16

Bioinformatics of the Brain

measurements. Early diagnosis is important for potential treatments to be

more effective. One possible way to enable early detection is to use ALS-

specific biomarkers [100]. These biomarkers (such as NfL, Tregs, miRNAs,

CK, hs-cTnT) have also gained importance in ALS patients to determine the

stage and to follow the progression of the disease. Studies on cerebrospinal

fluid (CSF) have been shown that the protein level detected by the ELISA

method increases during the progression of the disease [101].

ALS usually presents with weakness in the extremities, i.e., with spinal on-

set, or with difficulty in speaking and swallowing. Respiratory failure and the

problems that result from it typically cause death. Patients with progressed

muscle weakness to the point where they are unable to speak, swallow, move

their hands, or walk have significant difficulty in daily interactions [102]. Mus-

cle cramps are one of the most common symptoms of patients with ALS and

often occur several months before the onset of symptoms. Although muscle

cramps occur in healthy individuals and most commonly in the calf muscles,

ALS can occur in unusual muscles such as the thighs, abdomen, back, or

tongue [103].

Symptoms of muscle weakness vary depending on the motor dysfunction.

For instance, patients may find it difficult to turn keys, fasten buttons, open

bottle lids, or turn doorknobs as they start to lose strength in their hands

and fingers [104]. Patients may suffer low foot or instability as a result of the

weakening in the legs [105]. In bulbar muscle involvement, progressive dete-

rioration in bulbar functions such as babbling, hoarseness, and inability to

whistle or shout is observed. Fasciculations are often not the initial manifes-

tation of ALS but develop in almost all patients soon after onset. The absence

of fasciculations is a condition that requires a review of the diagnosis. In some

patients, fasciculation waves sometimes appear to spread towards the chest or

back [106].

Dysphagia and aspiration are troubling and dangerous complications and

are especially important in bulbar ALS. Muscle weakness, weight loss, and

malnutrition is accelerated with a decrease in oral intake. It should be ques-

tioned whether the patient is coughing or choking while swallowing [104].

High-calorie food supplementation should be used, and the form, as well as

structure of the meals, should be altered to prevent dysphagia and aspiration

[103]. In a prospective study on cognition in ALS, one-third of the patients

were found to have cognitive disabilities, and most patients diagnosed with

ALS have late-onset progressive personality, behavioral, and language impair-

ment without signs of motor neuron disease. ALS patients lose physical abili-

ties such as speaking, manual dexterity, using a pencil and pressing a button

over time due to progressive muscle weakness [107]. ALS has made a name for

itself with the advances made in its treatment in recent years. Riluzole is the

first approved drug used in the treatment of ALS and acts as a glutamatergic

transmission modulator [108]. In addition, Edaravone is a powerful antioxi-

dant and has been used in Japan in the treatment of ischemic stroke since

2001 and in the treatment of ALS since 2015. The oxidative stress pathway