Study Purpose:Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder with no effective disease-modifying therapies at present. The disease is sporadic in 90 % of the ALS patients. Up to 40 % familial ALS cases and up to 25% of familial frontotemporal dementia (FTD) are caused by autosomal dominant GGGGCC hexanucleotide repeat expansions in the C9orf72 gene. The presymptomatic phase of the disease represents a unique opportunity to evaluate mechanisms of disease propagation, characterise patterns of anatomical spread, validate staging systems and appraise the comparative sensitivity profile of emerging imaging modalities. Very few spinal cord imaging studies currently exist in ALS despite their potential to characterise both the lower and upper motor neuron components of the disease. This prospective longitudinal study of asymptomatic and symptomatic c9orf72 hexanucleotide carriers will use a purpose-designed spinal and brain imaging protocol and comprehensive clinical, genetic, electrophysiological and neuropsychological profiling. Newly developed imaging techniques such as spinal cord NODDI, spinal fMRI, quantitative thoracic cord imaging will be implemented in addition to established spinal cord and brain imaging techniques.
Not yet recruiting
Amyotrophic Lateral Sclerosis
Type of Intervention:
Neuroimaging and electrophysiology
Study Chair(s)/Principal Investigator(s):
Coordinating Center Contact Information
Full Study Summary:
1. The development of prognostic indicators based on spinal cord/ brain imaging and electrophysiology to foretell phenotypic manifestation (such as DFT or ALS) and age of onset.
2. The integrative evaluation of brain-cord interactions, comparing the relative detection sensitivity of spinal and cerebral imaging measures.
3. Assessing the imaging evidence for the prevailing 'corticofugal spread' or 'dying-forward' theory based on longitudinal spinal cord and cerebral data.
4. Characterizing associations between imaging and electrophysiology metrics of LMN and UMN integrity; correlation of segmental grey matte metrics to MUNE; TMS to corticospinal tract measures
5. The assessment if longitudinal cerebral and spinal cord imaging data are consistent with sequential TDP-43 pathological staging systems.
6. The cross validation of newly developed cord techniques (NODDI and fMRI) with established structural and diffusion imaging metrics and electrophysiology measures.
Assistance Publique - Hôpitaux de Paris
Estimated Study Start Date:
05 / 15 / 2022
Estimated Study Completion Date:
04 / 15 / 2025
Posting Last Modified Date:
05 / 03 / 2022
Date Study Added to neals.org:
05 / 03 / 2022
N/AInclusion criteria shared by all the different cohorts and controls :
- Age more than 18 years.
- Signature of a consent form for clinical, paraclinical and genetic assessment
- Fluent in French
- Affiliated to the French Security Healthcare System ("Sécurité Sociale")
- Absence of neurological comorbidity (stroke, tumor etc)
The inclusion criteria for asymptomatic relatives :
- Being a first-degree to a person carrying a C9orf72 mutation.
- Absence of proven clinical signs of FTD, ALS, language, praxic, memory disorders, Parkinsonian syndrome.
Inclusion criteria for symptomatic ALS patients :
- Patients fulfilling the El Escorial criteria for probable or definite ALS
- Presence of a C9orf72 mutation
Exclusion criteria for participants from all cohorts :
- Contraindication to MRI and TMS
- Impossibility to stay in decubitus during 1 hour,
- For women, childbearing or breastfeeding
- For women of childbearing potential: positive HCG test or positive urine pregnancy test