Severe acute demyelinating polyneuropathies: some aspects of clinical presentation, diagnosis and treatment

H. Koller, B. C. Kieseier, S. Jander and H.-P. Hartung New England Journal of Medicine 2005;352:1343-1356

Chronic inflammatory demyelinating polyneuropathy (CDDP) is common, although often underdiagnosed and potentially severe illness with an average width of approximately 0.5 cases/100 00 0 children and 1–2 stages/100,000 adults. The clinical similarity of the acute variant of demyelinating polyneuropathy (Guillain-Barré syndrome) and the positive effect of the recognition of immunosuppressors suggests an immune response rare pathogenesis. Since the first descriptions of steroid-reactive patients with chronic polyneuropathies, the range of clinical manifestations and diagnostic possibilities for them have expanded even more, and the same can be said about treatment. The division of the named will become a type of other widening of motor-sensory damage to the peripheral nerves that accompanies diabetes, alcoholism and malnutrition, is deprived of principles. This review outlines the current knowledge of the clinical picture of CIDP, diagnostic criteria and procedures for it, as well as treatment strategies based on the latest randomized control studies.

Classic chronic inflammatory demyelinating polyneuropathy

Classical CKD is characterized by the development of symmetrical weakness of the proximal and distal end organs, which progresses over at least 2 months. It is also associated with sensitive disorders, decreased or impaired tendon reflexes, displacements of the spinal cord (SMR), changes typical for demyelinization during Electrophysiological observations and signs of demyelization following biopsy results. This disorder can be recurrent or chronically progressive, and remains typical for diseases of the young age.

The fragments of this disease are increasingly being recognized and have been studied in various clinical studies, and several expert groups have identified the clinical significance of this variant of polyneuropathy (Table 1).
In all cases, it is important to base the diagnosis on clinical symptoms and the results of electrophysiological studies, since the need for additional CMR and biopsies varies depending on the level of clinical diagnostics. accuracy, which ranges from possible to accurate. Two remaining conditions are necessary to establish a clear diagnosis using the American Academy of Neurology criteria rather than the broader criteria of Saperstein et al. and the recommendations of the Group for the identification of causes and treatment of inflammatory neuropathies. Classic CKD responds well to treatment with corticosteroids, which helps in its differentiation from other forms of swelling demyelinating polyneuropathies. Table 1. Diagnostic criteria for CDDP

CIDP classification

The variety of manifestations allows us to distinguish the classic form of CIDP and atypical types. In the classic form, symmetrical muscle hypotonicity occurs in all parts of the extremities, and sensory disturbances occur, which intensify for more than 2 months. The development of the disease is slow, monotonous, gradual, and may be accompanied by exacerbations.

Among the atypical forms of CIDP, the following are distinguished:

• Distal - lesions are observed on the hands, forearms, feet, and legs. The limbs are damaged asymmetrically.
• Focal - one or more nerve fibers in the brachial or lumbosacral plexus are affected.
• Isolated (sensitive) - the demyelination process damages only sensory nerve fibers.

Demyelinating polyneuropathies, subtypes of classic CDDP

Local clinical analysis allows us to see other forms of swelling demyelinating polyneuropathies with similar autoimmune and dysimmune mechanisms, which are recognized as CKD. both in terms of the clinical picture and in terms of the therapeutic response. It is still unknown what these variants will become and what other clinical units will be.

Demyelinating distal symmetrical polyneuropathy has developed

They assume that the illness is in solidified form. Its characteristic manifestations are an increase in width in men and women over 50 years of age, sensory deficits and mild weakness, especially in the distal parts of the ends (as opposed to more generalized symptoms in X ZDP) and instability of movement. IgM paraproteinemia is evident in up to 2/3 of patients with this condition. Vin appears to respond poorly to immunosuppressive therapy.

Multifocal motor polyneuropathy

It is important to differentiate multifocal motor polyneuropathy from motor neuron disease. Persha is characterized by the presence of asymmetrical weakness without a sensitive defect, often starting in the muscles of the distal ends. Partial block of motor conduction in various places is a characteristic electrophysiological sign, although not in all patients. There is no doubt about the detection of circulating antiganglioside antibodies. Instead, protein and cell quantity are within the normal range. Although the use of corticosteroids and plasmapheresis in multifocal motor polyneuropathy is more important than ineffective treatment, it is treated with immunoglobulin or cyclophosphamide.

Onset of demyelinating multifocal motosensory polyneuropathy (Lewis-Sumner syndrome)

The onset of demyelinating multifocal motosensory polyneuropathy (Lewis-Sumner syndrome) is similar to CKD (motosensory deficit, movements of the protein in the SMR, pathological changes in electrophysiological studies), and with multifocal motor polyneuropathy (asymmetrical appearance of symptoms, often from the upper ends , presence of conductivity block). Some individuals with this condition exhibit antibodies to gangliosides and smells and react well to the internal administration of immunoglobulins and cyclophosphamide.

Other polyneuropathies close to CDDP

There are many other types of swelling and chronic polyneuropathies similar to CKD, they are classified into subgroups. This is axonal, sensory and motor and axonal chronic inflammatory demyelinating polyneuropathy. About their skin there is only one mystery in the literature. Basically, patients with demyelinization of peripheral nerves and a good and partial reaction to immunotherapy are considered to be such that there may be discord from the group of chronic inflated demyelinating sex Neuropathies. Depending on the structure of the clinical picture, such a diagnosis may be possible, reliable and clear. Chronic idiopathic axonal polyneuropathies are a heterogeneous group of progressively progressive neuropathies with painful and mild disability.

Treatment

The goal of treatment for polyneuropathy is to treat the underlying disease and minimize symptoms. If laboratory tests and other examinations indicate that there is no underlying disease, the doctor may recommend watchful waiting to see if the symptoms of neuropathy improve on their own. If there is exposure to toxins or alcohol, your doctor will recommend avoiding these substances.

Drug treatment

Medicines used to relieve pain from polyneuropathy include:

• Painkillers such as paracetamol or NSAIDs reduce pain
• Medicines containing opioids, such as tramadol (Conzip, Ultram ER and others) or oxycodone (Oxycontin, Roxicodone and others), can lead to dependence and addiction, so these drugs are generally prescribed only when other treatments have no effect.
• Anticonvulsants. Medications such as gabapentin (Gralise, Neurontin) and pregabalin (Lyrica), developed to treat epilepsy, can significantly reduce the pain of neuropathy. Side effects of these drugs may include drowsiness and dizziness.
• Capsaicin. A cream containing this substance (found naturally in hot peppers) can be used to provide some relief from the symptoms of neuropathy. But given the irritating effect of capsaicin on the skin, not all patients can tolerate the effects of capsaicin creams.
• Antidepressants. Some tricyclic antidepressants, such as amitriptyline, doxepin, and nortriptyline (Pamelor), can be used to reduce neuropathy pain through their actions on the central nervous system.
• The serotonin and norepinephrine reuptake inhibitor duloxetine (Cymbalta) and the antidepressant venlafaxine (Effexor XR) may also relieve pain from peripheral neuropathy caused by diabetes. Side effects may include dry mouth, nausea, drowsiness, dizziness, decreased appetite, and constipation.
• Intravenous immunoglobulin is the mainstay of treatment for chronic inflammatory demyelinating polyneuropathy and other inflammatory neuropathies.
• Alpha lipoic acid. Used to treat peripheral neuropathy in Europe for many years. This antioxidant helps reduce symptoms. You should discuss taking alpha lipoic acid with your doctor because it may affect your blood sugar levels. Other side effects may include stomach upset and skin rash.
• Herbs. Some herbs, such as evening primrose oils, may help reduce neuropathic pain in patients with diabetes.
• Amino acids. Amino acids such as acetyl-L-carnitine may help improve symptoms of peripheral neuropathy in patients undergoing chemotherapy and in patients with diabetes. Side effects may include nausea and vomiting.

In addition to drug treatment, other treatment methods may be used.

• Myostimulation allows, to a certain extent, to restore the conduction of nerve impulses through the muscles.
• Plasmapheresis and intravenous administration of immunoglobulin.
• Exercise therapy. If you have muscle weakness, physical activity can improve muscle strength and tone. Regular exercise, such as walking three times a week, can reduce neuropathy pain, improve muscle strength, and help control blood sugar levels. Exercises such as yoga and tai chi can also be quite effective.
• Acupuncture. Impact on biologically active points improves the sensitivity of nerve receptors and reduces pain.

Recommendations for patients with polyneuropathy

• It is necessary to take care of your feet, especially if you have diabetes. You should check your feet daily for blisters, cuts, or calluses. Soft, loose cotton socks and soft boots should be worn.
• You need to quit smoking. Smoking can affect circulation in the extremities, increasing the risk of foot problems and other neuropathy complications.
• Eat healthy. A healthy diet is especially important to ensure that the patient receives the necessary vitamins and minerals.
• We must avoid drinking alcohol. Alcohol can worsen the symptoms of polyneuropathy.
• Monitoring blood glucose levels in the presence of diabetes will help keep blood glucose levels under control and may help improve neuropathy.

Satellite illness

CKD may be associated with concomitant illnesses, such as HIV infection, hepatitis C, Sjögren's syndrome, inflammatory bowel disease, melanoma, lymphoma, blood diabetes and monoclonal IgM-, IgG- and Ig A-gammopathy. The pathogenetic importance of such associations becomes unconscious. Moreover, in response to the onset of demyelinating distal symmetrical polyneuropathy due to IgM paraproteinemia, clinical manifestations of the above-mentioned conditions due to muscle weakness The maximal and distal ends are practically identical to those with CKD and are treated with the same therapeutic approaches. Of particular interest is the association with diabetes, which has implications for diagnosis and treatment. In some cases, CKD may be associated with other polyneuropathy due to seizure disorders (Charcot-Marie-Tooth disease).

Infection of the central nervous system

Magnetic resonance imaging (MRI) of the brain reveals demyelinating lesions in some patients with CKD, despite the great rarity of cerebral or cerebellar symptoms in this population. At the same time, according to the results of one of the studies, demyelinization of the visual pathways, ascertained by the prolonged latency of the visual excitatory potentials, was observed in half of such patients. 5–30% of these patients also show symptoms of cranial nerve damage. It is important to note that clinical symptoms of cerebral origin, as well as brain lesions behind MRI findings in CKDP, can be recognized after the assessment of immunoglobulins.

Clinic of the disease

The symptoms of CIDP are based on sensorimotor polyneuropathy. The development of the pathological condition begins imperceptibly; patients cannot accurately indicate the period of onset of the first symptoms. The reason for seeking medical help is the appearance of weakness in the legs, difficulty walking, or climbing stairs. Weakness in the hands makes it difficult to do minor work. Patients complain of numbness and unsteadiness.

Muscle hypotonicity in CIDP develops symmetrically along an ascending path. The slow progression lasts for more than two months. In 16-20% of clinical cases, polyneuropathy has an acute onset, asthenia progresses quickly - up to a month.

Pathologies of the motor sphere develop in the proximal parts of the extremities. Upon examination, a decrease or loss of reflexes, primarily the Achilles reflex, is revealed. The vast majority of patients have sensory impairments that predominate over motor ones. HDVP is manifested by numbness of the feet and hands. Deep lesions of sensitivity are expressed by sensory ataxia. Some patients have pronounced pain syndrome.

Some body postures provoke the appearance of postural tremors of the hands. The oculomotor, facial, and trigeminal cranial nerves are often affected. Bulbar palsy develops much less frequently. The respiratory muscles may be involved in the process, followed by respiratory failure. It is important to note that autonomic disorders are not typical in CIDP.

Depending on the type of course, CIDP can be monophasic or chronic. The monophasic type develops slowly. When maximum symptoms are reached, regression occurs - partial or complete. No relapse is observed.

In a chronic course, the disease develops slowly, and gradual peaks of symptoms are possible. Clear periods of exacerbation are observed in 25-30% of patients.

The acute onset of CIDP is often mistaken for Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).

DIAGNOSTIC APPROACHES

The diagnosis of distal inflated demyelinating symmetrical polyneuropathy is important based on clinical manifestations and the results of tracing nerve conductivity, which is consistent with demyelin. zatsieyu (Table 1).
Growth instead of protein in SMR without pleocytosis and histological signs of demyelinization and remyelinization often from the follow-up of biopsy specimens provide additional information. In case of diagnostic doubts, we recommend performing a nerve biopsy, taking into account iatrogenic effects and serious side effects of trival immunomodulatory and immunosuppressive therapy. A look at the most basic elements of differential diagnosis of CKD is presented in Table 2. Table 2. Differential diagnosis of CKD

general information

CIDP received its final definition in 1982, when characteristic neurophysiological symptoms were identified. Previously, neurologists considered demyelinating polyneuropathy to be a type of Guillain-Barré syndrome.

The disease is recorded mainly in adults, 1-2 cases per 100 thousand population. Men get sick more often than women. In people over 50 years of age, CIDP is more severe. Most often, the disease develops against the background of HIV infection, amyloidosis, chronic glomerulonephritis, diabetes mellitus, malignant tumors, and paraneoplastic syndrome.

Electrophysiological diagnostic methods

Neural conduction studies reveal dramatic manifestations of demyelinization. A special committee of the American Academy of Neurology identified the main musculoskeletal neurophysiological signs typical for this country: partial conduction block of the roch nerves (Fig. 1A), decreased fluidity of them Apparently, the latency of the distal roch nerves is prolonged and the latency of the F nerve is prolonged. To clarify the inclusion criteria for clinical follow-up, the criteria were modified for demyelinization. Thaisethawatkul et al. rely on the dispersion of the distal folding meat potential as a very sensitive diagnostic sign of CKDP. Although scientifically advanced criteria may be highly specific, clinical options must be sensitive to identify patients who will require treatment.

Nerve biopsy

The diagnostic value of neural biopsy (especially the lithic nerve) in CKD is still being intensively debated. Some experts do not respect it for the diagnostic method, but others consider it to be the initial element in the diagnosis and treatment of over 60% of such patients. Bosboom et al. signs of demyelinization, axonal degeneration, regeneration and inflammation were observed in biopsy specimens of patients with CIDP and chronic idiopathic axonal polyneuropathy. Pathomorphological findings in most individuals from both groups are similar or extremely discordant. In addition, for a number of reasons, nerve biopsy has low diagnostic value in this case. The greatest severity of the disorder may be evident in the proximal neural segments of the motor nerves and spinal cords, which are not always anatomically accessible for this procedure. In addition, immediate or secondary axonal changes that begin in the early stages of the disease may obscure the developmental manifestations of demyelinization and inflammation until the time of biopsy.

Although unimportant in general terms, this method of design is still respected by many specialists (Fig. 1D-G). According to Haq et al., grafting of the lithoid nerve may result in sensitivity, consistent with electrophysiological studies. Similarly, Vallat et al. report that 8 patients in a series of 44 individuals had minor pathomorphological changes, which indicate CPDP based on the availability of electrophysiological data prior to demyelinization . It is important to note that 5 of them responded positively to the therapy.

Biopsy is strongly recommended in patients with clinical suspicion of CKD, in whom neural conduction studies do not indicate demyelination or underlying vascular compromise. that one In a series of 100 patients with this neurological disorder, Bouchard et al. They found that axonal structure during the procedure was the most sensitive prognostic indicator, which indicated an unpleasant progression of illness. They revealed demyelinization in 71% of patients, mixed axonal and demyelinating changes - in 21% and total axonal disorders - in only 5%. The basic diagnostic algorithm for CPDP is presented in Fig. 2.

Diagnostics

When diagnosing polyneuropathy, a doctor may be primarily interested in answers to the following questions:

• Does the patient have any medical conditions such as diabetes or kidney disease?
• When did the symptoms begin?
• Were the symptoms constant or sporadic?
• How severe are the symptoms?
• What causes symptoms to increase or decrease?
• Did anyone in the patient's family have similar symptoms?
• The doctor needs a complete medical history. The doctor will review the patient's medical history, including symptoms, lifestyle, exposure to toxins, bad habits, and family history of neurological diseases.
• During a neurological examination, the doctor can check tendon reflexes, muscle strength and tone, the ability to feel certain sensations, and coordination.

The doctor may order an examination

• Imaging or MRI tests can detect various diseases (including tumors).
• Neurophysiology. Electromyography records electrical activity in muscles, which can help determine whether symptoms, including weakness, are caused by muscle tissue damage or nerve damage. ENMG checks the conduction of impulses along the nerves and allows you to determine the degree of damage to the nerve fibers. Neurophysiological studies of the autonomic nervous system may also be performed - sensory tests that record how the patient feels touch, vibration, cold and heat.
• Nerve biopsy. A doctor may recommend removing a small portion of a nerve, usually a sensory nerve, to examine morphological changes in the nerve to determine the cause of the nerve damage.
• Skin biopsy. In this test, a small portion of skin is removed to examine the number of nerve endings. A decrease in the number of nerve endings indicates neuropathy.
• Laboratory research methods are necessary to exclude various diseases, such as diabetes mellitus, autoimmune diseases, kidney disease, etc.

Tomography

MRI can be used to demonstrate gadolinium enhancement (Figures 1B and 1C) and enhancement of the proximal spinal nerves or spinal cords, which reflect active inflammation and demilitarism. Insertion of the cauda equine or brachial plexus. Changes on the side of the rest (asymmetric swelling and increased intensity of the signal in T2 mode) were observed in more than 50% of patients with CKD. It is worth noting that the same changes were observed in patients with distal demyelinating polyneuropathy associated with IgM monoclonal gammopathy.

SUCHASNE LIKUVANNYA

The goal of treating the disorder to which this article is devoted is aimed at blocking patho-immune processes, suppressing inflammation and demyelinization and preventing secondary axonal degeneration. In patients who respond to the new therapy, therapy may be continued until maximum improvement is achieved and stabilization develops; In addition, there is a need for supportive treatment, which should be individualized for a specific patient by eliminating and reducing the frequency of illness or progression of illness. A positive therapeutic response is reflected in the marked improvement in motor skills and sensitivity, as well as the patient's ability to function in everyday life. It is important to remember that infections and fevers also interfere with demyelinization and can aggravate the clinical symptoms of CKDP. At the same time, the recognition of neurotoxic drugs and the presence of systemic diseases associated with polyneuropathies, theoretically, also have an effect on the manifestation of disease.

The most widely used lines of therapy for CKDP are the internal administration of immunoglobulins, plasmapheresis and the administration of corticosteroids (Table 3).
It is necessary to begin in the early stages of the disease to avoid progressive demyelinization and secondary axonal destruction, which leads to permanent disability. Based on the published data, there is clearly little difference in the effectiveness of these three strategies. The decision to choose a particular one takes into account the medical price, availability (for example, plasmapheresis) and side effects (especially if we are talking about serious side effects of corticosteroid infusions). Approximately 60–80% of patients with classic CKDPD have a swelling when they stop taking one of the lower steps, and the long-term prognosis here is determined by the moment of initiation of treatment and the stage associated axonal impulse. Azathioprine, cyclophosphamide, and cyclosporine have long been used as other agents in this disorder, but precise data on their effectiveness from randomized controlled studies are not available. For unclear reasons, the names of these drugs are much less harmful in polyneuropathy, which is accompanied by the presence of antibodies to myelin-associated glycoprotein. Table 3. Current trends in the treatment of CKD based on the results of randomized controlled studies*

Taking into account the obvious autoimmune cause of CDDP, as well as those that are pathogenetically similar to multiple sclerosis, research was carried out on immunomodulatory drugs that had their effect in other diseases. 20 patients with drug-resistant CKD were enrolled in a prospective study at a large center and were treated with intra-ulcer interferon β-1a at a dose of 30 mcg once a day for a 6-month treatment period. 35% of patients showed symptoms of symptoms worsening, and disease stabilization was observed in 50%, prompting the authors to recommend more placebo-controlled follow-up. At the same time, another study, in which 4 patients with CKD were treated, showed that interferon treatment only has an effect in combination with internal administration of immunoglobulin. Moreover, a small, randomized, double-blind, placebo-controlled, follow-up study of 10 patients with drug-resistant disease treated with interferon β-1a (3 times per week, approximately 3 million MO stretching 2 tizhnіv and 6 million MO stretching 10 Tizhniv), there were no reliable results from such a celebration. The role of α-interferon in CKD is unclear, but we would like to draw attention to the results of an open-label prospective pilot study on the measles of this agent.

There is no doubt that, based on a number of clues, the discord arises when both α- and β-interferons are stagnant. In addition, the rest were not effective in patients with IgM monoclonal gammopathy and Guillain-Barré syndrome. Such precautions caused the emergence of provocative nutrition: what is the cause of interferon mediators connected with the development of CKD and replacement of its suppression? Hughes et al. It has been concluded that to date there is no adequate evidence for the effectiveness of these drugs in this type of polyneuropathy.

Other treatment options were tested in recent studies on a small number of patients or in a number of patients. Positive results were reported in patients with a history of pharmacoresistant CDDP using a combination of plasmapheresis and intravenous administration of immunoglobulins, mycophenolate mofetil, cyclosporine, etanercept, cyclophosphamide I am undergoing autologous transplantation of hematopoietic cells. In patients with multifocal motor polyneuropathy or CKD, the addition of immunoglobulins and mycophenolate mofetil helped to reduce the dose of both primary and corticosteroids, which confirmed the dosage study of 6 patients and retrospective analysis of 21 patients. Two other large studies of 30 patients revealed an increase in clinical status among patients with IgM-associated demyelinating polyneuropathy against the background of treatment with rituximab, which is a chimeric human monoclonal antibody against the CD20 antigen and reduces the number of B lymphocytes. At the same time, there is no shortage of data from randomized control studies of a sufficient number of patients, on the basis of which it would be possible to develop clear recommendations for the treatment of these agents. Evidence for the effectiveness of plasmapheresis, intravenous administration of immunoglobulins and corticosteroids is limited to short-term studies. It is important for other physicians to note that the use of immunosuppressants makes it possible to reduce the frequency and eliminate plasmapheresis and immunoglobulin replacement with significant cost savings. There is clearly a need for controlled studies to assess long-term aspects of the treatment of chronic kidney disease.

Prevention options

Prevention of CIDP is only possible secondary, since a person cannot change his genetic code or avoid infection with viruses. In all conditions where weakness and sensory disturbances occur in the limbs, a thorough clinical examination is required.

CELT neurologists are always wary of such manifestations and make maximum use of diagnostic capabilities. Effective measures to prevent relapses and exacerbations, and reduce the severity of disease progression include complete completion of the treatment course prescribed by the doctor. You should not stop when minimal improvement has been achieved. Treatment must be carried out to the end and appear on time for repeated examinations by the attending physician.

Neurologists at the CELT multidisciplinary clinic have extensive practical experience and are constantly expanding their knowledge and are able to recognize complex forms of demyelinating inflammation.

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VISNOVKI

It is important to recognize CKD in a patient with chronic progressive or remitting polyneuropathy, as there are a number of therapeutic approaches available, including hormone therapy, plasmapheresis and immunoglobulins, which I would like it to be partially effective for the said disabled person. The diagnostic criteria for the rest have already been divided. This disorder is heterogeneous both in terms of clinical manifestations and in sensory immunopathogenesis. Further research may provide greater understanding of these fundamental mechanisms, which will facilitate the development of effective methods of liberation.

Prepared by Yuriy Matvienko

Prognosis for CIDP

Timely initiation of relevant therapy for CIDP makes it possible to obtain complete or almost complete regression of the disease and a decrease in the manifestations of polyneuropathy. The severity of symptoms persists or worsens in 10% of patients. Neurological deficit in minimal manifestations persists in 85% of patients 5 years after the first symptoms were recorded.

If symptoms that first appear continue to progress for more than three months, treatment may require a minimum amount of time—up to a year. Most patients with CIDP undergo fairly long-term therapy, and when it is discontinued, clinical symptoms recur.