Many patients ask questions about motor neuron disease (MND). For patients, the main concern is whether or not the disease is MND, i.e. the diagnosis of MND. For many diseases, the diagnosis can be confirmed based on certain tests. For example, in Kennedy’s disease, a genetic test can confirm or exclude the diagnosis. However, the diagnosis of MND is not as simple as this. Instead of relying on a specific test, the diagnosis of MND can only be made by combining the medical history, physical examination and the results of ancillary tests, and by excluding other diseases. Due to the complexity of its diagnosis, many patients often take many detours before they are finally diagnosed, delaying the most valuable time for treatment, and some patients are misdiagnosed as having MND and suffer unnecessary mental and financial burdens. In a broad sense, MND includes “amyotrophic lateral sclerosis” (ALS), “primary lateral sclerosis” (PLS), “progressive muscular dystrophy” (PMA), and “progressive myelopathy” (PMA). “progressive medullary paralysis” (PBP), and other types. However, on the one hand, ALS accounts for the majority of MND; on the other hand, many patients with early diagnosis of PLS, PMA, and PBP eventually derive from ALS as their disease progresses, so ALS also represents MND in a narrow sense. here we mainly introduce the diagnosis of ALS. The name “amyotrophic lateral sclerosis” indicates that amyotrophy is the main feature of the disease, and most patients have significant muscle atrophy and weakness. Since these symptoms only occur when the “lower motor neurons” of the brainstem and spinal cord are damaged, we refer to them collectively as “lower motor neuron” damage. In most patients, muscular atrophy begins in one hand and progresses to the proximal upper extremity, lower extremity, contralateral extremity, tongue muscles, and throat muscles. In some cases, the disease starts in the lower extremities or in the tongue or throat muscles, and generally progresses more rapidly in the throat. There is a specific type of ALS that is more symmetrical with bilateral proximal involvement of the upper extremities, known as “linked arm syndrome”, which is more common in men. In addition to the clinical symptoms, a helpful ancillary test to determine the damage to the “lower motor neurons” is the electromyogram. Because the body has a strong compensatory capacity, when muscle atrophy occurs, the damage to the “motor neurons” is often more than 30-50%, and electromyography can detect “lower motor neuron” damage before the appearance of muscle atrophy, so it is very important for early diagnosis. It is therefore very important for early diagnosis. Another important role of EMG is to differentiate it from other diseases that can also cause myasthenia such as “cervical spondylosis”, “peripheral neuropathy” and “muscular disease”. Lateral sclerosis” is a pathological change that refers to the lesion of the “lateral cord” of the spinal cord. The so-called “lateral cord” reflects damage to the “pyramidal tract”. In a broader sense, ALS patients are affected by both the motor cortex and the pyramidal tracts, which are all part of the “upper motor neurons” and are collectively referred to as “upper motor neuron” damage. Upper motor neuron damage is mainly based on clinical examination. Active tendon reflexes and pathological reflexes in the limbs are indicative of upper motor neuron damage. To diagnose ALS, both “lower motor neuron” and “upper motor neuron” damage must be present, and on this basis, there must be no sensory system involvement, no urinary or bowel dysfunction, no extrapyramidal or cerebellar (responsible for balance and coordination) involvement, no The first step in the diagnosis is to consider the possibility of motor neuron disease. The second step is to grade the diagnosis. Usually, we divide the involvement into four segments: ball, neck, thorax and lumbar, which represent the “tongue and throat area”, “upper extremity”, “respiratory muscles and trunk area” and “lower extremity”, respectively. “Lower extremities”. If three of the four segments showed both upper and lower motor neuron damage, the patient was considered to have “confirmed ALS”; if two segments showed both upper and lower motor neuron damage, the patient was considered to have “proposed ALS”; if one segment showed both upper and lower motor neuron damage, the patient was considered to have “probable ALS”. If there is damage to both upper and lower motor neurons in one segment, then it is “probable ALS”. The third step is to differentiate the disease from other diseases with similar clinical manifestations, including cervical spondylosis, spinal cord disease, peripheral neuropathy, muscle disease, and Kennedy’s disease. For cervical spondylosis, the key point of differentiation is that cervical spondylosis is usually associated with sensory abnormalities, while ALS is not; cervical spondylosis does not cause involvement of the tongue and throat muscles, while ALS does. For spinal cord disease, the difference is that spinal cord disease is usually associated with urinary and fecal dysfunction, whereas ALS is not. For peripheral neuropathies, myelopathies, and Kennedy’s disease, the key differentiation is that these diseases do not have upper motor neuron damage, whereas ALS does. The fourth step is to rule out “pseudo-motor neuron disease”. Clinically, some endocrine diseases, autoimmune diseases or malignant tumors can show symptoms very similar to ALS, and these symptoms may even appear before the primary disease, which is called “pseudomotor neuron disease”. A series of tests (thyroid function, autoimmune function and tumor indicators, etc.), lung CT (except for small cell lung cancer, which is the most likely cause of “pseudo-ALS”), ultrasound, etc. After these four steps, the diagnosis is basically confirmed, and the patient is then classified: those with no family history of ALS are classified as “disseminated ALS (SALS)”; those with family history are classified as “familial ALS (FALS)”. Many patients are concerned about whether ALS is hereditary. FALS is not a single gene disease, there are more than 10 genes related to ALS, the most important ones are SOD1 and TDP43, but the latter is less common in Chinese. With the development of genetic testing technology, instead of screening each gene individually, a single so-called “gene package” can be used to identify which gene is abnormal for FALS patients. In summary, the diagnosis of ALS can only be made by a combination of history, physical examination, ancillary tests, and the experience of the physician to exclude other diseases. Although no single test can confirm the diagnosis, electromyography is still very crucial for localizing the diagnosis and differential diagnosis, and can be considered the most important ancillary test. It is important to note that unlike other tests such as MRI, EMG requires good skills and experience of the operator, and only a few tertiary hospitals that specialize mainly in neuromuscular diseases have this capability. In conclusion, it is important to see an experienced neurologist at a regular hospital in order to get an accurate diagnosis as soon as possible.