LC, Acute : PO-25 ; Clinical significance of variations in the promoter region of the glutaminase gene on development of hepatic encephalopathy in Korean liver cirrhosis patients

( Chang Ha Kim ),( Soon Ho Um ),( Yeon Seok Seo ),( Jin Yong Jung ),( Jin Dong Kim ),( Hyung Joon Yim ),( Bora Keum ),( Yong Sik Kim ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Chang Duck 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: In liver cirrhosis patients, hepatic encephalopathy is a serious complication and is associated with poor prognosis. Systemic hyperammonemia occurs in patients with hepatic encephalopathy. The influx of glutamine into mitochondria in central nervous system is degraded into ammonia and glutamate by glutaminase, and this in turn leads to hepatic encephalopathy by activating ROS (reactive oxygen species) system. Romero et al. discovered GCA tandem repeats located in 5`untranslated regions (UTR) of glutaminase gene promoter region, and haplotype with more GCA tandem repeats (long-long haplotype) had significantly high risk of developing hepatic encephalopathy than those who did not (short-long or short-short haplotype). So, we validated this fact in Korean liver cirrhosis patients. Methods: We investigated 120 liver cirrhosis patients in Korea University Anam hospital and took blood sampling after taking informed consent. In patients with history of overt hepatic encephalopathy, baseline characteristics and laboratory findings were obtained by chart review at the time in development of encephalopathy. In patients who did not (control group), baseline characteristics and laboratory findings were determined at the time of blood sampling and then Psychometric Hepatic Encephalopathy Score (PHES) were conducted to identify minimal hepatic encephalopathy. Results: In patients with history of overt hepatic encephalopathy, multivariate analysis revealed that age (p=0.005), alkaline phosphatase (p=0.018), total cholesterol (p=0.019) as well as other well-known variables, such as Child-Pugh score (p= 0.008) and MELD score (p=0.035) were independent prognostic factors for development of overt hepatic encephalopathy. But, haplotype was not associated with development of overt hepatic encephalopathy (p=0.794). When the control group was divided into non-hepatic encephalopathy group and minimal hepatic encephalopathy group again, age (p=0.023), Hgb (p<0.001), prothrombin time (p<0.001), albumin (p<0.001), total bilirubin (p=0.005), alkaline phosphatase (p=0.006), blood urea nitrogen (p=0.008), total protein (p=0.010), total cholesterol (p<0.001), glucose (p=0.009), sodium (p<0.001), Child-Pugh score (p< 0.001) and MELD score (p<0.001) were significantly different among these three groups. Again, haplotype did not show any differences among three groups (p=0.907). Additionaly, in Child-Pugh grade A patients, there were no significant differences in haplotypes between non-hepatic encephalopathy group and minimal hepatic encephalopathy group (p=1.000). In Child- Pugh grade B, C patients, haplotype did not show any significant differences in development of minimal or overt hepatic encephalopathy (p=0.462) as well. Conclusions: In Korean liver cirrhosis patients, we did not find any significant associations between development of overt (minimal) hepatic encephalopahty and 5`UTR GCA tandem repeat region of glutaminase promoter gene. However further large scaled prospective study upon consideration of race is warranted.

LC,Acute : PO-25 ; Clinical significance of variations in the promoter region of the glutaminase gene on development of hepatic encephalopathy in Korean liver cirrhosis patients

( Chang Ha Kim ),( Soon Ho Um ),( Yeon Seok Seo ),( Jin Yong Jung ),( Jin Dong Kim ),( Hyung Joon Yim ),( Bora Keum ),( Yong Sik Kim ),( Yoon Tae Jeen ),( Hong Sik Lee ),( Hoon Jai Chun ),( Chang Duck 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: In liver cirrhosis patients, hepatic encephalopathy is a serious complication and is associated with poor prognosis. Systemic hyperammonemia occurs in patients with hepatic encephalopathy. The influx of glutamine into mitochondria in central nervous system is degraded into ammonia and glutamate by glutaminase, and this in turn leads to hepatic encephalopathy by activating ROS (reactive oxygen species) system. Romero et al. discovered GCA tandem repeats located in 5’untranslated regions (UTR) of glutaminase gene promoter region, and haplotype with more GCA tandem repeats (long-long haplotype) had significantly high risk of developing hepatic encephalopathy than those who did not (short-long or short-short haplotype). So, we validated this fact in Korean liver cirrhosis patients. Methods: We investigated 120 liver cirrhosis patients in Korea University Anam hospital and took blood sampling after taking informed consent. In patients with history of overt hepatic encephalopathy, baseline characteristics and laboratory findings were obtained by chart review at the time in development of encephalopathy. In patients who did not (control group), baseline characteristics and laboratory findings were determined at the time of blood sampling and then Psychometric Hepatic Encephalopathy Score (PHES) were conducted to identify minimal hepatic encephalopathy. Results: In patients with history of overt hepatic encephalopathy, multivariate analysis revealed that age (p=0.005), alkaline phosphatase (p=0.018), total cholesterol (p=0.019) as well as other well-known variables, such as Child-Pugh score (p= 0.008) and MELD score (p=0.035) were independent prognostic factors for development of overt hepatic encephalopathy. But, haplotype was not associated with development of overt hepatic encephalopathy (p=0.794). When the control group was divided into non-hepatic encephalopathy group and minimal hepatic encephalopathy group again, age (p=0.023), Hgb (p<0.001), prothrombin time (p<0.001), albumin (p<0.001), total bilirubin (p=0.005), alkaline phosphatase (p=0.006), blood urea nitrogen (p=0.008), total protein (p=0.010), total cholesterol (p<0.001), glucose (p=0.009), sodium (p<0.001), Child-Pugh score (p< 0.001) and MELD score (p<0.001) were significantly different among these three groups. Again, haplotype did not show any differences among three groups (p=0.907). Additionaly, in Child-Pugh grade A patients, there were no significant differences in haplotypes between non-hepatic encephalopathy group and minimal hepatic encephalopathy group (p=1.000). In Child- Pugh grade B, C patients, haplotype did not show any significant differences in development of minimal or overt hepatic encephalopathy (p=0.462) as well. Conclusions: In Korean liver cirrhosis patients, we did not find any significant associations between development of overt (minimal) hepatic encephalopahty and 5’UTR GCA tandem repeat region of glutaminase promoter gene. However further large scaled prospective study upon consideration of race is warranted.

알코올 사용 장애 환자에서 동반되는 베르니케 뇌병증의 선별검사로서 티아민 혈중농도의 진단적 유용성

최동렬(Dongryeol Choi),정영철(Young-Chul Jung) 한국중독정신의학회 2017 중독정신의학 Vol.21 No.1

Objectives : The purpose of this study was to evaluate the utility in measuring the blood thiamine and thiamine pyrophosphate (TPP) levels as screening tests for Wernicke encephalopathy in patients with alcohol use disorder. Methods : We analyzed the demographic, clinical and laboratory data from 35 patients with alcohol use disorder. The blood thiamine and TPP levels were acquired at admission prior to initiation of thiamine intravenous (IV) therapy. We examined whether the blood thiamine and TPP levels correlated with clinical symptoms by apply-ing the Caine’s criteria. Patients who met at least one of Caine’s criteria were considered at high risk for Wernicke encephalopathy and were treated with high-dose thiamine IV therapy. Results : There was no correlation between blood thiamine/TPP levels and clinical symptoms of Wernicke encephalopathy. Clin-ical manifestations of the below-normal TPP-level group were not different from the normal TPP-level group, except that the normal TPP-level group showed a higher revised clinical insti-tute withdrawal assessment for alcohol (CIWA) scores. Conclusion : Measuring blood thiamine/TPP levels was not sensitive as screening tests for Wernicke encephalopathy among patients with alcohol use disorder. High-dose thiamine IV therapy improved the clinical symptoms of Wernicke encephalopathy in patients with alcohol use disorder. Objectives : The purpose of this study was to evaluate the utility in measuring the blood thiamine and thiamine pyrophosphate (TPP) levels as screening tests for Wernicke encephalopathy in patients with alcohol use disorder. Methods : We analyzed the demographic, clinical and laboratory data from 35 patients with alcohol use disorder. The blood thiamine and TPP levels were acquired at admission prior to initiation of thiamine intravenous (IV) therapy. We examined whether the blood thiamine and TPP levels correlated with clinical symptoms by apply-ing the Caine’s criteria. Patients who met at least one of Caine’s criteria were considered at high risk for Wernicke encephalopathy and were treated with high-dose thiamine IV therapy. Results : There was no correlation between blood thiamine/TPP levels and clinical symptoms of Wernicke encephalopathy. Clin-ical manifestations of the below-normal TPP-level group were not different from the normal TPP-level group, except that the normal TPP-level group showed a higher revised clinical insti-tute withdrawal assessment for alcohol (CIWA) scores. Conclusion : Measuring blood thiamine/TPP levels was not sensitive as screening tests for Wernicke encephalopathy among patients with alcohol use disorder. High-dose thiamine IV therapy improved the clinical symptoms of Wernicke encephalopathy in patients with alcohol use disorder.

Acute Hyperammonemic Encephalopathy with Features on Diffusion-Weighted Images: Report of Two Cases

김자영,유인규 대한영상의학회 2015 대한영상의학회지 Vol.72 No.2

Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

간성뇌증과 연관이 있는 생화학적 단백질-칼로리 영양 평가지표

정지성 ( Ji Sung Chung ),김진일 ( Jin Il Kim ),조세현 ( Se Hyun Cho ),박수헌 ( Soo Heon Park ),한준열 ( Joon Yeol Han ),김재광 ( Jae Kwang Kim ),이영석 ( Young Sok Lee ),정규원 ( Kyu Won Chung ),선희식 ( Hee Sik Sun ) 대한내과학회 2006 대한내과학회지 Vol.70 No.6

Background: Most patients with hepatic encephalopathy have their protein intake restricted. Therefore, protein-calorie malnutrition becomes more severe and may cause more serious problems, such as infection and poor prognosis. The aim of this study is to determine better biochemical parameters for the assessment of nutritional status in patients with hepatic encephalopathy. Methods: A total 109 patients (30 normal controls and 79 chronic hepatitis B) were enrolled. 79 patients were divided into three groups: chronic HBV infection (hepatitis group, n=28), liver cirrhosis without past history of hepatic encephalopathy (cirrhosis group, n=27), liver cirrhosis with present or past history of hepatic encephalopathy (encephalopathy group, n=24). Serum albumin, total lymphocyte count, IGF-1, growth hormone, retinol binding protein, leptin and fibronectin were measured. Results: Serum albumin level, total lymphocyte count, IGF-1, and growth hormone were significantly lower in encephalopathy group than other groups (p<0.001, p=0.003, p<0.001, and p<0.001, respectively). However, RBP, leptin, and fibronectin were not different among the groups. The level of serum albumin and IGF-1 were significantly lower in encephalopathy group than cirrhosis group (p=0.002, p<0.001, respectively), but growth hormone was not significantly different between cirrhosis group and encephalopathy group. Conclusions: The level of serum albumin and IGF-1 may be important parameter for nutritional support in chronic liver disease, especially in patients with hepatic encephalopathy, because the level of serum albumin and IGF-1 relate with hepatic encephalopathy as well as reflect the progression of chronic liver disease.(Korean J Med 70:650-655, 2006)

Metronidazole-induced encephalopathy in a patient with liver cirrhosis

정형철,정택근,조영범,양봉준,김태현,김학철,조은영,김영우,김성림,박익성 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.2

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

Case Report : Metronidazole-induced encephalopathy in a patient with Liver cirrhosis

( Hyeong Cheol Cheong ),( Taek Geun Jeong ),( Young Bum Cho ),( Bong Joon Yang ),( Tae Hyeon Kim ),( Haak Cheoul Kim ),( Eun Young Cho ) 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.2

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

급성 저산소뇌병증의 예후 예측인자로서확산강조영상의 역할

김진수,노원영,임재성,김선정,박성호,윤창호 대한임상신경생리학회 2013 Annals of Clinical Neurophysiology Vol.15 No.2

Background: Diffusion-weighted image (DWI) might be useful to predict the prognosis of acute hypoxic encephalopathy. The aim of our study was to test whether the early change and extent of DWI abnormalities can be an indicator of the clinical outcome of hypoxic encephalopathy. Methods: Forty-four patients who were diagnosed as hypoxic encephalopathy due to the cardiorespiratory arrest were retrospectively identified. Clinical variables were determined, and the DWI abnormalities were counted by four areas: cortex, subcortical white matter, cerebellum and deep grey matter, and were divided into three groups by the extent of lesions. Prognosis was classified as 'poor' (Glasgow coma scale (GSC) at 30 days after arrest <9 or death) and 'good' (GSC at 30 days after arrest ≥9). Results: GCS at day 3 (p<0.001), presence of seizure (p=0.01), and presence of lesion (p<0.001) were significantly different in prognosis, but statistically there is no association with the extent of lesions and prognosis (p=0.26). Conclusions: Presence of early DWI changes could predict the clinical outcome of hypoxic encephalopathy after cardiorespiratory arrest. Background: Diffusion-weighted image (DWI) might be useful to predict the prognosis of acute hypoxic encephalopathy. The aim of our study was to test whether the early change and extent of DWI abnormalities can be an indicator of the clinical outcome of hypoxic encephalopathy. Methods: Forty-four patients who were diagnosed as hypoxic encephalopathy due to the cardiorespiratory arrest were retrospectively identified. Clinical variables were determined,and the DWI abnormalities were counted by four areas: cortex, subcortical white matter, cerebellum and deep grey matter, and were divided into three groups by the extent of lesions. Prognosis was classified as 'poor' (Glasgow coma scale (GSC) at 30 days after arrest <9 or death) and 'good' (GSC at 30 days after arrest ≥9). Results: GCS at day 3 (p<0.001), presence of seizure (p=0.01), and presence of lesion (p<0.001) were significantly different in prognosis,but statistically there is no association with the extent of lesions and prognosis (p=0.26). Conclusions: Presence of early DWI changes could predict the clinical outcome of hypoxic encephalopathy after cardiorespiratory arrest.

Toxic Encephalopathy

Kim, Yangho,Kim, Jae Woo Occupational Safety and Health Research Institute 2012 Safety and health at work Vol.3 No.4

This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure.

Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea

Byun, Jung-Ick,Lee, Soon-Tae,Jung, Keun-Hwa,Sunwoo, Jun-Sang,Moon, Jangsup,Kim, Tae-Joon,Lim, Jung-Ah,Kim, Soyun,Kim, Do-Yong,Han, Su-Hyun,Jang, Hyemin,Suh, Hong Il,Cho, A-Hyun,Kim, Dong Wook,Shin, Ju Elsevier 2016 Journal of neuroimmunology Vol.293 No.-

<P><B>Abstract</B></P> <P>We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Among 1699 patients with encephalopathy of unknown etiology, autoantibody was identified in 6.12%. </LI> <LI> Autoimmune encephalopathy comprised a significant portion of idiopathic cases. </LI> <LI> Anti-NMDA receptor antibody was the most common autoantibody in age under 40. </LI> <LI> Anti-LGI1 antibody was the most common autoantibody in age 40 and over. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>