stimulation in this patient underlines the need for early diagnosis and treatment including deep brain stimulation in children with myoclonus dystonia syndrome. Acknowledgments The study was performed at the Charite´-University Medicine, Berlin, Germany.
Author Contributions AAK conceptualized the study, supervised the clinical work at all stages, and wrote the manuscript. PK, KL, and CB performed the
The study was approved by the local ethics committee, Charite´-University Medicine, Berlin (EA2/149/12).
References 1. Ghosh D, Indulkar S. Primary myoclonus-dystonia: a diagnosis often missed in children. J Child Neurol. 2013;28(11):1418-1422. 2. Gruber D, Ku¨hn AA, Schoenecker T, et al. Pallidal and thalamic deep brain stimulation in myoclonus-dystonia. Mov Disord. 2010;25(11):1733-1743. 3. Rughani AI, Lozano AM. Surgical treatment of myoclonus dystonia syndrome. Mov Disord. 2013;28(3):282-287. 4. Isaias IU, Volkmann J, Kupsch A, et al. Factors predicting protracted improvement after pallidal DBS for primary dystonia: the role of age and disease duration. J Neurol. 2011;258(8):1469-1476. 5. Markun LC, Starr PA, Air EL, et al. Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia. Neurosurgery. 2012;71(2): 325-330. 6. Cif L, Valente EM, Hemm S, et al. Deep brain stimulation in myoclonus-dystonia syndrome. Mov Disord. 2004;19(6):724-727.
Downloaded from jcn.sagepub.com at TEXAS SOUTHERN UNIVERSITY on December 11, 2014
Early Surgical Treatment in a Case of Myoclonus Dystonia Syndrome
Journal of Child Neurology 1-2 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813513071 jcn.sagepub.com
Andrea A. Ku¨hn, MD1, Patricia Krause, MD1, Katharina Lauritsch1, Christian Zentner2, Christof Bru¨cke, PhD1, and Gerd-Helge Schneider, MD3
Abstract Myoclonus dystonia syndrome is often misdiagnosed in young children and appropriate treatment is delayed, which has a negative impact on motor development, participation, and emotional well-being. In severely affected patients, deep brain stimulation of the globus pallidus internus has been used successfully to treat both dystonia and myoclonus. Here, the authors present a case of early successful treatment of myoclonus dystonia syndrome by pallidal deep brain stimulation in a patient at the age of 17 years leading to 83% reduction in dystonia score and 89% reduction in myoclonus. The patient gained significant improvement in motor function as well as increased participation and reduced stigma. Keywords myoclonus, dystonia, deep brain stimulation, quality of life, pallidal Received September 23, 2013. Accepted for publication October 22, 2013.
Myoclonus dystonia syndrome is a rare disabling movement disorder with disease onset in early childhood.1 The definite diagnosis is often delayed in these children, resulting in unnecessary investigations or inappropriate therapy.1 In severely affected patients, deep brain stimulation of the globus pallidus internus has been used successfully to treat both dystonia and myoclonus.2 A recent meta-analysis suggested that a shorter disease duration and younger age at surgery may be related to improved outcome,3 similar to recent findings in idiopathic dystonia.4,5 Thus, early surgery is recommended in patients with myoclonus dystonia syndrome. However, data on pediatric patients who underwent deep brain stimulation for myoclonus dystonia syndrome are very limited.1,6 The mean age at surgery of the patients described so far was 39.5 years.3 Here, the authors describe another case of early successful treatment of myoclonus dystonia syndrome by pallidal deep brain stimulation in a patient at the age of 17 years that underscores the need for increased awareness of this condition among pediatric neurologists.
with standing and walking; and moderate jerks in both arms. He had developed tonic spasms of his right upper limb and myoclonic jerks at the age of 3 years that worsened over time. At the age of 7 years, dystonic posturing and jerks obviated writing. He relearned writing with his left hand but needed to change to a school for physically disabled children at the age of 13 years due to his motor impairment. At this time, the jerks of the neck and trunk became more significant. He became stigmatized and avoided joining friends in public. All neurological examinations and cranial magnetic resonance imaging (MRI) were unremarkable. He had no signs of psychiatric comorbidity. He was prescribed trihexyphenidyl, clonazepam, valproate, propranolol, tiapride, levodopa, and levetiracetam without any effect. Later, Psychological assessment suggested a learning disability and functional origin of jerks. In 2010 the diagnoses of myoclonus dystonia syndrome was made and was confirmed by genetic testing, and he received botulinum toxin treatment with moderate effect on dystonic symptoms for about 1 year.
Case Summary The authors report on an adolescent of European descent with genetically proven mutation in the gene that encodes epsilonsarcoglycan (SGCE; DYT-11).1 He was referred to the authors’ movement disorder center for further treatment options at the age of 16 years. He presented with moderate multifocal dystonia involving the neck, trunk, and both arms; severe myoclonic jerks of the upper trunk and neck with retropulsion interfering
1
Department of Neurology, Charite´-University Medicine, Berlin, Germany Department of Neurology, Martha Maria Hospital, Halle/Saale, Germany 3 Department of Neurosurgery, Charite´-University Medicine, Berlin, Germany 2
Corresponding Author: Andrea A. Ku¨hn, MD, Department of Neurology, Campus Virchow, Charite´University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Email: [email protected]
Downloaded from jcn.sagepub.com at TEXAS SOUTHERN UNIVERSITY on December 11, 2014
2
Journal of Child Neurology
Table 1. Progressive Improvement in Motor Symptoms During Continuous Pallidal Deep Brain Stimulation. Burke-Fahn-Marsden Dystonia Rating Scale Motor Score
Disability Score
Unified Myoclonus Rating Scalea
Global Clinical Impression
26 11 10.5 4.5
10 — 2 2
101 28 16 11
5 — — 1
Before surgery 3-mo follow-up 6-mo follow-up 9-mo follow-up a
Sum of scores for myoclonus at rest, with action, functional tests, Global Disability Score.
Results Pallidal deep brain stimulation was performed in early 2012 leading to a reduction of dystonia and severity of myoclonic jerks within days to weeks. Parameters used for bilateral deep brain stimulation were the following: monopolar (1–; case þ); 3.4 V; 90 ms; 130 Hz. Further improvement occurred up to the last follow-up (9 months after surgery) leading to an 83% reduction in dystonia score and an 89% reduction in myoclonus (Table 1). The patient reports easy, fast, and legible handwriting with his right hand and only residual mild myoclonic jerks of the trunk that occur during emotional stress. He further reports a significant gain in quality of life and self-confidence as he is now entirely independent. He started to join friends in public and pursue his hobbies, which he had given up before deep brain stimulation. He also reports improved concentration while at vocational training and even feels confident to switch training courses according to his personal choice, no longer restricted due to motor disability.
clinical scores, videos, and deep brain stimulation programming. CZ made the diagnosis and initiated deep brain stimulation therapy. GHS performed deep brain stimulation surgery.
Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AAK has received honoraria from Medtronic, St. Jude Medical, Boston Scientific, Novartis, and Bayer AG and support for travel to conferences by Ipsen Pharma. GHS has received honoraria from Medtronic and St. Jude Medical. PK and CB have received honoraria or support for travel to conferences by UCB and Medtronic.
Funding The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The project was supported by the DFG grant KFO 247.
Ethical Approval
Discussion Here, the authors report a case of an adolescent patient with myoclonus dystonia syndrome who experienced tremendous improvement after pallidal deep brain stimulation not only in motor symptoms but especially in quality of life and psychological well-being. Myoclonus dystonia syndrome usually affects young children, and the motor disability can also influence their emotional development and can even limit their access to secondary and higher education. The significant functional improvement after deep brain stimulation in this patient underlines the need for early diagnosis and treatment including deep brain stimulation in children with myoclonus dystonia syndrome. Acknowledgments The study was performed at the Charite´-University Medicine, Berlin, Germany.
Author Contributions AAK conceptualized the study, supervised the clinical work at all stages, and wrote the manuscript. PK, KL, and CB performed the
The study was approved by the local ethics committee, Charite´-University Medicine, Berlin (EA2/149/12).
References 1. Ghosh D, Indulkar S. Primary myoclonus-dystonia: a diagnosis often missed in children. J Child Neurol. 2013;28(11):1418-1422. 2. Gruber D, Ku¨hn AA, Schoenecker T, et al. Pallidal and thalamic deep brain stimulation in myoclonus-dystonia. Mov Disord. 2010;25(11):1733-1743. 3. Rughani AI, Lozano AM. Surgical treatment of myoclonus dystonia syndrome. Mov Disord. 2013;28(3):282-287. 4. Isaias IU, Volkmann J, Kupsch A, et al. Factors predicting protracted improvement after pallidal DBS for primary dystonia: the role of age and disease duration. J Neurol. 2011;258(8):1469-1476. 5. Markun LC, Starr PA, Air EL, et al. Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia. Neurosurgery. 2012;71(2): 325-330. 6. Cif L, Valente EM, Hemm S, et al. Deep brain stimulation in myoclonus-dystonia syndrome. Mov Disord. 2004;19(6):724-727.
Downloaded from jcn.sagepub.com at TEXAS SOUTHERN UNIVERSITY on December 11, 2014
