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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.101 no.11 Madrid nov. 2009

 

CLINICAL NOTE

 

Acquired chronic hepatocerebral degeneration due to cirrhosis from non-alcoholic steatohepatitis

Síndrome hepatocerebral crónico secundario a cirrosis por esteatohepatitis no alcohólica

 

 

A. Burgos, P. E. Bermejo1, J. L. Calleja, A. Vaquero1 and L. E. Abreu

Services of Gastroenterology and Hepatology, and 1Neurology. Hospital Universitario Puerta de Hierro. Majadahonda. Madrid, Spain

Correspondence

 

 


ABSTRACT

Introduction and objective: acquired chronic hepatocerebral degeneration, acquired hepatolenticular degeneration or pseudo-Wilson is an infrequent disorder with a hepatic origin. Cases in the literature are scarce and it is frequently confused with hepatic encephalopathy and Wilson's disease. The aim of this essay is to report a patient suffering from this disorder due to cirrhosis from non-alcoholic steatohepatitis.
Case report: we present a 54-year-old man diagnosed from cirrhosis grade B9 of the Child Pugh classification. He progressively developed a picture with bradylalia, mild postural and action tremor and spatial and temporal disorientation. Further studies demonstrated an increase of the values of hepatic transaminases and a hiperintensity in the basal nuclei in the cerebral magnetic resonance imaging. Clinical and radiological data established the diagnosis of hepatocerebral degeneration.
Conclusions: acquired chronic hepatocerebral degeneration is a disorder rarely reported in the literature that it is usually confused with other diseases. We alert about the need of having this diagnosis into account with patients developing neurological symptoms after hepatic disease.

Key words: Acquired hepatolenticular degeneration. Hepatic encephalopathy. Acquired chronic hepatocerebral degeneration. Wilson's disease.


RESUMEN

Fundamento y objetivo: el síndrome hepatocerebral crónico, también denominado degeneración hepatolenticular crónica adquirida (DHCA) o pseudo-Wilson, es un trastorno poco frecuente de origen hepático. Los casos recogidos en la literatura son escasos y frecuentemente es confundido con la encefalopatía hepática y con la enfermedad de Wilson. El objetivo de este artículo es presentar un paciente que sufre este trastorno de forma secundaria a una cirrosis por esteatohepatitis no alcohólica.
Caso clínico: se trata de un varón de 54 años diagnosticado de cirrosis en grado funcional de Child-Pugh B9 que presentó un cuadro progresivo de bradilalia, temblor postural y de acción leve y, en ocasiones, desorientación temporoespacial. Los estudios complementarios evidenciaron una elevación de las transaminasas hepáticas y una hiperintensidad de los núcleos basales en la resonancia magnética cerebral estableciéndose el diagnóstico de DHCA.
Conclusiones: la DHCA es un trastorno poco descrito en la literatura que en ocasiones es confundido con otras entidades. Es necesario descartar la presencia de esta patología en los pacientes cirróticos con alteraciones neurológicas tras una enfermedad hepática.

Palabras clave: Degeneración hepatolenticular crónica adquirida. Encefalopatía hepática. Síndrome hepatocerebral. Enfermedad de Wilson.


 

Introduction

Acquired chronic hepatocerebral degeneration (AHD), acquired hepatolenticular degeneration, or pseudo-Wilson is an infrequent neurological disorder provoked by a hepatic disorder that is usually mistaken for hepatic encephalopathy and Wilson's disease. It was initially described in 1914 by van Woerkom (1), although Victor et al. (2) reported a complete anatomopathological description in 1965 in an attempt to clearly differentiate it from Wilson's disease. Neuropathological findings included patchy cortical laminar neuronal loss, neuronal drop-out in the cerebellum and basal ganglia, proliferation of Alzheimer type II glia, and cytoplasmic glycogen granules in basal ganglia (3,4).

AHD has been described in patients suffering from severe liver disease because of several reasons, especially in those with surgically or spontaneously induced porto-systemic shunts. Other causes include hepatic parenchymal diseases such as cirrhosis, chronic and acute hepatitis, and hemochromatosis, or cholestatic diseases such as primary sclerosing cholangitis and primary biliary cirrhosis. However, similar cases to AHD have been described in patients without a history of liver disease (5). These case reports are scarce in the literature, many aspects of the disease are still unclear, and patients respond poorly to conventional therapy. We report the case of a patient suffering from this disorder due to cirrhosis from non-alcoholic steatohepatitis.

 

Case report

We report the case of a 54-year-old man with a history of type-2 diabetes mellitus and obesity, diagnosed with cirrhosis grade B9 in the Child Pugh classification (MELD score of 19) with portal hypertension (splenomegaly, collateral circulation, and esophageal varices) seven years ago. The results of hepatic investigations including no alcohol consumption, viral serologies, copper and iron studies, immunological studies and alpha1-antitrypsin were normal. Liver biopsy showed micronodular cirrhosis and parenchymal hepatic cells with clear cytoplasm, hepatocyte balloon degeneration with Mallory bodies, macrovesicular fat, megamitochondria, and absence of hemosiderin deposits. These biopsy findings and the clinical picture of the patient allowed to establish a diagnosis of non-alcoholic steatohepatitis.

He progressively developed a two-month picture with bradylalia, mild postural and action tremor, and spatial and temporal disorientation. These symptoms did not improve with lactulose and paramomycin therapy.

The patient scored 29/30 and 10/10 on Folstein's Mini-Mental Status Examination and the Clock Drawing Test, respectively. Neurological examination revealed dysarthria, bradylalia, mild action and postural tremor focalized on the left side of his body without flapping tremor, cog-wheel rigidity, and slow alternating movements in his left upper extremity. Laboratory tests revealed the following values: thrombocytopenia 105,000 platelets/dl, prothrombin activity 57%, glutamic-pyruvic transaminase (GPT) 36 U/l, glutamic-oxaloacetic transaminase (GOT) 52 U/l, bilirubin 8.1 mg/dl, alkaline phosphatase 85 U/l, gamma-glutamyl transpeptidase (GGT) 77U/l, albumin 3.3 g/100 ml, glucose 130 mg/100 ml, and lactate dehydrogenase 494 U/l. The results of other laboratory investigations, including thyrotropin (TSH), vitamin B12, and folic acid were all normal. His electroencephalogram showed a general slowing of brain waves (6 cycles per second) without asymmetries or paroxysmal activity. Cerebral tomography showed leukoaraiosis and T1- and T2-weighted magnetic resonance imaging (MRI) displayed symmetric high-intensity signal lesions in the basal nuclei and cerebral peduncles (Fig. 1). Clinical and radiological data established the diagnosis of hepatocerebral degeneration. The patient was treated with lactulose and paramomycin with initial improvement, which was followed by gradual neurological worsening over the next months. The patient was scheduled for liver transplantation, which was considered the best therapeutic option due to the lack of effectiveness of conventional treatments.

 

 

Discussion

Although the pathogenesis of AHD has not been well elucidated, studies have indicated that this disease is associated with multiple metabolic insults, such as ammonia, aromatic amino acids, or manganese, associated with an abnormal susceptibility of certain brain areas to hypoperfusion (3,6-9). The toxic effects of manganese might be a major determinant. It has been proved that manganese is cleared by the hepatobiliary system, and whole blood and cerebrospinal fluid manganese concentrations are several fold above the reference range in some patients with AHD, so that deposition of manganese in the brain is postulated that may induce diffuse degeneration in the cerebral parenchyma. Other theories relate AHD to the same osmotic mechanisms at work in central pontine/extrapontine myelinolysis because the radiologic picture may be similar to cases of central pontine/extrapontine myelinolysis (10).

Clinical symptoms are variable: psychiatric complaints such as apathy, lethargy, excessive somnolence or secondary dementia (11-13), movement disorders such as chorea, focal dystonia, postural tremor, myoclonus (8) or parkinsonism (6), cerebellar symptoms such as ataxia or dysarthria (14,15), or mielopathy -transverse myelitis (16-21)-. The most common symptoms are cognitive impairment, movement disorders or both. Most frequent movement disorders include tremor and chorea (3).

T1-weighted MRI usually shows a hyperintense signal in the basal nuclei (3,6,7), and fronto-parietal lobe and cerebellar atrophy is shown frequently. There seems to be a correlation between the intensity and extension of T1-weighted MRI hyperintensity areas and liver disease severity (22,23). However, this correlation seems not to exist between hyperintensity areas and neurological symptoms (23-26). Although the origin of this radiological hyperintensity is still unclear, recent studies performed by spectroscopy have demonstrated that this lesion is reversible and may show metabolic changes such as a deposition of paramagnetic substances not detoxified by the liver because of porto-caval shunt or hepatic dysfunction (26).

Some patients showing increased signal intensity in the bilateral dentate nuclei on T2-weighted sequences have also been reported, making the condition indistinguishable from Wilson's disease. The clinical symptoms, neuropathological features, and MRI appearance of AHD are rather uniform and similar to those seen in Wilson's disease. Discrimination depends on the following aspects: age at onset (AHD usually starts after severe liver disease), copper metabolism (out of balance only in Wilson's disease), and Kayser-Fleischer ring (characterizing Wilson's disease but not always present, and absent in AHD). Differences between Wilson's disease and AHD are shown in table I.

 

 

Moreover, the disease also differs from the more acute and transient episodes of hepatic encephalopathy: the neurological symptoms of hepatic encephalopathy disappear when the disease is relieved, and there is no organic damage in hepatic encephalopathy. However, individuals with AHD usually experience several episodes of hepatic encephalopathy before brain damage when typical AHD symptoms develop gradually (Table II).

 

 

Some patients respond to lactulose diet (3) or branched chain amino acid therapy (27), apart from symptomatic therapies for parkinsonism, including levodopa (6). It has also been reported that an endovascular occlusion of a porto-systemic shunt is temporarily effective. Liver transplantation in selected cases may be curative (6-8,27) but some studies reported a worsening after an initial period of some months of improvement (28,29). A complete resolution of neurological manifestations as well as of MRI findings in the basal nuclei has been described after liver transplantation (19,30,31), although this improvement has not been observed in all cases (13). In addition, we should not forget about the neurotoxic effects of calcineurin inhibitors (cyclosporine and tacrolymus), which are used for immunosuppression in liver transplantation.

AHD is a disorder rarely reported in the literature, but more and more diagnosed by clinical and radiological findings. We alert about the need of having this diagnosis into account with patients with cirrhosis who do not respond to conventional therapy for hepatic encephalopathy.

 

References

1. Van Woerkom W. La Cirrhose hepatique avec alteration dans les centres nerveux evoulant chez de sujets d'age moyen. Nouvelle iconographie de la Salpetriere. Clin Maladies System Nerveux 1914; 7 :41-51.        [ Links ]

2. Victor M, Adams RD, Cole M. The acquired (non-Wilsonian) type of chronic hepatocerebral degeneration. Medicine (Baltimore) 1965; 44: 345-96.        [ Links ]

3. Jog MS, Lang AE. Chronic acquired hepatocerebral degeneration: case reports and new insights. Mov Disord 1995; 10: 714-22.        [ Links ]

4. Levy VG, Cameron E, Ollat H, Opolon P, Darnis F, Contamin F. Chronic hepatic encephalopathies. Acquired cerebral degeneration not due to Wilson's disease. Sem Hop 1983; 59: 1369-73.        [ Links ]

5. Saporta MA, Andre C, Bahia PR, Chimelli L, Pais PH, Silva TS, et al. Acquired hepatocerebral degeneration without overt liver disease. Neurology 2004; 63: 1981-2.        [ Links ]

6. Burkhard PR, Delavelle J, Du Pasquier R, Spahr L. Chronic parkinsonism associated with cirrhosis: a distinct subset of acquired hepatocerebral degeneration. Arch Neurol 2003; 60: 521-8.        [ Links ]

7. Condat B, Dusoleil A, Bernardeau M, Roche A, Pelletier G, Buffet C. Chronic acquired hepatocerebral degeneration: the role of manganese and treatment by endovascular occlusion of a porto-systemic shunt. Gastroenterol Clin Biol 1999; 23: 268-70.        [ Links ]

8. Layrargues GP. Movement dysfunction and hepatic encephalopathy. Metab Brain Dis 2001; 16: 27-35.        [ Links ]

9. Hawker K, Lang AE. Hypoxic-ischemic damage of the basal ganglia. Case reports and a review of the literature. Mov Disord 1990; 5: 219-24.        [ Links ]

10. Kleinschmidt-DeMasters BK, Filley CM, Rojiani AM. Overlapping features of extrapontine myelinolysis and acquired chronic (non-Wilsonian) hepatocerebral degeneration. Acta Neuropathol 2006; 112: 605-16.        [ Links ]

11. Schomerus H, Hamster W. Neuropsychological aspects of portal-systemic encephalopathy. Metab Brain Dis 1998; 13: 361-77.        [ Links ]

12. Weissenborn K, Ennen JC, Schomerus H, Ruckert N, Hecker H. Neuropsychological characterization of hepatic encephalopathy. J Hepatol 2001; 34: 768-73.        [ Links ]

13. Lewis M, Howdle PD. The neurology of liver failure. QJM 2003; 96: 623-33.        [ Links ]

14. Park SA, Heo K. Prominent cerebellar symptoms with unusual magnetic resonance imaging findings in acquired hepatocerebral degeneration. Arch Neurol 2004; 61: 1458-60.        [ Links ]

15. Lewis MB, MacQuillan G, Bamford JM, Howdle PD. Delayed myelopathic presentation of the acquired hepatocerebral degeneration syndrome. Neurology 2000; 54: 1011.        [ Links ]

16. Spencer DC, Forno LS. February 2000: dementia with motor dysfunction in a patient with liver disease. Brain Pathol 2000; 10: 315-6, 9.        [ Links ]

17. Spitaleri DL, Vitolo S, Fasanaro AM, Valiani R. Choreoathetosis. Uncommon manifestation during chronic liver disease with portocaval shunt. Riv Neurol 1983; 53: 293-9.        [ Links ]

18. Thobois S, Giraud P, Debat P, Gouttard M, Maurizi A, Perret-Liaudet A, et al. Orofacial dyskinesias in a patient with primary biliary cirrhosis: a clinicopathological case report and review. Mov Disord 2002; 17: 415-9.        [ Links ]

19. Stracciari A, Guarino M, Pazzaglia P, Marchesini G, Pisi P. Acquired hepatocerebral degeneration: full recovery after liver transplantation. J Neurol Neurosurg Psychiatry 2001; 70: 136-7.        [ Links ]

20. Stracciari A, Mattarozzi K, D'Alessandro R, Baldin E, Guarino M. Cognitive functioning in chronic acquired hepatocerebral degeneration. Metab Brain Dis 2008; 23: 155-60.        [ Links ]

21. Lee J, Lacomis D, Comu S, Jacobsohn J, Kanal E. Acquired hepatocerebral degeneration: MR and pathologic findings. AJNR Am J Neuroradiol 1998; 19: 485-7.        [ Links ]

22. Pujol A, Graus F, Peri J, Mercader JM, Rimola A. Hyperintensity in the globus pallidus on T1-weighted and inversion-recovery MRI: a possible marker of advanced liver disease. Neurology 1991; 41: 1526-7.        [ Links ]

23. Pujol A, Pujol J, Graus F, Rimola A, Peri J, Mercader JM, et al. Hyperintense globus pallidus on T1-weighted MRI in cirrhotic patients is associated with severity of liver failure. Neurology 1993; 43: 65-9.        [ Links ]

24. Kulisevsky J, Ruscalleda J, Grau JM. MR imaging of acquired hepatocerebral degeneration. AJNR Am J Neuroradiol 1991; 12: 527-8.        [ Links ]

25. Krieger S, Jauss M, Jansen O, Theilmann L, Geissler M, Krieger D. Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis. Gastroenterology 1996; 111: 147-55.        [ Links ]

26. Spahr L, Vingerhoets F, Lazeyras F, Delavelle J, DuPasquier R, Giostra E, et al. Magnetic resonance imaging and proton spectroscopic alterations correlate with parkinsonian signs in patients with cirrhosis. Gastroenterology 2000; 119: 774-81.        [ Links ]

27. Ueki Y, Isozaki E, Miyazaki Y, Koide R, Shimizu Z, Yagi K, et al. Clinical and neuroradiological improvement in chronic acquired hepatocerebral degeneration after branched-chain amino acid therapy. Acta Neurol Scand 2002; 106: 113-6.        [ Links ]

28. Servin-Abad L, Tzakis A, Schiff ER, Regev A. Acquired hepatocerebral degeneration in a patient with HCV cirrhosis: complete resolution with subsequent recurrence after liver transplantation. Liver Transpl 2006; 12: 1161-5.        [ Links ]

29. Papapetropoulos S, Tzakis A, Sengun C, Reddy C, Boukas K, Zitser J, et al. Case of pediatric acquired chronic hepatocerebral degeneration. Pediatr Neurol 2008; 38: 67-70.        [ Links ]

30. Parkes JD, Murray-Lyon IM, Williams R. Neuropsychiatric and electro-encephalographic changes after transplantation of the liver. Q J Med 1970; 39: 515-27.        [ Links ]

31. Powell EE, Pender MP, Chalk JB, Parkin PJ, StrongR, Lynch S, et al. Improvement in chronic hepatocerebral degeneration following liver transplantation. Gastroenterology 1990; 98: 1079-82.        [ Links ]

 

 

Correspondence:
Aurora Burgos García.
Avda. General Perón, 4, 7o E. 28020 Madrid.
e-mail: burgos.aurora@gmail.com

Received: 20-01-09.
Accepted: 12-02-09.

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