Hepatic encephalomyelopathy : a complication following liver cirrhosis caused by Budd-Chiari syndrome and HBV

Progressive encephalomyelopathy is a rare neurological complication of chronic liver disease, even manifesting progressive spastic paraparesis. Few reports detailing the clinical and diagnostic aspects of this uncommon cause of neurological deterioration in patients with hepatic insufficiency have been published. Early recognition of this disorder will become more important in the future as patients with liver disease survive longer due to medical advances, including liver transplantation. The case of a patient with hepatic encephalomyelopathy associated with Budd-Chiari syndrome and HBV-related cirrhosis is presented.


Introduction
The development of hepatic encephalomyelopathy (HEM) in patients with a broad range of liver diseases is rare, but there is a significant impact on mobility and quality of life [1].HEM is usually associated with portal-caval shunts and the patients with HEM survive longer due to medical advances, including liver transplantation [2-4] .We report a patient with Budd-Chiari syndrome and hepatitis B virus (HBV) infection, who developed symptoms and signs of HEM later in life.

Case Report
A 37-year-old woman was admitted to the hospital with a 20 days history of walking difficulties.The bilateral legs weakness progressed and created difficulties in rising from a chair and climbing stairs in the previous two years.There were no symptoms related to cranial nerve dysfunction, tremors, or myoclonus.During that period, she experienced several episodes of mild encephalopathy.She had been diagnosed with Budd-Chiari syndrome and chronic hepatitis B for more than 10 years.Liver biopsy in 2008 demonstrated evidence of cirrhosis, and by 2010 gastroscopy revealed grade I esophageal varices.No evidence of diabetes mellitus, hypertension, and cardiopulmonary disease was found.Her past history was not significant for alcohol consumption.She denied bowel, bladder, or upper gastrointestinal bleeding.There was no family history of liver or neurological illnesses.
The patient had palmar erythema, spider angioma, and splenomegaly of about 2.0 cm on physical examination.K-F rings and skin hyperpigmentation were absent.She was alert, cooperative and had no speech disorder.Neurological examination revealed normal mental status and the presence of asterixis.Upper extremities strength was weak, especially for the left upper limb, with normal function.Upper extremity tendon reflexes were normal.Hoffman's sign was absent.In the lower extremities the tone was more noticeably increased with brisk deep tendon reflexes and there was clonus at the ankles.Plantar reflexes were extensor bilaterally.There was neither atrophy nor fasciculations.Both knee extensors and plantar flexors were normal in strength.Upper extremities sensation was without any deficits, but proprioception and vibration were mildly decreased in the toes, there was hyperesthesia to pinprick in the feet.The sensation of the trunk and crissum was normal.Gait was markedly spastic.There was no evidence of cerebellar dysfunction.After 3 weeks of conservative treatment with protein restriction, physiotherapy, and oral lactulose, the patient's mobility improved, with decreased spasticity but without significant changes in the neurological examination follow up though the asterixis was absent at this time.Plasma ammonia level decreased to 57μmol/L.The patient returned home following discharge.

Discussion
Hepatic myelopathy (HM) is commonly found in combination with hepatic encephalopathy (HE).At present, the pathophysiology of HEM remains poorly understood.The diagnosis of HEM has to be established on clinical grounds after exclusion of other possible pathologies [5].It has been hypothesized that ammonia and other neurotoxins may bypass the liver through spontaneous or surgical porto-systemic shunts.Porto-systemic shunts were found with radiological investigation in this patient.Neuropathological studies demonstrated selective demyelination of the lateral corticospinal tracts with varying degrees of axonal loss.These lesions were seen especially within the cervical levels of the spinal cord but occasionally within the brainstem with no involvement of other tracts [2,3,[6][7].
HEM caused by Budd-Chiari syndrome and HBVrelated cirrhosis is uncommon.The patient developed symptoms within two years after diagnosis of cirrhosis.Moreover, there was no considerable worsening of neurological features for the last 2 years.We suspect that early onset of encephalopathy and myelopathy may be caused by significant shunting as a result of several factors: cirrhosis and spontaneous shunting, portal-vein occlusion, and cavernoma leading to anastomosis.There are two factors involved in the cirrhosis including vascular disease and liver cell damage.Portacaval shunting plays a substantial role in the pathogenesis of HEM.Spontaneous shunting occurs within the liver as a compensatory mechanism.The patient had cirrhosis at the time of presentation and additional spontaneous portacaval shunting.Computer tomography (CT) scan confirmed the functioning of the portal-vein shunt and a twisted splenic vein.In addition, hyperammonemia was detected.The rare complication needs to be considered in patient as spontaneous portacaval shunting for relieving portal hypertension.However, whether it will provide insight regarding pathophysiological mechanism needs to be explored [1,8,[9][10].
Spastic paraparesis caused by HM has been shown to be refractory to medical treatment.In most patients, therapies aiming at reducing nitrogen absorption or lowering plasma ammonia levels have been generally unrewarding, which is similar to the therapeutic schedule of HE.Symptomatic treatment and administration have been demonstrated to temporarily benefit HEM symptoms.Protein restriction, oral neomycin, lactulose, and colonic exclusion have failed to produce significant improvement.At best, these measures prevented or decreased the numbers of encephalopathic episodes.Even so, progressive paraparesis was observed even when encephalopathy was effectively averted [1,8,[11][12].The improvement in spastic paraparesis was reported after liver transplantation in recent studies.
HIV, and HCV were absent.Markers of HBV infection assay were positive.The level of HBV-DNA was not detectable.Blood Vitamin B1, Vitamin B12, folate values, thyroid functions, and serum hexoseaminidase levels were in normal ranges.The upper endoscopy revealed grade II esophageal varices.CSF contained normal levels of glucose, proteins, and cell counts.Immunological tests of CSF for syphilis, tuberculosis were negative.MRI of the spinal cord and brain showed no intrinsic abnormality apart from bilateral symmetric pallidal hyperintensity.