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15астму в поеднанш з хрошчним обструктивним за-хворюванням легень: клшко-функцюнальна характеристика, ризики розвитку коморбвдно! патологи. Астма та алерпя, 3, 7-14.
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RAPID RESPONCE WITH USE IN RADIOSENSITIZER OF STEREOTACTIC RADIOSURGERY IN THE TREATMENT OF BRAIN METASTASES POSTERIOR FOSSA
Griazov A.
State Institution «Institute of neurosurgery named after academic A.P.Romodanov of NAMS of Ukraine», Kiev, Ukraine
Gryazov A.
P.L. Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine
Medvedovskaya Yu.
State Institution «Institute of neurosurgery named after academic A.P.Romodanov of NAMS of Ukraine», Kiev, Ukraine
ABSTRACT
The role of hypoxic radiosensitizers (RS), metronidazole (M) and nimorazole (N), during stereotactic radiosurgery (SRS) in the treatment of metastases (MTS) of the posterior fossa (PF) was studied. The results obtained during the first three weeks (7, 14, and 21 days after SRS) demonstrated the high efficiency of radiosurgery using MTS, in the form of a rapid decrease in tumor volume, swelling zone, and signs of mass effect, comparable to surgical resection.
Stereotactic radiosurgery + hypoxic radiosensitization (SRS+RS) was performed in 20 patients with metastases of posterior fossa, who took 2 g orally before a 2-hour radiosurgery session. metronidazole (12 patients), or 2g. nimorazole (8 patients). In 7 patients, the primary tumor was non-small cell lung cancer (NSCLC), in 6 - breast cancer (BC), in 4 - melanoma (ML) and in 3 - renal cell carcinoma (RCC).
Each patient was observed for 3 weeks, every 7 days. The control was carried out according to MRI. MRI data were compared before and after radiosurgery. Both linear dimensions and metastasis volume were measured, as well as a decrease in tumor volume as a percentage of the original volume. To compare the effect of treatment of SRS without the use of RS, a control group of 8 patients with metastases of PF who received SRS without prior administration of radiosensitization preparations was presented.
In all 20 patients, the size of metastases decreased already at the first MRI control, 7 days after SRS + M. On average, a decrease in the volume of metastases occurred by 40% of the initial volume (in the range from 20 to 60%) during the first 7 days after SRS + RS, by 46% (in the range from 24 to 68%) during 14 days and by 50 % (in the range from 30 to 70%) within 21 days after SRS + RS. Edema was completely reduced in 62.5% of foci after 7 days, in the remaining 37.5% it decreased by more than 50% 14 and 21 days after SRS + RS. Neurological status improved in all 20 patients during the first week after SRS + RS. There were no signs of local or remote tumor recurrence over the indicated period of time. Of the side effects apparently associated with taking metronidazole in two patients, hiccups were noted (on the second and third day after SRS + M).
In the control group, changes in the volume of metastases (increase or decrease) after SRS during the first three weeks did not occur.
The use of the metronidazole radiosensitizer during stereotactic radiosurgery significantly increases the effectiveness of the treatment of brain metastases, with a quick response to treatment, in the form of a decrease in the tumor volume, the area of perifocal edema and the elimination of signs of mass effect comparable to surgical resection. This is especially true for metastases of the posterior fossa, in which tumor recurrence after surgical resection and postoperative complications are more often observed.
Keywords: stereotactic radiosurgery, hypoxic radiosensitizers, metastases of the posterior fossa.
Introduction
The therapeutic effect of radiation therapy using linear accelerators for relatively large tumors more than a few centimeters in diameter is reduced to one third than for small tumors due to the presence of numerous hypoxic tumor cells and an abundance of antioxidant enzymes, including peroxidase and catalase. This is because approximately two-thirds of the therapeutic effect of linear accelerators is associated with the indirect action of x-rays and / or electrons on hydroxyl radicals in the cytoplasm and intracellular water molecules. Thus, in the absence of oxygen in tumor tissues, the effect of X-rays and electrons is reduced to one third of standard efficiency [1].
The so-called bioreductive agents are substances that are reduced by "biological" enzymes to active and toxic metabolites. The chemical nature of these substances is such that their metabolism is most active in the absence of oxygen, they have selectivity for anaerobic tumor tissue, on which their principle as a radiosensitizer is based [1,2]. Such hypoxic radiosensitizers include metronidazole and nimorazole, which, when cleaved in anaerobic tumor cells, generate reactive oxygen species [2].
There are not many articles in the world literature devoted to radiotherapy of brain metastases using met-ronidazole [3,4,5,6], where their role in the treatment of brain metastases is ambiguous, however, there are no works that would study the role of RS in carrying out SRS.
However, in 1994 the work of Acharya DK was published. , in which a retrospective analysis of the ra-diotherapeutic treatment of 717 patients with various oncological diseases in combination with metronida-zole was carried out. Metronidazole was used in a dosage of 2g, 4 hours before the radiotherapy session, for 5 days, for a total of 6-7 weeks. And according to the results of the study, a positive response of tumors to radiotherapy with metronidazole was noted [3]. On the contrary, in other works (Aiken R, Leavengood JM, Kim JH et al. 1984) on the use of metronidazole for irradiation of the whole brain (WBRT) brain metastases, it was noted that, on the one hand, the combination of WBRT with RS did not affect either on the median of survival, nor on the local and remote control of tumor growth, and on the other hand caused a number of side effects, including nausea and vomiting, because of which 10% of patients refused to take metronidazole during treatment [4]. This was confirmed by a randomized study by Eyre HJ, Ohlsen JD, Frank J at all, 1984, in which, in the group using WBRT alone, the average survival was 14 weeks, and in the group with WBRT + metronidazole, only 12 [5] or more a late 2009 study by Gustavo AV, Gustavo BM, Ellen C., at all, in which, by the example of a large group of patients (2013 patients with brain metastases), the average survival, local and
remote control of tumor growth in patients with WBRT and WBRT + were studied radiosensitizers (including metranidazole) and no reliable individuals in the group using radiosensitizers, with the exception of motexafin [6], the study of the therapeutic effect of which in combination with WBRT was carried out in other works in the treatment of multiple metastases with emphasis on neurocognitive functions during treatment, and further scientific work using metranidazole in combination with radiotherapy were deemed inappropriate [6,7].
Material and methods
For the period 2012-2017 (five years) at our institute, stereotactic radiosurgery was performed for patients with metastases in metranidazole - 12 patients and nimrazole - 8 patients.
In 8 patients, non-small cell lung cancer (NSCLC) was the primary tumor, in 6 - breast cancer (BC), in 4 -melanoma (ML) and in 3 - renal cell carcinoma (RCC). Patients were 11 men and 9 women. The average age was 55 years (ranging from 30 to 80 years). In 7 cases, there was a single (solitary) metastasis, in 5 - single (23 metastases) and in 8 - multiple metastases (from 4 to 12 lesions).
Each patient was observed for 3 weeks, every 7 days. With a small tolerance in 3 cases (for 2-3 days). The control was carried out according to MRI. MRI data were compared before and after radiosurgery. Both linear dimensions and metastasis volume were measured, as well as a decrease in tumor volume as a percentage of the original volume.
The treatment was carried out on a linear accelerator "Trilogy" (Varian, USA). Patients underwent fixation of the stereotactic frame, or the application of a BrainLAB thermoplastic mask and topometric CT preparation using the BrainLAB localizer. Planning was carried out on the iPlan workstation using MRI and CT data. The IMRT + Dyn Arc technique was used. 4 hours before SRS, patients took 4 oral metronidazole capsules (500 mg each) with a total dosage of 2 g, or a similar dose dosage nimrazole capsule. All patients tolerated treatment well.
Results
The most significant changes according to MRI data were already observed during the first 7 days in two patients with metastases to the brain of non-small cell lung cancer (NSCLC). Moreover, in one patient the metastasis volume for the first 7 days decreased by more than 7 cm3, which amounted to 27% of the initial volume (Fig. 1), for 14 days - by 10 cm3 (Fig. 2), for 21 days - by 14 cm3, then there are more than 50% of the original volume (Fig. 3). In another patient with NSCLC solitary metastasis, 7 days after SRS + M, the tumor volume decreased by 3 cm3, which amounted to 32% of the initial metastasis volume (Fig. 4) and in one patient by 2.587 cm3, which amounted to 20% of the primary volume (fig. 5). In a patient with melanoma
metastasis, the tumor volume decreased by 4 cm3 in the their volume decreased by more than 50%, the edema first 7 days, which amounted to 25% of the initial tumor zone was completely reduced (Figs. 7-8). In a patient volume (Fig. 6). In a patient with metastases of breast with 6 metastases of NSCLC 10 days after SRS + M, cancer (number 3), a decrease in foci after SRS + M there was a decrease in the size of all metastases by an was observed every subsequent 7 days, after 21 days average of 46.1% (Table 1).
Table 1.
MRI data of 6 brain metastases in a patient with NSCLC before and 10 days after SRS+M
№ tumor V before SRS+M (sm3) and dosis(Gr) V after SRS+M (10 day) in sm3 Volume reduction (percent) Reduction of the area of edema (in percent) Reduction of signs of mass effect Contrast reduction
Tumor 1 0,043 (12,5) 0,017 60 96 + +
Tumor 2 3,588 (12) 2,305 36 44 + +
Tumor 3 0,999 (12) 0,505 49 100 - +
Tumor 4 0,250 (12) 0,117 53 86 + +
Tumor 5 11,389 (11) 8,781 23 70 + -
Tumor 6 0,925 (12) 0,407 56 100 + +
Mean 2,865 (12Tp) 2,022 46,1 82,6 + +
Patients tolerated the treatment well. Neurological status improved in all patients during the first 7 days. Of the side effects after taking metronidazole, hiccups were noted on days 2 and 3 after SRS + M.
Treatment planning, treatment, and follow-up
All patients were initially examined by a neurosurgeon of a specialized clinic, and then by a radiation therapist, or the head of the department of radio neurosurgery, the final decision on radiosurgery was made by a multidisciplinary consultation, which included an oncologist, neurosurgeon-oncologist and chemotherapist.
The time of the first imaging was determined by the treating radiation therapist, according to the algorithm of the neuroimaging technique for monitoring patients after SRS. During the first 6 months, the department practiced more frequent MRI scans, every week for the first month, and then after 6 and 12 weeks, but the results showed that the peak of the exponent of an early decrease in tumor volume falls on the first week, when the average is 50 % of the treated foci decrease on average by 50% (Fig. 1)._
50% - fl
40% - rT
30% - km_
20% - rl | , -
10% -
0% ■ ■ v m
F-1-1-1-1 1 week 2 week 3 week 4 week
Fig. 1 Exponent for the reduction of metastases during the first 4 weeks after SRS
1 week - 50% (95% confidence interval 1.2100.0)
2 weeks - 20% (95% confidence interval 3.9336.07)
3 weeks - 15% (95% confidence interval 3.6-26.4)
4 weeks - 15% (95% confidence interval 1.2-28.8)
Therefore, the first week was chosen as the most
significant in the percentage exponent of the tumor's early response to SRS, as well as 6 and 12 weeks after SRS, as the generally accepted standard observation periods.
Patients were observed until death or until the observation stopped for other reasons.
Data measurement
Tumor volume analysis was performed using a T1-weighted post-contrast image with a slice thickness of 1 mm. All volume measurements for objectivity of calculations were carried out by an independent radiologist who did not have information on the patient at the workstation and radiation therapist at the planning station. Pictures were randomly selected from the total number of patients available and time points in order to limit bias during measurements. In patients with multiple metastases (> 4), only 4 of the largest metastases were measured.
Tumors were distributed at each subsequent point in time as follows:
* decrease (decrease by >20%)
* stability (± 20% of the original volume)
* increase in volume by > 20% compared to the original.
The observation was carried out: firstly, to compare the results of an early and quick response in groups with and without radiosensitization, and secondly, to exclude local and remote tumor recurrence and analyze the results of overall survival in groups.
A В
Fig. 2 A 52-year-old patient with solitary metastasis of NSCLC in the left hemisphere of the cerebellum. MRI (post-contrast T1VI) before (A) and after 7 days after SRS+M (B). The volume decreased by 27%, the area of
edema was reduced.
A B
Fig. 3 The same patient. MRI before (A) and 14 days after SRS+M (B)
HfifO
#. > W
• ; ; v
A B
Fig. 4. The same patient. MRI data before (A) and 21 days after SRS+M (B). From 26,200 cm3 the volume of metastasis as a whole decreased to 12 cm3 (by more than 14 cm3 in 21 days).
m j®
, 0 if * ;
A B C D
Fig. 5. The woman is 42 years old. Solitary metastasis of breast cancer in the left hemisphere of the cerebellum. MRI before SRS (A) and after SRS+M, in a week (B), 12 weeks (C) and 12 months (D). Within a week, the initial metastasis volume decreased from 22.0 cm3 to 6.8 cm3 (30.9%). After 12 weeks, the complete response (a small area of scar tissue remains), after 12 months, a small local expansion of the subarachnoid space at the tumor site. Prior to SRS, the KPS 60 index (pronounced stato-coordination disorders and speech impairment). A week later, neurological symptoms regressed. KPS increased from 60 to 90 points.
А B C D
Fig. 6. A 40-year-old patient with multiple breast cancer metastases. MRI data before (A), after 7 (B) 14 (C) and 21 days after SRS+M (D.) The focal volume decreased significantly. The area of edema was reduced after
7 days.
A B C D
Fig. 7. A 36-year-old patient with multiple breast cancer metastases (12 lesions). The treatment was carried out in three fractions of 7 Gy. MRI before fSRS (A), a week after fSRS+M (B), 3 weeks (C) and 6 weeks (D). Complete regression offoci in the right hemisphere of the cerebellum and in the brainstem. In general, the complete
answer is ten out of twelve metastasis. The clinical status showed significant improvement (there were pronounced stato-coordinating disorders, visual and speech disorders, functional dependence before SRS), a significant regression of neurological symptoms a week after SRS, KPS rose from 60 to 90 points.
ABC
Fig. 8. The man is 60 years old. Solitary metastasis of colorectal cancer. MRI before SRS (A) and after SRS+N
after a week (B) and 6 weeks (C).
A B C
Fig. 9. A woman with single breast cancer metastases, including in the brain stem. MRI before SRS (A) and after fSRS+N a week (B) and 12 weeks (C). Reduction of the lesion a week after fSRS+N from the initial volume from
9.0 cm3 to 4.0 cm3 (55.5%). Full answer in 12 weeks.
Discussion
Since in the world literature we did not find similar works on the single use of metronidazole (M) for single-fraction stereotactic radiosurgery in the treatment of brain metastases, we proceeded in determining the dosage of the drug from the work on the use of metra-nidazole for total brain irradiation [3,4,5,6 ]. That is why it was decided to use a dose of 2g. The first patient was a patient with non-small cell lung cancer (NSCLC).
Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality and the most common source of brain metastases. It is estimated that 30 to 50% of patients with lung cancer undergo metastasis to the brain during the course of the disease [8[. Without treatment, patients with metastases to the NSCLC brain have a median survival of 4 weeks and almost all die due to intracranial progression of the process, and not because of the development of the primary tumor [9]. Management and treatment of patients with metastatic
brain tumors are complex and depend on several factors, including: age, Karnowski status, number of metastases and control of the growth of the primary tumor. Treatment options for NSCLC metastases may include: WBRT and SRS [10]. However, a number of randomized trials showed an adverse effect of WBRT on neu-rocognitive functions, which, in turn, correlate with a decrease in the quality of life [8,9,10]. In contrast, SRS provides great benefits in locally controlling tumor growth, with little risk of neurological disorders [10,11].
The problem during SRS remains the decision on the choice of dose for large metastases [12].
We took into account the experience of our colleagues and the data of world literature, as well as the recommended RTOG protocols for tumors larger than 3 cm. Therefore, in the treatment of the first patient, based on the size of the metastasis (more than 26 cm3), the localization of the process in the PF, near the brain stem, we limited ourselves to the prescribed dose of 12 Gy [13], as well as in two cases with the presence of
multiple metastases (number 8), the prescribed doses in radiosurgical treatment of multiple metastases [14].
In addition, taking into account the literature data that a number of radiosensitizer preparations (such as metronidazole) increase the effectiveness of radiation therapy for malignant tumors, overcoming their hypox-icity, by saturating O2, we decided to use metronida-zole once in single-fraction SRS in order to determine the effectiveness of its role as a radiosensitizer.
The surprise after SRS + M of the first patient was the effect of a rapid decrease in tumor volume after 7 days. Further observation showed a decrease in metastasis after 14 days by another 3 cm3. Despite the fact that we determined a decrease in the volume of metastasis in 14 days by 10 cm3, the structure of the metastasis and even the shape practically did not change, and the diffusion coefficient (ADC) decreased from 1.2 to 1.0, apparently due to tumor cell densification. The decrease in tumor volume was due to the necrotic zone in the center of the focus. We have observed an effect that is best described by the term "tumor compression". And, most likely, it was a consequence of the action on metronidazole tumor cells, and not the actual radiosur-gical effect, the effect of which we expected no earlier than 4-6 weeks after SRS. Nevertheless, it was a significant reduction in tumor volume and complete reduction of the edema zone after 7 days that completely eliminated the signs of mass effect, which could lead to the development of occlusive hydrocephalus and posed a threat to the patient's life.
Further observations, however, showed that the size of metastases in NSCLC is also reduced due to the solid component of the tumor. So in another patient with a decrease in tumor volume by 32% in 7 days, this was due to the peripheral solid part of the tumor, the contrast intensity of which was almost halved. We also paid close attention to the perifocal zone of edema, signs of mass effect and the degree of contrast of the tumor. And in most cases, we observed either complete or partial reduction of the edema zone and signs of mass effect, with a decrease in the severity of contrast already 7 days after SRS + M.
The results of a quick response to SRS + M with NSCLC metastases have pushed us to use CPX + M for brain metastases of radioresistant melanoma and radiosensitive metastases of breast cancer, which also led to positive treatment results in the form of a quick response to SRS + M.
Thus, in our observations, the one-time use of metronidazole as a radiosensitizer, with stereotactic radiosurgery (SRS + M) of brain metastases, we found significant treatment efficacy in NSCLC, melanoma and breast cancer. It is worth considering that we considered the observation period during the first 3 weeks (until, as a rule, the expected SRS result without metronidazole within 4-6 weeks), precisely with the aim of observing a quick response to treatment and eliminating signs of a mass effect that pose a threat life of the patient. At the same time, we continue to monitor patients with the aim of local and remote control of tumor growth, followed by determination of median survival. Our plans also include SRS + M in patients with brain metastases in other primary tumors.
Conclusions
A single use of the metronidazole radiosensitizer during single-fraction stereotactic radiosurgery significantly increases the effectiveness of the treatment of brain metastases, with a quick response to treatment, in the form of a decrease in the tumor volume, the area of perifocal edema and the elimination of signs of mass effect comparable to surgical resection.
References
1. Acharya D.K. Role of metronidazole in radiation therapy (a review of 717 cancer cases). Indian J Med Sci1994 May;48(5):111-6.
2. Aiken R., Leavengood J.M., Kim J.H. et al. Metronidazole in the treatment of metastatic brain tumors. Results of a controlled clinical trial. J.Neuroon-col. 1984:2(2): 105-11.
3. Andrews D.W. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet/ Andrews D.W., Scott C.B., Sperduto P.W. [et al.] // 2004, 363:1665-1672.
4. Aoyama H., Shirato H., Tago M., et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295: 2483-2491, 2006.
5. Aoyama H., Tago M., Kato N., et al. Neu-rocognitive function of patients with brain metastases who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 68: 1388-1395, 2007.
6. Eyre H.J., Ohlsen J.D., Frank J. at all.: Randomized trial of radiotherapy versus radiotherapy plus metronidazole for the treatment of metastatic cancer to brain. Journal of Neuro-oncology 1984, 2:325-30.
7. Hall E.J. The oxygen effect and reoxygena-tion. In: Hall EJ, editor. Radiobiology for the Radiologist. 5th edition. J.B. Lippincott Co; Philadelphia, PA: 2000. pp. 91-111.
8. Harrison Harrison L.B., Chadha M., Hill R.J., Hu K., Shasha D. Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncologist 7 (6):2002. pp. 492-508.
9. Gustavo A.V., Gustavo B.M., Ellen C.F., at al. Whole brain radiotherapy with radiosensitizer for brain metastases. Jornal of Experemental&Clinical Cancer Research 2009, 28:1
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11. Meyers C.A., Smith J.A., Bezjak A., et al. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: Stereotactic Radiosurgery for Multiple Brain Metastases Journal of Radiosurgery and SBRT Vol. 1 2011 39 results of a randomized phase III trial. J Clin Oncol 22:157-165, 2004.
12. Molenaar R. et al. Relationship between volume, dose and local control in stereotactic radiosurgery
of brain metastasis. Br J Neurosurg,23(2009), pp.170178.
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14. Sahgal A, Barani IJ, Novotny J Jr, et al. Prescription dose guidelines based on physical criterion for multiple metastatic brain tumors treated with stereotac-tic radiosurgery. Int J Radiat Oncol Biol Phys 78: 605608, 2010.
ДИНАМ1КА ГЕМОДИНАМ1ЧНИХ ЗМ1Н У ХВОРИХ, ЩО ПЕРЕНЕСЛИ 1ШЕМ1ЧНИПЙ 1НСУЛЬТ, З Р1ЗНИМИ ПРОЯВАМИ НЕЙРОПСИХОЛОГ1ЧНИХ РОЗЛАД1В У В1ДНОВНОМУ
ПЕР1ОД1
Гудар'ян Ю.1.
ДЗ «Дтпропетровська медична академiя МОЗ Укра'ти»
(кафедра неврологИ)
THE DYNAMICS OF HEMODYNAMIC CHANGES IN PATIENTS WHO HAD A COURSE OF ISCHEMIC STROKE, WITH DIFFERENT MANIFESTATIONS OF NEUROPSYCHOLOGICAL
DISORDERS IN THE RECOVERY PERIOD
Gudarian Yu.
SI "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine "
(Department of Neurology)
АНОТАЦ1Я
Проведена УЗДГ у хворих у ранньому виновному перюда шсля перенесеного rneMi4Horo шсульту дозволила визначити неоднозначт клiнiко-допплepогpафiчнi змши захворювання. Церебральна гемоди-намiка в зонi сонних артерш (ВСА, СМА i ПМА) на бощ ураження характеризувалась бтш низькими показниками систолiчноi середньо! й максимально! лшшно! швидкостi кровотоку й найб№шою асимет-pieю кровотоку, нж з боку здорово! пiвкулi. Ця закономipнiсть спiввiдноситься з вiдомими даними лгге-ратури.
Установлено, що збiльшeння асиметрп кровотоку й наростання стpуктуpно-моpфологiчних судинних змш (зокрема атеросклерозу) асоцiйовано у хворих з iшeмiчним iнсультом поеднаними з основним захво-рюванням порушеннями аpтepiального тиску й системи гемостазу, змшами бiлкових фpакцiй кpовi, вмю-том глюкози в кpовi. Наявшсть у хворих з наслiдками iшeмiчного iнсульту перерахованих вiдхилeнь су-проводжуеться бiльш вираженим пpигнiчeнням цереброваскулярно! динашки, що характеризуеться зни-женням швидкосп кровотоку, ростом асимeтpii кpовообiгу, особливо в СМА i ПМА артергях бiльшою мipою на стоpонi ураження, н1ж у здоpовiй пiвкулi. Установлено, що мiж показниками церебрально! гемо-динамiки й нeвpологiчним статусом юнуе пряма залeжнiсть (r = 68). Вщзначено, що бiльш значущi гемо-динамiчнi змiни в каротидному басейт в пацiентiв з помipними невролопчними розладами, менш суттевi - в оаб з легкими проявами невролопчно! патологii.
ABSTRACT
Doppler ultrasonography performed in patients in the early recovery period after an ischemic stroke made it possible to determine ambiguous clinical and dopplerographic changes in the disease. Cerebral hemodynamics in the zone of the carotid arteries (ICA, MCA and PCA) on the affected side was characterized by lower systolic average and maximum linear blood flow velocities and greater asymmetry of blood flow than on the healthy hemisphere. This pattern is consistent with the known literature.
It was established that an increase in the asymmetry of blood flow and an increase in structural and morphological vascular changes (in particular atherosclerosis) are associated in patients with ischemic stroke, combined with the main disease of disorders of blood pressure and hemostasis, changes in blood protein fractions, and blood glucose. The presence of these deviations in patients with the consequences of ischemic stroke is accompanied by a more pronounced inhibition of cerebrovascular dynamics, which are characterized by a decrease in blood flow velocity, an increase in asymmetry of blood circulation, especially in the MCA and PCA arteries, to a greater extent on the side of the lesion than in the healthy hemisphere. It was found that between the indicators of cerebral hemodynamics and neurological status, there is a direct relationship (r = 68). It was noted that more significant hemodynamic changes in the carotid pool in patients with moderate neurological disorders, less significant in individuals with mild manifestations of neurological pathology.
Ключовi слова: iшeмiчний шсульт, когнггивш розлади, церебральна гемодинашка.
Keywords: ischemic stroke, cognitive impairment, cerebral hemodynamics.
Актуальшсть дослвдження. Висока актуаль- високими показниками непрацездатносл й шваль нють проблеми iшeмiчного шсульту визначаеться дизаци хворих, розвитком цшого ряду ускладнень i широтою й подальшим зростанням захворюваносп, високою смертшстю [1,2,3].
