Effect of phosphorylation on activities of Rap1A to interact with Raf-1 and to suppress Ras-dependent Raf-1 activation

OBJECTIVE: To develop a method for the detection of bilateral Horner's syndrome in patients with bilateral interruption of the cervical sympathetic pathway or widespread autonomic neuropathy. METHODS: Darkness pupil diameters and redilatation times during light reflexes have been recorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients with bilateral Horner's syndrome. The aetiologies of the last group were diabetic autonomic neuropathy (three cases), amyloidosis (four), pure autonomic failure (PAF) (four), dopamine-beta-hydroxylase deficiency (two), and one case each of hereditary sensory and autonomic neuropathy (HSAN) type III, carcinomatous sympathetic neuropathy, familial dysautonomia, multiple system atrophy, Anderson-Fabry disease, and anterior spinal artery thrombosis at C5,6 and one had had bilateral cervical sympathectomies. RESULTS: Darkness diameters on the affected side were below normal in 12 patients with unilateral Horner's syndrome, the measurement yielding only 26% sensitivity for detection of the condition. By contrast, the time taken to reach three quarter recovery in the light reflex (T3/4) was abnormally prolonged (redilatation lag) in 33 of the same eyes. The measurement yielded 70% sensitivity and 95% specificity for detection of the condition. In 20 cases, diagnosed on clinical grounds as having bilateral Horner's syndrome of various aetiologies, pupil diameters were abnormally small on both sides in five and on one side in three patients. Fourteen of these patients had significant redilatation lag in both eyes, five patients in one eye, and one patient had it in neither eye. Measurement of redilatation lag was therefore a more sensitive diagnostic test than pupil diameter in both unilateral and bilateral Horner's syndrome. CONCLUSIONS: Provided that the pupils are not tonic, bilateral Horner's syndrome can be diagnosed on the basis of redilatation lag. It occurs clinically in some generalised autonomic neuropathies and with interruption of the local sympathetic nerve supplies to the two eyes.