Annals of Neurosciences, Vol 14, No 1 (2007)
Annals of Neurosciences, Volume 14, Issue 1 (January), 2007
HEPATIC MYELOPATHY: AN UNUSUAL COMPLICATION OF ADVANCED HEPATIC DISEASE
Corresponding author:
Prof. A Agarwal
Department of Neurology
King George's Medical University Lucknow-226003
Abstract
Hepatic Myelopathy is a rare neurological complication of chronic liver disease usually seen in adults and presents as a disabling progressive pure motor spastic paraparesis which is almost always associated with overt liver failure and a systemic porto-caval shunt. We report a case of a 19 year old male who presented with rapidly progressive spastic paraparesis due to hepatic myelopathy and features of hepatic decompensation.
Key words: Hepatic myelopathy, Cirrhosis, Spastic paraparesis
Introduction
Leigh and Card (1) were the first to describe the occurrence of pure motor spastic paraparesis following liver failure in 1949 followed by a detailed description of hepatic or porto-systemic myelopathy by Brown (2) and Zieve et al (3). The first documentation of hepatic myelopathy from the Indian subcontinent was provided by Pant et al (4). Gospe et al (5) were the first to report a case of progressive myelopathy due to hepatic failure in a 14-year-adolescent. The characteristic presentation of this disorder is of an adult with underlying chronic hepatic disorder, developing insidious onset relentlessly progressive pure motor spastic paraparesis without bowel and bladder involvement and without evidence of any other underlying disease process. Typically, patients have bouts of hepatic encephalopathy preceding the development of myelopathy.
Case Report
A nineteen year old male farmer was admitted in the department of neurology with complaints of difficulty in walking due to stiffness of lower limbs and difficulty in bending the knees for 3 months, associated with weakness. To start with, the weakness was only present in the form of difficulty in standing from the sitting position or climbing stairs which over a period of couple of months progressed to slippage of footwear with knowledge and dragging of feet while walking. Fifteen days prior to admission, he assumed bed bound status and developed lack of attention with disturbed sleep wake cycle. There was no history of bowel and bladder involvement, ocular abnormalities, seizures, upper extremity involvement, diabetes mellitus, hypertension, tuberculosis, trauma, fever, exposure to drugs or toxins or radiation, tobacco or alcohol/jaundice, blood or blood component therapy, bleeding diatheses, promiscuity, similar complaints in the adjoining area or involvement of any family member or exposure to animal bite or contaminated eatables. General examination revealed normal vitals, generalized emaciation, pallor, icterus, hyperpigmented macules involving the back and tender hepatomegaly along with spleenomegaly. Other physical markers of liver disease were however, not present. Examination of the nervous system was suggestive of impaired attention and presence of postural and flapping tremors. Spastic (Grade III by Modified Ashworth Scale) paraparesis of 2/5 grade was present along with hyperreflexia and bilateral extensor plantar response. Sensory system was normal. There were no signs of meningeal irritation.
Investigations revealed hemoglobin 9.0gm%, serum bilirubin - 5.4mg% (direct - 3.7mg%, indirect - 1.7mg%), serum alkaline phosphatase - 293 U/L, SGPT - 549 U/L, SGOT - 406 U/L; serum electrolytes and blood counts were within normal limits. Cerebrospinal Fluid (CSF) examination showed cells < 5, protein - 34mg%, sugar - 81mg%, and was negative for gram's stain, acid fast bacilli and India ink staining. Ultrasound of the abdomen showed contracted liver with coarse echotexture, spleenomegaly and presence of mild ascites. Portal vein diameter was normal. Upper gastrointestinal endoscopy (UGIE) was normal. Electroencephalography revealed background slowing. Magnetic Resonance Imaging (MRI) of the spine and brain were normal. Patient's serum was nonreactive to Hepatitis A, B, C, D and E viral markers as well as to HIV I and II, by ELISA. Liver biopsy revealed micronodular cirrhosis without any evidence of steatosis or of increased iron stores. 24 hour urinary copper estimation was within normal limits. In view of a normal serology, diagnosis of cryptogenic cirrhosis was entertained in this patient.
Repeat liver function tests, done after 3 weeks, revealed a serum bilirubin of 1.21mg% (direct - 0.57mg%, indirect - 0.64mg%), serum alkaline phosphatase -158 U/L, SGPT - 63 U/L and SGOT - 42 U/L. Presently after 8 months, the patient is still bed bound with marked emaciation, moderate ascites and dilated veins over the abdomen, having developed two episodes of hepatic encephalopathy during this period. UGIE done 5 months after the initial study, showed grade II esophageal varices.
Discussion
The diagnosis of hepatic myelopathy entails the presence of an insidious onset rapidly progressive pure motor paraparesis without bowel bladder or sensory involvement in patients of documented hepatic insufficiency or those having undergone shunt surgery or liver transplantation (1–8). Imaging has been non-contributory in these cases.
There is marked paucity of data regarding the pathogenesis of hepatic myelopathy. There have been reports of chronic hepatic insufficiency (idiopathic and postinfective) and post-liver transplantation or shunt surgery (TIPSS - transjugular intrahepatic portal systemic shunting) patients developing hepatic myelopathy along with rare reports of infantile portal vein thrombosis (8), congenital hepatic fibrosis (9) and acute hepatitis E exposure (10) leading to the same.
The pathogenesis of both acquired hepatocerebral degeneration and hepatic myelopathy are poorly understood and it is usually thought that nitrogenous products bypassing the liver through the porto-caval shunt play an important role. There have been suggestions, however, that the acquired hepatocerebral degeneration syndrome simply represents the damage accumulated from multiple episodes of hepatic encephalopathy.
In most of the reported cases, episodes of overt hepatic encephalopathy have preceded the development of the myelopathy; it has therefore been postulated that nitrogenous products such as ammonia, fatty acids, indoles and mercaptans, bypassing the liver through the porto-caval shunt, play an important role. These nitrogenous products cause injury to the axon cylinder, neuronal cell bodies and myelin. Another explanation is the deficiency of essential nutrients to the central nervous system secondary to the alteration of the hepatic metabolism (11,12).
Differential diagnoses of hepatic myelopathy are amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), paraneoplastic effect, radiation myelopathy, HTLV-I associated myelopathy (HAM) and vascular spinal cord disease.
The age of presentation, rapidly developing disability, sparing of upper limbs, no sensory signs, bladder involvement with normal CSF findings and imaging, in a patient of chronic liver disease with features of hepatic decompensation favored the diagnosis of hepatic myelopathy.
This case merits attention in being one amongst the only couple of case reports of patients in the late adolescent age group, with cryptogenic cirrhosis without any evidence of porto-systemic shunting and presenting for the very first time in hepatic encephalopathy. It therefore illustrates that a good index of suspicion may actually reveal an underlying, fairly uncommon, pathogenetic mechanism.
Hepatic myelopathy has been shown to be relentlessly progressive, unresponsive to ammonia lowering measures and liver transplantation (barring rare documentations of recovery) (13- 15). With increase in incidence of the patients of liver disease due to medical advances, including shunting procedures such as TIPSS and liver transplantation, this entity may become important in time to come and probably more insight into the pathophysiology and treatment would be provided in view of the ongoing research.
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