RU2314527C1 - Method for establishing uremic genesis of polyneuropathy - Google Patents

Abstract

FIELD: medicine, neurology.

SUBSTANCE: one should study blood plasma due to wedge dehydration technique, moreover, it is important to fulfill pre-drying plasma drop upon a slide with subsequent microscopic analysis of the structure of the obtained sample. In case of combination of two signs - the fissures being at the angle to or parallel to the edge, and, also, the wrinkles in sample's peripheral area one should conclude upon uremic genesis of polyneuropathy. The present innovation enables to establish uremic genesis of polyneuropathy in patients with chronic renal failure. The method is simple and quick in application.

EFFECT: higher efficiency.

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Description

The invention relates to medicine, namely to neurology, and can be used to establish the genesis of polyneuropathy in urological patients, as well as for differential diagnosis in disputed cases.

Polyneuropathy (PNP) is one of the complex forms of the pathological process, where the dominant factor in the etiology of the disease has not yet been identified and a generalized theory of pathogenesis has not been developed. Polyneuropathies are not a single disease, but a group of diseases of various etiologies (1, 4, 8). This disease is one of the most common. It takes the fourth place among other causes of temporary disability - (1, 8).

Most peripheral nerves perform mixed functions and include motor, sensory and autonomic fibers. In accordance with this, mainly motor, sensory or autonomic polyneuropathies are distinguished (6, 8).

Depending on the predominant lesion of various peripheral nerve structures, parenchymal forms of polyneuropathy are distinguished: axonopathies, myelinopathies, interstitial polyneuropathies with lesions of the connective membranes and generalized (8, 13).

One of the types of polyneuropathy is uremic.

Currently, there is practically one way to establish the uremic genesis of field neuropathy, which requires the simultaneous fulfillment of the following three conditions: the presence of polyneuropathy; the presence of chronic renal failure (CRF); the absence of other diseases leading to the development of polyneuropathy (5).

The prevalence of uremic polyneuropathy in connection with the development of dialysis technologies in recent years tends to decrease. Subclinical uremic polyneuropathy also plays a role, predisposing to damage to nerve trunks under the influence of any additional adverse factors.

The pathogenesis of polyneuropathies in renal failure is not entirely clear. Serum creatinine and urea levels weakly correlate with the severity of clinical manifestations. At the same time, there are certain parallels between the severity of renal failure and the degree of damage to the peripheral nervous system. So, with the preservation of the filtering ability of the kidneys above 12 ml / min, polyneuropathy does not develop (14).

Currently, the theory of “medium molecules” dominates, according to which the pathological effect is due to the accumulation of neurotoxic molecules with a weight of 300-2000 Daltons, which can be gradually removed from the blood during dialysis, and this explains the therapeutic effect of dialysis in relation to manifestations of polyneuropathies (15), or remove completely in the presence of a kidney transplant (14). However, no specific toxic substances have been isolated so far, the level of concentration of which in the blood and tissues correlates with the severity of polyneuropathies (16). Polyamines, phenol derivatives, myoinositol, and parathyroid hormone are called potential toxic agents (17). Probably, these toxic substances also act on enzymes (in particular, transketolase, pyridoxalphosphate kinase), which are necessary for the normal functioning of nerves.

Similarly, a Na-K-ATPase inhibitor was found in biological fluids in patients with uremia, which prevents the elimination of sodium from cells and reduces the transmembrane resting potential, as a result of which depolarization and impulse conduction are slowed down.

However, recently the pathogenetic significance of inhibitors, like “middle molecules,” in the pathogenesis of peripheral nerve damage in uremia is questioned (17), but it is indisputable that only the total elimination of various substances that delay the blood flow in patients with uremia can prevent and alleviate its course (17). So, M.Sobh et al. (1998) achieved improvement in neuromuscular function in 22 hemodialysis patients, increasing KT / V to 1.3-1.6 and increasing protein and calorie intake. A cardinal solution to the problem is timely kidney transplantation, and the improvement of nerve conduction occurs even before the restoration of the excretory function of the transplant due to the latter's ability to metabolize toxic substances (17).

The clinic of the syndrome is represented by a progressive violation of sensitivity, often developing subacute in a period of several weeks to several months and characterized by pain, paresthesia, hyperalgesia, dysesthesia, numbness in the limbs, and sometimes in the perioral region. Violations usually begin in the distal regions and spread proximal, the lower extremities are more often affected. Objectively note a decrease in vibrational and articular-muscular feelings; motor disorders are absent, although some patients have some muscle weakness and hypotension. Tendon reflexes are reduced or fall out (8, 13). Electroneuromyography reveals impaired conduction along sensory nerves (2, 8, 13).

Uremic polyneuropathy is a common complication in patients with chronic renal failure (5). However, if a polyneuropathy is detected in a urological patient, it is not necessary that it is uremic polyneuropathy, it is quite possible there is a concomitant disease, such as diabetes mellitus, with the development of ANP. Clarification of the origin of polyneuropathy is relevant for resolving issues related to predicting outcome, correction of treatment of the underlying disease and polyneuropathy. In a situation when a patient is diagnosed with uremic polyneropathy, this opens up wide opportunities for more adequate treatment of the underlying disease, especially hemodialysis.

Thus, today there is practically only one way to establish the uremic genesis of polyneuropathy, which is quite complex, lengthy and time-consuming.

The objective of the invention is the development of a simple, affordable and quick way to establish the uremic genesis of PNP.

The task in the method of establishing the uremic genesis of PNP is achieved by the fact that the blood plasma is examined by the method of wedge-shaped dehydration, while a drop of plasma is preliminarily dried on a glass slide for 18-24 hours at room temperature and minimal air movement, then the structure of the obtained facies is analyzed under a microscope, and if there is a combination of two signs - cracks located at an angle or parallel to the edge of the facies, as well as wrinkles in the peripheral zone of the facies - conclude that the polyneurope thia has a uremic origin.

Figure 1 shows a micrograph (magnification × 40) of the blood plasma facies in the norm, where two zones are reflected - peripheral and central, in the peripheral zone there are radial cracks.

Figure 2 presents a micrograph (magnification × 40) of the plasma facies of a patient with chronic renal failure with uremic PNP, where cracks are shown parallel to the edge and located at an angle to the edge of the facies, as well as wrinkles in the peripheral zone of the facies.

Figure 3 presents a micrograph (magnification × 40) of the plasma facies of a patient with chronic renal failure without uremic polyneuropathy, which shows cracks parallel to the edge of the facies, and there are no wrinkles in the peripheral zone of the facies.

Figure 1-3 indicated:

1 - peripheral zone of the blood plasma facies,

2 - edge of the facies,

3 - radial cracks,

4 - cracks located at an angle and parallel to the edge of the facies,

5 - wrinkles,

6 - cracks parallel to the edge of the facies.

An interesting method is wedge-shaped dehydration, which allows one to make visible the molecular organization of biological fluids by transferring it to the macro level (12). After the droplet dries under standard conditions on a solid substrate, the amount of salts increases from the periphery to the center, and the amount of organic substances increases from the center to the periphery (11). Blood plasma turned out to be a much more complex object of study due to the great variability of its composition and properties. In addition to identifying zonal structures in diagnostics, the shape, number and size of cracks is important, as well as the identification of pathological structures in a dried film - facies - blood plasma (9). A method is proposed for assessing the state of homeostasis (10), in which the state of homeostasis is determined as normal or pathological, as well as stable or unstable, by the parameters of the zonal structures of the dried drop of biological fluid. But what specific pathology can be diagnosed is not indicated. And from the point of view of establishing the genesis and differential diagnosis of PNP, this method has not been used.

The study was conducted on the basis of the dialysis and gravitational blood surgery department of the Nizhny Novgorod Regional Clinical Hospital. N.A.Semashko. 63 patients with chronic renal failure (33 men and 30 women) aged 19 to 71 years (47.1 ± 1.5 years) were examined. Of the total number of patients, 22 patients were at the pre-dialysis stage of chronic renal failure with a duration of uremia from 1 to 4 years; 28 patients received programmed hemodialysis (PGD), the duration of which ranged from 1 to 15 years; 13 patients had a kidney allograft (transplantation duration ranged from 1 year to 15 years).

The complex of studies included neurological examination and electrophysiological methods: electroneuromyography (ENMG) and needle electromyography (EMG). Clinical examination included medical history, neurological examination.

Electroneuromyographic indicators were recorded on the apparatus "MBN-neuromyograph" (Russia). The electroneuromyographic study was carried out using a stimulating surface plate electrode (the cathode was located distally, the anode was proximal), and the lead was removed with a standard set of monopolar, plate electrodes with a diameter of 5 mm.

We used a constant rectangular current with a frequency of 1 Hz and a duration of 200 ms, and the current was selected supramaximal.

The following nerves were investigated.

1) Motor portions of the median nerves, peroneal nerves;

The following were estimated: the amplitude of the motor response (M-response), the form of the M-response, the duration of the M-response, the area of the M-response — a combined indicator, the latency of the M-response, the speed of the impulse (SPI), residual latency (RL).

2) Sensory portions of the median nerves and gastrocnemius nerves were studied by the antidromic technique (distal superposition of the discharge electrodes and stimulation are similar to the study of SPI on motor fibers);

The following were evaluated: the amplitude of the action potential (AP), the form of the AP, the duration of the AP, the area of the AP, the latency of the AP, the SPI of the sensor fibers.

3) Sympathetic portions of the median and tibial nerves;

The following were assessed: the amplitude of the induced cutaneous sympathetic potential (VKSP), the form of VKSP, the terminal latency of VKSP. These indicators reflected the state of predominantly postganglionic sympathetic fibers of the peripheral nerves.

Needle electromyography was performed with concentric bipolar needle electrodes with a cross sectional area of 0.07 mm.

A recording needle electrode was inserted into the motor point of the anterior tibial muscle on the right.

Spontaneous activity at rest was analyzed: administration activity, end plate activity, fibrillation potentials (PF), positive acute waves (POV), fasciculation potentials; and also parameters of potentials of motor units (PDE).

The potential of the motor unit was characterized by the following main parameters: the amplitude of the potential of the motor unit; duration, phase.

When processing the results of electroneuromyographic and electromyographic studies, normative indicators developed at the Department of Human Neuromuscular Pathology with the Russian Myasthenic Center Research Institute of General Pathology and Pathophysiology of the Russian Academy of Medical Sciences were used.

A neurological examination revealed manifestations of polyneuropathy with the presence of characteristic complaints (burning and tingling in the feet, unpleasant constricting sensations in the legs, restless legs syndrome, skin itching, segmental disorders of sensitivity, such as dysesthesia in the distal extremities), as well as changes in the neurological status (decrease in tendon reflexes, peripheral symmetric hypesthesia, decrease in muscular-articular sensation and vibration sensitivity) in (36) 57% of the examined patients with uremia.

At the same time, in 58 (92%) patients with chronic renal failure, statistically significant changes in ENMG and EMG parameters were recorded.

It should be noted that statistically significant changes in ENMG indices were recorded from sensory and sympathetic portions of the median nerves, calf, peroneal, and sympathetic portions of the tibial nerves.

Prior to treatment, all patients underwent a study of blood plasma by the method of wedge-shaped dehydration.

When comparing the results of a clinical, ENMG examination and the structure of the blood plasma facies, it turned out that 37 (90%) of 39 (100%) patients with chronic renal failure who were clinically and electroneuromyographically diagnosed with uremic PNP did not have a concomitant pathology (which could lead to the development of PNP), a combination of two signs was revealed - cracks parallel to the edge of the facies or located at an angle, as well as wrinkles in the peripheral zone of the facies. Nine (15%) of 58 (100%) patients with PUP had diabetes mellitus and 5 (8%) patients without PUP out of 63 (100%), no combination of these signs was noted. It should be noted that cracks located at an angle and parallel to the edge are one pathological sign of a different degree of severity (normally, cracks are located radially). Figure 2 presents a micrograph of the blood plasma facies of patient C. (magnification x40), cracks parallel to the edge and located at an angle (indicated by arrow 4), wrinkles in the peripheral zone of the facies (indicated by arrows 5).

Necessary equipment for the study of blood plasma by the method of wedge-shaped dehydration:

1) glass slides,

2) pipette microdoser,

3) a light microscope.

The proposed method is as follows: in patients with clinical signs of PNP, blood is taken from the ulnar vein on an empty stomach, centrifuged for 10 minutes at 1500 rpm, plasma in an amount of 0.01 ml is applied to a clean glass slide with a pipette microdoser and dried when room temperature in a closed cabinet. After 18-24 hours, the resulting facies is examined under a microscope in transmitted light at low magnification. If there is a combination of two signs - cracks parallel to the edge of the facies or located at an angle, as well as wrinkles in the peripheral zone of the facies - the conclusion is made that the PNP has a uremic origin.

The method can be used to establish the genesis of polyneuropathy in patients with chronic renal failure. With its simplicity and cheapness, the method has a sensitivity of 100%, specificity of 97%.

As mentioned above, uremic PNP has a toxic developmental mechanism. Neurotoxic molecules circulate in the blood, which are normally absent. The authors of the wedge-shaped dehydration method showed that wrinkles in the peripheral zone of the blood plasma facies are markers of intoxication (9). Their detection in urological patients is natural, since one of the syndromes accompanying the process of chronic renal failure is intoxication. We found that the presence of wrinkles in the peripheral zone of the blood plasma facies correlates with the concentration of albumin (by the gamma method r = 0.42, p = 0.034). Albumin is one of the main proteins in human blood plasma. One of the most important functions of albumin is transport, and it can carry various metabolites and toxins. The formation of wrinkles may also be due to the presence of “medium molecules” in the plasma, which are products of protein degradation (3).

Fractures parallel to the edge or located at an angle in the peripheral zone of the blood plasma facies are a sign of lipid metabolism disorders (7). In patients with chronic renal failure, all types of metabolism, including lipid metabolism, are impaired (7). In the group of patients examined by us, the presence of the above symptom correlated with the concentration of total cholesterol in blood plasma (according to the gamma method r = 0.6, p = 0.04).

In patients with chronic renal failure without neurological symptoms in the plasma and blood facies, in 20% of cases there were cracks at an angle and parallel to the edge, and in 20% of cases there were wrinkles in the peripheral zone of the facies, but a combination of these signs was noted in only one person.

As an illustration of the claimed diagnostic technology, we give examples confirming the practical application of this technique.

Clinical example No. 1.

Patient Ch-s, 26 years old, No. of case history 0515847. Received at OKB im. N.A.Semashko 03/15/05 with a diagnosis of chronic glomerulonephritis, terminal stage of chronic renal failure, corrected by program hemodialysis.

Heredity in relation to neurological pathology from the peripheral nervous system is not traced, there are no concomitant diseases.

Upon admission, he complained of a feeling of numbness, "crawling" in the distal parts of the lower extremities, as well as weakness in the muscles of the legs, especially the lower leg, and difficulty walking.

Considers himself ill for about three years.

In neurological status: reduced strength in the muscles of the legs to 4 points, tendon reflexes d = s, torpid from the legs, hypesthesia by the type of elongated gloves and golf.

In the blood test, an elevated level of serum creatinine up to 900 μm / l, urea up to 37 mmol / l is noteworthy.

In the study of vibration sensitivity: decrease from hands to 20 dB and from feet to 25 dB at all frequencies.

According to the ENMG study: the amplitude of M-responses in the study of the median nerves was 6.2 mV, TL 3.2 ms, duration 6.4 ms, area 22.3 μVs, RL 2.2 ms; the amplitude of M-responses from the peroneal nerves was 3.2 mV, the duration was 4.6 ms, and the area was 16.3 μV. From the peroneal nerves, TL 3.72 ms, RL 2.9 ms, SRV in the Far East from the median nerves 55.1 m / s, SRV in the Far East from the peroneal nerves 43.2 m / s. The amplitude indices of AP from the median nerves were 0.0061 mV, the duration of AP was 1.8 ms, and the area of AP was 0.0035 μV; TL 2.9 ms, SRV at NE 53.2 m / s. The amplitude of PD from the calf nerves was 0.0055 mV, the duration of PD was 1.51 ms, and the area of PD was 0.0033 μV; SRV for NE and TL were 46.1 m / s and 3.3 ms, respectively. The amplitude of the VKSP recorded from the palms was 148 μV, TL 2.33 s; when registering with stops, 125 μV, and TL 2.16 seconds. Spontaneous activity was recorded from the anterior tibial muscle with the presence of 6 potentials of fibrillations, 5 potentials of fasciculations, 5 positive acute waves. The potentials of the motor units were predominantly polyphase 35%, with an increased average amplitude of 860 μV, duration of 12.6 ms.

Based on the clinical picture and the results of the electroneuromyographic study, the diagnosis was made: uremic motor-sensory-autonomic polyneuropathy.

In the study of blood plasma by the method of wedge-shaped dehydration, a combination of two signs was revealed - cracks at an angle and parallel to the edge, as well as wrinkles in the peripheral zone of the facies. Figure 2 (magnification × 40) shows cracks parallel to the edge and located at an angle (indicated by arrow 4), wrinkles in the peripheral zone of the facies (indicated by arrows 5).

This clinical example illustrates the situation when the patient is diagnosed with uremic polyneuropathy, and when examining blood plasma by the method of wedge-shaped dehydration, both pathological signs were identified, indicating a uremic genesis of polyneuropathy.

Clinical example No. 2.

Patient A-yuk, 32 years old, case history No. 0515885. He entered the Design Bureau. N.A.Semashko 04/24/05 with a diagnosis of chronic glomerulonephritis, chronic renal failure stage 2a.

Heredity in relation to neurological pathology from the peripheral nervous system is not traced, there are no concomitant diseases.

Upon receipt of complaints of a neurological nature did not show.

Considers herself ill for about a year.

In neurological status unchanged.

In the blood test, an elevated level of serum creatinine up to 250 μm / l, urea up to 15 mmol / l is noteworthy.

According to the ENMG study: the amplitude of M-responses in the study of the median nerves was 6.3 mV, TL 3.2 ms, duration 6.4 ms, area 22.3 μVs, RL 2.2 ms; the amplitude of M-responses from the peroneal nerves was 3.8 mV, duration 4.6 ms, area 16.4 μVs. From the peroneal nerves, TL 3.72 ms, RL 2.81 ms, SRV along the DV from the median nerves 55.2 m / s, SRV along the DV from the peroneal nerves 43.3 m / s. The amplitude indices of AP from the median nerves were 0.0061 mV, the duration of AP was 1.8 ms, and the area of AP was 0.003 5 μV; TL 2.9 ms, SRV at NE 53.2 m / s. The amplitude of PD from the calf nerves was 0.0063 mV, the duration of PD was 1.51 ms, and the area of PD was 0.0032 μV; SRV for NE and TL were 46.1 m / s and 3.3 ms, respectively. The amplitude of the VKSP recorded from the palms was 364 μV, TL 1.36 s; when registering with stops, 255 μV, and TL 1.18 seconds. No spontaneous activity was recorded from the anterior tibial muscle. The parameters of the potentials of the motor units were within normal limits.

Based on the clinical picture and the results of the electroneuromyographic study, no signs of damage to the peripheral nervous system were found.

In the study of blood plasma by the method of wedge-shaped dehydration, cracks parallel to the edge in the peripheral zone of the facies were present. No wrinkles were detected in the peripheral zone of the facies. Figure 3 presents a micrograph of the facies (magnification × 40), which shows cracks parallel to the edge of the facies (indicated by arrows 6), and there are no wrinkles in the peripheral zone of the facies.

This clinical example illustrates the situation when, in the absence of clinical manifestations of polyneuropathy and normal ENMG, no wrinkles were noted in the peripheral zone of the facies, although cracks parallel to the edge were present.

Information sources

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Claims (1)

A method for establishing the uremic genesis of polyneuropathy in patients with chronic renal failure, characterized in that the blood plasma is studied by the method of wedge-shaped dehydration, while a drop of plasma is preliminarily dried on a glass slide for 18-24 hours at room temperature and minimal air movement, then the structure of the obtained facies under a microscope, and in the presence of a combination of two signs - cracks located at an angle or parallel to the edge of the facies, as well as wrinkles in the peripheral zone of the facies They conclude that polyneuropathy has a uremic origin.

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