Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders—Experience from Tertiary Care Center in North India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.344678
Source of Support: None, Conflict of Interest: None
Keywords: Myelitis, neuromyelitis optica spectrum disorders, optic neuritis, therapeutic plasma exchange
Neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating disorder of the central nervous system preferentially involving optic nerve and spinal cord. The resultant optic neuritis and myelitis result in varied symptomatology including weakness in all the four limbs, diaphragmatic paralysis, severe intractable hiccups, loss of bladder, and bowel control as well as visual deficits. In 2006, Wingerchuk et al. proposed revised diagnostic criteria for the diagnosis of NMO which included both absolute and supportive criteria. Absolute criteria include the presence of optic neuritis and longitudinal transverse myelitis while supportive criteria involved positive NMO aquaporin-4-immunoglobulin -G-positive (AQP4-IgG) test, longitudinally extensive transverse myelitis (LETM) on T2-weighted MRI of cord and MRI of brain not meeting multiple sclerosis (MS) criteria. These criteria were revised by Wingerchuk et al. in 2015 which includes the term NMO as NMO spectrum disorders (NMOSDs) and is classified further by serologic testing for AQP4-IgG.
NMO has a worldwide distribution and affects both children as well as adults. Presently, it is listed as category II (as per ASFA[American society for Apheresis] guidelines) for therapeutic plasma exchange (TPE) in patients presenting acutely and category III for patients requiring maintenance therapy.As a standard protocol in our institute, patients with NMOSDs who do not show a response to standard therapy (high-dose intravenous steroids) are referred to the department of Transfusion Medicine for TPE. In this study, we present our experience with plasma exchange in patients with NMOSD.
In the current study, 11 patients of NMO who underwent TPE over a period of 3 years (January 2013–December 2016) were studied retrospectively. The diagnosis of NMO was made on the basis of criteria laid by Wingerchuk et al. criteria. All these patients also fulfilled the criteria laid by Wingerchuk et al. in 2015.
TPE was done in the department of Transfusion Medicine using Cobe® spectra (Terumo BCT, Lakewood Co. USA), replacing total plasma equivalent to 1 or 1½ times patient's plasma volume with either a) 5% human serum albumin or b) fresh frozen plasma and 0.9% normal saline in the ratio of 80:20, in total of five procedures performed on every other day. Aquaporin channel 4-IgG autoantibody testing was done using an indirect immunofluorescence assay. The improvement in clinical signs and symptoms was recorded after each TPE procedure and at the end of the therapy.The follow-up of the patients was done by reviewing clinical records at follow-up visits as well as telephonically. Adverse reactions, if any, were also recorded.
We performed TPE in 11 patients of NMOSD with a mean age of 22.9 ± 19.53 years (4–68 years). M:F ratio was 1:2. Sixty-two TPE procedures were done on these 11 patients with an average of 5.6 (5–7) procedures per patient.
Prior to TPE, all patients had received high-dose immunosuppressant therapy (3 weeks to 2 years), without much clinical improvement. Out of 11 patients, 3 (27%) only had visual symptoms, 5 (46%) had both visual and cord deficits, whereas 3 (27%) had cord involvement only. Two out of three patients with pure cord involvement also had bladder involvement and one had symptoms of respiratory failure.
MRI scans revealed bulky optic nerves in patients with pure optic neuritis (n = 3), signal changes suggestive of transverse myelitis in patients with pure transverse myelitis (n = 3), and both optic neuritis and myelitis in patients with both cord and optic involvement (n = 5). AQP4-IgG antibodies were checked in seven patients and were positive in three (42.9%) patients.
All the eight patients with visual involvement showed improvement in their visual symptoms ranging from no vision/light perception to finger counting in two, and recovery of color vision and diplopia in six patients. Recovery in muscle power ranged from no power to grade1 (n = 1) to grade-2 (n = 7) as shown in [Table 1].
We observed adverse events in 8% (5/62) of the procedures. The most common adverse events were with allergic reactions to replacement fluid (n = 3) followed by hypotension (n = 2).
Follow-up was available in 7/11 (67%) of patients and are doing well on maintenance therapy. Two patients died during the follow-up; one due to respiratory failure after 3 months and the other due to progressive disease after 12 months. One patient had a relapse for which he underwent a second TPE cycle and continues to do well at 16 months of follow-up. Two were lost to follow-up. The association with any other autoimmune disease was not found in any of the eight patients screened for the same.
The rationale of TPE in patients is a pathogenic role by humoral autoimmunity against the aquaporin 4 water channel in NMOSD. These water channels are concentrated in the gray matter of spinal cord, astrocyte foot processes, and periventricular as well as periaqueductal region. Adding TPE to resistant cases will help in depleting circulating antibodies, cytokines, and complements extravasated due to inflammatory response during acute attacks of the disease and will stop further progression of the lesions. Therefore, early initiation of plasma exchange in the course of treatment is beneficial as reported by Bonnan et al. In addition, intermittent use of TPE can also be effective for steroid-resistant cases, was shown in one report. The results of our study also support the use of TPE in NMOSD patients refractory to standard immunosuppressive therapy.
Effect of therapeutic plasma exchange
Visual loss in NMO is generally bilateral, severe, and progressive and culminates in complete blindness if not treated. We observed visual improvement in all eight visually disabled patients after TPE treatment. Similar observations have been reported by Llufriu et al., Ruprecht et al., Harold et al., and Deschamps et al. A quick response to TPE was observed by Bonnan et al. when TPE was considered after the first attack of optic neuritis whereas, in patients where TPE was considered late, the patient had poor visual recovery.
In a study from south India, NMO-IgG antibody testing is recommended only in the acute phase of disease prior to the start of steroid therapy in optic neuritis patients. In our study, anti-AQP4-IgG antibodies were positive in 3/7 (42.9%) patients. However, these seronegative patients showed similar improvement to TPE as seen in seropositive patients. Our results were similar to those of Morgan et al. Thus, it is reasonable to recommend consideration for TPE in all patients with NMOSD without waiting for the results of AQP4-IgG antibody status. Furthermore, routine testing for autoantibody against myelin oligodendrocyte glycoprotein is not available which is associated with an increased relapse rate of bilateral anterior optic neuritis., TPE was done twice in one of our patients with seronegative NMOSD with good results. This may suggest a role of TPE in the prevention of relapses in severe disease.
In addition to visual loss, TPE also has a role in the management of myelitis refractory to standard immunosuppressant treatment., In the current study, all our patients with transverse myelitis showed an initial response to TPE, though two of them succumbed to disease-related complications later. One of these patients was lost to follow-up while five were maintaining improvement at the time of the last follow-up. The experience of various studies on TPE in NMSOD is shown in [Table 2].,
Current literature recommends a total of 5–7 TPEs (removal of total plasma equivalent to 1–1.5 times the index patient's plasma volume) to achieve remission in steroid-refractory patients. So, we performed 5–7 procedures per patient using 5% albumin/FFP and normal saline as replacement fluid. We noted adverse reactions such as allergic to replacement fluid (n = 3) and hypotension (n = 2) in 5/62 (8.1%) patients. These reactions could be managed easily with fluids and anti histaminic drugs. The incidence of adverse effects was much less in our study compared to previous studies. This may be related to advances in TPE protocols over a period of time. The relatively low incidence of adverse events rate in our study reflects that TPE is well tolerated by both adult and pediatric patients.
The addition of TPE as part of therapy for NMOSD patients (both adult and pediatric) is effective and safe in acute exacerbations of NMOSD.
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There are no conflicts of interest.
[Table 1], [Table 2]