Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study

MAKK, Raluca; STANCİOİU, Felician

doi:10.14744/ejmo.2019.49036

Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study

Felician STANCİOİU, (Department of Clinical Research, Bio-Forum Foundation, Bucharest, Romania)

Raluca MAKK (Department of Neurology, Center for Neurological Rehabilitation “Maria” Sanpetru, Brasov, Romania)

Eurasian Journal of Medicine and Oncology

3 0

Yıl: 2019 Cilt: 3 Sayı: 3 Sayfa Aralığı: 167 - 181 Metin Dili: İngilizce DOI: 10.14744/ejmo.2019.49036 İndeks Tarihi: 22-04-2020

Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study

Öz:

Objectives: Recovery of motor function after moderate to severe stroke is challenging given the paucity of therapeuticchoices; we propose an effective treatment with a new combination of drugs which protect neuronal mitochondriafrom oxidative stress, inflammation, and subsequent apoptosis; also decrease excitotoxicity mostly by modulating thebrain derived neurotrophic factor (BDNF), insulin growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β).Methods: The new combination consists of medications approved for human use in multiple pathologies: glutathione,oxytocin, dimethylsulfoxide (DMSO), deproteinated veal serum (Actovegin), vitamins C, B1, B6, B12, which were administered intravenously in an open-label, pilot study. Motor function was evaluated with the National Institutes of HealthStroke Scale (NIHSS) in 15 consecutive hemiplegic patients initially and at 1 month after administering first intravenoustreatment, and subsequently.Results: When treatment was administered during days 10-35 post-stroke, motor improvement at 1 month evaluationpost-treatment (mean ΔNIHSS score=-3.6, n=5) was significantly better than when administered at 35-100 days poststroke (mean ΔNIHSS=-0.83, n=6, p=0.02), or when given after 3 months post-stroke (mean ΔNIHSS=0, n=4). Motorimprovements at 2 and 3 months post-treatment were seen only in the group treated at 10-35 days post-stroke, withone complete recovery of hemiplegia at 6 months.Conclusion: Excellent results were obtained in subacute stroke patients with hemorrhagic transformation of ischemic stroke, recommending it as a much needed addition to the current treatment options for stroke and moreample clinical trials.

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1.Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al; on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics–2018 update: a report from the American Heart Association. Circulation 2018;137:e67–e492.
2. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017;135:e146–e603.
3. Krishnamurthi RV, Moran AE, Feigin VL, Barker-Collo S, Norrving B, Mensah GA, et al.; GBD 2013 Stroke Panel Experts Group. Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Adults Aged 20-64 Years in 1990-2013: Data from the Global Burden of Disease 2013 Study. Neuroepidemiology 2015;45:190–202.
4. Quillinan N, Herson PS, Traystman RJ. Neuropathophysiology of Brain Injury. Anesthesiol Clin 2016;34:453–64.
5. Sifat AE, Vaidya B, Abbruscato TJ. Blood-Brain Barrier Protection as a Therapeutic Strategy for Acute Ischemic Stroke. AAPS J 2017;19:957–972.
6. Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017;38:1167–86.
7. Kellner CP, Sauvageau E, Snyder KV, et al. The VITAL study and overall pooled analysis with the VIPS non-invasive stroke detection device. J NeuroIntervent Surg 2018;10:1079–84.
8. http://bio-forum.net/PSIOM_10F.pdf Accessed November 22 2018.
9. Knecht T, Story J, Liu J, Davis W, Borlongan CV, Dela Peña IC. Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment. Int J Mol Sci 2017;18:2756.
10. Matei N, Camara J, McBride D, Camara R, Xu N, Tang J, et al. Intranasal wnt3a Attenuates Neuronal Apoptosis through Frz1/PIWIL1a/FOXM1 Pathway in MCAO Rats. J Neurosci 2018;38:787-6801.
11. Kofke WA, Ren Y, Augoustides JG, Li H, Nathanson K, Siman R, et al. Reframing the Biological Basis of Neuroprotection Using Functional Genomics: Differentially Weighted, Time-Dependent Multifactor Pathogenesis of Human Ischemic Brain Damage. Frontiers in Neurology 2018;9:497.
12. Stancioiu F, Catanas D. Neuropsychological, Post-Stroke Improvement with a New Combination of Approved Substances: A Case Series Report. International Journal of Clinical Medicine Research 2016;3:64–71.
13. Marí M, Morales A, Colell A, García-Ruiz C, Fernández-Checa JC. Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal 2009;11:2685–700.
14. Yin B, Barrionuevo G, Weber SG. Mitochondrial GSH Systems in CA1 Pyramidal Cells and Astrocytes React Differently during Oxygen-Glucose Deprivation and Reperfusion. ACS Chem Neurosci 2018;9:738–48.
15. Anderson MF, Nilsson M, Eriksson PS, Sims NR. Glutathione monoethyl ester provides neuroprotection in a rat model of stroke. Neurosci Lett 2004;354:163–5.
16. Jacob SW, Herschler R. Pharmacology of DMSO. Cryobiology 1986;23:14–27.
17. https://www.ema.europa.eu/ documents/orphan-designation/e u/3/05/263-public-summary-positive- opinion-orphan-des ignation-dimethyl-sulfoxide-treatment-severeclosed_en.pdf. Accessed November 15, 2018.
18. Jacob SW, de la Torre JC. Pharmacology of dimethyl sulfoxide in cardiac and CNS damage. Pharmacological Reports 2009;61:225–35.
19. Lu C, Mattson MP. Dimethyl sulfoxide suppresses NMDA- and AMPA-induced ion currents and calcium influx and protects against excitotoxic death in hippocampal neurons. Exp Neurol 2001;170:180–5.
20. Egorin MJ, Rosen DM, Sridhara R, Sensenbrenner L, Cottler-Fox M. Plasma concentrations and pharmacokinetics of dimethylsulfoxide and its metabolites in patients undergoing peripheral-blood stem-cell transplants. J Clin Oncol 1998;16:610–5.
21. Gurtovenko AA, Anwar J. Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide. J Phys Chem B 2007;111:10453–60.
22. Nasrallah FA, Garner B, Ball GE, Rae C. Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO). J Neurosci Res 2008;86:208–14.
23. Geron N, Meiri H. The fusogenic substance dimethyl sulfoxide enhances exocytosis in motor nerve endings. Biochim Biophys Acta 1985;819:258–62.
24. Huang SS, Chen C-L, Huang FW, Hou W-H, Huang JS. DMSO Enhances TGF-β Activity by Recruiting the Type II TGF-β Receptor From Intracellular Vesicles to the Plasma Membrane. Journal of cellular biochemistry 2016;117:1568–79.
25. Carletti F, Ferraro G, Rizzo V, Cannizzaro C., Sardo P. Antiepileptic effect of dimethyl sulfoxide in a rat model of temporal lobe epilepsy. Neuroscience Letters Vol 546, 24 June 2013, pp 31–35.
26. Sanmartín-Suárez C, Soto-Otero R, Sánchez-Sellero I, Méndez-Álvarez E. Antioxidant properties of dimethyl sulfoxide and its viability as a solvent in the evaluation of neuroprotective antioxidants. J Pharmacol Toxicol Methods 2011;63:209– 15.
27. Yi X, Liu M, Luo Q, Zhuo H, Cao H, Wang J, et al. Toxic effects of dimethyl sulfoxide on red blood cells, platelets, and vascular endothelial cells in vitro. FEBS Open Bio 2017;7:485–94.
28. de Abreu Costa, Lucas & Henrique Fernandes Ottoni, Marcelo & Geralda dos Santos, et al. Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes. Molecules 2017;22. pii: E1789.
29. Elisia I, Nakamura H, Lam V, Hofs E, Cederberg R, Cait J, et al. DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis. PLoS ONE 2016;11:e0152538.
30. Buchmayer F, Pleiner J, Elmlinger MW, Lauer G, Nell G, Sitte HH. Actovegin®: a biological drug for more than 5 decades. Wien Med Wochenschr 2011;161:80–8.
31. Meilin S, Machicao F, Elmlinger M. Treatment with Actovegin improves spatial learning and memory in rats following transient forebrain ischaemia. J Cell Mol Med 2014;18:1623–30.
32. Machicao F, Muresanu D, Hundsberger H, Guekht A. Pleiotropic neuroprotective and metabolic effects of Actovegin's mode of action. Journal of the neurological sciences 2012;322:222–7.
33. Yurinskaya MM, Astashkin E, Grachev SV, Vinokurov MG. Actovegin protects human neuroblastoma cells SK-N-SH from apoptosis induced by hydrogen peroxide through the PI3K and p38 MAPK signaling pathways. Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology 2016;10:68– 72.
34. Kanowski S, Kinzler E, Lehman E, Kuntz G. Confirmed Clinical Efficacy of Actovegin ® in Elderly Patients with Organic Brain Syndrome. Pharmacopsychiatry 1995;28:125–33.
35. Derev'yannykh EA, Bel'skaya GN, Knoll EA, Krylova LG, Popov DV. Experience in the use of Actovegin in the treatment of patients with cognitive disorders in the acute period of stroke. Neurosci Behav Physiol 2008;38:873–5.
36. Guekht A, Skoog I, Edmundson S, Zakharov V, Korczyn AD. ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment. Stroke 2017;48:1262–70.
37. https://clinicaltrials.gov/ct2/show/results/NCT01582854?sect=Xc0156#outcome6 accessed November 7, 2018.
38. Ullegaddi R, Powers HJ, Gariballa SE. B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke. Clin Sci (Lond) 2004;107:477–84.
39. Ullegaddi R, Powers HJ, Gariballa SE. Antioxidant supplementation with or without B-group vitamins after acute ischemic stroke: a randomized controlled trial. JPEN J Parenter Enteral Nutr 2006;30:108–14.
40. Wang L, Cui W, Nan G, Yu Y. Meta-analysis reveals protective effects of vitamin B on stroke patients. Translational Neuroscience 2015;6:150–6.
41. Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-Lowering Therapy and Stroke Risk, Severity, and Disability Additional Findings From the HOPE 2 Trial. Stroke 2009;40:1365–72.
42. Cavalieri M, Schmidt R, Chen C, Mok V, de Freitas GR, Song S, et al.; VITATOPS Trial Study Group. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy. Stroke 2012;43:3266–70.
43. Hankey GJ, Eikelboom JW, Yi Q, Lees KR, Chen C, Xavier D, et al.; VITATOPS trial study group. Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial. Lancet Neurol 2012;11:512–20.
44. Jadavji NM, Emmerson JT, MacFarlane AJ, Willmore WG, Smith PD. B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiol Dis 2017;103:89–100.
45. Jadavji NM, Emmerson JT, Shanmugalingam U, MacFarlane AJ, Willmore WG, Smith PD. A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke. Exp Neurol 2018;309:14–22.
46. May JM. Vitamin C transport and its role in the central nervous system. Subcell Biochem 2012;56:85–103.
47. Sotiriou S, Gispert S, Cheng J, Wang Y, Chen A, HoogstratenMiller S, et al. Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med 2002;8:514–7.
48. Shaghaghi MA, Kloss O, Eck P. Genetic Variation in Human Vitamin C Transporter Genes in Common Complex Diseases. Adv Nutr 2016;7:287–98.
49. Muñoz-Montesino C, Roa FJ, Peña E, González M, Sotomayor K, Inostroza E, et al. Mitochondrial ascorbic acid transport is mediated by a low-affinity form of the sodium-coupled ascorbic acid transporter-2. Free Radic Biol Med 2014;70:241–54.
50. Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med 2009;46:719–30.
51. Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis 2016;22:463–93.
52. Chatterjee IB, Majumder AK, Nandi BK, Subramanian N. Synthesis and some major functions of vitamin C in animals. Ann N Y Acad Sci 1975;258:24–47.
53. Subramanian VS, Sabui S, Subramenium GA. Tumor necrosis factor alpha reduces intestinal vitamin C uptake: a role for NFκB-mediated signaling. Am J Physiol Gastrointest Liver Physiol 2018;315:G241–G248.
54. Portugal CC, da Encarnação TG, Socodato R, Moreira SR, Brudzewsky D, Ambrósio AF, et al. Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-κB (NF-κB). J Biol Chem 2011;287:3860–72.
55. Ang A, Pullar JM, Currie MJ, Vissers MCM. Vitamin C and immune cell function in inflammation and cancer. Biochem Soc Trans 2018;46:1147–59.
56. Zhang M, Jativa DF. Vitamin C supplementation in the critically ill: A systematic review and meta- analysis. SAGE Open Med 2018;6:2050312118807615.
57. Carter SC. The Oxytocin-Vasopressin Pathway in the Context of Love and Fear. Front Endocrinol (Lausanne) 2017;8:356.
58. Bakos J, Srancikova A, Havranek T, Bacova Z. Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection. Neural Plast 2018;4864107.
59. Grace SA, Rossell SL, Heinrichs M, Kordsachia C, Labuschagne. Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology 2018;96:6–24.
60. Caruso S, Agnello C, Campo MG, Nicoletti F. Oxytocin reduces the activity of N-methyl-D-aspartate receptors in cultured neurons. J Endocrinol Invest 1993;16:921–4.
61. Banasiak KJ, Xia Y, Haddad GG. Mechanisms underlying hypoxia-induced neuronal apoptosis. Prog Neurobiol 2000;62:215– 49.
62. Nallamshetty S, Chan SY, Loscalzo J. Hypoxia: a master regulator of microRNA biogenesis and activity. Free Radic Biol Med 2013;64:20–30.
63. Cramer SC, Procaccio V; GAIN Americas; GAIN International Study Investigators. Correlation between genetic polymorphisms and stroke recovery: analysis of the GAIN Americas and GAIN International Studies. Eur J Neurol 2012;19:718–24.
64. Kim J-M, Stewart R, Park M-S, et al. Associations of BDNF Genotype and Promoter Methylation with Acute and LongTerm Stroke Outcomes in an East Asian Cohort. Jeltsch A, ed. PLoS ONE 2012;7:e51280.
65. Stewart JC, Cramer SC. Genetic Variation and Neuroplasticity: Role in Rehabilitation After Stroke. J Neurol Phys Ther 2017;41 Suppl:S17–S23.
66. Yue YH, Liu LY, Hu L, Li YM, Mao JP, Yang XY, et al. The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang. Lipids Health Dis 2017;16:120.
67. Gu L, Wu Y, Hu S, Chen Q, Tan J, Yan Y, et al. Analysis of Association between MAP2K4 Gene Polymorphism rs3826392 and IL-1b Serum Level in Southern Chinese Han Ischemic Stroke Patients. J Stroke Cerebrovasc Dis 2016;25:1096–101.
68. Zhang G, Li W, Guo Y, Li D, Liu Y, Xu S. MMP Gene Polymorphisms, MMP-1 -1607 1G/2G, -519 A/G, and MMP-12 -82 A/G, and Ischemic Stroke: A Meta-Analysis. J Stroke Cerebrovasc Dis 2018;27:140–152.
69. Wen D, Du X, Nie SP, Dong JZ, Ma CS. Association between matrix metalloproteinase family gene polymorphisms and ischemic stroke: a meta-analysis. Mol Neurobiol 2014;50:979– 85.
70. Wei LK, Au A, Menon S, Gan SH, Griffiths LR. Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke. J Stroke Cerebrovasc Dis 2015;24:2017–25.
71. Kumar A, Kumar P, Prasad M, Sagar R, Yadav AK, Pandit AK, et al. Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis. Neurol Res 2015;37:568–77.
72. Michels AJ, Hagen TM, Frei B. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu Rev Nutr 2013;33:45– 70.
73. He HY, Liu MZ, Zhang YL, Zhang W. Vitamin Pharmacogenomics: New Insight into Individual Differences in Diseases and Drug Responses. Genomics Proteomics Bioinformatics 2017;15:94–100.
74. Schleicher RL, Carroll MD, Ford ES, Lacher DA. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr 2009;90:1252–63.
75. Fain O, Pariés J, Jacquart B, Le Moël G, Kettaneh A, Stirnemann J, et al. Hypovitaminosis C in hospitalized patients. Eur J Intern Med 2003;14:419–25.
76. Cahill LE, El-Sohemy A. Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid. J Nutrigenet Nutrigenomics 2009;2:292–301.
77. de la Torre JC, Surgeon JW. Dexamethasone and DMSO in experimental transorbital cerebral infarction. Stroke 1976;7:577– 83.
78. de la Torre JC. Synergic activity of combined prostacyclin: dimethyl sulfoxide in experimental brain ischemia. Can J Physiol Pharmacol 1991;69:191–8.
79. Laha RK, Dujovny M, Barrionuevo PJ, DeCastro SC, Hellstrom HR, Maroon JC. Protective effects of methyl prednisolone and dimethyl sulfoxide in experimental middle cerebral artery embolectomy. J Neurosurg 1978;49:508–16.
80. Little JR, Spetzler RF, Roski RA, Selman WR, Zabramski J, Lesser RP. Ineffectiveness of DMSO in treating experimental brain ischemia. Ann N Y Acad Sci 1983;411:269–77.
81. Bardutzky J, Meng X, Bouley J, Duong TQ, Ratan R, Fisher M. Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model. J Cereb Blood Flow Metab 2005;25:968–77.
82. Karaça M, Kiliç E, Yazici B, Demir S, de la Torre JC. Ischemic stroke in elderly patients treated with a free radical scavenger-glycolytic intermediate solution: a preliminary pilot trial. Neurol Res 2002;24:73–80.
83. Hong JS, Kim JM, Kim HS. Correlation between ambulatory function and clinical factors in hemiplegic patients with intact single lateral corticospinal tract: A pilot study Medicine (Baltimore) 2016;95:e4360.
84. Font MA, Arboix A, Krupinski J. Angiogenesis, neurogenesis and neuroplasticity in ischemic stroke. Curr Cardiol Rev 2010;6:238–44.
85. Palma-Tortosa S, García-Culebras A, Moraga A, Hurtado O, Perez-Ruiz A, Durán-Laforet V, et al. Specific Features of SVZ Neurogenesis After Cortical Ischemia: a Longitudinal Study. Sci Rep 2017;7:16343.

APA	STANCİOİU F, MAKK R (2019). Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. , 167 - 181. 10.14744/ejmo.2019.49036
Chicago	STANCİOİU Felician,MAKK Raluca Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. (2019): 167 - 181. 10.14744/ejmo.2019.49036
MLA	STANCİOİU Felician,MAKK Raluca Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. , 2019, ss.167 - 181. 10.14744/ejmo.2019.49036
AMA	STANCİOİU F,MAKK R Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. . 2019; 167 - 181. 10.14744/ejmo.2019.49036
Vancouver	STANCİOİU F,MAKK R Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. . 2019; 167 - 181. 10.14744/ejmo.2019.49036
IEEE	STANCİOİU F,MAKK R "Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study." , ss.167 - 181, 2019. 10.14744/ejmo.2019.49036
ISNAD	STANCİOİU, Felician - MAKK, Raluca. "Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study". (2019), 167-181. https://doi.org/10.14744/ejmo.2019.49036

APA	STANCİOİU F, MAKK R (2019). Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. Eurasian Journal of Medicine and Oncology, 3(3), 167 - 181. 10.14744/ejmo.2019.49036
Chicago	STANCİOİU Felician,MAKK Raluca Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. Eurasian Journal of Medicine and Oncology 3, no.3 (2019): 167 - 181. 10.14744/ejmo.2019.49036
MLA	STANCİOİU Felician,MAKK Raluca Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. Eurasian Journal of Medicine and Oncology, vol.3, no.3, 2019, ss.167 - 181. 10.14744/ejmo.2019.49036
AMA	STANCİOİU F,MAKK R Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. Eurasian Journal of Medicine and Oncology. 2019; 3(3): 167 - 181. 10.14744/ejmo.2019.49036
Vancouver	STANCİOİU F,MAKK R Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study. Eurasian Journal of Medicine and Oncology. 2019; 3(3): 167 - 181. 10.14744/ejmo.2019.49036
IEEE	STANCİOİU F,MAKK R "Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study." Eurasian Journal of Medicine and Oncology, 3, ss.167 - 181, 2019. 10.14744/ejmo.2019.49036
ISNAD	STANCİOİU, Felician - MAKK, Raluca. "Post - Stroke Recovery of Motor Function with a New Combination of Medicines – A Pilot Study". Eurasian Journal of Medicine and Oncology 3/3 (2019), 167-181. https://doi.org/10.14744/ejmo.2019.49036