ASSOCIATION OF BETA-ENDORPHIN LEVELS WITH PROGNOSTIC FACTORS AND OUTCOME IN CHILDREN WITH CEREBRAL MALARIA. 1 1 1 2 Saheed BA OSENI Oluwatosin E OLORUNMOTENI Oluwagbemiga O ADEODU Efere M OBUOTOR 1 Department of Paediatrics, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife. 2 Department of Biochemistry, Obafemi Awolowo University, Ile-Ife. BACKGROUND AND OBJECTIVES Cerebral malaria is a diffuse, rapidly progressive febrile encephalopathy in which Plasmodium falciparum parasitaemia is accompanied by altered consciousness in the absence of other causes. It is the most lethal and most devastating form of severe malaria with some identified poor prognostic factors. Beta (β)- endorphin is an endogenous opioid peptide neurotransmitter produced in the brain and it functions in analgesia, autonomic regulation, modulation of cardiovascular responses and cerebral blood flow. Trigger factors for its production include: stress, acidosis, hypoxia and inflammation. These factors occur in cerebral malaria. The association between β-endorphin and poor prognostic factors in CM has not been previously studied. This study sets out to and some identifiable poor prognostic factors of the disease in children with cerebral malaria. METHODS In this cross-sectional study of 40 children with CM aged between eight and 84 months, we obtained relevant medical history and carried out physical examination on the subjects in order to find the association between β- endorphin levels and these poor prognostic factors. CSF and plasma β- endorphin levels were determined using ELISA kit at the Department of Biochemistry, Obafemi Awolowo University (OAU) Ile-Ife. Other relevant investigations were also done. Data was analysed using the Statistical Programme for Social Sciences (SPSS) software for Windows version 16.0. RESULTS The mean (± SD) CSF β-endorphin level: 1.8 ± 0.9 pmol/ L. while the mean (± SD) plasma β-endorphin level is 3.1 ± 2.0 pmol/ L while other poor prognostic factors show no significant relationship to BE levels. The mean plasma β-endorphin level obtained from subjects with low serum bicarbonate was significantly higher than those with normal bicarbonate level (p = 0.029). No significant relationship between β-endorphin levels and depth or duration of coma in this study. CSF β-endorphin levels was observed to rise with increasing fever clearance time (FCT) but declined with increasing admission temperature. Higher β-endorphin levels was observed in patients who died compared to those who recovered fully or with neurological sequelae. This was however not statistically significant. Table I: Relationship between CSF and plasma ß endorphin levels and poor prognostic factors in CM (Neurologic Signs) Neurologic findings Frequency Meanplasma p value Mean CSF p value (n =40) ß-endorphin ß-endorphin Blantyre coma score 0 3 4.6 ± 2.5 0.241 2.3 ± 1.4 0.450 1 11 2.4 ± 1.8 1.6 ± 0.9 2 26 3.2 ± 2.0 1.8 ± 0.9 Retinal changes Present 14 3.3 ± 2.5 0.536 1.8 ± 0.9 0.417 Absent 26 2.9 ± 1.8 1.7 ± 0.9 Pupillary size Pin-point 2 2.7 ± 0.8 0.883 1.1 ± 0.1 0.495 Normal 34 3.2 ± 2.2 1.8 ± 0.9 Dilated 3 1.9 ± 0.6 1.8 ± 1.4 Pupillary reaction Brisk 29 2.4 ± 0.8 1.8 ± 0.9 Sluggish 11 3.4 ± 2.3 0.090 1.4 ± 0.9 0.420 Abnormal Posturing Present 6 3.5 ± 1.0 0.525 2.0 ± 1.2 0.090 Absent 34 3.0 ± 2.1 1.7 ± 0.9 Corneal reflex Present 18 3.0 ± 2.5 0.771 1.8 ± 0.9 0.936 Absent 22 3.2 ± 1.6 1.8 ± 1.0 *One-wayANOVA **Independent t-test Table II: Relationship between CSF and plasma levels and β-endorphin laboratory poor prognostic factors in CM (laboratory findings). Prognostic Factors Frequency Mean Plasma p-value Mean CSF (Laboratory Findings) N(%) ß-endorphin Random blood Sugar* Hypoglycaemia 2 (5.0) 2.5 ± 1.1 1.8 ± 0.9 Normoglycaemia 34 (85.0) 3.2 ± 2.1 1.8 ± 0.9 Hyperglycaemia 4 (10.0) 2.1 ± 1.1 0.552 2.1 ± 1.3 0.735 Serum bicarbonate** 15 - 20 17 (42.5) 3.9 ± 2.4 0.029 2.9 ± 0.1 0.201 20 - 30 23 (57.5) 2.5 ± 1.5 1.6 ± 0.9 Packed cell volume* < 15 3 (7.5) 2.4 ± 0.6 0.912 1.7 ± 0.8 0.669 15-20 10 (25.0) 3.2 ± 2.1 1.9 ± 0.9 21-30 16 (40.0) 3.3 ± 2.4 1.6 ± 0.8 >30 11 (27 . 5) 2 . 9 ± 1 . 8 2 . 1 ± 1 . 1 Serum <5.8 mmo / L 20 (50.0) 2.9 ± 1.8 0.578 1 .8 ± 0.9 0.996 >5. 8mmol/ L 20 (50.0) 3.3 ± 2.3 1.8 ± 0.9 *One-wayANOVA **Independent t-test ß-endorphin p-value Figure 1: Relationship between -endorphin levels at admission and β coma recovery time. β-endorphin pmol/L β-endorphin pmol/L r = 0.044 p = 0.802 r = 0.076 p = 0.664 Coma recovery time Plasma β-endorphin CSF β-endorphin DISCUSSION Acidosis, probably resulting from anaerobic glycolysis with resultant increased serum lactate usually in cerebral malaria are known triggers of β- endorphin release. This may explain why higher β-endorphin levels were seen in subjects with low serum bicarbonate. Fig 1 implies that the lower the β- endorphin levels at admission, the longer the coma recovery time suggesting a poor response of the body to the stress of the encephalopathy. CSF β- endorphin levels was observed to rise with increasing FCT but declined with increasing admission temperature. This suggests that duration and not extent of fever affects β-endorphin levels. The weak association found between β- endorphin levels and some poor prognostic factors may become a strong association if the study is replicated using a larger sample size. CONCLUSION This study shows a weak association between β-endorphin levels and poor prognostic factors in CM except for low serum bicarbonate which has significant association. A larger study using a much higher sample size probably multicentre may be required to further establish the significance of the association between β-endorphin levels and poor prognostic factors in cerebral malaria. REFERENCES 1. Ogala WN. Infectious diseases: Malaria. In: Azubuike JC, Nkanginieme KEO, editors. Paediatrics and child health in a tropical region. 2nd ed. Owerri: African Educational Services; 2007. 596-604. 2. World Health Organisation. World Malaria Report 2013. WHO; 2013. 3. Oguche S, Omokhodion SI, Adeyemo A, Olumese PE. Low plasma bicarbonate predicts poor outcome of cerebral malaria in Nigerian children. WAJM 2002; 21:276-9. 4. Von Seidlein L, Olaosebikan R, Hendriksen I CE , Lee SJ, Adedoyin OT, Agbenyega T et al. Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial. Clinical Infectious Diseases 2012:1-11. 5. Oluwayemi OI, Brown BJ, Oyedeji OA, Adegoke SA, Adebami OJ, Oyedeji GA. Clinical and laboratory predictors of outcome in cerebral malaria in suburban Nigeria. J Infect Dev Ctries 2013; 7(8):600-7. 6. Nagamitsu S. CSF beta-endorphin levels in pediatric neurologic disorders. Kurume Med J 1993; 40:233-41. 7. Veening JG, Gerrits PO, Barendregt HP. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review. Fluids and Barriers of the CNS 2012; 9:16 Dr. Oluwatosin Eunice Olorunmoteni Department of Paediatrics, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria. E mail: [email protected] or [email protected] Phone number: +234803 941 3535 SP37
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ASSOCIATION OF BETA-ENDORPHIN LEVELS WITH PROGNOSTIC FACTORS AND OUTCOME IN CHILDREN WITH CEREBRAL MALARIA.
1 1 1 2Saheed BA OSENI Oluwatosin E OLORUNMOTENI Oluwagbemiga O ADEODU Efere M OBUOTOR1Department of Paediatrics, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife.
2Department of Biochemistry, Obafemi Awolowo University, Ile-Ife.
BACKGROUND AND OBJECTIVES
Cerebral malaria is a diffuse, rapidly progressive febrile encephalopathy in which Plasmodium falciparum parasitaemia is accompanied by altered consciousness in the absence of other causes. It is the most lethal and most devastating form of severe malaria with some identified poor prognostic factors. Beta (β)-endorphin is an endogenous opioid peptide neurotransmitter produced in the brain and it functions in analgesia, autonomic regulation, modulation of cardiovascular responses and cerebral blood flow. Trigger factors for its production include: stress, acidosis, hypoxia and inflammation. These factors occur in cerebral malaria. The association between β-endorphin and poor prognostic factors in CM has not been previously studied. This study sets out to and some identifiable poor prognostic factors of the disease in children with cerebral malaria.
METHODSIn this cross-sectional study of 40 children with CM aged between eight and 84 months, we obtained relevant medical history and carried out physical
examination on the subjects in order to find the association between β-endorphin levels and these poor prognostic factors. CSF and plasma β-endorphin levels were determined using ELISA kit at the Department of Biochemistry, Obafemi Awolowo University (OAU) Ile-Ife. Other relevant investigations were also done. Data was analysed using the Statistical Programme for Social Sciences (SPSS) software for Windows version 16.0.
RESULTSThe mean (± SD) CSF β-endorphin level: 1.8 ± 0.9 pmol/ L. while the mean (± SD) plasma β-endorphin level is 3.1 ± 2.0 pmol/ L while other poor prognostic factors show no significant relationship to BE levels. The mean
plasma β-endorphin level obtained from subjects with low serum bicarbonate was significantly higher than those with normal bicarbonate level
(p = 0.029). No significant relationship between β-endorphin levels and depth or duration of coma in this study. CSF β-endorphin levels was observed to rise with increasing fever clearance time (FCT) but declined with
increasing admission temperature. Higher β-endorphin levels was observed in patients who died compared to those who recovered fully or with neurological sequelae. This was however not statistically significant.
Table I: Relationship between CSF and plasma ß endorphin levels and poor prognostic factors in CM (Neurologic Signs)
Neurologic findings Frequency Meanplasma p value Mean CSF pvalue
(n
=
40)
ß-endorphin
ß-endorphin
Blantyre coma score
0
3
4.6
±
2.5
0.241
2.3
±
1.4
0.450
1
11
2.4
±
1.8
1.6
±
0.9
2
26
3.2
±
2.0
1.8
±
0.9
Retinal changes
Present
14
3.3
±
2.5
0.536
1.8
±
0.9
0.417
Absent
26
2.9
±
1.8
1.7
±
0.9
Pupillary size
Pin-point
2
2.7
±
0.8
0.883
1.1
±
0.1
0.495
Normal
34
3.2
±
2.2
1.8
±
0.9
Dilated
3
1.9
±
0.6
1.8
±
1.4
Pupillary reaction
Brisk
29
2.4
±
0.8
1.8
±
0.9
Sluggish
11
3.4
±
2.3
0.090
1.4
±
0.9
0.420
Abnormal Posturing
Present
6
3.5
±
1.0
0.525
2.0
±
1.2
0.090
Absent
34
3.0
±
2.1
1.7
±
0.9
Corneal reflex
Present
18
3.0
±
2.5
0.771
1.8
±
0.9
0.936
Absent
22
3.2
±
1.6
1.8
±
1.0
*One-way
ANOVA
**Independent t-test
Table II: Relationship between CSF and plasma levels and β-endorphin laboratory poor prognostic factors in CM (laboratory findings).
Prognostic Factors Frequency Mean Plasmap-value
Mean CSF (Laboratory Findings)
N(%)
ß-endorphin
Random blood
Sugar*
Hypoglycaemia
2
(5.0)
2.5
±
1.1
1.8
±
0.9
Normoglycaemia
34
(85.0)
3.2
±
2.1
1.8
±
0.9
Hyperglycaemia
4
(10.0)
2.1
±
1.1
0.552
2.1
±
1.3
0.735
Serum bicarbonate**
15
-
20
17
(42.5)
3.9
±
2.4
0.029
2.9
±
0.1
0.201
20
-
30
23
(57.5)
2.5
±
1.5
1.6
±
0.9
Packed cell volume*
<
15
3
(7.5)
2.4
±
0.6
0.912
1.7
±
0.8
0.669
15-20
10
(25.0)
3.2
±
2.1
1.9
±
0.9
21-30
16
(40.0)
3.3
±
2.4
1.6
±
0.8
>
30
11
(27.5)
2.9
±
1.8
2.1
±
1.1
Serum
<
5.8
mmo/
L
20
(50.0)
2.9
±
1.8
0.578
1.8
±
0.9
0.996
>
5.
8mmol/
L
20
(50.0)
3.3
±
2.3
1.8
±
0.9
*One-way
ANOVA
**Independent
t-test
ß-endorphinp-value
Figure 1: Relationship between -endorphin levels at admission and βcoma recovery time.
β-endorphin pmol/L
β-e
nd
orp
hin
pm
ol/
L
r = 0.044p = 0.802
r = 0.076p = 0.664Coma recovery time
Plasma β-endorphinCSF β-endorphin
DISCUSSIONAcidosis, probably resulting from anaerobic glycolysis with resultant
increased serum lactate usually in cerebral malaria are known triggers of β-endorphin release. This may explain why higher β-endorphin levels were seen in subjects with low serum bicarbonate. Fig 1 implies that the lower the β-endorphin levels at admission, the longer the coma recovery time suggesting
a poor response of the body to the stress of the encephalopathy. CSF β-endorphin levels was observed to rise with increasing FCT but declined with increasing admission temperature. This suggests that duration and not extent
of fever affects β-endorphin levels. The weak association found between β-endorphin levels and some poor prognostic factors may become a strong association if the study is replicated using a larger sample size.
CONCLUSIONThis study shows a weak association between β-endorphin levels and poor prognostic factors in CM except for low serum bicarbonate which has significant association. A larger study using a much higher sample size probably multicentre may be required to further establish the significance of
the association between β-endorphin levels and poor prognostic factors in cerebral malaria.
REFERENCES1. Ogala WN. Infectious diseases: Malaria. In: Azubuike JC, Nkanginieme KEO, editors. Paediatrics and child health in a tropical region. 2nd ed. Owerri: African Educational Services; 2007. 596-604.2. World Health Organisation. World Malaria Report 2013. WHO; 2013.3. Oguche S, Omokhodion SI, Adeyemo A, Olumese PE. Low plasma bicarbonate predicts poor outcome of cerebral malaria in Nigerian children. WAJM 2002; 21:276-9.4. Von Seidlein L, Olaosebikan R, Hendriksen I CE , Lee SJ, Adedoyin OT, Agbenyega T et al. Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial. Clinical Infectious Diseases 2012:1-11.5. Oluwayemi OI, Brown BJ, Oyedeji OA, Adegoke SA, Adebami OJ, Oyedeji GA. Clinical and laboratory predictors of outcome in cerebral malaria in suburban Nigeria. J Infect Dev Ctries 2013; 7(8):600-7.6. Nagamitsu S. CSF beta-endorphin levels in pediatric neurologic disorders. Kurume Med J 1993; 40:233-41.7. Veening JG, Gerrits PO, Barendregt HP. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review. Fluids and Barriers of the CNS 2012; 9:16
Dr. Oluwatosin Eunice OlorunmoteniDepartment of Paediatrics, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria. E mail: [email protected] or [email protected] Phone number: +234803 941 3535
SP37
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