| Abstract|| |
INTRODUCTION: Neuromyelitis optica (NMO) is an idiopathic demyelinating disorder characterized mainly by optic neuritis and myelitis, causing gradual loss of vision and deterioration of neurological function. The underlying pathogenesis mainly involves antibodies against aquaporin 4. The effectiveness of therapeutic plasma exchange (TPE) has been shown by many studies across the globe but are only a few from India. We studied ten cases of NMO retrospectively to find out the safety and efficacy of plasma exchange and to know the outcome of those patients who underwent the procedure.
MATERIALS AND METHODS: We retrospectively analyzed ten cases of NMO who underwent TPE from January 2017 to July 2021. Out of 153 patients on whom plasma exchange procedures were done during this period, ten cases of NMO were diagnosed and managed with TPE.
RESULTS: In our study, we found that 6 of our patients (60%) had a marked improvement noticed clinically with an increase in baseline power of limbs from 0–2/5 to 3–5/5. However, two patients expired after despite TPE. The other two did not show any improvement. Four of our patients started showing clinical improvement after the 2nd–3rd cycles of treatment. TPE was initiated early (within 5 days). There were no notable events in most of the procedures except in one procedure where the patient developed hypotension, her saturation started to drop, and the procedure had to be aborted.
CONCLUSION: Our study supports the effectiveness of timely initiation of plasma exchange to improve the overall mortality rate of the patients.
Keywords: Neuromyelitis optica spectrum disorders, Optic neuritis, plasmapheresis, plasma exchange, TPE
|How to cite this URL:|
Sahoo D, Silwal P, Basavarajegowda A. Safety and efficacy of therapeutic plasma exchange in neuromyelitis optica: A retrospective study from South India. Asian J Transfus Sci [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajts.org/preprintarticle.asp?id=356874
| Introduction|| |
Neuromyelitis optica (NMO) is an inflammatory central nervous system (CNS) syndrome. It is a distinct disease entity from multiple sclerosis associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Optic nerve and spinal cord involvement are diagnostic criteria for NMO; however, more restricted or extensive CNS involvement may occur. There is gradual loss of vision and deterioration of neurological function. The underlying pathogenesis mainly involves antibodies against the AQP4 channel expressed mainly in the apical domain of astrocytes but is also highly expressed in spinal cord gray matter, posterior optic nerve, the floor of the 4th ventricle, and area postrema. The antibody is mainly IgG, but IgM and complement have also supported the disease process. The histological report shows hyalinized capillaries, neutrophils, and eosinophils invasion within the lesions. The diagnostic criteria for NMO spectrum disorders are the presence of core clinical characteristics such as optic neuritis, longitudinally extensive transverse myelitis (LETM), along with or without AQP4 IgG positivity. Acute attacks of NMO are usually managed by high-dose steroids followed by oral steroids. In patients where symptoms failed to resolve, therapeutic plasma exchange (TPE) was added. Currently, TPE is considered category II, Grade 1B for acute attacks of NMO. To prevent further acute attacks, immunosuppressive prophylaxis was advised. Many case reports have shown TPE benefits in corticosteroid-refractory NMO exacerbation. One clinical trial showed that TPE added to pulsed intravenous corticosteroids is more effective than pulsed intravenous corticosteroids alone. TPE can be considered an initial treatment for severe attacks, particularly when previous attacks have responded well to apheresis therapies but not to steroids. Prompt initiation of TPE is a strong predictor of a beneficial outcome in the severe attacks of NMO. The effectiveness of TPE has been shown by many studies across the globe but are only a few from India. We studied ten cases of NMO retrospectively to find out the safety and efficacy of plasma exchange and to know the outcome of those patients who underwent the procedure.
| Materials and Methods|| |
The present study is a retrospective observational study done in the transfusion medicine department in a tertiary care hospital in South India. All patient details were obtained from hospital records (TPE register). We analyzed all cases that underwent TPE from January 2017 to July 2021. Out of 153 patients who underwent plasma exchange procedures during this period, ten cases of NMO were diagnosed and managed with TPE. Patients were evaluated in the emergency department and outpatient department's, and those with suspicion of NMO with unstable vitals were shifted to medicine intensive care unit (ICU) and planned for TPE. The study duration was 4 year and 6 months. We hardly get 1–3 patients of NMO per year for TPE. Our hospital is tertiary care referral center. Each year we do TPE for 30–40 patients (100–150 procedures). Out of these, only one to three cases are of NMO. All cases TPE done in medicine ICU. Most of them were complicated and sick patients. Confirmation of diagnosis was done subsequently with either magnetic resonance imaging (MRI) or antibody identification or both. The procedure was initiated as early as possible in ICU. All subclavian, jugular, or femoral veins were used for the procedure. Prior to the procedure, the flow of the central line was checked.
Preprocedural vitals were recorded, and periodical vitals monitoring was also done. Haemonetics (MCS + 9000) was used for the procedure, and a TPE kit was used. The patient's plasma volume was calculated, and replacement volume and solution were estimated. As per our SOP, 60% of normal saline and 40% of fresh-frozen plasma (FFP)/albumin was used as replacement fluid. Each FFP volume of approximately 150 ml and 5% human albumin (500 ml); reconstituted from 20% bottle was used. Calcium supplementation was done through peripheral line routinely to prevent citrate toxicity, and 10 ml of 10% calcium gluconate was given slowly over 45 min to 1 h. One plasma volume was exchanged in each case. Alternate day cycles for a minimum of five cycles were planned. In one case when the patient was desaturated in the second procedure, and the procedure had to be aborted. Total duration of 3–5 h was required depending on the plasma volume and blood flow in the patient's line. Routine complete blood count, electrolytes, and serum calcium were sent every day, and any abnormalities were corrected immediately. Postprocedure vitals were taken, and the patient was evaluated clinically before the next cycle.
| Results|| |
Of 10 patients, 5 were male and 5 were female, with the median age being 24 years (18–63) [Table 1]. Blood group distribution was 3 O positive, 4 B positive, 2 A positive, and 1 AB positive. Most of the patients underwent five cycles of TPE except two patients who underwent 2 and 7 cycles, respectively. The average duration of initiation of TPE was around 8 days after the initiation of symptoms. Methylprednisolone was started in 6 cases either simultaneously or prior to the procedure. Single volume exchange was done in all the cases, and an average of 2400 ml of plasma volume was exchanged using normal saline and FFP's. In 2 cases, 5% albumin was used as a colloid replacement. Our study found out that 6 of our patients (60%) had improvement clinically with an increase in baseline power of limbs from 0–2/5 to 3–5/5. However, two patients expired after despite TPE. The other two patients did not show any improvement. Four of our patients started showing clinical improvement after 2nd–3rd cycles of treatment. TPE was initiated early (within 5 days). Since none of our patients had visual involvement, this aspect could not be observed. There were no notable events in most of the procedures except in one procedure where the patient developed hypotension, her saturation started to drop, and the procedure had to be aborted.
|Table 1: Demographic Characteristics, TPE details & Outcome of the Patients|
Click here to view
| Discussion|| |
NMO is a neurological disorder affecting the optic nerve and spinal cord segments. NMO can have either a monophasic or relapsing course. Approximately 90% of patients with NMO have relapsing course, which has a poor prognosis: 50% of patients become legally blind or wheelchair-bound, and 30% die of respiratory failure within 5 years. The disease may worsen by incomplete recovery with each acute attack. Autoantibodies against AQP4-IgG at the blood-brain barrier are pathogenic in NMO. IgG binding to AQP4 leads to complement-dependent astrocyte cytotoxicity, cytokine release, leukocyte infiltration, and blood-brain barrier disruption, resulting in loss of myelin, oligodendrocyte death, and neurons death. Antibodies to myelin oligodendrocyte glycoprotein-IgG are a marker of autoimmune Optic Neuritis and often longitudinally extensive transverse myelitis (LETM). Since steroids only cause immunomodulatory effects, more focus should be laid on the ultimate treatment for this disease and plasma exchange is one of the evolving modes of treatment for the case in recent years. We also initiated plasma exchange in 10 diagnosed cases of NMO who did not show improvement despite steroid treatment. Four of our patients started showing clinical improvement after the 2nd–3rd cycles of treatment, and such a clinical response could suggest a significant, pathogenic role of humoral immune factors in these patients. NMO-IgG potentially plays a direct and significant role in the pathogenesis of NMO, and removal of NMO IgG might be playing a significant role in the therapeutic efficacy of PE in NMO.
A study done by Morgan et al. showed mild-to-moderate improvement in all patients who underwent TPE, whereas only 60% of our patients showed improvement. This could be due to the early diagnosis and initiation of TPE in their patients. The patients in the study had TPE intolerability of 23%. However, there were no significant events in most of our procedures except in one procedure where the patient developed hypotension, and her saturation started to drop, and the procedure had to be aborted. A meta-analysis done by Huang et al. showed that the optimal timing of initiation of TPE is from 8 to 23 days for the effectiveness of therapy. Plasma exchange was initiated in an average of 8 days of the appearance of symptoms in our patients. Several case reports have shown TPE benefits in corticosteroid-refractory NMO exacerbation. Similar findings were observed in the present study. One clinical trial showed that TPE added to pulsed IV corticosteroids is more effective than pulsed IV corticosteroids alone. Mostly given as escalation therapies, TPE can be considered an initial treatment for severe attacks, particularly when previous attacks have responded well to apheresis.
Isolated myelitis responded better to TPE than high-dose pulsed intravenous corticosteroids as the first treatment course. In our study population, none had isolated myelitis. Early initiation of apheresis (≤5 days since clinical onset) was recommended by Bonnan et al. The strongest predictors of complete remission were the use of apheresis as the first-line therapy, time from onset of attack to start of apheresis therapy, and presence of AQP4-IgG. We also had a similar observation in the present study. The patients in whom TPE were initiated early showed improvement. Our study supports the effectiveness of timely initiation of plasma exchange to improve the overall mortality rate of the patients. The limitation of our study is that it is a retrospective study with small sample size. Since NMO is a rare disease to diagnose and treat, there could be difficulties as we mostly diagnosed the cases based on clinical findings and MRI scans. Furthermore, the patient outcome could not be categorized based on different scoring systems.
| Conclusion|| |
As NMO is a complex disease, more attention should be focused on diagnosing the disease and plasma exchange should be initiated as soon as possible to reduce the mortality and increase the overall outcome of the patient. Our study supports the effectiveness of timely initiation of plasma exchange to improve the overall mortality rate of the patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Watanabe S, Nakashima I, Misu T, Miyazawa I, Shiga Y, Fujihara K, et al.
Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult Scler 2007;13:128-32.
Bonnan M, Cabre P. Plasma exchange in severe attacks of neuromyelitis optica. Mult Scler Int 2012;2012:787630.
Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al.
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-89.
Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, et al.
Guidelines on the use of therapeutic apheresis in clinical practice – Evidence-based approach from the writing committee of the American society for apheresis: The eighth special issue. J Clin Apher 2019;34:171-354.
Merle H, Olindo S, Jeannin S, Valentino R, Mehdaoui H, Cabot F, et al.
Treatment of optic neuritis by plasma exchange (add-on) in neuromyelitis optica. Arch Ophthalmol 2012;130:858-62.
Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Hellwig K, et al.
Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm 2018;5:e504.
Morgan SM, Zantek ND, Carpenter AF. Therapeutic plasma exchange in neuromyelitis optica: A case series. J Clin Apher 2014;29:171-7.
Huang X, Wu J, Xiao Y, Zhang Y. Timing of plasma exchange for neuromyelitis optica spectrum disorders: A meta-analysis. Mult Scler Relat Disord 2021;48:102709.
Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, et al.
Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol 2016;79:206-16.
Bonnan M, Valentino R, Debeugny S, Merle H, Fergé JL, Mehdaoui H, et al.
Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry 2018;89:346-51.
Department of Transfusion Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry
Source of Support: None, Conflict of Interest: None