Clinical and Neuroelectrophysiological Characteristics of Split Face Phenomenon in Patients with Amyotrophic Lateral Sclerosis

Objective Amyotrophic lateral sclerosis (ALS) is a chronic, progressive degenerative disease affecting both upper and lower motor neurons, primarily characterized by skeletal muscle weakness and atrophy. Notably, the same muscle group may exhibit asynchronous involvement. This study aims to investigate the involvement patterns of the orbicularis oculi (OOc) and orbicularis oris (OOr) in ALS patients, compare the findings with healthy controls (HCs) and myasthenia gravis (MG) patients, and explore the characteristics and clinical significance of facial muscle involvement in ALS.

Methods Clinical and neuroelectrophysiological data were collected and analyzed in ALS patients (ALS group), HCs (HCs group) and MG patients (MG group). Clinical data included age, gender, clinical symptoms and signs, and the revised ALS Functional Rating Scale (ALSFRS-R) score. Split-face (SF) phenomenon was defined as OOc muscle strength being greater than OOr muscle strength. The negative peak amplitudes of compound motor action potential (CMAP) recorded from OOc and OOr, namely CMAP_OOc and CMAP_OOr, were collected for electrophysiological evaluation.

Results Number of patients enrolled in each group: 137 in the ALS group, 42 in the HCS group, and 33 in the MG group.Of the 137 ALS patients, 74 presented clinical SF manifestation. The CMAP_OOc amplitude in the ALS group was 2.00 (1.66, 2.40) mV, showing no significant difference compared with 2.20 (1.86, 2.58) mV in the HCs group (P > 0.05). The CMAP_OOr amplitude in the ALS group was significantly lower than that in the HCs group 2.80 (1.91, 3.85) mV vs. 4.50 (4.00, 5.10) mV, P < 0.0001, while the CMAP_OOc/CMAP_OOr ratio was significantly higher 0.71 (0.54, 1.06) vs. 0.47 (0.40, 0.54), P < 0.0001. Compared with ALS patients without SF, those with SF had a higher proportion of bulbar onset ALS (ALS-BO) (26/74 vs. 7/63, P=0.0012), a faster disease progression rateΔFS: 0.75 (0.50, 1.17) vs. 0.50 (0.25, 1.00), P=0.0081, and lower ALSFRS-R bulbar scores9 (6, 12) vs. 12 (11, 12), P < 0.0001. No SF was observed in all MG patients. The CMAP_OOc/CMAP_OOr ratio was significantly higher in ALS-BO patients than in MG patients 0.82 (0.59, 1.22) vs. 0.48 (0.38, 0.59), P < 0.0001. The sensitivity and specificity of SF for distinguishing ALS-BO from MG were 78.79% and 100%, respectively.

Conclusions More than half of ALS patients have SF phenomenon, and neuroelectrophysiological indicators can provide objective evidence for SF. SF is correlated with bulbar onset, severe bulbar symptoms and rapid disease progression, and can serve as a potential indicator for the differential diagnosis between ALS-BO and MG.