High Resolution Manofluorographic Study in Patients With Multiple System Atrophy: Possible Early Detection of Upper Esophageal Sphincter and Proximal Esophageal Abnormality

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P < 0.01). MSA-P patients had more rapid functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03; confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed similar survival. Onset in older individuals showed increased risk of confinement to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01). Patients initially complaining of motor symptoms had accelerated risk of aid-requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared with those initially complaining of autonomic symptoms, while the time until confinement to a bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA.

Multiple system atrophy (MSA) and Lewy body disorders (LBDs) are associated with impaired control of gastrointestinal and cardiac functions. The dorsal vagal nucleus (DMV) innervates enteric neurons, whereas the ventrolateral nucleus ambiguus (NAmb) innervates the heart. The relationship between DMV and NAmb involvement and the gastrointestinal or cardiovagal manifestations in MSA and LBD is unclear. The authors counted the cholinergic neurons in the DMV and NAmb in 15 cases of neuropathologically confirmed MSA, 14 of LBD (4 brainstem, 3 limbic, and 7 neocortical), and 12 control cases. All MSA and 8 of the 14 LBD cases had gastrointestinal symptoms; 8 of 12 MSA and 1 of 4 LBD cases had laboratory evidence of cardiovagal failure; 5 of the MSA and no LBD cases had laryngeal stridor. There was loss of cholinergic DMV neurons in all MSA and LBD cases. The degree of DMV cell loss was similar in LBD patient with or without gastrointestinal symptoms. In MSA but not in LBD cases, there was neuronal loss in the ventrolateral NAmb, with lower counts in patients with cardiovagal failure. There is comparable involvement of the dorsal vagal nucleus (DMV) in multiple system atrophy (MSA) and different stages of Lewy body disorders (LBDs). The relationship of DMV involvement and gastrointestinal symptoms is uncertain. Loss of neurons in the ventrolateral nucleus ambiguus may explain the more consistent cardiovagal failure in MSA than in LBD.