Acquired Hepatocerebral Degeneration

Acquired hepatocerebral degeneration is an irreversible, slowly progressive neurological syndrome in patients with chronic liver disease and portosystemic shunting. It causes parkinsonism, ataxia, tremor, chorea and cognitive decline.

It is uncommon, found in under 1% to 2% of cirrhosis, mostly in patients with several episodes of overt hepatic encephalopathy and large shunts. Many are men aged 50 to 70 years.

Pathophysiology.

Chronic exposure to ammonia and manganese (which accumulates in the globus pallidus and substantia nigra) causes astrocytic changes (Alzheimer type II cells), microcavitation and neuronal loss in the basal ganglia, cerebellum and cortex.

Fluctuating cognition progressing to dementia, a parkinsonian syndrome (bradykinesia, rigidity, postural tremor) that responds poorly to levodopa, cerebellar ataxia and dysarthria, asterixis, myoclonus, orofacial dyskinesia and spastic paraparesis.

Red flags.

• Acute confusion or a drop in level of consciousness.
• Sudden focal deficit.
• Falls with injury.

Brain magnetic resonance imaging shows symmetrical T1 hyperintensity in the globus pallidus and substantia nigra from manganese deposition. Ammonia is raised. CT or Doppler shows shunting. Exclude Wilson disease (ceruloplasmin and 24-hour urine copper), other parkinsonian disorders, Creutzfeldt-Jakob disease, structural lesions and drug causes (antipsychotics, metoclopramide).

Differential diagnosis.

• Wilson disease.
• Idiopathic Parkinson disease.
• Multiple system atrophy.
• Manganese toxicity from parenteral nutrition.
• Chronic alcoholic cerebellar degeneration.

Liver transplantation is the only effective treatment and can reverse the syndrome if done early. Reduce shunting where feasible (embolisation or TIPS reduction) and control encephalopathy.

• Lactulose: 20 to 30 mL orally two to three times daily, titrated to 2 to 3 soft stools daily; maximum 120 mL daily; monitor sodium, potassium and hydration; reduce for diarrhoea.
• Rifaximin: 550 mg orally twice daily long term; maximum 1,100 mg daily; monitor diarrhoea and Clostridioides difficile infection; no renal adjustment.
• Levodopa with carbidopa (short course for parkinsonism, limited benefit): levodopa 100 mg with carbidopa 25 mg orally three times daily, increased every 1 to 2 weeks to a maximum of 800 mg of levodopa daily; stop if no benefit after 8 weeks; monitor for nausea, hypotension, dyskinesia and confusion; start at half the dose in older adults and in hepatic impairment.

Avoid benzodiazepines and antipsychotics. Provide physiotherapy and falls prevention.

Monitoring. Neurological scoring and cognition every 3 months; MRI if the syndrome changes.

Referral and escalation. Hepatology, neurology and the liver transplant centre.