Amyotrophic lateral sclerosis

Introduction and Facts

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that attacks motor neurons. Amyotrophy indicates atrophy of muscle fibers, which are innervated by degenerating anterior horn cells, leading to muscle weakness and fasciculations. Lateral Sclerosis shows ossification of the lateral and anterior corticospinal tracts where motor neurons in that area degenerate through the process of gliosis (Rowland and Shenider, 2001). Through the combination of these terms, it can be illustrated that in this disease there is a mixed lesion of Upper Motor Neuron with Lower Motor Neuron.

The incidence of ALS in 1990 was reported to be between 1.5 - 2.7 per 100,000 population/year (mean 1.89 per 100,000/year) in Europe and North America (Worms, 2001). The incidence of ALS is higher in men than in women, with an overall ratio of 1.5:1. According to geographic location, the prevalence of ALS in the western Pacific including Guam, Mariana Island, Honsu Island and southern West New Guinea is reported to be 50–100 times. higher than other places. The onset of ALS can occur from adolescence to the age of 80 years, but the age of peak incidence occurs between the ages of 55-75 years. The mean age of onset of sporadic ALS (SALS) is 65 years, the mean age of onset of familial ALS (FALS) is 46 years (Steele and Mc. Geer, 2008).

Pathophysiology

The pathological features of ALS are degeneration and loss of motor neurons with astrocytic gliosis and the presence of intraneuronal inclusions in degenerating neurons and glia. The pathology of UMN in ALS is characterized by depopulation of Betz cells in the motor cortex (Brodmann area 4), astrocytic gliosis affecting the gray matter and white matter of the subcortical with loss of axons in the descending pyramidal motor pathway due to gliosis and damage to myelin in the corticospinal tract (Wijesekera and Nigel, 2009). ). The cell count can be reduced by up to 50% at autopsy in ALS patients.

Clinical Symptoms and Complications

The diagnosis of ALS is based on clinical findings. A person is suspected of having ALS if there is a gradual or progressive loss of motor function in one or more parts of the body, without sensory disturbances and for no apparent cause.

Symptoms of ALS usually do not appear until the patient is 50 years old, but can appear slowly at a young age. Symptoms of ALS appear when motor neurons in the brain and spinal cord begin to degenerate. ALS progression may be so slow that early symptoms are often overlooked and considered an aging process (McCarthy, 2009). The part of the body that is affected in the early symptoms of ALS depends on which muscle is attacked first. In some cases, the symptoms initially affect one leg, and the patient has difficulty walking or running and the patient stumbles more often than before.

Some sufferers experience hand discomfort for the first time when they have difficulty performing simple movements that require hand skills, such as buttoning a shirt, writing, or inserting and turning a key in a keyhole. While the other patients, experienced problems with the sound first. In 75-80% of patients, symptoms begin with limb involvement, whereas 20-25% of patients present with bulbar symptoms. In patients with bulbar symptoms, the patient may experience problems with speech (dysarthria) or decreased volume of the voice. Swallowing disorders (dysphagia), aspiration or choking while eating may occur, due to the involvement of the VII, IX, X, XI and XII cranial nerves.

In some patients, complaints may be accompanied by cognitive changes. Cognitive dysfunction is experienced by 20–50% of people with ALS, and 3–15% progresses to dementia which is categorized as frontotemporal lobar degeneration (FTLD). Cognitive changes are characterized by personality changes, irritability, and deficits in executive function. The diagnosis is confirmed by the finding of joint UMN and LMN weakness in the limbs, muscle weakness, muscle atrophy, muscle fasciculations, combined with hyperreflexia.

Diagnosis

According to the World Federation of Neurology (WFN), the diagnosis of ALS is:

1. Definite ALS: presence of UMN and LMN symptoms at 3 levels

2. Probable ALS: presence of UMN and LMN symptoms at 2 levels

3. Possible ALS: presence of UMN and LMN symptoms at 1 level or UMN symptoms at 2 levels

4. Suspect ALS: LMN symptoms at 2 levels or UMN symptoms at 1 level.

In using the WFN criteria, there are 4 regions that must be known: Bulbar, cervical, thoracic and lumbosacral.

ALS is difficult to diagnose early on because it has symptoms similar to some other neurological diseases and so additional tests are needed to rule out other conditions. Checks that can be carried out include:

1. Electrophysiology

Electrophysiology is used to detect the presence of LMN lesions in the involved area as well as to exclude other disease processes. (Wijesekera and Nigel, 2009).

a. Motor and sensory nerve conduction. Nerve conduction is needed to diagnose and rule out other disorders of the peripheral nerves, neuromuscular junction, and muscles that can mimic or confound the diagnosis of ALS (Wijesekera and Nigel, 2009).

b. Electromyography. Concentric needle electromyography (EMG) provides evidence of LMN dysfunction necessary to support the diagnosis of ALS and must be found in at least two of the four CNS regions: brain (bulbar), neck, thoracic, or lumbosacral spinal cord (anterior horn of motor neurons). c. Transcranial magnetic stimulation and Central motor conduction studies Transcranial magnetic stimulation (TMS) allows non-invasive evaluation of the corticospinal motor pathways, and allows detection of UMN lesions in patients without signs of UMN.

d. Quantitative Electromyography. Motor Unit Number Estimation (MUNE) is a specialized electrophysiological technique that can provide a quantitative estimate of the number of axons that innervate a muscle or muscle group.

2. Neuroimaging

Head/spinal MRI is performed to rule out structural lesions and other diagnoses in patients with suspected ALS such as tumors, spondylitis, syringomyelia, bilateral stroke, and multiple sclerosis (Wijesekera and Nigel, 2009).

3. Muscle biopsy and neuropathology

Primarily performed in patients with an atypical clinical presentation, especially those with poorly defined LMN lesions. A biopsy is used to rule out the presence of myopathy, such as inclusion body myositis (Wijesekera and Nigel, 2009).

4. Other lab tests

Clinical laboratory tests that may be abnormal in otherwise typical cases of ALS include:

• Muscle Enzymes (unusual serum creatinine kinase above ten times the upper limit of normal, ALT, AST, LDH)

• Serum creatinine (associated with loss of skeletal muscle mass)

• Hypochloremia, increased bicarbonate (associated with advanced respiratory distress) (Wijesekera and Nigel, 2009).

Management and Care

Riluzole (a glutamate antagonist) 50 mg twice daily is recommended, with regular monitoring. Administration of 100 mg of oral riluzole daily after 18 months prolongs the life expectancy of ALS sufferers by about three months. The side effects of riluzole are fatigue and asthenia. To date, there is no effective therapy for ALS (Lacomblez et al, 1996).

Various drugs are entering phase II/III trials: arimoclomol, ceftriaxone, edaravone, IGF-1 polypeptide, minocycline, sodium phenylbutyrate, tamoxifen, thalidomide. Drugs being considered and planned to enter phase III trial: AEOL 10150, celastrol, coenzyme Q10, copaxone, IGF-1 – viral delivery, memantine, NAALADase inhibitors, nimesulide, ritonavir, hydroxyurea, scriptaid, talampanel and trehalose (Andersen et al, 2005) . Recombinant human insulinlike growth factor (rhIGF-I) therapy - a genetically modified human protein - is expected to improve and strengthen motor neuron survival in ALS. It is given daily by subcutaneous injection. Stem cell therapy is promising, but its effectiveness still requires further research

The nutritional status of ALS sufferers also needs to be evaluated, given the frequent occurrence of dysphagia, hypermetabolism, and various comorbidities. Nutritional management includes diet, swallowing strategies, possible insertion of a feeding tube directly into the stomach (gastrostomy tube placement), and vitamin and mineral supplementation (Braun et al, 2012). When nutritional status is compromised by dysphagia and weight loss (5%-10% of usual body weight) or body mass index <20 kg/m (2) without weight loss, percutaneous endoscopic gastrostomy is indicated (Greenwood, 2013).

Symptomatic therapy to treat spasticity that interferes with the patient's daily activities is the administration of baclofen or diazepam. To overcome excessive saliva production (sialorrhea) can be given trihexyphenidyl or amitriptyline. If refractory, botulinum toxin type B injection can be given in the parotid and submandibular glands. Radiation therapy with a dose of 7–7.5 Gy bilaterally effectively reduces saliva production, but there are side effects, such as: erythema and nausea (Jackson et al, 2008).

Depression is treated with antidepressants, for example: amitriptyline or SSRI groups. Insomnia treated with amitriptyline or hypnotics, such as: zolpidem, diphenhydramine. Anxiety is treated with bupropion or diazepam 0.5 mg 2-3 times daily, or sublingual lorazepam.

Pseudobulbar affect, excessive crying-laughing, or impaired involuntary emotional expression are experienced by 20–50% of people with ALS, especially in cases of pseudobulbar palsy. The combination of 30 mg of dextromethorphan and 30 mg of quinidine twice daily is effective in treating pseudobulbar affect. Use oxygen only in cases of symptomatic hypoxia.

Respiratory complications are a common cause of morbidity and mortality in ALS patients. Management of respiratory insufficiency with non-invasive ventilation improves the quality and survival of ALS patients. Oxygen is usually given only in conjunction with NIV to prevent respiratory obstruction in evaluating carbon dioxide levels

Reference: 

Arimbawa IK, Pramaswari AAAA. AMYOTROPHIC LATERAL SCLEROSIS (ALS). [Internet]. [Cited 29/8/2021]. Available from: https://simdos.unud.ac.id/uploads/file_penelitian_dir/a27a02ff66676c092e0a41f3948ba25e.pdf