Atrophic lateral sclerosis

Introduction to atrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) has exactly the same meaning as motoneuron disease in the early stage, especially an independent disease of the first lower motor neuron damage, followed by upper motor neuron damage. However, it was later discovered that there are two other variations, that is, only the upper motor neurons or the lower motor neurons are always involved in the course of the disease. The former is called primary lateral sclerosis, and the latter is called spinal muscular atrophy. The literature still uses motor neuron disease to specifically refer to amyotrophic lateral sclerosis. Most scholars are accustomed to different types of motor neuron involvement, including motor atrophic lateral sclerosis, primary lateral sclerosis, and spinal muscular atrophy. Recent studies suggest that the muscle atrophy side Sclerotherapy has a common pathological basis with a variety of related diseases, including primary lateral sclerosis, ALS-dementia, ALS-related frontal lobe dementia, progressive spinal muscular atrophy, multiple system atrophy, and lewy small body disease. Pathological examination revealed that these diseases also contained ubiquitin-positive inclusion bodies and transparent mass inclusion bodies, but various clinical combinations appeared only when different anatomical sites were damaged. basic knowledge The proportion of illness: 0.0025% Susceptible people: no special people Mode of infection: non-infectious Complications: dementia, muscle atrophy, paraplegia, malnutrition

Causes of atrophic lateral sclerosis

(1) Causes of the disease

The etiology of sporadic ALS is still unknown, and familial ALS is mostly autosomal dominant.

(two) pathogenesis

The exact pathogenesis is still unclear. Recent studies have focused on the theory of copper-zinc superoxide dismutase gene mutation, excitatory amino acid toxicity theory, autoimmune theory and neurotrophic factor theory.

1. Copper-zinc superoxide dismutase gene mutation theory

Studies have shown that 20% of familial ALS have SODI (Cu/Zn superoxide dismutase) gene mutation, which is located in human chromosome 21q22.1, and its mutation can cause loss of SOD1 activity, which weakens the detoxification effect of superoxide. Excessive accumulation of free radicals, cell damage, and some sporadic ALS may also have mutations at the 2lq22 site.

2. Excitatory amino acid toxicity theory

Excitatory amino acids include glutamic acid, aspartic acid and its derivative kainate (KA), making quisqualic acid (QA), amanitalin (IA) and N-methyl d-aspartate (NMDA), the excitotoxicity of excitatory amino acids may be involved in the pathogenesis of LIS. The combination of glutamate and NMDA receptors can cause calcium influx, activate a series of proteases and protein kinases, and increase protein breakdown and free radical production. The peroxidation process is strengthened, the neurons dissolve themselves, and excess calcium can activate endonuclease to cleave DNA and disintegrate. The pathological changes of ALS are mainly related to the glutamate uptake system. The uptake system is located in the cell membrane of glial cells and nerve cells, and can rapidly transport the glutamate in the synaptic cleft space into the cell, terminating its effects, and discovering the cortical motor cells of ALS, the valley of spinal cord glial cells and spinal cord gray matter cells. Reduced amino acid uptake system, animal studies have also shown that intrathecal injection of KA and NMDA in mice can cause spinal cord neuron degeneration.

3. Autoimmune theory

The increase in anti-neuronal antibodies in cerebrospinal fluid and serum in patients with ALS suggests that the pathogenesis may be related to autoimmunity. For example, L-type voltage-dependent calcium channel antibodies present in the serum of ALS patients can bind to the channel protein and change their electrophysiological properties. Causes neuronal damage.

4. Pathological changes

Microscopic observation showed that the anterior horn cells of the spinal cord were reduced, accompanied by glial cell proliferation, residual anterior horn cells atrophy, stratified structure of cerebral cortex was intact, pyramidal cells were reduced with glial cell proliferation, and spinal cord pyramidal bundles were demyelinated. The motor cortical neuron cells are intact, indicating that the initial changes originate from the distal end of the axons, gradually retrograde and involve the pyramidal cells in the anterior cerebral gyrus. This change is also called retrograde death. Neuronal signs of ALS patients, post-mortem autopsy showed significant corticospinal demyelination changes, indicating that the anterior horn cells function severely, masking the signs of upper motor neuron damage, and some clinical manifestations of typical ALS, its pathology The changes are similar to multisystem degeneration, ie extensive spinal cord structural damage, anterior horn of the spinal cord, pyramidal tract, spinal dorsal cerebral pedicle, intermuscular region of the posterior cord of the spinal cord, Clarke nucleus and hypothalamus, cerebellar dentate nucleus and red nucleus Both neuronal cell loss and glial cell proliferation (Terao, 1991).

Abnormal ubiquitin-positive inclusion bodies can be found in nerve cells at different parts of the central nervous system using immunohistochemical staining (Arima, 1998, Kinoshita et al, 1997, Zhang Wei, 2001).

These inclusion bodies include the following types:

(1) The wire-like inclusion body, under the electron microscope, the inclusion body is a strip or a tube, usually with a central bright area for acidophilic or two-staining, surrounded by a light-stained halo area, which is not easily seen in HE staining.

(2) Transparent inclusion body, which is a granular filament inclusion body, the filament diameter is 15-20 nm, the granular material is mixed with the filament to form a small pompon-like dense structure, and the periphery often has lysosomal-like bodies and fats. A membrane structure such as brown pigment is surrounded.

(3) Louis body-like inclusion body, which is a circular inclusion body composed of irregular line-like structure and ribosome-like particles. The center is an amorphous substance or a particle-like electron dense substance. These substances are embedded in 18nm filaments. The arrangement is tight or loose, and the outer circumference has a densely dyed ring, similar to the Louise body.

(4) Bunina corpuscle is a more specific pathological change of ALS. These inclusion bodies are mainly distributed in the anterior horn cells of the spinal cord and brainstem motor nuclear nerve cells, and may also occur in hippocampal granulosa cells of some patients with motor neuron disease. And pyramidal cells, dentate gyrus, olfactory cortex, amygdala, Onuf nucleus, small frontal nucleus and large pyramidal cytoplasm (Arima, 1998, Kinoshita et al, 1997).

Atrophic lateral sclerosis prevention

There is no effective prevention method, symptomatic treatment, and strengthening clinical medical care, which is an important part of improving the quality of life of patients.

Atrophic lateral sclerosis complications Complications, dementia, muscle atrophy, paraplegia, malnutrition

Dementia, difficulty breathing, muscle atrophy, paraplegia, malnutrition, increased muscle tone.

Symptoms of atrophic lateral sclerosis Common symptoms Dysphagia, muscle atrophy, spinal muscular atrophy, pseudobulbar, paralysis, paralysis, dementia, weakness, weight loss, reflex

1. The onset is hidden and slowly progresses.

2. The first symptom of half of the patients was limb weakness with muscle atrophy (5%) and fasciculation (4%). The distal extremity was particularly prominent. At this time, the quadriplegia was reduced, no pyramidal tract sign, and the clinical manifestation was similar to spinal cord. Muscle atrophy.

3. With the development of the disease, the patient gradually showed typical signs of upper and lower motor neuron damage, which showed extensive and severe muscle atrophy, increased muscle tone, positive pyramidal tract sign, and 60% of patients had obvious upper and lower motor neurons. Signs, when the motor neuron degeneration reaches a certain level, the muscles are extensively denervated. At this time, there is no fasciculation, the sputum reflex is reduced or disappeared, and there is no pathological sign.

4. About 10% of patients showed only progressive muscle atrophy throughout the course of the disease without signs of motor neuron damage.

5. About 30% of patients have onset of motor nucleus of the brainstem, which is characterized by difficulty in swallowing, unclear articulation, difficulty in breathing, atrophy of the tongue muscles and fibrillation. Later, the limbs and trunk are gradually involved, and the mood is unstable (strong Crying and laughing) is a sign of upper motor neuron involvement and pseudobulbaric paralysis.

6. Amyotrophic lateral sclerosis with spinal cord lateral cord involvement as the first symptom is rare, 9% of patients may have painful spasm, the latter is a manifestation of upper motor neuron damage, mostly in the proximal end of the affected lower limb, common in In the early stages of the disease, 10% of patients have subjective distal paresthesia or numbness, unless there is no other peripheral neuropathy, ALS has no objective sensory signs, bladder and rectal function remains good throughout the course of the disease, and eye movement is usually not impaired.

7. Patients with simple ALS generally do not have mental retardation. When ALS is associated with symptoms and signs of other neurodegenerative diseases, it is called ALS-plus syndrome. This syndrome occurs mainly in the western Pacific, Guam, Japan. In areas such as North Africa, the combined symptoms and signs include extrapyramidal symptoms, cerebellar degeneration, dementia, autonomic and sensory system symptoms, and abnormal eye movements.

8. Neuromuscular electrophysiological changes

Mainly manifested as extensive neurogenic damage, acute neurogenic damage (2 to 3 weeks after denervation) characterized by fibrillation potential, positive sharp wave, tremor potential and giant potential, chronic denervation with regenerative performance For the light contraction of the muscles, the action potential time limit is widened, the amplitude is obviously increased, and the percentage of multiphase waves is increased. When the muscles are vigorously contracted, the movement unit is lost. The neurogenic damage of ALS usually involves more than 3 regions (brain Nerve, neck, chest, lumbosacral nerve innervation area), tongue muscle, sternocleidomastoid and diaphragm muscle can also be manifested as neurogenic damage, the latter because of less involvement in cervical spondylosis, it can be used for both Identification (Kant, 1994), MCV can be slightly slowed down, the evoked potential amplitude decreases, and the sensory conduction velocity is normal.

Magnetic Stimulation Motor Evoked Potential: Transcranial stimulation of cerebral cortical motor neurons and recording of action potentials in the corresponding muscles. This method can measure the central motor conduction time and is of great value in determining the damage of the corticospinal tract.

Muscle biopsy is not necessary for the diagnosis of ALS, but in some cases helps to identify neurogenic muscle atrophy.

In 1994, the World Federation of Neurology proposed a screening diagnostic criteria for ALS for large-scale ALS clinical treatment research, which is not practical for clinical practice.

Atrophic lateral sclerosis examination

Blood test

Blood routine, serum immunology and blood biochemical tests are helpful for differential diagnosis.

2. Cerebrospinal fluid examination

CSF pressure is normal, the number of cells is normal or slightly increased, the protein is slightly increased, and anti-neuron antibodies in the cerebrospinal fluid and serum of patients can be increased.

3. Neuromuscular electrophysiological examination

It manifests itself in a wide range of neurogenic damage.

Acute neurogenic damage (2 to 3 weeks after denervation) is characterized by fibrillation potential, positive sharp wave, tremor potential and giant potential. When chronic denervation is accompanied by regeneration, it is manifested as motor unit action potential during muscle contraction. The time limit is widened, the amplitude is obviously increased, and the percentage of multiphase waves is increased. When the muscles are vigorously contracted, the movement unit is lost.

4. Magnetic stimulation motor evoked potential

The measurement of central motor conduction time is of great value in determining the damage of the corticospinal tract.

5. Muscle biopsy

Helps identify neurogenic muscle atrophy.

Diagnosis and differentiation of atrophic lateral sclerosis

Diagnostic criteria

In 1998, Rowland revised on this basis and proposed the following diagnostic criteria:

1. Conditions that ALS must have

(1) Onset after 20 years of age.

(2) Progressive, no obvious remission period and platform period.

(3) All patients have muscle atrophy and muscle weakness, and most have tremor.

(4) Electromyography shows extensive denervation.

2. Support conditions for spinal muscular atrophy (SMA)

(1) The above-mentioned lower motor neuron signs.

(2) The sputum reflection disappears.

(3) No Hoffmann and Babinski sign.

(4) The nerve conduction velocity is normal.

3. Support ALS conditions

(1) The lower motor neuron signs supporting the diagnosis of spinal muscular atrophy.

(2) There must be a Hoffmann or Babinski sign positive or knee, shocked.

(3) There may be pseudobulbaric paralysis and emotional instability or emotional lability.

(4) Mostly thin body type.

4. ALS with suspected upper motor neurone signs (ie ALS-PUMNS)

(1) The above-mentioned lower motor neurons are affected by signs.

(2) The limbs have muscle weakness and muscle atrophy but the tendon reflex remains and there is muscle twitching.

(3) No Hoffmann or Babinski sign or knee, shocked.

5. Diagnostic criteria for primary lateral sclerosis

(1) Necessary conditions:

1 adult onset;

2 History of remission without a history of stroke or support for multiple sclerosis;

There is no similar medical history in the 3 family;

4 paraplegia;

5 lower extremity spasm hyperreflexia;

6Babinski sign positive or shocked;

7 no localized muscle weakness, muscle atrophy and limb or tongue muscle tremor;

8 no persistent paresthesia or a certain lack of sense;

9 no dementia;

10 EMG evidence of no denervation.

(2) Conditions for compliance and support for diagnosis:

1 pseudobulbaric palsy (dysphagia, dysarthria);

2 upper motor neuron signs of the upper limbs (hand movement is not flexible, rotation action is slow and awkward, arms are reflected, active, Hoffmann sign positive);

3 spastic bladder symptoms;

4MRI showed motor cortical atrophy and cortical spinal cord high signal;

5 magnetic resonance spectroscope has evidence of cortical acetyl aspartate loss;

6 motor cortical magnetic stimulation showed central motor conduction damage.

(3) Diagnosis of primary lateral sclerosis should also be noted to exclude the following diseases:

1MRI excludes multiple sclerosis, hindbrain malformation, optic occipital macroporous compression, cervical spondylotic myelopathy, syringomyelia and multiple cerebral infarction;

2 blood test to exclude vitamin Bl2 deficiency, HTLV-1 (human T lymphocyte leukemia virus), very long chain fatty acids (excluding adrenal white matter dystrophy), Lyme antibody, syphilis serum test, immunoelectrophoresis (excluding paraproteinemia);

3 cerebrospinal fluid examination to exclude multiple sclerosis, HTLV-1 infection and neurosyphilis.

The clinical diagnosis of primary lateral sclerosis is a definitive diagnosis, and the diagnosis depends on autopsy.

Differential diagnosis

The differential diagnosis of ALS is complicated. According to Belsh and Schiffman, 27% of the disease is misdiagnosed as other diseases in the early stage, and 10% of cases in the National ALS Registry in Ireland are misdiagnosed.

The diagnosis of ALS in the middle and late stages is not difficult, but it needs to be identified in the early stages of the disease.

Cervical spondylosis spinal cord

Cervical spondylotic myelopathy can be manifested as hand muscle weakness and atrophy with lower extremity paralysis, and cervical spondylosis and ALS are good in middle-aged people, the two are easily confused, the compression spinal cord damage caused by cervical spondylosis rarely exceeds C4 Therefore, electromyography of the lingual and sternocleidomastoid muscles revealed that denervation strongly suggests ALS, and extensive fasciculation of more than one nerve root distribution region also supports the diagnosis of ALS. MRI can show the spinal cord in cervical spondylotic myelopathy. Under pressure, but this imaging change can not rule out ALS. On the one hand, although some patients have evidence of cervical spinal cord compression, they do not necessarily lead to symptoms and signs of spinal cord injury. On the other hand, cervical spondylosis can be Concurrent with ALS.

2. Inclusion body myositis (IBM)

It is the most easily confusing disease with ALS after cervical spondylotic myelopathy. Brannagan (1999) reviewed 20 cases of IBM, half of which were misdiagnosed as ALS or peripheral neuropathy in the early stage. The common symptom of both is the muscle atrophy of the hand muscle or the extremities. The sputum reflex disappeared without sensory disturbance and paresthesia (except for IBM with peripheral neuropathy).

IBM patients' flexor weakness is usually more obvious, but the flexor weakness is only when the ALS is significantly affected by other hand muscles in the late stage, and the first interosseous muscle is not atrophy. IBM often has obvious quadriceps atrophy. Difficulties in standing and standing up, but no signs of tremor and upper motor neuron damage, muscle biopsy in IBM patients can be seen in the identification of rims and inflammatory infiltration.

3. Multifocal motor neuropathy

Is a peripheral neuropathy, because it has obvious muscle weakness and muscle atrophy with fasciculation, while tendon reflexes are normal or hyperthyroidism, easily confused with ALS or SMA, neurophysiological examination found motor block, motor nerve biopsy found off Myelin changes and IVIG experimental treatment effectively support multifocal motor neuropathy. Magnetic resonance spectroscopy with cortical acetyl aspartate loss and motor cortical magnetic stimulation found central motor conduction disorder suggesting ALS.

4.Kennedy-Alter-Song syndrome

Common with ALS is that both have symptoms and signs of motor neuron damage. Kennedy-Alter-Song syndrome has the following characteristics to identify with ALS: 1X linkage genetic pattern; 2 posture tremor with breast Swollen; 3 symptoms and signs of no upper motor neurons; 4 proximal muscle weakness, facial muscles and swallowing muscles are easily affected, pouting action can induce chin twitching; 5 sometimes accompanied by skin paresthesia and Loss of sensation; 6 loss of sensory potential activity in the sural nerve; 7 gene analysis has a triple increase in trinucleotide (CAG).

5. Aminohexosidase deficiency

Also known as GM2 ganglioside accumulation disease or Tay-Sach disease, the signs of upper and lower motor neuron damage are easily confused with ALS, the difference is that the former is mostly children or adolescents with onset, slow progress, cerebellar signs, some Patients may be associated with depressive psychosis and dementia.

6. Benign muscle tremor

The cause is unknown. It is characterized by extensive tremor without muscle weakness, abnormal muscle atrophy and tendon reflex. Normal people are prone to fatigue, cold, anxiety, strenuous exercise, smoking and drinking coffee. EMG has spontaneous electrical activity, but no The shape of the motor unit changes. In a few cases, tremor can be the first symptom of ALS, which should be noticed. The fasciculation is highly suggestive of peri-nuclear lesions of motor neurons. In addition to multifocal motor neuropathy and starch peripheral neuropathy, other peripheral neuropathy Rarely, patients with myopathy should be alert to the possibility of merging with peripheral neuropathy.

7. Pingshan disease

Also known as monomelic spinal muscular atrophy or distal muscle atrophy of the upper extremity, characterized by onset of 20 years old, clinical manifestations of muscle atrophy, muscle weakness, fasciculation and convulsions, symptoms progress for about 1 year Stop, MRI can be normal or see spinal cord atrophy, some patients early manifested as Pingshan disease, and later developed into ALS.

8. Myasthenia gravis

The affected part of the throat must be differentiated from ALS with medullary paralysis as the first symptom. The former has typical muscle weakness and morbid fatigue. It improves after rest, the neostigmine test is positive, the EMG is normal, the repetitive stimulation test is positive, and some ALS Patients with Neostigler's posterior muscle weakness symptoms also have a certain degree of improvement, should pay attention to the identification of myasthenia gravis.

9. Postpolio syndrome

It refers to the progressive progression of myasthenia gravis and muscle atrophy in patients with spastic polio after 20 to 25 years of illness. It is more common in the most severe part of muscular sequelae, occasionally involving other unaffected muscle groups, slow progress, no upper movement. Signs of neurons and almost no life can be identified with ALS.

10. Hyperthyroidism combined with ALS symptom group

Nearly 20 cases have been reported in foreign countries. Patients with hyperthyroidism can be combined with simple lower motor neurons, signs of motor neuron signs and upper and lower motor neuron damage, and 84% of patients have improved ALS symptoms after antithyroid treatment. The exact mechanism of these reversible ALS symptoms in patients with hyperthyroidism is unclear, but it is certainly neurological involvement, not thyroid myopathy.

11. Paraneoplastic ALS

Although many studies have shown that the incidence of tumors in ALS patients does not increase compared with normal people, some ALS patients with tumors can completely disappear after the tumor resection, and the symptoms and signs of ALS can disappear completely, indicating that the two have pathological mechanisms. Certainly, the relationship between lymphoma and ALS seems to be more closely related. Although lymphoma combined with simple motor neuron damage may be associated with motor peripheral neuropathy, foreign scholars report 61 cases of ALS with lymphoma, more than half of which combined with exercise. Neuronal signs, and in autopsy cases, more than half of the corticospinal tracts are seen, and a small number (less than 10%) of patients with ALS can be relieved after immunosuppressive therapy.

12. Multisystem degeneration of the central nervous system

Clinically typical ALS symptoms can be combined with dementia, Parkinson's symptom group and cerebellar signs, etc., known as ALS superposition syndrome, which should be associated with multiple system atrophy, CJD, Alzheimer's disease, Huntington's disease and Machado-Joseph disease. Identification.

13. Other myelopathy

Subacute combined degeneration, human T lymphocytic leukemia virus-associated myelopathy (HAM), Lyme disease, syphilis and multiple sclerosis can sometimes also cause ALS-like symptoms.

14. Toxic peripheral neuropathy

Toxic peripheral neuropathy caused by lead, mercury, organophosphorus and organochlorine pesticides can sometimes appear clinically similar to ALS and should be identified.

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