Cranial nerve involvement in Charcot-Marie-Tooth disease (CMT) is rare, though there are a number of CMT syndromes in which vocal cord paralysis is a characteristic feature. CMT disease due to mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) has been reported to be associated with vocal cord and diaphragmatic palsy. In order to address the prevalence of these complications in patients with GDAP1 mutations we evaluated vocal cord and respiratory function in nine patients from eight unrelated families with this disorder. Hoarseness of the voice and inability to speak loudly were reported by eight patients and one had associated symptoms of respiratory insufficiency. Patients were investigated by means of peripheral and phrenic nerve conduction studies, flexible laryngoscopy, pulmonary function studies and polysomnography. Nerve conduction velocities and pathological studies were compatible with axonal CMT (CMT2). Flexible laryngoscopy showed left vocal cord palsy in four cases, bilateral cord palsies in four cases and was normal in one case. Restrictive respiratory dysfunction was seen in the eight patients with vocal cord paresis who were all chair-bound. These eight had confirmed phrenic nerve dysfunction on neurophysiology evaluation. The patient with normal vocal cord and pulmonary function had a less severe clinical course.This study shows that CMT patients with GDAP1 mutations develop severe disability due to weakness of limb muscles and that laryngeal and respiratory muscle involvement occurs late in the disease process when significant proximal upper limb weakness has developed. The early and predominant involvement of the left vocal cord innervated by the longer left recurrent laryngeal nerve suggests a length dependent pattern of nerve degeneration. In GDAP1 neuropathy, respiratory function should be thoroughly investigated because life expectancy can be compromised due to respiratory failure.

Noninvasive positive-pressure home ventilation (NIPPHV) improves arterial blood gases, dyspnea and health-related quality of life (HRQL) in patients with restrictive thoracic diseases. Whether these changes persist during the follow-up remains unclear. The aim of this study was to investigate the long-term effects of NIPPHV upon dyspnea, HRQL, lung function and hospitalization rate in 35 patients with kyphoscoliosis and 27 individuals with several neuromuscular disorders. So, we measured dyspnea, HRQL, lung function and nocturnal oxygen saturation (SaO2) before and after 3, 6, 9, 12 and 18 months after NIPPHV. Dyspnea was assessed with the Borg scale and HRQL was measured using the Spanish validated version of the SF-36 questionnaire. The kyphoscoliosis group showed significant improvement of PaCO2 and SaO2 at 3 months and minor dyspnea changes at 6 months after NIPPHV had been started. These patients also showed improved health status in the following categories: "physical role" and "emotional role" at 3 months and in the categories "social functioning", "vitality" and "mental health" at 6 months after NIPPHV; some of these changes persisted at 9, 12 and 18 months. In the neuromuscular group, a significant improvement of SaO2 was observed at 3 months and this persisted for 18 months. Changes of HRQL in this group included a significant improvement in "physical role" at 3 months, "emotional role" and "social functioning" at 6 months and "physical functioning" at 9 months. The hospitalization rate decreased significantly in all patients from a mean annual admission rate of 1.1 (1.4) before NIPPHV to 0.6 (1.1) after 12 months of ventilatory support (P<0.005). We conclude that: (a) NIPPHV had a higher impact on arterial blood gases, dyspnea and health-related quality of life in patients with kyphoscoliosis than in those with neuromuscular disorders; (b) most clinical and functional changes persisted at long term and (c) a significant decrease in the hospitalization rate after NIPPHV occurred in both groups.

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