**6. Conclusion**

586 Amyotrophic Lateral Sclerosis

ALS is a relentless pathology that causes progressive muscle dysfunction. Therefore respiratory capacity eventually fails, despite NIPPV treatment. Indeed, at first, NIPPV is generally used for intermittent nocturnal support to alleviate symptoms of nocturnal hypoventilation, although as respiratory function worsens, patients tend to require increasing daytime support and eventually continuous support. When all the respiratory aids fail to maintain adequate blood oxygen saturation, the only intervention that allows survival of these patients is invasive mechanical ventilation through a tracheostomy tube. Treatment failure seems not to be dependent on lung or respiratory muscle function but on

When placed on invasive ventilation patients are supported from a respiratory point of view; however, the loss of motor neurons goes on progressively, leading to complete paralysis and muscular atrophy. Some patients may eventually reach a "locked in" state in which they cannot communicate at all, because there is also total paralysis of the extraocular muscles. When connected to tracheostomy tubes patients may survive for many years, with respiratory tract infections the most frequent cause of death (Bradley et al., 2002; Hayashi & Oppenheimer, 2003; Lo Coco et al., 2007; Marchese et al., 2008; Vianello et al., 2011). Median survival time usually ranges from 2 to 4 years. Interestingly, the amyotrophic lateral sclerosis functional rating scale (ALSFRS), a disease-specific rating scale that assesses functional impairment, has been shown to predict both length of hospital stay as a result of acute respiratory failure and survival after initiation of invasive ventilation in these patients

Notwithstanding its effect on survival, only a minority of patients with ALS receive invasive mechanical ventilation, at least in the western Countries (Moss et al., 1993; Miller et al., 2000; Neudert et al., 2001). On the contrary, in Japan the frequency of invasive ventilation is considerably higher. Many patients are treated in emergency without advance planning, because of a respiratory crisis, whereas the number of patients that electively choose this treatment is low (Moss et al., 1993, 1996; Cazzoli & Oppenheimer, 1996; Lo Coco et al., 2007). Socio-economic reasons may be one of the possible explanations for the low prevalence of invasive ventilation in ALS, given the relatively high costs of this treatment. Moreover there is a need for 24-hour-caregiving, which could be perceived by caregivers and relatives as extremely burdensome. A recent study suggested that the choice of invasive ventilation was consistent with a sustained sense that life was worth living in any way possible, at least for some time and within certain boundaries, although it may involve unrealistic expectations of cure by some (Rabkin et al., 2006). Moreover, the attitudes of the treating physician have also a great influence (Moss et al., 1993), and there is concern that tracheostomy will prolong

life beyond the point that the patient can communicate or interact with others.

Despite these many doubts and concerns, the majority of patients that underwent invasive ventilation were positive about their choice (Moss et al., 1993), reporting a satisfying quality of life (Cazzoli & Oppenheimer, 1996; Kaub-Wittemer et al., 2003), and indicating that they would repeat the choice again in the same situation. Caregivers were more frequently burdened and distressed by this intervention and they frequently witnessed a marked reduction of social life activities (Cazzoli & Oppenheimer, 1996; Gelinas et al., 1998; Kaub-

It is good practice that patients together with their families discuss end-of-life issues and preferences with the physician, so that advance directives and patient's wishes are well

**5. Invasive mechanical ventilation** 

bulbar dysfunction (Bach et al., 2004).

Wittemer et al., 2003; Rabkin et al., 2006).

(Lo Coco et al., 2007).

Recent publications provided important contributions to many aspects of respiratory care for patients with ALS, such as non-invasive ventilation and assisted cough. There is a need for regular assessment and follow up of respiratory function, and investigations should include daytime assessment of respiratory function (including FVC and SNIP) as well as sleep studies in order to ensure early recognition of patients with respiratory muscle impairment (Lo Coco et al., 2008).

At present time the only approved pharmacological treatment for ALS is riluzole, which extends survival by about 2 months (Miller et al., 2007). On the other hand, NIPPV treatment allows survival for longer periods of time, improves quality of life, and may probably alter the disease course. As a consequence, NIPPV should be considered a major treatment option in patients with chronic hypoventilation or in whom respiratory impairment has become evident during sleep despite normal diurnal respiratory function. Every effort, then, should be made to improve NIPPV implementation in the management of patients with ALS worldwide, since it is still underutilized. The degree of hypoventilation that should prompt introduction of NIPPV must be defined further, even if there is a general tendency toward earlier intervention. Nocturnal hypoventilation could be particularly useful for this purpose.

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Prevention of aspiration and pneumonia, and adequate management of bronchial secretions are two other important issues. Adequate treatment of sialorrhea and dysphagia are important in the reduction of pneumonia risk. Insufficient cough is a condition that can be diagnosed by measuring peak cough flow and should, whenever present, be treated in patients with ALS. There is some evidence that the MI-E device could be of help in cough assistance, except for patients with severe bulbar dysfunction, but further research is needed, as well as randomized trials that compare the MI-E with other techniques of assisted coughing.
