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International Journal of Trend in Scientific Research and Development (IJTSRD)
Volume: 3 | Issue: 2 | Jan-Feb 2019 Available Online: www.ijtsrd.com e-ISSN: 2456 - 6470
@ IJTSRD | Unique Reference Paper ID – IJTSRD21593 | Volume – 3 | Issue – 2 | Jan-Feb 2019 Page: 1074
Sympathetic Skin Response in
Children with Iron Deficiency Anemia
Abdurrahman Sönmezler, Mahmut Abuhandan, Tahir Kurtulus Yoldas,
Yeşim Oymak, Mustafa Çalık, Bülent Güzel, Hakim Çelik
Assistant Professor, Department of Neurology,
Adana City Research and Training Hospital, Adana, Turkey
ABSTRACT BACKGROUND: Iron deficiency anemia (IDA) is particularly highin children indevelopingcountries .Sympathetic
skin response (SSR) is a polysynaptic reflex, and its final efferent pathway involves pre- and post-ganglionic sympathetic
sudomotor fibers that ultimately activate the sweat glands through sympathetic outflow . The aim of this study was to
investigate whether IDA is involved in SSR.
METHODS: 24 patients (17 girls, 7 boys) with IDA and 20 healthy children (11 girls, 9 boys) were enrolled in the study.
RESULTS: Significant differences were observed between the palmar SSR results (latency, ms) of the patient and the control
groups (1.09±0.24, 0.92±0.30, p= 0.048). There was no correlation between ferritin levels and SSRresultsofthepatientgroup(
p=0.65 ).
CONCLUSIONS: The evidence from this preliminary study suggests that efferent C fibers of the sympathetic nervous system
may not intact in IDA. The sudomotor autonomic function test may be useful to detect autonomic involvement earlier.
Keywords: Iron deficiency anemia, sympathetic skin response, children
INTRODUCTION
Iron deficiency anemia (IDA) is particularly high in children
in developing countries 1.Iron plays an important role in
various neurometabolic processes, which can be altered by
iron deficiency. Hypoxia may lead to neuronal dysfunctions
in IDA2, 3, 4, 5, 6, 7, 8, 9. Sympathetic skin response (SSR) is a
polysynaptic reflex, and its final efferent pathway involves
pre- and post-ganglionic sympathetic sudomotor fibers that
ultimately activate the sweat glands through sympathetic
outflow 10.SSR is coordinated in the posterior hypothalamus
or upper brainstem reticular formation 11. The aim of this
study was to investigate whether sympathetic skin
responses are affected by the presence of iron deficiency
anemia.
Materials and methods
This study was performed prospective at Harran University
Hospital it was approved by the local ethics committee.
There was informed consent obtained fromtheparents of all
study participants.24 children (17 girls, 7 boys, mean age
:13.7±1.79) with IDA and 20 healthy children(11 girls, 9
boys,mean age 12.4±1.93) were enrolled in the study.
Patients with IDA with a hemoglobin value of less than 5
gr/dl were excluded from this study. All children were
thoroughly examined clinically to rule out other causes of
neuropathy. Electrophysiological testing was carried out
according to the Technical Standards of the International
Federation of Clinical Neurophysiology12. Childrens were
investigated in a dark and silent room in a supine position
with their eyes closed. Body,and skin temperature was
controlled, temperature were same. EMG was performed
using a filter setting of 0.1–32 Hz, a sensitivity setting of 1
mV divˉ¹, and a sweep rate of 5 s. The SSR was recordedwith
surface electrodes (palmar ) on the skin ( Electromyography
machine Dantec, Keypoint, Denmark).The study data were
analyzed using SPSS (Statistical Package for Social Sciences)
for Windows version 11.5. Differences between groupswere
evaluated with the Mann-Whitney U-test. A valueof p 0.05
was accepted as statistically significant. Relations between
variables were studied by the Pearson correlation test.
Results
All physical examination results of the children involved in
this study were normal. The children did not report any
symptoms of autonomic dysfunction. Significant differences
were observed between the palmarSSRresults (latency, ms)
of the the children with IDA and the control groups
(1.09±0.24, 0.92±0.30, p= 0.048). There was no correlation
between ferritin levels and SSR results of the the children
with IDA group ( p=0.65 ).
Discussion
The palmar SSR results of the the children with IDA were
different from those of the control group. There was no
correlation between ferritin levels and SSR results of the
children with IDA. Iron plays an important role in various
metabolic and enzymatic processes. Iron deficiency may
have an effect on neurological and intellectual functions.
Many of the iron containing enzymes of the central and
peripheral nervous systems could be affected adversely by
IDA 7,14. SSR is coordinated in the posterior hypothalamus or
upper brainstem reticular formation 11.SSRis anindicatorof
sudomotor function mediated by amyelinic efferent Cfibers
of the sympathetic nervous system 13.
International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
@ IJTSRD | Unique Reference Paper ID – IJTSRD21593 | Volume – 3 | Issue – 2 | Jan-Feb 2019 Page: 1075
IDA alters the behavior of infants in thecognitive,motor, and
socio emotional domains and interferes with optimal
development. Iron plays key roles in the normalprogression
of several neurofunctional systems. The mechanisms by
which chronic iron deficiency in infancy could contribute to
adverse adult outcomes are undoubtedly complex.
From animal models, it is clear that early-life iron deficiency
adversely impacts the developing brain. IDA is associated
with altered short and long-term neurofunctional
development, including impaired myelination and
dendritogenesis; altered neurotransmitter functioning;
changes in neurometabolism in the hippocampus, striatum,
and cortex; and altered gene and protein profiles 15, 16, 17, 18.
In our study, there was no correlation between ferritin levels
and SSR results of the children with IDA. Interestingly, we
identified prolonged latency of SSR in the extremities.SSR is
a polysynaptic reflex. The data may suggest that there are
affected areas in the amyelinic efferent C-fibers or other
parts of the reflex arc, but it is not clear. Becauseof theSSRis
coordinated in the posterior hypothalamus or upper
brainstem reticular formation.To ourknowledge,thereis no
previous description of whether there is a correlation
between ferritin levels and SSR latency in children and of
differences between SSR of the children with IDA and a
healthy group. This study is preliminary, and SSR in IDA
should be studiedinlargerrandomizedgroups.Theevidence
from this preliminary study suggests that efferent Cfibers of
the sympathetic nervous system may not intact in IDA. The
sudomotor autonomic function test may be useful to detect
autonomic involvement earlier.
Acknowledgement
The authors have no financial or personal relationships with
other people or organizations that could pose a conflict of
interest in connection with the present work.
This article was presented as a poster at 7th World Congress
on Controversies in Neurology (CONy)
References
[1] DeMaeyer E, Adiels-Tegman M.The prevalence of
anemia in the world,World Health Stat Q1985; 38:302-
16.
[2] Karabiber H, Ozgen U, Ozen C, Soylu H, Kutlu O, Sarıbaş
S, Kaya M, Demir Eksikliği Anemili Cocuklarda
Tedavinin Mental Skor ve Uyarılmış Potansiyellere
Etkisi. Turk Hematoloji Onkoloji Dergisi2000;10; 194-
8.
[3] Fairbanks VF, Beutler E. Iron deficiency. In: Beutler E,
Lichtman MA, Coller BS, Kipps TJ, editors. Williams
Haematology, Fifth edition, New York: McGraw-Hill,
1995; 490-511.
[4] Beard JL, Connar JL. Iron status and neuralfunctioning.
AnnRev Nutr 2003; 23:41-58.
[5] Beard JL. Iron deficiency alters brain developmentand
functioning. J Nutr 2003; 133:1468-72.
[6] Connor JR, Menzies SL. Relationship of iron to
oligodendrocytes and myelination. Glia 1996; 17:83-
93.
[7] Kabakus N, Ayar A, Yoldas TK, Ulvi H, Dogan Y, Yilmaz
B, Kilic N. Reversal of iron deficiency anemia-induced
peripheral neuropathy by iron treatment in children
with iron deficiency anemia. J Trop Pediatr 2002;
48:204-9.
[8] El-Sebae AH, Soliman SA, Ahmed NS.Delayed
neuropathy in sheep by the phosphonothioate
insectiticide cyanofenphos. J Environ Sci Health 1979;
14:247-63.
[9] Brett EM.Vascular disorders of the nervous system in
childhood. In: Brett EM (ed.), Pediatric Neurology, 3rd
edn. Churchill Livingstone, New York; 1997; 579.
[10] Shahani BT, Halperin JJ, Boulu P, Cohen J. Sympathetic
skin response — a method of assessing unmyelinated
axon dysfunction in peripheralneuropathies.Journalof
Neurology NeurosurgeryandPsychiatry1984;47,536–
542.
[11] GR Arunodaya, Arun B Taly. Sympathetic skin
response: a decade later. Journal of the Neurological
Sciences 1995; 129, 81–89.
[12] Claus D, Schondorf R. In: Deuschl, G, Eisen, E (Eds.),
Recommendations for the practice of clinical
neurophysiology (EEG) (Suppl. 52). Elsevier,1999.
276–277.
[13] Elie B, Guiheneuc P. Sympatheticskin response:normal
results in different experimental conditions.
Electroencephalographyand Clinical Neurophysiology
1990; 76,258–267.
[14] Lozoff B, Jimenez E, Wolf AW. Long-term
developmental outcome of infantswith irondeficiency.
N Engl J Med 1991; 325:687-94.
[15] Lozoff B, Beard J, Connor J, et al. Long-lasting neural
and behavioral effects of iron deficiency in infancy.
Nutr Rev 2006; 64:S34–S43.
[16] Lozoff B. Iron deficiency and child development.
FoodNutr Bull 2007; 28:560–S571.
[17] Georgieff MK. Long-term brain and behavioral
consequences of early iron deficiency. Nutr Rev 2011;
69:43–S48.
[18] Lozoff B. Early iron deficiency has brain and behavior
effects consistent with dopaminergic dysfunction. J
Nutr 2011; 141:740–746.

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Sympathetic Skin Response in Children with Iron Deficiency Anemia

  • 1. International Journal of Trend in Scientific Research and Development (IJTSRD) Volume: 3 | Issue: 2 | Jan-Feb 2019 Available Online: www.ijtsrd.com e-ISSN: 2456 - 6470 @ IJTSRD | Unique Reference Paper ID – IJTSRD21593 | Volume – 3 | Issue – 2 | Jan-Feb 2019 Page: 1074 Sympathetic Skin Response in Children with Iron Deficiency Anemia Abdurrahman Sönmezler, Mahmut Abuhandan, Tahir Kurtulus Yoldas, Yeşim Oymak, Mustafa Çalık, Bülent Güzel, Hakim Çelik Assistant Professor, Department of Neurology, Adana City Research and Training Hospital, Adana, Turkey ABSTRACT BACKGROUND: Iron deficiency anemia (IDA) is particularly highin children indevelopingcountries .Sympathetic skin response (SSR) is a polysynaptic reflex, and its final efferent pathway involves pre- and post-ganglionic sympathetic sudomotor fibers that ultimately activate the sweat glands through sympathetic outflow . The aim of this study was to investigate whether IDA is involved in SSR. METHODS: 24 patients (17 girls, 7 boys) with IDA and 20 healthy children (11 girls, 9 boys) were enrolled in the study. RESULTS: Significant differences were observed between the palmar SSR results (latency, ms) of the patient and the control groups (1.09±0.24, 0.92±0.30, p= 0.048). There was no correlation between ferritin levels and SSRresultsofthepatientgroup( p=0.65 ). CONCLUSIONS: The evidence from this preliminary study suggests that efferent C fibers of the sympathetic nervous system may not intact in IDA. The sudomotor autonomic function test may be useful to detect autonomic involvement earlier. Keywords: Iron deficiency anemia, sympathetic skin response, children INTRODUCTION Iron deficiency anemia (IDA) is particularly high in children in developing countries 1.Iron plays an important role in various neurometabolic processes, which can be altered by iron deficiency. Hypoxia may lead to neuronal dysfunctions in IDA2, 3, 4, 5, 6, 7, 8, 9. Sympathetic skin response (SSR) is a polysynaptic reflex, and its final efferent pathway involves pre- and post-ganglionic sympathetic sudomotor fibers that ultimately activate the sweat glands through sympathetic outflow 10.SSR is coordinated in the posterior hypothalamus or upper brainstem reticular formation 11. The aim of this study was to investigate whether sympathetic skin responses are affected by the presence of iron deficiency anemia. Materials and methods This study was performed prospective at Harran University Hospital it was approved by the local ethics committee. There was informed consent obtained fromtheparents of all study participants.24 children (17 girls, 7 boys, mean age :13.7±1.79) with IDA and 20 healthy children(11 girls, 9 boys,mean age 12.4±1.93) were enrolled in the study. Patients with IDA with a hemoglobin value of less than 5 gr/dl were excluded from this study. All children were thoroughly examined clinically to rule out other causes of neuropathy. Electrophysiological testing was carried out according to the Technical Standards of the International Federation of Clinical Neurophysiology12. Childrens were investigated in a dark and silent room in a supine position with their eyes closed. Body,and skin temperature was controlled, temperature were same. EMG was performed using a filter setting of 0.1–32 Hz, a sensitivity setting of 1 mV divˉ¹, and a sweep rate of 5 s. The SSR was recordedwith surface electrodes (palmar ) on the skin ( Electromyography machine Dantec, Keypoint, Denmark).The study data were analyzed using SPSS (Statistical Package for Social Sciences) for Windows version 11.5. Differences between groupswere evaluated with the Mann-Whitney U-test. A valueof p 0.05 was accepted as statistically significant. Relations between variables were studied by the Pearson correlation test. Results All physical examination results of the children involved in this study were normal. The children did not report any symptoms of autonomic dysfunction. Significant differences were observed between the palmarSSRresults (latency, ms) of the the children with IDA and the control groups (1.09±0.24, 0.92±0.30, p= 0.048). There was no correlation between ferritin levels and SSR results of the the children with IDA group ( p=0.65 ). Discussion The palmar SSR results of the the children with IDA were different from those of the control group. There was no correlation between ferritin levels and SSR results of the children with IDA. Iron plays an important role in various metabolic and enzymatic processes. Iron deficiency may have an effect on neurological and intellectual functions. Many of the iron containing enzymes of the central and peripheral nervous systems could be affected adversely by IDA 7,14. SSR is coordinated in the posterior hypothalamus or upper brainstem reticular formation 11.SSRis anindicatorof sudomotor function mediated by amyelinic efferent Cfibers of the sympathetic nervous system 13.
  • 2. International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470 @ IJTSRD | Unique Reference Paper ID – IJTSRD21593 | Volume – 3 | Issue – 2 | Jan-Feb 2019 Page: 1075 IDA alters the behavior of infants in thecognitive,motor, and socio emotional domains and interferes with optimal development. Iron plays key roles in the normalprogression of several neurofunctional systems. The mechanisms by which chronic iron deficiency in infancy could contribute to adverse adult outcomes are undoubtedly complex. From animal models, it is clear that early-life iron deficiency adversely impacts the developing brain. IDA is associated with altered short and long-term neurofunctional development, including impaired myelination and dendritogenesis; altered neurotransmitter functioning; changes in neurometabolism in the hippocampus, striatum, and cortex; and altered gene and protein profiles 15, 16, 17, 18. In our study, there was no correlation between ferritin levels and SSR results of the children with IDA. Interestingly, we identified prolonged latency of SSR in the extremities.SSR is a polysynaptic reflex. The data may suggest that there are affected areas in the amyelinic efferent C-fibers or other parts of the reflex arc, but it is not clear. Becauseof theSSRis coordinated in the posterior hypothalamus or upper brainstem reticular formation.To ourknowledge,thereis no previous description of whether there is a correlation between ferritin levels and SSR latency in children and of differences between SSR of the children with IDA and a healthy group. This study is preliminary, and SSR in IDA should be studiedinlargerrandomizedgroups.Theevidence from this preliminary study suggests that efferent Cfibers of the sympathetic nervous system may not intact in IDA. The sudomotor autonomic function test may be useful to detect autonomic involvement earlier. Acknowledgement The authors have no financial or personal relationships with other people or organizations that could pose a conflict of interest in connection with the present work. This article was presented as a poster at 7th World Congress on Controversies in Neurology (CONy) References [1] DeMaeyer E, Adiels-Tegman M.The prevalence of anemia in the world,World Health Stat Q1985; 38:302- 16. [2] Karabiber H, Ozgen U, Ozen C, Soylu H, Kutlu O, Sarıbaş S, Kaya M, Demir Eksikliği Anemili Cocuklarda Tedavinin Mental Skor ve Uyarılmış Potansiyellere Etkisi. Turk Hematoloji Onkoloji Dergisi2000;10; 194- 8. [3] Fairbanks VF, Beutler E. Iron deficiency. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, editors. Williams Haematology, Fifth edition, New York: McGraw-Hill, 1995; 490-511. [4] Beard JL, Connar JL. Iron status and neuralfunctioning. AnnRev Nutr 2003; 23:41-58. [5] Beard JL. Iron deficiency alters brain developmentand functioning. J Nutr 2003; 133:1468-72. [6] Connor JR, Menzies SL. Relationship of iron to oligodendrocytes and myelination. Glia 1996; 17:83- 93. [7] Kabakus N, Ayar A, Yoldas TK, Ulvi H, Dogan Y, Yilmaz B, Kilic N. Reversal of iron deficiency anemia-induced peripheral neuropathy by iron treatment in children with iron deficiency anemia. J Trop Pediatr 2002; 48:204-9. [8] El-Sebae AH, Soliman SA, Ahmed NS.Delayed neuropathy in sheep by the phosphonothioate insectiticide cyanofenphos. J Environ Sci Health 1979; 14:247-63. [9] Brett EM.Vascular disorders of the nervous system in childhood. In: Brett EM (ed.), Pediatric Neurology, 3rd edn. Churchill Livingstone, New York; 1997; 579. [10] Shahani BT, Halperin JJ, Boulu P, Cohen J. Sympathetic skin response — a method of assessing unmyelinated axon dysfunction in peripheralneuropathies.Journalof Neurology NeurosurgeryandPsychiatry1984;47,536– 542. [11] GR Arunodaya, Arun B Taly. Sympathetic skin response: a decade later. Journal of the Neurological Sciences 1995; 129, 81–89. [12] Claus D, Schondorf R. In: Deuschl, G, Eisen, E (Eds.), Recommendations for the practice of clinical neurophysiology (EEG) (Suppl. 52). Elsevier,1999. 276–277. [13] Elie B, Guiheneuc P. Sympatheticskin response:normal results in different experimental conditions. Electroencephalographyand Clinical Neurophysiology 1990; 76,258–267. [14] Lozoff B, Jimenez E, Wolf AW. Long-term developmental outcome of infantswith irondeficiency. N Engl J Med 1991; 325:687-94. [15] Lozoff B, Beard J, Connor J, et al. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006; 64:S34–S43. [16] Lozoff B. Iron deficiency and child development. FoodNutr Bull 2007; 28:560–S571. [17] Georgieff MK. Long-term brain and behavioral consequences of early iron deficiency. Nutr Rev 2011; 69:43–S48. [18] Lozoff B. Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J Nutr 2011; 141:740–746.