Early and rapidly progressing respiratory failure in a patient with amyotrophic lateral sclerosis: when FVC% is misleading

Introduction Respiratory failure is the leading cause of death in amyotrophic lateral sclerosis (ALS) [1]. The involvement of respiratory function is a negative predictor of survival, which can be in part overcome by a prompt initiation of non-invasive mechanical ventilation (NIV). Seated forced vital capacity (FVC%) is a widely used measure to monitor respiratory function, and it is often taken as a surrogate outcome measure in clinical trials. However, it may be within a normal range in ALS patients with respiratory dysfunction [2]. Here we report on a case of an ALS patient with a rapidly evolving respiratory insufficiency, despite a rather normal FVC%. Case presentation The patient, a 67-year-old man with non-significant past medical history, was referred to our Neurology Unit with 7-month history of progressive impairment of neck muscles that caused dropped head. Symptom onset was subtle, and it was followed by camptocormia. The neurological examination documented the camptocormic posture with a dropped head, and disclosed a mild tongue atrophy, slight hypophonia, and a mild dysphagia, with a moderate proximal and distal weakness and atrophy of the upper limbs; the lower limbs were clinically unaffected. Reflexes were present but not brisk in the four limbs. A complete diagnostic work-up according to current guidelines, including determination of serum anti-ganglioside antibodies, was performed which allowed the diagnosis of ALS. Spirometry was performed to assess the respiratory function: FVC was 80% of predicted, a value within the normal range. Diaphragm compound muscle action potentials (CMAPs) were not measured. The patient did not complain shortness of breath. Physical examination and X-ray showed no sign of diaphragmatic dysfunction. The revised ALS functional rating scale (ALSFRSR) was 42/48 [3], with a predicted intermediate rate of progression (ΔFS = 0.86). The respiratory subscores of the ALSFRS-R were 12/12. The dropped head was corrected with a collar. He started riluzole, and a 4-month follow-up visit was scheduled. Some 30 days after diagnosis, he became increasingly lethargic over a few days and was admitted to the Emergency Unit. Altered arterial blood gases were found (PaO2 26.4 mmHg, PaCO2 93.0 mmHg, pH 7.32). A CT scan of the lungs did not show radiological evidences of pneumonia or atelectasis. When inquired, relatives reported that the patient had his usual lifestyle, that he did not complain in the past days of significant respiratory problems, and that he did not take medications other than riluzole. The patient was intubated and placed on invasive mechanical ventilation, with a prompt improvement of the blood gases, i.e., PaO2 74.3 mmHg, PaCO2 46.0 mmHg, pH 7.47, and a recovery of full consciousness. The assisted mechanical ventilation was continued. One week later, the tracheal tube was removed and noninvasive ventilation (NIV) was started. In the following days,......................