Surgical management prospects for myasthenia gravis in Nigeria: A preliminary report of Enugu experience

Ijeoma B Ndionuka; Ikenna O Onwuekwe; Stella O Ekenze; Birinus Ezeala-Adikaibe

doi:10.4103/ijmh.ijmh_39_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 27 | Issue : 4 | Page : 410-413

Surgical management prospects for myasthenia gravis in Nigeria: A preliminary report of Enugu experience

Ijeoma B Ndionuka, Ikenna O Onwuekwe, Stella O Ekenze, Birinus Ezeala-Adikaibe
Department of Internal Medicine, University of Nigeria Teaching Hospital, Enugu, Nigeria

Date of Submission	25-Feb-2022
Date of Decision	14-Jun-2022
Date of Acceptance	15-Jun-2022
Date of Web Publication	22-Sep-2022

Correspondence Address:
Ijeoma B Ndionuka
Department of Internal Medicine, University of Nigeria Teaching Hospital, Enugu
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmh.ijmh_39_22

Abstract

Background: Myasthenia gravis (MG) is an acquired autoimmune neuromuscular disease characterized by fatigable and variable weakness of skeletal muscles as a result of autoimmune attack on postsynaptic antigenic targets. There is paucity of data on the outcome of treatment options available in resource-poor settings. Objective: The aim of this study was to determine the treatment outcome of surgical thymectomy for MG with regard to the local experience in Enugu, southeast Nigeria. Materials and Methods: It was a preliminary report of patients with MG seen at the Neurology Clinic of the University of Nigeria Teaching Hospital, Enugu, Nigeria, from February 2016 to October 2019. The treatment outcomes of the patients were analyzed following thymectomy to determine the effectiveness of the surgical management. Data obtained included patients’ age, response to treatment, intensive care unit (ICU) stay, and total hospital stay. Results: The mean age of the patients was 35.7 ± 15.1. The mean duration of stay at the ICU was 3.9 ± 4.6 days, while the mean total hospital stay was 12 ± 9.70 days. All the patients (100%) had symptomatic improvement following thymectomy and 40% had remission. Conclusion: The general outcome of MG patients following thymectomy was favorable. Thymectomy appears to improve the prognosis of MG in the local setting of Enugu, Nigeria.

Keywords: Enugu, myasthenia gravis, thymectomy

How to cite this article:
Ndionuka IB, Onwuekwe IO, Ekenze SO, Ezeala-Adikaibe B. Surgical management prospects for myasthenia gravis in Nigeria: A preliminary report of Enugu experience. Int J Med Health Dev 2022;27:410-3

How to cite this URL:
Ndionuka IB, Onwuekwe IO, Ekenze SO, Ezeala-Adikaibe B. Surgical management prospects for myasthenia gravis in Nigeria: A preliminary report of Enugu experience. Int J Med Health Dev [serial online] 2022 [cited 2023 Jun 5];27:410-3. Available from: https://www.ijmhdev.com/text.asp?2022/27/4/410/356631

Introduction

Myasthenia gravis (MG) is a relatively rare, acquired, autoimmune disorder caused by an antibody-mediated blockade of neuromuscular transmission resulting in skeletal muscle weakness with variable presentation, e.g., limb weakness, ocular weakness, bulbar weakness. The autoimmune attack occurs when autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at the neuromuscular junction (NMJ) of skeletal muscles.^[1],[2] Although the chief target of the autoimmune attack in most cases is the skeletal muscle nicotinic acetylcholine receptor, other antigenic targets that are components of the NMJ have also been implicated and include the muscle-specific tyrosine kinase (MUSK), low-density lipoprotein receptor-related protein (LRP4), and Agrin. These maintain the structure of the NMJ.

The four basic therapies for MG include symptomatic therapy with an acetylcholinesterase inhibitor (pyridostigmine), chronic immunosuppressive therapies, rapid but transient immunomodulatory therapies (plasma exchange and intravenous immune globulin), and thymectomy. Thymectomy is performed to potentially avoid chronic immunosuppressive therapy, or if immunotherapy has failed or patients have had intolerable side effects from immunotherapy. The major treatment options in resource-poor settings are thymectomy and pharmacotherapy. In non-thymomatous generalized MG, thymectomy has become the standard, despite a lack of evidence from a good prospective clinical trial. Two systematic reviews of the existing thymectomy literature emphasized this knowledge gap and recommended the MG field perform a randomized, controlled trial.^[3],[4],[5] However, owing to the difficulty of performing controlled trials involving thoracic surgery in a rare disease, high-quality evidence about thymectomy had been lacking. A recently completed landmark international, randomized, rater-blinded clinical trial controlling for medical treatment was designed to address this uncertainty.^[6]

One hundred twenty-six recently diagnosed patients, ages 18 through 65 with AChR antibody-positive generalized MG, were randomized to receive either extended transsternal thymectomy plus prednisone or medical management with prednisone. Over a 3-year follow-up period, the time-weighted average Quantitative Myasthenia Gravis score was lower in the patients who underwent thymectomy (6.15 vs. 8.99). Similarly, the thymectomy group had a lower time-weighted alternate-day prednisone dose requirement (initially reported at 44 vs. 60 mg), which was later corrected to 32 vs. 54 mg (95% confidence interval, 12–32 mg). Also, in the thymectomy group, there were fewer patients requiring additional immunosuppression, fewer adverse events, and fewer admissions for myasthenic crises. These data provide support for thymectomy as a first-line treatment modality that can improve MG status and decrease the required dose and duration of immunotherapy in generalized MG. The operation should be scheduled when the patient is neurologically optimized, because perioperative events can exacerbate myasthenic weakness. Patients with persistent bulbar, respiratory, or limb weakness should be treated with plasma exchange (PLEX) before surgery. Surprisingly, the effects of the thymectomy could be observed as early as 3–4 months and were maintained for the entire 3-year study.^[6]

There are no available data found on the incidence rate (IR) of MG in Nigeria, but Cape Town recorded an annual IR of 12.6 per million.^[7] It is estimated that MG affects more than 700,000 people worldwide and approximately 36,000–60,000 patients in the USA.

The IR of MG varies with age, gender, and ethnic groups.^[8] Estimates of incidence range from 0.3 to 2.8 per 100,000 worldwide, and the median global estimated prevalence is 10 per 100,000.^[9]

There is paucity of data on the outcome of treatment options available in resource-poor settings. This study aims to determine the treatment outcome of surgical thymectomy for MG in Enugu, southeast Nigeria.

Materials and Methods

This is a preliminary report of 10 patients of MG seen at the Neurology Clinic of the University of Nigeria Teaching Hospital (UNTH) from February 2016 to February 2019. They were five males and five females, at different ages, varying durations of symptoms, different stages of MG, varying antibody titer, and ultimately one of two outcomes following thymectomy. The patients were counseled on the use of thymectomy as a treatment option to improve management outcome. Thymectomy was done by the general surgeons of the hospital using a trans-sternal approach. Patients were monitored in the intensive care unit (ICU) for a few days on low-dose Pyridostigmine 30 mg 8 hourly before discharge to the general ward. The patients were subsequently discharged home after remarkable recovery with partial and for some complete weaning off from medications.

Results

The mean age of the patients was 35.7 ± 15.13. Males and females were of equal number. The median duration of stay at the ICU was 2 days, interquartile range 6. The mean total hospital stay was 12 ± 9.70 days. All the patients (10/10, 100%) had symptomatic improvement following thymectomy. 40% (n = 4) achieved medication-free remission status (WD); 60% were on low doses of Pyridostigmine medication (LD). Medication-free remission status was seen with lower mean age of 29 years [Figure 1], male sex (three out of five males), lower mean duration of symptoms 56 months [Table 1], Osserman stage 2A [Table 2], and higher acetylcholine receptor antibody titer. Six (60%) of the patients had non-thymomatous MG, one (10%) was thymomatous, and three were unknown because of the missing histopathology result.

Figure 1: Treatment outcome following thymectomy and mean age

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Table 1: The outcome following thymectomy and duration of symptoms of MG

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Table 2: Osserman staging of MG and treatment outcome following thymectomy

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Discussion

This was a preliminary descriptive report of 10 patients with MG seen at the Neurology Clinic of the UNTH from February 2016 to February 2019. Males and females were of equal number, with age range 18–72 and a mean age of 35.70 years. A lower mean age of 29 years was noted in the patients with remission or minimal manifestation. However, studies have observed that patients were more likely to go into remission when the diagnosis was made in the first year of the disease and if symptoms started before the age of 40.^[10] The study observed that patients with mild disease (Osserman stage IIA) were more likely to do better following thymectomy. Similar findings were reported by Aydin et al.,^[11] but however differed from findings by Diaz et al.,^[12] who observed that patients with severe disease were more likely to achieve remission following thymectomy. Tansel et al.^[13] found early and late postoperative remission rates (RRs) of 44.6% and 73%, respectively. They found no correlation among sex, age, duration of symptoms, and preoperative classification. However, symptomatic improvement increased in late follow-up.

RRs specifically for non-thymomatous MG (no tumor in the thymus gland) ranged from 38% to 72% with up to 10 years of follow-up.^[11] Higher mean antibody titer was associated with remission in 4 patients out of 10, as observed in this study. Lower mean duration of symptoms was also noted to be associated with remission. In a similar study, 15 patients undergoing thoracoscopic thymectomy were identified with a mean age of 11.3 years at the time of diagnosis and average treatment duration of 12.5 months prior to operative intervention. Of these patients, most presented with Osserman stage IIB (8) or stage III (5) disease and two patients with Osserman stage IIA disease. Results of thoracoscopic thymectomy were not considered curative, rather appeared to make generalized juvenile MG more amenable to long-term medical management.^[14] Thymectomy in MUSK, LRP4, and Agrin antibody-positive patients is not supported by current evidence.^[15] MUSK antibody was not routinely done by the patients in this study due to financial constraints. The major limitation of this study is the small sample size making inferential statistics difficult, and thus the conclusion is to be interpreted with caution. A future study with larger sample size and inferential statistics is expected as fresh recruitments and follow ups are being continued.

Conclusion

Thymectomy improves the likelihood of remission in patients with MG, particularly those with mild disease. There may be need to improve the availability of thymectomy services for patients with MG and also to consider this treatment option as first line to reduce the burden and cost of management of MG, especially in resource-poor settings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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