Cortical Silent Period in Laryngeal Dystonia

Spasmodic Dysphonia Clinical Trial

— cSPDystonia  

Official title:

Cortical Silent Period in Laryngeal Dystonia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05580302
• Other study ID #: 003-08/22-03/0003
• Status: Recruiting
• Start date: October 10, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2023
• Source: University of Split, School of Medicine
• Contact: Maja Rogic Vidakovic, PhD
• Phone: +385098508210
• Email: maja.rogic[@]mefst.hr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of this observational study is to evaluate the cortical silent period (cSP) in cricothyroid muscle (CT) in laryngeal dystonia and control healthy subjects. The study will provide norms related to latency and amplitude of motor evoked potentials (MEPs) and duration of cSP in CT muscle in laryngeal dystonia and control healthy subjects. Findings may give a baseline in comparison to findings in laryngeal diseases and insight into maladaptive cortical control function during phonation in laryngeal diseases like laryngeal dystonia.

Description:

Transcranial magnetic stimulation (TMS)-induced cSP provide a noninvasive "in vivo" insight into how the human motor cortical inhibitory pathway function by generating electric current at a specific brain area through electromagnetic induction. The stimulator generates a changing electric current within the coil, which induces a magnetic field that then causes a second inductance of inverted electric charge within the brain itself. A single supra-threshold pulse of TMS over the human motor cortex elicits multiple descending volleys (I-waves) that generate a motor evoked potential (MEP) followed by a period of electromyographic silence in the tonically contracted target muscle (cSP). To date, methodologies for mapping the primary motor cortex (M1) with TMS and intraoperatively by electrical stimulation techniques have been previously developed to record corticobulbar motor evoked potentials (MEP) from laryngeal muscles. Except for estimating the amplitude and latency of MEPs recorded from laryngeal muscles, the cSP was investigated from thyroarytenoid muscle (TA) as a measure of M1 excitability in the TMS study. Previous work using TMS has indicated reduced inhibition to be characteristic of focal laryngeal dystonia. According to investigators' knowledge, cSP from other laryngeal muscles other than TA has not been investigated so far. The proposed study analyses neurophysiological CNS data, including motor evaluation of corticospinal and corticobulbar pathways by recording MEPs and cSP using TMS. Firstly, a questionnaire will be given to check for any previous neurological conditions, and subjects will provide signatures on participation in the study. The MRI of the subject's brain will be performed, and then 3D reconstructed for the use of TMS. The evaluation of the MRI will be done by radiologists at University Hospital Split. With the subject comfortably seated, the MRI is co-registered to the subject's head using the tracking system with TMS's unique forehead tracker. After TMS measurement of the MEP and cSP of CT muscle of individual subjects will be recorded. Data collected will be analyzed using MATLAB 2022a (MathWorks, USA). Measurements and data evaluation will be performed at the School of Medicine University in Split. An otorhinolaryngology specialist will be consulted for the correct placement of the recording electrodes (Hookwire IOM electrodes, disposable subdermal needle electrode, 0.4 x 13 mm, SGM d.o.o, G. Novaka 22 a, 21000 Split, Croatia) into the CT muscle.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• adults (18-65 years old), no implanted metals in the body (e.g. pacemaker, metal prosthesis in the skull and oral cavity).

Exclusion Criteria:

• pregnancy, other neurological disorders (except laryngeal dystonia in the laryngeal dystonia group), psychiatric disorders, epilepsy or history of previous epilepsy attack, using of brain-affecting pharmaceuticals, traumatic, tumor, infectious, metabolic brain lesions, heart conditions. The composition of the group is represented is both gender, various age gap, and different height.

Related Conditions & MeSH terms

• Dysphonia
• Dystonia
• Dystonic Disorders
• Hoarseness
• Laryngeal Dystonia
• Spasmodic Dysphonia

Intervention

Other:
• Transcranial Magnetic Stimulation (TMS)
An anatomical T1 magnetic resonance image (MRI) with high resolution will be acquired on a separate day before the TMS experiment. The image will be imported into the neuronavigation system (Nexstim, Helsinki, Finland) to guide the localization of the primary motor cortex (M1) for laryngeal muscle representation. Prior to M1 mapping for laryngeal muscle representation, mapping of the representation for hand muscle representation will be performed. Hand region excitability (abductor pollicis brevis, APB) will be evaluated by using surface electrodes attached to the right-hand APB muscle. The cSP threshold is defined as the lowest TMS intensity that elicits a cSP in 5 out of 10 consecutive trials. Single-pulse cortical stimulations will be performed during the vocalization of sustained /i/ sound.

Locations

Country	Name	City	State
Croatia	University of Split School of Medicine	Split

Sponsors (2)

Lead Sponsor	Collaborator
University of Split, School of Medicine	University Hospital of Split

Country where clinical trial is conducted

Croatia, 

References & Publications (8)

Blitzer A, Brin MF, Stewart CF. Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): a 12-year experience in more than 900 patients. Laryngoscope. 2015 Aug;125(8):1751-7. doi: 10.1002/lary.25273. No abstract available. — View Citation

Chen M, Summers RL, Goding GS, Samargia S, Ludlow CL, Prudente CN, Kimberley TJ. Evaluation of the Cortical Silent Period of the Laryngeal Motor Cortex in Healthy Individuals. Front Neurosci. 2017 Mar 7;11:88. doi: 10.3389/fnins.2017.00088. eCollection 2017. — View Citation

Chen M, Summers RLS, Prudente CN, Goding GS, Samargia-Grivette S, Ludlow CL, Kimberley TJ. Transcranial magnetic stimulation and functional magnet resonance imaging evaluation of adductor spasmodic dysphonia during phonation. Brain Stimul. 2020 May-Jun;13(3):908-915. doi: 10.1016/j.brs.2020.03.003. Epub 2020 Mar 13. — View Citation

Deletis V, Rogic M, Fernandez-Conejero I, Gabarros A, Jeroncic A. Neurophysiologic markers in laryngeal muscles indicate functional anatomy of laryngeal primary motor cortex and premotor cortex in the caudal opercular part of inferior frontal gyrus. Clin Neurophysiol. 2014 Sep;125(9):1912-22. doi: 10.1016/j.clinph.2014.01.023. Epub 2014 Feb 11. — View Citation

Pirio Richardson S, Wegele AR, Skipper B, Deligtisch A, Jinnah HA; Dystonia Coalition Investigators. Dystonia treatment: Patterns of medication use in an international cohort. Neurology. 2017 Feb 7;88(6):543-550. doi: 10.1212/WNL.0000000000003596. Epub 2017 Jan 11. — View Citation

Rogic Vidakovic M, Schonwald MZ, Rotim K, Juric T, Vulevic Z, Tafra R, Banozic A, Hamata Z, Dogas Z. Excitability of contralateral and ipsilateral projections of corticobulbar pathways recorded as corticobulbar motor evoked potentials of the cricothyroid muscles. Clin Neurophysiol. 2015 Aug;126(8):1570-7. doi: 10.1016/j.clinph.2014.11.001. Epub 2014 Nov 8. — View Citation

Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10. — View Citation

Simonyan K, Barkmeier-Kraemer J, Blitzer A, Hallett M, Houde JF, Jacobson Kimberley T, Ozelius LJ, Pitman MJ, Richardson RM, Sharma N, Tanner K; The NIH/NIDCD Workshop on Research Priorities in Spasmodic Dysphonia/Laryngeal Dystonia. Laryngeal Dystonia: Multidisciplinary Update on Terminology, Pathophysiology, and Research Priorities. Neurology. 2021 May 25;96(21):989-1001. doi: 10.1212/WNL.0000000000011922. Epub 2021 Apr 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Motor evoked potential (MEP) latency	MEP latency is expressed in milliseconds	MEP latency evaluated on the first day of the arrival on TMS experiment
Primary	Motor evoked potential (MEP) amplitude	MEP amplitude is expressed in microvolts	MEP amplitude evaluated on the first day of the arrival on TMS experiment
Primary	Duration of cortical silent period (cSP)	cSP is expressed in milliseconds	cSP duration evaluated on the first day of the arrival on TMS experiment