Assessing Motor Neuron Disease Mechanisms by Threshold Tracking Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy

Summary

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which cases the death of neurons controlling the voluntary muscles. The death of motor neurons leads eventually to muscle weakness and muscle atrophy and as a consequence thereof, ALS patients die in average within three years after symptom onset due to respiratory failure.

No cure for ALS is currently known, and the medical diagnosis and clinical treatment are impeded by the lack of reliable diagnostic tools for objective disease assessment, and by the limited insight in disease pathophysiology since the underlying disease mechanisms still have not been fully elucidated.

An unbalance in the concentrations of GABA and glutamate, the most important inhibitory and excitatory brain metabolites, is suggested to play a role in the disease mechanisms of ALS. By applying Magnetic Resonance Spectroscopy (MRS), a magnetic resonance method which allows for quantification of brain metabolites, GABA and glutamate concentration can be quantified and thus hopefully elucidate their role in ALS disease mechanism.

Threshold Tracking Transcranial Magnetic Stimulation (TT-TMS) studies carried out by a single research group have demonstrated cortical hyperexcitability (a physiology state in which neurons in the cerebral cortex are easier activated) as an early feature in ALS patients. For this reason, TT-TMS was suggested as a biomarker of ALS by the research group. However, to be able to suggest a test as a biomarker, one must show the test is reliable and reproducible.

The objectives of this study are therefore: to explore the pathophysiology of ALS by investigating the interaction between neuronal networks as assessed by TT-TMS and conventional TMS and MRS, and to investigate the reliability and reproducibility of TT-TMS. The aim is to examine the utility of TT-TMS and MRS as diagnostic tools for objective detection of ALS in the early disease stage.

The study will include 60 participants in total, subdivided into two groups: 30 healthy participants and 30 patients with clinical suspicion of motor neuron disease or ALS. Each participant will undergo examination with TMS and MRS, the primary outcomes will be compared between the two groups and the results from the TMS examinations and the MRS-scans will be correlated.

Conditions

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Cortical Excitability

Interventions

DIAGNOSTIC_TEST

MRS, conventional TMS and treshold tracking TMS

Using * two MagStim 200 magnetic stimulator and a figure-of-eightc double 70 mm coil * SPECIAL MR Spectroscopy sequence In addition, each group will undergo neurological examination

Sponsors & Collaborators

• Lundbeck Foundation

  collaborator OTHER

• Aage og Johanne Louis-Hansens Fond

  collaborator OTHER

• The A.P Moeller Foundation for Advancement of Medical Science

  collaborator UNKNOWN

• Danish Council for Independent Research

  collaborator OTHER

• Aarhus University Hospital

  collaborator OTHER

• Central Denmark Region

  collaborator OTHER

• Sándor Beniczky

  lead OTHER

Principal Investigators

• Hatice Tankisi, MD, PhD · Department of Clinical Neuropysiology, Aarhus University Hospital

Eligibility

Min Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-02-16

Primary Completion

2023-12-31

Completion

2024-02-01

Countries

• Denmark

Study Locations