Volume 03 Issue 04-2023
34
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
ABSTRACT
This article discusses the comparative analysis of the clinical efficacy of combined neuroprotection in patients with
ischemic stroke on the background of COVID-19. To study the effect of the developed measures for drug and non-drug
therapy, which included exercises (exercise therapy), patients were observed for the first 3 months of treatment. The
second subgroup MG-2 received standard therapy with observation at the same time. Exercise therapy was developed
in collaboration with instructors and rehabilitation specialists.
KEYWORDS
Comparative analysis, combined neuroprotection, ischemic stroke, background of COVID-19, non-drug therapy,
exercise therapy, treatment, standard therapy.
INTRODUCTION
In most modern medical scientific research, the
rehabilitation treatment of post-stroke patients is
characterized by the introduction of combined
neuroprotection (3,5,6,8,9). The main focus of
rehabilitation
treatment
with
combined
neuroprotection is on the ability of the nervous tissue
Research Article
COMPARATIVE ANALYSIS OF THE CLINICAL EFFICACY OF COMBINED
NEUROPROTECTION IN PATIENTS WITH ISCHEMIC STROKE ON THE
BACKGROUND OF COVID-19
Submission Date:
April 08, 2023,
Accepted Date:
April 13, 2023,
Published Date:
April 18, 2023
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume03Issue04-05
M. M. Yuldasheva
Tashkent Pediatric Medical Institute, Uzbekistan
E.N. Majidova
Tashkent Pediatric Medical Institute, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 03 Issue 04-2023
35
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
to structural and functional restructuring and
reorganization (1). Such a combination are nootropic
drugs with neurotransmitter properties, and drugs of
neuropeptide origin. The most famous of them are
“Citicoline” and “Edaravone” (4,4,7). In our opinion,
the combination of these drugs is interesting and
relevant, since the multidirectional properties of these
drugs can significantly increase the effectiveness of the
rehabilitation treatment of patients with ischemic
stroke.
Purpose of the study. To analyze the clinical efficacy of
combined neuroprotection in patients with ischemic
stroke on the background of COVID-19.
Material and research methods. Patients with AT and
CE subtypes of stroke were selected for the study at
this stage due to the presence of pronounced
neurological symptoms in them. When prescribing
drug therapy, the MG and CG groups were divided into
subgroups 1 and 2. MG-1 included 48 patients from the
study MG - 29 (61.5%) men and 19 (39.6%) women. MG-
2 included 30 patients - 19 (63.3%) men and 11 (36.7%)
women (v.6.1) CG-1 included 23 patients - 13 (56.5%)
men and 10 (43 .5% of women, CG-2 included 21 people
- 10 men (47.6%) and 11 (52.4%) women (v.1).
Table 1.
Subgroups of MG and CG depending on gender
Patients MG-2 and CG-2 received conventional therapy
(basic and differentiated). In addition to conventional
therapy, the following neuroprotective drugs were
added to patients MG-1 and CG-1:
Volume 03 Issue 04-2023
36
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
- Citicoline (Ceraxon, Takeda, Japan) was administered
at a dose of 1000 mg/day intravenously for 10 days;
- Edaravone (Xavron, Yuria-Pharm, Ukraine) in the form
of 30 mg of the drug (1 ampoule) twice a day, in the
morning and in the evening, by intravenous infusion for
30 minutes, 10 days.
To study the effect of the developed measures for drug
and non-drug therapy, which included exercises
(exercise therapy), patients were observed for the first
3 months of treatment. The second subgroup MG-2
received standard therapy with observation at the
same time. Exercise therapy was developed in
collaboration with instructors and rehabilitation
specialists.
To objectify the severity of the condition, the severity
of focal neurological deficit and assess the dynamics of
clinical parameters, the National Institutes of Health
Stroke Score Scale (NIHSS) was used, the degree of
functional recovery was assessed using the modified
Rankin scale, and the assessment of cognitive status
was measured using the Montreal Cognitive
Assessment Scale (MoCA). The data obtained indicate
the effectiveness of the combined neuroprotection of
“Citicoline” and “Edaravone” in the acute period of
ischemic stroke in comparison with conventional
therapy.
The survey was carried out by the method of
continuous research, the results of observations were
used. Statistical processing of clinical and instrumental
materials in accordance with the recommendations for
processing the results of biomedical research at a
significance level of p<0.05 was carried out using the
practical statistical package STATISTICA.
Research results. Neurological symptoms in most
patients were due to focal lesions of one of the
cerebral hemispheres. So, in MG-1 in 56.3% (27) patients
in the left hemisphere, the focus was in 43.8% (21) of
patients in the right hemisphere. In patients in MG-2,
the focus of ischemia was localized in 18 (61.5%)
patients - in the left hemisphere and in 40.0% (12)
patients - in the right hemisphere of the brain (Table
6.2). In CG-1 right hemispheric stroke (RHS) LHS was in
13 patients (56.5%), RHS was in 10 patients (43.5%), CG-
2 LHS was detected in 11 patients 952.4%), and RHS was
in 10 (47.6%) patients (vol. 2).
Table 2.
Distribution of patients in subgroups depending on the focus
Volume 03 Issue 04-2023
37
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Note: RHS - right hemisphere stroke, LHS - left hemisphere stroke.
In general, neurological symptoms and severity of IS
were more pronounced in MG compared to CG, which
can be explained by the presence in OH patients of a
new risk factor for endothelial dysfunction - COVID-19.
The dynamics of neurological symptoms before and
after treatment in the MG and HC is shown in Table 3.
When examining the cranial nerves (CN), gaze paresis
was noted in 13 (27.1%) in MG-1, in 7 (23.3%) in MG-2, in 9
(18.8%) in CG-1 and in 5 (16.7%) in CG-2, which regressed
after treatment in all patients. In earlier periods, gaze
paresis leveled out in patients of the CG-1 subgroup.
Neurological
symptoms
associated
with
the
appearance of a lesion in the brain were presented,
first of all, by signs of damage to the pyramidal tract on
the side opposite to the affected hemisphere. Thus,
central paresis of the VII pair - in the form of smoothing
of the nasolabial fold and the impossibility of
performing lower facial tests was detected in 45
(93.8%) in MG-1, in 26 (86.7%) in MG-2, in 20 (87 0%) in
CG-1 and in 18 (85.7%) in HC-2, which after treatment
regressed to HC on the background of neuroprotective
therapy (subgroup CG-1) much faster. The regression
of neurological symptoms in MG-1 was more effective
than in MG-
2 with a significant difference in the “gain
of i
mprovement”
-
Δ for many symptoms (t.6.3).
Hemiparesis of varying severity or hemiplegia was
present in a large number of patients, since we took
severe subtypes of IS-AT and CE to study the dynamics
of neurological symptoms. Thus, mild hemiparesis was
detected in 10 (20.8%) in MG-1, in 6 (20.0%) in MG-2, in 7
(30.4%) in CG-1 and in 7 (33, 3%) in CG-2, as seen in Table
6.3. mild paresis was more common in CG patients than
in MG patients (p<0.05). Severe hemiparesis was
detected in 17 (35.4%) in MG-1, in 12 (40.0%) in MG-2, in
8 (34.8%) in CG-1 and in 8 (38.1%) in CG-2. Hemiplegia
was in a fairly large number of patients in the MG
compared with the CG. Thus, hemiplegia was detected
Volume 03 Issue 04-2023
38
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
in 21 (43.8%) in MG-1, in 12 (40.0%) in MG-2, in 8 (34.8%)
in CG-1 and in 6 (28.6%) %) in CG-2.
Table 3.
Dynamics of neurological symptoms in patients with IS during treatment, depending on the history of COVID-19.
Hereinafter -
Note: Δ
-
dynamics of improvement in symptoms during treatment (%). “After treatment”
-
examination after 90 days.
During treatment, many patients experienced a
transformation of severe hemiparesis and hemiplegia
into mild hemiparesis and severe hemiparesis,
respectively. “Increase in improvement”
-
Δ in
subgroups MG-1 and CG-1 was greater compared to
subgroups MG-2 and CG-2, respectively, and had
significant differences (v.3).
Volume 03 Issue 04-2023
39
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Pathological reflexes were characteristic of most of
the examined patients: in 46 (95.8%) in MG-1, in 29
(96.7%) in MG-2, in 20 (86.9%) in CG-1 and in 18 (85.7%) in
CG-2. After treatment, the percentage of patients with
pathological reflexes decreased in MG-1 by 25.0%, in
MG-2 by 13.3%, in CG-1 by 17.4%, in CG-2 by 14.3%. With
significant differences between subgroups MG-1 and
MG-2 and CG-1 and CG-2.
Among other focal neurological symptoms in the
examined patients, there were violations of sensitivity
on the side opposite to the affected hemisphere - in 42
(87.5%) in MG-1, in 24 (80.0%) in MG-2, in 19 (82.6%) %) in
CG-1 and in 17 (81.0%) in CG-2. In the dynamics against
the background of treatment, there was an
improvement
in
symptoms
(hemihypesthesia
regressed) by 16.7% in MG-1, by 13.3% in MG-2, by 13.0%
in CG-1 and by 4.5% in CG-1. 2. Significantly good
regression of hemihypesia was observed in subgroups
with the addition of neuroprotective therapy (v.3).
Meningeal symptoms were not detected in patients.
Dysfunction of the pelvic organs was expressed in
urination disorders in the form of urinary incontinence
of central origin, stool retention and was observed in 7
(14.6%) in MG-1, in 4 (13.3%) in MG-2, in 3 (20, 8%) in CG-1
and 5 (23.8%) in CG-2. Improvement of this
symptomatology in MG-1 was observed by 12.5%, in MG-
2 by 13.0%, in CG-1 by 9.5%. There were no significant
differences in this category of symptoms.
Cortical speech disorders were observed in 10 (20.8%)
in MG-1, in 5 (10.4%) in MG-2, in 4 (17.4%) in CG-1 and in 5
(23.8% ) in CG-2. On the background of treatment, a
good dynamics was observed in the subgroups MG-1
and CG-2 (p<0.05).
According to the research results, it can be noted that
the transferred COVID-19 slowed down the recovery of
impaired functions, which is especially evident in MG-2
compared to CG-2, despite standard therapy and
exercise therapy. During treatment with the addition
of
neuroprotective
therapy,
there
was
an
improvement in symptoms in both groups with
significant differences in many symptoms.
Volume 03 Issue 04-2023
40
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Здесь и далее: Примечание: достоверность различий *
-
р
˂
0,05; **-
р
˂
0,005.
Figure 1. Dynamics of indicators on the Rankin scale over the observation period.
According to the Rankin scale in MG-1 and MG-2 there
were initially high scores -4.6+1.2 and 4.5+1.1 points,
respectively. During treatment, the scores significantly
decreased to 2.9+0.2 and 3.1+0.5, respectively. Prior to
treatment in the acute period, the Rankin scores in CG-
1 and CG-2 were significantly lower compared to MG-1
and MG-2. But after treatment, positive dynamics was
also observed in these subgroups, and based on Figure
1, in groups where patients received additional
neuroprotective therapy, a rapid and significant
regression of symptoms was observed.
According to the NIHSS scale used to determine the
level of neurological deficit in MG-1 and MG-2, the
following indicators were initially -23.52 and 23.68
points, respectively. In the dynamics against the
background of treatment, the indicators improved,
this was especially noticeable in the MG-1 subgroup
(p<0.005) - 16.47 and 17.61, respectively. In subgroups
CG-1 and CG-2, the NIHSS scores were 18.23 and 18.59
points, respectively, after rehabilitation measures -
14.28 and 15.12 points, respectively. In these subgroups,
it is also noticeable that patients on the background of
neuroprotection showed better results on the NIHSS
scale.
Volume 03 Issue 04-2023
41
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Figure 2. Dynamics of changes in indicators on a scale over the observation period.
According to the MoCA scale in the MG-1 mental status
assessment conducted after treatment, the average
value of the indicator is 20.3 ± 1.8 points, which
corresponds to moderate cognitive impairment and is
(20.5 ± 2.17) (Fig. 3) . When ranking the results of the
MoCA scale for assessing the mental status in MG-1, the
test result significantly improved - 24.6+1.3 points
(p<0.05).
Figure 3. Dynamics of changes in indicators on the MoCa scale for the observation period.
Volume 03 Issue 04-2023
42
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
In MG-2, there was also a positive dynamics of the
results of the MoCA scale before and after treatment -
21.8+1.6 and 23.9+0.9 points, no significant differences
were found. In CG-1 and CG-2, initially the results of the
MoCA scale were 22.5+1.8 and 22.1+1.2 points,
respectively. During the treatment, positive dynamics
was also observed - 25.8+1.5 and 25.2+1.7, respectively,
no significant differences were found (Fig. 3).
When detailing the results of testing on the MoCA
scale, in general, the examined patients were
dominated by changes in the executive function of
drawing a broken line, optical-spatial disorders, and
worsening of delayed word reproduction (hearing-
speech memory). At the same time, auditory-verbal
memory disorders were more often observed in
patients with MG.
Table 4
Dynamics of changes in indicators on the MoCa scale (detailed)
In the MG, psycho-emotional disorders were more
common in the form of dysphoria, irritability,
demonstrative behavior, a decrease in the level of
attention and faster exhaustion when performing a
task.
Volume 03 Issue 04-2023
43
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
When detailing the results of the MoCa scale for
assessing the mental status in MG-1, cognitive
impairments were observed in a larger number of
patie
nts in the categories “Visual
-
constructive praxis”,
“Name
of
images”,
“Attention”,
“Speech”,
“Abstraction”,
“Delayed
reproduction”,
“Orientation”
- 41.7%, 41.7%, 58.3%, 27.1%, 52.1%, 60.4%,
12.5%, respectively, which is significantly more frequent
compared to CG-1, where for these categories, the
distribution of percentages was as follows - 34.8%,
26.1%, 26.1%, 21.7%, 34.8%, 17.4%, 8.7%, respectively (p <
0.05). Against the background of treatment in
subgroups of patients who received neuroprotective
therapy, positive dynamics was observed in a larger
number of patients compared with subgroups of both
groups, where only standard therapy was used (t.4).
CONCLUSION
Thus, the results of the study of indicators of
neurological status and cognitive sphere showed that
patients with hemispheric ischemic stroke who
underwent
COVID-19
have
more
pronounced
neurological symptoms and cognitive deficits. Three
months after treatment, patients with hemispheric
ischemic stroke who received neuroprotective therapy
showed a significant trend towards a decrease in
cognitive deficit in patients in the recovery period of an
ischemic stroke. In the subgroups of patients who
were on standard therapy, a slower dynamics of
recovery of the neurological status and cognitive
sphere was observed. Probably, such a not so
pronounced picture of recovery was associated with
insufficient standard treatment for this category of
patients, due to the aggravation of the transferred
COVID-19.
REFERENCES
1.
Baer,
M.
Neuroprotection:
models,
mechanisms, therapy / M. Baer. - Moscow:
BINOM. knowledge laboratory,2011.
–
P. 429.
2.
Domashenko M.A., Maksimova M.Yu., Sergeev
D.V., Piradov M.A. Citicoline in the treatment of
ischemic disorders of cerebral circulation // BC.
2013. № 30. P. 1540–
1542.
3.
Lomonosov,
O.V.
Cerebral
strokes:
rehabilitation of patients and disabled people
of working age in the metropolis: Abstract of
the
thesis.
cand.
honey.
Sciences.
/
Lomonosova O.V. - St. Petersburg, 2021.
–
P. 24.
4.
Sergeev D.V., Piradov M.A. Citicoline in the
treatment of ischemic stroke - new evidence of
effectiveness // BC. 2012. № 31. P.1552–
1554.
5.
Starodubtseva O.S., Begicheva S.V. Analysis of
the incidence of stroke using information
technology // Fundamental research. 2012. № 8
(v. 2). P. 424
–
427
6.
Stakhovskaya, L.V. Stroke. Guide for doctors.
Edited by L.V. Stakhovskaya, S.V. Kotov. - 2014.
–
P. 400.
Volume 03 Issue 04-2023
44
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
04
P
AGES
:
34-44
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
7.
Overgaard K. The effects of citicoline on acute
ischemic stroke: a review // J. Stroke
Cerebrovasc. Dis. 2014. Vol. 23 (7). P.1764
–
1769.
8.
Jauch,
E.C.
Guidelines
for
the
early
management of patients with acute ischemic
stroke: a guideline for healthcare professionals
from the American Heart Association /
American Stroke Association / E.C. Jauch, J.L.
Saver, H.P. Adams et al. // Stroke. - 2013. - V.
44(3). - P. 870-947.
9.
Xin, T. Trends in hospitalizations and cost
associated with stroke by age, United States
2003-2012 / T. Xin, G.G. Mary, G. Cathleen, M.
Robert // International journal of stroke. - 2016.
- Vol. 11, Is. 8.
