Abstracts
Objective
The objective of this study was to evaluate the relationship between unilateral spatial neglect (USN) and haemoglobin (Hb) level in acute phase of stroke.
Method
Cross-sectional study was performed after right hemisphere ischemic stroke. Independent variable: Hb level (mg/dL); Outcome: USN; Potential confounding factors: Age, National Institutes of Health Stroke Scale (NIHSS), and glycaemia (mg/dL); Characterization variables were obtained from electronic medical records, Hb, mean corpuscular volume (MCV) and glycaemia by laboratory exams, and USN by cancellation and bisection tasks. The relationship between Hb and USN was assessed by Spearman correlation and linear regression model.
Results
40 individuals were evaluated; it was observed that the higher the Hb level, the better the USN test performance, with the two being negatively correlated. There was no significant correlation between VCM level and USN performance.
Conclusion
Low hemoglobin levels may indicate a worse performance in USN cancellation and bissection tests in acute phase of stroke.
stroke; perceptual disorders; haemoglobins
Objetivo
O objetivo do estudo foi avaliar a relação entre a negligência espacial unilateral (NEU) e hemoglobina (Hb) na fase aguda do acidente vascular cerebral (AVC).
Método
Foi realizado estudo transversal em pacientes com AVC de hemisfério direito dentro das primeiras 48 horas do ictus. Variáveis independentes: nível de Hb (mg/dL); Desfecho: NEU; Fatores potenciais de confundimento: Idade, National Institutes of Health Stroke Scale (NIHSS) e glicemia (mg/dL); A caracterização das variáveis foram obtidas por meio de prontuários eletrônicos, Hb e glicemia por exames laboratoriais, e NEU por meio do Line Cancellation (LCT), Star Cancelation (SCT), e Line Bisection Tasks (LBT).
Resultados
40 indivíduos foram avaliados e foi observado que quanto maior os níveis de Hb, melhor o desempenho nos testes de NEU, demonstrando correlação negativa entre eles.
Conclusão
Níveis baixos de hemoglobina podem indicar pior desempenho nos testes de NEU na fase aguda do AVC.
acidente vascular cerebral; transtornos da percepção; hemoglobinas
Low haemoglobin (Hb) is a common condition in the elderly population and is associated
with increased mortality and worsening functional performance, independent of cause11 . Hao Z, Wu B, Wang D, Lin S, Tao W, Liu M. A cohort study of
patients with anemia on admission and fatality after acute ischemic stroke. J
Clin Neurosci. 2013;20(1):37-42.
http://dx.doi.org/10.1016/j.jocn.2012.05.020
https://doi.org/10.1016/j.jocn.2012.05.0...
,22 . Tanne D, Molshatzki N, Merzeliak O, Tsabari R, Toashi M,
Schwammenthal Y. Anemia status, haemoglobin concentration and outcome after
acute stroke: a cohort study. BMC Neurol. 2010;10(4):22.
http://dx.doi.org/10.1186/1471-2377-10-22
https://doi.org/10.1186/1471-2377-10-22...
. Many people in acute phase of stroke present low
haematocrit levels, which are associated with higher mortality and worsening long-term
results; but the importance of low haemoglobin in stroke clinical presentation has not
been clearly established33 . Gottesman RF, Bahrainwala Z, Wityk RJ, Hillis AE. Neglect is more
common and severe at extreme haemoglobin levels in right hemispheric stroke.
Stroke. 2010;41(8):1641-5.
http://dx.doi.org/10.1161/STROKEAHA.110.585265
https://doi.org/10.1161/STROKEAHA.110.58...
,44 . Kimberly WT, Wu O, Arsava EM, Garg P, Ji R, Vangel M et al. Lower
haemoglobin correlates with larger stroke volumes in acute ischemic stroke.
Cerebrovasc Dis Extra. 2011;1(1):44-53.
http://dx.doi.org/10.1159/000328219
https://doi.org/10.1159/000328219...
,55 . Sico JJ, Concato J, Wells CK, Lo AC, Nadeau SE, Williams LS et al.
Anemia is associated with poor outcomes in patientes with less severe ichemic
stroke. J Stroke Cerebrovasc Dis. 2013;22(3):271-8.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2011.09.003
https://doi.org/10.1016/j.jstrokecerebro...
,66 . Kellert L, Martin E, Sykora M, Bauer H, Gussmann P, Diedler J et
al. Cerebral oxygen transport failure?: decreasing haemoglobin and hematocrit
levels after ischemic strokepredict poor outcome and mortality: STroke: RelevAnt
Impact of haemoGlobin, Hematocrit and Transfusion (STRAIGHT): an observational
study. Stroke. 2011;42(10):2832-7.
http://dx.doi.org/10.1161/STROKEAHA.110.606665
https://doi.org/10.1161/STROKEAHA.110.60...
,77 . Kimberly WT, Wu O, Arsava EM, Garg P, Ji R, Vangel M et al. Lower
haemoglobin correlates with larger stroke volumes in acute ischemic stroke.
Cerebrovasc Dis Extra. 2011;1(1):44-53.
http://dx.doi.org/10.1159/000328219
https://doi.org/10.1159/000328219...
.
Currently, interest is growing in the effects of Hb concentration on cognitive decline.
Critical Hb levels, high or low, have been associated with worsening cognitive
performance in the elderly, but their mechanisms are poorly understood, with the
hypothesis of the presence of ischemia, hypoxia or central nervous system oxidative
stress88 . KurellaTamura M, Wadley VG, Newsome BB, Zakai NA, McClure LA,
Howard G et al. Haemoglobin concentration and cognitive impairment in the renal
REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. J
Gerontol A Biol Sci Med Sci. 2010;65(12):1380-6.
http://dx.doi.org/10.1093/gerona/glq126
https://doi.org/10.1093/gerona/glq126...
,99 . Shah RC, Wilson RS, Tang Y, Dong X, Murray A, Bennett DA. Relation
of haemoglobin to level of cognitive function in older persons.
Neuroepidemiology. 2009;32(1):40-6.
http://dx.doi.org/10.1159/000170905
https://doi.org/10.1159/000170905...
. Based on the results of several
studies, there is speculation that reduced aerobic capacity and cerebral vascular
dysfunction could also contribute to cognitive decline, and that normal haematocrit
levels reduce the transfer velocity within cerebral capillaries, improve oxygen
extraction by cerebral tissue, and have a positive effect on cortex functions1010 . Hare GM. Anaemia and the brain. Curr Opin Anaesthesiol.
2004;17(5):363-9.,1111 . Metry G, Wikström B, Valind S, Sandhagen B, Linde T, Beshara
S et al. Effect of normalization of hematocrit on brain circulation and
metabolism in hemodialysis patients. J Am Soc Nephrol.
1999;10(4):854-63..
In the present study, we evaluated the relationship between Unilateral Spatial Neglect (USN) by means of cognitive with perception tests, haemoglobin (Hb) and mean corpuscular volume (MCV) level in acute phase of stroke. The study hypothesizes that low haemoglobin values are associated with poorer performance on tests of unilateral spatial neglect, given that anaemia may influence the performance of activities that place high demands on the perceptual system, increasing errors on tests of cancelling and bisection of lines.
METHOD
This was cross-sectional study of ischemic stroke patients of both sexes presenting with right hemisphere lesion – confirmed by cranial computerized tomography (CT) or magnetic resonance imaging (MRI) – of anterior circulation origin, with defined aetiology, in the acute ictus phase (in the first 48 hours after ictus), under conservative treatment and admitted to the Stroke Unit at Botucatu Medical School University Hospital – Universidade Estadual Paulista “Júlio de Mesquita Filho”. Patients were excluded if they presented at least one of the following conditions: haemorrhagic or posterior circulation stroke, left hemisphere ischemia, previous Modified Rankin Scale (mRS)≥1, pre-existing dementia, aphasia, visual deficits, other neurological diseases, as were patients who had undergone surgical procedures, thrombolytic treatment, blood transfusion or presented a history of alcohol abuse, hypothyroidism, chronic obstructive pulmonary disease, liver disease, kidney failure or marked leukocytosis on laboratory exams.
Procedures
Individuals were evaluated through three USN exams, two for cancellation and one
for bisection: a) Cancellations tests: Line Cancellation Task (LCT), scored by
lines cancelled in relation to a total number of 40 lines on a sheet of
paper1212 . Albert ML. A simple test of visual neglect. Neurol.
1973;23(6):658-64.; Star Cancellation
Task (SCT), scored by 52 stars cancelled in between distractors1313 . Schenkenberg T, Bradford DC, Ajax ET. Line bisection and
unilateral visual neglect in patients with neurologic impairment. Neurol.
1980;30(5):509-17. http://dx.doi.org/10.1212/WNL.30.5.509
https://doi.org/10.1212/WNL.30.5.509...
; b) Bisection test: Line
Bisection Task (LBT), based on the number of deviations to the right in relation
to middle of line marked by patient on each line of the sheet1414 . Halligan PW, Burn JP, Marshall JC, Wade DT. Visuo-spatial neglect:
qualitative differences and laterality of cerebral lesion. J Neurol Neurosurg
Psychiatry. 1992;55(11):1060-8.
http://dx.doi.org/10.1136/jnnp.55.11.1060
https://doi.org/10.1136/jnnp.55.11.1060...
. In all USN tests the
examiner placed the test sheet in front of the patient with the centre of the
sheet 50 cm from the glabella, the objective being to measure USN severity.
Hb level (in g/dL), MCV (in fL) and other laboratory exams were performed through a standard protocol by nurses trained in vein puncture to collect blood samples using a sterile technique. The blood sample was collected in a 10 ml tube on the same day that USN tests were applied, and transferred to the clinical laboratory for automated processing. After analysis of the exams, anaemia was defined as Hb<12 g/dL in women and Hb<13 g/dL in men1515 . World Health Organization. Nutritional anaemias: report of a WHO Scientific Group. Geneva: World Health Organization; 1968. (Technical report series; vol 405). The individuals classified as anaemic were divided into microcytic (MCV<80 fL), normocytic (MCV=80-100) or macrocytic (MCV>100 fL)1616 . Bross MH, Soch K, Smith-Knuppel T. Anemia in older persons. Am Fam Physician. 2010;82(5):480-7..
The National Institutes of Health Stroke Scale (NIHSS) and mRS were applied simultaneously with the USN tests to define neurological deficit severity and functional independence; demographic and anthropometric data were obtained from electronic hospital records on the same USN test date.
Statistical analysis
The relationship between potential confounding factors (age, sex, neurological deficit severity, functional independence and glycaemia) and USN was assessed by the Spearman correlation and Mann-Whitney test, whereas the relationship between Hb level, MCV and NSU was explored by the Spearman correlation and linear regression model. Significance was set at p less than .05. Statistical analyses were performed using the software SPSS v.15.0.
Ethics
The study was approved by Human Research Ethics Committee of UNESP/Botucatu. All individuals or relatives consented to participate in the study.
RESULTS
One hundred and forty consecutive patients with stroke admitted to our University Hospital between June and December 2012, and a total of 40 patients were included in present data. The general demographic data and baseline characteristics are displayed in Table 1, and the potential confounders are presented in Table 2.
Figures 1 and 2 show the negative correlation between Hb and LCT (r=-0.35; p=0.02) and SCT (r=-0.27; p=0.09). The relationship between Hb level and USN evaluated by LBT (Figure 3) reveals its negative correlation with the number of deviations to the right (r=-0.36; p=0.03). These associations were independent of age, sex, neurological deficit, incapacity level or blood glucose.
In the linear regression model, it was demonstrated that the higher the Hb level, the fewer lines and starswere cancelled, with an average of around three lines (β=-3.1) and three stars (β=-3.2) left un-cancelled for each unit increase in Hb (Tables 3 and 4).
Table 5 demonstrates an absence of a statistically significant correlation between the VCM level and the degree of unilateral spatial neglect by means of LCT (r=-0.089; p=0.616), SCT (r=0.001; p=0.997) and LBT (r=0.063; p=0.723).
DISCUSSION
In our study we found a relationship between Hb level and the presence or absence of
USN, and that age, sex, severity (NIHSS), incapacity (mRS) and glycaemia are not
confounding factors in the final NSU result. This result is consistent with a
physiological mechanism, as the much lower haemoglobin levels reduce cerebral
oxygen, and thus worsen USN in the acute phase by establishing a larger area of
ischemic penumbra and delimiting the lesion area much earlier88 . KurellaTamura M, Wadley VG, Newsome BB, Zakai NA, McClure LA,
Howard G et al. Haemoglobin concentration and cognitive impairment in the renal
REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. J
Gerontol A Biol Sci Med Sci. 2010;65(12):1380-6.
http://dx.doi.org/10.1093/gerona/glq126
https://doi.org/10.1093/gerona/glq126...
. Studies have shown that erythropoietin levels have
neuroprotective properties that can regulate some caspases, and therefore prevent
neuron death, which is important for reducing the ischemic area and improving
neurological deficits1717 . Ismailov RM. Cognitive decline in the stroke belt and
erythropoietin. Ann Neurol. 2013;73(1):146.
http://dx.doi.org/10.1002/ana.23801.
In the first study where this association was found, a “U” pattern was
suggested in the correlation between Hb and USN, where the critical levels, high or
low, had determined worse USN33 . Gottesman RF, Bahrainwala Z, Wityk RJ, Hillis AE. Neglect is more
common and severe at extreme haemoglobin levels in right hemispheric stroke.
Stroke. 2010;41(8):1641-5.
http://dx.doi.org/10.1161/STROKEAHA.110.585265
https://doi.org/10.1161/STROKEAHA.110.58...
. Our
results highlight the drop in Hb in the acute phase as a factor of severity and
cognitive decline as measured by the USN tests. In an observational study66 . Kellert L, Martin E, Sykora M, Bauer H, Gussmann P, Diedler J et
al. Cerebral oxygen transport failure?: decreasing haemoglobin and hematocrit
levels after ischemic strokepredict poor outcome and mortality: STroke: RelevAnt
Impact of haemoGlobin, Hematocrit and Transfusion (STRAIGHT): an observational
study. Stroke. 2011;42(10):2832-7.
http://dx.doi.org/10.1161/STROKEAHA.110.606665
https://doi.org/10.1161/STROKEAHA.110.60...
, the authors reported that anaemia
in stroke acute phase results in worse functional performance in the first three
months and that this relation is associated with increased penumbra area and
cerebral infarct77 . Kimberly WT, Wu O, Arsava EM, Garg P, Ji R, Vangel M et al. Lower
haemoglobin correlates with larger stroke volumes in acute ischemic stroke.
Cerebrovasc Dis Extra. 2011;1(1):44-53.
http://dx.doi.org/10.1159/000328219
https://doi.org/10.1159/000328219...
.
Although the Hb level demonstrated an association the all USN tests, it was weakly
correlated with LBT, because the latter test has a relatively poor sensitivity for
detecting USN. The other tests applied (LCT and SCT) are generally the most
sensitive in perceptual disorders1818 . Agrell BM, Dehlin OI, Dahlgren CJ. Neglect in elderly stroke
patients: a comparison of five tests. Psychiatry Clin Neurosci.
1997;51(5):295-300.
http://dx.doi.org/10.1111/j.1440-1819.1997.tb03201.x
https://doi.org/10.1111/j.1440-1819.1997...
,1919 . Ferber S, Karnath HO. How to assess spatial neglect: line
bisection or cancellation tasks? J Clin Exp Neuropsychol. 2001;23(5):599-607.
http://dx.doi.org/10.1076/jcen.23.5.599.1243
https://doi.org/10.1076/jcen.23.5.599.12...
. This information is important because the association
between Hb and LBT can be influenced by the sensitivity of the test to detect
USN.
The results of MCV did not show a statistical correlation with performance on NSU
tests. In a descriptive analysis of our data, the patients with macrocytic anaemia
presented worse performance on tests of cancelling of lines and stars. This datum
has been little explored in the literature, where worsening has been reported only
in patients with a deficit in the spatial attention network and cognitive decline in
patients with macrocytic anaemia2020 . Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam
Physician. 2009;79(3):203-8.,2121 . Gamaldo AA, Ferrucci L, Rifkind J, Longo DL, Zonderman AB.
Relationship between mean corpuscular volume and cognitive performance inolder
adults. J Am Geriatr Soc. 2013;61(1):84-9.
http://dx.doi.org/10.1111/jgs.12066
https://doi.org/10.1111/jgs.12066...
. This finding presents little consistency with our study
in which only 4 patients presented macrocytic anaemia.
The limitations of the present study were small sample size, the fact that individuals could have received electrolyte replacement therapy, and other confounding factors, such as tobacco smoking, poor dietary habits or nutrition status. However, our results not only consistently demonstrate a negative association between Hb and USN severity, but also demonstrate the importance of the research objective of establishing ideal haemoglobin levels in the acute phase to avoid cognitive and perceptual decline and improve functional prognosis. We recommend that longitudinal follow-up studies be performed to observe long-term functional outcome and verify whether USN is reduced with haemoglobin replacement.
Based on the results, we conclude that low hemoglobin levels may indicate a worse performance in USN cancellation and bissection tests in acute phase of stroke. Further studies are needed with the inclusion of new confounding factors.
References
-
1Hao Z, Wu B, Wang D, Lin S, Tao W, Liu M. A cohort study of patients with anemia on admission and fatality after acute ischemic stroke. J Clin Neurosci. 2013;20(1):37-42. http://dx.doi.org/10.1016/j.jocn.2012.05.020
» https://doi.org/10.1016/j.jocn.2012.05.020 -
2Tanne D, Molshatzki N, Merzeliak O, Tsabari R, Toashi M, Schwammenthal Y. Anemia status, haemoglobin concentration and outcome after acute stroke: a cohort study. BMC Neurol. 2010;10(4):22. http://dx.doi.org/10.1186/1471-2377-10-22
» https://doi.org/10.1186/1471-2377-10-22 -
3Gottesman RF, Bahrainwala Z, Wityk RJ, Hillis AE. Neglect is more common and severe at extreme haemoglobin levels in right hemispheric stroke. Stroke. 2010;41(8):1641-5. http://dx.doi.org/10.1161/STROKEAHA.110.585265
» https://doi.org/10.1161/STROKEAHA.110.585265 -
4Kimberly WT, Wu O, Arsava EM, Garg P, Ji R, Vangel M et al. Lower haemoglobin correlates with larger stroke volumes in acute ischemic stroke. Cerebrovasc Dis Extra. 2011;1(1):44-53. http://dx.doi.org/10.1159/000328219
» https://doi.org/10.1159/000328219 -
5Sico JJ, Concato J, Wells CK, Lo AC, Nadeau SE, Williams LS et al. Anemia is associated with poor outcomes in patientes with less severe ichemic stroke. J Stroke Cerebrovasc Dis. 2013;22(3):271-8. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2011.09.003
» https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.09.003 -
6Kellert L, Martin E, Sykora M, Bauer H, Gussmann P, Diedler J et al. Cerebral oxygen transport failure?: decreasing haemoglobin and hematocrit levels after ischemic strokepredict poor outcome and mortality: STroke: RelevAnt Impact of haemoGlobin, Hematocrit and Transfusion (STRAIGHT): an observational study. Stroke. 2011;42(10):2832-7. http://dx.doi.org/10.1161/STROKEAHA.110.606665
» https://doi.org/10.1161/STROKEAHA.110.606665 -
7Kimberly WT, Wu O, Arsava EM, Garg P, Ji R, Vangel M et al. Lower haemoglobin correlates with larger stroke volumes in acute ischemic stroke. Cerebrovasc Dis Extra. 2011;1(1):44-53. http://dx.doi.org/10.1159/000328219
» https://doi.org/10.1159/000328219 -
8KurellaTamura M, Wadley VG, Newsome BB, Zakai NA, McClure LA, Howard G et al. Haemoglobin concentration and cognitive impairment in the renal REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. J Gerontol A Biol Sci Med Sci. 2010;65(12):1380-6. http://dx.doi.org/10.1093/gerona/glq126
» https://doi.org/10.1093/gerona/glq126 -
9Shah RC, Wilson RS, Tang Y, Dong X, Murray A, Bennett DA. Relation of haemoglobin to level of cognitive function in older persons. Neuroepidemiology. 2009;32(1):40-6. http://dx.doi.org/10.1159/000170905
» https://doi.org/10.1159/000170905 -
10Hare GM. Anaemia and the brain. Curr Opin Anaesthesiol. 2004;17(5):363-9.
-
11Metry G, Wikström B, Valind S, Sandhagen B, Linde T, Beshara S et al. Effect of normalization of hematocrit on brain circulation and metabolism in hemodialysis patients. J Am Soc Nephrol. 1999;10(4):854-63.
-
12Albert ML. A simple test of visual neglect. Neurol. 1973;23(6):658-64.
-
13Schenkenberg T, Bradford DC, Ajax ET. Line bisection and unilateral visual neglect in patients with neurologic impairment. Neurol. 1980;30(5):509-17. http://dx.doi.org/10.1212/WNL.30.5.509
» https://doi.org/10.1212/WNL.30.5.509 -
14Halligan PW, Burn JP, Marshall JC, Wade DT. Visuo-spatial neglect: qualitative differences and laterality of cerebral lesion. J Neurol Neurosurg Psychiatry. 1992;55(11):1060-8. http://dx.doi.org/10.1136/jnnp.55.11.1060
» https://doi.org/10.1136/jnnp.55.11.1060 -
15World Health Organization. Nutritional anaemias: report of a WHO Scientific Group. Geneva: World Health Organization; 1968. (Technical report series; vol 405)
-
16Bross MH, Soch K, Smith-Knuppel T. Anemia in older persons. Am Fam Physician. 2010;82(5):480-7.
-
17Ismailov RM. Cognitive decline in the stroke belt and erythropoietin. Ann Neurol. 2013;73(1):146. http://dx.doi.org/10.1002/ana.23801
-
18Agrell BM, Dehlin OI, Dahlgren CJ. Neglect in elderly stroke patients: a comparison of five tests. Psychiatry Clin Neurosci. 1997;51(5):295-300. http://dx.doi.org/10.1111/j.1440-1819.1997.tb03201.x
» https://doi.org/10.1111/j.1440-1819.1997.tb03201.x -
19Ferber S, Karnath HO. How to assess spatial neglect: line bisection or cancellation tasks? J Clin Exp Neuropsychol. 2001;23(5):599-607. http://dx.doi.org/10.1076/jcen.23.5.599.1243
» https://doi.org/10.1076/jcen.23.5.599.1243 -
20Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam Physician. 2009;79(3):203-8.
-
21Gamaldo AA, Ferrucci L, Rifkind J, Longo DL, Zonderman AB. Relationship between mean corpuscular volume and cognitive performance inolder adults. J Am Geriatr Soc. 2013;61(1):84-9. http://dx.doi.org/10.1111/jgs.12066
» https://doi.org/10.1111/jgs.12066
Publication Dates
-
Publication in this collection
Oct 2014
History
-
Received
23 Aug 2013 -
Reviewed
12 June 2014 -
Accepted
11 July 2014