Bass shape. Amyotrophic lateral sclerosis - what is it and how to treat it

Amyotrophic lateral sclerosis (ALS; Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized by the death of central and / or peripheral motor neurons, steady progression and death (based on the fact that the disease is based on selective damage to motor neurons ALS is also called motor neuron disease "; In the literature ALS is also referred to as Charcot's disease, Lou Gehrig's disease). The death of the above motoneurons is manifested by skeletal muscle atrophy, fasciculations, spasticity, hyperreflexia and pathological pyramidal signs in the absence of oculomotor and pelvic disorders.

It usually takes about 14 months from the onset of the first symptoms of the disease to the final diagnosis in ALS patients. Most frequent reasons a long period of diagnosis are unusual clinical manifestations of the disease, the doctor's lack of thought about the possibility of developing ALS in a particular case, and incorrect interpretation of the results of neurophysiological and neuroimaging examinations. Unfortunately, the delay in the diagnosis of the disease leads to the appointment of such patients inadequate therapy and the emergence of psychosocial problems in the future.

ALS is observed all over the world. Analysis of the results of population studies shows that the incidence of ALS in European countries is 2-16 patients per 100 thousand people per year. In 90%, these are sporadic cases. Only 5-10% are hereditary (family) forms. Attempts to identify a clear genetic pattern characteristic of sporadic ALS variants have so far been unsuccessful. With regard to familial forms of ALS, 13 genes and loci have been identified that have a significant relationship with ALS. The typical clinical phenotype of ALS occurs when the following genes are mutated: SOD1 (responsible for Cu / Zn ion-binding superoxide dismutase), TARDBP (also known as TDP-43; TAR DNA-binding protein), FUS, ANG (encodes angiogenin, ribonuclease) and OPTN (encodes optineurin). The SOD1 mutation is associated with rapid disease progression (ALS), the pathophysiological pattern of which is not fully understood.

read also the article “Molecular structure of amyotrophic lateral sclerosis in the Russian population” by N.Yu. Abramycheva, E.V. Lysogorskaya, Yu.S. Shpilyukova, A.S. Vetchinova, M.N. Zakharova, S.N. Illarioshkin; Federal State Budgetary Scientific Institution "Scientific Center of Neurology"; Russia, Moscow (journal "Neuromuscular diseases" No. 4, 2016) [read]

It is assumed that the main pathogenetic factor in mutations in the SOD1 gene is the cytotoxic effect of the defective enzyme, and not a decrease in its antioxidant activity. Mutant SOD1 is capable of accumulating between the layers of the mitochondrial membrane, disrupting axonal transport, interacting with other proteins, causing their aggregation and disrupting degradation. Sporadic cases of the disease are probably associated with exposure to unknown triggers, which (like mutant SOD1) realize their effects under conditions of increased functional load on motor neurons, which leads to their selective vulnerability associated with increased energy expenditure, high demand for intracellular calcium, with low expression of calcium-binding proteins, glutamate receptors such as AMPA, some antioxidants and antiapoptotic factors. Strengthening the functions of motor neurons causes an increased release of glutamate, glutamate excitotoxicity, accumulation of excess intracellular calcium, activation of intracellular proteolytic enzymes, release of excess free radicals from mitochondria, damage to microglia and astroglia, as well as the motor neurons themselves, with subsequent degeneration.

ALS is more common in men. At the same time, the incidence of the disease in familial forms of ALS does not differ significantly between men and women. Most often ALS debuts at the age of 47 - 52 years with its familial variants and at 58 - 63 years old with sporadic forms of the disease. According to foreign authors, significant risk factors for the development of ALS are male sex, age over 50, smoking, mechanical injury received within 5 years before the onset of the disease, sports and intense physical labor. The disease is practically not observed after 80 years. The average life expectancy of ALS patients is 32 months (however, the life expectancy of some ALS patients can reach 5-10 years after the onset of the disease).

There are the following clinical forms diseases: [ 1 ] the classic spinal form of ALS with signs of central (CMN) and peripheral motor neuron (PMN) lesions on the arms or legs (cervicothoracic or lumbosacral localization); [ 2 ] the bulbar form of ALS, manifesting impaired speech and swallowing, with the subsequent addition of movement disorders in the limbs; [ 3 ] primary lateral sclerosis, manifested by signs of damage exclusively to the CMN, and [ 4 ] progressive muscle atrophy, when only PMN symptoms are observed.

The main clinical criterion for diagnosing ALS is the presence of signs of CMN and PNM lesions at the bulbar and spinal levels. Possible debut of the disease with the development of stem disorders (about 25%), dysfunctions of movement in the limbs (about 70%), or with primary lesions of the trunk muscles (including respiratory) - 5%, followed by the spread of the pathological process to other levels.

The defeat of the CMN is manifested by spasticity and weakness in the limbs, revitalization of deep reflexes and the appearance of pathological signs. The pathological process involving PNM is manifested by fasciculations, muscle atrophy and weakness. To the signs pseudobulbar paralysis, observed in ALS, includes spastic dysarthria, characterized by slow, difficult speech, often with a tinge of nasal nasal, increased chin and pharyngeal reflexes, the appearance of symptoms of oral automatism. Bulbar paralysis is manifested by atrophy and fasciculations in the tongue, dysphagia. Dysarthria in this case is accompanied by severe nasolalia, dysphonia and weakening of the cough reflex.

Typical clinical sign ALS are fasciculations - visible involuntary contractions of individual muscle groups. They arise due to the spontaneous bioelectrical activity of intact motor units (i.e. motoneurons). The detection of tongue fasciculations is a highly specific sign of ALS. Muscle atrophy and decreased motor activity are also the most common symptoms of ALS. At a certain stage of the disease, the severity of these disorders requires outside help in everyday life. Dysphagia develops in most ALS patients and is accompanied by weight loss, which is associated with a poor prognosis of the disease. Respiratory disorders are formed in the majority of patients with ALS, which leads to shortness of breath during exercise, orthopedic, hypoventilation, hypercapnia, morning headaches. The appearance of dyspnea at rest is a sign of imminent death.

An atypical pattern of initial signs of ALS includes weight loss (prognostically unfavorable sign), the presence of cramps, fasciculations in the absence of muscle weakness, emotional disordersas well as cognitive disorders of the frontal type.

In most patients, the sensory nerves and the autonomic nervous system, which controls the functions of the internal organs (including the pelvic organs), are usually not damaged, but isolated cases of disorders are still found. The disease also does not affect a person's ability to see, smell, taste, hear, or feel touch. The ability to control the eye muscles is almost always preserved, except in exceptional cases, which is very rare.

Elderly age, early development of respiratory impairment and the onset of the disease from bulbar disorders are significantly associated with low patient survival, while the classical spinal ALS, young age and a long period of diagnostic search for this pathology are independent predictors of higher patient survival. Moreover, the clinical form of ALS with "loose joints" and progressive muscle atrophy are characterized by a slower increase in symptoms than other clinical variants of the disease. With the bulbar form of ALS, most often observed in women over 65 years of age, in cases where the oropharyngeal muscles are damaged with a clinical picture of predominantly pseudobulbar paralysis, the prognosis of life is 2-4 years. In addition, the progression of the disease in patients with primary lateral sclerosis occurs more slowly than in patients with the classical form of ALS.

The existence of some diseases with a similar clinical pattern to ALS requires careful diagnosis of all patients with suspicion of this pathology. The standard in diagnostics is neuro-physiological, neuro-imaging examinations, as well as a number of laboratory tests. In cases of isolated PMN lesions, genetic testing for Kennedy's disease, X-linked bulbospinal atrophy, and spinal muscular atrophy is necessary. In addition, a muscle biopsy may be performed to exclude certain myopathies, such as polyglucosane body disease. At the same time, the detection of mixed-type atrophy in muscle biopsy is a pathognomonic sign of ALS.

about the clinic of ALS and differential diagnosis of ALS, see also the article: Clinic and differential diagnosis of amyotrophic lateral sclerosis (to the website)

Currently, the only purpose of neuroimaging studies (usually MRI) in patients with ALS is exclusion (differential diagnosis of an alternative pathological process). MRI of the brain and spinal cord in ALS patients in about half of the cases reveals signs of degeneration of the pyramidal tracts, which is more typical for the classical and pyramidal variants of ALS. Other signs include atrophy of the motor cortex of the brain. In patients with clinically significant ALS and bulbar and / or pseudobulbar syndromes, the role of neuroimaging is not significant.

Routine neurophysiological evaluation of patients with suspected ALS includes a study of the speed of conduction of impulses along nerve fibers, electromyography (EMG), and sometimes transcranial magnetic stimulation (which can reveal a decrease in the time of central motor conduction along the corticolumbar and / or corticocervical pyramidal tracts, as well as a decrease in excitability motor cortex). Examination of the peripheral nerves is extremely important to rule out some diseases similar to ALS, especially demyelinating motor neuropathies.

The "gold standard" for diagnosing PMN lesions is needle electromyography (EMG), which is performed at three levels (head or neck, arm, leg). Signs of PMN damage in this case are: spontaneous activity in the form of the potentials of fasciculations, fibrillations, and positive acute waves, as well as a tendency to an increase in the duration, amplitude and number of phases of motor unit potentials (signs of neuronal denervation).

Only laboratory method, allowing to confirm the diagnosis of ALS, molecular genetic analysis of the SOD1 gene. The presence of a mutation of this gene in a patient with suspected ALS makes it possible to refer it to the highly reliable diagnostic category of “clinically reliable laboratory confirmed ALS”.

Biopsy of skeletal muscle, peripheral nerve, and other tissues is not required in the diagnosis of motor neuron disease [ !!! ] except for those cases when there are clinical, neuro-physiological and neuro-radiological data not characteristic of the disease.

note! Respiratory status should be assessed in patients with ALS from the moment of diagnosis every 3 to 6 months (Lechtzin N. et al., 2002). According to American and European guidelines, all ALS patients should have regular spirometry. Other recommendations include nighttime pulse oximetry, arterial blood gas, polysomnography, maximum inspiratory and expiratory pressures (MEP) and ratios, trans-diaphragmatic pressure, nasal pressure (SNP) (if circular muscle of the mouth is weak). The inclusion of these studies in the assessment of respiratory disorders in combination with the determination of forced vital capacity (FVC) can help in the early detection of changes in respiratory function and the conduct of non-invasive ventilation (NIV) at the initial stages of respiratory failure (for more details in article # 12 - see below) ...

The problem with ALS treatment is that 80% of motor neurons die before clinical manifestations disease. To date, there is no effective treatment for ALS in the world. The gold standard for ALS treatment is riluzole (also known as Rilutek). This drug (which is not registered in Russia) has a pathogenetic effect, since it reduces glutamate excitotoxicity. But due to the fact that it slows down the progression of the disease by only 2 - 3 months, in fact, its effect can be attributed to palliative. The drug is recommended to be taken while the ALS patient participates in self-care, 50 mg 2 times a day before meals, while the preservation of speech and swallowing during tetraparesis is also considered participation in self-care. The drug is canceled or not prescribed: with severe tetraparesis and bulbar disorders, ALS patients who were diagnosed more than 5 years after the onset of ALS, with extremely rapid progression, with tracheostomy and mechanical ventilation, with hepatic and renal failure... Another gold standard for ALS palliative care is non-invasive ventilation (NVL). NVL reduces fatigue of the respiratory muscles and the tension of the respiratory neurons, which are the most resistant to ALS. This leads to an extension of the life of ALS patients for a year or more, provided that the patient regularly consults with a doctor, does spirography, increases the inspiratory and expiratory pressure with a difference of 6 cm aq. column in the device. Please note: there is no pathogenetic treatment for ALS - riluzole and NVL can prolong the patient's life by several months.

Learn more about ALS in the following sources:

1 ... chapter "Amyotrophic lateral sclerosis" V.I. Skvortsova, G.N. Levitsky. M.N. Zakharova; Neurology. National leadership; GEOTAR-Medicine, 2009 [read];

2 ... article "Amyotrophic lateral sclerosis ( modern views, prediction of outcomes, evolution of medical strategy) "Zhivolupov SA, Rashidov NA, Samartsev IN, Galitskiy SA, Military Medical Academy. CM. Kirov, St.Petersburg (magazine "Bulletin of the Russian military medical academy"No. 3, 2011) [read];

3 ... article "Amyotrophic lateral sclerosis: clinic, modern methods of diagnosis and pharmacotherapy (literary review)" Sklyarova E.A., Shevchenko P.P., Karpov S.M., Stavropol State Medical University, Department of Neurology, Neurosurgery and Medical Genetics, Stavropol [read];

4 ... lecture "On the pathogenesis and diagnosis of motor neuron disease (lecture)" V.Ya. Latysheva, Yu.V. Tabankova, Gomel State Medical University (journal "Problems of Health and Ecology" No. 1, 2014);

5 ... article "Recommendations for the provision of palliative care in amyotrophic lateral sclerosis" M.N. Zakharova, I.A. Avdyunina, E.V. Lysogorskaya, A.A. Vorobieva, M.V. Ivanova, A.V. Chervyakov, A.V. Vasiliev, Federal State Budgetary Scientific Institution Scientific Center of Neurology; Russia, Moscow (journal "Neuromuscular diseases" No. 4, 2014) [read];

6 ... article "Amyotrophic lateral sclerosis: clinical heterogeneity and approaches to classification" I.S. Bakulin, I. V. Zakroyshikova, N.A. Suponeva, M.N. Zakharova; Federal State Budgetary Scientific Institution "Scientific Center of Neurology"; Moscow (journal "Neuromuscular Diseases" No. 3, 2017 ) [to read ];

7 ... article "Clinical polymorphism of amyotrophic lateral sclerosis" EA Kovrazhkina, O.D. Razinskaya, L.V. Gubsky; FSBEI HE “Russian National Research Medical University named after N.I. Pirogov ", Moscow (Journal of Neurology and Psychiatry, No. 8, 2017) [read];

8 ... article " Deontological aspects amyotrophic lateral sclerosis "TM Alekseeva, V.S. Demeshonok, S.N. Zhulev; FSBI National Medical Research Center named after V.A. Almazov "Ministry of Health of the Russian Federation, St. Petersburg; FSBEI HE North-West State Medical University named after I.I. Mechnikov "Ministry of Health of the Russian Federation, St. Petersburg (journal" Neuromuscular diseases "No. 4, 2017) [read];

9 ... article "Preclinical medical genetic counseling in amyotrophic lateral sclerosis" Yu.A. Shpilyukova, A.A. Roslyakova, M.N. Zakharova, S.N. Illarioshkin; Federal State Budgetary Scientific Institution "Scientific Center of Neurology", Moscow (journal "Neuromuscular Diseases" No. 4, 2017) [read];

10 ... article "Clinical case of late onset of spinal amyotrophy in an adult patient - a stage in the development of amyotrophic lateral sclerosis?" T.B. Burnashev; Center for Israeli Medicine, Almaty, Kazakhstan (journal "Medicine" No. 12, 2014) [read];

11 ... article "Amyotrophic lateral sclerosis with expansion of the central canal of the spinal cord according to magnetic resonance imaging" Mendelevich EG, Mukhamedzhanova GR, Bogdanov EI; FSBEI HE "Kazan State Medical University" of the Ministry of Health of the Russian Federation, Kazan (journal "Neurology, neuropsychiatry, psychosomatics" No. 3, 2016) [read];

12 ... article "Methods of diagnosis and correction of respiratory disorders in amyotrophic lateral sclerosis" A.V. Vasiliev, D.D. Eliseeva, M.V. Ivanova, I.A. Kochergin, I. V. Zakroyshikova, L.V. Brylev, V.A. Shtabnitsky, M.N. Zakharova; Federal State Budgetary Scientific Institution "Scientific Center of Neurology", Moscow; GBUZ "City Clinical Hospital named after V.M. Buyanova ", Moscow; FSBEI HE “Russian National Research Medical University named after N.I. Pirogov ", Moscow (journal" Annals of Clinical and Experimental Neurology "No. 4, 2018) [read];

13 ... article "Amyotrophic lateral sclerosis: mechanisms of pathogenesis and new approaches to pharmacotherapy (literature review)" T.M. Alekseeva, T.R. Stuchevskaya, V.S. Demeshonok; FSBI National Medical Research Center named after V.A. Almazov "Ministry of Health of the Russian Federation, St. Petersburg; SPb GBUZ "City multidisciplinary hospital No. 2" St. Petersburg; FSBEI HE North-West State Medical University named after I.I. Mechnikov "Ministry of Health of the Russian Federation, St. Petersburg (journal" Neuromuscular diseases "No. 4, 2018 ) [to read ];

article "Syndrome of upper flaccid paraparesis in ALS and ALS-like syndromes: questions differential diagnosis"M.N. Zakharova, I. V. Zakroyshikova, I.S. Bakulin, I.A. Kochergin; FGBNU Scientific Center of Neurology, Moscow (magazine "Medica Mente" №1, 2016) [read]

Fund for assistance to patients with amyotrophic lateral sclerosis (information for patients and relatives)

© Laesus De Liro

Definition
Amyotrophic lateral sclerosis (ALS, Charcot's disease) is a chronic progressive disease of the nervous system, characterized by systemic damage to the motor neurons of the spinal cord and brain, with an unfavorable prognosis, significant limitation of life and disability already at early stage.

Epidemiology
It is a relatively common disease (2-5 cases per 100,000 population). It makes up about 80% of motor neuron diseases, which include various types of spinal amyotrophies. The age of patients is usually 50-70 years old, although there has been an increase in cases of the disease in 40 years and earlier. Men get sick twice as often as women. Sporadic and familial cases are known. The latter make up about 5-10% and are usually found only in some regions, for example, on the island of Guam and the Kii Peninsula in Japan.

Etiology and pathogenesis
The etiology of sporadic ALS remains unknown. Currently, the prevailing concept of the exogenous nature of the disease. The possible role of prions is considered, which is indirectly evidenced by the high activity of arginase in the brains of mice infected with scrapie (slow infection) and in the cerebrospinal fluid of patients with ALS (Zavalishin I.A., 1996). This corresponds to similar morphological changes in the brain (spongiosis, degeneration of synapses), which, apparently, is facilitated by arginine deficiency. The role of an autoimmune factor and genetic determination of the risk of ALS disease is possible (according to the study of cellular and humoral immunity and histocompatibility antigens). Familial ALS cases are obviously genetic in origin. In 50% of patients, mutations of the gene located on the 21st chromosome and encoding the synthesis of the enzyme superoxide dismutase, which is an endogenous antioxidant, are detected. This can lead to cell death of the anterior horns due to free radical oxidation. Recently, attempts have been made to explain the progressive degeneration of motor neurons in ALS by impaired metabolism of amino acids, neurotransmitters, and neuropeptides that regulate genetically determined apoptosis or programmed cell death (Olinak M. M. et al., 1996).
The process begins with segmental and cortical motoneurons, the pyramidal pathway is affected secondarily, as well as smooth muscles.

Classification
There are three variants of Charcot's disease:
1) sporadic (classic) ALS;
2) familial forms of ALS, in which the clinical picture is often characterized by additional symptoms (dementia, extrapyramidal, less often cerebellar disorders, peripheral neuropathy);
3) ALS complex - parkinsonism - dementia.
Depending on the main initial manifestations of the disease, the following clinical forms of classic sporadic ALS are distinguished (Khondkarian O.A. et al., 1978):
1) high (cerebral);
2) bulbar;
3) cervicothoracic;
4) lumbosacral.

Clinic and diagnostic criteria
1. Anamnestic information. Initial symptoms: paresthesia, fatigue, then weakness in the limbs (mainly in the hands), awkwardness in performing fine movements with the fingers, unilateral, in dynamics bilateral weight loss of the muscles of the hand, forearm, choking, swallowing disorders, fasciculations. The latter, more often in the beginning in separate groups of skeletal muscles, often muscles of the tongue, can occur 1-3 years before amyotrophies and conduction disorders. The precursors of ALS are cramps (in 30% of patients), often 3-6 months ahead of other manifestations of the disease (Shtulman DR, 1995).
2. A typical clinical picture in expanded form: a combination of spastic and flaccid paralysis of the extremities, muscle atrophies, bulbar and pseudobulbar disorders. Characterized by agitation of reflexes, pathological foot marks, widespread fasciculations, atrophy of the muscles of the tongue, long-term preservation of superficial abdominal reflexes, pelvic functions.
3. High cerebral form (in 1-2% of patients): spastic tetraparesis, pseudobulbar syndrome with dysphagia, dysarthria, violent phenomena with mild anterior nerve disorders, and sometimes nuclear (atrophy and fasciculations in the muscles of the tongue). Possible options: with lesions of the extrapyramidal system (parkinsonism), progressive dementia of the frontal type. In other cases, intelligence, as a rule, does not suffer.
4. In the bulbar form (25% of patients), the beginning of the process from the medulla oblongata, bulbar syndrome dominates due to damage to the nuclei IX-XII cranial nerves... Often, dysarthria and dysphagia develop early, followed by anterior amyotrophies, pyramidal insufficiency.
5. Cervicothoracic form is the most common (about 50% of cases). It begins with the distal upper extremities, then muscle hypotrophy of the entire arm, shoulder girdle, chest, a combination of amyotrophies with an increase in spastic tone, high reflexes. In dynamics - bulbar violations.
6. The lumbosacral form (in 20-25% of patients) begins with lesions of the lower extremities (usually the peroneal muscle group of the legs with a drooping foot). At the same time, or yes, are preserved; but tendon reflexes are revived not only in the muscles of the legs, but also in the pelvic girdle. Further, a slow upward current.
7. Some features of neurological symptomatology that are of diagnostic value: a) uniform lesion of the anterior nerve structures and conduction systems (classic version); b) the predominance of amyotrophies due to primary damage to the spinal cord motor neurons (poliomyelitis variant in 10-12% of patients); c) the prevalence of conduction disorders (spastic variant). Symptoms that go beyond the concept of ALS systemicity (rarely detected, expressed insignificantly): coordinating, vestibular, sensitive (paresthesia, pain, often with "cramps, joint stiffness). The peculiarity of trophic disorders: due to the rapid disappearance of subcutaneous adipose tissue and changes the structure of collagen fibers of the skin does not have bedsores (even at the late stage of the disease).

8. Data from additional studies:
- EMG, ENMG: regular rhythmic fasciculations due to widespread damage to the cells of the anterior horns, a decrease in the speed of conduction along the motor fibers during normal conduction along the sensitive ones. The amplitude of the H-reflex is reduced in atrophy and increased in the case of a predominance of spasticity. The significance of the study is great: clarification of the localization of the pathological process, the degree of its prevalence, the ratio of damage to the central and peripheral Motor neurons, identification early sign diseases - damage to motor neurons of the anterior horns and generalization of the process;
- MRI. Has not only differential diagnostic
value, but allows one to judge the morphological changes caused by ALS. It is possible to detect atrophy and bilateral degeneration of the cortico-spinal tracts (high signal on Tg and T2-weighted tomograms) in the posterior thigh of the inner capsule, in the trunk and spinal cord, which is confirmed pathomorphologically. However, the lack of change does not provide a basis for excluding Charcot disease (Hoffman et al., 1992);
- CT is successfully used for the differential diagnosis of ALS in cerebral form;
- PET (positron emission tomography) makes it possible to identify pathology in the area of \u200b\u200bthe precentral gyrus of the brain (to reduce glucose metabolism), which, however, in itself is not enough for diagnostic conclusions;
- EEG is used for differential diagnostic purposes in cerebral ALS;
- CSF study. Sometimes an increase in the protein content (0.6-0.9 g / l), a distinct increase in the activity of the arginase enzyme, correlating with the severity of the disease (Zavalishin IA, 1996);
- experimental psychological research (with cerebral form).

Differential diagnosis
He is always responsible for an unfavorable prognosis with true ALS, possible errors in solving expert questions. In cases of doubt, observation is necessary.
It is advisable to distinguish differentiation in the case of ALS syndrome with a similar clinical picture (except for the nature of the course, prognosis) and in some other diseases that cause damage to the upper and lower motor neurons and are accompanied by atrophies and bulbar disorders.
1.With a chronic progressive form tick-borne encephalitis... The fact of the acute period of encephalitis (especially of the focal form), pre-lesion lesion, relatively slow progression, and the role of hereditary factors in the pathogenesis of progression are taken into account.
2. Cervical ischemic myelopathy. It is characterized by slow progression, often with a stop of the process, irregularity and limited fasciculations. Spondylography is important, and especially MRI and EMG studies, taking into account the characteristics clinical picture and the course of the disease.
3. Subacute poliomyelitis (with poliomyelitis variant of ALS). There are no signs of defeat of the pyramidal path until the death of the patient (Konovalov N.V., 1958).
4. Spinal amyotrophy of adults, bulbospinal amyotrophy of Kennedy. Slow benign course with periods of stabilization, pyramidal signs are rare and late.
5. Syringomyelia (frontal form) - segmental sensory and trophic disorders, MRI results.
6. Amyotrophic leukospongiosis. Differentiation with the poliomyelitis form of ALS: the pyramidal pathway does not suffer, there is no bulbar paresis throughout the course of the disease.
7. Tumors of the cervical spinal cord (especially intramedullary). The decisive importance of the results of MRI, myelography in doubtful cases.
8. Lumbosacral spondylogenic radiculomyeloischemias (with lumbosacral ALS). Features of development, radicular syndrome, usually partial or even complete restoration of motor functions.
9. Post-poliomyelitis syndrome (10-40 years after the acute period of poliomyelitis). Anamnesis, slow progression of amyotrophies, rare pyramidal symptoms.
10. Tunnel neuropathy of the ulnar nerve: one-sidedness and locality of the lesion, the absence of pyramidal signs. Relevance only at an early stage of ALS.
11. Creutzfeldt-Jakob disease (with a high form of ALS - parkinsonism — dementia).

Course and forecast
The course is steadily progressing with a lethal outcome. Stabilization of the process for 1-3 years is occasionally possible. The dependence of life expectancy on the time of onset of bulbar disorders, localization initial symptoms, the age of the patient at the time of the appearance of the first signs of the disease. Young patients have a long duration of the disease.

Life expectancy of patients, taking into account the form of ALS:
- high (cerebral) - up to 4-6 years;
- bulbar - up to 1-3 years (sometimes up to 5 years);
- cervicothoracic - up to 6-8 years;
- lumbosacral - up to 10-12, sometimes 9-16 years.
In general, the survival rate is more than 5 years in 29% of patients, more than 10 in 16%.

Disability onset time(roughly): bulbar form — 10 months; cervicothoracic - 2 years, lumbosacral - 3-4 years.

The development of the disease in stages:
Stage I (usually not diagnosed) - subjective complaints (see "History"). Duration up to 2-3 years. Restrictions on life, as a rule, are not observed, the ability to work is preserved;
Stage II - focal motor, bulbar, cerebral disorders. Duration, depending on the primary localization, from 6 months to 1.5 years and much longer, sometimes many years (with lumbosacral form). The degree of limitation of life activity depends on the severity of motor disorders and their localization. The ability to work is limited, it can be lost (earlier - with bulbar disorders, rapid progression);
Stage III - common paresis, paralysis, bulbar (pseudobulbar) disorders, sometimes dementia. Duration from 4 months to 2 years. The ability to work is lost, many patients need outside help;
Stage IV - terminal. Bulbar disorders predominate. Duration from 3 months to 1 year. A sharp limitation of life. The need for care.

Treatment principles
1. Patients with suspected ALS need to be admitted to a neurological hospital for diagnosis and treatment.
2. There is no really effective therapy for ALS. In order to stabilize the patient's condition, drugs with neurotrophic properties are used: vitamins of group B (especially B12), vitamin E, synthetic analogue of leyenkephalin dalargin (increases the survival of neurons), anabolic hormones.
3. Symptomatic therapy: with severe spasticity - muscle relaxants, in the case of cramps - diphenin; stimulants (securinin), nootropics, etc.
4. Antidepressants and other psychotropic drugs to improve mental state sick.
5. Care is required, orthopedic devices are used (collar to support the head, splints). It is better to feed the patient with nutritious semi-liquid food, in case of bulbar disorders - tube feeding. The patient's ability to move independently and self-service should be maintained as long as possible. Switching to controlled breathing is inappropriate.

Medical and Social Expertise Criteria of VUT

1. Patients are temporarily disabled during the period of diagnosis and treatment (within 1.5-2 months).
2. With lumbosacral ALS sick leave can be issued to working patients (including disabled people
III group) with a temporary worsening of the condition. In case of a reportable progression of the disease, they should be directed to BMSE.

The main reasons for limitation of life
1. A motor defect due to mixed, peripheral paresis or paralysis of the limbs, leading to a decrease in manual activity, limiting or making it impossible to move, perform applied actions necessary in everyday life. In this regard, social insufficiency is revealed early, and in the future there is an inability to self-service.
2. Bulbar (sometimes pseudobulbar) disorders, sharply limiting life activity due to impaired ability to speak (anarthria), eat (dysphagia).
3. Dementia, extrapyramidal paresis (in the case of ALS complex - parkinsonism-dementia) additionally significantly restrict vital activity, necessitate constant care of the patient.

Contraindicated types and working conditions
Significant for patients with delayed progression, relative remissions (mainly in the lumbosacral form): physical stress, walking, forced body position, vibration, hypothermia, etc.

Indications for referral to BMSE
In almost all cases of ALS diagnosed (starting from stage II of the disease) due to unfavorable clinical and labor prognosis.
2. In lumbosacral form (at the onset of the disease) - the presence of adverse factors in labor activity, the need to reduce the amount of work.

Required minimum examination for referral to BMSE
1. EMG, ENMG (preferably in dynamics).
2. MRI of the spinal cord and brain (if possible).
3. Data of experimental psychological research (with cerebral form, if necessary).
4. Analyzes of cerebrospinal fluid, blood, urine.
5. Data of somatic examination.

Criteria for establishing disability groups

Group I (38% of patients): rapid progression (especially in the bulbar form), pronounced movement disorders (according to the criterion of limiting the ability to self-service of the third degree).

Group II (in 53% of patients): a clearly progressive course, initial bulbar disorders, pronounced movement disorders (according to the criteria for limiting the ability to move, self-service of the second degree).

Group III (in 9% of patients): a) more often in the lumbosacral form at the initial stage of the disease (mild lower mono-, paraparesis); b) in the absence of bulbar disorders, mild paresis, slow progression in the case of the cervicothoracic form (rarely); c) in patients with an unspecified diagnosis due to the need for systematic observation, re-examination, changes in conditions and nature of work (physical labor is contraindicated). The criteria for limiting the ability to work, movement of the first degree are used.

The reason for the disability: usually a common disease.

Rehabilitation options are extremely limited due to the lack of effective therapy. Patients need dispensary observation (examination by a neuropathologist at least 3-4 times a year), repeated inpatient treatment. Vocational rehabilitation in the form of employment in the professions of the humanitarian or administrative and clerical profile with a small amount of work is possible in the case of the lumbosacral form.
Social rehabilitation should include training a disabled person in self-service, psychological assistance, and other measures of social protection.

Update: December 2018

Amyotrophic lateral sclerosis or Lou Gehrig's disease is a rapidly progressive disease of the nervous system, characterized by damage to the motor neurons of the spinal cord, cortex, and brain stem. Also, the motor branches of cranial neurons (trigeminal, facial, glossopharyngeal) are involved in the pathological process.

Epidemiology of the disease

The disease is extremely rare, about 2-5 people per 100,000. It is believed that men are more likely to get sick after 50 years. Lou Gehrig's disease makes no exception for anyone; it affects people of different social status and different professions (actors, senators, Nobel laureates, engineers, teachers). The most famous patient was the world baseball champion Loi Gering, after whom the disease got its name.

In Russia, amyotrophic lateral sclerosis is widespread. Currently, the number of sick people is approximately 15,000-20,000 in the population. Among famous people Russia with this pathology can be noted the composer Dmitry Shostakovich, the politician Yuri Gladkov, pop singer Vladimir Migulya.

Causes of amyotrophic lateral sclerosis

The disease is based on the accumulation of pathological insoluble protein in the motor cells of the nervous system, leading to their death. The cause of the disease is currently unknown, but there are many theories. The main theories include:

• Viral - this theory was popular in the 60-70s of the 20th century, but has not been confirmed. Scientists from the USA and the USSR carried out experiments on monkeys, injecting them with extracts of the spinal cord of sick people. Other researchers have tried to prove participation in the formation of the disease.
• Hereditary - in 10% of cases, the pathology is hereditary;
• Autoimmune - This theory is based on the detection of specific antibodies that kill motor nerve cells. There are studies proving the formation of such antibodies against the background of other serious diseases (for example, with lung cancer or Hodgkin's lymphoma);
• Genetic - in 20% of patients, a violation of genes encoding a very important enzyme Superoxide dismutase-1 is found, which converts Superoxide, toxic to nerve cells, into oxygen;
• Neural - British scientists believe that glial elements are involved in the development of the disease, that is, cells that provide the vital activity of neurons. Studies have shown that with insufficient function of astrocytes, which remove glutamate from nerve endings, the likelihood of developing Lou Gehrig's disease increases tenfold.

Classification of amyotrophic lateral sclerosis:

Symptoms of amyotrophic lateral sclerosis

Any form of the disease has the same onset: patients complain of increasing muscle weakness, a decrease muscle mass and the appearance of fasciculations (muscle twitching).

Bulbar form of ALS characterized by symptoms of cranial nerve damage (pairs 9, 10 and 12):

• In sick people, speech, pronunciation worsens, it becomes difficult to move the tongue.
• Over time, the act of swallowing is disturbed, the patient constantly chokes, food can be poured out through the nose.
• Patients experience involuntary twitching of the tongue.
• The progression of ALS is accompanied by complete atrophy of the muscles of the face and neck, patients completely lack facial expressions, they cannot open their mouths, chew food.

Cervicothoracic option the disease affects, first of all, the upper limbs of the patient, symmetrically on both sides:

• At first, patients feel a deterioration in the functionality of the hands, it becomes harder to write, play musical instruments, and perform complex movements.
• At the same time, the muscles of the arm are very tense, tendon reflexes are increased.
• Over time, the weakness spreads to the muscles of the forearm and shoulder, they atrophy. The upper limb resembles a dangling whip.

Lumbosacral form usually begins with a feeling of weakness in the lower extremities.

• Patients complain that it has become more difficult for them to do work while standing on their feet, walk long distances, and climb stairs.
• Over time, the foot begins to sag, the muscles of the legs atrophy, patients cannot even stand on their feet.
• Pathological tendon reflexes (Babinsky) appear. Patients develop urinary and fecal incontinence.

Regardless of which option prevails in patients at the beginning of the disease, the outcome is still the same. The disease is steadily progressing, spreading to all muscles of the body, including the respiratory. When the respiratory muscles fail, the patient begins to require mechanical ventilation and constant care.

In my practice, I have observed two ALS patients, a man and a woman. They were distinguished by their red hair color and relatively young age (up to 40 years). Outwardly, they were very similar: there is not even a hint of the presence of muscles, an expressionless face, always a slightly open mouth.

Such patients die in most cases from concomitant diseases (pneumonia, sepsis). Even with proper care, they develop bedsores (see), hypostatic pneumonia. Realizing the severity of their illness, patients fall into depression, apathy, and cease to be interested outside world and their loved ones.

Over time, the patient's psyche undergoes dramatic changes. The patient whom I observed for a year was characterized by moodiness, emotional lability, aggressiveness, and incontinence. Intellectual tests showed a decrease in his thinking, mental abilities, memory, attention.

Diagnostics of the amyotrophic lateral sclerosis

The main diagnostic methods include:

• MRI of the spinal cord and brain - the method is quite informative, reveals atrophy of the motor regions of the brain and degeneration of pyramidal structures;
• cerebrospinal puncture - usually reveals normal or increased content squirrel;
• neurophysiological examinations - electroneurography (ENG), electromyography (EMG) and transcranial magnetic stimulation (TCMS).
• molecular genetic analysis - studies of the gene encoding Superoxide dismutase-1;
• biochemical blood test - reveals an increase of 5-10 times in creatine phosphokinase (an enzyme formed during muscle breakdown), a slight increase in liver enzymes (ALT, AST), accumulation of toxins in the blood (urea, creatinine).

What happens with ALS

Due to the fact that ALS has similar symptoms to other diseases, differential diagnosis is made:

• brain diseases: tumors of the posterior cranial fossa, multisystem atrophy,
• muscle diseases: oculopharengial myodystrophy, Rossolimo-Steinert-Kurshman myotonia
• systemic diseases
• spinal cord diseases: lymphocytic leukemia or lymphoma, spinal cord tumors, spinal amyotrophy, syringomyelia, etc.
• peripheral nerve diseases: Personage-Turner syndrome, Isaacs neuromyotonia, multifocal motor neuropathy
• myasthenia gravis, Lambert-Eaton syndrome - diseases of the neuromuscular synapse

Treatment of amyotrophic lateral sclerosis

Treatment of the disease is currently ineffective. Medication and proper patient care only prolong life without ensuring complete recovery. Symptomatic therapy includes:

• Riluzole (Rilutek) Is a well-established drug in the US and UK. Its mechanism of action is to block glutamate in the brain, thereby improving the work of Superoxide dismutase-1.
• RNA interference Is a very promising method of treating ALS, the creators of which were awarded the Nobel Prize in Medicine. The technique is based on blocking the synthesis of pathological proteins in nerve cells and preventing their subsequent death.
• Stem cell transplant - studies have shown that stem cell transplantation to the central nervous system prevents the death of nerve cells, restores neural connections, improves the growth of nerve fibers.
• Muscle relaxants - eliminate muscle spasm and twitching (Baclofen, Sirdalud).
• Anabolics (Retabolil) - to increase muscle mass.
• Anticholinesterase drugs (Proserin, Kalimin, Pyridostigmine) - prevent the rapid destruction of acetylcholine in the neuromuscular synapses.
• B vitamins (Neurorubin, Neurovitan), vitamins A, E, C - these funds improve the conduction of the impulse along the nerve fibers.
• Broad spectrum antibiotics (cephalosporins of 3-4 generations, fluoroquinolones, carbopenems) - are indicated for the development of infectious complications, sepsis.

IN complex therapy necessarily include feeding through a nasogastric tube, massage, exercise therapy with a doctor, psychologist consultations.

Forecast

Sadly, but the prognosis for amyotrophic lateral sclerosis is unfavorable. Patients die literally after a few months or years, the average life expectancy for patients:

• only 7% live more than 5 years
• with bulbar debut - 3-5 years
• with lumbar - 2.5 years

A more favorable prognosis in hereditary cases of the disease associated with mutations in the superoxide dismutase-1 gene.

The situation in Russia is overshadowed by the fact that patients are not provided with adequate assistance, as evidenced by the fact that Riluzot is a drug that slows down the course of the disease, until 2011 in Russia it was not even registered, and only in the same year the disease itself was included in the list " rare ". But in Moscow there are:

• Fund for Assistance to Patients with Amyotrophic Lateral Sclerosis at the Martha-Mariinsky Mercy Center
• G. N. Levitsky Charitable Foundation for ALS Patients

Finally, I would like to add about the Ice Bucket Challenge charity event that took place in July 2014. It was aimed at raising funds in support of patients with amyotrophic lateral sclerosis and was widely used. The organizers managed to raise more than $ 40 million.

The essence of the action was that a person either doused himself with a bucket of ice water and captured it on video, or donated a certain amount of money to a charitable organization. The action has become quite popular due to the participation of popular performers, actors and even politicians.

It used to be thought that ALS only affected the motor neurons that control muscles. However, now there is an understanding of the changes occurring in this disease in the brain, which affect the processes of thinking, the expression of emotions and the behavior of patients. This article will help you understand the nature of changes in the processes of higher mental functions in ALS.

What does "change in higher mental (cognitive) functions" mean?

Cognitive functions (lat.cognitio — knowledge) — these are the highest brain function: memory, attention, psychomotor coordination, speech, counting, thinking, orientation, planning and control of higher mental activity. They also include verbal communication, such as the ability to pronounce words, respond to and interact with other people.

With regard to the violation of the higher mental functions of people with ALS, it can be divided into four categories according to the degree of impairment:

• no cognitive changes;
• subtle changes in behavior and cognition processes;
• pronounced changes in behavior and cognitive processes with the development of frontotemporal dementia (FTD);
• people with LVD who develop movement disorders and who are diagnosed with ALS after dementia.

Some people experience subtle, subtle changes, while changes in others are more noticeable.

LVD — This is a type of dementia (dementia) in which serious changes in cognition and behavior develop. About 5% of people with ALS also suffer from LVD. This type is different from Alzheimer's disease, which is the most common form of dementia.

How often do people with ALS experience changes in thinking and behavior?

Recent research suggests that up to 50% of ALS patients never experience noticeable changes in thinking and behavior that go beyond normal psychological responses. As for the second half of patients, about 25% of them may experience frontotemporal dementia.

What are the risk factors for the development of such disorders in ALS?

Older age, bulbar disease, other family history of dementia and previously identified neurological disorders are considered factors that increase the likelihood of developing cognitive and behavioral impairments in ALS. But there have been cases of the development of these symptoms in people who did not face the mentioned risk factors. To date, the only confirmed risk factor for the development of cognitive and behavioral impairments is a disruption in the C9ORF72 gene.

External manifestations of changes in higher mental functions

Changes in higher mental functions can manifest themselves in different forms... Some people find it difficult to:

• concentrate, for example, while reading;
• start something new or learn to use new equipment;
• start a conversation;
• keep up a conversation if there is a distraction;
• plan any sequence of actions;
• starting a business or assignment;
• bring things to the end;
• do more than one thing at a time, such as talking to someone while watching TV;
• remember the names of objects that they previously knew;
• understand complex sentences.

As a result, some changes develop:

• awkward, infantile, or simply uncharacteristic behavior for the patient;
• inappropriate comments;
• high consumption of sweet or one specific type of food, or chewing food for too long;
• reduced attention to hygiene issues, for example, when visiting the toilet or refusing to regularly bathe, cut a hair, or change clothes;
• loss of judgment necessary for making decisions, or making decisions that are very different from what the patient said earlier;
• lack of responsiveness or indifference to the emotional states of others;
• fixation on some one routine matter;
• increased aggression;
• the patient may say "yes" instead of "no" or vice versa, or be unsure of the answer to simple questions;
• a feeling of breaking the connection between the thought of wanting to move a certain part of the body and the action itself;
• incorrect construction of phrases;
• inability to find the right word during a conversation;
• feeling anxious;
• misuse of words;
• using meaningless sentences;
• inability to follow instructions during physical therapy or other manipulation;
• forgetting what the patient intended to do;
• lack of motivation or initiative;
• impulsive actions without considering the consequences.

A sick person may not be aware of the changes taking place. This is usually very upsetting to others and family members.

Changes in thinking and behavior in ALS can be associated not only with the development of the disease, but also with other factors, for example, insufficient breathing (low oxygen or high carbon dioxide), side effects of drug therapy, depression or anxiety, sleep disturbance, or a pre-existing mental or neurological disorder. It is very important to report all symptoms to healthcare professionals so that they can determine the cause of the problem, especially if it can be corrected.

What else can be in violation of higher mental functions?

Mood

Naturally, attempts to adapt your life to progressive ALS lead to mood swings. Many people with this condition feel very empty.

For some, these sensations are so strong that depression develops. If a person has difficulty doing something or has trouble concentrating, this may be due to a low mood, rather than a change in consciousness. Some people take medications for these conditions, such as antidepressants. Consultation with a specialist may be required.

Emotional lability

Some people with ALS become emotionally unstable. This leads to uncontrollable laughter or, conversely, crying in response to something that is not funny or sad enough to give such a strong reaction, such as a television program. Sometimes it looks very inappropriate and confuses others. ALS patients be prone to emotional lability with no other cognitive, behavioral, or psychological symptoms.

Breath

If ALS affects the breathing process, it affects the quality of sleep, which also leads to changes in the processes of concentration and memory. When a ventilator is used to aid breathing, it is worth checking the settings to ensure that it is working correctly.

Wellbeing

Sometimes confused thinking can be a consequence infectious diseases respiratory tract or genitourinary system. Therefore, it is worth paying attention to the presence of factors inherent in infection, such as fever, feeling unwell.

How are cognitive and behavioral impairments diagnosed in ALS?

To find out whether the symptoms are associated with ALS or another process, it is necessary to contact to conduct an appropriate assessment of the patient's condition. This can usually be done by your doctor or neuropsychologist. The assessment is made on the basis of various tests that reflect how a person processes information. For example, a doctor may ask you to name as many words as possible that start with a specific letter of the alphabet, or memorize the maximum number of words and re-name them, or spell words. The results obtained are compared with the standard indicators for people of the same age and with the same level of education. This makes it possible to establish whether there are indeed violations, and if so, what kind. The professional may need to discuss the situation not only with the patient, but also with the people caring for him and / or who know him well.

What happens after the diagnosis is confirmed?

Some relatives and caregivers experience relief after confirmation of the impairment, because in this case they know for sure that the cognitive and behavioral changes in the patient with ALS are not associated with psychological reasons or attempts to confront other people. If the ALS patient is aware of their actions, they can document their wishes for further care and therapy. This is especially important because cognitive and behavioral impairments, like other ALS symptoms, worsen as the disease progresses.

If the patient is already disabled, family members, carers and healthcare professionals need to balance their expectations of the patient with reality. In this situation, one should not expect that a person will change his behavior. The environment must change. Patient expectations should be matched to their capabilities. If the patient begins to withdraw or worry when asked to do something, it may be a sign that expectations are exceeding their capabilities. Moreover, if family members or caregivers begin to feel frustrated or resentful when communicating with the patient, expectations of the situation need to be simplified. In the case of dementia, all professionals working with the patient must focus on educating and involving caregivers and family members, since the patient cannot change of his own accord.

Family members and caregivers can benefit from attending counseling sessions, counseling groups, spiritual meetings, or taking more care of themselves, which will also increase their resources (physical and emotional) to care for someone with ALS.

How does the presence of such disorders affect the progression of ALS?

There is evidence that people with cognitive and behavioral impairments with ALS live shorter lives than patients without these symptoms. Many ongoing studies are aimed at finding out whether the presence or absence of such disorders affects the effectiveness of medications, treatment and other procedures for ALS. This is an important area of \u200b\u200bscientific research.

What's next?

Your doctor may advise you to get tested. This will help identify the reason for the change. You may also be told about options for overcoming some difficulties. The doctor can give advice on how to communicate with the person, for example, asking questions with only "yes" or "no" answers, avoiding long and complex sentencesrequiring clarification.

There are many ways to make communication and daily activities easier. The ultimate goal of these recommendations — help the person with ALS control themselves. It will also be very helpful to caregivers and family members.
If you understand the reasons for the changes in a person's consciousness, then the caregivers will act more confidently.

• Learn and improve.
• Take care of yourself.
• Try to make communication with the patient as easy as possible. Use short phrases. Ask questions that can be answered yes or no. Speak slowly.
• Accompany the patient during any meetings to make sure that the exchange of information between the patient and the interlocutors is in the right way.
• Align your expectations for the ALS patient with reality. If your request causes irritation, resentment or rejection by the patient or yourself, expectations should be changed to meet the needs and capabilities of the person concerned.
• Tell the professionals involved in patient care and treatment about his condition.
• Continue to maintain relationships and do activities that bring you joy, and take a break from those that cause stress.

Who can help?

Symptoms of amyotrophic lateral sclerosis Simply put - from our experience - it is worth pondering when the growing weakness continues with burr, begins to drag stop or massively begin to beat the plates in the kitchen, falling out of hands. Attention - this is not always ALS - you may just you are experiencing tremendous stress and nervous strain! “Symptoms of amyotrophic lateral sclerosis are symptoms of damage to the lower motor neuron, including weakness, atrophy, cramps and fasciculations, 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 may be involved, strengthening the already developed disease at the level of the brain stem. Amyotrophic lateral sclerosis is an adult disease and does not begin in persons under 16 years of age. The most important clinical marker initial stages amyotrophic lateral sclerosis is asymmetric progressive muscle atrophy with hyperreflexia (as well as fasciculations and cramps). The disease can begin with any striated muscles. Allocate high (progressive pseudobulbar paralysis "), bulbar ("Progressive bulbar palsy"), cervicothoracic and lumbosacral forms). Death is usually associated with the involvement of the respiratory muscles after about 3-5 years. Most frequent symptom amyotrophic lateral sclerosis, occurring in about 40% of cases, is progressive muscle weakness of one upper limb, usually starting from the hand (starting from the proximal located muscles reflects a more favorable variant of the disease). If the onset of the disease is associated with the appearance of weakness in muscles of the hand, then the thenar muscles are usually involved in the form of weakness of adduction (adduction) and opposition thumb... it makes it difficult to grasp with the thumb and forefinger and leads to a violation of fine motor control. The patient feels difficulty picking up small items and dressing (buttons). If the leading hand is affected, then progressive difficulty in writing, as well as in everyday life. In the typical course of the disease, there is a steadily progressive involvement of other muscles of the same limb and then spread to the other hand before being struck lower limbs or bulbar muscles. The disease can start from the muscles of the face or mouth and tongue, from the muscles of the trunk (the extensors suffer more flexors) or the lower extremities. At the same time, the involvement of new muscles never "catches up" the muscles with which the disease began. Therefore, the shortest life expectancy is observed in the bulbar form: patients die from bulbar disorders while remaining on their feet (patients do not have time to live to paralysis in the legs). A relatively favorable shape is the lumbosacral. With the bulbar form, one or another variant of a combination of symptoms of bulbar and pseudobulbar paralysis is observed, which is manifested mainly by dysarthria and dysphagia, and then by respiratory disorders. A characteristic symptom almost all form of amyotrophic lateral sclerosis is an early increase in the mandibular reflex. Dysphagia when swallowing liquid food occurs more often than solid food, although swallowing solid food as the disease progresses finds it difficult. Weakness of the masticatory muscles develops, the soft palate hangs down, the tongue in the oral cavity is motionless and atrophic. There is anarthria, continuous saliva flow, inability to swallow. The risk of aspiration pneumonia increases. It is also helpful to remember that krumpy (often generalized) occurs in all ALS patients and is often the first symptom of the disease. It is characteristic that atrophies throughout the course of the disease are clearly selective. Thenar are amazed on the hands, hypotenar, interosseous muscles and deltoids; on the legs - muscles that carry out dorsiflexion of the foot; in bulbar musculature - muscles of the tongue and soft palate. The most resistant to damage in amyotrophic lateral sclerosis are the oculomotor muscles. Sphincter disorders are considered rare in this disease. Another intriguing feature of amyotrophic lateral sclerosis is lack of bedsores even in patients who are paralyzed and bedridden (immobilized) long time... Known also that dementia is rare in amyotrophic lateral sclerosis (with the exception of some subgroups: familial forms and with the complex "parkinsonism-ALS-dementia" on the island of Guam). Forms with uniform involvement of the upper and lower motoneurons, with a predominance of damage to the upper (pyramidal syndrome in "primary lateral sclerosis") or lower (anterior horn syndrome) motor neuron. Among paraclinical studies, electromyography has the most significant diagnostic value. Revealed widespread damage to the cells of the anterior horns (even in clinically intact muscles) with fibrillation, fasciculations, positive waves, changes in the potentials of motor units (their amplitude and duration increase) with normal speed of conduction of excitation along the fibers of the sensory nerves. The content of CPK in plasma can be slightly increased. " (http://ilive.com.ua/)