Role of therapeutic plasma exchange in neuromyelitis optica: A case series

Rashmi Parashar; Amit Sharma; Ankit Sharma

doi:10.4103/gjtm.gjtm_19_22

CASE SERIES

Year : 2022 | Volume : 7 | Issue : 2 | Page : 201-204

Role of therapeutic plasma exchange in neuromyelitis optica: A case series

Rashmi Parashar, Amit Sharma, Ankit Sharma
Department of Immunohematology and Transfusion Medicine, SMS Medical College and Hospital, Jaipur, Rajasthan, India

Date of Submission	06-Mar-2022
Date of Decision	08-Apr-2022
Date of Acceptance	16-Aug-2022
Date of Web Publication	5-Nov-2022

Correspondence Address:
Rashmi Parashar
Department of Immunohematology and Transfusion Medicine, SMS Medical College and Hospital, Jaipur, Rajasthan
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/gjtm.gjtm_19_22

Abstract

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the optic nerves and spinal cord and generally has a relapsing course. It is an autoimmune demyelinating disorder of the central nervous system caused by the binding of aquaporin-4 immunoglobulin G to water channel protein at the astrocyte foot process. Here, we are presenting the effectiveness of therapeutic plasma exchange (TPE) therapy in the improvement of disability scores of 11 patients with NMO. A total of 49 procedures were done, and the mean number of TPE sessions was 4.45. The outcome was analyzed in the form of improvement in the Expanded Disability Status Scale score and visual acuity.

Keywords: Disability improvement, neuromyelitis optica, therapeutic plasma exchange

How to cite this article:
Parashar R, Sharma A, Sharma A. Role of therapeutic plasma exchange in neuromyelitis optica: A case series. Glob J Transfus Med 2022;7:201-4

How to cite this URL:
Parashar R, Sharma A, Sharma A. Role of therapeutic plasma exchange in neuromyelitis optica: A case series. Glob J Transfus Med [serial online] 2022 [cited 2023 Mar 28];7:201-4. Available from: https://www.gjtmonline.com/text.asp?2022/7/2/201/360476

Introduction

The neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the optic nerves and spinal cord and generally has a relapsing course.^[1] The disease having a relapsing–remitting course of neurological deficits. Each incomplete recovery of episode leads to a deterioration of visual and neurological functions.^[2] It is an autoimmune demyelinating disorder of the central nervous system caused by the binding of aquaporin-4 immunoglobulin G to water channel protein at the astrocyte foot process. There is no specific outcome analysis tool. The outcome is assessed as a change in Expanded Disability Status Scale (EDSS) score and improvement in visual acuity (VA) for disability. The prognosis of the disease depends on the severity of the primary attack and also the number of relapses within the first 2 years. Therefore, early aggressive treatment after the initial attacks is usually considered a significant tool that would markedly affect the long-term outcome of patients with neuromyelitis optica spectrum disorder (NMOSD).

High-dose corticosteroids are currently the standard first-line therapy. Plasma exchange is taken into account where no significant improvement is after steroid therapy. Plasma exchange eliminates pathologic antibodies present in circulation and inflammatory cytokines, which are the mediators of NMOSD attack.^[1] Currently, NMOSD acute attack and relapse come under category II with grade 1B recommendation, while maintenance treatment come under category III with 2C recommendation.^[3]

Case Series

The study was conducted in a tertiary care hospital in northwestern India, over 1 year from January 2021 to December 2021.

Diagnostic criteria

A total of 11 patients with NMO were treated with therapeutic plasma exchange (TPE) during the study time. All patients were fulfilling the diagnostic criteria suggested by Wingerchuk et al.^[4]

The initiation of TPE therapy was decided on the patient's clinical condition and when the patient failed to improve after steroid therapy or in steroid-refractory cases. Written informed consent was taken from the patient was taken.

Procedure – patient's complete blood counts, serum electrolytes, liver function tests, renal function tests, coagulation profile, and vitals were checked before starting the procedure, and corrective action was taken where necessary. A minimum of five sessions were planned over 2 weeks for each patient. The plasma volume removed was approximately one plasma volume in each session. Intermittent cell separator (Haemonetics) machines and continuous cell separator (Spectra Optia) machines were used during these procedures. Twelve-French double-lumen dialysis catheters were used uniformly for central or femoral line access. Acid-citrate-dextrose was used for anticoagulation in all procedures. Replacement fluid 5% purified human albumin was uniformly used. An infusion of 10% calcium gluconate in 10-ml saline was given during the procedure to avoid citrate toxicity. The outcome was estimated by the change within the EDSS score of the patient and improvement in VA. The outcome was assessed after the completion of therapy. The amount of plasma to be exchanged was calculated using the patient's weight and hematocrit using the formula. EPV = (0.65 × weight [kg]) × [1 − hematocrit].^[5] All patients were closely observed for adverse events during the TPE procedure, and documentation was done for the same if occurs.

Outcome analysis

Evaluation of the effect of TPE on the degree of recovery from NMO was done after each procedure. Both subjective and objective clinical response to TPE was assessed. The overall outcome was documented after treating clinician assessment of response after the last TPE. The outcome of TPE was documented in the form of sensory improvement and power improvement in each limb before and after therapy. In each patient, pre- and post-TPE EDSS score was also performed, which is another measure of disability. The patient demographic detail and time of onset of disease and other investigations were also noted.

Results

In our study, a total of 11 patients were included who were fulfilling diagnostic criteria for NMO. Initial treatment with IV methylprednisolone was given to all patients. TPE was started as second-line therapy after the patient was refractory to high-dose steroid treatment or did not show moderate to marked improvement. The majority of patients having spinal involvement were bedridden, before the start of therapy. In our study, the majority of patients were females – 72.7% (eight) and the rest – 27.2% (three) were male. The mean age of the patients was 32.3 years (range = 17–62 years). The median age of NMO diagnosis was 30 years (range = 17–62 years), and the median duration of disease was 9.6 months (range = 0–6 years). In our series, a total of five (45.4%) patients had only spinal components, four (36.3%) had spinal with optic involvement, and two (18.1%) patients had only optic nerve involvement. Optic nerve involvement was present in six (54.5%) patients, of which four (66.6%) had bilateral and two (33.3%) had unilateral optic involvement. Autoimmune component was present in only one (9.09%) case, and it was anti- ANA. In this study, nine patients (81.8%) started plasma exchange within 15 days of symptom onset and the rest two (18.1%) were started late within 30 days. Out of 11 patients, 3 (27.2%) had a prior history of NMO. One had a previous history of NMO attack 6 years before and this time showed marked improvement. The second patient had the previous attack 4 months ago, and now, the patient was refractory to immunosuppressants also. This patient after TPE showed only improvement in sensory function and no significant improvement in motor function was seen. The third patient had a 5^th attack over a 2.5 years period and showed no significant improvement after plasma exchange. This patient expired 7–8 days after discharge. The cause of mortality was not directly related to TPE but was attributed to residual disease. Demographic detail and other parameters of patients are summarized in [Table 1]. In our series, a total of 49 TPE procedures were performed. Meantime of starting of TPE during an acute attack was 14.7 (standard deviation [SD] ± 5.18) days. The mean number of TPE sessions was 4.45 (SD ± 1.52). The mean volume of plasma exchange was 2168 ml (SD ± 253.33). The mean time duration was 165.2 min (SD ± 30.18) with Haemonetics and 51.3 (±6.32) min with Optia. All the procedures were well tolerated by the patient. In our series, we noticed procedure-related thrombocytopenia in one patient, and catheter-related problems were noticed in one procedure which was managed by the critical care team. In this study, mortality was found only in one patient during the follow-up. There was marked improvement in three (27.2%) patients, moderate improvement in four (36.3%) patients, mild improvement in two (18.1%), and no improvement in two patients (18.1%) as per the Keegan et al. criteria.^[6] No improvement with TPE therapy was seen in those patients who were immunosuppressant refractory too. Patients having EDSS score at the initiation of TPE was 6.9 ± 1.46 (range = EDSS 6.5–9) and after TPE was 5.13 ± 1.49. Most patients started to show improvement while on TPE therapy. VA improvement is summarized in [Table 2]. After TPE, patients were kept on disease-modifying immune-modulatory therapies such as azathioprine and tapering dose of prednisolone and followed up.

Table 1: Patient demographic detail

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Table 2: Visual acuity improvement

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Discussion

The NMO is a type of inflammatory demyelinating disorder which is specifically associated with the optic nerve and spinal cord. Involvement of the optic nerve may be unilateral or bilateral. (Not clear).

(Repetition of results). Chances of relapse are much more with NMO, and approximately 50% of patients become blind with optic involvement.^[7] The disease worsens with each acute attack due to incomplete recovery. In this study, 27.2% of the patient presented with a repeat attack, of which two (66.6%) patients had a relapse within 2 years. Poor outcome was seen in these patients having a relapse over a brief duration of time.

Initially, NMO, considered a clinical variant of multiple sclerosis, is now considered a definite debilitating neurological autoimmune disorder. After standard neurological examination and therefore the exclusion of infection, steroids are the initial standard treatment given for 5 consecutive days with a dose of 1 g methylprednisolone per day intravenously.

High-dose steroids are generally used as the first line of therapy, and, if symptoms worsen or do not resolve completely, TPE is added as a second line of treatment. TPE acts by removing the pathogenic mediator of disease from blood. TPE may be considered a first line of treatment in patients with severe attacks or relapse of disease with steroids.^[8],[9]

As per some studies, the time from the onset of attack to the beginning of therapy should be minimized as this is a strong variable influencing complete recovery.^[10],[11] In our study, nine patients (81.8%) were started on TPE within 15 days of onset of attack and two (18.1%) patients presented late because of the slow and less severe form of motor involvement.

We analyzed the clinical effectiveness of TPE in 11 patients and we observed that seven patients showed moderate to marked improvement after initiation of TPE, while two patients only show minimal improvement in the variety of sensory improvement or partial vision recovery. The time of the starting of TPE after the disease onset was approximately 10–15 days. The immediate response to TPE as a disease-modifying therapy in acute episodes suggests a reduction in anti-AQP-4 antibody levels as significant, although we did not estimate the titer of antibody. In our series, out of 11 patients, 7 patients showed major improvement (63.6%, moderate/marked), whereas 2 patients (18.1%) had mild improvement, and 2 patients had no improvement (18.1%). The responsiveness of TPE in our series was 60%–80% which was comparable to other studies.^{[6],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24]} This is not your study. In our series, we also used the EDSS for neurological disability assessment as eight of our patients had improvement within the EDSS score as compared to their pre-TPE score.^{[9],[14],[17]} The one patient who failed to respond to TPE was refractory to immunosuppression also attributed to a severe type of NMO with a malignant course.^[11] TPE is a safe and well-tolerated procedure. There were only 2 (4.08%) adverse events noted in over 49 procedures of TPE. This was similar to other studies reported (ranged 4.6%–21%).^{[25],[26],[27]} The low rate of adverse events was also because of lack of allergic reaction and citrate toxicity, as we used 5% albumin as replacement fluid. Adverse events were successfully resolved with no sequel. They included thrombocytopenia which was treated with steroids, and another was catheter-related problem.

Systemic review and meta-analysis have also shown responsiveness of therapy with TPE done on patients with NMO. No randomized controlled trials (RCTs) have been done using TPE for NMO, as NMO is a rare disease, with ethical difficulties in conducting RCTs.^[27] Steroids have only an immune-modulatory effect; hence, significant improvement after steroids might not be noticed in all patients.^[16],[28] The study strengthens and provides data for the use of TPE during a refractory acute attack in NMO. TPE is the more practical modality of treatment as it also removes the antibodies.

Limitation of study and future directions

Our study had a small sample size with a short duration of follow-up. We do not have results of long-term follow-up. However, with new diagnostic technologies and increasing clinical awareness, improved ways of TPE for such patients may be possible in the future.

Conclusion

This study suggests that early and aggressive treatment of acute attacks of NMO with TPE, rapidly improves the neurological status. Utilization of TPE during the NMOSD attack is related to a significantly improved disability status immediately after treatment and through follow-up.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) have given their consent for their clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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