Syndrome of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (Charcot's disease (Gehrig's disease) is a responsible diagnosis, equivalent to a medical "verdict".

This diagnosis is not always simple, because in recent years the range of diseases has significantly expanded, in the clinical manifestations of which there can be observed not a disease but a syndrome of amyotrophic lateral sclerosis. Therefore, the most important task is to distinguish Charcot's disease from the syndrome of amyotrophic lateral sclerosis and clarify the etiology of the latter.

Amyotrophic lateral sclerosis is a severe organic disease of unclear etiology, characterized by the defeat of upper and lower motoneurons, a progressive course and resulting inevitably with a lethal outcome.

Symptoms of amyotrophic lateral sclerosis

Symptoms of amyotrophic lateral sclerosis, according to this definition, are symptoms of lower motoneuron failure, including weakness, atrophy, cramp and fasciculation, and symptoms of damage to the cortico-spinal tract - spasticity and increased tendon reflexes with pathological reflexes in the absence of sensory disturbances. Cortico-bulbar tracts can be involved, strengthening the already developed disease at the level of the brainstem. Amyotrophic lateral sclerosis is an adult disease and does not begin in individuals younger than 16 years.

The most important clinical marker of the initial stages of amyotrophic lateral sclerosis is asymmetric progressive muscular atrophy with hyperreflexia (as well as fasciculations and cramps). The disease can begin with any striated muscles. High (progressive pseudobulbar paralysis), bulbar ("progressive bulbar paralysis"), cervicothoracic and lumbosacral forms are distinguished). Death is usually associated with the involvement of respiratory muscles in about 3-5 years.

The most frequent symptom of amyotrophic lateral sclerosis, occurring in approximately 40% of cases, is the progressive weakness of the muscles of one upper limb, usually beginning with the hand (the beginning of the proximal muscles reflects a more favorable variant of the disease). If the onset of the disease is associated with the appearance of weakness in the muscles of the hand, then usually the muscles of the tenar are involved in the form of weakness of adduction (reduction) and opposition of the thumb. This makes it difficult to grasp the thumb and index finger and leads to a violation of fine motor control. The patient feels difficult when picking up small items and when dressing (buttons). If the leading hand is affected, then there are progressive difficulties in writing, as well as in everyday household activities.

In a typical course of the disease, there is a steadily progressing involvement of other muscles of the same limb and then spreading to the other arm before the lower limbs or bulbar muscles are affected. The disease can begin with the muscles of the face or mouth and tongue, with the muscles of the trunk (extensors suffer more flexors) or lower limbs. At the same time, the involvement of new muscles never "catches up" with the muscles from which the disease began. Therefore, the shortest life expectancy is observed in bulbar form: patients die from bulbar disorders, remaining on their feet (patients do not have time to survive to paralysis in the legs). Relatively favorable form - lumbosacral.

In bulbar form, there are certain variants of a combination of symptoms of bulbar and pseudobulbar paralysis, which is manifested mainly by dysarthria and dysphagia, and then by respiratory disorders. A characteristic symptom of almost all forms of amyotrophic lateral sclerosis is an early increase in the mandibular reflex. Dysphagia when swallowing liquid food is observed more often than hard, although swallowing of solid food as the disease progresses becomes more difficult. The weakness of the chewing muscles develops, the soft palate hangs, the tongue in the mouth is immobile and atrophic. There is anarthria, continuous flow of saliva, inability to swallow. The risk of aspiration pneumonia increases. It is also useful to remember that krampi (often generalized) are observed in all patients with ALS and are often the first symptom of the disease.

It is characteristic that atrophy throughout the course of the disease is clearly selective. Tenar, hypotenar, interosseous muscles and deltoid are amazed on the hands; on the legs - the muscles that perform the rear bending of the foot; in the bulbar musculature - the muscles of the tongue and soft palate.

Osteo-motor muscles are most resistant to amyotrophic lateral sclerosis. Sphincter disorders are considered rare in this disease. Another intriguing feature of amyotrophic lateral sclerosis is the lack of decubitus even in patients paralyzed and bedridden (immobilized) for a long time. It is also known that dementia is rare in amyotrophic lateral sclerosis (with the exception of some subgroups: the family form and the parkinsonism-BAS dementia complex on the island of Guam).

Forms with uniform involvement of upper and lower motoneurons are described, with predominance of upper lesions (pyramidal syndrome in "primary lateral sclerosis") or lower motoneuron (antero-neural syndrome).

Among paraclinical studies, the most significant diagnostic value is electroneuromyography. The widespread damage of the cells of the anterior horns (even in clinically preserved muscles) with fibrillations, fasciculations, positive waves, changes in the potentials of motor units (their amplitude and duration increases) at a normal rate of excitation along the fibers of the sensory nerves. The content of CK in plasma can be slightly increased.

Diagnosis of amyotrophic lateral sclerosis

Diagnostic criteria for amyotrophic lateral sclerosis (according to Swash M., Leigh P 1992)

For the diagnosis of amyotrophic lateral sclerosis, the presence of:

• symptoms of lower motor neuron damage (including EMG confirmation in clinically preserved muscles)
• Symptoms of affection of the upper motor neuron are progressive.

[1], [2], [3], [4], [5],

Criteria for exclusion of amyotrophic lateral sclerosis (negative diagnostic criteria)

The diagnosis of amyotrophic lateral sclerosis requires the absence of:

• sensory disorders
• sphincter disorders
• visual disorders
• vegetative disorders
• Parkinson's disease
• dementia of the Alzheimer's type
• ALS-imitating syndromes.

[6], [7], [8],

Criteria for confirmation of amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis is confirmed:

Fasciculations in one or more regions of EMG-signs of neuronopathy by the normal rate of excitation of motor and sensory fibers (distal motor latencies can be increased) by the absence of a block of conduction.

[9], [10]

Diagnostic categories of amyotrophic lateral sclerosis

Significant amyotrophic lateral sclerosis: the presence of symptoms of the lower motor neuron, plus the symptoms of an upper motor neuron injury in 3 regions of the body.

Probable amyotrophic lateral sclerosis: symptoms of lower motor neuron injury plus symptoms of an upper motor neuron lesion in 2 regions of the body with symptoms of upper motor neurone roast than symptoms of the lower motor neuron.

Possible amyotrophic lateral sclerosis: symptoms of lower motoneuron plus symptoms of upper motoneuron in the body region 1 or symptoms of upper motor neuron in 2 or 3 regions of the body such as monomelic amyotrophic lateral sclerosis (manifestations of amyotrophic lateral sclerosis in one limb), progressive bulbar paralysis and primary lateral sclerosis.

Suspicion of amyotrophic lateral sclerosis: symptoms of lower motor neuron in 2 or 3 regions such as progressive muscular atrophy or other motor symptoms.

To clarify the diagnosis and conduct a differential diagnosis with amyotrophic lateral sclerosis the following examination of the patient is recommended:

• Blood test (ESR, hematological and biochemical blood test);
• Radiography of the chest;
• ECG;
• Thyroid function research;
• Determination of vitamin B12 and folic acid in the blood;
• Creatine kinase in serum;
• EMG;
• MRI of the head and, if necessary, the spinal cord;
• Lumbar puncture.

[11], [12], [13], [14],

Syndromes that mimic or resemble amyotrophic lateral sclerosis

1. Spinal Cord Injuries:
   1. Cervical myelopathy.
   2. Other myelopathies (radiation, vacuolar with AIDS, electric injury).
   3. Ventral tumor of the spinal cord.
   4. Syringomyelia (anterrhoeic form).
   5. Subacute combined degeneration of the spinal cord (insufficiency of vitamin B12).
   6. Family spastic paraparesis.
   7. Progressive spinal amyotrophy (bulbospinal and other forms).
   8. Postpiolo-syndrome.
2. Lymphogranulomatosis and malignant lymphomas.
3. Gangliosidosis GM2.
4. Intoxication with heavy metals (lead and mercury).
5. Syndrome of ALS in paraproteinemia.
6. Creutzfeldt disease - Jacob.
7. Multifocal motor neuropathy.
8. Axonal neuropathy in Lyme disease.
9. Endocrinopathies.
10. Malabsorption syndrome.
11. Benign fasciculations.
12. Neuroinfections.
13. Primary lateral sclerosis.

Spinal cord injuries

Cervical myelopathy, among other neurological manifestations, often reveals typical symptoms of amyotrophic lateral sclerosis with hypotrophy (more often on the hands), fasciculations, tendinous hyper-flexion and spasticity (more often on the legs). The syndrome of amyotrophic lateral sclerosis in the picture of spondylogenous cervical myelopathy differs relatively favorable course and prognosis.

The diagnosis is confirmed by the detection of other neurological manifestations of cervical myelopathy (including posterior-columned sensory disorders and Sometimes bladder function disorders) and neuroimaging of the cervical spine and spinal cord.

Some other myelopathies (radiation, vacuolar myelopathy in HIV infection, effects of electrical injury) can also manifest similar or similar syndrome of amyotrophic lateral sclerosis.

Ventral tumor of the spinal cord at the cervicothoracic level can manifest at certain stages purely motor symptoms, reminiscent of the cervico-thoracic form of amyotrophic lateral sclerosis. Therefore, patients with spastico-paretic atrophies on the arms and spastic paraparesis in the legs always need a thorough examination to exclude compression of the spinal cord at the cervical and cervicothoracic levels.

Syringomyelia (especially its anterolateral form) at this level of the spinal cord can manifest itself in a similar clinical picture. The decisive role in its recognition is the detection of sensory disorders and neuroimaging inspection.

Subacute combined degeneration of the spinal cord with deficiency of vitamin B12 or folic acid (funicular myelosis) usually develops against the background of somatogenic malabsorption syndromes and is manifested in typical cases by symptoms of hindbrain and lateral columns of the spinal cord at the cervical and thoracic levels. The presence of lower spastic paraparesis with pathological reflexes in the absence of tendon reflexes sometimes makes it differentiate with lateral amyotrophic sclerosis. Diagnosis is assisted by the presence of sensory disorders (violations of deep and surface sensitivity), ataxia, sometimes - pelvic disorders, as well as the identification of a medical condition (anemia, gastritis, language, etc.). Of decisive importance in diagnosis is the study of the level of vitamin B12 and folic acid in the blood.

Family spastic paraparesis (paraplegia) Strympel refers to hereditary diseases of the upper motoneuron. Since there are forms of amyotrophic lateral sclerosis with a predominant lesion of the upper motoneuron, a differential diagnosis between them sometimes becomes very relevant. In addition, there is a rare variant of this disease ("hereditary spastic paraparesis with distal amyotrophy"), in which first of all it is necessary to exclude amyotrophic lateral sclerosis. Diagnosis is helped by the family history of Stryumpel's disease and its more favorable course.

Progressive spinal amyotrophies

1. Bulbospinal, X-linked, Kennedy-Stephanie-Chukagoshi amyotrophy is observed almost exclusively in men with the onset of the disease most often on 2-3 decade of life and is manifested by fasciculations in the face (in the lower part), amyotrophic and paretic syndrome in the extremities (begins with the hand) and a rough bulbar syndrome. Characteristic family history, transient episodes of weakness and the syndrome of endocrine disorders (gynecomastia occurs in 50% of cases). Sometimes there is a tremor, a crump. The course is benign (compared with amyotrophic lateral sclerosis).
2. The bulbar form of progressive spinal amyotrophy in children (Fazio-Londe's disease) is inherited by autosomal recessive type, begins at the age of 1-12 years and manifests itself as progressive bulbar paralysis with the development of dysphagia, intense salivation, repeated respiratory infections and respiratory disorders. General weight loss, decrease of tendon reflexes, weakness of facial muscles, ophthalmoparesis can develop.
3. Differential diagnosis with amyotrophic lateral sclerosis may require other forms of progressive spinal amyotrophy (proximal, distal, scapulo-peroneal, oculo-pharyngeal, etc.). Unlike amyotrophic lateral sclerosis, all forms of progressive spinal amyotrophy (PSA) are characterized by lesion of only the lower motor neuron. They all manifest progressive muscular atrophy and weakness. Fasciculations are not always available. Sensory disturbances are absent. The sphincter function is normal. In contrast to amyotrophic lateral sclerosis, already in the onset of PSA manifest a fairly symmetrical muscular atrophy and have a much better prognosis. There are no symptoms of upper motoneuron damage (pyramidal signs). For the diagnosis, the EMG study has a crucial importance.

Postpiolo-syndrome

Approximately a quarter of patients with residual paresis after the transferred poliomyelitis after 20-30 years develop progressive weakness and atrophy of previously affected and previously unaffected muscles (post-poliomyelitis syndrome). Usually, weakness develops very slowly and does not reach a significant degree. The nature of this syndrome is not entirely understandable. In these cases, a differential diagnosis with amyotrophic lateral sclerosis may be necessary. The above criteria for the diagnosis of amyotrophic lateral syndrome are used.

Lymphogranulomatosis, as well as malignant lymphoma

These diseases can be complicated by a paraneoplastic syndrome in the form of a lower motor neuronopathy, which is not easily differentiated from amyotrophic lateral sclerosis (but still its flow is more benign with improvement in some patients). The predominant symptoms of lower motoneuron predominate with subacute progressive weakness, atrophy and fasciculations in the absence of pain. Weakness is usually asymmetric; mainly suffer from lower limbs. When studying the excitation of nerves, demyelination is noted in the form of a block of conduction along the motor nerves. Weakness precedes lymphoma or vice versa.

Gangliosidosis GM2

The inadequacy of type A hexosaminidase in adults, which is phenomenologically different from the well-known Tay-Sachs disease in infants, may be accompanied by symptoms reminiscent of motor neuron disease. The manifestations of type A hexosaminidase deficiency in adults are highly polymorphic and can resemble both amyotrophic lateral sclerosis and progressive spinal amyotrophy. Another close genotype, which is based on the deficiency of hexosaminidase type A and B (Sendhoff disease), may also be accompanied by symptoms reminiscent of motor neuron disease. Although the amyotrophic lateral sclerosis syndrome appears to be the main manifestation of hexosaminidase-A deficiency in adults, the clinical spectrum of its manifestations suggests that multisystemic degeneration is at the heart of it.

Intoxication with heavy metals (lead and mercury)

These intoxications (especially mercury) are currently rare, but they can cause the development of amyotrophic lateral sclerosis syndrome with a predominant lesion of the lower motor neuron.

Syndrome of amyotrophic lateral sclerosis with paraproteinemia

Paraproteinemia is a kind of dysproteinemia, which is characterized by the presence in the blood of a pathological protein (paraprotein) from the group of immunoglobulins. Paraproteinemia include multiple myeloma, Waldenstrom's macroglobulinemia, osteosclerotic myeloma (more often), primary amyloidosis, plasmacytoma and paraproteinaemia of unknown origin. At the heart of some neurological complications in these diseases is the formation of antibodies to myelin or axon components. Most often observed polyneuropathy (including in the picture of POEMS syndrome), there is less frequent cerebellar ataxia, the phenomenon of Raynaud, but since 1968 the syndrome of amyotrophic lateral sclerosis (motor neuronopathy) with weakness and fasciculation is periodically mentioned. Paraproteinemia is described as with classical ALS, and with a variant of amyotrophic lateral sclerosis syndrome with slow progression (in rare cases, immunosuppressive therapy and plasmapheresis led to some improvement in the condition).

Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease belongs to the group of prion diseases and begins in typical cases at the age of 50-60 years; it has a subchronic flow (usually 1-2 years) with a fatal outcome. For Creutzfeldt-Jakob disease is characterized by a combination of dementia, extrapyramidal syndromes (akinetic-rigid, myoclonus, dystonia, tremor), as well as cerebellum, anteroluminal and pyramidal signs. Quite often there are epileptic seizures. For the diagnosis, great importance is attached to the combination of dementia and myoclonus with typical changes in the EEG (the three-phase and polyphasic activity of the acute form with an amplitude of up to 200 microvolts, occurring at a frequency of 1.5-2 per sec) against the background of the normal CSF composition.

[15], [16], [17], [18]

Multifocal motor neuropathy

Multifocal motor neuropathy with conduction blocks is found mainly in men and is clinically characterized by progressive asymmetric weakness in the limbs without (or with minimal) sensory disturbances. Weakness is usually (in 90%) expressed distally and more in the hands than in the legs. The weakness of muscles in its distribution is often asymmetrically "attached" to individual nerves: the radial ("hanging brush"), the ulnar and the median. Atrophies are often detected, but may be absent in the early stages. Fasciculations and cramps are observed in almost 75% of cases; sometimes - myokimii. Approximately 50% of cases tendon reflexes are reduced. But occasionally reflexes remain normal and even accented, which gives reason to differentiate multifocal motor neuropathy from ALS. An electrophysiological marker is the presence of multifocal partial blocks of excitation (demyelination).

Axonal neuropathy in Lyme disease

Lyme disease (Lyme borreliosis) is caused by a spirochete penetrating the human body through the tick bite, and is a multisystem infectious disease that most often affects the skin (migratory annular erythema), the nervous system (aseptic meningitis, facial nerve neuropathy, often bilateral, polyneuropathy) , joints (recurrent mono- and polyarthritis) and the heart (myocarditis, atrioventricular block and other heart rhythm disturbances). Subacute polyneuropathy in Lyme disease can sometimes be differentiated from Guillain-Barre syndrome (especially with diplegia facialis). However, patients with polyneuropathy in Lyme disease almost always find pleocytosis in the cerebrospinal fluid. In some patients with borreliosis, motor polyradiculitis mainly develops, which may resemble motor neuronopathy with symptoms similar to ALS. The differential diagnosis can again be helped by the study of cerebrospinal fluid.

[19], [20],

Endocrinopathies

Hypoglycemia associated with hyperinsulinism is one of the known endocrinopathies described in foreign and domestic literature that can lead to the development of amyotrophic lateral sclerosis syndrome. Another form of endocrinopathy - thyrotoxicosis - may resemble amyotrophic lateral sclerosis with pronounced total weight loss and the presence of symmetrically high tendon reflexes (sometimes there is a Babinsky symptom and fasciculation), which is often observed with untreated thyrotoxicosis. Hyperparathyroidism is most often caused by an adenoma of the parathyroid gland and leads to violations of calcium metabolism (hypercalcemia) and phosphorus. Complications from the nervous system concern either mental functions (memory loss, depression, less often - psychotic disorders), or (less often) - motor problems. In the latter case, sometimes develop atrophy and muscle weakness, usually more noticeable in the proximal parts of the legs and often accompanied by pain, hyperreflexia and fasciculations in the tongue; develops a dysbasia, sometimes resembling a duck's gait. Preserved or increased reflexes against a background of muscular atrophy sometimes serve as a basis for suspicion of amyotrophic lateral sclerosis. Finally, in practical work, sometimes there are cases of diabetic "amyotrophy", requiring a differential diagnosis with ALS. In the diagnosis of motor disorders in endocrinopathies, it is important to recognize endocrine disruption and apply criteria for diagnosis (and exclusion) of amyotrophic lateral sclerosis.

[21], [22], [23]

Malabsorption syndrome

The gross violations of absorption are accompanied by a violation of the exchange of vitamins, electrolytes, anemia, various endocrine and metabolic disorders, which sometimes leads to severe neurological disorders in the form of encephalopathy (more often with stem, cerebellar and other manifestations) and lesions of the peripheral nervous system. Among the neurological manifestations of severe malabsorption as a rare syndrome there is a symptom complex resembling amyotrophic lateral sclerosis.

Benign fasciculations

The presence of some fasciculations without EMG signs of denervation is not sufficient for the diagnosis of ALS. Benign fasciculations last for years without any signs of involvement of the motor system (there is no weakness, atrophy, relaxation time does not change, reflexes do not change, the rate of excitation is along the nerves, there are no sensitive disorders, muscle enzymes remain normal). If, for some reason, there is a general weight loss of the patient, sometimes in such cases there is a reasonable suspicion of ALS.

[24], [25], [26], [27], [28],

Neuroinfections

Some infectious diseases of the nervous system (poliomyelitis (rare), brucellosis, epidemic encephalitis, tick-borne encephalitis, neurosyphilis, HIV infection, Lyme disease mentioned above, "Chinese paralytic syndrome") can be accompanied by a variety of neurological syndromes, including pyramidal and anterolone symptoms, which can cause suspicion of ALS syndrome at certain stages of the disease.

Primary lateral sclerosis

Primary lateral sclerosis is an extremely rare disease in mature and advanced age that is characterized by progressive spastic tetraparesis, preceding or following pseudobulbar dysarthria and dysphagia, which reflects the combined involvement of corticospinal and corticobulbar tracts. Fascination, atrophy and sensory disturbances are absent. EMG and muscle biopsy do not show signs of denervation. Although long survival among patients with primary lateral sclerosis is described, patients with the same rapid course that is characteristic of ALS are found. The final nosological affiliation of this disease is not established. The predominant view is that primary lateral sclerosis is an extreme variant of ALS, when the disease is limited to the defeat of only the upper motoneuron.

In the literature, single descriptions of syndromes resembling amyotrophic lateral sclerosis can be found, in such diseases as radiation damage to the nervous system (motor neuronopathy), myositis with inclusion bodies, paraneoplastic encephalomyelitis with the involvement of anterior horn cells, juvenile spinal muscular atrophy with distal atrophies in the hands, disease Machado-Joseph, multiple systemic atrophy, Gallervorden-Spatz disease, some tunneling neuropathies, abnormalities of the craniovertebral transition.