Ms. D’s brain MRI from months earlier showed bilateral periventricular and subcortical white-matter changes. Based on these findings, a cervical and thoracic spine MRI was obtained to rule in or out multiple sclerosis. No focal lesion of the spinal cord was noted.
Laboratory studies included rheumatoid arthritis and antinuclear antibody titer, Lyme serology, HIV screen, rapid plasma reagin, and cardiolipin antibody screen, all of which were negative. A complete blood count as well as B12 and thyroid-stimulating hormone levels were within normal range. Heavy-metal screen was negative. At the time she presented to the neurologist, the patient’s liver function was normal; however eight months later, on presenting to the primary-care office, her liver enzymes were markedly elevated: alkaline phosphatase 195 units/L (reference range 35-104), alanine aminotransferase (ALT) 238 units/L (0-31), and aspartate aminotransferase (AST) 463 units/L (0-31). These results prompted a check of ethanol level (which was normal) and a hepatitis panel (also normal) to rule out a viral etiology. The poor liver function also prompted an ammonia determination, which was 132 μg/dL (reference range <47).
Ms. D was given a diagnosis of hepatic encephalopathy (HE). Also known as portosystemic encephalopathy, HE is a syndrome marked by impaired brain function in persons with liver failure. Ammonia is the most notable neurotoxin in the pathogenesis of HE. The condition can be reversed by lowering the ammonia level. The GI tract is the primary source of ammonia; however, muscle wasting (common in this patient group) can also lead to elevated levels in the diseased liver. Hyperammonemia interferes with the uptake of amino acids at the blood-brain barrier, and ammonia itself affects brain function at several sites, each of which can develop encephalopathy. Brain atrophy and brain edema have been found in patients with HE.
Though Ms. D’s presentation fits the HE pattern, the syndrome can present in a wide spectrum of severity, ranging from minor signs of altered brain function to overt neuropsychological signs to coma. The diurnal sleep pattern often becomes disturbed. Generalized muscle weakness and fatigue are present along with dysorientation and confusion. Neurologic deficits include slurred speech, ataxia, and alterations in reflexes that can eventually result in actual loss of reflexes in more severe cases. The clinician may also find hypotension, nystagmus, and poor cognition and recollection on mental status exam. Asterixis is a notable finding in HE when the ammonia level is significantly elevated.
Treatment is aimed at reducing the ammonia level. There is a paucity of evidence from randomized controlled trials supporting the use of lactulose (lactitol solution) for this purpose. Nevertheless, lactulose is considered the mainstay of therapy because of its notable efficacy over placebo. Diarrhea, cramping, and flatulence are major side effects of lactulose. Enemas using lactulose have also proven effective in improving the symptoms of HE.
In addition to abstaining from alcohol, Ms. D was treated with 30 mL of lactulose syrup p.o. twice daily for 10 days. Laboratory results obtained two weeks later were much improved (alkaline phosphatase 106, ALT 28, and AST 27). Her ammonia level quickly returned to normal (39 μg/dL). Symptomatically, she was significantly better on follow-up. Her confusion had abated, and her energy level was up. Ms. D resumed exercising and was able to return to work. After being educated about her diagnosis and the role of ammonia, alcoholism, and liver disease in her overall health, she vowed to avoid alcohol.