Hyperkinetic Movements in Patients With Disease of Motor Neurons and Their Response to Treatment With Nusinersen

NCT04825119 | Unknown

• 1 other identifier: 0120-293/2019/8/1
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Hyperkinetic movement disorders in patients with diseases of motor neurons will be studied. Patients with spinal muscular atrophy (SMA) and motor neuron disease patients will be studied. Involuntary movements will be video recorded and accelerometry with electromyography (EMG) will be recorded in a subset of patients. Hyperkinetic involuntary movements studied will be tremor and minipolymyoclonus. Tremor is defined as involuntary, rhythmic, oscillatory movements of a body part, and minipolymyoclonus are intermittent and irregular movements, with amplitudes sufficient to produce visible movements of the joints. Hyperkinetic movement disorders may be of central or peripheral origin and using accelerometry with EMG may help distinguish the two mechanisms. In patients with SMA the investigators will explore the effect of Nusinersen treatment on phenomenology and amplitude of tremor and minipolymyoclonus. Aims: To explore the prevalence and phenomenology of hyperkinetic movement disorders in patients with MND and SMA and to study the underlying pathological mechanisms with the use of accelerometry and EMG. To explore the effect of Nusinersen treatment on phenomenology and amplitude of involuntary movements. Hypotheses: Based on clinical observations the investigators believe it will proven that hyperkinetic movement disorders are common in patients with disease of motor neurons. The investigators hypothesize that hyperkinetic movement disorders in MND and SMA patients are of peripheral origin, being caused by uneven graduation of contraction in the wasted muscles with large motor units being active with no sufficient previous recruitment of small units to smooth contraction of large motor units. If tremor and minipolymyoclonus in SMA are due to the activation of enlarged motor units which are caused by reinnervation of muscle fibers, the treatment with Nusinersen will increase the amplitude of tremor and minipolymyoclonus. Methods: Presence, quality, and regularity of hyperkinetic movement disorders will be defined using clinical examination, accelerometry and EMG. Hyperkinetic movements will be classified as minipolymyoclonus or tremor. In patients with SMA, the measurements will be repeated 6-12 months after initiation of treatment with Nusinersen.

Conditions

Tremor; Involuntary Movements; SMA; MND (Motor Neurone DIsease)

Keywords

Tremor; Minipolymyoclonus; Nusinersen; SMA; MND; ALS

Outcome Measures

Primary Outcomes (9)

• Prevalence of involuntary movements in patients with SMA before starting treatment with nusinersen

  All patients will be clinically examined and video-recorded before starting treatment with nusinersen. The presence of involuntary movements will be evaluated as present or not present while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task.

  Baseline (before starting nusinersen treatment)

• The effect of nusinersen on the prevalence of involuntary movements in patients with SMA

  All patients will be clinically examined and video-recorded 6-12 months after starting treatment with nusinersen. The presence of involuntary movements will be evaluated as present or not present while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task.

  6-12 months after starting nusinersen

• Characteristics of involuntary movements in patients with SMA before starting treatment with nusinersen

  The quality and regularity of involuntary movements will be evaluated in the standard positons before starting treatment with nusinersen. Based on regularity and distribution, movements observed will be classified as minipolymyoclonus or tremor.

  Baseline (before starting nusinersen treatment)

• The effect of nusinersen on the characteristics of involuntary movements in patients with SMA

  The quality and regularity of involuntary movements will be evaluated in the standard positons 6-12 moths after starting treatment with nusinersen. Based on regularity and distribution, movements observed will be classified as minipolymyoclonus or tremor.

  6-12 months after starting nusinersen

• Amplitude of involuntary movements in patients with SMA before starting treatment with nusinersen

  The quality and regularity of involuntary movements will be evaluated in the standard positons before starting treatment with nusinersen. Accelerometry with EMG will be recorded in all patients with hyperkinetic movements. Amplitude of involuntary movements will be graded on a scale from 0 to 3.

  Baseline (before starting nusinersen treatment)

• The effect of nusinersen on the amplitude of involuntary movements in patients with SMA

  The quality and regularity of involuntary movements will be evaluated in the standard positons 6-12 moths after starting treatment with nusinersen. Accelerometry with EMG will be recorded in all patients with hyperkinetic movements. Amplitude of involuntary movements will be graded on a scale from 0 to 3.

  6-12 months after starting nusinersen

• Prevalence of involuntary movements in patients with MND

  Patients will be clinically examined by movement disorders experts and video-recorded. The presence of involuntary movements will be evaluated while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task.

  Day 1

• Characteristics of involuntary movements in patients with MND

  The quality and regularity of involuntary movements will be evaluated while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task. Based on regularity and distribution, hyperkinetic movements will be classified as minipolymyoclonus or tremor.

  Day 1

• Amplitude of involuntary movements in patients with MND

  In 10 patients accelerometry with electromyography will be recorded at standard positions.

  Day 1

Study Arms (2)

MND patients

Patients with ''clinically definite ALS'' or ''clinically probable ALS'' or ''clinically probable ALS - laboratory supported'' according to the revised El Escorial diagnostic criteria or with the diagnosis of PMA or PLS will be included.

SMA patients

SMA patients type I, II, III, and IV will be included.

Drug: Nusinersen

Interventions

Nusinersen DRUG

Patients with SMA who will be treated with nusinersen will be included.

Also known as: Spinraza

SMA patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Consecutive patients with ALS, PMA, or PLS followed in MND outpatient clinic will be included in the study. Consecutive SMA patients treated with Nusinersen and followed in MND outpatient clinic will be included.

You may qualify if:

• Genetically proven SMA patients treated with Nusinersen
• ''clinically definite ALS'' or ''clinically probable ALS'' or ''clinically probable ALS - laboratory supported'' according to the revised El Escorial diagnostic criteria or diagnosis of PMA or PLS

You may not qualify if:

• No.

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

Related Publications (4)

• Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.

  PMID: 11464847 BACKGROUND

• Pupillo E, Bianchi E, Messina P, Chiveri L, Lunetta C, Corbo M, Filosto M, Lorusso L, Marin B, Mandrioli J, Riva N, Sasanelli F, Tremolizzo L, Beghi E; Eurals Consortium. Extrapyramidal and cognitive signs in amyotrophic lateral sclerosis: A population based cross-sectional study. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(5-6):324-30. doi: 10.3109/21678421.2015.1040028. Epub 2015 May 12.

  PMID: 25967544 BACKGROUND

• Dawood AA, Moosa A. Hand and ECG tremor in spinal muscular atrophy. Arch Dis Child. 1983 May;58(5):376-8. doi: 10.1136/adc.58.5.376.

  PMID: 6859919 BACKGROUND

• Wurster CD, Ludolph AC. Nusinersen for spinal muscular atrophy. Ther Adv Neurol Disord. 2018 Mar 13;11:1756285618754459. doi: 10.1177/1756285618754459. eCollection 2018. No abstract available.

  PMID: 29568328 BACKGROUND

MeSH Terms

Conditions

Tremor; Dyskinesias; Amyotrophic Lateral Sclerosis

Interventions

nusinersen

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases; Spinal Cord Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Maja Kojović, PhD, MD

  University Medical Centre Ljubljana

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maja Kojović, PhD, MD

CONTACT

1 522 4323; maja.kojovic@kclj.si

Katarina Vogelnik, MD

CONTACT

1 522 4323; vogelnik.kata@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: April 1, 2021
• Study Start: October 1, 2017
• Primary Completion: July 30, 2021
• Study Completion: July 30, 2021
• Last Updated: April 1, 2021

Record last verified: 2021-03

Locations

SL (1)