At our institution, the 20 August 1953 Hospital in Casablanca, the majority of acute respiratory distress cases are of obstructive otolaryngological origin, most commonly related to neoplastic diseases such as laryngeal carcinoma, hypopharyngeal carcinoma, or locally advanced anaplastic thyroid carcinoma, as well as infectious causes such as cervicofacial cellulitis leading to airway compression. Consequently, before conducting a thorough interview with the patient and her family, an upper airway pathology of ENT origin was initially suspected. However, the cervical CT scan revealed no abnormalities. Following nasofibroscopy and a detailed history, a neurological etiology appeared more likely.

It is noteworthy that the patient’s symptoms had been evolving for approximately 12 months prior to hospitalization. She had previously consulted a pulmonologist due to exertional dyspnea, which prompted thoracic imaging. Nonetheless, at no point was a neurological evaluation sought, despite the presence of axial hypotonia and cervical weakness, which were key clinical features pointing toward a neuromuscular disorder.

Atypical forms of ALS account for a significant proportion of diagnostic delays. Clinicians must be able to recognize the hallmark features of ALS while carefully excluding other potentially treatable conditions. Throughout this process, it is essential to remain vigilant for the onset of respiratory or bulbar symptoms that require urgent management, to take into consideration treatment delays, access to clinical trials, as well as the psychological impact of diagnostic uncertainty on patients and their families. The diagnostic work-up should be targeted, pragmatic, and tailored to each clinical context in order to ensure both reliability and timeliness.

In our patient, the diagnosis was only confirmed after a 15-day stay in the intensive care unit. The initial ENMG was inconclusive, and myasthenia gravis was considered due to the presence of fatigability, dysarthria, and dysphagia, although immunological testing was negative. Cerebellar involvement was also discussed, as certain clinical manifestations may initially mimic a neuromuscular disorder; however, brain MRI findings were normal.

The positive diagnosis of ALS is based on clinical assessment and electromyography (ENMG). The new diagnostic criteria (the “Gold Coast” criteria, proposed in 2020) [2] include:

• Progressive motor impairment, documented by history or serial clinical examinations, following a period of normal motor function, and:
• Either evidence of both upper and lower motor neuron involvement in at least one body region (if limited to one region, both central and peripheral signs must be present),
• Or evidence of lower motor neuron involvement in at least two body regions, and;
• Exclusion of alternative pathological processes through appropriate paraclinical investigations, depending on the clinical context.

In our case, after 15 days of hospitalization, a repeat ENMG was performed and reviewed by neurologists specialized in ALS, who confirmed the diagnosis of bulbar-onset ALS. The patient was subsequently transferred to the neurology department, tracheostomized and breathing spontaneously on room air, for further management. Unfortunately, she died three days later due to acute respiratory failure.

A key question remains whether reliable biomarkers could help distinguish ALS from other clinically similar disorders at an earlier, even preclinical stage. Among the most promising candidates are neurofilaments, which are cytoskeletal proteins of Neurons Composed of Light (NFL), medium, and heavy chains [3]. In ALS, plasma and cerebrospinal fluid NFL concentrations are significantly elevated compared with healthy controls and patients with other neurological conditions. Although no threshold value is specific to ALS, NFL levels are correlated with disease prognosis [4], [5]. In addition, serum creatinine has been shown to inversely correlate with survival [6], while elevated creatine kinase (CPK) levels are associated with longer survival [7]. Several other molecular biomarkers are currently under investigation [8].

Unfortunately, NFL measurement is not available in our setting, and other laboratory parameters in our patient were within normal limits.

It is clear that ALS is an incurable and fatal neurodegenerative disease, however, it would likely have been possible to slow the progression of the disease if the diagnosis had been made earlier and improve the quality of life of this patient, who was diagnosed after a year of progression and at the stage of acute respiratory distress. For this reason, it is crucial to expand the clinical and communication skills of healthcare professionals, starting as early as medical training [9]. Furthermore, diagnostic criteria must emphasize the persistent challenge of ALS recognition, which remains a common problem in clinical practice [9].