Amyotrophic lateral sclerosis (ALS) is the commonest clinical form of the wider neurodegenerative
syndrome encompassed by the term motor neuron disease (MND). ALS has a consistent
incidence of 1-2/100,000/year, and a lifetime risk estimated at 1 in 400. The disease
is characterized by the progressive death of upper motor neurons (UMNs) of the cerebral
primary motor cortex and corticospinal tract, in combination with degeneration of
lower motor neurons (LMNs) whose origins lie in the brainstem and spinal anterior
horns. Loss of motor neurons in general results in weakness, but specifically loss
of LMNs results in secondary wasting of the downstream musculature and spasticity
arises from loss of UMNs[1].
About 10% of cases are considered as being familial (fALS), whereas the remaining
90% seem to occur sporadically (sALS) with no family history of ALS. Since the first
discovery of SOD1 mutations being causative for ALS in 1993[2], researchers all over the world have made great effort to further delineate the
genetic basis underlying ALS. Today, more than 30 confirmed major disease genes are
listed by the Amyotrophic Lateral Sclerosis Online genetics Database (ALSoD), the
most frequently affected being C9orf72 (40% fALS, 5–6% sALS; pathogenic repeat expansion
in the non-coding region between exons 1a and 1b, detection by repeat analysis), SOD1
(20% fALS, 3% sALS), FUS (5% fALS, <1% sALS) and TARDBP (3% fALS,2% sALS)[3].
In addition to this clinically heterogeneous syndrome a pathologically overlapping
with frontotemporal dementia motor signs have been detected by neuropsychological
tests in about 50% of sALS patients. Furthermore typical frontotemporal dementia (FTD)
occurs in approximately 10% of the patients[4], and the term frontotemporal dementia-motor neuron disease (FTD-MND) continuum was
proposed to describe this association[4], which occurs mostly in C9ORF72-linked fALS[5].
Despite all this clinical and etiopathogenic complexity, some faces of ALS, including
FTD-MND continnum, have been elucidated by magnetic resonance imaging (MRI) techniques,
which have proved to be useful to reveal microstructural brain abnormalities associated
with different rates of symptom progression[6],[7]. A plausible biomarker for upper motor neuron degeneration in ALS is becoming tangible
after recent advances in high-throughput MRI techniques, through which one can believe
that we are going to the forefront of a breakthrough able to translate research findings
into reliable clinical tests that will support the practice of personalized medicine[8],[9],[10].
Advances in neuroimaging have enabled mapping of some endpoints in functional, structural,
and molecular aspects of ALS pathology. Menke et al.[8] have recently reported imaging abnormalities even before clinical symptoms, offering
the potential for neuroprotective intervention, particularly in familial cases. Current
literature points to DTI technique as the most promising candidate for imaging biomarker
in ALS, able to elucidate the brain phenotype of ALS and also detect white matter
tract changes in extramotor regions[8],[10].
The results of Chaves et al.[11] using a 1.5 Tesla MR equipment reinforce the clinical use of fractional anisotropy
(FA) to detect extra-motor brain abnormalities in ALS patients. Despite this further
multicenter validation with larger cohorts of patients remains mandatory prior to
the integration of this technique into the clinical routine as biomarker able to contribute
in standard clinical decision-making algorithms.
