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

IntroductionRespiratory failure is the leading cause of death in amyotrophiclateral sclerosis (ALS) [1]. The involvement of respiratory functionis a negative predictor of survival, which can be in partovercome by a prompt initiation of non-invasive mechanicalventilation (NIV).Seated forced vital capacity (FVC%) is a widely used measureto monitor respiratory function, and it is often taken as asurrogate outcome measure in clinical trials. However, it maybe within a normal range in ALS patients with respiratorydysfunction [2].Here we report on a case of an ALS patient with a rapidlyevolving respiratory insufficiency, despite a rather normalFVC%.Case presentationThe patient, a 67-year-old man with non-significant past medicalhistory, was referred to our Neurology Unit with 7-monthhistory of progressive impairment of neck muscles that causeddropped head. Symptom onset was subtle, and it was followedby camptocormia. The neurological examination documentedthe camptocormic posture with a dropped head, and discloseda mild tongue atrophy, slight hypophonia, and a mild dysphagia,with a moderate proximal and distal weakness and atrophyof 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. Physicalexamination 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 theALSFRS-R were 12/12. The dropped head was corrected witha collar. He started riluzole, and a 4-month follow-up visit wasscheduled.Some 30 days after diagnosis, he became increasingly lethargicover a few days and was admitted to the EmergencyUnit. Altered arterial blood gases were found (PaO226.4 mmHg, PaCO2 93.0 mmHg, pH 7.32). A CT scan ofthe lungs did not show radiological evidences of pneumoniaor atelectasis. When inquired, relatives reported that the patienthad his usual lifestyle, that he did not complain in the pastdays of significant respiratory problems, and that he did nottake medications other than riluzole. The patient wasintubated and placed on invasive mechanical ventilation, witha prompt improvement of the blood gases, i.e., PaO274.3 mmHg, PaCO2 46.0 mmHg, pH 7.47, and a recoveryof full consciousness. The assisted mechanical ventilationwas continued.One week later, the tracheal tube was removed and noninvasiveventilation (NIV) was started. In the following days,......................