Guillain-Barre Syndrome

Guillain-Barre syndrome (acute idiopathic polyneuritis, Landry paralysis, acute inflammatory demyelinating polyradiculoneuropathy) is an acute, usually rapidly progressive inflammatory polyneuropathy characterized by muscle weakness and moderate prolapse of distal sensitivity. Autoimmune disease. Diagnosis according to clinical data. Treatment of Guillain-Barre syndrome: plasmapheresis, y-globulin, according to indications, artificial ventilation of the lungs. The outcome of the syndrome is significantly improved with adequate maintenance treatment in the intensive care unit and the use of modern methods of immunomodulatory therapy.

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

Epidemiology

The incidence ranges from 0.4 to 4 cases per 100 000 population per year. Guillain-Barre syndrome is observed in any age group, but more often in persons 30-50 years old, with equal frequency in men and women. Racial, geographical and seasonal differences in incidence for Guillain-Barre syndrome are generally not typical, with the possible exception of cases of acute motor axonal neuropathy, which are most common in China and are usually associated with intestinal infection caused by Campylobacter jejuni and therefore occur more frequently in the summer.

The incidence significantly increases after 40 years. A year from the Guillain-Barre syndrome in the United States, an average of 600 people die. Thus, Guillain-Barre syndrome is a very important health problem, especially relevant for the elderly.

[5], [6], [7], [8], [9],

Causes of the guillain-Barre syndrome

The most common of the acquired inflammatory neuropathies. The autoimmune mechanism is not fully understood. Several variants are known: in some, demyelination predominates, in others the axon suffers.

Approximately in 2/3 of cases, the syndrome appears after 5 days - 3 weeks after an infection, surgery or vaccination. In 50% of cases, the disease is associated with infection with Campylobacter jejuni, enteroviruses and herpes viruses (including cytomegalovirus and viruses that cause mononucleosis), as well as Mycoplasma spp. In 1975 there was an outbreak associated with the vaccination program against swine flu.

[10], [11], [12], [13],

Pathogenesis

Demyelination and inflammatory infiltration in the roots of the spinal nerves and proximal nerves can explain the clinical symptoms of Guillain-Barre syndrome. It is believed that both humoral and cellular immunity are involved in the pathogenesis of the disease. The presence of lymphocytes and macrophages in the perivenotic zones and their interaction with myelinated axons testify, first of all, to the possible role of autoimmune reactions in the demyelinating process. This situation is confirmed by earlier observations, according to which the immunization of laboratory animals with peripheral myelin with adjuvant causes experimental allergic neuritis. Although it was later shown that purified myelin proteins - for example, myelin basic protein P2 or peptide fragments P2 and protein PO - are capable of causing experimental neuropathy, antibodies to these compounds are rarely detected in Guillain-Barre syndrome. T cells isolated from spleen and lymph nodes of rats immunized with P2-synthetic peptide 53-78 can experimentally reproduce severe experimental allergic neuritis in syngeneic mice. Thus, cellular and, possibly, humoral immune mechanisms can mediate the creation of an experimental model of inflammatory damage of peripheral nerves.

Recent studies have focused on the role of glucoconjugates and lipopolysaccharides of the myelin sheath, Schwann cell membrane or axonal membrane as the main antigens that initiate the inflammatory / immune reaction in Guillain-Barre syndrome. In a detailed study in Japan, the patients identified Campylobacter jejuni antigens . In this study, the Penner method was used to detect thermostable lipopolysaccharides, and the Lior method was used to determine thermolabile protein antigens. The antigens PEN 19 and LIO 7 C. Jejuni were more often isolated in patients with Guillain-Barre syndrome (respectively, in 52 and 45% of cases) than in patients with sporadic enteritis caused by S. Jejuni (respectively 5 and 3%), and were associated with an increase in antibody titer to GM1 (possibly due to the presence of a GM1-like lipopolysaccharide antigen). According to reports from other countries, S. Jejuni infection is much less likely to precede the development of the SGB. In addition, the percentage of patients with anti-ganglioside antibodies was much more variable, ranging from 5% to 60%. In addition, no correlation was found between the presence of antibodies to GM1 and the clinical and electrophysiological manifestations of the disease.

In Miller Fischer's syndrome, antibodies to GQlb are often detected. With the help of immunohistochemical methods, GQlb was detected in the paranodal area of the human cranial nerves, innervating the eyes. It has been established that antibodies to GQlb can block transmission in the neuromuscular system of mice.

In the axonal motor variant of Guillain-Barre syndrome, the disease was often preceded by S. Jejuni infection, and antibodies to ganglioside GM1 and the product of complement activation of C3d were associated with axolemma of motor fibers.

Antibodies to GMI can also be associated with Ranvier interceptions, thereby impairing impulses. In addition, these antibodies are able to cause degeneration of the endings of motor fibers and intramuscular axons, which was recently shown in patients with acute motor axonal polyneuropathy. Enteritis caused by C. Jejuni, can provoke Guillain-Barre syndrome, enhancing the production of gamma-delta-T-lymphocytes, which are able to actively participate in inflammatory / immune processes. A high serum level of tumor necrosis factor-alpha (TNF-a), but not interleukin-1b or soluble interleukin-2 receptor, correlated with electrophysiological changes in Guillain-Barre syndrome. Examination of samples obtained at autopsy indicates that at least in some cases the classic acute inflammatory demyelinating form of Guillain-Barre syndrome is complemented, as indicated by the detection on the outer surface of Schwann cells of C3d and C5d-9 components forming the membrane-attack complex.

Thus, with Guillain-Barre syndrome, most of the components that normally participate in the pathogenesis of immuno-mediated diseases are represented. Although antibodies against glucoconjugates are likely to be involved in the pathogenesis of several different clinical forms of the Guillain-Barre syndrome, their exact role is unknown. Even if antibodies to GM1 are present, they can bind not only to GM1, but also to other glycolipids or glycoproteins having similar carbohydrate sites. In this regard, the specific antigens of Schwann cells or the axonal membrane against which the inflammatory / immune response is directed, as well as the possible role of immunoglobulins require clarification. Moreover, in many cases of Guillain-Barre syndrome, there are no signs of a prior or concomitant C. Jejuni infection , an antibody to GM1 or signs of another microorganism whose antigens can initiate an immune reaction (for example, due to molecular mimicry).

A study of materials obtained from nerve biopsy and autopsy shows that cellular immune mechanisms also contribute to the development of Guillain-Barre syndrome. In severe cases of Guillain-Barre syndrome, lymphocytes and macrophages are present throughout the motor fibers from the roots to the ends, and the activated macrophages are in close contact with myelin or phagocytose myelin. Although the experimental model of inflammatory neuropathy obtained data confirming the involvement of T-lymphocytes in nerve damage, there is no convincing evidence that this occurs in patients with Guillain-Barre syndrome. The data accumulated to date confirm the involvement of activated T-lymphocytes crossing the blood-brain barrier and initiating demyelination together with antibodies to specific antigens of nerve fibers, cytokines (such as TNF-a and interferon-y), complement components, possibly including membrane-attack complex and activated macrophages . More research is needed to clarify the role of each of these elements, as well as the sequence in which they participate in the pathogenesis of Guillain-Barre syndrome.

[14], [15], [16], [17], [18], [19], [20],

Symptoms of the guillain-Barre syndrome

Symptoms of Guillain-Barre syndrome consist in the dominance of flaccid paresis (the more proximal, the more profound), the sensitivity disorders are less pronounced. Typically, an almost symmetrical weakness with paresthesia begins with the legs, less often with the hands or head. In 90% of cases, the weakness reaches a maximum at the 3rd week of the disease. Deep tendon reflexes fall out. The function of the sphincter is preserved. In severe cases in half the cases, the weakness of the facial and oropharyngeal muscles is evident. In 5-10% of cases, intubation and ventilation are required in connection with paralysis of the respiratory muscles.

Sometimes (apparently, in variant form) develops a pronounced autonomic dysfunction with fluctuations in blood pressure, abnormal secretion of antidiuretic hormone, arrhythmias, intestinal stasis, urinary retention, and impaired pupillary response to light. Fischer's syndrome is a rare variant of Guillain-Barre syndrome, it presumes ophthalmoplegia, ataxia and areflexia.

The first symptoms, the order of their appearance and dynamics

In typical cases, Guillain-Barre syndrome begins with muscle weakness and / or sensory disorders (numbness, paresthesia) in the lower extremities that spread to the upper limbs in a few hours or days.

The first symptoms of Guillain-Barre are disorders of sensitivity, for example, paresthesia in the feet. Although objective signs of impaired sensitivity are detected quite often, they usually are mild. Early and extremely unpleasant for patients manifestations of the disease can be deep aching back pain and painful dysesthesia in the extremities. Paralysis can initially involve the lower extremities, and then quickly, within a few hours or days, spread in the ascending direction to the upper limbs, mimic, tabloid and respiratory muscles. However, a different development of events is also possible, when the disease begins with weakness in mimic muscles and upper limbs, then involves lower limbs. From the very beginning, the symptoms are usually symmetrical, and the paralysis is accompanied by the loss or weakening of tendon and periosteal reflexes. Guillain-Barre syndrome often involves vegetative fibers. Autonomic symptoms are detected in about 50% of cases, but the function of sphincters usually does not suffer. The disease has a monophasic course: after a period of increasing symptoms lasting for several days or weeks, a plateau period lasting from several days to several months follows, followed by a recovery for several months. In 1976-1977, there was a slight increase in the incidence of Guillain-Barre syndrome associated with the immunization of swine influenza vaccine, but no immunization with another variant of the influenza vaccine was registered in 1980-1988.

In classic cases, manifested by a combination of motor, sensory and vegetative symptoms, which are based on demyelinating polyradiculoneuropathy, the diagnosis of Guillain-Barre syndrome rarely causes difficulties. However, there is also an axonal variant of Guillain-Barre syndrome, mainly manifested by motor disorders, and acute motor-sensory axonal neuropathy. The acute axonal form usually shows a more coarse functional defect and has a more unfavorable prognosis. The combination of ophthalmoplegia, ataxia and aireflexia is characteristic of another variant of the Guillain-Barre syndrome, known as the Miller Fisher syndrome. From a diagnostic point of view, in the absence of symptoms of cranial nerve damage, even with the preserved function of sphincters, it is necessary to exclude the compression of the spinal cord by means of neuroimaging. In differential diagnosis, it is also important to bear in mind acute intermittent porphyria, metal intoxication capable of causing acute polyneuropathy, as well as systemic diseases such as infectious mononucleosis, paraneoplastic syndromes, or various metabolic disorders. HIV-infected patients are predisposed to the development of polyneuropathy or polyradiculoneuropathy, which may be associated with Guillain-Barre syndrome, cytomegalovirus polyradiculoneuropathy or lymphoma. These conditions are difficult to differentiate, based only on clinical manifestations, but the study of cerebrospinal fluid in polyradiculoneuropathy associated with HIV infection usually reveals neutrophilic pleocytosis and signs of viral replication.

Vegetative dysfunction (including accommodation disorders, abdominal and thoracic pain, arterial hypotension, tachycardia) can significantly aggravate the patient's condition and serves as an unfavorable prognostic sign. In one of the studies, subclinical signs of involvement of both the sympathetic and parasympathetic nervous system, revealed using tests for autonomic functions, were noted in the vast majority of patients.

North American scale of gravity of impellent deficiency

Power	Symptoms
0	Norm
I	Minimal movement disorders
II	Ability to pass 5 m without support (support)
III	Ability to walk 5 m with support (support)
IV	Impossibility to pass 5 m with support or support (bed rest or wheelchair)
V	Need for ventilation

• A third of patients develop respiratory failure.
• In most cases, there are disorders of surface sensitivity in the form of mild or moderate hypo- or hyperesthesia according to the polyneuric type (such as "socks and gloves"). Often there are pains in the hips, lumbar and gluteal regions. They can be both nociceptive (muscular) and neuropathic (caused by damage to sensory nerves). Disorders of deep sensitivity (especially vibrational and muscular-joint feeling), which are very coarse (up to complete loss), are detected in approximately half of the patients.
• Lesions of the cranial nerves are observed in most patients. It is possible to involve any cranial nerves (except for I and II pairs) in the process, but with the greatest persistence observe the damage of VII, IX and X pairs, which is manifested by paresis of facial muscles and bulbar disorders.
• Autonomic disorders are observed in more than half of patients and can be represented by the following disorders.
  • Transient or persistent arterial hypertension or less often arterial hypotension.
  • Cardiac arrhythmias, most often sinus tachycardia.
  • Sweating disorder [local (palms, feet, face) or general hyperhidrosis].
  • Violations of the functions of the digestive tract (constipation, diarrhea, in rare cases, intestinal obstruction).
  • Violations of the functions of the pelvic organs (usually the retention of urine) are rare, they are usually mild and transient.
• With Miller-Fisher syndrome, ataxia predominates in the clinical picture, which usually has the features of the cerebellar, in rare cases - mixed (cerebellar-sensitive), and partial or total ophthalmoplegia, possibly also the defeat of other cranial nerves (VII, IX, X). Pareses are usually mild, in a quarter of cases there are sensory disorders.

[21], [22], [23], [24], [25]

Diagnostic criteria of Guillain-Barre syndrome

[26], [27], [28], [29], [30]

Signs of Guillain-Barre syndrome required for diagnosis

• A. Progressive muscle weakness in more than one limb
• B.Areflexia (absence of tendon reflexes)

Symptoms of Guillain-Barre syndrome supporting the diagnosis

• A. Clinical signs (listed in order of importance)
  • Progression: muscle weakness develops quickly, but stops progressing within 4 weeks after the onset of the disease.
  • Relative symmetry: symmetry is rarely absolute, but when the limb is injured, the opposite is also affected (commentary: patients often report asymmetric symptoms at the onset of the disease, but by the time of objective examination the lesions are usually symmetrical).
  • Subjective and objective symptoms of sensitivity disorders.
  • Defeat of cranial nerves: paresis of facial muscles.
  • Recovery: usually begins 2-4 weeks after the disease progresses, but it can sometimes be delayed for several months. Most patients observe complete recovery of functions.
  • Vegetative disorders: tachycardia and other arrhythmias, postural arterial hypotension, arterial hypertension, vasomotor disorders.
  • Absence of fever in the onset of the disease (in some cases, fever in the onset of the disease is possible due to intercurrent diseases or other causes, the presence of fever does not exclude Guillain-Barre syndrome, but increases the likelihood of another disease, in particular poliomyelitis).
• B. Options
  • Pronounced sensitivity disorders with pain.
  • Progression more than 4 weeks. Sometimes progression of the disease is possible for many weeks or the presence of small relapses.
  • Cessation of progression without subsequent recovery or persistence of a persistent residual symptomatology.
  • Functions of sphincters: usually sphincters are not affected, but in some cases, there may be a violation of urination.
  • CNS lesion: Guillain-Barre syndrome affects the peripheral nervous system, there is no reliable evidence of the possibility of CNS damage. Some patients have a rough cerebellar ataxia, extensor-type pathological extras, dysarthria, or an unclear level of sensory impairment (implying a conductive type of disorder), but they do not exclude the diagnosis of Guillain-Barre syndrome if there are other typical symptoms
• C. Changes in cerebrospinal fluid confirming the diagnosis
  • Protein: 1 week after the onset of the disease, the concentration of protein in the cerebrospinal fluid becomes elevated (within the first week, it may be normal).
  • Cytosis: the content of mononuclear leukocytes in CSF is up to 10 in 1 μl (with a white blood cell count of 20 in 1 μl or more, a thorough examination is necessary.) If their content is more than 50 in 1 μl, the diagnosis of Guillain-Barre syndrome is rejected, except for patients with HIV infection and Lyme borreliosis).

Symptoms of Guillain-Barre syndrome, which cause doubts in the diagnosis

1. Strong asymmetry of paresis.
2. Persistent pelvic disorders.
3. The presence of pelvic disorders in the debut of the disease.
4. The content of mononuclear leukocytes in CSF is more than 50 in 1 μl.
5. Presence of polymorphonuclear leukocytes in the cerebrospinal fluid.
6. A clear level of sensitivity disorders

Signs of Guillain-Barre syndrome, excluding diagnosis

1. Abuse of currently volatile organic solvents (substance abuse).
2. Disorders of porphyrin metabolism, implying the diagnosis of acute intermittent porphyria (increased urinary excretion of porphobilinogen or aminolevulinic acid).
3. Recently transferred diphtheria.
4. Presence of symptoms of neuropathy due to intoxication with lead (paresis of muscles of the upper limb, sometimes asymmetric, with pronounced weakness of the extensor of the hand) or evidence of lead intoxication.
5. The presence of exclusively sensory disorders.
6. Reliable diagnosis of another disease, manifested similar to Guillain-Barre syndrome symptoms (poliomyelitis, botulism, toxic polyneuropathy).

Recently, some authors, as a casuistically rare atypical form of Guillain-Barre syndrome, consider acute sensory neuropathy, which is manifested by extremely sensitive disorders.

Forms

Currently, in the Guillain-Barre syndrome, four main clinical variants are distinguished.

• Acute inflammatory demyelinating polyradiculoneuropathy is the most frequent (85-90%), the classical form of the Guillain-Barre syndrome.
• The axonal forms of the Guillain-Barre syndrome are observed much less frequently (10-15%). Acute motor axonal neuropathy is characterized by an isolated lesion of motor fibers, the most common in the countries of Asia (China) and South America. In acute motor-sensory axonal neuropathy both motor and sensitive fibers are affected, this form is associated with prolonged course and unfavorable prognosis.
• The syndrome of Miller-Fisher (no more than 3% of cases) is characterized by ophthalmoplegia, cerebellar ataxia and areflexia with usually mild paresis.

In addition to the main, recently a few more atypical forms of the disease have been identified - acute pandisavtonomia, acute sensory neuropathy and acute cranial polyneuropathy, which are very rare.

[31], [32], [33], [34], [35],

Diagnostics of the guillain-Barre syndrome

When collecting anamnesis, it is necessary to clarify the following aspects.

• Presence of provoking factors. In about 80% of cases, the development of Guillain-Barre syndrome in 1-3 weeks is preceded by certain diseases or conditions.
• - Infections of the gastrointestinal tract, upper respiratory tract or other localization. The association with intestinal infection caused by Campylobacter jejuni is most consistently detected . In persons who have undergone campylobacteriosis, the risk of developing Guillain-Barre syndrome within 2 months after the disease is approximately 100 times higher than in the general population. Guillain-Barre syndrome can also develop after infections caused by herpes viruses (cytomegalovirus, Epstein-Barr virus, varicella-zoster virus ), Haemophilus influenzae, mycoplasmas, measles, mumps, Lyme-borreliosis, etc. In addition, Guillain-Barre syndrome can develop with HIV infection.
• Vaccination (anti-rabies, tetanus, against flu, etc.).
• Operative interventions or injuries of any location.
• Taking certain medications (thrombolytic drugs, isotretinoin, etc.) or contact with toxic substances.
• Sometimes Guillain-Barre syndrome develops against the background of autoimmune (systemic lupus erythematosus) and tumoral (lymphogranulomatosis and other lymphomas) diseases.

Laboratory and instrumental research

• General clinical studies (general blood test, general urine analysis).
• Biochemical blood test: the concentration of serum electrolytes, the arterial blood gas composition. When planning specific therapy with class G immunoglobulins, it is necessary to determine Ig fractions in the blood. Low concentration of IgA is usually associated with his hereditary deficit, in such cases the risk of developing an anaphylactic shock is high (immunoglobulin therapy is contraindicated).
• Studies of cerebrospinal fluid (cytosis, protein concentration).
• Serologic studies with suspicion of the etiological role of certain infections (markers of HIV, cytomegalovirus, Epstein-Barr virus, Borrelia burgdorferi, Campylobacter jejuni, etc.). If polio is suspected, virological and serological (antibody titre in paired sera) are required.
• EMG, the results of which are of fundamental importance for confirming the diagnosis and determining the form of Guillain-Barre syndrome. It should be borne in mind that the results of EMG can be normal during the first week of the disease.
• Neuroimaging methods (MRI) do not confirm the diagnosis of Guillain-Barre syndrome, but may be necessary for differential diagnosis with CNS pathology (acute cerebrovascular accident, encephalitis, myelitis).
• ECG.
• Monitoring the function of external respiration [determining the vital capacity of the lungs (JEL) for the timely detection of indications for the transfer of the patient to the ventilator.
• In severe cases (especially with the rapid progression of the disease, bulbar disorders, expressed autonomic disorders), as well as during ventilation, monitoring of the vital vital signs (in the conditions of intensive care unit) is necessary: arterial pressure, ECG, pulse oximetry, respiratory function and others depending on the specific clinical situation and the therapy used).

[36], [37], [38]

Neurophysiological criteria for classification of Guillain-Barre syndrome

Norm (all of the following signs should be present in all the investigated nerves)

1. Distal motor latency <100% of the upper limit of normal.
2. The F-wave safety and its latency <100% of the upper limit of the norm.
3. SRV> 100% of the lower limit of the norm.
4. The amplitude of the M-response when stimulated at the distal point is> 100% of the lower limit of the norm.
5. Amplitude of the M-response with stimulation at the proximal point> 100% of the lower limit of the norm.
6. Ratio "Amplitude of M-response for proximal stimulation / Amplitude of M-response for stimulation at distal point"> 0.5

Primary demyelinating lesions (it is necessary to have at least one of the signs in at least two investigated nerves or the presence of two signs in one nerve if all other nerves are not excitable and the amplitude of the M-response when stimulated at the distal point is> 10% of the lower limit of the norm ).

1. SRV <90% of the lower limit of the norm (<85%, if the amplitude of the M-response with stimulation at the distal point <50% of the lower limit of the norm).
2. Dystopic motor latency> 110% of the upper limit of the norm (> 120%, if the amplitude of the M-response with stimulation at the distal point <100% of the lower limit of the norm).
3. The ratio of the amplitude of the M-response for stimulation at the proximal point / Amplitude of the M-response for stimulation at the distal point is <0.5 and the amplitude of the M-response with stimulation at the distal point is> 20% of the lower limit of the norm.
4. Latency of the F-wave> 120% of the upper limit of the norm

Primary-axonal lesion

• The absence of all the demyelinization features listed above in all the nerves examined (one of them can be tolerated in one of the nerves, if the amplitude of the M-response with stimulation at the distal point <10% of the lower limit of the norm) and the amplitude of the m-response when stimulated at the distal point <80 % of the lower limit of the norm, at least in two nerves

Nerve excitability

• M-response with stimulation in the distal point can not be caused in any of the nerves (or can only be caused in one nerve with its amplitude <10% of the lower limit of the norm)

Uncertain defeat

Does not meet the criteria of any of the above forms

This form can include cases of primary severe axonopathy, severe distal demyelination with the conduction block and secondary Waller degeneration after demyelination; neurophysiologically they can not be distinguished.

Indications for consultation of other specialists

• Treatment of patients with severe forms of Guillain-Barre syndrome is carried out in conjunction with the doctor of intensive care unit.
• In severe cardiovascular disorders (persistent severe arterial hypertension, arrhythmias), a cardiologist consultation may be required.

Data from additional research methods

An important diagnostic value for Guillain-Barre syndrome is electromyography (EMG) and a study of the speed of impulses along the nerves, as well as the study of cerebrospinal fluid. Starting from the 3rd-7th day after the appearance of the first symptoms, electrophysiological examination reveals a slowing down of motor and, to a lesser extent, sensory fibers, lengthening of the distal latency and the latent period of the F wave, a decrease in the amplitude of the total muscle potential of the action (M-response ) and sometimes sensory action potentials, as well as focal and asymmetric conduction blocks that indicate segmental demyelinating polyneuropathy. On the other hand, in acute motor axonal polyneuropathy, the amplitude of the sensory action potentials and the speed of the sensory fibers can be normal, but the amplitude of the total muscular action potential decreases and only the slowing down of the conduction along motor fibers is noted. With the defeat of both motor and sensory fibers, the total muscle potentials of action and the sensory action potentials can be roughly changed, and the distal latency and speed of the exercise can be difficult to measure, which indicates severe motor-sensory axonopathy. With Miller Fischer's syndrome, manifested by ataxia, ophthalmoplegia and aireflexia, the muscle strength remains intact, and the EMG and the speed of the nerves of the limbs can be normal.

In the study of cerebrospinal fluid in patients with Guillain-Barre syndrome, an increase in the protein content to a level exceeding 60 mg / dL is observed with normal cytosis (not more than 5 cells per 1 μl). However, in the first days of the disease, the protein content in the cerebro-spinal fluid can be normal, while an increase in the cytosis of up to 30 cells per 1 μL does not exclude the diagnosis of Guillain-Barre syndrome.

Since there are usually no signs of inflammation or demyelination in the study of the gastrocnemius biopsy, this method is not part of the standard research package for most patients with Guillain-Barre syndrome, but may be important in scientific research. Pathomorphological studies indicate that the Guillain-Barre syndrome mainly affects the proximal nerves and roots of the spinal nerves: it is in them that the edema, segmental demyelination, infiltration of endonervia by mononuclears, including macrophages, are detected. Mononuclear cells interact with both Schwann cells and myelin sheath. Although Guillain-Barre syndrome is a polyradiculoneuropathy, pathological changes can be detected in the central nervous system (CNS). In most of the 13 autopsy cases, mononuclear infiltration of lymphocytes and activated macrophages was detected in the spinal cord, medulla oblongata, and the bridge. However, no primary demyelination was detected in the central nervous system. With prolonged flow, the predominant type of inflammatory cells in the central and peripheral nervous system were activated macrophages, in addition, CD4 ⁺ and CD8 ⁺ T-lymphocytes were detected there .

[39], [40], [41], [42], [43], [44], [45], [46], [47],

Differential diagnosis

Guillain-Barre syndrome must be differentiated from other diseases manifested by acute peripheral paresis, primarily from poliomyelitis (especially in young children) and other polyneuropathies (diphtheria, in porphyria). In addition, a similar clinical picture can have lesions of the spinal cord and brain stem (transverse myelitis, stroke in the vertebrobasilar system) and diseases with a violation of neuromuscular transmission (myasthenia gravis, botulism).

• In case of differential diagnosis with poliomyelitis, the epidemiological history should be taken into account, the presence of fever in the onset, symptoms of the gastrointestinal tract, asymmetry of the lesion, absence of objective sensitivity disorders, high cytosis in the cerebrospinal fluid. The diagnosis of poliomyelitis is confirmed with the help of virologic or serological studies.
• Polyneuropathy in acute intermittent porphyria may resemble Guillain-Barre syndrome, but, as a rule, is accompanied by a variety of psychopathological symptoms (delirium, hallucinations, etc.) and severe abdominal pain. The diagnosis is confirmed by revealing an increased concentration of porphybolinogen in the urine.
• For transverse myelitis characterized by early and persistent impairment of pelvic organs, the presence of a level of sensitive disorders, the absence of lesions of the cranial nerves.
• Symptomatic, reminiscent of that in the Guillain-Barre syndrome, is possible with extensive cerebral infarction with the development of tetraparesis, which in the acute period has features of the peripheral. However, such cases are characterized by acute development (usually within a few minutes) and in most cases, oppression of consciousness (coma), which is not observed in the Guillain-Barre syndrome. Finally, the diagnosis is confirmed by MRI.
• Myasthenia gravis differs from Guillain-Barre syndrome with symptomatic variability, absence of sensitive disorders, and characteristic changes in tendon reflexes. The diagnosis is confirmed with the help of EMG (detection of the decrement phenomenon) and pharmacological tests.
• For botulism, in addition to the corresponding epidemiological data, the descending type of paresis distribution, the preservation in some cases of tendon reflexes, the absence of sensitive disorders and changes in cerebrospinal fluid are characteristic.

Treatment of the guillain-Barre syndrome

The purposes of treatment of Guillain-Barre syndrome are maintenance of vital functions, relief of autoimmune process with the help of specific therapy, prevention of complications.

Indications for hospitalization

All patients with Guillain-Barre syndrome are hospitalized in a hospital with intensive care unit.

Non-drug treatment for Guillain-Barre syndrome

Approximately 30% of cases of Guillain-Barre syndrome develop severe respiratory failure (due to paresis of the diaphragm and respiratory muscles), necessitating the necessity of mechanical ventilation. Indications for performing intubation with further ventilation - ZHOL decrease to 15-20 ml / kg, P _and O ₂ <60 mm Hg or S _a 0 ₂ <95% with additional oxygen inhalation, P _and CO ₂ > 50 mm Hg The duration of mechanical ventilation (from several days to months) is determined on an individual basis, guided by ZHEL, restoration of swallowing and cough reflex and the overall dynamics of the disease. Disconnect the patient from the ventilator gradually, through the stage of intermittent forced ventilation.

In severe cases with pronounced paresis, the principal importance for preventing complications associated with prolonged immobility of the patient (bedsores, infections, thromboembolic complications, etc.), has the right care: periodic (every 2 hours or more) patient change, skin care, prevention aspiration [sanitation of the mouth and nose, feeding through the nasogastric tube, sanitation of the trachea and bronchi (during ventilation)], control of the functions of the bladder and intestines, passive gymnastics and massage of the extremities, etc.

With persistent bradyarrhythmias with the threat of developing asystole, a temporary pacemaker may be required.

Medicinal treatment and plasmapheresis

As a specific therapy for Guillain-Barre syndrome aimed at arresting the autoimmune process, pulse therapy with class G immunoglobulins and plasmapheresis is currently being used. The methods of specific therapy are shown in case of severe (assessment of the North American gravity of the motor deficit of 4 and 5 points) and the moderate (2-3 points) of the course of the disease. The effectiveness of both methods is approximately the same, their simultaneous conduct is impractical. The method of treatment is chosen individually, taking into account the availability, possible contraindications, etc.

• Plasmapheresis is an effective method of treating Guillain-Barre syndrome, which significantly reduces the severity of paresis, the duration of mechanical ventilation and improves the functional outcome. Usually, 4-6 operations are performed at intervals of one day; The volume of replacement plasma in one operation should be at least 40 ml / kg. As substitute media use 0.9% solution of sodium chloride, rheopolyglucin, albumin solution. Plasmapheresis is relatively contraindicated in liver failure, severe cardiovascular pathology, blood clotting disorders, and infections. Possible complications - hemodynamic disorders (falling blood pressure), allergic reactions, electrolyte disorders, hemorrhagic disorders, development of hemolysis. All of them are observed quite rarely.
• Immunoglobulin class G is administered intravenously at a dose of 0.4 g / kg once a day for 5 days. Treatment with immunoglobulin, like plasmapheresis, reduces the duration of ventilation and improves the functional outcome. The most common side effects are headaches and muscle pains, fever, nausea; their severity can be reduced by reducing the rate of infusion. Severe side effects, such as thromboembolism, aseptic meningitis, hemolysis, acute renal failure, etc., are very rare. Immunoglobulin human normal is contraindicated in congenital IgA deficiency and the presence in the anamnesis of anaphylactic reactions to immunoglobulin preparations.

Symptomatic treatment of Guillain-Barre syndrome

• Infusion therapy for the correction of violations of acid-base, water-electrolyte balance, severe arterial hypotension.
• With persistent severe arterial hypertension, antihypertensive drugs (beta-adrenoblockers or slow calcium channel blockers) are prescribed.
• With severe tachycardia prescribe beta-adrenoblockers (propranolol), with bradycardia - atropine.
• With the development of intercurrent infections, antibiotic therapy is needed (broad-spectrum drugs are used, for example, fluoroquinolones).
• To prevent deep vein thrombosis and pulmonary embolism, low-molecular-weight heparin is prescribed in prophylactic doses twice a day).
• For pain of nociceptive origin (muscular, mechanical), paracetamol or NSAIDs are recommended, in the case of neuropathic pain, the drugs of choice are gabapentin, carbamazepine, pregabalin.

Operative treatment of Guillain-Barre syndrome

If a prolonged (more than 7-10 days) ventilation is necessary, tracheostomy is advisable. In severe and prolonged bulbar disorders, gastrostomy may be required.

General principles of treatment of Guillain-Barre syndrome

Treatment of the acute and rapidly growing manifestations of Guillain-Barre syndrome requires maintenance therapy in the intensive care unit, as well as the impact on the immune mechanisms of the development of the disease. Patients with Guillain-Barre syndrome should be hospitalized for careful monitoring of the state of breathing and autonomic functions. The faster the paralysis increases, the higher the likelihood that artificial ventilation will be required. In the period of increasing symptoms, regular neurologic examination, assessment of vital capacity of the lungs, maintenance of airway patency with regular suction of mucus are necessary. At an early stage of the disease, constant alertness is necessary, because even in the absence of obvious violations of respiratory and bulbar functions, a small aspiration can significantly increase vegetative dysfunction and provoke respiratory failure.

Improvement in the prognosis and mortality reduction in Guillain-Barre syndrome, achieved in recent years, is mainly explained by early hospitalization of patients in intensive care units. Indications for the transfer of a patient to the intensive care unit and consideration of the question of intubation can be a decrease in the vital capacity of the lungs below 20 ml / kg and difficulties in removing secretions from the respiratory tract. The purpose of early translation is to avoid urgent intubation in conditions of severe respiratory failure with sudden fluctuations in blood pressure and heart rate, which can trigger dysfunction or myocardial infarction. One of the most important tasks of maintenance therapy is the prevention and timely treatment of pulmonary and urinary infections, as well as the prevention of deep vein thrombosis and subsequent pulmonary artery thromboembolism by subcutaneous administration of heparin (5000 units 2 times a day). It is also necessary to monitor the nutrition and function of the intestine. Because autonomic dysfunction has a significant effect on mortality, continuous monitoring of cardiac activity and arterial pressure is necessary.

One of the important aspects of helping patients with Guillain-Barre syndrome in the intensive care unit, which, however, is not always taken into account, is the correction of a pronounced anxiety, which is caused by the complete immobilization of the patient against a background of reserved intelligence. In this regard, psychological support is important. Patients need to explain the essence of the disease, the features of its course, including the possibility of progression, to familiarize with the methods of treatment at various stages. It is important for them to explain that the probability of complete recovery is very high, even if for a while they will be on artificial ventilation. The establishment of contact with the help of eye movements reduces the feeling of isolation from the world that arises in patients. In our experience, the administration of 0.5 mg of lorazepam every 4 to 6 hours is effective in night hallucinations. It is also possible to administer 0.5 mg of risperidone or 0.25 mg of olanzapine.

The practice of treating Guillain-Barre syndrome has undergone significant changes over the past decade. For example, the effectiveness of plasmapheresis has been proven. Although the mechanism of its action remains unknown, it is believed that it can be associated with the excretion of antibodies, cytokines, complement and other mediators of the immune-inflammatory reaction. In an open, multicenter, North American study comparing the outcomes of the disease with plasmapheresis and in the absence of specific treatment, it has been shown that performing plasmapheresis for five consecutive days reduces the duration of hospitalization and leads to a greater improvement than in the control group. Treatment was more effective if it started in the first week of the disease. Similar results were obtained by the French Cooperative Group, which conducted a randomized multicentre study and showed that four sessions of plasmapheresis lead to a faster recovery in 220 patients enrolled in the study (French Cooperative Group, 1987). A study of these same patients a year later showed that complete recovery of muscle strength was noted in 71% of patients who underwent plasmapheresis and only 52% of patients in the control group (French Cooperative Group, 1992). The next study compared the effectiveness of a different number of plasmapheresis sessions in 556 patients with Guillain-Barre syndrome with different symptoms (French Cooperative Group, 1997). In patients with mild symptoms, who underwent two sessions of plasmapheresis, recovery was more significant than in patients whose treatment regimen did not include plasmapheresis. In patients with moderate symptomatology, four sessions of plasmapheresis were more effective than two sessions of plasmapheresis. At the same time, six sessions of plasmapheresis were not more effective than four sessions in patients with both moderate and severe symptoms. Currently, most centers specializing in the treatment of Guillain-Barre syndrome continue to use five to six sessions, which are conducted for 8-10 days, to avoid the stress associated with the daily conduct of this procedure. Exchange transfusion is performed using a Shili catheter. Plasmapheresis is also effective in children with Guillain-Barre syndrome, accelerating the process of restoring the ability to move independently. Although plasmapheresis is a relatively safe procedure, its conduct in Guillain-Barre syndrome requires extreme caution because of the dangers of autonomic dysfunction in patients and their propensity to develop infections.

Intravenous administration of high doses of immunoglobulin is also recognized as an effective treatment for Guillain-Barre syndrome, which can significantly reduce the duration and severity of the disease. As in the case of plasmapheresis, the mechanism of therapeutic action of immunoglobulin remains unclear. It is suggested that it can eliminate pathogenic antibodies due to anti-idiotypic antibodies, block the Fc-component of antibodies on target cells, and also inhibit the deposition of complement, dissolve immune complexes, weaken lymphocyte function, disrupt production, or interfere with the function of cytokines. Immunoglobulin is prescribed in a total dose of 2 g / kg, which is administered for 2-5 days. In a randomized study comparing the effect of immunoglobulin and plasmapheresis, it was shown that with the use of plasmapheresis, an average improvement occurs after 41 days, and with the use of immunoglobulin - after 27 days. In addition, patients who received an immunoglobulin showed significantly fewer complications and to a lesser extent required artificial ventilation. The main adverse prognostic factor was the elderly age. A subsequent randomized multicenter study of plasmapheresis and immunoglobulin in 383 patients who received these procedures within the first 2 weeks after the onset of symptoms showed that both methods have comparable efficacy, but their combination does not have significant advantages over each method separately.

The introduction of immunoglobulin at a dose of 2 g / kg for 2 days proved to be an effective and safe method of treatment in children with severe Guillain-Barre syndrome. Side effects were mild and rarely observed. Part of the patients, especially those suffering from migraine, had a headache, which was sometimes accompanied by aseptic meningitis with pleocytosis in the cerebrospinal fluid. Sometimes chills, fever and myalgia were also observed, as well as acute renal dysfunction with the development of renal failure. When an immunoglobulin is administered, an anaphylactic reaction is possible, especially in persons with immunoglobulin A deficiency. The main disadvantage of both immunoglobulin and plasmapheresis is a high cost. Nevertheless, it is clearly outweighed by the effectiveness of these treatments, which is evident even in the present era, which makes counting money.

A double-blind, placebo-controlled, multicenter trial in 242 patients with Guillain-Barré syndrome showed that intravenous high-dose corticosteroids (methylprednisolone, 500 mg per day for 5 days) did not affect any of the indicators that evaluated the outcome of Guillain- Barre, as well as the likelihood of his recurrence. In a subsequent open study in which 25 patients with Guillain-Barré syndrome were treated with iv immunoglobulin (0.4 g / kg / day for 5 days) and methylprednisolone (500 mg / day for 5 days), the effect was compared with control data obtained earlier with the use of one immunoglobulin. With the combination of immunoglobulin and methylprednisolone, the recovery was better, with an improvement of at least one functional stage seen in 76% of patients at the end of the 4th week - in the control group, a similar degree of recovery was noted in only 53% of patients. This may indicate that corticosteroids can still play a role in the treatment of Guillain-Barre syndrome. In order to clarify this issue and to determine whether a significant improvement in the outcome of the disease is noted, if intravenously administered corticosteroids are added to the plasmapheresis or immunoglobulin, randomized clinical trials are needed.

Further management

After the end of the acute period, complex rehabilitation measures are required, the plan of which is individually determined depending on the severity of residual symptoms (exercise therapy, massage, etc., while thermal procedures are contraindicated!).

Patients who have suffered Guillain-Barre syndrome should be informed of the need to observe a protective regime for at least 6-12 months after the end of the disease. Physical overloads, overheating, hypothermia, excessive insolation, and alcohol intake are inadmissible. Also during this period, one should refrain from vaccination.

Forecast

Mortality in Guillain-Barre syndrome is 5% on average. The cause of death may be respiratory failure, a fatal outcome is also possible due to aspiration pneumonia, sepsis and other infections, thromboembolism of the pulmonary artery. Lethality significantly increases with age: in children under 15 years of age it does not exceed 0.7%, while in persons older than 65 years it reaches 8.6%. Other unfavorable prognostic factors for complete recovery include a prolonged (more than 1 month) period of ventilation, the presence of previous lung diseases.

In the majority of patients (85%) complete functional recovery is observed for 6-12 months. Residual residual symptoms persist in approximately 7-15% of cases. Predictors of unfavorable functional outcome - age over 60 years, rapidly progressing course of the disease, low amplitude of M-response with stimulation at the distal point (implying severe axon lesion). The recurrence rate of Guillain-Barre syndrome is approximately 3-5%.

[48], [49], [50],