Amyotrophic lateral sclerosis (ALS) or “Lou Gehrig’s disease” (after the famous American baseball player who was diagnosed with the disorder) is a rare degenerative disorder of motor neurons of the cerebral cortex, brain stem, and spinal cord that results in progressive wasting and paralysis of voluntary muscles. The age of onset is in middle adult life. It progresses rapidly and most of the affected individuals die within 3–5 years from onset of symptoms.
The cause of the disease is still elusive, except in familial cases (about 10%) where the most common cause is linked to mutations in the gene encoding cytosolic copper–zinc superoxide dismutase (SOD1, an enzyme responsible for scavenging free radicals).
Essential features of ALS are progressive signs and symptoms of lower motor neuron dysfunction. These include focal and multifocal weakness, atrophy, cramps, and fasciculations associated with corticospinal tract signs (spasticity, enhanced, and pathological reflexes) in the absence of sensory findings. Usually, the symptoms initially affect a limb, but in some cases there might be a bulbar onset with difficulties in speaking and swallowing. Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses.

No treatment prevents, halts, or reverses the disease, although marginal delay in mortality has been noted with the drug riluzole.

ALS is a difficult disease to diagnose as there are many other, more treatable diseases which mimic it. Thus, the diagnosis is primarily based on the symptoms and signs observed by the physician and a series of tests to rule out other diseases. To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes. Electromyography (EMG) provides objective evidence of lower motor neuron involvement. When the lower motor neuron involvement is severe, the upper motor neuron signs may be masked and its involvement can be missed. In this context, MR methods can be very useful to detect early involvement of upper motor neuron involvement, potentially shortening the time to diagnosis.
Recent MRI studies have shown the diagnostic utility of hyperintensity of the corticospinal tract on FLAIR sequences in ALS. Other studies, using diffusion images or quantitative morphometry, have provided evidence of abnormalities of extramotor areas, supporting the view that ALS is a multisystem degenerative disease.

1H-MRS

Among the recent MR technologies used to improve detection of upper motor neuron involvement, 1H-MRS can provide insights into the metabolic integrity of these pathways. Not surprisingly, in the brain of ALS patients, NAA is decreased in a spatially dependent manner that reflects its pathologic distribution and mI is often increased in the motor cortex. This has led to the proposal of using the NAA/mI ratio, (Fig-1 and 2) which would enhance the ability of MRS to distinguish patients with ALS from control subjects. This might become a useful biomarker in ALS. In recent pilot studies, 1H-MRS has been used to monitor whether riluzole does have a mild disease-altering effect. The finding of an increase in NAA/Cr ratio in the motor cortex of ALS patients after a brief treatment with riluzole should be confirmed in controlled studies involving larger patient populations.
Since the main goal is to study the regional distribution of metabolites in the corticospinal tract, both single-voxel 1H-MRS and 1H-MRSI can be used. The assessment of both mI and NAA should be pursued, therefore short TE (30–35 ms) acquisitions are preferable.

Fig-1: NAA distribution over the motor and premotor cortex in patient with ALS.

Fig-2: Same patient as in fig-1 with NAA/MI ratio in the same area.

Figure-3: This MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS. However, typically MRI imaging is unremarkable in a patient with ALS.

Figure-4: PCD C3-4 with spinal cord compression with spinal artery syndrome can mimic the clinical picture of the patient. This patient suffering from muscle atrophy for 16 years with inability to walk with full blown picture of ALS. The high levels of NAA is against the ALS in MRS.

Figure-5: The NAA/Inositol ration is not decreased, instead it is increased, ruling out the presence of ALS.

Figure-6: MRI of patient with ALS with the increased signal of T2 in the posterior part of the internal capsule left side.

Figure-7: The same signal in the right side of the same case of figure 6.

Figure-8: The same patient in figure-6 with normal pattern of Short TE spectroscopy.

Fifure-9: The same patient with normal values of NAA.

Figure-10: The same patient in figure 6 showing normal ratio of NAA/Inositol. From these data from figure 6-10, it seems that the presence of T2 shadows in the posterior limb of the internal capsules are more reliable than the spectroscopic data.