Neurological guidelines: guidelines for the diagnosis and treatment of amyotrophic lateral sclerosis in China

The early clinical manifestations of ALS are diverse
.
Lack of specific biologic diagnostic indicators
.
Detailed medical history, meticulous physical examination and standardized neuroelectrophysiological examination play a key role in early diagnosis, and other auxiliary examinations such as imaging have certain value
in differential diagnosis.
In the process of clinical diagnosis, determining the extent of upper and lower motor neuron involvement is a key step in diagnosis, and according to the anatomical location of the patient's symptoms and signs, the affected area is usually divided into four regions
: brainstem, neck, thoracic and lumbosacral segment.

1 Clinical examination

The diagnosis of ALS is based on a detailed history and physical examination, looking for evidence of co-involvement of
upper and lower motor neurons in the four regions of the brainstem, cervix, thoracic segment, and lumbosacral segment.
Depending on the situation, appropriate ancillary tests may be selected to rule out other diseases, such as neuroelectrophysiology, imaging, and laboratory tests
.
For ALS diagnosed early in the onset, especially when the clinical presentation is atypical or the progression course is unclear, follow-up should be performed regularly (3 months) to reassess the diagnosis
.

1 Medical history

The main evidence of progressive disease progression should be followed by the time course
of symptom progression, exacerbation, and expansion from one area to another, starting at the site of initial weakness.
Pay attention to inquire about swallowing, respiratory function, and whether there is any sensory impairment, urine and stool disorders, etc.

2 Physical examination

The presence of both upper and lower motor neuron involvement in the same area is the key point
in diagnosing ALS.
(1) Signs of lower motor neuron involvement mainly include muscle weakness, atrophy and fasciculation
.
The tongue, face, throat, neck, limbs, back, and thoracic abdomen muscles
are usually examined.
(2) Signs of upper motor neuron involvement mainly include increased muscle tone, hyperreflexia of tendons, clonic, positive pathological signs, etc
.
The sucking reflex, gag reflex, chin reflex, palmochin reflex, limb tendon reflex, muscle tone, Hoffmann sign, lower extremity pathology, abdominal wall reflex, and pseudobulbar palsy such as crying and laughter are usually examined
.
(3) Clinical physical examination is the main method
to detect upper motor neuron involvement.
In areas where pronounced muscle atrophy weakness appears, if the tendon reflexes are not low or active, even if there are no pathological signs.
May also indicate damage
to the cone Cambodia.
(4) Follow-up of patients and dynamic observation of changes in signs can also reflect the progressive development process
of the disease.

3 Whether there are other medical conditions

When some manifestations that cannot be explained by ALS are found in the medical history and physical examination, such as stability or improvement during the course of the disease, numbness and pain in the limbs, etc.
, the diagnosis of ALS should be cautious and pay attention to whether there are other diseases
.

2 Neuroelectrophysiological examination

When ALS is considered clinically, neuroelectrophysiologic testing is indicated to confirm that the clinically affected area is lower motor neuron pathology, and to find lower motor neuron pathology present in clinically unaffected areas and to exclude other conditions
.
Neuroelectrophysiologic examination can be seen as an extension of the clinical physical examination and should be completed by a professional electromyography physician and technologist and judged according to clear criteria
.

1 Nerve conduction assay

Nerve conduction assays are primarily used to diagnose or rule out peripheral nerve disease
.
Motor and sensory nerve conduction assays should include at least 2 nerves
in the upper and lower extremities.

(1) Motor nerve conduction determination: the distal motor latency and nerve conduction velocity are usually normal, and there is no motor nerve partial block or abnormal waveform discreteness
.
With the development of the disease, the amplitude of the action potential of the compound muscle can be significantly reduced, and the conduction speed can also be slightly slowed down
.

(2) Sensory nerve conduction measurement: generally normal
.
Sensory nerve conduction can be abnormal
when impaction perineuropathy is present or other peripheral neuropathy is present.

(3) F-wave assay: usually normal
.
When the muscles are significantly atrophied, the corresponding nerve can see a decrease in the occurrence rate of F waves, while the conduction speed is relatively normal
.

2 Electromyography of the cocentric needle

Lower motor neuron lesions are mainly determined by cocentric needle electromyography, which can confirm the manifestations
of progressive and chronic nerve loss.
When EMG shows the presence of lower motor neuron involvement in a certain area, its diagnostic value is the same as the
value of clinical findings of muscle weakness and atrophy.

(1) Progressive nerve loss manifestations: mainly including fibrillation potential and positive sharp wave
.
When the measured muscles are simultaneously present with chronic nerve loss, the bundle fibrillation potential is of equal clinical significance
as the fibrillation potential and positive sharp wave.

(2) Manifestations of chronic nerve loss: (1) The time limit of the motor potential widens and the amplitude increases, usually accompanied by an increase in polyphasic waves; (2) When the force is contracted, the movement recruitment decreases, the amplitude increases, and in severe cases, it is simple phase; (3) Most ALS can be seen to emit unstable and complex waveform motion potentials
.

(3) When the electromyography of the same muscle shows the coexistence of progressive nerve loss and chronic nerve loss, it has a stronger support value
for the diagnosis of ALS.
In some muscles, there may be only chronic anoneropathy without fibrillation potentials or sharp waves
.
If there are no progressive manifestations of nerve loss in all measured muscles, the diagnosis of ALS requires caution
.

(4) Detection range of electromyography in the diagnosis of ALS: electromyography should be performed
in all 4 areas.
The brainstem region can optionally measure a muscle, such as the sternocleidomastoid muscle, tongue muscle, facial muscle, or masseter muscle
.
The thoracic segment can be measured
by paraspinal muscles or rectus abdominis muscles below the level of thoracic 6.
In the cervical and lumbosacral segments, at least 2 muscles
innervated by different nerve roots and different peripheral nerves should be measured.

(5) In the early stage of ALS disease, EMG examination can only occur 1 or 2 areas of lower motor neuron damage, at this time, for patients with clinical suspicion of ALs, follow-up review is required at intervals of 3 months
.

(6) When there is motor neurogenic damage in 3 or more regions on electromyography, not all of them are ALS
.
Electrophysiologic findings should be closely analyzed clinically to avoid interpretation
of EMG results in isolation.

3 motion evoked potentials

Helpful in detecting upper motor neuron lesions under ALS clinically, but not highly
sensitive.

3 Neuroimaging

4 Diagnostic criteria for AIS

1 Basic conditions for ALS diagnosis

(1) Progressive development of the disease: through medical history, physical examination or electrophysiological examination, it is confirmed that clinical symptoms or signs are progressively developing in one area, or from one region to other areas
.

(2) Clinical, neuroelectrophysiological or pathological examination confirmed evidence of
lower motor neuron involvement.

(3) Clinical physical examination confirmed evidence of
upper motor neuron involvement.

(4) Exclude other diseases
.

2 Diagnostic grading of AIS

(1) Clinically confirmed ALS: through clinical or neuroelectrophysiological examination, it is confirmed that there is evidence of simultaneous involvement of upper and lower motor neurons in at least 3 of
the 4 regions.

(2) Clinical probable ALS: through clinical or neuroelectrophysiological examination, it is confirmed that there is evidence
of simultaneous involvement of upper and lower motor neurons in at least 2 of the 4 regions.

(3) Clinical possible ALS: through clinical or neuroelectrophysiological examination, it is confirmed that there is evidence of simultaneous involvement of upper and lower motor neurons in only 1 area, or only evidence of
upper motor neuron involvement in 2 or more regions.
Imaging and laboratory tests have been performed to rule out other conditions
.

5 Differential diagnosis

In the diagnosis of ALS, according to the different signs and symptoms, it is necessary to distinguish from a variety of diseases, common are cervical spondylosis, lumbar spondylosis, multifocal motor neuropathy, Hirayama disease, spinal muscular atrophy, Kennedy disease, hereditary spastic paraplegia, paraneoplastic syndrome, etc
.

Treatment of 6ALS

Although ALS is still an incurable disease
.
But there are many ways to improve the quality of life of patients, and should be diagnosed early and treated
early.
Maximize survival
.
In addition to the use of drugs to delay the progression of the disease, the treatment also includes comprehensive treatment
such as nutritional management, respiratory support and psychotherapy.

1 Drugs that delay the progression of the disease

(1) riluzole: chemical name is 2-amino-6 (trifluoromethoxy)-benzothiazole, its mechanism of action includes stabilizing the inactivation of voltage-gated sodium channels, inhibiting presynaptic glutamate release, activating postsynaptic glutamate receptors to promote glutamate uptake
.
A clinical study conducted in France in 1994 first reported that the drug could slow the progression of
ALS.
In 1996, the US Food and Drug Administration approved rilutek for the treatment of ALS, which is currently the only drug that has been confirmed by a number of clinical studies to delay the development of the disease to a certain extent, with a dosage of 50mg orally twice a day
.
Common adverse reactions are fatigue and nausea, and individual patients may have elevated alanine aminotransferase, requiring attention to monitoring liver function
.
It is not recommended to continue taking
it when patients with advanced stages of the disease are already using an invasive ventilator to assist breathing.

(2) Other drugs: In animal experiments, although there are multiple drugs that have shown certain efficacy in the treatment of ALS animal models, such as creatine, high-dose vitamin E, coenzyme Q10, lithium carbonate, ciliary neurotrophic factor, insulin-like growth flash, lamotrigine, etc.
, they have not been proven effective
in clinical studies on ALS patients.

2 Nutrition management

(1) When you can eat normally, you should adopt a balanced diet, and when you have difficulty swallowing, you should adopt a high-protein, high-calorie diet to ensure nutritional intake
.

(2) For patients with difficulty chewing and swallowing, they should change their diet, eat soft food, semi-liquid food, and eat small and frequent meals
.
For people with limb or neck weakness, the eating position and utensils
can be adjusted.

(3) When patients have obvious difficulty swallowing, weight loss, dehydration or the risk of choking and 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 soon as possible before the forced vital capacity (FVC) falls to 50% of the expected value, otherwise it needs to be assessed for anesthesia risk and supported by a ventilator
.
For those who refuse or are unable to take PEG, a nasogastric tube 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 of patients, and use bi-level positive airway pressure (BiPAP)
as soon as possible 。 Indications for initiation of noninvasive ventilation include orthopnea, or forceful inspiratory nasal pressure (SNP) < 40 cm H2O (1 cmH2O = 0.
098 kPa), or maximal inspiratory pressure (MIP) < 60 cm H2O, or a decrease in nocturnal oxygen saturation, or a 70% FVC <
.

(3) When the patient coughs weakly (the peak of cough expiratory airflow is less than 270L/min), a sputum suction device or artificial assisted cough should be used to exclude respiratory secretions
.
(4) When ALS progresses, non-invasive ventilation cannot maintain blood oxygen saturation > 90%, carbon dioxide partial pressure < 50mmHg (1mmHg = 0.
133kPa), or excessive secretions cannot be discharged, an invasive ventilator can be selected to assist breathing
.
After using an invasive ventilator to assist breathing, weaning
is often difficult.

4 Comprehensive treatment

At different stages of the ALS course, patients face different problems, such as depression and anxiety, insomnia, salivation, dysarthria, difficulty communicating, limb spasms, pain, etc.
, and should be given targeted guidance and treatment
according to the specific situation of patients.
Selection of appropriate medications and auxiliary facilities, improvement of quality of life, strengthening of care, prevention of various complications
.