19 Nov 2022


Multiple sclerosis (MS) - Symptoms and causes

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The article “Association of Nonmyeloablative Hematopoietic Stem Cell Transplantation with Neurological Disability in Patients with Relapsing-Remitting Multiple Sclerosis” (Burt et al., 2019) highlights an improvement in neurological disability and other clinical outcomes for patients with relapsing-remitting multiple sclerosis (MS) when nonmyeloablative hematopoietic stem cell transplantation (HSCT). The multiple sclerosis patients employed in the study undertook a hematopoietic stem cell transplantation at Northwestern University. The study was aimed at studying the relationship of neurological disability for relapsing-remitting multiple sclerosis and hematopoietic stem cell transplantation that was nonmyeloablative (Burt et al., 2019). One of the study criteria was that the patients had to have relapsing-remitting multiple sclerosis, which is outlined as the critical relapses followed by complete or partial recovery and steady clinical symptoms between relapses. Some of the patients were treated off the research practice as they had secondary-progressive multiple sclerosis, which was outlined as the slow progression of disability in the presence or absence of superimposed relapses. The study findings demonstrated a positive association of nonmyeloablative HSTC with neurological disability in multiple sclerosis patients, which led to improvements in the neurological disability. 


Multiple sclerosis (MS) is a chronic illness that affects the central nervous system and is principally an immune-mediated disease. This disease has been declared to be the main cause of neurological disabilities amongst the majority of young adults in the world (Feng et al., 2019). Multiple sclerosis is majorly characterized by demyelination, neurodegenerative pathological processes, and inflammation. Currently, there is no identified medication or treatment to reverse the neurological disabilities and damages to the central nervous system caused by multiple sclerosis. However, some of the therapies used by physicians are believed to prevent the progression of neurological disabilities and also reduce relapses of multiple sclerosis. 

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The onset of multiple sclerosis is characterized by clinically isolated syndrome (CIS), which is a severe clinical episode that includes paresis, optic neuritis, fatigue, and paresthesia (Marzullo et al., 2019). The CIS later evolves into relapsing-remitting multiple sclerosis (RRMSS) phase, and after a delay of 15 to 20 years, it evolves into secondary-progressive multiple sclerosis phase, which can result in the permanent disability of the patient. The phases of the disease and the development of permanent disability in patients vary, highly because it depends on how individual patients respond to the available therapies. Neurologists are engaged in the formulation of therapy or approach that provides reliable treatment from the onset of the disease to its evolution in individual patients. This is because the standard therapies do not prevent patients from entering the secondary-progressive phase. 

It is also estimated that 50 percent of patients are unable to proceed with their work for 10 years after the diagnosis of the disease, and might require ambulatory assistance by 15 years, while others are not able to walk by 25 years (Marzullo et al., 2019). These portray the severity of the effects of the disease, coupled with high costs of treatment and therapies for patients. As such, the autologous hematopoietic stem cell transplantation is applied to reset the immune system of patients in the quest to prevent the progression of neurological disability. Conversely, recent studies have depicted that nonmyeloablative hematopoietic stem cell transplantation for patients with RRMSS offers an improvement of neurological disability and also improves the quality of life of these patients (Burt et al., 2019). The treatment with a nonmyeloablative regimen, however, requires at least 6 months follow up to have better outcomes. 

Method of Study 

All the patients involved in the study undertook hematopoietic stem cell transplants, and also fulfilled the criteria of; having relapsing-remitting multiple sclerosis, unsuccessful treatment with at least 1 FDA-approved medication, satisfied the revised McDonald Diagnostic Criteria for multiple sclerosis, aged between 18 and 55 years, and having an Extended Disability Status Scale (EDSS) score of between 2.0 and 6.0 (Burt et al., 2019). The collection of stem cells was done from the peripheral blood cells ten days after the patients were administered with cyclophosphamide and filgrastim. The components of blood were irradiated until the leukocytes were exhausted. “The habituation (immunoablative) regimen contained 50mg/kg/d of cyclophosphamide administered 5 to 2 days prior to stem cell infusion (day0) plus either 20mg of alemtuzumab given 2days before stem cell infusion (22 patients) or 0.5 mg/kg of thymoglobulin 5 days before stem cell infusion, 1.0 mg/kg 4 days before, and 1.5 mg/kg on 3 days, 2 days, and 1 day before stem cell infusion” (Burt et al., 2019). The study end points were outlined by the EDSS score, Neurologic Rating Scale (NRS) score, Short Form 36 (SF-36) score, and Multiple Sclerosis Functional Composite (MSFC) score. Statistical analyses based on two-tailed paired t-tests were used to provide a comparison of the outcomes before and after the nonmyeloablative hematopoietic stem cell transplantation. 


The study depicted improvement of neurological disability and other clinical outcomes after the administration of the nonmyeloablative hematopoietic stem cell transplantation (HSCT) on the patients of the study. After undertaking the HSCT, the EDSS score of the patients improved by signifying decrease equal to or greater than 1.0. The study reported that 50 percent and 64 percent of the patients started showing improvements after 2 and 4 years correspondingly. Consequently, the improvements in the EDSS scores of the patients were also marked by respective improvements in the NRS scores and SF-36 scores of the patients. 

This was the first relevant improvement in the EDSS scores of patients after any treatment of multiple sclerosis, thus marking the significance of using nonmyeloablative hematopoietic stem cell transplantation to treat MS (Burt et al., 2019). The improvements of the SF-36 scores outlined an increase by 15 points for physical health, 19 points for total health, and 20 points for mental health. The treatment of MS in this cohort of patients did not also portray any aspects of treatment-related mortality or infections, hence, ruling out any risks of the HSCT approach. The outcomes of the study also outline that patient selection is pertinent to the delivery of expected results. 

Some of the patients that had secondary-progressive multiple sclerosis did not record any improvements in their EDSS scores, as well as, those who had the disease for over 10 years (Burt et al., 2019). An unfavorable prognostic factor that was realized in the neurological recovery of patients is fever, which depicts a side-effect of the HSCT treatment approach. However, the administration of corticosteroids in the standard of care helps in reducing peritransplant fever that could lead to increased disability years after treatment. The study faced various limitations one of them being the use of patients in one institution, which can result in bias. Consequently, a long-term follow up of the patients, for instance, over 4 years was not possible in the study, and this could affect the findings. The lack of a control group in this observational cohort study could also jeopardize the workability of the HSCT treatment method. 


Multiple sclerosis is a chronic illness that affects the central nervous system and has been attributed to the increase in disabilities among the majority of young adults in the world. However, to this date, there is still no FDA-approved medication of this chronic illness. Relapsing-remitting multiple sclerosis, which is an advanced course of MS, is quite severe and could lead to neurological disabilities and other clinical conditions that reduce the quality of life of the patients. This uncontrolled study, however, outlines that the administration of nonmyeloablative hematopoietic stem cell transplantation helps in improving neurological disability for patients of relapsing-remitting multiple sclerosis. The improvements of the NRS scores, SF-36 scores, and MSFC scores of the patients also indicate that the nonmyeloablative hematopoietic stem cell transplantation improves other clinical outcomes of the patients. 


Burt, R. K., Balabanov, R., Burman, J., Sharrack, B., Snowden, J. A., Oliveira, M. C., ... & Carlson, K. (2019). Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing- remitting multiple sclerosis: a randomized clinical trial. Jama , 321 (2), 165-174. 

Feng, J., Offerman, E., Lin, J., Fisher, E., Planchon, S. M., Sakaie, K., ... & Ontaneda, D. (2019). Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Multiple Sclerosis Journal–Experimental, Translational and Clinical , 5 (2), 2055217319856035. 

Marzullo, A., Kocevar, G., Stamile, C., Durand-Dubief, F., Terracina, G., Calimeri, F., & Sappey-Marinier, D. (2019). Classification of Multiple Sclerosis Clinical Profiles via Graph Convolutional Neural Networks. Frontiers in Neuroscience , 13

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StudyBounty. (2023, September 16). Multiple sclerosis (MS) - Symptoms and causes .


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