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Liver diseases may give rise to variable degrees of neurological impairment, which mostly consist of the syndrome of hepatic encephalopathy, due to the toxic effect of ammonia on the brain during episodes of liver decompensation. In a minority of patients, repeated episodes of liver failure can lead to a chronic progressive encephalopathy, not necessarily related to hyperammonaemia, known as acquired hepatocerebral degeneration (AHD).1 The pathogenesis of AHD is unclear, but the relation with the acute form of hepatic encephalopathy seems a crucial point. Cerebral deposition of manganese may have a pathogenetic role. The disease may appear after one or more episodes of hepatic coma or, rarely, become manifest in the absence of them. Neuropathology typically discloses degenerative changes in the basal ganglia. The modern techniques of neuroimaging disclose these lesions in vivo.2 The clinical picture varies, neuropsychiatric changes and movement disorders usually being prominent. The syndrome is poorly responsive to medical therapy, thus being considered largely irreversible.
We report on a patient with AHD who was cured by liver transplantation.
A 59 year old man came to us in November 1997 for a neurological consultation before inclusion in the waiting list for liver transplantation. He had a history of chronic hepatic disease—alcohol and HCV related liver cirrhosis—which had begun some years before. No familial hepatic or neurological diseases were reported. In 1995 he had an episode of hepatic encephalopathy, consisting in somnolence and confusion lasting 36 hours. At the time of examination, the patient had stopped alcohol consumption 1 year before; liver failure was grade C-10 of the Child-Pugh classification. Copper balance was normal. Neurological examinations and EEG gave normal results. The patient was put on the waiting list for liver transplantation. In February and March 1998, he had two episodes of mild ascites with signs of encephalopathy (confusion and asterixis), both reversed by medical therapy. In April 1998 the patient began to complain of sleep disorders, tremor, dysarthria, motor slowness, and subtle cognitive dysfunction, not reversed by medical therapy for hepatic dysfunction. On 6 June 1998, his neurological suitability for liver transplantation was reconsidered. He seemed alert, oriented, and cooperative, with a slight slowness of psychomotor activity. The neurological examination showed hypomimia, dysarthria, bradykinesia, oral dyskinesia, and mild bilateral hand tremor. Neuropsychological examination showed a remarkable impairment of information processing control (attention, vigilance, psychomotor speed, intelligence) with sparing of memory (table). An EEG disclosed diffuse slow activity. Cerebral MRI showed circumscribed bilateral lucencies on the lentiform nuclei on T1 weighted images. On 10 July liver transplantation was performed, with a successful course and a rapid improvement of the neurological disturbances. Immunosuppressive treatment with cyclosporine did not induce neurological complications. One month after liver transplantation only a mild dysarthria persisted. An EEG was normal. A neuropsychological assessment 3 months after surgery showed a remarkable improvement in the cognitive performances, especially in information processing control tasks (table), whereas cerebral MRI was unchanged. Twelve months later, neurological examination was normal and cerebral MRI disclosed a reduction of basal ganglia lucencies. Neuropsychological testing documented a slight further improvement in control functions of information processing, with a slight decline in some memory performances (table). No other neurological problems emerged during subsequent months.
This patient had an AHD presenting with movement and cognitive disorders. The first consisted in disabling movement disorders, with severe bradykinesia and dysarthria. The cognitive impairment included both a decreased functioning of the frontal executive functions and single function deficits (expecially visuospatial abilities and language), conveying a picture of “hepatic dementia”. Cerebral MRI documented the basal ganglia lesions usually seen in AHD.2Both the clinical and the neuroradiological abnormalities were reversed by liver transplantation. After surgery, the recovery from neurological impairment was prompt and complete, whereas neuroimaging improvement occurred later. This outcome resembles that previously seen in a patient with Wilson's disease.3 Despite the different pathogenesis, the similarities between AHD and Wilson's disease are remarkable for pathological lesions and clinical and neuroradiological presentation.1 2 Liver transplantation has been reported to reverse neurological manifestations in most patients with Wilson's disease.3 Liver transplantation in AHD is confined to two cases. A cirrhotic patient with improved chronic cognitive and motor disorders after liver transplantation was described in 1970.4 Twenty years later, Powell et al 5 reported a case of successful liver transplantation in AHD. Their patient had a significant improvement in intellectual functions and chronic neurological signs early after surgery. Our present finding confirms these positive results and also documents that neuroradiological abnormalities are reversible. It is conceivable that both Wilson's disease and AHD are characterised by an early stage neuropathological process mainly affecting the basal ganglia, where MRI detectable hepatocerebral degeneration is slowly reversible and liver transplantation can rapidly improve neurological symptoms. The duration of the disease does not seem to be a crucial factor, as patients with long standing encephalopathy may also recover after liver transplantation both in AHD5 and in Wilson's disease.3
This conclusion has pathogenetic and therapeutic implications: the presence of signs and symptoms of chronic hepatocerebral degeneration, both in Wilson's disease and in the acquired non-Wilsonian form, should not be considered a contraindication for liver transplantation and surgery may be the elective treatment for the neurological syndrome.
We are indebted to Dr Katia Mattarozzi who administered the neuropsychological tests.