Intermittent disconjugate gaze: A novel finding in nonalcoholic steatohepatitis and cryptogenic cirrhosis
Authors: Abdullah M. S. Al‐Osaimi, Carl L Berg, Stephen H. Caldwell
Journal: Hepatology (2005)

Nonalcoholic steatohepatitis (NASH) is a chronic liver condition that can progress to end-stage liver disease, and possibly present as cryptogenic cirrhosis (CC).1, 2 The prevalence of NASH is unknown, but it afflicts about 8 million adults in the United States.2 The pathogenesis of NASH remains poorly understood, but mitochondrial dysfunction has been proposed.3 Ocular muscle dysfunction is a common feature of systemic mitochondrial disorders.4 Having sporadically observed intermittent disconjugate gaze (IDG), in patients with NASH and CC, we sought to determine the prevalence of IDG in both populations in comparison to hepatitis C virus (HCV) patients of similar disease severity. One-hundred and nineteen outpatients seen in our hepatology practice with NASH-proven by histology (n = 43), CC (n = 31), and HCV (n = 45) were prospectively examined for presence of IDG. IDG was detected by examining the ocular muscles range of motion (Fig. 1). In all cases, the dysfunction involved horizontal but not vertical gaze, and only few of the patients were aware of its presence, in some cases dating to childhood. We found that five of 43 (12%) NASH patients, 7 of 31 (23%) CC patients, and none of the HCV group had IDG, P = .05, and P = .001, respectively, when compared to HCV patients (12 of 74 combined NASH and CC vs. 0 of 45 HCV, P = .01). The 12 patients with IDG (age 54 years ± 10) consisted of 5 females and 7 males, with a mean BMI of 37 ± 7. Nine had type two diabetes mellitus, 5 had modest past alcohol intake, while 7 were lifelong abstainers, and 3 did not have cirrhosis. The patients denied any knowledge of muscle or mitochondrial disorders in their family. However, in the IDG patients the family history was positive in two for cerebral palsy and three had family history of neurodegenerative disorders (2 Parkinson's and 1 Alzheimer disease). (A) Eyes in resting position. (B) Eyes when looking to the left and then moving the followed object to the center of the visual field, showing the lag of the left eye to follow. (C) Eyes when looking to the right and then moving the followed object to the center of the visual field, showing the lag of the right eye to follow. (D) Eyes when focusing on object in the center of the visual field. The abnormality fluctuates and was not typically present at all times. Intermittent disconjugate gaze, a form of ocular muscle dysfunction distinct from diabetic ocular neuropathy, was significantly detected in patients with NASH and CC compared to HCV patients. Mitochondrial dysfunction, observed in some ocular myopathy,4 might explain variable susceptibility to oxidative stress in different tissues. Such conditions could result from acquired or congenital alterations in the balance between oxidative stress and the anti-oxidant system or from impaired energy metabolism in metabolically active tissue.5 The recently described presence of mitochondrial dysfunction in the skeletal muscle of the insulin resistance offspring of patients with type 2 diabetes supports the role of the mitochondrion in this disorder.5 We speculate that IDG is a distinctive feature of NASH, and may further indicate the systemic nature of fatty liver disease and lipotoxicity that warrants further investigation. Abdullah M. S. Al-Osaimi*, Carl L Berg*, Stephen H. Caldwell*, * University of Virginia Health System, Internal Medicine, Division of Gastroenterology and Hepatology, Charlottesville, VA.