Ambiguous mechanisms of dysphagia in multiple system atrophy.

Sir, we read with great interest the article by Schwarzacher et al. (2011) describing the neuroanatomical characteristics of the human pre-Bötzinger complex and its involvement in multiple system atrophy and spinocerebellar ataxia 3 (SCA3). In this study, the authors provide a thorough analysis of the pre-Bötzinger complex and demonstrate that somatostatin and neurokinin 1 receptor expressing neurons are severely reduced in a neurodegenerative disorder presenting with severe central respiratory dysfunction (multiple system atrophy), but spared in patients with no history of such respiratory deficits (SCA3). This study provides strong neuropathological evidence that degeneration of the preBötzinger complex occurs in multiple system atrophy and extends previous findings showing a drastic reduction of putative brainstem chemosensory neurons in this disease (Benarroch, 2007). Altogether, these findings strongly support the hypothesis that degeneration of these brainstem respiratory neurons underlies respiratory dysfunction in multiple system atrophy. In addition to the characterization of the pre-Bötzinger complex, Schwarzacher et al. (2011) also provide a detailed analysis of the nucleus ambiguus in multiple system atrophy and SCA3. In both diseases, the ventral part of the nucleus ambiguus (containing pre-ganglionic cardiovagal neurons) display severe neuronal loss, which also has been shown by others (Benarroch et al., 2003, 2006). Although less documented for SCA3, these findings may explain altered heart rate control occurring in both diseases (Cohen et al., 1987; Pradhan et al., 2008). Analysis of the dorsal portion of the nucleus ambiguus (which contains branchimotor neurons innervating the larynx, pharynx and oesophagus) revealed a drastic reduction of the number of cholinergic neurons in patients with SCA3. Conversely, this dorsal portion of the nucleus ambiguus was spared in patients with multiple system atrophy, in accordance with previous results (Benarroch et al., 2003). Clinical and pathological data from patients with SCA3 support the authors’ conclusions that degeneration of ambigual motoneurons is one of the underlying mechanisms of dysphagia in this disease. However, if dysphagia is a prominent clinical feature of SCA3, affecting 460% of patients (Jardim et al., 2001), it is also commonly observed in multiple system atrophy. Accordingly, severe dysphagia has been described in 32% of patients with multiple system atrophy in one post-mortem study (O’Sullivan et al., 2008) and dysphagia was a subjective complaint in 73% of patients with multiple system atrophy in a smaller post-mortem study (Muller et al., 2001). In both studies, the presence of dysphagia was unequivocally associated with a bad prognosis and a short survival time. In our prospective cohort of patients with multiple system atrophy who are followed at the French multiple system atrophy reference centre, we found that 64.1% of the patients (n = 78) who were examined in 2010 with the Unified Multiple System Atrophy Rating Scale (UMSARS) displayed at least some degree of dysphagia (Table 1 and Fig. 1A). Moreover, of the 12 patients with multiple system atrophy who died in 2010, 25.0% received gastrostomy feeding at the end of life. The severity of dysphagia doi:10.1093/brain/awr185 Brain 2012: 135; 1–3 | e205