Available via license: CC BY 4.0
Content may be subject to copyright.
R E S E A R C H Open Access
Serum vitamin D levels in acute stroke
patients
Fayrouz O. Selim
1
, Rasha M. Fahmi
2*
, Ayman E. Ali
3
, Nermin Raafat
4
and Ahmed F. Elsaid
5
Abstract
Background: Vitamin D deficiency has been proposed as a risk factors of cerebrovascular stroke.
Objectives: The aim of this study was firstly, to assess the serum level of vitamin D in cerebral stroke patients and
secondly, to examine if its deficiency was associated with stroke severity and outcome.
Methods: We utilized a case-control study design and recruited 138 acute stroke patients and 138 age- and sex-
matched controls from subjects attending outpatient clinic for other reasons. All participants were subjected to full
general and neurological examination. Brain imaging CT and/or MRI was performed. Blood samples were collected for
measurement of serum level of vitamin D (ng/ml) by ELISA, alkaline phosphatase, serum calcium, and phosphorous.
The stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) and stroke outcome was
assessed by modified Rankin Scale (mRS).
Results: Stroke patients had significant lower levels of vitamin D compared with the control group. Vitamin D deficiency
remained significantly associated with the NIHSS stroke severity scoreandthemRS3-monthstrokeoutcomeafter
controlling for other significant factors such as age, dyslipidemia, and infarction size using multivariable logistic regression
analysis.
Conclusion: Our results demonstrated that stroke patients suffer from vitamin D deficiency, which was associated with
both stroke severity and poor outcome. Vitamin D supplementation could exert a therapeutic role in the management of
cerebral stroke.
Keywords: Vitamin D, Stroke, NIHSS, mRS
Introduction
Vitamin D is one of the fat-soluble steroid hormones
which is responsible for calcium and phosphate homeo-
stasis and musculoskeletal health. Vitamin D is synthe-
sized from 7-dehydrocholesterol in the skin’s epidermal
layer in the presence of ultraviolet light. Then, undergo
two hydroxylation steps: first inactive vitamin D is hy-
droxylated in the liver to form 25-hydroxyvitamin D,
then classically in the kidney by 1-α-hydroxylase
(CYP27B) to become biologically active form 1,25-dihy-
droxyvitamin D
3
. The second hydroxylation step can
also occur in macrophages, T cells, and neurons [1,2].
Vitamin D has an important regulatory effect on im-
mune function and inflammation [3]. Low vitamin D
levels were associated with many illnesses such as cal-
cium metabolism disorders, type 2 diabetes mellitus,
autoimmune diseases, cardiovascular disease, stroke,
multiple sclerosis, and some infectious diseases and
cancers [4,5].
Stroke is one of the most frequent causes of death and
disability worldwide with a significant clinical and socio-
economic impact. It has a heterogeneous etiology in-
cluding unmodifiable risk factors such as genetic, age
and sex, and modifiable risk factors including hyperten-
sion, diabetes mellitus, dyslipidemia, sedentary lifestyle,
and smoking [6]. Low serum vitamin D levels have been
found in acute stroke patients compared with normal
controls [6,7]. Vitamin D is essential for regulation of
brain growth, function, and cerebrovascular physiology
[8]. It has been linked to vasoprotective potential includ-
ing slowing down of atherosclerosis, promotion of
endothelial function, suppression of renin–angiotensin–
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
* Correspondence: rashafahmi@zu.edu.eg
2
Department of Neurology, Faculty of Medicine, Zagazig University, Sharkia,
Egypt
Full list of author information is available at the end of the article
The Egyptian Journal of Neurology
,
Psychiatry and Neurosurgery
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
(2019) 55:80
https://doi.org/10.1186/s41983-019-0129-0
aldosterone system thereby reduction of the risk of
hypertension. Therefore, its deficiency might be involved
in the development of several diseases, including dia-
betes, hypertension, heart failure, ischemic heart dis-
eases, and stroke [9]. Moreover, deficiency of vitamin D
influences vascular remodeling through modulation of
smooth muscle cell proliferation, inflammation, and
thrombosis. These vascular changes can eventually cause
stroke [10].
However, results of different researches showed that
vitamin D deficiency is a risk factor of stroke; the associ-
ation between the severity and outcome of stroke with
the level of vitamin D has not been examined closely.
The aim of this study is to evaluate the serum vitamin D
levels in cerebral stroke patients and assesses association
between vitamin D deficiency with severity and outcome
of stroke.
Subjects and methods
Sample size
The sample size of the current case-control study was
calculated based on the previously reported vitamin D
deficiency rate of 48.8% in stroke patients and 31.6% in
control subjects [6]. At 5% two-sided level of signifi-
cance, we found that a sample size of 260 subjects (130
subjects/group) to achieve a power of 80% using the
Kelsey method, Epi Info, version 7.2 (CDC, 2018). We
recruited 138 subjects for each of the case and control
groups.
Study design and subject recruitment
We utilized a case-control study design that included
138 cerebral stroke patients and 138 control subjects
from patients attending outpatient clinics for other rea-
sons. Patients and control subjects were matched for sex
and age ± 5 years. Systemic random technique, recruit-
ing every 3rd subject, was used for randomly selecting
patients and control. Stroke patients were recruited from
intensive care and stroke units of Internal Medicine and
Neurology Departments, Zagazig University, between
June 2016 and June 2017. All participants were informed
with the study design and a written informed consent
was collected from all participants or their relatives.
Approval for performing the study was obtained from
Institutional Review Board (IRB) of Zagazig University.
Inclusion and exclusion criteria
Any stroke patients with first-ever acute onset stroke
were eligible for the study. We excluded patients with
the following criteria: (1) patients with history of hepatic
and renal impairment; (2) patients with brain neoplasm
or malignancy; (3) patients with endocrinal diseases; (4)
patients with vitamin D or Ca supplementation and ster-
oid therapy; and (5) patients with bone diseases. Control
included 138 healthy volunteers that were age and sex
matched with no prior history of stroke or transient is-
chemic attacks.
Brain imaging
All patients were submitted to computed tomography
(CT) using GE ProSpeed Dual Slice F II CT with
MX135 Tube (Cleveland, USA) and/or magnetic res-
onance imaging (MRI) using 1.5 T MR Scanner
(Achieva, Philips Medical System) of the brain on ad-
mission to differentiate patients with cerebral infarc-
tion from hemorrhage and to determine the site and
size of the lesion. When there was no positive data
on the admission CT scan, another CT scan or MRI
was performed. The infarct size was determined by
the largest diameter of the lesion [11].
Laboratory investigations
One venous blood sample was obtained for each subject.
Blood samples were obtained within 48 h of the onset of
stroke. Complete blood count (CBC), random blood glu-
cose level, liver chemistry tests, kidney function tests, C-
reactive protein (CRP), arterial blood gases, serum so-
dium and potassium, erythrocyte sedimentation rate
(ESR), lipid profile (total cholesterol, triglycerides, HDL,
and LDL), alkaline phosphatase, serum calcium and
phosphorous, and vitamin D were performed for all par-
ticipant. Measurement of serum level of vitamin D (ng/
ml) was done using enzyme-linked immunosorbent assay
(ELISA) following manufacturer’s instruction of the Kit
(Immunodiagnostic Systems Ltd, Bolden, UK). The assay
utilize as monoclonal antibody that binds to 25-OH vita-
minD
3
. Vitamin D deficiency was defined if its level was
< 20 ng/ml [6].
Stroke severity and outcome assessment
The severity of the stroke was assessed by the National
Institutes of Health Stroke Scale (NIHSS) [12]. Stroke
severity was categorized as mild (NIHSS score < 8),
moderate (NIHSS score 8–14), and severe stroke
(NIHSS score ≥15) [13]. Short-term functional outcome
was measured using modified Rankin Scale (mRS) after
3-months. mRS score of ≤2 was considered as good
functional outcome while poor functional outcome was
defined as mRS score of ≥3[14].
Other measures
All patients of this study were subjected to detailed
history taking with paying special attention to medical
history of stroke risk factors, according to criteria
determined by Mouradian and colleagues [15]. Full gen-
eral and neurological examinations including Glasgow
Coma Scale (GCS) were performed. Obesity is defined as
body mass index ≥30 kg/m
2
[16]. Chest X-ray,
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 2 of 8
electrocardiography, and echocardiography were done
for patients with cardiac lesions.
Statistical analysis
Data were analyzed using the Statistical Package for the
Social Sciences (SPSS) version 20 (IBM corporation,
Armonk, New York) [17]. Quantitative variables were
expressed as mean ± standard deviation (SD), whereas
qualitative variables were expressed as frequencies and
percentages. Comparison between patients and controls
was performed using Student ttest or chi-square test as
deemed appropriate. Univariate followed by multivari-
able regression analysis was performed to identify inde-
pendent significant factors associated with stroke
severity and outcome. Measures of association were
expressed as odds ratios (ORs) and 95% confidence
interval (CI). pvalues ≤0.05 and ≤0.01 were considered
significant and highly significant, respectively.
Partial correlation, after controlling of other significant
risk factors, was performed to examine the association
between vitamin D and NIHSS, and mRS scores was
performed. We assessed the vitamin D cutoff levels asso-
ciated with bad stroke severity and stroke outcome using
the receiver-operating characteristic (ROC) analysis. Best
sensitivity and specificity associated with cutoff levels
was presented. ROC curve analysis was performed using
the MedCalc software version 7.50 (Mariakerke,
Belgium).
Results
This case-control study included 138 patients with a
mean age (± SD) of 64.27 years (± 12.36), and 138 con-
trol subject with a mean age (± SD) of 64.65 years (±
10.2). According to stroke type, 30 (21.7%) of our stroke
patients had intracerebral hemorrhage, and 108 patients
(78.3%) had ischemic stroke (27.6% had lacunar infarc-
tion, 32% had medium-sized infarction, whereas only
18.7% presented with large infarction).
There were no statistically significant differences re-
garding age and sex. As regard to other risk factors, dia-
betes mellitus (DM) was significantly more common in
stroke patients (59.4%) followed by hypertension
(58.7%), obesity (42%), dyslipidemia (40.6%), smoking
(33.3%), atrial fibrillation (AF) (32.6%), peripheral vascu-
lar disease (21.7%), and ischemic heart disease (20.3%)
when compared with controls (31.9%, 14.5%, 28.9%,
13%, 8.7%, 7.2%, 3.6%, and 8.7% respectively). Our stud-
ied stroke patients had statistically significant lower
levels of vitamin D when compared with the control
group. However, serum total Ca, phosphorus, and alka-
line phosphatase showed no statistically significant dif-
ference between patients and control (Table 1).
Stroke severity was assessed using NIHSS. Univariable
analysis showed that age, hypertension, diabetes mellitus,
dyslipidemia, AF, vitamin D deficiency, CRP, large in-
farction size, and intracerebral hemorrhage were signifi-
cantly associated with stroke severity. Further
multivariable analysis of the significant variables showed
that old age (OR = 1.072), dyslipidemia (OR = 3.588),
vitamin D deficiency (OR = 4.790), and large infarction
size (OR = 7.462) was independently associated with
stroke severity. The odds to have severe stroke is 1 with
old age (OR = 1.072), 3 with dyslipidemia (OR = 3.588),
and increased to be almost 5 with vitamin D deficiency
(OR = 4.790), and 7 with large infarction size (OR =
7.462) (Table 2).
As regards stroke outcome using mRS, hypertension,
diabetes mellitus, dyslipidemia, vitamin D deficiency,
CRP, GCS, NIHSS, large infarction size, and intracere-
bral hemorrhage were significantly associated with bad
outcome. Multivariable analysis was used to analyze the
association of significant factors with stroke outcome in
Table 1 Baseline characteristics of patients and control
Variables Stroke
patients
(N= 138)
Control
(N= 138)
Test of
significant
pvalue
Age (years):
mean ± SD
64.27 ± 12.36 64.65 ± 10.2 0.29
a
0.33
Sex
Male 72 (52.2%) 60 (43.5%) 2.09
b
0.18
Females 66 (47.8%) 78 (56.5%)
Vascular risk factors:
N(%)
Hypertension 81 (58.7%) 20 (14.5%) 58.10
b
0.000*
Diabetes mellitus 82 (59.4%) 44 (31.9%) 21.08
b
0.000*
Dyslipidemia 56 (40.6%) 18 (13%) 26.66
b
0.000*
Smoking 46 (33.3%) 12 (8.7%) 25.23
b
0.000*
Atrial fibrillation 45 (32.6%) 10 (7.2%) 27.81
b
0.000*
Ischemic heart
disease
28 (20.3%) 12 (8.7%) 7.48
b
0.006*
Peripheral vascular
disease
30 (21.7%) 5 (3.6%) 20.45
b
0.000*
Alcohol 8 (5.8%) 4 (2.9%) 1.39
b
0.37
Obesity 58 (42.0%) 40 (28.9%) 5.12
b
0.02*
Laboratory findings:
mean ± SD
Calcium level
(mg/dl)
8.69 ± 0.92 8.73 ± 0.99 0.34
a
0.63
Phosphorus level
(mg/dl)
3.96 ± 0.69 4.06 ± 0.54 1.34
a
0.18
Vitamin D (ng/ml) 13.47 ± 7.04 37.62 ± 4.4 34.17
a
0.000*
Alkaline
phosphatase (μ/L)
68.43 ± 19.6 66.65 ± 20.82 0.73
a
0.46
NNumber, SD standard deviation
a
ttest
b
Chi-squared
*Significant at pvalue ≤0.05
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 3 of 8
univariable analysis. NIHSS score, vitamin D deficiency,
and large infarction size were significant independent
risk factors associated with stroke outcome. The odds to
have bad outcome increase from 1 with high NIHSS
score (OR = 1.094) to 2.8 with vitamin D deficiency (OR
= 2.899) and 3.7 with large infarction size (OR = 3.774)
(Table 3).
Partial correlation of vitamin D serum level with
NIHSS stroke severity score after controlling for age,
dyslipidemia, and infarction size was done, and a sig-
nificant negative correlation was found between vita-
min D serum level and NIHSS (p= 0.002, r=−
0.267) (Fig. 1). Also, partial correlation of vitamin D
serum level with mRS stroke outcome score after
controlling for NIHSS and infarction size was done
and a significant negative correlation was found be-
tween serum vitamin D level and mRS (p= 0.01, r=
−0.207) (Fig. 2).
Receiver operator characteristics (ROC) curve analysis
of vitamin D serum level that best predict stroke severity
as determined by NIHSS score was used. Vitamin D
serum level of ≤9 ng/ml was shown to predict stroke se-
verity with sensitivity of 74.2% and specificity of 71%.
The overall performance of vitamin D marker was 77%
as determined by area under curve (AUC) and was sig-
nificantly different from the 50% chance diagonal line (p
< 0.0001) (Fig. 3).
Moreover, using the ROC curve analysis, we tested
the vitamin D serum level that best predict stroke out-
come as determined by mRS score. Vitamin D serum
level of ≤17 ng/ml was shown to predict stroke out-
come with sensitivity of 81.4% but with low specificity
of 42.7%. The overall performance of vitamin D marker
was 65.4% as determined by area under curve (AUC)
that was significantly different from the 50% chance di-
agonal line (p< 0.001) (Fig. 4).
Discussion
In the current study, the most prevalent risk factors
of stroke were all modifiable. Diabetes mellitus was
the most common followed by hypertension, obesity,
dyslipidemia, smoking, AF, peripheral vascular disease,
ischemic heart disease, and vitamin D deficiency. In
general, this result was in agreement with the results
derived from many previous epidemiological studies
[18,19]. Strong evidence for the association of low
vitamin D with higher risk of cerebral stroke stems
from several meta-analyses studies [20,21]. The inci-
dence of cerebral stroke was reported to increase by
morethandoubleinthepresenceofischemicheart
disease, more than triple in the presence of hyperten-
sion, more than quadruple in the presence of heart
failure, and nearly quintupled when AF was present
[22]. In the present study, stroke patients had
Table 2 Univariable and Multivariable Logistic Regression analysis of factors with stroke severity (NIHSS)
Variables Univariate Multivariate
OR 95% CIs pvalue OR 95% CIs pvalue
Age 1.057 1.017–1.098 0.005* 1.072 1.016–1.130 0.01*
Hypertension 3.795 1.441–9.994 0.007* 2.889 0.822–10.153 0.09
Diabetes mellitus 2.897 1.150–7.296 0.02* 1.446 0.442–4.727 0.54
Dyslipidemia 3.586 1.551–8.289 0.003* 3.588 1.240–10.382 0.01*
Smoking 1.620 0.711–3.688 0.251
Atrial fibrillation 2.406 1.059–5.469 0.03* 1.489 0.500–4.433 0.47
Ischemic heart disease 1.513 0.591–3.873 0.38
Peripheral vascular disease 1.065 0.408–2.782 0.89
Alcohol 1.161 0.222–6.061 0.86
Obesity 1.955 0.872–4.384 0.10
Vitamin D deficiency 3.921 1.399–10.993 0.009* 4.790 1.282–17.903 0.02*
CRP 2.706 1.179–6.213 0.01* 1.711 0.581–5.033 0.32
GCS 0.875 0.755–1.015 0.08
Intracerebral hemorrhage 3.123 1.292–7.548 0.01* 3.217 0.876–11.812 0.08
Infarction size:
Small (reference) 1
Medium 1.706 0.644–4.515 0.28 1.716 0.466–6.324 0.41
Large 4.253 1.522–11.884 0.006* 7.462 1.795–31.030 0.006*
CRP C-reactive protein, GCS Glasgow Coma Scale, NIHSS National Institute of Health Stroke Scale, OR odds ratio, CI confidence interval
*Significant at pvalue ≤0.05
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 4 of 8
statistically significant lower levels of vitamin D when
compared with control group. This was concomitant
with non-significant reduction of lower serum total
Ca and phosphorus and increased alkaline phosphat-
ase levels in stroke patients compared with controls.
These results were in agreement with the results ob-
tained by other studies [23–26].
The association of vitamin D deficiency with stroke se-
verity and outcome after controlling for other risk fac-
tors suggests a role for vitamin D in the pathogenesis of
Fig. 1 Partial correlation analysis after controlling for age, dyslipidemia, and infarction size shows that vitamin D serum level (ng/ml)
demonstrated significant negative correlation with NIHSS stroke severity score
Table 3 Univariable and multivariable logistic regression analysis of factors with stroke outcome (mRS)
Variables Univariate Multivariate
OR 95% CIs pvalue OR 95% CIs pvalue
Age 1.026 0.994–1.059 0.11
Hypertension 2.974 1.278–6.921 0.01* 2.385 0.843–6.749 0.10
Diabetes mellitus 2.857 1.228–6.650 0.01* 1.521 0.550–4.207 0.41
Dyslipidemia 2.294 1.073–4.906 0.03* 1.325 0.513–3.422 0.56
Smoking 1.982 0.916–4.288 0.08
Atrial fibrillation 1.522 0.699–3.315 0.29
Ischemic heart disease 0.849 0.328–2.198 0.73
Peripheral vascular disease 0.455 0.160–1.291 0.14
Alcohol 2.824 0.669–11.918 0.16
Obesity 1.004 0.471–2.140 0.991
Vitamin D deficiency 3.480 1.400–8.647 0.007* 2.899 1.003–8.384 0.04*
CRP 2.300 1.072–4.936 0.03* 1.407 0.550–3.602 0.47
GCS 0.843 0.732–0.971 0.02* 0.883 0.744–1.049 0.15
NIHSS 1.151 1.074–1.233 0.000* 1.094 1.014–1.182 0.02*
Intracerebral hemorrhage 2.539 1.086–5.936 0.03* 2.821 0.867–9.173 0.08
Infarction size
Small (reference) 1
Medium 1.774 0.732–4.303 0.20 1.909 0.644–5.656 0.24
Large 3.626 1.361–9.660 0.01* 3.774 1.049–13.581 0.04*
CRP C-reactive protein, GCS Glasgow Coma Scale, NIHSS National Institute of Health Stroke Scale, OR odds ratio, CI confidence interval
*Significant at pvalue ≤0.05
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 5 of 8
stroke that could be invoked by several mechanisms. For
example, vitamin D has a role in arterial hypertension
via the suppression of the renin–angiotensin–aldoster-
one system (RAS). RAS is a key regulator of blood
pressure, electrolyte, and volume homeostasis. Overacti-
vation of the RAS system leads to hypertension which is
one of the most important modifiable risk factor for all
types of stroke [27,28]. Type 2 diabetes was associated
with low vitamin D levels, which was linked to pancre-
atic βcell dysfunction and disturbed insulin secretion
[29]. In addition, vitamin D acts as a modulator of
depolarization potential and stimulated insulin secretion
via releasing of intracellular calcium stores [30]. More-
over, vitamin D regulates parathyroid hormone (PTH)
Fig. 2 Partial correlation analysis after controlling for NIHSS score and infarction size shows that vitamin D serum level (ng/ml) demonstrated
significant negative correlation with mRS stroke outcome score
Fig. 3 Receiver operator characteristics (ROC) analysis showed that
vitamin D serum level ≤9 ng/ml best predict stroke severity (as
determined by NIHSS score) with sensitivity and specificity of 74.2%
and 71%, respectively. Area under curve (AUC) of 77% was
significantly different from the random 50% (p< 0.0001)
Fig. 4 Receiver operator characteristics (ROC) analysis showed that
vitamin D serum level −17 ng/ml that best predict stroke outcome
(as determined by mRS score) with sensitivity and specificity of
81.4% and 42.7%, respectively. Area under curve (AUC) was 65.4%
was significantly different from the random 50% (p< 0.001)
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 6 of 8
concentration which is associated with insulin synthesis
and secretion in the pancreas [29]. Vitamin D deficiency
induces secondary hyperparathyroidism and increased
PTH level that was associated with diabetes by causing β
cell dysfunction and insulin resistance [30]. Furthermore,
vitamin D deficiency was shown to be associated with
dyslipidemia among stroke patients [31,32]. It was ob-
served that low vitamin D concentrations were associ-
ated with higher triglycerides and total cholesterol and
lower levels of HDL cholesterol [31]. In this study, the
results of multivariable logistic regression analysis
showed that after controlling other risk factors, age, dys-
lipidemia, vitamin D deficiency, and large infarction size
were statistically significant independent factors associ-
ated with stroke severity. This was in agreement with
other studies which showed that vitamin D deficiency
was associated with stroke severity [25,33]
Regarding stroke outcome, multivariable logistic re-
gression analysis showed that high NIHSS score, vitamin
D deficiency, and large infarction size were significantly
associated with mRS. Our result was in accordance with
the result of other studies demonstrated that vitamin D
level is a good biomarker for prognosis, functional out-
come, and death in patients with acute ischemic and
hemorrhagic stroke [25,26,33,34]. This could be ex-
plained by the neuroprotection role of vitamin D via ac-
tivation of detoxification pathways, upregulation of
antioxidation/anti-inflammatory mechanisms, inhibition
of inducible nitric oxide synthase, and regulation of
neuronal calcium metabolism [35,36]. Interestingly, the
result of a recent experimental trial demonstrated that
administration of vitamin D can attenuate infarct devel-
opment after stroke probably by modulating the inflam-
matory response to cerebral ischemia [37].
In the current study, partial correlation of vitamin D
serum level with NIHSS score severity and mRS score
outcome after controlling for other variables showed a
significant negative correlation between serum vitamin
D level with stroke severity and outcome. Furthermore,
ROC curve analysis of vitamin D serum level that best
predict stroke severity was ≤9 ng/ml and vitamin D
serum level of ≤17 ng/ml was the best cutoff for stroke
outcome. Our finding was in agreement with other stud-
ies reported 10–12 ng/mL as the best cutoff value of
vitamin D for mortality [38,39]. However, another study
estimated a higher cutoff value of serum 25(OH) D
levels as indicator for early neurological deterioration to
be 42.5 nmol/l [40]. These cutoff values could be used to
identify patients at a higher risk of severe stroke and bad
outcome that need more intensive monitoring.
Some limitations of our study include enrolling pa-
tients over different seasons. It is known that vitamin D
levels exhibits some seasonal variation. In addition, we
did not collect information regarding previous dietary
intake and sunlight exposure. Unavailable data on serum
parathyroid hormone represent another limitation.
In conclusion, our results demonstrated that vitamin
D deficiency was an independent risk factor significantly
associated with cerebral stroke severity and outcome
after controlling other known risk factors. This result
suggests a therapeutic role for vitamin D supplementa-
tion in the management of cerebral stroke. Further pro-
spective studies are needed to verify whether correcting
vitamin D deficiency may affect the severity and out-
come of the stroke as well as to establish the appropriate
therapeutic dose of vitamin D for supplementation in
stroke patients. Screening for serum vitamin D concen-
trations is likely to identify individuals who are at the
highest risks, particularly those with old age, diabetes,
and large infarction.
Abbreviations
CBC: Complete blood count; CI: Confidence interval; CRP: C-reactive protein;
CT: Computed tomography; ESR: Erythrocyte sedimentation rate;
GCS: Glasgow Coma Scale; IRB: Institutional Review Board; MRI: Magnetic
resonance imaging; mRS: Modified Rankin Scale; N: Number; NIHSS: National
Institutes of Health Stroke Scale; OR: Odds ratio; ROC: Receiver operator
characteristics; SD: Standard deviation
Acknowledgements
Not applicable
Authors’contributions
FOS, RMF, AEA, NR, and AFE contributed to the design of the study, data
collection, analyzed, and interpreted the data. All authors were responsible
for writing the manuscript, guidance, and follow-up the final revision. All au-
thors were involved in drafting the article or revising it critically for important
intellectual content. All authors approved the final version to be published.
Funding
This study received no funding.
Availability of data and materials
The data results generated or analyzed during this study are included in this
published article.
Ethics approval and consent to participate
The study protocol was approved by the ethics committee of the faculty of
Medicine, Zagazig University. The reference number is 3836/21-6-2017. The
purpose of the study was explained, and an informed written consent was
taken before taking any data or doing any investigations. The participants
were informed that their participation was voluntary and that they could
withdraw from the study at any time without consequences.
Consent for publication
Is not applicable in this section.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Department of Internal Medicine, Zagazig University, Sharkia, Egypt.
2
Department of Neurology, Faculty of Medicine, Zagazig University, Sharkia,
Egypt.
3
Department of Internal Medicine, Zagazig University, Sharkia, Egypt.
4
Department of Medical Biochemistry, Zagazig University, Sharkia, Egypt.
5
Department of Public Health and Community Medicine, Zagazig University,
Sharkia, Egypt.
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 7 of 8
Received: 20 March 2019 Accepted: 6 November 2019
References
1. Holick MF. Vitamin D deficiency, N Engl J Med. 2007;357:266.
2. Lugg ST, Howells PA, Thickett DR. Optimal vitamin D supplementation
levels for cardiovascular disease protection. Dis Markers. 2015;2015:1.
3. Clancy N, Onwuneme C, Carroll A, McCarthy R, McKenna MJ, Murphy N,
et al. Vitamin D and neonatal immune function. J Matern Fetal Neonatal
Med. 2013;26:639.
4. Wacker M, Holick MF. Vitamin D effects on skeletal and extraskeletal health
and the need for supplementation. Nutrients. 2013;5:111.
5. Fahmi RM, Lotfy SM, Mohamed WS, Elsaid AF, Murad MH, Abdulmoneem G.
Vitamin D levels in patients with multiple sclerosis. Egypt J Neurol Psychiatr
Neurosurg. 2014;51:145.
6. Chaudhuri JR, Mridula KR, Alladi S, Umamahesh M, Balaraju B, Swath A, et al.
Serum 25-hydroxyvitamin D deficiency in ischemic stroke and subtypes in
Indian patients. J STROKE. 2014;16:44.
7. Alfieri DF, Lehmann MF, Oliveira SR, Flauzino T, Delongui F, de Araújo MC,
et al. Vitamin D deficiency is associated with acute ischemic stroke, C-
reactive protein, and short-term outcome. Metab Brain Dis. 2017;32:493.
8. Eyles DW, Liu PY, Josh P, Cui X. Intracellular distribution of the vitamin D
receptor in the brain: comparison with classic target tissues and
redistribution with development. Neuroscience. 2014;268:1.
9. Carvalho LS, Sposito AC. Vitamin D for the prevention of cardiovascular
disease: are we ready for that? Atherosclerosis. 2015;241:729.
10. Thapa L, Pokhrel B, Shrestha A, Pradhan M, Bhandari TR, Shrestha S, et al.
Status of vitamin D and its association with stroke risk factors in patients
with acute ischemic stroke in a tertiary care hospital. J Nepal Med Assoc.
2014;52:935.
11. Shine P, Shwu W, Tzy W, Lee TK, Tony C. Location and size of infarct on
functional outcome of non cardioembolic ischemic stroke. Disabil Rehabil.
2006;28:977.
12. Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, et al.
Measurements of acute cerebral infarction: a clinical examination scale.
Stroke. 1989;20:864.
13. NIH Stroke Scale. National Institute of Neurological Disorder website. https://
www. ninds.nih.gov/sites/default/files/NIH_Stroke_Scale.
14. Uyttenboogaart M, Stewart RE, Vroomen PC, De Keyser J, Luijckx GJ.
Optimizing cutoff scores for the Barthel index and the modified Rankin
Scale for defining outcome in acute stroke trials. Stroke. 2005;36:1984.
15. Mouradian MS, Majumdar SR, Senthilselvan A, Khan K, Shuaib A. How well
are hypertension, hyperlipidemia, diabetes, and smoking managed after a
stroke or transient ischemic attack? Stroke. 2002;33:1656.
16. Organization WHO. Obesity and overweight. World Health Organization.
http://www.who.int/mediacentre/factsheets/fs311/en/.
17. Corp IBM. IBM SPSS Statistics for Windows, Version 20. IBM Corp: Armonk,
NY; 2010.
18. Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, et al. Age
at stroke: temporal trends in stroke incidence in a large, biracial population.
Neurology. 2012;79:1781.
19. SmajlovićD. Strokes in young adults: epidemiology and prevention. Vasc
Health Risk Manag. 2015;11:157.
20. Zhou R, Wang M, Huang H, Li W, Hu Y, Wu T. Lower vitamin D status is
associated with an increased risk of ischemic stroke: a systematic review
and meta-analysis. Nutrients. 2018;10:277.
21. Brondum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M. 25-
hydroxyvitamin D and symptomaticischemic stroke: an original study and
meta-analysis. Ann Neurol. 2013;73:38.
22. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk
factor for stroke: the Framingham Study. Stroke. 1991;22:983.
23. Alfieri DF, Lehmann MF, Oliveira SR, Flauzino T, Delongui F, de Araújo MC,
et al. Vitamin D deficiency is associated with acute ischemic stroke, C-
reactive protein, and short-term outcome. Metab Brain Dis. 2017;32:493.
24. Chatterjee K, Mandal SK, Chatterjee S. Assessment of vitamin D level in
cerebrovascular accident patients in Eastern India. Natl J Med Res. 2014;4:264.
25. Fahmy E, Sharaf S, Helmy H, Sherif S. Vitamin D status in acute ischemic
stroke: relation to initial severity and short-term outcome. Egypt J Neurol
Psychiatr Neurosurg. 2019; 55: 18.
26. Wajda J, Świat M, Owczarek AJ, Brzozowska A, Glinianowicz MO, Chudek J.
Severity of vitamin D deficiency predicts mortality in ischemic stroke
patients. Dis Markers. 2019;2019:1.
27. Kannel WB, Wolf PA. Framingham study insights on the hazards of elevated
blood pressure. JAMA. 2008;300:2545.
28. Santoro D, Caccamo D, Lucisano S, Buemi M, Sebekova K, Teta D, et al.
Interplay of vitamin D, erythropoiesis, and the renin-angiotensin system. Bio
Med Res Int. 2015;2015:1.
29. Afzal S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of
type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem.
2013;59:381.
30. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, et al. Blood
25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of
prospective studies. Diabetes care. 2013;36:1422.
31. Ponda MP, Huang XX, Odeh MA, Breslow JL, Kaufman HW. Vitamin D may
not improve lipid levels: a serial clinical laboratory data study. Circulation.
2012;126:270.
32. Zittermann AF, Gummert J, Borgermann J. The role of vitamin D in
dyslipidemia and cardiovascular disease. Curr Pharm Design. 2011;17:933.
33. Tu WJ, Zhao SJ, Xu DJ, Chen H. Serum 25-hydroxyvitamin D predicts the
short-term outcomes of Chinese patients with acute ischaemic stroke. Clin
Sci. 2014;126:339.
34. Park KY, Chung PW, Kim YB, Moon HS, Suh BC, Won YS, et al. Serum vitamin
D status as a predictor of prognosis in patients with acute ischemic stroke.
Cerebrovasc Dis. 2015;40:73.
35. Michos ED, Gottesman RF. Vitamin D for the prevention of stroke incidence
and disability: promising but too early for prime time. Eur J Neurol. 2013;20:3.
36. Witham MD, Dove FJ, Sugden JA, Doney AS, Struthers AD. The effect of
vitamin D replacement on markers of vascular health in stroke patients—a
randomised controlled trial. Nutr Metab Cardiovas. 2012;22:864.
37. Evans MA, Kim HA, Ling YH, Uong S, Vinh A, De Silva TM, et al. Vitamin D3
supplementation reduces subsequent brain injury and inflammation
associated with ischemic stroke. Neuromol Med. 2018;20:147.
38. Moraes RB, Friedman G, Wawrzeniak C, Marques LS, Nagel FM, Lisboa TC,
etal. Vitamin D deficiency is independently associated with mortality among
critically ill patients. Clinics (Sao Paulo). 2015; 70: 326.
39. Venkatram S, Chilimuri S, Adrish M, Salako A, Patel M, Diaz-Fuentes G.
Vitamin D deficiency is associated with mortality in the medical intensive
care unit. Crit Care. 2011;15:R292.
40. Hu W, Liu D, Qin L, Wang L, Tang Q, Wang G. Decreasing serum
25hydroxyvitamin D levels and risk of early neurological deterioration in
patients with ischemic stroke. Brain and Behav. 2019;9:1227.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Selim et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2019) 55:80 Page 8 of 8
