RU2496414C1 - Method of predicting unfavourable outcome of guillain-barre syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, in particular, to neurology. In the first two weeks from the set of disease electroneuromyographic examination of excitation conduction by ulnar nerve is performed. Magnitude of value of amplitude of dM-response of motor portions of ulnar nerve is measured. If amplitude value is 2.5 mV and lower, unfavourable outcome of Guillain-Barre syndrome in form of preservation of manifested residual paresis in remote period of disease is predicted.

EFFECT: method makes it possible to objectively show degree of affection and spread of pathological process and increase accuracy of prognosis.

4 tbl, 3 ex

Description

The invention relates to medicine, in particular to neurology, and can be used to predict an adverse outcome of Guillain-Barré syndrome (GBS).

GBS is characterized by a favorable prognosis of recovery: most patients, as a rule, fully recover and return to their previous occupation. However, according to numerous studies, residual motor deficiency of varying severity can be observed in 20-40% of cases, residual sensory disturbances and pain syndrome in 40-65% of patients (Bernsen RA, Jager A.E., Schmitz PI et al. Long-term sensory deficit after Guillain-Barre syndrome. Neurology 2001; 248 (6): 483-6).

Considering the fact that GBS affects, as a rule, people of active working age, the issue of early detection of factors of an unfavorable prognosis for recovery in this disease is socially and economically significant. The solution to this problem will allow us to identify patients from the risk group of an unfavorable prognosis of recovery already in the early stages, to timely select the optimal type and sufficient amount of pathogenetic therapy, as well as organize the early start of the whole complex of rehabilitation measures and the necessary duration of their implementation.

Today, the significance of clinical, immunological, biochemical and neurophysiological prognosis criteria for GBS is being studied.

Most of the generally accepted clinical prognosis factors, excluding the form of the disease, according to different authors and their own experience, do not always satisfy the task:

- despite the fact that many authors agree on a more severe course and insufficient degree of recovery from GBS in older people, the significance of this age criterion varies over a fairly wide range - from 40 to 60 years or more (Van Koningsveld R., Steyerberg EW , Hughes RA et al. A clinical prognostic scoring system for Guillain-Barre syndrome. Lancet neurology 2007; 6: 589-594);

- There is no doubt the association of previous diarrhea caused by Campylobacter jejuni with the development of axonal forms of GBS and incomplete restoration of motor functions (Hughes RA, Hadden RD et al. The prognosis and main prognostic indicators of Guillain-Barre syndrome. A multicentre prospective study of 297 patients. The Italian Guillain-Barre Study Group.Brain 1996; Vol.ll9, No.6,2053-2061). However, diarrhea in the premorbid period of GBS can be caused by other reasons (rotavirus, E. coli, Salmonella, Shigella, medication, lactase deficiency, etc.), and therefore without laboratory confirmation of acute campylobacteriosis (the presence of IgA antibodies to C.jejuni) its prognostic reliability decreases;

- the severe and extremely severe condition of the patient in the acute period is not always associated with an unfavorable prognosis of recovery;

- the initial positive reaction to plasmapheresis does not in all cases indicate a rapid subsequent recovery. Immunological and biochemical prognostic criteria for GBS, such as determining the levels of antibodies to peripheral nerve gangliosides, serum gliofibrillar acid protein, tauprotein and neurofilament in cerebrospinal fluid, etc. are currently proving their value only in the framework of research work (Suponeva N. A., Komelkova L.V., Zhirnova I.G., Piradov M.A., Nikitin S.S. Immunological study of acute and chronic acquired polyneuropathies.Allergology and Immunology, 2009, Volume 10, No. 2, p.265- 266; Nikitin S.S., Suponeva N.A., Gracheva L.A., Bykova L.P. Antibodies to gangliosides in acute and chronic autoimmune polyneuropathies.Vestnik Ural Medical Academic Science, 2009, No. 2/1, p.126 -128). In addition, some of these techniques are quite expensive.

The only recognized EMG criterion for an unfavorable prognosis of recovery after GBS is a decrease in the amplitude of the distal motor response (dM response) ≤1 mV, determined for n.medianus in the acute period of the disease (Ropper A.N., Wijdicks E., Truax B. Guillain- Barre syndrome. - Philadelphia: FA Davis Company, 1991 - 369). However, it is known that the median nerve is quite often subject to compression in the area of the carpal tunnel, which, in the absence of information on the amplitude values before the disease, can significantly affect the analyzed EMG parameter, stating a false-positive result in GBS.

The technical result of our proposed method for predicting an adverse outcome of GBS is to increase the accuracy of the forecast due to the fact that the used values of the DM response obtained in the study of the ulnar nerve most objectively reflect the severity and prevalence of the pathological process in this disease. In addition, this forecasting method is affordable, technically easy to implement, relatively inexpensive and non-invasive.

The technical result is achieved by the fact that to predict an unfavorable outcome of Guillain-Barré syndrome, an electroneuromyographic examination of the patient is carried out, while an electroneuromyographic study of excitation in the patient's elbow nerve is carried out in the first two weeks from the onset of the disease, the magnitude of the amplitude of the dM response of the motor portions of the ulnar n is measured one limb and with a value of 2.5 mV or less predict an unfavorable outcome of Guillain-Barré syndrome in the form of conservation manifestations of pronounced residual paresis in the long-term period of the disease.

The method is as follows.

A patient with GBS in the acute period (the first 2 weeks from the onset of the disease) is given a stimulating ENMG according to the standard method using cutaneous electrodes: an active electrode is applied to the motor point of the muscle, a reference electrode is placed on the tendon of this muscle or a bone protrusion distal to the active electrode, and grounding is between diverting and stimulating electrodes; A stimulating bipolar electrode is applied in the projection of the nerve innervating this muscle, in the place of its most superficial location. Stimulation is carried out with rectangular pulses with a duration of 0.2 ms, a frequency of 1 Hz, gradually increasing the current strength until the amplitude of the received M-response stops increasing (Nikolaev S.G. Clinical Electromyography Workshop. - Ivanovo: Ivan. State Medical Academy, 2003 - 264 p.). In our study, the examination was carried out using the Keypoint Clinical System (Medtronic, USA) and Nikolet Viking Selekt (USA) myographs. Investigate the conductive function of the nerve ulnaris from one upper limb. Then, the amplitude value of the negative phase of the dM response obtained by examining the ulnar nerve is evaluated. The normative values were the criteria developed by B.M. Geht, according to which the amplitude of the DM response is normal when examining the ulnar nerve is> 6 mV (Geht B.M. Theoretical and clinical electromyography.- Leningrad: Nauka, 1990. - 230 from.).

If the amplitude of the dM response obtained by examining the ulnar nerve is 2.5 mV or less, the persistence of expressed residual motor impairment of 3 points or less is predicted in the long-term period of GBS. In this case, in the acute period of the disease, it is required to organize professional measures for the care of the patient, the conduct of pathogenetic therapy in full, as well as the whole range of rehabilitation measures that are optimal in duration.

Assessment of the severity of motor deficiency using the North American scale is carried out as follows: stage 0 - normal; Stage 1 - minimal motor impairment; Stage II - the ability to walk 10 m without support or support; Stage III - the ability to walk 10 m with support or support; Stage IV - inability to walk 10 m with support or support (bedridden or wheelchair); Stage V - impaired respiratory function and the need for mechanical ventilation.

There is also a scale for assessing the severity of paresis - by the degree of decrease in muscle strength and by the severity of paresis, which are inverse to each other:

0 points of “muscle strength” - no voluntary movements, paralysis;

1 point - barely noticeable muscle contractions, without movements in the joints;

2 points - the range of motion in the joint is significantly reduced, movements are possible without overcoming gravity (along the plane);

3 points - a significant reduction in the range of motion in the joint, muscles are able to overcome the force of gravity, friction (in fact, this means the possibility of separation of the limb from the surface);

4 points - a slight decrease in muscle strength, with a full range of motion;

5 points - normal muscle strength, full range of motion.

Method implementation examples

As a demonstration of the prognostic capabilities of our proposed criterion - the amplitude of the DM response n.ulnaris, we present the following clinical cases (Table 1).

Example 1

Patient F., 32 years old, suffered an axonal form of GBS 9 months ago at the age of 32 years. On admission, on the seventh day from the onset of the disease, a stimulatory ENMG was performed using the Keypoint Clinical System myograph (Medtronic, USA), during which an ulnar nerve was examined with a DM response, the negative phase amplitude of which was 2.5 mV, which indicated a high probability of maintaining a pronounced residual motor deficit in the long-term period of the disease. During the period of maximum development, the severity of the patient's condition corresponded to 4 stages according to the ASP, characterized by the inability to walk 10 meters with support or support and confined to a bed and a wheelchair. The patient was promptly started with pathogenetic therapy - a plasmapheresis course with a total volume of removed plasma of 8 l (120 ml / kg / course), against which a positive trend was noted: a gradual regression of neurological deficit with a recovery within 4 weeks to stage 3 of ASP (there was his ability to walk 10 meters or more with support or support). During a follow-up neurological examination, 9 months after the disease, persistent residual distal paresis was recorded up to 4 points in the hands, up to 3 points in the feet, which corresponded to stage 2 according to ASP. This clinical example shows that when the amplitude of the DM response is 2.5 mV, obtained as a result of the study of the ulnar nerve in the acute period, pronounced residual motor impairments persist in the long-term period of the disease.

Example 2

Patient K., 51 years old, suffered an axonal form of GBS 2 years ago at the age of 49 years. On admission on the seventh day from the onset of the disease, a stimulating ENMG was performed using the Nikolet Viking Selekt myograph (USA), during which a DM response was obtained, the amplitude of the negative phase of which was 0.7 mV, which also indicated a high probability of incomplete recovery in distant period of the disease. During the period of maximum GBS development, the severity of the patient's condition corresponded to 4 stages according to SAS. The patient was promptly started on a course of program plasmapheresis (total volume of removed plasma 10.3 L, which amounted to 150 ml / kg / course). However, despite ongoing pathogenetic therapy, there was a further increase in neurological symptoms. The recovery period to stage 3 according to ASP was approximately 3 months. During the follow-up neurological examination, 2 years after the disease, persistent residual distal paresis of up to 3 points in the hands and feet was recorded, which corresponded to stage 2 according to SAS. The presented clinical example also demonstrates the relationship between the magnitude of the dM response of the ulnar nerve in the range from 2.5 to 0 mV (in this case 0.7 mV) with an unfavorable prognosis of the outcome of GBS syndrome.

Example 3

Patient D., 17 years old, suffered acute inflammatory demyelinating polyneuropathy (OVDP) 1 year and 2 months ago at the age of 16 years. It was retrospectively established that upon admission on the eighth day from the onset of the disease, a stimulatory ENMG was performed using the Keypoint Clinical System myograph (Medtronic, USA), during which an ulnar nerve examination received a DM response with a negative phase amplitude of 3.1 mV , which indicated a high likelihood of developing stage 4 disease according to ASP. During the period of maximum development, the severity of the patient's condition corresponded to 4 stages according to SAS. The patient was promptly started a course of pathogenetic therapy (TIG 150 g per course), against the background of which there was a positive trend: a gradual regression of neurological deficit with recovery to stage 3 of the ASP after 3 weeks. During the follow-up neurological examination, after 1 year and 2 months after the disease, muscle paresis was not detected, which corresponded to stage 0 by SAS. The presented clinical example demonstrates that, despite the severity of the disease, this patient did not develop an adverse outcome in the long-term period of the disease, as indicated by a 3.1 mV DM response.

Thus, in all the presented clinical examples, the high significance of the EMG prognosis criterion — the amplitude of the dM response n.ulnaris — was demonstrated. In these patients with an initially equal severity of the disease during the period of maximum development of symptoms, it was possible to predict in advance, at the stage of diagnosis, in the first week from the onset of the disease the probability of an unfavorable outcome of GBS.

Table 1 Comparative characteristics of the course and outcome of GBS in patients with different values of the amplitude of the dM response obtained by examining the ulnar nerve in the first 2 weeks of the disease. Patient F. Patient K. Patient D. Age at the time of the disease, years 32 49 16 GBS form axonal axonal OVDP The duration of ENMG in the acute period, a day from the onset of the disease 7 7 8 The amplitude of the DM response n.ulnaris in the first 2 weeks of the disease (mV) 2,5 0.7 3,1 The severity of the disease in the acute period, stage according to ASP four four four Mechanical ventilation - - - Pathogenetic therapy PF
(ml / kg / course) 120 150 TIG
(g / kg / course) - 2 2 The duration of the recovery period to 3 tbsp. by ASP> 1 month - + Follow-up examination period 9 months 2 years 1 year 2 months Severity of motor deficiency in follow-up, stage according to ASP 2 2 0

Research results

The results of this study were obtained on the basis of an analysis of extracts from case histories and protocols of an ENMG examination of the acute period of the disease in 50 patients who underwent GBS diagnosed in accordance with WHO criteria (1993) from 3 months to 15 years ago (Table 2). The values of the amplitudes of the negative phase of the DM responses n.n.medianus, ulnaris and peroneus from one limb were evaluated. This parameter was compared using ROC analysis, which was carried out using the MedCalc 12.2.1 software package (MedCalc Software, Belgium), to maintain a pronounced residual motor deficit of 3 points or less in the long-term GBS period. In the course of the ROC analysis, the areas under the ROC curves (AUROC), sensitivity values and specificity were estimated. Models were taken into account with good (with AUROC 0.7-0.8) and very good (with AUROC> 0.8) predictive ability with optimal levels of sensitivity and specificity. The results of the ROC analysis are presented in tables 3 and 4.

table 2 Clinical and demographic characteristics of 50 patients who underwent GBS and included in the study Characteristic people (%) Number of persons 50 (67) Number of women 25 (50) Number of men 25 (50) Age at time of inspection (M ± s) 44 ± 15 years (16 to 75 years) Duration of illness (Me [LQ; UQ]) 2.5 years [3 months; 3 years] The transferred form of GBS OVDP 37 (74) Axonal 12 (24) Martin fisher syndrome 12) Residual
deficiency in
follow-up
com inspection motor 24 (48) sensitive 16 (32) norm 10 (20)

Table 3 The results of the ROC analysis of the predictive ability of the values of the amplitudes of the DM responses with respect to maintaining a pronounced residual motor deficit of 3 points or less (stage 2 according to ASP) * Engine-
nerve Area Significant Sensitivity Specificity under p threshold (%) (%) crooked amplitude (AUROC) dm response (mV) n.medianus 0.760 0.0015 ≤1.3 75.00 77.78 n.ulnaris 0.885 <0.0001 ≤2.5 80.00 93.94 n.peroneus 0.749 0.005 ≤0 50.00 97.4

* The model with the highest predictive ability is highlighted in bold.

Table 4 Amplitudes of dM responses with predictive significance for the adverse outcome of GBS (mV) * Adverse SGB Outcome n.medianus n.ulnaris n.peroneus Persistent residual paresis ≤3 points in follow-up ≤1.3 ≤2.5 ≤0

* models with the highest predictive ability (AUROC≥0.8) are highlighted in bold;

the remaining values indicated are good predictive models (AUROC 0.7-0.8).

The analysis showed that the EMG criterion with the highest AUROC value (Table 3), i.e. with the highest level of predictive ability, is the value of the amplitude of the DM response n.ulnaris, equal to 2.5 mV or less. It is this indicator, in our opinion, that can be used as a prognostic criterion.

Thus, the proposed method for predicting the adverse outcome of Guillain-Barré syndrome is highly accurate, since it most objectively reflects the severity and prevalence of the pathological process in this disease. The methodology for studying the DM response is affordable and technically easy to do.

The method can be recommended for use in practical medicine.

Claims (1)

A method for predicting an adverse outcome of Guillain-Barré syndrome (GBS), including an electroneuromyographic examination of a patient, characterized in that an electroneuromyographic study of excitation in the patient’s ulnar nerve is performed in the first two weeks from the onset of the disease, and the magnitude of the dM response amplitude of the ulnar motor portions is measured one limb and with a value of 2.5 mV or less, an unfavorable outcome of Guillain-Barré syndrome is predicted in the form of maintaining a pronounced remainder full-time paresis in the long-term period of the disease.