Comparison of Nutech Functional Score with European Stroke Scale for Patients with Cerebrovascular Accident Treated with Human Embryonic Stem Cells: NFS for CVA Patients Treated with hESCs Geeta Shroff Director, Nutech Mediworld, New Delhi, India
Abstract Journal of Vascular and Interventional Neurology, Vol. 9
Purpose—Stem cell therapy is a promising modality for treatment of patients with chronic cerebrovascular accident (CVA) in whom treatment other than physiotherapy or occupational therapy does not address the repair or recovery of the lost function. In this study, the author aimed at evaluating CVA patients treated with human embryonic stem cell (hESC) therapy and comparing their study outcomes with globally accepted European Stroke Scale (ESS) to that with novel scoring system, Nutech functional score (NFS), a 21point positional and directional scoring system for assessing patients with CVA. Materials and Methods—Patients diagnosed with CVA were assessed with NFS and ESS before and after hESC therapy. NFS assessed the patients in the direction of 1–5 (bad to good), where 5 was considered as the highest possible grade (HPG). The findings were obtained for the patients who scored HPG, and had shown improvement by at least one grade. Results—Overall, 66.7% of patients scored HPG level on the NFS scale and about 62.5% of the patients scored HPG according to the ESS scale. Approximately, 52.2% patients showed an improvement of 100% (by at least one grade) on NFS scale. None of the patients showed 100% improvement in the alteration of the score by at least one grade when scored with ESS. Conclusion—NFS and ESS scores show that a large population of CVA patients was benefitted with hESC therapy. NFS was found to give more convincing results than ESS, and overcomes the shortcomings of ESS. Keywords Nutech functional score (NFS); European Stroke Scale (ESS); cerebrovascular accident (CVA); stroke; human embryonic stem cell (hESC)
1. Introduction Cerebrovascular accident (CVA) or stroke occurs due to the obstruction of blood supply caused by any blockage or rupture of an artery in the brain resulting in lack of oxygen and eventually death of neurons [1,2]. It can also be caused by hemorrhage of a burst vessel [3]. As per 2015 report by the American Heart Association (AHA), stroke occurs in people every 40 s and deaths due to stroke occurs every 4 min in USA. Approximately, 610,000 stroke events are the first time events and 185,000 are the recurrent ones (ischemic or hemorrhagic) [4].
It is quite challenging to manage the patients with acute ischemic stroke and provide them beneficial care; AHA and American Stroke Association have published various guidelines for managing and providing emergency care to the stroke patients, immediately after occurrence of stroke [5]. Though several conventional therapies are available for the treatment of stroke such as thrombolysis, neuroprotective drugs (calcium channel blockers, calcium chelators, free radical scavengers, and antioxidants), and the other treatment approaches have been applied for neuroprotection in pre-clinical models but
Vol. 9, No. 4, pp. 35–43. Published June, 2017. All Rights Reserved by JVIN. Unauthorized reproduction of this article is prohibited *Corresponding Author: Geeta Shroff, Nutech Mediworld, H-8, Green Park Extension, New Delhi 110016, India. Tel.: (91) 11-26565548; fax: (91) 11-46057841. [email protected].
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Journal of Vascular and Interventional Neurology, Vol. 9
these are not found to be effective enough when studied in clinical trials [2,6]. However, new research in stem cell transplantation is found to be helpful in the management of stroke in humans. Chang and colleagues reported a decrease in the gliosis and apoptosis of the brain cells after transplanting human embryonic stem cells (hESCs)-neural precursor cells (NPCs), suggesting their potential for regeneration of damaged neural tissue [7]. It has been proved in various studies that stem cells, when administered in stroke patients, help in restoring neurological functions in stroke conditions [8,9]. Being pluripotent, capable of self-renewal, and having the capacity of differentiating into other cell types, hESCs can replace damaged neurons [10,11]. The safety and efficacy of hESC therapy has been previously evaluated in 22 CVA patients, and these patients were assessed with the European Stroke Scale (ESS) before and after the therapy. A symptomatic improvement was observed in the patients after receiving hESC therapy [12]. Management of CVA depends on precise measurement of disease outcomes, which should include both the neurological as well as functional parameters of the patients. The various well-recognized stroke scales available for the assessment of CVA, viz., ESS, Cincinnati Stroke Scale, modified Rankin scale, National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, Glasgow coma scale, Hunt and Hess scale, Mathew Stroke Scale, and stroke-specific quality-of-life measure, are not found to be promising scoring systems to assess patients with CVA. These scales were inappropriate in explaining the patient’s psychosocial and functional status of health, were also lacking in adequate sensitivity, and were less defined in terms of level of improvement of patients [13–17]. Few items of NIHSS are found redundant due to high internal consistency of the scale. In addition, the scale provides inadequate information about exact condition of the stroke patient. For instance, the NIHSS score of “1” represents “excellent” outcome, but on assessment, the patient’s actual condition was not found to be excellent as per described from the score [17]. A new scoring system called Nutech functional score (NFS) has been developed, which overcomes these limitations and can assess all the neurological and functional symptoms that are associated with CVA. It is simpler, uniform, and efficient scoring system in contrast to ESS and able to assess the overall condition of patients, thus helps in better management of CVA patients [18]. In this study, the patients with CVA have been evaluated using NFS and ESS, before and after hESC therapy to check for the differences in the detailed improvement in the patients.
2. Materials and Methods 2.1. Study Population A written informed consent was obtained from the patients prior to the conduct of this study. The patients who were previously diagnosed with CVA elsewhere and have not received any kind of hESC therapy before admitting to the hospital were included in this study. Pregnant and lactating women were excluded from this study. 2.2. Study Design hESCs were derived from a single, spare, expendable, and pre-implantation stage in vitro fertilized ovum. The safety and efficacy of these cell lines has been previously established [19]. This study was conducted in accordance with the approval provided by the Independent Institutional Ethics Committee. The treatment schedule consisted of six treatment phases having gap phases in between [12]. Briefly, a test dose of 0.05 mL was given subcutaneously to check for any hypersensitivity, pain, or inflammation at the site of injection (within 24 h). Intensive dosing was started within 24 h when no hypersensitivity reactions occurred in the patients. In the treatment phase, 0.25 mL of hESCs was given for eight weeks, twice daily. An intravenous infusion of hESCs diluted in 100-mL normal saline was given every 10 days. Furthermore, a dose of hESCs was given via supplemental routes (caudal, deep spinal, brachial plexus, and epidural) by random exchange for every 5–14 days. The patients were also given physiotherapy and occupational therapy simultaneously. NFS and ESS scores for the patients were documented before and after the treatment by the concerned doctor or physiotherapist. The results were recorded for the patients whose scores reached highest possible grade (HPG) (i.e., 5 in case of NFS) and whose condition showed improvement by at least one grade at the end of therapy.
3. Results 3.1. Study Patients Of the 24 CVA patients included in this study, nine were women. The mean age of the patients was 60.5 years. 3.2. Measurements for Patients’ Scores using NFS and ESS (Table 1) 3.2.1. Patients who Scored Less than HPG at Baseline and Reached HPG at the End of Ther-
Shroff
37
Table 1. Comparison between Nfs and Ess for Number of Parameters that Scored
Abstract Journal of Vascular and Interventional Neurology, Vol. 9
Purpose—Stem cell therapy is a promising modality for treatment of patients with chronic cerebrovascular accident (CVA) in whom treatment other than physiotherapy or occupational therapy does not address the repair or recovery of the lost function. In this study, the author aimed at evaluating CVA patients treated with human embryonic stem cell (hESC) therapy and comparing their study outcomes with globally accepted European Stroke Scale (ESS) to that with novel scoring system, Nutech functional score (NFS), a 21point positional and directional scoring system for assessing patients with CVA. Materials and Methods—Patients diagnosed with CVA were assessed with NFS and ESS before and after hESC therapy. NFS assessed the patients in the direction of 1–5 (bad to good), where 5 was considered as the highest possible grade (HPG). The findings were obtained for the patients who scored HPG, and had shown improvement by at least one grade. Results—Overall, 66.7% of patients scored HPG level on the NFS scale and about 62.5% of the patients scored HPG according to the ESS scale. Approximately, 52.2% patients showed an improvement of 100% (by at least one grade) on NFS scale. None of the patients showed 100% improvement in the alteration of the score by at least one grade when scored with ESS. Conclusion—NFS and ESS scores show that a large population of CVA patients was benefitted with hESC therapy. NFS was found to give more convincing results than ESS, and overcomes the shortcomings of ESS. Keywords Nutech functional score (NFS); European Stroke Scale (ESS); cerebrovascular accident (CVA); stroke; human embryonic stem cell (hESC)
1. Introduction Cerebrovascular accident (CVA) or stroke occurs due to the obstruction of blood supply caused by any blockage or rupture of an artery in the brain resulting in lack of oxygen and eventually death of neurons [1,2]. It can also be caused by hemorrhage of a burst vessel [3]. As per 2015 report by the American Heart Association (AHA), stroke occurs in people every 40 s and deaths due to stroke occurs every 4 min in USA. Approximately, 610,000 stroke events are the first time events and 185,000 are the recurrent ones (ischemic or hemorrhagic) [4].
It is quite challenging to manage the patients with acute ischemic stroke and provide them beneficial care; AHA and American Stroke Association have published various guidelines for managing and providing emergency care to the stroke patients, immediately after occurrence of stroke [5]. Though several conventional therapies are available for the treatment of stroke such as thrombolysis, neuroprotective drugs (calcium channel blockers, calcium chelators, free radical scavengers, and antioxidants), and the other treatment approaches have been applied for neuroprotection in pre-clinical models but
Vol. 9, No. 4, pp. 35–43. Published June, 2017. All Rights Reserved by JVIN. Unauthorized reproduction of this article is prohibited *Corresponding Author: Geeta Shroff, Nutech Mediworld, H-8, Green Park Extension, New Delhi 110016, India. Tel.: (91) 11-26565548; fax: (91) 11-46057841. [email protected].
36
Journal of Vascular and Interventional Neurology, Vol. 9
these are not found to be effective enough when studied in clinical trials [2,6]. However, new research in stem cell transplantation is found to be helpful in the management of stroke in humans. Chang and colleagues reported a decrease in the gliosis and apoptosis of the brain cells after transplanting human embryonic stem cells (hESCs)-neural precursor cells (NPCs), suggesting their potential for regeneration of damaged neural tissue [7]. It has been proved in various studies that stem cells, when administered in stroke patients, help in restoring neurological functions in stroke conditions [8,9]. Being pluripotent, capable of self-renewal, and having the capacity of differentiating into other cell types, hESCs can replace damaged neurons [10,11]. The safety and efficacy of hESC therapy has been previously evaluated in 22 CVA patients, and these patients were assessed with the European Stroke Scale (ESS) before and after the therapy. A symptomatic improvement was observed in the patients after receiving hESC therapy [12]. Management of CVA depends on precise measurement of disease outcomes, which should include both the neurological as well as functional parameters of the patients. The various well-recognized stroke scales available for the assessment of CVA, viz., ESS, Cincinnati Stroke Scale, modified Rankin scale, National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, Glasgow coma scale, Hunt and Hess scale, Mathew Stroke Scale, and stroke-specific quality-of-life measure, are not found to be promising scoring systems to assess patients with CVA. These scales were inappropriate in explaining the patient’s psychosocial and functional status of health, were also lacking in adequate sensitivity, and were less defined in terms of level of improvement of patients [13–17]. Few items of NIHSS are found redundant due to high internal consistency of the scale. In addition, the scale provides inadequate information about exact condition of the stroke patient. For instance, the NIHSS score of “1” represents “excellent” outcome, but on assessment, the patient’s actual condition was not found to be excellent as per described from the score [17]. A new scoring system called Nutech functional score (NFS) has been developed, which overcomes these limitations and can assess all the neurological and functional symptoms that are associated with CVA. It is simpler, uniform, and efficient scoring system in contrast to ESS and able to assess the overall condition of patients, thus helps in better management of CVA patients [18]. In this study, the patients with CVA have been evaluated using NFS and ESS, before and after hESC therapy to check for the differences in the detailed improvement in the patients.
2. Materials and Methods 2.1. Study Population A written informed consent was obtained from the patients prior to the conduct of this study. The patients who were previously diagnosed with CVA elsewhere and have not received any kind of hESC therapy before admitting to the hospital were included in this study. Pregnant and lactating women were excluded from this study. 2.2. Study Design hESCs were derived from a single, spare, expendable, and pre-implantation stage in vitro fertilized ovum. The safety and efficacy of these cell lines has been previously established [19]. This study was conducted in accordance with the approval provided by the Independent Institutional Ethics Committee. The treatment schedule consisted of six treatment phases having gap phases in between [12]. Briefly, a test dose of 0.05 mL was given subcutaneously to check for any hypersensitivity, pain, or inflammation at the site of injection (within 24 h). Intensive dosing was started within 24 h when no hypersensitivity reactions occurred in the patients. In the treatment phase, 0.25 mL of hESCs was given for eight weeks, twice daily. An intravenous infusion of hESCs diluted in 100-mL normal saline was given every 10 days. Furthermore, a dose of hESCs was given via supplemental routes (caudal, deep spinal, brachial plexus, and epidural) by random exchange for every 5–14 days. The patients were also given physiotherapy and occupational therapy simultaneously. NFS and ESS scores for the patients were documented before and after the treatment by the concerned doctor or physiotherapist. The results were recorded for the patients whose scores reached highest possible grade (HPG) (i.e., 5 in case of NFS) and whose condition showed improvement by at least one grade at the end of therapy.
3. Results 3.1. Study Patients Of the 24 CVA patients included in this study, nine were women. The mean age of the patients was 60.5 years. 3.2. Measurements for Patients’ Scores using NFS and ESS (Table 1) 3.2.1. Patients who Scored Less than HPG at Baseline and Reached HPG at the End of Ther-
Shroff
37
Table 1. Comparison between Nfs and Ess for Number of Parameters that Scored
