Management of acute myasthenic crisis in developing countries

To the Editor,

Myasthenia gravis (MG) is a rare disorder affecting the neuromuscular junction.^[1,2] It remains a challenging condition in intensive care medicine, particularly when complicated by myasthenic exacerbation or myasthenic crisis.^[2] An acute exacerbation is characterized by worsening MG symptoms, which may be associated with respiratory involvement, bulbar dysfunction, or tetraparesis. A myasthenic crisis is defined as respiratory failure requiring intubation due to MG-related muscle weakness. While international guidelines recommend intravenous immunoglobulins or plasma exchange as first-line therapies, these options are unavailable in many low-resource countries.^[2] We report our experience in Dakar, Senegal, where a cohort of MG patients was managed in an intensive care unit (ICU) without access to these standard treatments.

Diagnosis was established according to international guidelines, using electroneuromyography, detection of anti-acetylcholine receptor (AChR) antibodies and anti-muscle-specific kinase (MuSK) antibodies. All patients underwent assessment using the myasthenic muscle score and the Myasthenia Gravis Foundation of America (MGFA) classification. Chest computed tomography (CT) scans were performed in all anti-AChR–positive patients. The activities of daily living (ADL) score was evaluated at discharge.

Between June 1, 2022, and June 1, 2024, 31 patients (median age: 31 years; 21 female, 67.7%) were admitted to the neurological and neurosurgical ICUs of the Fann National University Hospital Center, Senegal. Six patients (19.4%) had a prior diagnosis of MG, but only two were receiving treatment with cholinesterase inhibitors and corticosteroids. The mean duration of symptoms was 16 months. All patients presented with acute respiratory failure at ICU admission. None were able to lift their head or elbows off the bed, and all exhibited bulbar symptoms. The median myasthenic muscle score was 22, and MGFA classes were ⅣB and Ⅴ. Anti-AChR antibodies were positive in 25 patients (80.6%), while anti-MuSK antibodies were detected in 6 patients (19.4%). Chest CT revealed thymoma in 2 patients (6.5%).

Management of acute respiratory failure included invasive mechanical ventilation (MV), non-invasive ventilation (NIV), and high-flow oxygen therapy (HFOT). Eight patients (25.8%) required MV. Five patients (16.1%) with hypercapnia were treated with NIV, while 18 patients (58.1%) received HFOT as an alternative. Intubation was performed using a rapid sequence induction technique. All eight mechanically ventilated patients underwent early tracheostomy (48–72 h), with a mean duration of MV of 12 days.

Notably, none of the patients experiencing myasthenic crisis or exacerbation received plasma exchange or intravenous immunoglobulins. Management relied on acetylcholinesterase inhibitors, corticosteroids, immunosuppressive therapy, and optimized supportive care. Specifically, 24 patients (77.4%) received oral pyridostigmine, 4 patients (12.9%) were treated with ambenonium chloride, and 3 patients (9.7%) received a combination of pyridostigmine and ambenonium. Corticosteroids were administered at doses of 1.0–1.5 mg/(kg·day). Immunosuppressive therapy included azathioprine in 22 patients (71.0%), mycophenolate mofetil in 6 patients (19.4%), and rituximab (500 mg intravenous) in 3 patients (9.7%) who experienced therapeutic failure with first- and second-line treatments.

Tracheostomized patients were eligible for decannulation once they were stable, awake, and cooperative, without signs of respiratory distress or fatigue, with effective cough, normal swallowing, fraction of inspired oxygen (FiO₂) <30%, and oxygen saturation >94%. A 48-h T-tube weaning trial was performed prior to decannulation. Regular suctioning and a speech test were conducted. After decannulation, oxygen therapy was initially administered via face mask with titrated concentration and subsequently discontinued. No patient required reintubation after decannulation. At discharge, the median myasthenic muscle score was 76, and the median ADL score was 2. Despite optimized management, mortality remained significant, with 4 deaths (12.9%). Two deaths were related to infectious complications, while the other two occurred in the context of severe acute respiratory failure complicated by cardiac arrest, likely secondary to profound hypoxemia. Among the eight patients who required MV, favorable outcomes were observed in six patients, corresponding to a success rate of 75.0%.

The young age and female predominance observed in our cohort are consistent with the classically described bimodal distribution of MG, characterized by female predominance before the age of 40 and male predominance after 50 years, in agreement with previous reports.^[3]

Anti-AChR antibodies were detected in 80.6% of patients, whereas anti-MuSK antibodies were present in 19.4%. This distribution is generally consistent with the literature, which reports a predominance of anti-AChR antibodies in autoimmune MG.^[3] The relatively high proportion of anti-MuSK–positive cases in our series may be explained by the preferential recruitment of severe patients admitted to the ICU, as these forms are classically associated with more pronounced bulbar involvement and a higher risk of respiratory failure.

Tracheostomy was performed to facilitate early decannulation. This strategy was based on the clinical experience of the team, as the unavailability of specific rescue therapies complicates the management of severe myasthenic crises.

The incidence of thymoma in our study was relatively low. This may be explained by the fact that all patients underwent chest CT scanning, but none received thoracic magnetic resonance imaging (MRI), which could account for the low number of detected thymomas.

Azathioprine was used as first-line maintenance therapy, while mycophenolate mofetil was considered second-line treatment. After 18 months of therapy, patients receiving azathioprine or mycophenolate with a myasthenic muscle score <40 and an ADL score >5 were considered to have therapeutic failure. Only these patients were eligible for rituximab therapy. It is important to note that no patient received azathioprine and mycophenolate simultaneously. Table 1 summarizes the treatments available for MG in Senegal, along with their associated costs.

Table 1.

A summary table showing the treatments, equipment, and diagnostic facilities available in Senegal.

Categories	Availability	Estimated cost (FCFA)	Estimated cost (USD)
Treatments
Corticosteroids	Always available	Prednisone 5 mg = 1300	Prednisone 5 mg = 2.31
		Prednisone 20 mg = 3050	Prednisone 20 mg = 5.42
Azathioprine	Always available	Azathioprine 25 mg = 9950 Azathioprine 50 mg = 28,900	Azathioprine 25 mg = 17.67 Azathioprine 50 mg = 51.33
Mycophenolate mofetil (only 500 mg form available)	Always available	58,000	103.02
Rituximab (only 500 mg form available)	Always available	500,000	888.1
Intravenous immunoglobulins	Rarely available (price varies depending on type)	1,500,000–2,500,000	2664.3–4440.5
Plasma exchange	Not available	Not available	Not available
Equipment
Mechanical ventilators	Not always available	Not always available	Not always available
CPAP and/or non-invasive ventilation machines	Rarely available	Rarely available	Rarely available
Immunological and imaging investigations
Acetylcholine receptor antibodies	Always available	25,000	44.4
Anti-muscle-specific kinase antibodies	Always available	100,000	177.62
Chest computed tomography scan	Always available	75,000	133.21
Magnetic resonance imaging	Always available	160,000	284.19

FCFA stands for the CFA franc. 1000 FCFA is equivalent to 1.77 USD. These amounts represent the cost of medications for the patients.

The high mortality observed in our study can be mainly attributed to two factors: first, two patients who required intubation were unable to receive MV; second, two intubated patients receiving MV died as a result of infectious complications. The absence of treatment with intravenous immunoglobulins and plasmapheresis also represents a contributing factor that may explain these deaths.

This experience highlights disparities in the management of critical conditions between high-income and low-income countries. In Senegal, as in many other sub-Saharan African settings, access to advanced immunotherapies is limited by cost and availability.^[4,5]

CRediT authorship contribution statement

Serigne Abdou Aziz Fall: Writing – review & editing, Writing – original draft, Resources, Methodology, Investigation, Conceptualization. Hélène Bassama: Validation, Methodology, Investigation. Mamadou Diawo Bah: Validation. Mamadou Ka: Investigation. Adjaratou Dieynabou Sow: Conceptualization. Ndiaga Matar Gaye: Resources. Moustapha Ndiaye: Supervision.

Managing Editor: Jingling Bao/Zhiyu Wang