Amyotrophic lateral sclerosis (ALS; also known as motor neuron disease or Lou Gehrig’s disease) is a widely heterogeneous multisystem neurodegenerative syndrome,
which affects both the upper and lower motor neurons with a welter of pathophysiological mechanisms and multiple clinical phenotypes.
To add to the complexity of the entity,
an overlap between ALS and frontotemporal dementia has been suggested,
attributed to a common genetic cause (hexanucleotide repeat expansions in C9orf72),
forming a probable continuum of a single multispectral disease.
Special attention should be given to ALS mimickers such as primary lateral sclerosis (PLS),
which targets exclusively the upper motor neuron and has a better prognosis than ALS.
However,
differentiating it from an initially upper motor neuron-predominant ALS can be challenging.
Progressive spinal muscular atrophy (PSMA),
characterised by lower motor neuron degeneration,
has been debatably grouped under the umbrella of ALS variants,
since autopsies have constated corticospinal tract (CST) involvement.
The vast majority of ALS cases are sporadic (around 90%),
the rest being familial,
mostly inherited as dominant traits.
In terms of epidemiology,
an estimation of 2.6-3.0 cases of ALS per 100,000 people of European ancestry has been described,
with a mean age of onset being 65 years.
Survival is variant,
not exceeding though 3-4 years after initial presentation,
mostly due to respiratory failure.
As for the clinical presentation,
it is highly versatile and insidious,
ranging from dysarthria to a foot drop,
which may develop within weeks or even months.
No treatment offers a substantial clinical benefit for patients with ALS up to date. Therapy is supportive and includes mainly riluzole which provides a limited improvement in survival.
Although conventional MRI is widely used in everyday practice,
its use is restricted in excluding mimickers of ALS and in individual cases for disease monitoring.
Advanced neuroimaging techniques have been a game changer in the study of ALS (Diffusion tensor MRI-DTI in the study of the CST,
Voxel-based morphometry-VBM in the study of Gray Matter,
Spectroscopy etc).
DTI generates quantitative data about water diffusion in three-dimensional space.
It should be noted that diffusivity is higher along fiber tracts compared to directions perpendicular to them.
Diffusion is quantified using mean diffusivity (MD) and fractional anisotropy (FA).
MD is a measure of the directionally averaged magnitude of diffusion and is related to the integrity of the local brain tissue.
FA represents the degree of diffusion anisotropy and reflects the degree of alignment of cellular structures.