0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

The Neurophysiological Features of Myoclonus-Dystonia and Differentiation From Other Dystonias

Traian Popa, MD, PhD1,2; Paolo Milani, MD2,3; Aliénor Richard, MSc2; Cécile Hubsch, MD2,4; Vanessa Brochard, PhD5; Christine Tranchant, MD, PhD6; Anna Sadnicka, MRCP7; John Rothwell, PhD7; Marie Vidailhet, MD2,4; Sabine Meunier, MD, PhD2; Emmanuel Roze, MD, PhD2,4
[+] Author Affiliations
1Centre de Neuroimagerie de Recherche, Institut du Cerveau et de la Moelle Épinière, Paris, France
2Centre de Recherche de l’Institut du Cerveau et de la Moelle Épinière, Institut National de la Santé et de la Recherche Médicale U1127, Centre de Recherche de Neurosciences–Unité Mixte de Recherche 7225, Université Pierre et Marie Curie–Paris 6 UMR_S975, Paris, France
3Service de Physiologie Clinique, Hôpital Lariboisière, Assistance Publique– Hôpitaux de Paris (AP-HP), Paris, France
4Département de Neurologie, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France
5Centre d’Investigation Clinique Pitié Neurosciences 1422, Hôpital Pitié-Salpêtrière, Paris, France
6Centre de Compétence des Maladies Neurologiques Génétiques Rares, Service de Neurologie, Hôpital de Hautepierre, Strasbourg, France
7Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, England
JAMA Neurol. 2014;71(5):612-619. doi:10.1001/jamaneurol.2014.99.
Text Size: A A A
Published online

Importance  Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown.

Objective  To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias.

Design, Setting, and Participants  We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale.

Exposure  Myoclonus-dystonia with a proven SGCE mutation.

Main Outcomes and Measures  We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores.

Results  We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other forms of primary dystonia. Myoclonus-dystonia patients also shared some common pathophysiological features of dystonia, including enhanced responsiveness of the motor cortex to plasticity induction and abnormal response to cerebellar conditioning as tested by EBCC.

Conclusions and Relevance  Specific underlying dysfunctions are associated with the very particular clinical phenotype of M-D and make it a unique entity that stands apart from other primary dystonias.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

First Page Preview

View Large
First page PDF preview

Figures

Place holder to copy figure label and caption
Figure 1.
Intracortical Excitability of the Primary Motor Cortex

A, Correlation between the baseline cortical excitability of the primary motor cortex and the self-rated global disability score. Dotted lines represent the 95% CI for the linear regression (solid line); dots, individual patients with myoclonus-dystonia (M-D). B, Mean amplitude of the conditioned motor evoked potential (MEP) after short-interval intracortical inhibition represented for each intensity of the conditioning stimulus. C, Mean amplitude of the conditioned MEP after short-interval intracortical facilitation represented for each interstimulus interval between the conditioning and the test stimuli. AMT indicates active motor threshold.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Associative Plasticity of the Primary Motor Cortex

The variation in motor evoked potential (MEP) amplitude after rapid paired associative stimulation (RPAS) is represented for each time point after intervention as a percentage of the mean baseline MEP amplitude. A, The MEP amplitude normalized to baseline for the abductor policis brevis muscle. B, The MEP amplitude normalized to baseline for the adductor digiti minimi muscle. C, Correlation between the mean MEP amplitude after RPAS and the self-rated global disability score. Dotted lines represent the 95% CI for the linear regression (solid line); dots, individual patients with myoclonus-dystonia (M-D).aP = .05, post hoc analysis.bP = .01, post hoc analysis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Eye Blink Classic Conditioning

A, In the acquisition phase, the number of conditioned responses (CRs) is represented as the percentage of the total number of responses within each block. B, In the extinction phase, the percentages of CRs are compared between block 6 of the acquisition phase and the extinction block.aP = .02.bP < .01.

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
brightcove.createExperiences();