Guillain-Barré syndrome

Guillain-Barré syndrome (acute idiopathic polyneuritis; Landry's paralysis; acute inflammatory demyelinating polyradiculoneuropathy) is an acute, usually rapidly progressive inflammatory polyneuropathy characterized by muscle weakness and moderate loss of distal sensitivity. Autoimmune disease. Diagnosis based on clinical data. Treatment of Guillain-Barré syndrome: plasmapheresis, γ-globulin, artificial ventilation if indicated. The outcome of the syndrome is significantly improved by adequate supportive care in the intensive care unit and the use of modern methods of immunomodulatory therapy.

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Epidemiology

The incidence is 0.4 to 4 cases per 100,000 population per year. Guillain-Barré syndrome occurs in all age groups, but is more common in people aged 30-50 years, with equal frequency in men and women. Racial, geographic, and seasonal differences in the incidence of Guillain-Barré syndrome are generally not characteristic, 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 somewhat more often in the summer.

The incidence increases significantly after age 40. On average, 600 people die from Guillain-Barré syndrome in the United States each year. Thus, Guillain-Barré syndrome is a very important public health problem, especially relevant for older people.

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Causes Guillain-Barré 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.

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

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Pathogenesis

Demyelination and inflammatory infiltration in the spinal nerve roots and proximal nerves may explain the clinical symptoms of Guillain-Barré 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 perivenous zones and their interaction with myelinated axons indicate, first of all, a possible role of autoimmune reactions in the demyelinating process. This position is confirmed by earlier observations according to which immunization of laboratory animals with peripheral myelin with an adjuvant causes experimental allergic neuritis. Although it was subsequently shown that purified myelin proteins - for example, myelin basic protein P2 or peptide fragments of P2 and protein PO - are able to cause experimental neuropathy, antibodies to these compounds are rarely detected in Guillain-Barré syndrome. T cells isolated from the spleen and lymph nodes of rats immunized with the P2 synthetic peptide 53-78 can experimentally reproduce severe experimental allergic neuritis in syngeneic mice. Thus, cellular and possibly humoral immune mechanisms may mediate the creation of an experimental model of inflammatory damage to peripheral nerves.

Recent studies have focused on the role of glucoconjugates and lipopolysaccharides from the myelin sheath, Schwann cell membrane, or axonal membrane as the major antigens initiating the inflammatory/immune response in Guillain-Barré syndrome. In a detailed study conducted in Japan, Campylobacter jejuni antigens were identified in patients. In this study, the Penner method was used to detect heat-stable lipopolysaccharides and the Lior method was used to detect heat-labile protein antigens. PEN 19 and LIO 7 antigens of C. jejuni were isolated more frequently in patients with Guillain-Barré syndrome (52 and 45% of cases, respectively) than in patients with sporadic enteritis caused by C. jejuni (5 and 3%, respectively), and were associated with an increase in the titer of antibodies to GM1 (possibly due to the presence of GM1-like lipopolysaccharide antigen). According to reports from other countries, infection with C. jejuni much less often precedes the development of GBS. In addition, the percentage of patients with antiganglioside 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.

Antibodies to GQlb are frequently detected in Miller Fisher syndrome. Using immunohistochemical methods, GQlb has been detected in the paranodal region of 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-Barré syndrome, the disease was often preceded by C. jejuni infection, and antibodies to the ganglioside GM1 and the complement activation product C3d were associated with the axolemma of motor fibers.

Anti-GMI antibodies can also bind to nodes of Ranvier, thereby interfering with impulse conduction. In addition, these antibodies can cause degeneration of motor fiber terminals and intramuscular axons, as recently demonstrated in patients with acute motor axonal polyneuropathy. Enteritis due to C. jejuni can trigger Guillain-Barré syndrome by enhancing the production of gamma-delta T cells, which can actively participate in inflammatory/immune processes. High serum levels of tumor necrosis factor-alpha (TNF-a), but not interleukin-1b or soluble interleukin-2 receptor, correlated with electrophysiological changes in Guillain-Barré syndrome. Examination of autopsy specimens suggests that complement is involved in at least some cases of the classic acute inflammatory demyelinating form of Guillain-Barré syndrome, as indicated by the detection of C3d and C5d-9 components of the membrane attack complex on the outer surface of Schwann cells.

Thus, most of the components commonly involved in the pathogenesis of immune-mediated diseases are present in Guillain-Barré syndrome. Although anti-glucoconjugate antibodies are likely involved in the pathogenesis of several different clinical forms of Guillain-Barré syndrome, their precise role is unknown. Even if anti-GM1 antibodies are present, they may bind not only to GM1 but also to other glycolipids or glycoproteins that have similar carbohydrate moieties. Therefore, the specific Schwann cell or axonal membrane antigens against which the inflammatory/immune response is directed, as well as the possible role of immunoglobulins, require clarification. Furthermore, many cases of Guillain-Barré syndrome lack evidence of prior or concomitant C. jejuni infection, anti-GM1 antibodies, or evidence of another organism whose antigens might initiate an immune response (e.g., by molecular mimicry).

Nerve biopsy and autopsy studies suggest that cellular immune mechanisms also contribute to the development of Guillain-Barré syndrome. In severe cases of Guillain-Barré syndrome, lymphocytes and macrophages are present along the entire length of the motor fibers from the roots to the endings, with activated macrophages in close contact with myelin or phagocytizing myelin. Although experimental models of inflammatory neuropathy have shown evidence of T-lymphocyte involvement in nerve damage, there is no convincing evidence that this occurs in patients with Guillain-Barré syndrome. The data accumulated to date support the involvement of activated T lymphocytes crossing the blood-brain barrier and initiating demyelination, together with antibodies to specific nerve fiber antigens, cytokines (such as TNF-α and interferon-γ), complement components, possibly including the membrane attack complex, and activated macrophages. Further studies are needed to clarify the role of each of these elements, as well as the sequence in which they participate in the pathogenesis of Guillain-Barré syndrome.

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Symptoms Guillain-Barré syndrome

Symptoms of Guillain-Barré syndrome include the dominance of flaccid paresis (the more proximal, the deeper), sensory disturbances are less pronounced. Typically, almost symmetrical weakness with paresthesias begins in the legs, less often in the arms or head. In 90% of cases, weakness reaches its maximum in the 3rd week of the disease. Deep tendon reflexes are lost. Sphincter function is preserved. In severe cases, weakness of the facial and oropharyngeal muscles is obvious in half of the cases. Intubation and artificial ventilation are required in 5-10% of cases due to paralysis of the respiratory muscles.

Sometimes (apparently in the variant form) severe autonomic dysfunction develops with fluctuations in blood pressure, abnormal secretion of antidiuretic hormone, arrhythmias, intestinal stasis, urinary retention, and impaired pupillary response to light. Fisher syndrome is a rare variant of Guillain-Barré syndrome, involving ophthalmoplegia, ataxia, and areflexia.

The first symptoms, the order of their appearance and dynamics

In typical cases, Guillain-Barré syndrome begins with muscle weakness and/or sensory disturbances (numbness, paresthesia) in the lower extremities, which after a few hours or days spread to the upper extremities.

The first symptoms of Guillain-Barré are sensory disturbances, such as paresthesia in the feet. Although objective signs of sensory disturbance are detected quite often, they are usually mild. Early and extremely unpleasant manifestations of the disease for patients can be deep aching pain in the back and painful dysesthesia in the extremities. Paralysis may initially involve the lower extremities, and then quickly, within a few hours or days, spread in an ascending direction to the upper extremities, facial, boulevard and respiratory muscles. However, another development of events is also possible, when the disease begins with weakness in the facial muscles and upper extremities, then involves the lower extremities. From the very beginning, the symptoms are usually symmetrical, and the paralysis is accompanied by loss or weakening of tendon and periosteal reflexes. In Guillain-Barré syndrome, vegetative fibers are often involved. Vegetative symptoms are detected in approximately 50% of cases, but sphincter functions are usually not affected. The disease has a monophasic course: a period of increasing symptoms lasting several days or weeks is followed by a plateau period lasting from several days to several months, after which recovery occurs over several months. In 1976-1977, there was a slight increase in the incidence of Guillain-Barré syndrome associated with immunization with the swine flu vaccine, but no similar phenomenon was recorded with immunization with another version of the flu vaccine in 1980-1988.

In classical cases, which present with a combination of motor, sensory, and autonomic symptoms based on demyelinating polyradiculoneuropathy, the diagnosis of Guillain-Barré syndrome is rarely difficult. However, there are also axonal variants of Guillain-Barré syndrome, which are predominantly characterized by motor disorders, and acute motor-sensory axonal neuropathy. The acute axonal form usually presents with a more severe functional defect and has a more unfavorable prognosis. A combination of ophthalmoplegia, ataxia, and areflexia is characteristic of another variant of Guillain-Barré syndrome, known as Miller Fisher syndrome. From a diagnostic point of view, in the absence of symptoms of cranial nerve damage, even with intact sphincter function, it is necessary to exclude spinal cord compression using neuroimaging. In the differential diagnosis, it is also important to consider acute intermittent porphyria, metal intoxication that can cause acute polyneuropathy, and systemic diseases such as infectious mononucleosis, paraneplastic syndromes, or various metabolic disorders. HIV-infected patients are predisposed to developing polyneuropathy or polyradiculoneuropathy, which may be associated with Guillain-Barré syndrome, cytomegalovirus polyradiculoneuropathy, or lymphoma. These conditions are difficult to differentiate based on clinical manifestations alone, but cerebrospinal fluid examination in HIV-associated polyradiculoneuropathy typically reveals neutrophilic pleocytosis and evidence of viral replication.

Autonomic dysfunction (including accommodation disorders, abdominal and chest pain, arterial hypotension, tachycardia) can significantly worsen the patient's condition and is an unfavorable prognostic sign. In one study, subclinical signs of involvement of both the sympathetic and parasympathetic nervous systems, detected using autonomic function tests, were noted in the vast majority of patients.

North American Motor Deficit Severity Scale

Degree	Signs
0	Norm
I	Minimal movement disorders
II	Ability to walk 5 m without support
III	Ability to walk 5 m with support
IV	Inability to walk 5 m with support or assistance (bedridden or wheelchair bound)
V	The need for artificial ventilation

• A third of patients develop respiratory failure.
• In most cases, there are disorders of superficial sensitivity in the form of mild or moderate hypo- or hyperesthesia of the polyneuritic type (of the "socks and gloves" type). Pain in the hips, lumbar and gluteal regions is often noted. They can be both nociceptive (muscular) and neuropathic (caused by damage to the sensory nerves). Disorders of deep sensitivity (especially vibration and muscle-joint sense), which can be very severe (up to complete loss), are detected in approximately half of patients.
• Cranial nerve lesions are observed in most patients. Any cranial nerve may be involved in the process (except for the first and second pairs), but lesions of the seventh, ninth and tenth pairs are most frequently observed, which manifests itself as paresis of the facial muscles and bulbar disorders.
• Vegetative disorders are observed in more than half of patients and can be represented by the following disorders.
  • Transient or persistent arterial hypertension or, less commonly, arterial hypotension.
  • Cardiac arrhythmias, most often sinus tachycardia.
  • Sweating disorder [local (palms, feet, face) or general hyperhidrosis].
  • Disorders of the gastrointestinal tract (constipation, diarrhea, in rare cases intestinal obstruction).
  • Pelvic organ dysfunction (usually urinary retention) is rare and is usually mild and transient.
• In Miller-Fisher syndrome, the clinical picture is dominated by ataxia, which usually has features of cerebellar, in rare cases - mixed (cerebellar-sensory), and partial or total ophthalmoplegia, damage to other cranial nerves (VII, IX, X) is also possible. Paresis is usually mild, in a quarter of cases there are sensitivity disorders.

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Diagnostic criteria for Guillain-Barré syndrome

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Signs of Guillain-Barré syndrome needed to make a diagnosis

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

Signs of Guillain-Barré syndrome that support the diagnosis

• A. Clinical signs (listed in order of importance)
  • Progression: Muscle weakness develops rapidly but stops progressing within 4 weeks of onset.
  • Relative symmetry: symmetry is rarely absolute, but if one limb is affected, the opposite limb is also affected (comment: patients often report asymmetry of symptoms at the onset of the disease, but by the time of objective examination, the lesions are usually symmetrical).
  • Subjective and objective symptoms of sensory impairment.
  • Cranial nerve damage: paresis of facial muscles.
  • Recovery: Usually begins 2-4 weeks after the disease stops progressing, but can sometimes be delayed for several months. Most patients experience full recovery of function.
  • Vegetative disorders: tachycardia and other arrhythmias, postural arterial hypotension, arterial hypertension, vasomotor disorders.
  • Absence of fever at the onset of the disease (in some cases, fever at the onset of the disease is possible due to intercurrent diseases or other causes; the presence of fever does not exclude Guillain-Barré syndrome, but increases the likelihood of another disease, in particular poliomyelitis).
• B. Options
  • Severe sensory disturbances with pain.
  • Progression over 4 weeks. Sometimes the disease may progress over many weeks or have minor relapses.
  • Cessation of progression without subsequent recovery or persistence of severe persistent residual symptoms.
  • Sphincter functions: usually the sphincters are not affected, but in some cases urination disorders are possible.
  • CNS involvement: Guillain-Barré syndrome affects the peripheral nervous system, there is no reliable evidence for the possibility of CNS involvement. Some patients have severe cerebellar ataxia, pathological extensor foot signs, dysarthria or unclear level of sensory impairment (implying conductive type of impairment), however, they do not exclude the diagnosis of Guillain-Barré syndrome if other typical symptoms are present
• 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 (during the first week it may be normal).
  • Cytosis: the content of mononuclear leukocytes in the cerebrospinal fluid is up to 10 in 1 μl (if the content of leukocytes is 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-Barré syndrome is rejected; the exception is patients with HIV infection and Lyme borreliosis).

Signs of Guillain-Barré syndrome that raise doubts about the diagnosis

1. Pronounced persistent asymmetry of paresis.
2. Persistent pelvic disorders.
3. The presence of pelvic disorders at the onset of the disease.
4. The content of mononuclear leukocytes in the cerebrospinal fluid is more than 50 in 1 μl.
5. The presence of polymorphonuclear leukocytes in the cerebrospinal fluid.
6. Clear level of sensitivity disorders

Signs of Guillain-Barré syndrome that exclude the diagnosis

1. Current abuse of volatile organic solvents (substance abuse).
2. Disorders of porphyrin metabolism, implying a diagnosis of acute intermittent porphyria (increased excretion of porphobilinogen or aminolevulinic acid in the urine).
3. Recently suffered from diphtheria.
4. The presence of symptoms of neuropathy due to lead intoxication (paresis of the muscles of the upper limb, sometimes asymmetrical, with severe weakness of the extensors of the hand) or evidence of lead intoxication.
5. The presence of exclusively sensory impairments.
6. A reliable diagnosis of another disease that manifests itself with symptoms similar to Guillain-Barré syndrome (poliomyelitis, botulism, toxic polyneuropathy).

Recently, some authors have considered acute sensory neuropathy, manifested exclusively by sensory disturbances, as a casuistically rare atypical form of Guillain-Barré syndrome.

Forms

Currently, four main clinical variants are distinguished within the framework of Guillain-Barré syndrome.

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

In addition to the main ones, recently several more atypical forms of the disease have also been identified - acute pandysautonomia, acute sensory neuropathy and acute cranial polyneuropathy, which are observed very rarely.

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Diagnostics Guillain-Barré syndrome

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

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

Laboratory and instrumental studies

• General clinical studies (complete blood count, complete urine analysis).
• Blood biochemistry: serum electrolyte concentration, arterial blood gas composition. When planning specific therapy with immunoglobulins of class G, it is necessary to determine Ig fractions in the blood. Low IgA concentration is usually associated with its hereditary deficiency, in such cases there is a high risk of developing anaphylactic shock (immunoglobulin therapy is contraindicated).
• Cerebrospinal fluid studies (cytosis, protein concentration).
• Serological studies if there is a suspicion of an etiological role of certain infections (markers of HIV, cytomegalovirus, Epstein-Barr virus, Borrelia burgdorferi, Campylobacter jejuni, etc.). If poliomyelitis is suspected, virological and serological (antibody titer in paired sera) studies are necessary.
• EMG, the results of which are of fundamental importance for confirming the diagnosis and determining the form of Guillain-Barré syndrome. It should be taken into account that EMG results may be normal during the first week of the disease.
• Neuroimaging methods (MRI) do not allow confirming the diagnosis of Guillain-Barré syndrome, but may be necessary for differential diagnosis with CNS pathology (acute cerebrovascular accident, encephalitis, myelitis).
• ECG.
• Monitoring of external respiratory function [determination of vital capacity of the lungs (VC) for timely identification of indications for transferring the patient to mechanical ventilation.
• In severe cases (especially with rapid progression of the disease, bulbar disorders, severe autonomic disorders), as well as during mechanical ventilation, monitoring of the main vital signs is necessary (in the intensive care unit): blood pressure, ECG, pulse oximetry, respiratory function and others (depending on the specific clinical situation and the therapy being administered).

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Neurophysiological criteria for classification of Guillain-Barré syndrome

Norm (all the signs below should be present in all nerves examined)

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

Primary demyelinating lesion (at least one of the signs must be present in at least two nerves examined, or two signs must be present in one nerve if all other nerves are not excitable and the amplitude of the M-response during stimulation at the distal point is >10% of the lower limit of normal).

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

Primary axonal lesion

• Absence of all the above signs of demyelination in all the nerves examined (the presence of one of them in one of the nerves is acceptable if the amplitude of the M-response during stimulation at the distal point is <10% of the lower limit of normal) and the amplitude of the M-response during stimulation at the distal point is <80% of the lower limit of normal in at least two nerves

Nerve insensitivity

• The M-response during stimulation at the distal point cannot be evoked in any of the nerves (or can be evoked only in one nerve with its amplitude <10% of the lower limit of normal)

Uncertain defeat

Does not meet the criteria for any of the above forms

This form may include cases of primary severe axonopathy, severe distal demyelination with conduction block, and secondary Wallerian degeneration after demyelination; they cannot be distinguished neurophysiologically.

Indications for consultation with other specialists

• Treatment of patients with severe forms of Guillain-Barré syndrome is carried out in collaboration with a physician from the intensive care unit.
• In case of severe cardiovascular disorders (persistent severe arterial hypertension, arrhythmia), a consultation with a cardiologist may be required.

Data from additional research methods

Of great diagnostic value in Guillain-Barré syndrome are electromyography (EMG), nerve conduction velocity studies, and cerebrospinal fluid examination. Starting from the 3rd to 7th day after the onset of the first symptoms, electrophysiological studies reveal slowing of conduction along motor and (to a lesser extent) sensory fibers, prolongation of the distal latency and latent period of the F-wave, decreased amplitude of the total muscle action potential (M-response) and sometimes sensory action potentials, as well as focal and asymmetric conduction blocks, which indicate segmental demyelinating polyneuropathy. On the other hand, in acute motor axonal polyneuropathy, the amplitude of sensory action potentials and conduction velocity along sensory fibers may be normal, but there is a decrease in the amplitude of the total muscle action potential and only a slight slowing of conduction along motor fibers. When both motor and sensory fibers are affected, both total muscle action potentials and sensory action potentials may be grossly altered, and distal latency and conduction velocities may be difficult to measure, indicating a severe motor-sensory axonopathy. In Miller Fisher syndrome, which presents with ataxia, ophthalmoplegia, and areflexia, muscle strength is preserved, and EMG and nerve conduction velocities in the extremities may be normal.

When examining the cerebrospinal fluid in patients with Guillain-Barré syndrome, an increase in protein content to a level exceeding 60 mg/dl is detected, with normal cytosis (no more than 5 cells in 1 μl). However, in the first days of the disease, the protein content in the cerebrospinal fluid may be normal, while an increase in cytosis to 30 cells in 1 μl does not exclude the diagnosis of Guillain-Barré syndrome.

Since sural nerve biopsy usually does not reveal signs of inflammation or demyelination, this method is not included in the standard set of studies in most patients with Guillain-Barré syndrome, but it can be important in scientific research. Pathomorphological studies indicate that Guillain-Barré syndrome predominantly affects the proximal parts of the nerves and the roots of the spinal nerves: it is in them that edema, segmental demyelination, and infiltration of the endonervium by mononuclear cells, including macrophages, are detected. Mononuclear cells interact with both Schwann cells and the myelin sheath. Although Guillain-Barré syndrome is a polyradiculoneuropathy, pathological changes can also be detected in the central nervous system (CNS). In most of the 13 autopsy cases, mononuclear infiltration with lymphocytes and activated macrophages was found in the spinal cord, medulla oblongata, and pons. However, primary demyelination was not detected in the CNS. In the long-term course, the predominant inflammatory cell type in the central and peripheral nervous system were activated macrophages, in addition, CD4 ⁺ and CD8 ⁺ T lymphocytes were detected there.

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Differential diagnosis

Guillain-Barré syndrome must be differentiated from other diseases that manifest as acute peripheral paresis, primarily poliomyelitis (especially in young children) and other polyneuropathies (diphtheria, porphyria). In addition, lesions of the spinal cord and brainstem (transverse myelitis, stroke in the vertebrobasilar system) and diseases with impaired neuromuscular transmission (myasthenia, botulism) may have a similar clinical picture.

• In differential diagnostics with poliomyelitis, it is necessary to take into account the epidemiological anamnesis data, the presence of fever at the onset of the disease, gastrointestinal symptoms, asymmetry of the lesion, the absence of objective sensitivity disorders, and high cytosis in the cerebrospinal fluid. The diagnosis of poliomyelitis is confirmed by virological or serological studies.
• Polyneuropathy in acute intermittent porphyria may resemble Guillain-Barré syndrome, but is usually accompanied by a variety of psychopathological symptoms (delusions, hallucinations, etc.) and severe abdominal pain. The diagnosis is confirmed by detecting an increased concentration of porphobilinogen in the urine.
• Transverse myelitis is characterized by early and persistent dysfunction of the pelvic organs, the presence of a level of sensory disorders, and the absence of damage to the cranial nerves.
• Symptoms resembling those of Guillain-Barré syndrome are possible in cases of extensive brainstem infarctions with the development of tetraparesis, which in the acute period has features of peripheral paresis. However, such cases are characterized by acute development (usually within a few minutes) and, in most cases, depression of consciousness (coma), which is not observed in Guillain-Barré syndrome. The diagnosis is finally confirmed using MRI.
• Myasthenia differs from Guillain-Barré syndrome by the variability of symptoms, the absence of sensory disorders, and characteristic changes in tendon reflexes. The diagnosis is confirmed by EMG (detection of the decrement phenomenon) and pharmacological tests.
• In addition to the corresponding epidemiological data, botulism is characterized by a descending type of paresis spread, preservation of tendon reflexes in some cases, absence of sensory disorders and changes in the cerebrospinal fluid.

Treatment Guillain-Barré syndrome

The goals of treatment of Guillain-Barré syndrome are to maintain vital functions, stop the autoimmune process with the help of specific therapy, and prevent complications.

Indications for hospitalization

All patients with Guillain-Barré syndrome are subject to hospitalization in a hospital with a resuscitation and intensive care unit.

Non-drug treatments for Guillain-Barré syndrome

In approximately 30% of cases of Guillain-Barré syndrome, severe respiratory failure develops (due to paresis of the diaphragm and respiratory muscles), requiring artificial ventilation. Indications for intubation with subsequent artificial ventilation are a decrease in VC to 15-20 ml/kg, PaO2 < _60mmHg or _SaO2 <95% with additional oxygen inhalation, PaCO2 _> 50 mmHg. The duration of artificial ventilation (from several days to months) _{is determined individually, focusing on VC, restorationof} swallowing and cough reflex, and the general dynamics of the disease. The patient is disconnected from the ventilator gradually, through the stage of intermittent forced ventilation.

In severe cases with pronounced paresis, proper care is of fundamental importance for preventing complications associated with prolonged immobility of the patient (bedsores, infections, thromboembolic complications, etc.): periodic (every 2 hours or more often) change of the patient's position, skin care, prevention of aspiration [sanitation of the oral cavity and nose, feeding through a nasogastric tube, sanitation of the trachea and bronchi (during artificial ventilation)], monitoring of the functions of the bladder and intestines, passive gymnastics and massage of the limbs, etc.

In case of persistent bradyarrhythmia with the risk of developing asystole, installation of a temporary pacemaker may be required.

Drug therapy and plasmapheresis

As a specific therapy for Guillain-Barré syndrome, aimed at stopping the autoimmune process, pulse therapy with immunoglobulins of class G and plasmapheresis are currently used. Specific therapy methods are indicated for severe (score on the North American scale of motor deficit severity of 4 and 5 points) and moderate (2-3 points) disease. The effectiveness of both methods is approximately the same, their simultaneous use is inappropriate. The treatment method is selected individually, taking into account availability, possible contraindications, etc.

• Plasmapheresis is an effective method of treating Guillain-Barré syndrome, significantly reducing the severity of paresis, the duration of mechanical ventilation and improving the functional outcome. Usually 4-6 operations are carried out with an interval of one day; the volume of replaced plasma during one operation should be at least 40 ml / kg. 0.9% sodium chloride solution, rheopolyglucin, albumin solution are used as replacement media. Plasmapheresis is relatively contraindicated in liver failure, severe cardiovascular pathology, blood clotting disorders, and infections. Possible complications are hemodynamic disorders (drop in blood pressure), allergic reactions, electrolyte imbalances, hemorrhagic disorders, and the 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 stay on mechanical ventilation and improves functional outcome. The most common side effects are headaches, muscle pain, fever, nausea; their severity can be reduced by reducing the infusion rate. Severe side effects, such as thromboembolism, aseptic meningitis, hemolysis, acute renal failure, etc., are extremely rare. Human normal immunoglobulin is contraindicated in congenital IgA deficiency and a history of anaphylactic reactions to immunoglobulin preparations.

Symptomatic treatment of Guillain-Barré syndrome

• Infusion therapy for the correction of acid-base, water-electrolyte balance disorders, and severe arterial hypotension.
• In case of persistent severe arterial hypertension, antihypertensive drugs (beta-blockers or calcium channel blockers) are prescribed.
• In case of severe tachycardia, beta-blockers (propranolol) are prescribed; in case of bradycardia, atropine.
• In the development of intercurrent infections, antibiotic therapy is necessary (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 case of neuropathic pain, the drugs of choice are gabapentin, carbamazepine, pregabalin.

Surgical treatment of Guillain-Barré syndrome

If long-term (more than 7-10 days) artificial ventilation is required, it is advisable to apply a tracheostomy. In case of severe and long-term bulbar disorders, it may be necessary to apply a gastrostomy.

General principles of treatment of Guillain-Barré syndrome

Treatment of acute and rapidly increasing manifestations of Guillain-Barré syndrome requires supportive care in the intensive care unit, as well as an impact on the immune mechanisms of disease development. Patients with Guillain-Barré syndrome should be hospitalized for careful monitoring of the respiratory and autonomic functions. The faster the paralysis increases, the higher the likelihood that artificial ventilation will be required. During the period of increasing symptoms, regular neurological examination, assessment of the vital capacity of the lungs, maintenance of airway patency with regular suction of mucus are necessary. In the early stages of the disease, constant vigilance is necessary, since even in the absence of obvious disorders of respiratory and bulbar functions, minor aspiration can significantly increase autonomic dysfunction and provoke respiratory failure.

Improved prognosis and decreased mortality in Guillain-Barré syndrome in recent years are largely due to early admission of patients to intensive care units. Indications for transferring a patient to the intensive care unit and considering intubation may include a decrease in vital capacity below 20 ml/kg and difficulty in removing secretions from the respiratory tract. The goal of early transfer is to avoid emergency intubation in the setting of severe respiratory failure with sharp fluctuations in blood pressure and heart rate, which may provoke myocardial dysfunction or infarction. One of the most important goals of supportive care is the prevention and timely treatment of pulmonary and urinary infections, as well as the prevention of deep vein thrombosis of the leg and subsequent pulmonary embolism by subcutaneous administration of heparin (5000 IU 2 times a day). It is also necessary to monitor nutrition and bowel function. Since autonomic dysfunction has a significant impact on mortality, constant monitoring of cardiac activity and blood pressure is necessary.

One of the important aspects of care for patients with Guillain-Barré syndrome in the intensive care unit, which, however, is not always taken into account, is the correction of severe anxiety, which can be caused by complete immobilization of the patient against the background of preserved intelligence. In this regard, psychological support is of great importance. Patients need to be explained the nature of the disease, the features of its course, including the possibility of progression, familiarize themselves with the methods of treatment at various stages. It is important to explain to them that the probability of complete recovery is very high, even if they are on artificial ventilation for some time. Establishing contact through eye movements reduces the feeling of isolation from the world that patients experience. In our experience, the administration of 0.5 mg lorazepam every 4-6 hours is effective in treating nocturnal hallucinations. It is also possible to prescribe 0.5 mg risperidone or 0.25 mg olanzapine.

Treatment of Guillain-Barré syndrome has changed significantly over the past decade. For example, plasmapheresis has been shown to be effective. Although its mechanism of action remains unknown, it is thought to be related to the release of antibodies, cytokines, complement, and other mediators of the immune-inflammatory response. An open, multicenter North American study comparing outcomes with plasmapheresis and no specific treatment showed that plasmapheresis administered for five consecutive days reduced the length of hospital stay and resulted in greater improvement than in the control group. Treatment was more effective if started in the first week of illness. Similar results were obtained by the French Cooperative Group, which conducted a randomized, multicenter study and showed that four plasmapheresis sessions resulted in faster recovery in 220 patients included in the study (French Cooperative Group, 1987). A study of the same patients one year later showed that complete recovery of muscle strength was noted in 71% of patients who underwent plasmapheresis, and only in 52% of patients in the control group (French Cooperative Group, 1992). The next study compared the effectiveness of different numbers of plasmapheresis sessions in 556 patients with Guillain-Barré syndrome with different severity of symptoms (French Cooperative Group, 1997). In patients with mild symptoms who underwent two plasmapheresis sessions, recovery was more significant than in patients whose treatment regimen did not include plasmapheresis. In patients with moderate symptoms, four plasmapheresis sessions were more effective than two plasmapheresis sessions. At the same time, six plasmapheresis sessions were no more effective than four sessions in patients with either moderate or severe symptoms. Currently, most centers specializing in the treatment of Guillain-Barré syndrome still use five to six sessions, which are carried out over 8 to 10 days, to avoid the stress associated with daily procedures. Exchange transfusion is performed using a Shealy catheter. Plasmapheresis is also effective in children with Guillain-Barré syndrome, accelerating the process of restoring the ability to move independently. Although plasmapheresis is a relatively safe procedure, its use in Guillain-Barré syndrome requires special caution due to the risk of autonomic dysfunction in patients and their tendency to develop infections.

Intravenous administration of high doses of immunoglobulin is also recognized as an effective method of treating Guillain-Barré 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 assumed that it can eliminate pathogenic antibodies due to anti-idiotypic antibodies, block the Fc component of antibodies on target cells, as well as inhibit complement deposition, dissolve immune complexes, weaken the functions of lymphocytes, disrupt the production or interfere with the implementation of the functions 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 plasmapheresis, improvement occurs on average after 41 days, and with immunoglobulin - after 27 days. In addition, patients who received immunoglobulin had significantly fewer complications and required less mechanical ventilation. The main adverse prognostic factor was older age. A subsequent randomized multicenter study of plasmapheresis and immunoglobulin in 383 patients who were given these methods within the first 2 weeks after the onset of symptoms showed that both methods had comparable efficacy, but their combination did not have significant advantages over the use of either method alone.

The administration 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-Barré syndrome. Side effects were mild and rare. Some patients, especially those suffering from migraine, experienced headache, which was sometimes accompanied by aseptic meningitis with pleocytosis in the cerebrospinal fluid. Chills, fever and myalgia, as well as acute renal dysfunction with the development of renal failure, were also sometimes observed. Anaphylactic reactions are possible with the administration of immunoglobulin, especially in individuals with immunoglobulin A deficiency. The main disadvantage of both immunoglobulin and plasmapheresis is their high cost. However, it is clearly outweighed by the effectiveness of these treatments, which is obvious even in the current era, which forces us to count money.

A double-blind, placebo-controlled, multicenter study of 242 patients with Guillain-Barré syndrome showed that high-dose intravenous corticosteroids (methylprednisolone, 500 mg daily for 5 days) did not affect any of the parameters assessing the outcome of Guillain-Barré syndrome or the likelihood of its recurrence. In a subsequent open-label study in which 25 patients with Guillain-Barré syndrome were treated with intravenous immunoglobulin (0.4 g/kg daily for 5 days) and methylprednisolone (500 mg daily for 5 days), the effect was compared with control data obtained earlier with the use of immunoglobulin alone. With the combination of immunoglobulin and methylprednisolone, recovery was better, with 76% of patients showing at least one functional improvement by the end of week 4, compared with 53% of patients in the control group. This may indicate that corticosteroids may still play a role in the treatment of Guillain-Barré syndrome. Randomized clinical trials are needed to clarify this issue and determine whether intravenous corticosteroids are added to plasmapheresis or immunoglobulin to significantly improve outcome.

Further management

After the acute period is over, comprehensive rehabilitation measures are necessary, the plan for which is drawn up on an individual basis depending on the severity of residual symptoms (exercise therapy, massage, etc., while thermal procedures are contraindicated!).

Patients who have had Guillain-Barré syndrome should be informed of the need to follow a protective regimen for at least 6-12 months after the end of the disease. Physical overload, overheating, hypothermia, excessive insolation, and alcohol consumption are unacceptable. Vaccination should also be avoided during this period.

Forecast

The mortality rate for Guillain-Barré syndrome averages 5%. The cause of death may be respiratory failure, but death may also result from aspiration pneumonia, sepsis and other infections, or pulmonary embolism. Mortality increases significantly with age: in children under 15, it does not exceed 0.7%, while in people over 65, it reaches 8.6%. Other unfavorable prognostic factors for a full recovery include a prolonged period of mechanical ventilation (more than 1 month), and the presence of previous lung diseases.

Most patients (85%) experience complete functional recovery within 6-12 months. Persistent residual symptoms persist in approximately 7-15% of cases. Predictors of poor functional outcome include age over 60 years, rapidly progressive disease, and low amplitude of the M-response during stimulation at the distal point (implying severe axonal damage). The recurrence rate of Guillain-Barré syndrome is approximately 3-5%.

[ 45 ], [ 46 ], [ 47 ]