Abstract & Commentary
Source: Tsuda T, et al. Impaired chemosensitivity to hypoxia is a marker of multiple system atrophy. Ann Neurol. 2002;52: 367-371.
Multiple system atrophy (MSA) is a neurodegerative disorder that can take protean forms. Patients develop symptoms and signs in 1 or more of 3 neurologic systems: autonomic, cerebellar and parkinsonian. The major forms of MSA are Shy-Drager syndrome (autonomic failure), Olivo-Ponto-Cerebellar-Atrophy (cerebellar degeneration), and Striatonigral degeneration (parkinsonism that is usually poorly responsive to levodopa). These entities are united by a common pathologic feature, the presence of oligodendroglial cytoplasmic inclusions. During life it can be difficult to secure the diagnosis of MSA, particularly in older patients who present with pure cerebellar symptoms and signs. In this elegant paper, Tsuda and colleagues show that patients with the cerebellar form of MSA can be distinguished from idiopathic cerebellar degeneration before other signs of autonomic or parkinsonian disability develop.
Tsuda et al followed 9 control patients, 31 patients with idiopathic Parkinson’s disease, 6 patients with Striatonigral degeneration, and 13 patients diagnosed with a sporadic cerebellar degeneration not linked to a trinucleotide repeat expansion. Of these 13 patients, 6 eventually developed parkinsonian and autonomic features consistent with MSA, and 7 did not. Chemosensitivity to hypoxia and hypercapnia were measured in each patient.
There was no difference in sensitivity to hypercapnia between any patient group and control. In contrast, the hypoxic ventilatory response was moderately depressed in patients with Parkinson’s disease and severely depressed in those with Striatonigral degeneration. The 6 cerebellar patients who eventually developed other features of MSA had a profound depression in hypoxic ventilatory response even before parkinsonian and autonomic symptoms developed, while the 7 who remained with purely cerebellar signs did not.
Patients with MSA are at risk for sudden death for several reasons. They are prone to develop vocal cord abductor paresis, leading to nocturnal stridor. Stridor is a neurologic emergency, and once recognized should lead the astute clinician to intervene with nasal continuous positive airway pressure or even tracheostomy. However even patients who undergo tracheostomy can die from ventilatory failure. Tsuda et al’s study offers a possible explanation for this problem. MSA patients have a profound impairment in chemosensivity to hypoxia. This is true even in those patients with the pure cerebellar form of the illness.
While tests of hypoxic ventilatory drive are not routinely available, this study suggests a useful approach to identify patients at risk for sudden death. It also implies that the neurodegenerative process in MSA affects neural systems important in ventilatory drive. —Steven Frucht
Dr. Frucht, Assistant Professor of Neurology, Movement Disorders Division, Columbia-Presbyterian Medical Center, is Assistant Editor of Neurology Alert.