Brain Diseases and Disorders

15

symptoms constitute the major reasons for the burden on families and are

considered the most important predictors of a decrease in daily functions and

placement in care institutions and hospitalizations [90]. To properly address

genetic testing counseling, a multidisciplinary team effort with a psychiatrist

or psychologist is required, considering all hereditary factors and risks [91].

Sufficient genetic and clinical information should be given to the at-risk indi-

vidual. The consultant should adopt a neutral stance, neither endorsing nor

opposing the prognostic test. A decision to get tested must take into account

factors such as depression, hopelessness, anxiety, suicidal thoughts, and the

existence of social support [92].

1.6.4

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a progressive disease characterized by

degeneration of upper and lower motor neurons of the brain and spinal cord.

The disease is usually inherited as an autosomal dominant (OD) [93] and

clinical findings usually begin between the ages of 50 and 60 [94]. In familial

cases, the age of onset of the disease is earlier. This disease occurs due to the

loss of motor nerve cells in the CNS. Various combinations of findings resulting

from upper and lower motor neuron involvement determine the clinical picture.

Sleep-related respiratory disorders are quite common in ALS patients. It rises

with phrenic denervation and diaphragm weakness, develops in proportion to

the severity of respiratory and upper airway muscle weakness, and increases

significantly during rapid eye movement (REM) sleep, when postural muscular

inhibition takes place [95].

Familial ALS cases account for approximately 10% of all ALS cases and, are

phenotypically and genetically heterogeneous. It has been suggested that ge-

netic causes, glutamate excitotoxicity, viral infections, autoimmune reactions,

and heavy metal intoxications such as lead, mercury and aluminum play a

role in the onset of the disease [96]. In 20% of familial cases and 1–5% of spo-

radic cases, there is a mutation on the gene encoding the Cu/Zn-superoxide

dismutase 1 (SOD1) enzyme localized on chromosome 21. While only 2% of

the disease was predicted to be genetically transmitted in the 1990s, with the

increase in scientific studies on the subjects over the recent years, this rate

has increased to approximately 23% today [93].

The etiology of ALS is not fully known. Due to its complex pathophysi-

ology, which involves multiple pathways including oxidative stress, mitochon-

drial failure, endoplasmic reticulum stress, and axonal transport problem, the

disease is challenging to detect. The precursors of ALS are usually not specific

to this disease and may mimic other neuromuscular diseases. These diseases

are often called mimic syndromes. Errors in early diagnosis could postpone the

identification of ALS [97]. After clinical diagnosis, ALS symptoms gradually

worsen over time [98]. Factors leading to a delay in diagnosis include famil-

ial form of the disease, place of initial involvement, and gender [99]. Current

diagnostic criteria are based on clinical examination and electrophysiological