Objective: Bulbar-ALS generally portends a poor prognosis. Rarely, patients present with isolated bulbar palsy (IBP) with comparatively better prognosis. To define this phenotype, the present study compared the clinical and neurophysiological characteristics of patients with IBP to more typical bulbar-ALS.
Methods: All patients with bulbar onset disease were prospectively identified. IBP was diagnosed if no significant limb progression developed over six months. Patient demographics, clinical features and conventional neurophysiological biomarkers were recorded. Cortical excitability was studied using threshold tracking transcranial magnetic stimulation.
Results: Thirty two patients with bulbar onset disease (11 males, 21 females, age 64.1 +/- 9.0 years) were identified. Twelve patients were defined as IBP (3 male, 9 female, age 61.1 +/- 8.2 years) and twenty had more typical bulbar-ALS (8 males, 12 females, age 65.9 +/- 9.3 years). IBP patients were more likely to be female with predominantly UMN bulbar features. In contrast, patients with bulbar-ALS had more prominent LMN features. CMAP amplitude was preserved in patients with IBP compared to patients with bulbar-ALS (7.1mv compared to 4.2mV, P < 0.05) as was the neurophysiological index (1.22 compared to 0.45, P < 0.05). Furthermore, cortical excitability was normal in IBP patients and abnormal in patients with bulbar-ALS, who had features of cortical hyperexcitability.
Conclusions: IBP patients were predominantly female with UMN bulbar features. Neurophysiologically, IBP patients had no evidence of peripheral LMN dysfunction and had normal cortical excitability. Identification of IBP predicts a better prognosis and stratification of patients for clinical trials.