Amyotrophic lateral sclerosis: symptoms and signs, etiology, epidemiology, diagnosis, and treatment

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), the latter name is commonly used in the United Kingdom, France is also called Charcot disease, and the United States is also called Lou Gehrig disease, is an unknown cause, mainly involving the cerebral cortex, brainstem and spinal cord motor neurons of the neurodegenerative disease

First, the general overview

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration and eventual death

2.

ALS causes a combination of upper and lower motor neuron disease, and symptoms vary

Although symptoms of ALS can begin at any time in adulthood, they are most common in individuals

Although ALS is primarily seen as a disorder that affects motor neurons, non-motor symptoms can be observed in up to half of affected individuals

3.

The underlying cause of sporadic ALS is unclear

Approximately 10% of ALS cases are familial (hereditary

Familial ALS is most often caused

Dominant genetic disease occurs when only one copy of an abnormal gene is needed to cause a specific disease

Since the 1990s, more than 20 genetic mutations

4.

ALS is a rare disease that occurs in 1.

The annual incidence in Europe and the United States is 2/100,000 to 3/100,000, and the prevalence is (3-5)/100,000

5.

ALS variant

There are several motor neuron disease subtypes that have some overlapping features and pathologies
with ALS.
These motor neuron disease phenotypes are often associated
with a better prognosis compared to classical ALS.
Biologically, it is unclear whether these entities are continuously present with ALS, or whether they represent significantly different diseases
.

Primary lateral sclerosis (PLS) is a rare neurological disorder characterized by progressive loss
of upper motor neurons.
Loss of upper motor neurons can lead to spasms and weakness in the muscles of the arms and legs, manifested by unsteadiness, tripping, or difficulty
using the hands or arms.
Loss of upper motor neurons in the bulbar muscles leads to speech and swallowing abnormalities, although bulbar symptoms are usually not the initial manifestations
of PLS.
PLS causes progressive disability, but usually progresses much more slowly
than ALS.
Unlike ALS, PLS does not affect lower motor neurons
.
(For more information about this disease, select "primary lateral sclerosis" as your search term in the Rare Disease Database.

) ）

Progressive muscle atrophy (PMA) involves only progressive loss
of lower motor neurons.
This disease is characterized by muscle weakness and atrophy, especially in the
legs.
On examination, a weakening of tone and reflexes is noted
.
If upper motor neuron symptoms do not appear within two years, then there is less possibility of DEVELOPING ALS in the
future.

Focal or monosomy atrophy affects only one area of the body's lower motor neurons, most commonly in the muscles
of the hands and arms.
The affected muscles will develop atrophy and weakness
.
Onset usually occurs in early
adulthood.
The disease usually progresses within a few months and then causes patients to develop fixed dysfunction
.

Other related diseases

Symptoms of the following disorders may sometimes have characteristics
similar to ALS.
Comparison may be helpful in the differential diagnosis
.

Spinal muscular atrophy (SMA) is a group of rare inherited neurological disorders that are most common in infancy and are characterized by progressive degeneration
of lower motor neurons.
SMA is most common in infancy or childhood, but adult-onset SMA
may be considered in the differential diagnosis in patients who predominantly present with sublimb motor neuron disease.
(For more information about this disease, select Spinal Muscular Atrophy as your search in the Rare Diseases database.

) ）

Multifocal motor neuropathy (MMN) is a rare disorder characterized by dysfunction of the lower motor neurons, primarily the
arms and legs.
The disease is thought to be immune-mediated, which means inflammation
due to abnormal immune system function and the presence of specific autoantibodies against specific proteins in the body.
The term multifocal means "from two or more anatomical locations.
"
The disease acquires at some point in a person's life; A person is not born with this disease
.
Multifocal motor neuropathy usually responds
to intravenous immunoglobulin (IVIG) therapy.
MMN is considered the differential diagnosis in patients with limb weakness, particularly hand weakness, and the findings are consistent
with lower motor neuron dysfunction.
(For more information about this disease, select "Multifocal motor neuropathy" as your search in the rare disease database.

) ）

Hereditary spastic paraplegia (HSP) is a large class of genetic disorders that primarily affect upper motor neurons
.
The main symptom of HSP is difficulty
walking due to weakness and spasms in the leg muscles.
HSPs have more than 80 different genetic types
.
There may be significant differences in the severity of leg weakness (from nothing to significant), degree of spasm (from minimal to severe), and other neurologic symptoms that occur between different genetic types of HSPs, as well as differences in the severity
of symptoms between individuals with exactly the same HSP gene type.
For patients with predominantly motor neuron symptoms, particularly leg symptoms, HSP
is considered in the differential diagnosis.
(For more information about this disease, select "Hereditary spastic paraplegia" as your search in the Rare Diseases database.

) ）

Kennedy's disease or spinal bulbar muscular atrophy is a rare X-linked disorder that can lead to progressive submotor neuron disease and symptoms
of androgen dysfunction in adult men.

6.
Diagnosis

ALS is a clinical diagnosis
.
This means that no single test can reliably diagnose the disease
.
Therefore, the diagnosis of ALS focuses on a careful patient history and neurologic examination
.
Depending on the clinical presentation, laboratory and imaging tests may be helpful in ruling out other disorders
.
Diagnosis of ALS requires a history of progressive muscle weakness that has spread to one or more anatomical areas and clinical evidence of upper and lower motor neuron disease, although only one motor neuron dysfunction may predominate early in the course (see Signs and Symptoms section above for details on the clinical manifestations of upper and lower motor neuron disease).

Electrical diagnostic studies, such as electromyography (EMG) and nerve conduction studies (NCS), which assess the transmission of nerve impulses to muscles and the conduction of nerve impulses between neurons, can complement physical examination and show further evidence
of motor neuron dysfunction.
Brain imaging, such as magnetic resonance imaging (MRI), is usually performed
in patients with suspected ALS.
Although some degree of brain atrophy can be seen in ALS, imaging is primarily done to rule out other causes
of motor neuron disease.
Genetic testing is particularly useful
in cases of suspected familial ALS.
Diagnostic delay is a common problem with ALS, with an average diagnostic delay of 1 year
from symptom onset.

Early clinical manifestations of ALS are diverse and lack specific biological diagnostic markers
.
A detailed history, meticulous physical examination, and standardized electromyography are critical to early diagnosis
.
Other adjunctive tests, such as imaging, are of some value
in differential diagnosis.
According to the anatomical location of the symptoms and signs presented by the patient, it can be divided into four areas: brainstem, neck, chest and lumbosacral; Depending on the number of upper and lower motor neurons affected by clinical and electromyography, there are different levels of ALS diagnosis (EI Escorial Standard Revision) (table 4-1).

1.
Clinically confirmed ALS is clinically or electrophysiologically examined to confirm evidence of simultaneous involvement of upper and lower motor neurons in at least 3 of the 4 regions
.

2.
Clinically proposed ALS confirms evidence
of simultaneous upper and lower motor neuron involvement in at least 2 of the 4 regions by clinical or electrophysiological examination.

3.
Simultaneous involvement of upper and lower motor neurons in laboratory-supported als1 areas of proposed diagnosis or involvement of only upper motor neurons with electrophysiological examination suggests lower motor neuron involvement in at least 2 areas, and imaging and laboratory tests rule out other disorders
.

4.
Clinically possible ALS may confirm evidence of simultaneous upper and lower motor neuron involvement in only 1 area by clinical or electrophysiological examination, or only evidence of upper motor neuron involvement in 2 or more areas
.
Imaging and laboratory tests have been done to rule out other disorders
.

Diagnosis and treatment process

7.
Treatment

Treatment of ALS often requires multidisciplinary teamwork, and should include neurologists, physiotherapists, speech pathologists, pulmonologists, lung therapists, medical social workers, dietitians, psychologists, and nurses with specialty.

Multidisciplinary care at ALS has been linked
to improved survival and patient satisfaction.

Treatment with ALS has two main components: therapies that slow the progression of the disease (disease modification therapy) and the therapies that help control symptoms and improve quality of life (supportive care).

Unfortunately, there is no cure for
ALS.

Disease improvement therapy

Rilutek is the first drug
approved by the U.
S.
Food and Drug Administration (FDA) for the treatment of ALS.
In clinical trials, riluzole has been shown to extend survival by an average of three to five months, although it has not significantly delayed muscle degeneration
.
Another FDA-approved treatment for ALS disease is Radicava
.
It has been shown to slow the rate
of functional decline in some patients with ALS.
The benefit appears to be more pronounced
in patients with early ALS.

Symptomatic treatment

Symptomatic treatment of ALS has two main components: pharmacotherapy and non-pharmacological therapy
.

Several medications can be used to help relieve the symptoms
of ALS.
Muscle spasms and bundle tremors can be controlled
with muscle relaxants such as baclofen, tizanidine, or diazepam.
In some patients with severe and disabling spasms, baclofen may use a device called an intrathecal pump to inject directly into the spinal canal (intrathecal administration
).
Some people with cramps may also benefit
from cannabinoid treatment.
Muscle spasms can be painful and can be treated
with medications such as quinine sulfate, levetiracetam, or meximethorrium.
Some patients with ALS may experience hypersecretion (salivation) and inability to control the pooling of secretions; This can be controlled
by drugs such as atropine, scopolamine, amitriptyline, glyconium bromide or botulinum toxin injections.
Oral suction devices also have benefits
.
Mood changes, such as depression or behavioral symptoms associated with frontotemporal dementia, can be controlled
with antidepressants such as selective serotonin reuptake inhibitors (SSRIs).
Some people with ALS may feel pain for different reasons and can be treated
with multiple medications depending on the type of pain.

Physical and occupational therapy is very important and should include daily range of activity exercises
.
These exercises can help maintain flexibility in the affected joint and prevent muscle immobilization (contracture).

It is also important
for people with ALS to maintain proper nutrition.
Weight loss is an independent predictor
of a poor prognosis for ALS.
Patients with dysphagia should choose soft foods
carefully.
When insufficient nutrients and fluids cannot be maintained due to difficulty swallowing, a gastric feeding tube may be considered
.
Speech therapy and augmented communication devices are useful
for patients with dysarthria.

Once an individual develops respiratory muscle weakness, noninvasive positive pressure ventilation (NIPPV) can help aid breathing
.
Cough assist devices can also be used to clear secretions
.
Eventually, ventilation weakness progresses to the point where the patient is unable to breathe on their own, and some patients choose to have a tracheostomy and permanent mechanical ventilation
.
For patients who decide not to use mechanical ventilation, home hospice services can provide supportive care and assist with comfort measures
.

8.
Rare disease information registration

If you are willing to seek constantly updated information, it is recommended that you register the patient's information here, even if you are not fully diagnosed, you can register, click to enter:

Patient Information Registry System for Rare Diseases

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