Modern ideas about idiopathic inflammatory polyneuropathies

Currently, about 100 kinds of polyneuropathies are considered in medical practice. Idiopathic inflammatory polyneuropathies belong to the rare forms of polyneuropathies, therefore it is very important to know these forms, to be able to diagnose them correctly and, most importantly, to treat them quickly and adequately, as these diseases in most cases have a progressive course, invariably leading to disability, and in a number of cases to death.

Idiopathic inflammatory polyneuropathies are a group of heterogeneous diseases of the peripheral nervous system associated with the development of an autoimmune attack against antigens of peripheral nerve fibers, the cause of which remains unclear. With the flow, depending on the specificity of the autoimmune process, they are divided into acute, subacute and chronic. Depending on the type of antigen against which an autoimmune attack occurs, they are demyelinating or axonal, symmetric or asymmetric.

[1], [2], [3], [4], [5], [6]

Guillain-Barre Syndrome

Guillain-Barre syndrome (SGB) is one of the brightest representatives of idiopathic inflammatory polyneuropathies. The incidence of Guillain Barre syndrome ranges from 1 to 2 cases per 100 000 population per year, is more common in men, and two peak incidence rates are noted: between the ages of 15 to 35 and 50 to 75 years.

In the Guillain-Barre Syndrome, acute inflammatory demyelinating polyneuropathy (OVDP) is isolated, with a frequency of more than 85%; Acute motor axonal neuropathy (OMAN) - 3%, as its variant - acute motor-sensory axonal neuropathy (OMSAN) with a frequency of less than 1% and Miller-Fisher syndrome, which is about 5% of cases.

What causes the Guillain-Barre Syndrome?

An important role in the etiology of the Guillain-Barre syndrome is attributed to an autoimmune reaction directed against antigens of the peripheral nervous tissue. For 1-6 weeks before the first symptoms appear, more than 60% of patients have signs of respiratory or gastrointestinal infection. However, by the time of the first signs of the Guillain-Barre syndrome, the symptoms of a previous infection usually regress. Provocative agents are influenza A and B viruses, parainfluenza, ECHO, Coxsackie, hepatitis B, measles, Campylobacter jejuni. A definite relationship of Guillain-Barre syndrome with cytomegaloviruses (15% of cases), Epstein-Barr virus (10% of cases) and Mycoplasma pneumonia (up to 5% of cases) is established. The transferred infection, apparently, serves as a provoking factor that triggers an autoimmune reaction. The role of the triggering factor can also be performed by vaccination (against influenza, less often against rabies, measles, mumps, rubella), surgical interventions, blood transfusion. Cases of Guillain-Barre syndrome in patients with lymphogranulomatosis and other lymphoproliferative diseases, systemic lupus erythematosus, hypothyroidism, heroin addiction are described.

Symptoms of Guillain-Barre Syndrome

Guillain-Barre syndrome makes its debut with the emergence of general weakness and pain in the limbs. Muscular weakness, beginning with the distal or proximal parts of the legs, develops in the ascending direction. A few days (less often weeks) develops a deep flaccid tetraparesis, sometimes a plethia with extinction of tendon reflexes, hypotonia of muscles. There is a possibility of bilateral prozoplegia, lesions of the oculomotor nerves, bulbar disorders. In 1/3 of cases, the weakness of the respiratory muscles develops. Approximately one-third of patients have decreased surface sensitivity and joint-muscle feeling. At later stages of the disease, muscle hypotrophy develops. The expressed painful syndrome occurs in 50% of cases with the Guillain-Barre syndrome. In 10-20% of cases, sphincter disorders occur in the form of a transient urinary retention, which quickly disappear in the first few days after the onset of the disease. Virtually all patients have vegetative disorders, which can be one of the possible causes of sudden death of patients.

Guillain-Barre syndrome has a classic monophasic course consisting of three periods: the progression of neurologic symptoms (2-4 weeks); stabilization or plateau (2-4 weeks); recovery, lasting from a few months to 1-2 years.

Timely application of effective methods of treatment contributes to the shortening of the natural nature of the course, reduces the number of deaths.

How to recognize the Guillain-Barre Syndrome?

Diagnosis of the disease on the basis of the clinical picture and additional research methods. Pathognomonic for the disease is considered protein-cell dissociation in cerebrospinal fluid with high protein numbers (up to 3-5 times up to 10 g / l) for both lumbar and occipital punctures.

To date, electromyographic (EMG) study is the most sensitive of objective research methods for diagnosis of Guillain-Barre syndrome. In the EMG, a decrease in the speed of sensory and motor nerve fibers, or signs of denervation and death of axons that develop in parallel with muscle atrophy, and usually portend an unfavorable outcome, are revealed.

For the first time, diagnostic criteria for Guillain-Barre Syndrome were developed by a special group of the American Academy of Neurology back in 1978. Later they were revised several times, but they did not change radically. The most recent official criteria refer to 1993 and are proposed by WHO.

Signs necessary for the diagnosis of Guillain-Barre syndrome: progressive muscle weakness in two or more limbs, tendon areflexia.

Signs that support the diagnosis of Guillain-Barre syndrome: the increase in symptoms for several days or weeks (up to 4 weeks); beginning of recovery 2-4 weeks after cessation of progression; relative symmetry of symptoms; light sensitive disorders; involvement of cranial nerves, often - bilateral defeat of facial nerves; good recovery in most patients; absence of fever at the beginning of the disease, but its appearance does not exclude the SGB; autonomic dysfunction; changes in cerebrospinal fluid (CSF): high protein content with normal or slightly increased cytosis (no more than 10 cells in mm ³ )

Symptoms that raise doubts in the diagnosis: a marked remaining asymmetry of motor disorders; persistent dysfunction of sphincter function; The absence of sphincter disorders in the onset; presence of more than 50 mononuclear and polymorphonuclear leukocytes in the CSF; a clear level of sensitive disorders.

Differential diagnosis of Guillain-Barre syndrome should be performed with myasthenia gravis, toxic polyneuropathy, hypokalemia, botulism, diphtheria, hysteria, porphyria, acute cerebrovascular accident in vertebro-basilar basin, stem encephalitis, AIDS.

How is Guillain-Barre's syndrome treated?

Even mild cases of the Guillain-Barre syndrome in the acute phase refer to urgent conditions requiring immediate hospitalization. The therapeutic measures in the Guillain-Barre Syndrome are divided into specific and nonspecific. Specific methods of treatment of Guillain-Barre syndrome include programmed plasmapheresis and intravenous pulse-therapy with class G immunoglobulins, and these methods are effective not only in the treatment of classical Guillain-Barre syndrome, but also in its variants, including Miller-Fisher syndrome. The course of operations of plasmapheresis includes 3-5 sessions with the replacement of approximately 1 volume of plasma (40-50 ml / kg), which are carried out every other day. An alternative method of treatment of Guillain-Barre syndrome is intravenous pulse therapy with class G immunoglobulins, the standard course of treatment is made at the rate of 0.4 g per 1 kg of body weight of the patient daily for 5 days. It is possible to administer the same exchange rate and according to a more rapid schedule: 1g / kg / day in 2 injections for 2 days. According to data from randomized, blind controlled studies, plasmapheresis and intravenous immunoglobulin improved symptomatically in severe Guillain-Barre syndrome. The combined application of these methods did not bring any additional benefit.

The effectiveness of corticosteroids in the Guillain-Barre syndrome was studied in six randomized trials, which led to the conclusion that it was not appropriate to use these drugs.

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

Acute / subacute idiopathic sensory neuronopathy (ganglopathy)

Acute / subacute idiopathic sensory neuronopathy (ganglopathy) is a rare disease associated with diffuse inflammatory lesions of spinal ganglia. In the clinical picture of this disease, three forms are distinguished: atactic, hyperalgesic and mixed.

Atactic form is characterized by paresthesia, numbness, impaired coordination of movements, instability, increasing when closing eyes, but the strength of muscles remains intact. The examination reveals a decrease in the vibration, joint and muscle sensations, sensitive ataxia, a violation of stability in the Romberg sample, amplified with closed eyes, pseudoathetosis, hypo- and areflexia.

The hyperalgic form is manifested by dysesthesia, neuropathic pain, a decrease in pain and temperature sensitivity, autonomic dysfunction (sweating, orthostatic hypotension) are revealed during examination.

A mixed form combines the features of the two forms described above.

Most often debuts the disease with a sharp onset, neurological symptoms increase for several days, but there is a slower subacute - the symptoms are increasing for several months. During the period of the increase in neurologic symptoms follows the period of stabilization of the disease, in some cases with a further partial regression of symptoms, but in most cases there is a persistent neurological deficit, which continues to increase gradually.

When conducting EMG with the study of sensory fibers, there is a decrease in the amplitude or absence of action potentials. In the study of motor fibers, no pathological changes are detected. With needle EMG, pathological changes also do not appear.

The key to the treatment of this pathology is the early onset of treatment. As an immunotherapy, corticosteroids (prednisolone 1-1.5 mg / kg / day) are administered orally daily for 2-4 weeks, followed by a decrease in dose and a transition to reception every other day. Or methylprednisolone at a dose of 1 g IV in the cap for 5 days, followed by a lower dose with prednisolone inside. A combination of corticosteroids with IV immunoglobulin or with plasmapheresis is possible. Adequate symptomatic therapy and physical rehabilitation of patients are important.

Subacute inflammatory demyelinating polyneuropathy (PVID) can be diagnosed in cases of neurological symptoms increase during 4-8 weeks, however, its nosological status is not definitively determined. More common in men, characterized by symmetric motor-sensory polyneuropathy, less often - isolated motor polyneuropathy. In the EMG study, signs of demyelination are noted. In the study of CSF, protein-cell dissociation is noted. The early administration of corticosteroids (prednisolone at a dose of 1-1.5 mg / kg / day) gives good results. In severe forms of the disease, combined corticosteroid therapy with IV immunoglobulin, plasmapheresis, and cytostatics is used. Duration of admission is assessed by regression or persistent stabilization of neurological symptoms.

Chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CVD) is an autoimmune disease similar to Guillain-Barre syndrome in pathogenesis and clinical manifestations, but differing with the course. It can have a steady or staged progressing course, proceed as separate exacerbations separated by remissions. Symptoms reach a maximum no earlier than 2 months after the onset of the disease. Frequency of occurrence varies from 1 to 2 cases per 100 000 population, men are more often ill. The average age of onset of the disease is from 45 to 55 years. Unlike SGB, the infection rarely precedes the onset or relapse of the disease, a more important role is assigned to hereditary immunogenetic factors. In patients with CVD, HLA genes are most often detected: DRw3, Dw3, B8, A1, Aw30, Aw31.

The disease begins gradually or subacute and subsequently acquires a progressive, recurrent or chronic monophasic nature. The type of CVD (progressive, recurrent, monophasic) in each individual patient does not change during the course of the disease. The severity of the symptoms and the severity of the condition may be different in different phases of the CVD.

In most cases, the disease begins sensorimotor disorders in the distal parts of the limbs. Muscle weakness is the leading symptom. In the subsequent, a distal or diffuse tetraparesis is formed, as a rule, symmetrical. Characterized by diffuse hypotension of the muscles and the absence of deep reflexes on the limbs. With prolonged flow there is a moderate diffuse muscle atrophy, more noticeable in the distal parts of the limbs.

Sensitive disorders (paresthesia, hyperesthesia, hyperpathy, hyperalgesia such as "socks", "gloves") also increase with exacerbation of the disease, but never go to the forefront of the clinic. Severe pain syndrome occurs infrequently.

In rare cases, the cranial nerves are affected (facial and bulbar cranial nerves are more often affected), and this always indicates the activity of CVD.

Vegetative disorders are noted in most cases of CVD. A quarter of patients have a postural-kinetic tremor in their hands, which disappears after recovery, and if the disease recurs, it may reappear.

Almost half of patients with CVD during magnetic resonance tomography reveal foci of demyelination in the brain, which most often remain asymptomatic.

The main diagnostic criteria, as in SGB, are areflexia: progressive symmetrical muscle weakness and protein-cell dissociation in the CSF, while the protein content can be very high. EMG often involves the involvement of axons and one or more conduction blocks, and a different degree of denervation process is detected in the muscles, depending on the severity and duration of the disease. Comprehensive examination of the patient with determination of clinical, biochemical, virological indicators (or markers), as well as antibodies to ganglioside GM1 and myelin-associated glycoprotein is mandatory.

Forecast of CVD: in 10% of cases, patients die, 25% remain chained to a bed or wheelchair, but about 60% retain the ability to move around and return to work. Relapses are observed in 5-10% of cases.

With adequate immunotherapy, 70-90% of patients with CVD can be improved, but the main problem of treatment is to maintain the positive effect. The main therapeutic measures are the appointment of corti-kosteroids, non-steroid immunosuppressors, immunoglobulin IV and plasmapheresis.

Corticosteroids are first-line drugs in the treatment of CVD, especially with mild or moderate symptoms. Treatment begins with prednisolone at a dose of 1-1.5 mg / kg / day (usually 80-100 mg / day) once, in the morning every day. After achieving a good effect (usually it takes about 1 month) the dose is gradually reduced, switching to taking the drug every other day at a dose of 1-1.5 mg / kg (for this every two weeks the dose is reduced by 10 mg). With further improvement or stabilization of the process, after 8-10 weeks, a subsequent dose reduction is started. An alternative regimen for managing patients with CVD is to continue taking prednisolone at the indicated dose prior to the normalization of muscle strength (up to 6 months). Then the dose is reduced by 5 mg every 2-3 weeks until it reaches 20 mg every other day, a further reduction is carried out 2.5 mg every 2-4 weeks. To avoid recurrence, the maintenance dose (5-10 mg every other day) is retained for several years. If there is no effect, corticosteroids are canceled earlier.

Sometimes treatment begins with pulse therapy with methylprednisolone at a dose of 1000 mg IV cap. On 200 ml of physiological solution or 5% glucose for 3-5 days, then you can repeat every 4-6 weeks.

The efficacy of plasmapheresis has been proven in two double-blind, placebo-controlled studies. At the same time, a temporary clinical improvement is achieved. There is currently no experience of long-term use of plasmapheresis. In a comparative study, the effectiveness of immunoglobulin therapy in / in and plasmapheresis was approximately equal. If it was possible to achieve a positive effect, then to maintain it requires sessions of plasmapheresis with the addition of 50 mg of prednisolone per day, which can reduce the need for plasmapheresis.

The effectiveness of IV immunoglobulin in CVDV has been demonstrated in several open placebo-controlled studies. The initial dose is 0.4 g / kg / day for 5 days. If there is an effect, the patient should be under dynamic observation, and reassignment of immunoglobulin should not be performed. With a secondary deterioration of the state, it is recommended to repeat the course of treatment with / in immunoglobulin before stabilizing the condition (depending on the severity of the symptoms, this daily dose is administered once every 2-4 weeks). With frequent relapses, it is advisable to attach small doses of prednisolone 0.5 mg / kg / day or cytostatics.

Cytotoxic drugs are prescribed for long-term CVD and allow avoiding the use of corticosteroids in the presence of contraindications to them. Cytotoxic drugs are rarely used as monotherapy, more often they are combined with plasmapheresis and intravenous immunoglobulin.

Active rehabilitation, including exercises in therapeutic gymnastics, massage, orthopedic adaptations contribute to a faster functional recovery of patients.

[7], [8], [9], [10], [11], [12], [13]

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN), based on selective demyelination of motor fibers, is caused by an autoimmune attack against myelin mainly in the Ranvier intercept region. Pathomorphologically, with multifocal motor neuropathy, signs of demyelination and remyelination with the formation of "bulbous heads" are revealed, sometimes axonal degeneration and regeneration.

Multifocal motor neuropathy occurs mainly in men at any age, most often at the age of 40-45 years, is clinically characterized by progressive asymmetric weakness in the limbs without or with minimal sensory impairment. In the overwhelming majority of patients, weakness is expressed distally and more in the hands than in the legs. Only in 10% of cases, weakness is more pronounced in the proximal or lower extremities. Atrophies of muscles are often detected, but may be absent in the early stages of the disease. Fasciculations and crampias are observed in 75% of cases, miokims are possible. In most patients, tendon reflexes with paretic muscles are reduced or absent, which often leads to asymmetry in reflexes. Less often reflexes remain normal or even accented, which gives reason to differentiate multifocal motor neuropathy with lateral amyotrophic sclerosis (ALS). Cranial nerves and nerves, innervating the respiratory muscles, are extremely scarce.

Characteristically, the slow progression of the disease with possible spontaneous remissions.

Electrophysiological marker of this disease is the presence of multifocal partial blocks of conduction on motor fibers during normal conduction by sensory ones. To diagnose multifocal motor neuropathy, it is necessary to identify a block of conduction in at least 2 nerves, and outside the zones of frequent compression of the nerves. Conduction blocks are often determined in the nerves of the hands at the level of the forearm, less often - the shoulder or axillary region. In addition to the blocks of conduct, other signs of demyelination are often determined. With needle EMG against the background of secondary axonal degeneration, signs of denervation are revealed.

In the study of CSF, a slight increase in protein is determined, in 2/3 of patients, the level of creatine phosphokinase in blood is increased 2-3 times. In 40-60% of patients, high titers of IgM autoantibodies to ganglthiosides, primarily to GM1, are determined in the blood, however this criterion is not reliable for diagnosis of multifocal motor neuropathy, since a moderately elevated antibody titer is determined in both ALS and CVD.

The drugs of choice in the treatment of multifocal motor neuropathy are IV immunoglobulin and cyclophosphamide. Corticosteroids and plasmapheresis do not have a good curative effect. Immunoglobulin is given iv at a dose of 0.4 g / kg for 5 days, an alternative scheme is 0.4 g / kg once a week for 6 weeks. A positive effect in the form of muscle strength increase is noted to 2-4 weeks, in the future immunoglobulin is administered at 0.4-2 g / kg once every month. A good recovery of muscle strength is noted with early therapy, long-term pareses with muscle atrophies remain stable.

The multifocal acquired demyelinating sensorimotor neuropathy (MPDSMS) combines the signs of both multifocal motor neuropathy, involving not only locomotor, but sensory fibers, as well as CVD, differing from it by the multifocal asymmetric nature of the lesion. Mostly men are ill, the process begins with the defeat of the distal part of the upper limbs, remains asymmetric for a long time. The involvement of sensory fibers is manifested by the development of pain syndrome and paresthesia in the innervation zone of the affected nerves. Tendon reflexes weaken or completely fall out, but remain intact in unaffected muscles].

The disease progresses rapidly over several months, leading to a significant functional defect and disability of the patient.

When the EMG study determines the blocks of conduct and signs of demyelination, a lack or decrease in the amplitude of the potentials of sensory nerves is detected. In a number of patients, antibodies to gangliosides are found in the blood.

In the treatment of drugs of choice are corticosteroids and iv injection of immunoglobulin in the same dosages as in the treatment of CVD. If they are ineffective, the use of cyclophosphamide is indicated.

Assoc. O. L. Pelekhova. Kharkov Medical Academy of Postgraduate Education // International Medical Journal - №4 - 2012

Classification of idiopathic inflammatory polyneuropathies

Symmetrical:

• Acute inflammatory polyradiculoneuropathy (Guillain-Barre syndrome):
  • demyelinating (classical) variant;
  • axonal variants; the Miller-Fisher syndrome.
• Acute / subacute sensory neuronopathy (ganglion pathology).
• Subacute inflammatory demyelinating polyradiculoneuropathy:
  • chronic inflammatory demyelinating polyradiculoneuropathy;
  • chronic inflammatory axonal polyneuropathy.

Asymmetrical:

1. Multifocal motor neuropathy.
2. Multifocal acquired demyelinating sensomomotor neuropathy.
3. Multifocal acquired axonal sensorimotor neuropathy.

[14], [15], [16], [17],