Amyotrophic lateral sclerosis is a neurodegenerative disease that is accompanied by the death of central and peripheral motor neurons. The main manifestations of the disease are skeletal muscle atrophy, fasciculations, spasticity, hyperreflexia, pathological pyramidal signs in the absence of pelvic and oculomotor disorders. It is characterized by a steadily progressive course, leading to a fatal outcome. Amyotrophic lateral sclerosis is diagnosed on the basis of neurological status, ENG, EMG, MRI of the spine and brain, analysis of cerebrospinal fluid and genetic studies. Unfortunately, to date, medicine does not have an effective pathogenetic therapy for ALS.
G12.2 Motor neuron disease
The concept of “amyotrophic lateral sclerosis” also corresponds to: motor neuron disease, familial motor neuron disease, progressive muscular atrophy, progressive bulbar paralysis. The incidence of amyotrophic lateral sclerosis is 1.5-5 cases per 100,000 population. According to various statistics, ALS is 1.5-3 times more common in men. The average age of the manifestation is 40-60 years. In 5-10% of cases, the disease has a family character.
Amyotrophic lateral sclerosis is the “final path” of a cascade of general pathological reactions initiated by various known or unknown triggers. In some cases, amyotrophic lateral sclerosis may be caused by mutations in the superoxide dimutase-1 gene, when the main pathogenetic factor is the cytotoxic effect of a defective enzyme. Mutant superoxide dismutase-1 accumulates between the layers of the mitochondrial membrane, disrupting axonal transport; interacts with other proteins, which leads to disruption of their degradation.
The occurrence of sporadic cases of amyotrophic lateral sclerosis is facilitated by unknown triggers, which, like mutant superoxide dismutase-1, are capable of realizing their effects under conditions of increased functional load on motor neurons, which causes their selective vulnerability.
To date, the exact pathogenetic mechanisms of amyotrophic lateral sclerosis are unknown. There are several theories: the theory of disturbances in the transport of excitatory amino acids (glutamate and aspartate) in the motor areas of the central nervous system; the theory of the formation of autoantibodies to various types of Ca channels, which leads to the death of neurons; the theory of the lack of neurotrophic factor.
Recently, in the research environment, the most popular hypothesis is mitochondrial dysfunction, which consists in the fact that due to the increased permeability of mitochondria, free radicals that damage motor neurons, microglial and astroglial cells occur, followed by the development of neurodegeneration.
According to the predominant lesion of the central nervous system , the following forms of ALS are distinguished:
- High (cerebral);
According to the rate of progression of clinical symptoms , there are 3 types of ALS:
- Fast – progressing;
- Slowly progressing.
Amyotrophic lateral sclerosis symptoms
ALS with a neck opening
In the classical version of amyotrophic lateral sclerosis with cervical debut, an asymmetric upper flaccid paraparesis with hyperreflexia and pathological pyramidal signs is formed at the beginning of the disease at the same time. Along with this, asymmetric lower spastic paraparesis develops with hyperreflexia and pathological signs. In the future, a combination of bulbar and pseudobulbar syndromes joins, even later amyotrophy of the lower extremities, predominant in the extensor muscle group, is more pronounced.
In the segmental nuclear variant of amyotrophic lateral sclerosis with cervical debut, an asymmetric upper flaccid paraparesis is formed at the beginning of the disease, which is accompanied by hyporeflexia and pathological pyramidal signs in the lower extremities (without hypertonus). At the time of the development of plegia in the proximal extremities, the minimal pyramidal symptoms in the hands fade away, patients at this time retain the ability to move independently. With the development of the disease, bulbar syndrome also joins, even later there are distinct amyotrophy and paresis in the lower extremities.
In the classical variant of amyotrophic lateral sclerosis with diffuse onset, the disease starts with the development of sluggish asymmetric tetraparesis. Along with this, bulbar syndrome develops in the form of dysphonia and dysphagia. There is rapid fatigue, marked weight loss, inspiratory shortness of breath.
ALS with lumbar debut
In the classical variant of amyotrophic lateral sclerosis with lumbar debut, an asymmetric lower flaccid paraparesis with hyperreflexia and pathological pyramidal signs is formed at the beginning of the disease. At the same time, there is an asymmetric upper paraparesis with amyotrophy, muscle hypertonus, hyperreflexia and pathological pyramidal signs. At the time of the development of sluggish paraplegia, patients retain the ability to use their hands. Later, bulbar and pseudobulbar syndromes join.
In the segmental nuclear variant of amyotrophic lateral sclerosis with lumbar onset, the disease starts with the formation of a lower flaccid asymmetric paraparesis with atrophy and early extinction of tendon reflexes. In the future, the upper flaccid asymmetric paraparesis is joined with early extinction of tendon reflexes. Subsequently developing bulbar syndrome manifests itself in the form of dysphonia and dysphagia. There is pronounced inspiratory dyspnea due to the early involvement of auxiliary respiratory muscles in the pathological process, as well as a pronounced decrease in body weight.
In the pyramidal variant of amyotrophic lateral sclerosis with lumbar debut, the disease manifests with the formation of lower spastic asymmetric paraparesis with hyperreflexia, amyotrophy and pathological pyramidal signs; later, it is joined by upper spastic paraparesis with the same signs, after which pseudobulbar syndrome develops.
ALS with progressive bulbar paralysis
In the classic version of amyotrophic lateral sclerosis with progressive bulbar paralysis, dysarthria, dysphagia, nasophonia, atrophy and fasciculations of the tongue develop at the beginning of the disease. Subsequently, upper flaccid asymmetric paraparesis develops with hyperreflexia, atrophy and pathological pyramidal signs. Then the lower spastic asymmetric paraparesis with hyperreflexia and pathological pyramidal signs joins. There is a marked decrease in body weight, and in the late stage of the disease respiratory disorders are added.
In the segmental nuclear variant of amyotrophic lateral sclerosis with progressive bulbar paralysis, the disease starts with the development of dysphonia, dysphagia, dysarthria, loss of pharyngeal and mandibular reflexes. Then the upper flaccid asymmetric paraparesis develops with hyperreflexia, atrophy and pathological pyramidal signs. Later, the lower spastic asymmetric paraparesis with hyperreflexia and pathological signs joins. Due to dysphagia, body weight is significantly reduced. In the late stage of the disease, respiratory disorders are added.
Due to the pronounced weakening of muscle tone, joint contractures occur. Almost all patients in the outcome gradually develop complete paralysis of the affected part of the body (upper, lower limbs, neck) with loss of the ability to walk and self-care. The most serious complications include aspiration pneumonia, which is caused by bulbar and pseudobulbar disorders occurring in 67% of patients.
Half of the patients are characterized by a decrease in memory and mental performance. In 5% of patients, dementia is combined with Parkinsonian syndrome (muscle rigidity, gait stiffness, fine-pitched tremor). Disorders of pelvic functions, such as urinary incontinence and involuntary defecation, are atypical for amyotrophic lateral sclerosis and occur only in the later stages of the disease.
Neurologists are involved in the supervision of patients suffering from amyotrophic lateral sclerosis. In some patients, it is possible to identify a positive family history (a close relative with this disease). When examining the patient, there is a decrease in muscle tone, bulbar disorders, the presence of crampy – painful muscle contractions. To clarify the diagnosis, an additional examination is prescribed, including:
- EMG. When performing needle electromyography, there is a decrease in the speed of the pulse, an increase in the amplitude and duration of the action potential of motor units, episodes of spontaneous electrical activity (fibrillation, fasciculation).
- Muscle biopsy. The histological picture of the nerve biopsy shows signs of demyelination, swelling, decay and death of axial cylinders.
- MRI. Brain MRI is performed in order to exclude other neurodegenerative diseases that have a similar clinical picture. In rare cases, patients with ALS have an amplification of the signal from the cortical-spinal tracts.
- DNA analysis. By polymerase chain reaction, mutations in the superoxide dismutase-1 (SOD1) and C9orf72 genes can be detected in some patients. In cases of familial forms of amyotrophic lateral sclerosis, mutations of the FUS, TARDBP genes are found.
To differentiate amyotrophic lateral sclerosis from potentially curable and/or having a benign prognosis of diseases, an MRI of the spine and brain is performed. With its help, signs of degeneration of the pyramidal tracts are revealed, which are characteristic of the pyramidal and classical variants of ALS.
In addition, due to similar symptoms and clinical picture, amyotrophic lateral sclerosis must be differentiated from:
- muscle diseases (myositis with cellular abnormalities, Rossolimo-Steinert-Kurschmann dystrophic myotonia, oculopharengial myodystrophy);
- diseases with neuromuscular synapse damage (myasthenia gravis, Lambert-Eaton syndrome);
- peripheral nerve diseases (multifocal motor neuropathy with conduction blocks, Personage-Turner syndrome, isolated motor polyneuropathies, proximal diabetic motor polyneuropathy, Isaacs neuromyotonia);
- spinal cord diseases (bulbospinal Kennedy amyotrophy, as well as other spinal amyotrophy of adults, chronic vertebrogenic ischemic myelopathy, syringomyelia, spinal cord tumors, familial spastic paraplegia, hexosaminidase deficiency, chronic lymphocytic leukemia or lymphoma with peripheral motor neurone damage);
- diseases of the brain (dyscirculatory encephalopathy, multisystem atrophy, syringobulbia, tumors of the posterior cranial fossa and craniospinal junction);
- systemic diseases.
Amyotrophic lateral sclerosis treatment
All patients with this diagnosis should be hospitalized in the neurological department. There is no effective treatment that can stop the progression of the disease. The only drug affecting the pathogenesis of amyotrophic lateral sclerosis is riluzole.
This drug inhibits the release of glutamate from neurons, an amino acid that triggers the process of degeneration of nerve cells. Its use makes it possible to prolong the patient’s life by an average of 3 months. All therapeutic measures are aimed at relieving or relieving the main symptoms of ALS – bulbar disorders and spasticity:
- Exercise therapy. Regular physical activity is recommended to maintain muscle tone. At the initial stages of the disease, active exercises are performed, at later stages, when independent movements are difficult, passive ones are performed.
- Orthopedic devices. Orthoses, corsets, immobilizing splints are used to fix various parts of the body in order to prevent bone deformations and joint contractures.
- Food. With the development of bulbar disorders due to the weakening of the muscles of the pharynx and tongue, there is a danger of food entering the respiratory tract. Therefore, it is recommended to eat semi-solid foods (porridge, puree), meals should be performed in an upright position. In severe dysphagia, endoscopic gastrostomy is performed.
- Maintenance of respiratory function. A very important aspect in the treatment of patients with amyotrophic lateral sclerosis. Depending on the severity of oxygen deficiency, oxygen inhalation through a nasal cannula or a facial mask, non-invasive ventilation of the lungs through portable ventilators are prescribed.
- Providing communication. In severe patients with severe muscular atrophy and dysarthria, various electronic or mechanical communication devices are used to facilitate communication with others.
All of the above measures will have the maximum therapeutic effect only if they are used together and regularly, as well as supplemented with pharmacotherapy. The following medications are prescribed for the treatment of ALS patients:
- Muscle relaxants and anticonvulsants. Muscle-relaxing drugs (baclofen, tolperizone) and anticonvulsants (carbamazepine, phenytoin) are effective to combat muscle spasticity and painful seizures.
- Holinoblockers. With pronounced salivation, medications that suppress the production of saliva are used – blockers of m-cholinergic receptors (atropine, hyoscine).
- Dextromethorphan and quinidine. These drugs have proven themselves well for the correction of bulbar disorders.
- Mucolytics and expectorants. In patients with respiratory muscle weakness, drugs that dilute sputum (acetylcysteine) and stimulate its expectoration (terpinghydrate) are used to eliminate problems such as weak expectoration and accumulation of thick sputum in the respiratory tract.
Clinical research is continuously conducted to find and develop an effective method of treating ALS. The most promising direction at the moment is considered to be cellular technologies, namely, intraspinal injection of mesenchymal stem cells. Once in the spinal cord cavity, stem cells are able to differentiate into neurons and gradually replace the dead nerve tissue.
Also, some successes in the form of increasing the life expectancy of ALS patients were demonstrated by studies in which recombinant human erythropoietin, ciliary neurotropic factor and insulin-like factor-1 were used. The drug edaravon showed little effectiveness.
With amyotrophic lateral sclerosis, the prognosis is always unfavorable. An exception may be hereditary cases of ALS associated with certain mutations in the superoxide dismutase-1 gene. The duration of the disease with lumbar debut is about 2.5 years, with bulbar — about 3.5 years. No more than 7% of patients diagnosed with ALS live for more than 5 years.
There are no methods of specific prevention of amyotrophic lateral sclerosis. The only effective way to prevent the development of the disease is prenatal diagnosis (detection of mutations in amniotic fluid or chorionic villi) and termination of pregnancy. Secondary prevention is to prevent complications.