**1. Introduction**

578 Amyotrophic Lateral Sclerosis

World Health Organization (2001). International Classification of Functioning, Disability

Yorkston, K.M.;Strand E.;Miller R.;Hillel A. & Smith K. (1993). Speech deterioration in

amyotrophic lateral sclerosis: implications for the timing of intervention. *J Med* 

and Health (ICF). Geneva: World Health Organization

*Speech-Language Pathol,* Vol. 1, pp. 35-46

Amyotrophic Lateral Sclerosis (ALS) is a relatively rare neurodegenerative disorder that causes progressive dysfunction of voluntary muscle groups secondary to motor neurons death. The relentless involvement of all skeletal muscles of the body, characterized by weakness and atrophy to complete paralysis, invariably involves respiratory muscles (particularly the diaphragm) resulting in a failure to deliver adequate amounts of oxygen to, and remove carbon dioxide from blood. As a result, respiratory failure, frequently complicated by pneumonia related to respiratory muscle weakness and ineffective cough, is the most frequent cause of death in these patients (Lo Coco et al., 2008).

Considering the natural history of ALS, only a few number of patients shows respiratory muscle dysfunction at the onset of the disease (Marti-Fabregas et al., 1995; De Carvalho et al., 1996), and the majority of patients maintains an almost normal pulmonary function for months or years. Patients thus need to be regularly and progressively evaluated to identify early signs of respiratory muscle weakness so that adequate treatment can be implemented. Indeed, in the last few years it has been repeatedly shown that non-invasive positivepressure ventilation (NIPPV), the treatment of choice for chronic hypoventilation and respiratory failure in ALS, allows a significant improvement in survival and quality of life (Heiman-Patterson & Miller, 2006). Many tests are available to objectively assess the performances of the respiratory system, and there is increasing interest toward those able to sensitively detect mild impairment. Moreover, great attention has to be put on monitoring of cough effectiveness, management of respiratory secretions and prevention of respiratory infections. For all these reasons the management of respiratory dysfunction has become a

*2Neurorehabilitation Unit, Fondazione Salvatore Maugeri, Mistretta (ME), Italy 3Università Degli Studi dell'Insubria, Varese, Italy* 

<sup>\*</sup> Paolo Volanti2, Domenico De Cicco2, Antonio Spanevello3, Gianluca Battaglia2, Santino Marchese4, Alfonsa Claudia Taiello1, Rossella Spataro1 and Vincenzo La Bella1

*<sup>1</sup>ALS Clinical Research Center, Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNeC), University of Palermo, Palermo, Italy* 

*<sup>4</sup>Respiratory Intensive Care Unit, Ospedale Civico ARNAS, Palermo, Italy* 

Assessment and Management of

late signs of respiratory failure in ALS.

Respiratory Dysfunction in Patients with Amyotrophic Lateral Sclerosis 581

Arterial blood gas analysis may also be of help in the evaluation of patients with ALS, especially in those with severe bulbar involvement, since it could reveal resting hypercapnia (PaCO2 > 6.5 kPa) and/or hypoxemia (PaO2 < 80 mmHg). However, these are usually very

Sniff nasal inspiratory pressure (SNIP) is regarded as a good measure of diaphragmatic strength, and is probably more accurate than FVC, especially at later stages, although even SNIP may underestimate respiratory function in patients with bulbar involvement, because of upper airway collapse. However, a sniff nasal pressure test < 40% of predicted value (or < 60 cmH2O) is a significant predictor of sleep disordered breathing, nocturnal hypoxemia,

Finally, nocturnal hypoventilation and sleep-disordered breathing are common problems in ALS with the progression of the disease, and can occur even when respiratory muscle function is only mildly affected and in the presence of normal daytime gas exchange (Gay et al., 1991; Ferguson et al., 1996; Arnulf et al., 2000). Nocturnal hypoventilation is particularly severe during rapid eye movements (REM) sleep, when all postural and accessory muscles are physiologically atonic, and only the diaphragm, which may itself be impaired, is left to sustain ventilation and overcome any upper airway resistance (Ferguson et al., 1996). Then, since nocturnal oximetry is easily performed and can be executed domiciliary, it has become frequently used in clinical practice for the evaluation of respiratory involvement in patients with ALS and as a guide to initiate mechanical ventilation. Nocturnal oximetry correlated with survival (mean SaO2 < 93 mmHg was associated with mean survival of 7 months vs 18 months when mean SaO2 > 93 mmHg) (Velasco et al., 2002), and nocturnal desaturations < 90% for 1 cumulative minute was a more sensitive indicator of nocturnal hypoventilation than either FVC or MIP (Jackson et al., 2001). Polysomnography is not routinely performed, because is costly and demanding, although it can reveal causes of poor sleep quality different from

hypercapnia and mortality (Fitting et al., 1999; Lyall et al., 2001b; Carrat et al., 2011).

disordered breathing, such as motor activity during sleep (Lo Coco et al., 2011).

Long-term mechanical ventilation in patients with neuromuscular problems was first introduced between 1950 and 1960 in France and Sweden as a consequence of the poliomyelitis epidemics. During the following decades, the concept of home mechanical ventilation expanded rapidly, and long-term non-invasive positive-pressure ventilation (NIPPV) was implemented in many other countries and for many other conditions,

Chronic alveolar hypoventilation is a state characterized by reduced arterial oxygen tension and increased carbon dioxide tension, which the patient may correct at least partially by voluntary hyperventilation. The underlying mechanisms are not yet fully understood and may involve impairment of lung mechanics or airway function and cough, ventilationperfusion mismatch, blunted central ventilatory drive, or respiratory muscle fatigue. Abnormalities may occur while awake or during sleep. In most cases, chronic alveolar hypoventilation leads to daytime fatigue, hypersomnia, and changes in psychological

The application of ventilatory assistance in ALS, most frequently non-invasively, has led in the last fifteen years to a revolution in respiratory assistance and ventilatory support in these patients, with a significant impact on the natural history of the disorder. Indeed, NIPPV has been shown to alleviate respiratory symptoms, to extend survival considerably,

**3. Non-invasive mechanical ventilation** 

function.

including ALS, to treat chronic alveolar hypoventilation.

major issue in the multidisciplinary assessment of patients with ALS, and the pulmonologist has gained an increasing role in this process. However, there is still little consensus on pulmonary care worldwide, and clinical practice varies widely from country to country, especially when NIPPV becomes inadequate to support respiratory muscle failure. It is, then, good practice to discuss respiratory issues in advance with the patients and their carers in order to avoid emergency interventions or unwanted treatments, and frequently review these decisions during the course of the disease.

This chapter focuses on the recent advances that have emerged in the management of pulmonary dysfunction in patients with ALS with emphasis on respiratory evaluation and mechanical ventilation.
