Heavy! The latest expert consensus on the diagnosis and treatment of amyotrophic lateral sclerosis was released

Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron disease, the general incidence of middle-aged and elderly people is more common, the peak of ALS onset age in China is about 50 years old, and the age of onset has a younger trend, a small number of patients can be about 20 years old to become ill

Diagnostic criteria for ALS

(A) ALS diagnosis points

1.

2.

3.

(2) Problems that need to be paid attention to in the process of ALS diagnosis

1.

2.

3.

4.

5.

6.

Clinical type of ALS

1.
ALS classic type: includes ALS, PMA and PBP
.

PMA can be seen as ALS for the onset of lower motor neurons, and PBP is ALS for the onset of myela symptoms, which can be classified as ALS in clinical diagnosis; However, PLS is significantly different from the first three and may be a relatively independent disease entity, and a small number of PLS may manifest as bulb onset and spastic dysarthria
for a long time.

Patients with motor neuron onset above clinical incidence may resemble PLS in the early stage, but usually have manifestations of motor neuron involvement within 4 years of onset
.

2.
Flail arm syndrome: clinical weakness of the proximal extremities above the main manifestation, can be symmetrical or asymmetrical onset, gradually and slowly progress, involving both upper extremities, with the progression of the disease, can affect the distal end, tendon reflex can be reduced or disappeared, there may be positive Hoffman sign, within 1 year after the onset of the disease, the symptoms are still limited to the upper extremities
.

3.
Flail leg syndrome: clinical weakness of the lower limbs is the main manifestation, can be symmetrical or asymmetrical onset, gradually and slowly progress, tendon reflex can be reduced or disappeared, the lower extremities may have pathological signs, within 1 year after the onset of the disease, the symptoms are still limited to the lower extremities
.

As the disease progresses, both lower extremities can be completely paralyzed and spread to other areas
.

4.
ALS with frontotemporal dementia: the first symptoms and main manifestations of patients can be mainly involved in upper and lower motor neurons, or cognitive and psychobehavioral abnormalities, and symptoms and signs
of both aspects of involvement occur with the development of the disease.

Patients often have a family history
.

differential diagnosis

ALS has a variety of clinical phenotypes, the onset site can be upper extremities, lower extremities, medulla oblongata or respiratory muscles, early signs can be simple lower motor neuron involvement, upper and lower motor neurons simultaneous involvement or simple upper motor neuron involvement, some patients may be accompanied by cognitive impairment
.

In the early diagnosis process, according to the symptoms and signs, it is necessary to distinguish from a variety of diseases, common are cervical spondylosis, lumbar spondylosis, multifocal motor neuropathy, Hirayama's disease, late-onset spinal muscular atrophy, Kennedy disease, hereditary spastic paraplegia, paraneoplastic syndrome, ALS superposition syndrome and so on
.

Clinically, according to the specific manifestations of each patient, the necessary auxiliary tests should be selected for different diseases to carry out individualized differential diagnosis
.

Treatment of ALS

Although ALS is still an incurable disease, there are many ways to improve the quality
of life of patients.

Early diagnosis and early treatment should be used to prolong survival as long as possible
.

In addition to the use of drugs that delay the progression of the disease, comprehensive treatment such as nutritional management, respiratory support, symptomatic and psychotherapy is also included
.

(1) Drugs that delay the progression of the disease

1.
Riluzole (riluzole): chemical name is 2-amino-6 (trifluoromethoxy)-benzothiazole, and its mechanism of action includes stabilizing the inactive state of voltage-gated sodium channels, inhibiting the release of presynaptic glutamic acid, activating postsynaptic glutamate receptors to promote glutamic acid uptake, etc
.

The drug has been confirmed by multiple clinical trials to delay the progression of the disease to a certain extent, and the use is 50 mg orally
twice a day.

Common adverse effects are fatigue and nausea, and some patients may have elevated alanine aminotransferase, and liver function
should be monitored.

When patients with advanced disease have already used an invasive ventilator to assist breathing, it is not recommended to continue taking it
.

2.
Edalaphon injection: Edaravone is a free radical scavenger with antioxidant stress effect, commonly used in the treatment of acute cerebral infarction
.

The recommended method of use of edarabon for the treatment of ALS is: 60 mg of Idalaphon, diluted with 100 ml of normal saline, intravenous infusion within 60 min, once a day; The combination of the administration period and the discontinuation period is 28 days for 1 cycle, a total of 6 cycles: the first cycle of continuous administration for 14 days, discontinuation of the drug for 14 days; administered for 10 days (5 d/week) within 14 days from the 2nd cycle; After that, the drug is discontinued for 14 days and repeated (cycle 2 to 6).

3.
Other drugs: sodium phenylbutyrate combined with taurine ursodeoxycholic acid has been confirmed in clinical trials to significantly delay the decline of ALS functional score and prolong survival
.

Preliminary findings on the treatment of antisense oligonucleotides in patients with SOD1 gene mutation ALS also showed some effect
.

In animal experiments, although a number of drugs have shown certain efficacy in the treatment of ALS animal models, such as rasagiline, high-dose vitamin B12, dexpramipexole, creatine, high-dose vitamin E, coenzyme Q, lithium carbonate, ciliary neurotrophic factor, insulin-like growth factor, lamotrigine, etc.
, they have not been confirmed to be effective
in clinical studies of patients with ALS.

(2) Nutrition management

1.
When you can eat normally, you should use a balanced diet, and when swallowing difficulties, you should use a high-protein, high-calorie diet to ensure nutritional intake
.

2.
For patients with chewing and swallowing difficulties, they should change the diet, eat soft food, semi-liquid food, and eat less and more meals
.

For people with limb or neck weakness, the eating position and utensils can be adjusted
.

3.
When the patient has obvious difficulty swallowing, weight loss, dehydration or there is a risk of choking cough aspiration, percutaneous endoscopic gastrostomy (PEG) should be performed as soon as possible, which can ensure nutritional intake, stabilize body weight, and prolong survival
.

It is recommended that PEG should be performed as early as possible before the FVC is reduced to 50% of the project, otherwise it needs to be performed with ventilator support to assess the risk of
anesthesia.

For those who refuse or are unable to perform PEG, nasogastric canal feeding
may be used.

(3) Respiratory support

1.
It is recommended to check lung function
regularly.

2.
Pay attention to the early manifestations of respiratory muscle weakness in patients and use bi-level positive airway pressure as soon as possible
.

Indications for initiating noninvasive ventilation include sitting breathing, or sniff nasal pressure< 40 cmH2O (1 cmH₂O = 0.
098 kPa), or maximal inspiratory pressure (maximal inspiratory pressure) <60 cmH_2O, or decreased oxygen saturation at night.
or FVC < 70%.

3.
When the patient coughs weakly (the peak of cough and exhalation flow is less than 270L/min), a suction device or artificial assisted cough should be used to exclude respiratory secretions
.

4.
When ALS progresses, noninvasive ventilation cannot maintain blood oxygen saturation >90%, carbon dioxide partial pressure < 50mmHg (1mmHg = 0.
133 kPa) or excessive secretion can not be discharged, invasive ventilator can be selected to assist breathing
.

After invasive ventilators are used to assist breathing, it is usually difficult to go offline
.

(4) Comprehensive treatment

At different stages of the ALS course, patients face different problems, such as depression and anxiety, insomnia, salivation, dysarthria, communication difficulties, limb spasms, pain, etc.
, and should be given targeted guidance and treatment
according to the patient's specific situation.

Choose appropriate medications and assistive facilities, improve quality of life, enhance care, and prevent complications
.

(5) Problems that should be paid attention to in the treatment of ALS

1.
When communicating the condition, it should avoid bluntly informing ALS that there is no cure, and it is recommended to gently inform the current status of treatment and future hopes
.

The effect and advantages and disadvantages of the current treatment drugs should be objectively communicated, and it is recommended to discuss with the patient's family and choose the drug treatment plan
according to the economic situation and personal wishes.

2.
Paying attention to comprehensive treatment such as nutritional support and respiratory support is essential
to improve the quality of life and survival of ALS patients.

Medical pulse is sorted from: Amyotrophic lateral sclerosis collaborative group of the Neurology Branch of the Chinese Medical Association.
"Amyotrophic lateral sclerosis diagnosis and treatment of Chinese expert consensus 2022".
Chinese Journal of Neurology, 2022, 55(6): 581-588