Научная статья на тему 'Dynamics of neuron-specific enolase patients with non-motor manifestations of Parkinson's disease'

Dynamics of neuron-specific enolase patients with non-motor manifestations of Parkinson's disease Текст научной статьи по специальности «Клиническая медицина»

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Ключевые слова
Parkinson's disease / neuron specific enolase. / болезнь Паркинсона / нейрон - специфическая энолаза.

Аннотация научной статьи по клинической медицине, автор научной работы — N. M. Buchakchiyskaya, I. V. Maramukha, A. V. Kutsak, V. I. Maramukha, L. V. Bahareva

The aim was to study the dynamics of the concentration values neuron-specific enolase (NSE) and their relationship to non-motor manifestations of Parkinson’s disease (PD). After analyzing the data, we found that the level of NSE more than 30 mkg/ml have an adverse marker of the disease.

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ДИНАМИКА ПОКАЗАТЕЛЕЙ НЕЙРОН-СПЕЦИФИЧЕСКОЙ ЭНОЛАЗЫ У БОЛЬНЫХ С НЕМОТОРНЫМИ ПРОЯВЛЕНИЯМИ ПРИ БОЛЕЗНИ ПАРКИНСОНА

Целью исследования было изучение динамики концентрационных значений нейрон-специфической энолазы (НСЭ) и их связи с немоторными проявлениями при болезни Паркинсона (БП). Проанализировав полученные данные, мы выяснили, что уровень НСЭ более 30 мкг/мл есть маркером неблагоприятного течения заболевания.

Текст научной работы на тему «Dynamics of neuron-specific enolase patients with non-motor manifestations of Parkinson's disease»

11 Lesser H., Sharma U., LaMoreaux L., Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial // Neurology, 2004. - 63 (11). - P. 2104-2110.

12 Lopez-Trigo J., Sancho Rieger J. Pregabalin. A new treatment for neuropathic pain // Neurologia, 2006. -21 (2). - P. 96-103.

13 Luo Z., Chaplan S., Higuera E. et al. Upregulation of dorsal root ganglion (alpha) 2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats // J Neurosci, 2001. -21. - P.1868-1875.

14 LYRICA Study Group Pregabalin for peripheral neuropathic pain: results of a multicenter, non-comparative, open-label study in Indian patients // Int J ClinPract, 2006. - 60 (9). - P. 1060-1067.

15 Management of chronic pain in adults. Best practice statement-2006 // NHS Quality Improvement. - Scotland: 2006.

16 Matthews EA, Dickenson AH. Effects of spinally delivered N- and P-type voltagedependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy // Pain, 2001. - 92. - P. 235-246.

17 Richter R., Portenoy R., Sharma U. et al. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial // J Pain, 2005. - 6 (4). - P.253-260.

18 Rosenstock J., Tuchman M., LaMoreaux L., Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial // Pain, 2004. - 110 (3). - P. 628-638.

19 Sabatowski R., Galvez R., Cherry DA. 1008-045 Study Group. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial // Pain, 2004. -109 (1-2). - P.26-35.

Р.А.БЕЛЯЕВ, Н.А.ЕВСТАФЬЕВА, В.К.АЙМАГАМБЕТОВА, Ю.А.КРИВЕГА, Э.М.САНАЕВ

НЕВРОПАТИЯЛЫ^ АУРУ СИНДРОМДАРЫ - ЕМДЕУ ТАКТИКАСЫ

Туйш: Ма;алада ауру синдромдардарымен нау;астарда прегабалин дэрiaн крлданудыц кептеген зерттеу нэтижелерi бертген, сонымен ;атар Keki6ip зерттеулер мультиорталы;ты; плацебо-ба;ылау дизайнында болган жэне ;ос со;ыр эдiaмен орындалган.

Туш^ сездер: невропатиялы; ауру синдромдары, прегабалин.

R.A.BELYAEV, N.A.EVSTAFEVA, V.K.AIMAGAMBETOVA, Y.A.KRIVEGA, E.M.SANAEV

NEUROPATHIC PAIN SYNDROMES - TREATMENT STRATEGY

Resume: The article presents the results of numerous studies of the drug pregabalin in patients with pain syndromes, and a series of studies was multicenter, placebo-controlled design and was performed double blind. Keywords: neuropathic pain syndromes, pregabalin.

yflK 616.858-074:577.15

N. M. BUCHAKCHIYSKAYA, I. V. MARAMUKHA A. V. KUTSAK, V. I. MARAMUKHA L. V. BAHAREVA A. V. LEVADNA

PP "Zaporozhye Medical Academy of Postgraduate Education, Ministry of Health of Ukraine." Zaporozhye, Ukraine

DYNAMICS OF NEURON-SPECIFIC ENOLASE PATIENTS WITH NON-MOTOR MANIFESTATIONS OF PARKINSON'S DISEASE

The aim was to study the dynamics of the concentration values neuron-specific enolase (NSE) and their relationship to non-motor manifestations of Parkinson's disease (PD). After analyzing the data, we found that the level of NSE more than 30 mkg/ml have an adverse marker of the disease. Keywords: Parkinson's disease, neuron - specific enolase.

Introduction: As is known, the diagnosis of Parkinson's disease (PD) is based on the detection and identification of specific motor manifestations, which are a direct consequence of lack of dopaminergic transmission in the nigrostriatal system. However, there are non-motorized appearances PD, which also are characteristic of nosology [1,2,4]. In the later stages of PD, non-motor manifestations begin to dominate as the factors affecting the quality of life of the patient, at certain moments become more important and disabling [3,5,6]. It should be noted that data on the pathogenetic importance neuron-specific proteins as markers of non-motor disorders in the

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scientific literature is quite small. General marker of differentiated neurons is a neuron -specific enolase (NSE). Therefore, a comprehensive analysis of the clinical manifestations of PD, biochemical parameters, severity of non-motor fluctuations in PD patients, depending on the concentration values of the NSE . Objective: To study the dynamics of NSE concentration values and their relation to non-motor manifestations in PD and evaluate their clinical, diagnostic and prognostic value in patients with PD. Materials and Methods. Us on the basis of neurological clinic Zaporozhye Medical Academy of Postgraduate Education examined

64 PD patients, whose average age was 65,84 ± 1,59 years, with an average disease duration 7,2 ± 0,6 years . When the diagnosis is considered the criteria of the Bank of the brain of Parkinson's Disease Society of Great Britain. On a scale of Hoehn and Yahr disease severity was assessed. With one stage PD scale Hoehn and Yahr we watched 8 people, with 2 stage - 22, with stage 3 - 25, with stage 4 - 9. 6 patients were diagnosed with trembling PD form, akinetic-rigid form - in 8, mixed form - 50.

To assess non-motor manifestations of the use of the following methods: 1) Section I (non-motor manifestations of the disease in daily life) Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS, 2008); 2) short scale assessment of mental status - Mini Mental State Examination (MMSE); 3) to study the regulatory functions - battery of frontal dysfunction (BFD); 4) Quality of Life - Parkinson's Disease Quality of Life Questionnaire- 39 (PDQ- 39); 5) to identify and assess the severity of depression and anxiety - Hospital Anxiety and Depression Scale (HADS); 6) numeric rating scale of pain intensity - Numerical Rating Scale (NRS); 7) to evaluate the quality of sleep - Parkinson's Disease Sleep Scale (PDSS); 8) the presence of chronic constipation is determined in accordance with the "Rome Criteria III»; 9) the presence of orthostatic hypotension were detected using the orthostatic test .

Quantitative indicators of NSE in serum were determined using a set of «CanAg NSE EIA» (USA). In the control group, normal values for NSE were examined 25 healthy individuals.

Normality of the distribution of the studied quantitative criteria evaluated by Kolmogorov-Smirnov (D) and Lilliefors, Shapiro-Wilk (W). In the case of distribution, which differs from the normal, or analysis of ordinal variables using Mann-Whitney U for 2 unrelated samples for a larger number of samples - test Kruskal-Wallis H with further comparison to Games-Howell. Comparison groups on the basis of quality criteria were performed using x 2 with the analysis of contingency tables. The study results are processed using the statistical software package «SPSS 16», «Microsoft Excel 2003», «STATISTICA ® for Windows 7.0» (StatSoft Inc.). For all types of analysis were considered statistically significant differences at a significance level of less than 0,05. To assess the impact of specific value factor underlying the grouping of a combination of other factors affecting the score sign carried calculation coefficient of determination

(r|2). The resulting value is multiplied by 100%, thus defining, in what percentage of cases investigated trait variation is determined by the factors studied. To assess the functional interdependence between the studied parameters was also calculated empirical correlation ratio (rp).

Results of the study.

Cognitive impairment occurred in 83 % of cases, depressive disorders -in 79,3%, and constipation - in 78,9% , and sleep disorders - 72,1% , pain - 31,9 %, orthostatic hypotension - 21,5%. The reference values for NSE norms defined as 99 percentile values of healthy individuals without extrapyramidal disease (so spread data does not obey the normal distribution according to the Kolmogorov-Smirnov test (D) and Lilliefors, and Shapiro-Wilk (W)), which was rounded to 14 mkg/ml. Analysis of the distribution pattern of NSE levels in PD patients showed that, overall, the data were not significantly different from the parametric distribution. Assessing the clinical diagnostic and prognostic significance of intracellular enzyme - NSE was isolated group of patients - the top quartile (21 people, 42,85 % of males and 57,15 % females) with the highest values of serum NSE , more than 30 mkg/ml (corresponding to 75 percentile) .

Patients in this subgroup recorded depressive disorders and anxiety disorders according HADS (over 11 score), which requires the appointment of therapy (^2=6,21, p=0,013), significantly expressed under NRS pain more than 5 points ("/2=20,31, p<0,001), as well as violations of quality of life - more than 100 points on the PDQ- 39 (x2=8,53, p=0,003) were more common, according to the results of a battery of tests of frontal dysfunction (less than 15 points) and MMSE (less 28 score) , mild cognitive impairment and dementia severity (X2=13,13, p<0,001 m %2=9,37, p=0,002, respectively) and the frequency of constipation, as a manifestation of autonomic dysfunction (x2=18,63, p<0,001).

To establish the direction and degree of impact on the level of NSE response dependent variables, we conducted analysis for univariate scheme, where as a grouping (factor) trait considered NSE index value (broken down by quartiles), adequately characterizes the severity of cerebral destruction in various diseases, and as efficient features exposed an independent factor used indicators characterizing nonmotor fluctuations in PD. The data obtained are presented in the table.

Table 1 - Indicators univariate analysis to assess the impact on the studied parameters NSE.

Figures F п П2 Р

Hospital Anxiety and Depression Scale (HADS), score 10,170 0,513 0,263 0,0002

Intensity of pain according to the digital grading scale (NRS), score 5,029 0,387 0,15 0,0097

Quality of life for PDQ-39, score 11,926 0,543 0,295 р<0,001

Cognitive impairment according to the battery of frontal dysfunction, score 19,969 0,642 0,412 р<0,001

Severity of dementia by MMSE, score 17,917 0,621 0,386 рс0,001

«F» - F-value ratio; «r|2» - specific value impact factor underlying the grouping of a set of factors that affect the score sign; «r|» - empirical correlation ratio.

Hus, had the highest impact on the level of NSE indicators characterizing cognitive impairment according to BFD and severity of dementia by MMSE. This factor statistically determined 48,5 % of the variation of frontal dysfunction (F=19,97, p<0,001) and the risk of

dementia (F=17,92, p<0,01), and it is necessary to note the presence of reliable functional interdependence between NSE performance and cognitive abilities , as evidenced by significantly empirical correlation ratio (0,64 and 0,62) . Less influence had chosen as a

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grouping feature NSE index on quality of life and severity of depression. Thus, calculated for the considered parameters are empirical coefficients of determination made r|2=0,26 and r]2=0,3, which suggests that about a third of the total dispersion characteristics of the quality of life and severity of dissonance is due to the influence of mood disorders with increasing concentrations of NSE. Thus, evaluating the results of the univariate analysis of variance for the scheme, it can be concluded that the examined groups of patients was statistically significant impact on the dynamics of the level of severity of non-motorized NSE disorders.

We carried out a binary regression analysis, which showed the level of interdependence among NSE PD patients considered an independent risk factor, the amount of total ballroom indicator according NADS, reflecting the severity and clinical significance of anxiety/depression, which in our model is the dependent variable. This dependence is directly proportional to the nature and reliably approximated by a logarithmic regression model of the form: score

HADS = -72,067 +65,55*log10 (NSE), which allows note: all patients with PD at NSE values of more than 30 mkg/ml with 95% probability sum more than 15 score.

Approximation error and the magnitude of the residual variance demonstrate high accuracy linear model. Problem was solved by regression analysis: R=0,88, R2=0,78, normalized R2=0,776 at F = 153,48, standard error of 2,76, p<0,001. Identified logarithmic correlation indicates that more than 85 % of the total dispersion characteristic changes of mood disorders in PD is associated with progression of brain damage associated with elevation of enzyme NSE. The greatest increase observed in our relationship in the range of 20 to 30 score. From which it follows that there is a severity indicator association of anxiety and depression and severity of changes in the activity of the enzyme NSE to therapy. NSE level of more than 30 mkg/ml is a marker of adverse outcome of the disease, as well as the risk of developing emotional and psychotic disorders in PD

I I 40

I I Э5

I I Э0

I I 25

I I 20

I I 15

Figure 1 - Changes in the activity of quality of life and severity of pain in PD patients with different concentrations of serum NSE

Information displayed in Fig. 1 allows us to observe the relationship between the intensity of pain in patients with PD and increase the quality of life change. Patients with severe pain more than 8 score, more than 90% of cases recorded a statistically significant increase in activity as NSE (more than 30 mkg/ml), and a sharp deterioration in life satisfaction (score of PDQ- 39 over 110).

Conclusions:

1. Patients with PD, except of motor disorders, as there are non-motor symptoms: cognitive impairment (83%), depressive disorders (79,3%), vegetative disorders (constipation - 78,9%, orthostatic hypotension -21,5%), sleep disorders (72,1%) , pain ( 31,9%).

2. Elevated levels of NSE (more than 30 mkg/ml) is associated with an increased incidence of cognitive impairment, sensory, autonomic dysfunction, progression of anxiety-depressive disorders.

3. NSE more than 30 mkg/ml - an indicator of high risk of developing dementia and affective disorders

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REFERENCES

1 Chaudhuri K. R., Healy D. G., Schapira A. H. V. Non-motor symptoms of Parkinsons disease: diagnosis and management // Lancet Neurol, 2006. - № 5. - P. 235 - 245.

2 Dubois B., Slachevsky A., Litvan I., Pillon B. The FAB. A frontal assessment battery at bedside // Neurology, 2000. - №55. - P. 1621-1626.

3 Litvan I., Goldman J.G., Troster A.I., et al. Diagnostic criteria for mild cognitive impairment in Parkinson s disease: movement disorder sociaty task force guidelines// Mov. Disord, 2012. - №27. - P.349-356.

4 Martinez-Martine P., Schapira A. H. V., Stocchi F. et al. Prevalence of non-motor symptoms in Parkinsons disease in an international setting: study using non-motor symptoms questionnaire in 545 patients // Mov. Dis., 2007. - № 22. - P. 1623 -1629.

5 5. Pagonabarraga J., Kulisevsky J. Cognitive impairment and dementia in Parkinson s disease//Neurobiol.Dis.,2012. - №46. -Р.590-596.

6 Olde Dubbelink K. T., Stoffers D., Deijen J.B. et al. Cognitive decline in Parkinson s disease is associated with slowing of resting-state brain activity: longitudinal study// Neurobiol. Aging., 2013. - № 34. - P. 408- 418.

Н.М. БУЧАКЧИЙСКАЯ, В.И. МАРАМУХА, Л.В. БАХАРЕВА, И.В. МАРАМУХА, А.В. КУЦАК, А.В. ЛЕВАДНАЯ

ГЗ "Запорожская медицинская академия последипломного образования МЗ Украины"

ДИНАМИКА ПОКАЗАТЕЛЕЙ НЕЙРОН-СПЕЦИФИЧЕСКОЙ ЭНОЛАЗЫ У БОЛЬНЫХ С НЕМОТОРНЫМИ ПРОЯВЛЕНИЯМИ ПРИ

БОЛЕЗНИ ПАРКИНСОНА

Резюме: Целью исследования было изучение динамики концентрационных значений нейрон-специфической энолазы (НСЭ) и их связи с немоторными проявлениями при болезни Паркинсона (БП). Проанализировав полученные данные, мы выяснили, что уровень НСЭ более 30 мкг/мл есть маркером неблагоприятного течения заболевания. Ключевые слова: болезнь Паркинсона, нейрон - специфическая энолаза.

Н.М. БУЧАКЧИЙСКАЯ, В.И. МАРАМУХА, Л.В. БАХАРЕВА, И.В. МАРАМУХА, А.В. КУЦАК, А.В. ЛЕВАДНАЯ

КвРСЕШШТЕРДН, ДИНАМИКАСЫ НЕЙРОН-ЕРЕКШЕ ЭНОЛАЗЫ АУРУ ПАРКИНСОНА АУРУДА НЕМОТОРНЫМИ ЭСЕР

ЕТУЛЕРМЕН

Т\йЫ: Зерттеулер ма^сатпен нейрон-ерекше шогырлану мэндердщ динамикалар зертте^ ед энолазы (НСЭ) жэне Паркинсона (БП) ауруыцца немоторными эсер eтулeрiмeн олардыц байланыстары. Талдап алган осы, б^з аныктады^. не децгей кэаби аурулар щлайсыз агымдары танбалатышпен НСЭ кеп 30 мкг/мл бар. T\MÍHgi создер: Паркинсон ауруы, нейрон - энолаза ерекше.

УДК 616.831-009.11+616.853]-036.82/.85+343.148.22

В.В. ГОЛИКОВА

Государственное учреждение «Республиканский научно-практический центр медицинской

экспертизы и реабилитации» п. Городище, Республика Беларусь

РЕАБИЛИТАЦИОННО-ЭКСПЕРТНЫЕ ОСОБЕННОСТИ СИМПТОМАТИЧЕСКОЙ ЭПИЛЕПСИИ У ПАЦИЕНТОВ С ДЕТСКИМ

ЦЕРЕБРАЛЬНЫМ ПАРАЛИЧОМ

Оценка реабилитационных возможностей при симптоматической эпилепсии у детей-инвалидов с ДЦП характеризуется ранним началом, зависит от наличия провоцирующих факторов первых приступов, развития как общих, так и фокальных приступов, высокой степени полиморфизма и обусловлена клинической формой ДЦП. Критерии медико-социальной оценки ограничений жизнедеятельности у больных с ДЦП и симптоматической эпилепсией, количественной оценки частоты рецидивов припадков эпилепсии у детей, оценка степени ограничения жизнедеятельности созданы и научно доказаны.

Ключевые слова: детский церебральный паралич (ДЦП), эпилепсия, дети, медико-социальная экспертиза.

Введение. Детский церебральный паралич (ДЦП) - одно доминирует в структуре детской инвалидности,

из самых социально значимых заболеваний детского обусловленной патологией нервной системы. Это

возраста, так как в качестве причинного фактора связано, как с достаточно высокой частотой его

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