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Klüver–Bucy syndrome following status epilepticus associated with hepatic encephalopathy
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Epilepsy & Behavior 12 (2008) 337–339 www.elsevier.com/locate/yebeh
Case Report
Klu¨ver–Bucy syndrome following status epilepticus associated with hepatic encephalopathy Kosuke Naito, Takao Hashimoto *, Shu-ichi Ikeda Department of Neurology, Shinshu University School of Medicine, Matsumoto, Japan Center for Neurological Diseases, Aizawa Hospital, Matsumoto, Japan Received 6 August 2007; revised 19 September 2007; accepted 20 September 2007 Available online 5 November 2007
Abstract Described here is the case of a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions on MRI and Klu¨ver– Bucy syndrome following status epilepticus. Herpes encephalitis, paraneoplastic syndrome, Hashimoto’s encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were judged not to be involved on the basis of laboratory results. The possible cause of the temporo-occipital lesions on MRI in this patient was cortical damage related mainly to status epilepticus and partially to coexisting hepatic encephalopathy. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Klu¨ver–Bucy syndrome; Status epilepticus; Hepatic encephalopathy; Magnetic resonance imaging; Temporo-occipital lobe lesions
1. Introduction Klu¨ver and Bucy [1,2] described the following peculiar syndrome in rhesus monkeys after removal of both temporal lobes, including the uncus and hippocampus: psychic blindness, oral tendencies, hypermetamorphosis, emotional changes, and increased sexual behavior. We describe a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions manifesting as Klu¨ver–Bucy syndrome following status epilepticus. 2. Case report A 55-year-old woman with a 3-year history of alcoholic liver cirrhosis, but no history of epilepsy, experienced repetitive generalized seizures including status epilepticus over the 5 weeks prior to admission. She was intubated and ventilated during the period of status epilepticus. She was removed from the ventilator after resolution of sei*
Corresponding author. Address: 2-5-1 Honjo, Matsumoto 390-8510, Japan. Fax: +81 263 33 8609. E-mail address: [email protected] (T. Hashimoto). 1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.09.017
zures with phenytoin sodium (300 mg/day), but her stuporous state persisted. She was then transferred to our hospital. On admission, blood test results were as follows: platelet count 6.7 K/lL, prothrombin time 15.1 seconds (normal: 10–13 seconds), serum aspartate transaminase 81 U/L, serum alanine transaminase 41 U/L, blood ammonia 240 lg/dL (normal: 20–70 lg/dL), branched chain amino acid/tyrosine ratio 3.9 (normal: 4.4–10), negative HBs antigen, and negative HCV antibody. Upper endoscopy revealed esophageal varices, and abdominal CT revealed mild splenomegaly and no ascites. An electroencephalogram on the second day of admission showed diffuse slowing with synchronous periodic sharp waves or triphasic waves (Fig. 1). MRI FLAIR images of the brain taken on the day of admission showed a small hemorrhage in the right putamen and slightly high signal intensity in the bilateral temporo-occipital lobes (Fig. 2A). We diagnosed her as having hepatic encephalopathy and treated her, but her serum ammonia level remained elevated for 3 weeks after admission. She gradually became alert and free from seizures after admission, but a peculiar constellation of behavioral changes were manifested: oral tendencies (biting anything
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Case Report / Epilepsy & Behavior 12 (2008) 337–339
Fig. 1. This electroencephalogram obtained on the second day of admission shows diffuse slowing with synchronized periodic sharp waves or trochaic waves, which are compatible with hepatic encephalopathy.
Fig. 2. (A) MRI FLAIR images obtained on admission reveal slightly high signal intensity in the bilateral temporo-occipital lobes (arrows). (B) MRI FLAIR images taken 12 days after admission show more extended high-signal-intensity areas. (C) MRI FLAIR images taken 78 days after admission reveal bilateral temporo-occipital lobe atrophy without cortical high-signal areas.
she saw or touched); groping movements (extending her hands to grasp the examiner’s clothes); jargon (ceaseless incomprehensible speech); and partial cortical blindness. MRI FLAIR images taken 12 days after admission revealed that the high-signal-intensity areas in the bilateral temporo-occipital lobes were more extended and slightly edematous (Fig. 2B). Additional blood tests revealed no hypothyroidism, and titers of anti-thyroid, anti-nuclear, anti-SS-A, anti-SS-B, and anti-neuronal (anti-Hu, antiYo, anti-Li) antibodies were not elevated. The serum level of sodium was maintained in the normal range after admis-
sion. Serum levels of lactate and pyruvate were normal. Cerebrospinal fluid (CSF) analysis revealed no elevation of protein or white blood cells. Herpes simplex virus (HSV) polymerase chain reaction was negative, and the IgG antibody and IgM antibody titers from the enzymelinked immunosorbent assay against HSV did not show a rise in a paired sample of CSF. We started a 3-day course of intravenous methylprednisolone 1000 mg daily on the 23rd day after admission, followed by intravenous dexamethasone 12 mg daily. Her speech improved and contained less jargon, but she occa-
Case Report / Epilepsy & Behavior 12 (2008) 337–339
sionally uttered sexual expressions to the men around her. Her visuognosis also improved. Oral prednisolone 50 mg daily followed dexamethasone and was tapered 10 weeks later. MRI FLAIR images taken 78 days after admission revealed bilateral temporo-occipital lobe atrophy without cortical hyperintense areas (Fig. 2C). The signs of Klu¨ver–Bucy syndrome disappeared except for mild oral tendencies and partial cortical blindness a year after onset. 3. Discussion Before developing Klu¨ver–Bucy syndrome, our patient had repetitive generalized epilepsy including an episode of status epilepticus. Severe hepatic encephalopathy was presumed to cause the status epilepticus, as has been reported [3]. Complete or partial forms of Klu¨ver–Bucy syndrome have been reported in association with epilepsy without structural lesions [4,5]; however, development of the syndrome after resolution of seizures, and improvement of the syndrome along with evolution of the temporo-occipital lesions suggest that the structural damage caused by the bilateral cortical lesions produced the syndrome in our patient. Herpes encephalitis is the most frequently reported etiology of Klu¨ver–Bucy syndrome [6], and the MRI findings in our patient resembled those of bilateral herpes encephalitis; however, the lack of CSF pleocytosis, the negative polymerase chain reaction for HSV DNA, and the lack of an increase in CSF HSV titers do not support that possibility. Paraneoplastic syndrome, Hashimoto’s encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were other possible causes, but all were judged not to be involved in our patient on the basis of laboratory results and clinical course. It is also known that transient magnetic resonance signal changes characterized by focally increased T2 signal intensity with mild swelling can occur following status epilepticus [7]. The mechanisms are believed to be hypermetabolic neural necrosis and an excitotoxic mechanism mediated by both NMDA and non-NMDA receptors [8]. In these cases, the lesion sites are restricted to the epileptogenic areas, but the lesions in our patient were located in wide areas of the bilateral temporo-occipital cortices. Acute hepatic encephalopathy with evidence of cortical lesions on MRI has been reported. Kinoshita et al [9] described two children with Reye’s syndrome whose T2weighted MRI scans revealed a diffuse cortical laminar
339
high signal with cerebral edema in the acute stage and, in addition, cortical white matter changes in the chronic stage. Arnold et al. [10] described a patient with acute hepatic encephalopathy whose MRI scan revealed widespread cortical signal changes and cerebral edema. The causes of these cortical lesions were speculated to be mitochondrial insult to the cortex [9] or the toxic effects of ammonia [10]. Hepatic encephalopathy may have accounted for the cortical lesions in our patient; however, we have found no published report of a person manifesting Klu¨ver–Bucy syndrome caused by structural temporal lesions in association with hepatic encephalopathy. In conclusion, the probable cause of the temporo-occipital lesions revealed by MRI in our patient was cortical damage related mainly to status epilepticus, and coexisting severe hepatic encephalopathy may have contributed somewhat to development of the lesions. The efficacy of corticosteroids in the treatment of Klu¨ver–Bucy syndrome and cortical lesions in our patient suggest that the inflammation provoked under epilepsy-induced metabolic changes and the hyperammonemia constitute a part of the disease process. References [1] Klu¨ver H, Bucy PC. An analysis of certain effects of bilateral temporal lobectomy in the rhesus monkey, with special reference to ‘‘psychic blindness’’. J Psychol 1938;5:33–54. [2] Klu¨ver H, Bucy PC. Preliminary analysis of functions of the temporal lobes in monkeys. Arch Neurol Psychiatry 1939;42:979–1000. [3] Tanaka H, Ueda H, Kida Y, et al. Hepatic encephalopathy with status epilepticus: a case report. World J Gastroenterol 2006;12:1793–4. [4] Varon D, Pritchard PB III, Wagner MT, Topping K. Transient Klu¨ver–Bucy syndrome following complex partial status epilepticus. Epilepsy Behav 2003;4:348–51. [5] Janszky J, Fogarasi A, Magalova V, et al. Hyperorality in epileptic seizures: periictal incomplete Klu¨ver–Bucy syndrome. Epilepsia 2005;46:1235–40. [6] Jha S, Patel R. Klu¨ver–Bucy syndrome: an experience with six cases. Neurology India 2004;52:369–71. [7] Kim JA, Chung JI, Yoon PH, et al. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. Am J Neuroradiol 2001;22:1149–60. [8] Donaire A, Carreno M, Go´mez B, et al. Cortical laminar necrosis related to prolonged focal status epilepticus. J Neurol Neurosurg Psychiatry 2006;77:104–6. [9] Kinoshita T, Takahashi S, Ishii K, et al. Reye’s syndrome with cortical laminar necrosis: MRI. Neuroradiol 1996;38:269–72. [10] Arnold SM, Ells T, Sprier J, Schumacher M. Acute hepatic encephalopathy with diffuse cortical lesions. Neuroradiology 2001;43:551–4.
Epilepsy & Behavior 12 (2008) 337–339 www.elsevier.com/locate/yebeh
Case Report
Klu¨ver–Bucy syndrome following status epilepticus associated with hepatic encephalopathy Kosuke Naito, Takao Hashimoto *, Shu-ichi Ikeda Department of Neurology, Shinshu University School of Medicine, Matsumoto, Japan Center for Neurological Diseases, Aizawa Hospital, Matsumoto, Japan Received 6 August 2007; revised 19 September 2007; accepted 20 September 2007 Available online 5 November 2007
Abstract Described here is the case of a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions on MRI and Klu¨ver– Bucy syndrome following status epilepticus. Herpes encephalitis, paraneoplastic syndrome, Hashimoto’s encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were judged not to be involved on the basis of laboratory results. The possible cause of the temporo-occipital lesions on MRI in this patient was cortical damage related mainly to status epilepticus and partially to coexisting hepatic encephalopathy. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Klu¨ver–Bucy syndrome; Status epilepticus; Hepatic encephalopathy; Magnetic resonance imaging; Temporo-occipital lobe lesions
1. Introduction Klu¨ver and Bucy [1,2] described the following peculiar syndrome in rhesus monkeys after removal of both temporal lobes, including the uncus and hippocampus: psychic blindness, oral tendencies, hypermetamorphosis, emotional changes, and increased sexual behavior. We describe a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions manifesting as Klu¨ver–Bucy syndrome following status epilepticus. 2. Case report A 55-year-old woman with a 3-year history of alcoholic liver cirrhosis, but no history of epilepsy, experienced repetitive generalized seizures including status epilepticus over the 5 weeks prior to admission. She was intubated and ventilated during the period of status epilepticus. She was removed from the ventilator after resolution of sei*
Corresponding author. Address: 2-5-1 Honjo, Matsumoto 390-8510, Japan. Fax: +81 263 33 8609. E-mail address: [email protected] (T. Hashimoto). 1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.09.017
zures with phenytoin sodium (300 mg/day), but her stuporous state persisted. She was then transferred to our hospital. On admission, blood test results were as follows: platelet count 6.7 K/lL, prothrombin time 15.1 seconds (normal: 10–13 seconds), serum aspartate transaminase 81 U/L, serum alanine transaminase 41 U/L, blood ammonia 240 lg/dL (normal: 20–70 lg/dL), branched chain amino acid/tyrosine ratio 3.9 (normal: 4.4–10), negative HBs antigen, and negative HCV antibody. Upper endoscopy revealed esophageal varices, and abdominal CT revealed mild splenomegaly and no ascites. An electroencephalogram on the second day of admission showed diffuse slowing with synchronous periodic sharp waves or triphasic waves (Fig. 1). MRI FLAIR images of the brain taken on the day of admission showed a small hemorrhage in the right putamen and slightly high signal intensity in the bilateral temporo-occipital lobes (Fig. 2A). We diagnosed her as having hepatic encephalopathy and treated her, but her serum ammonia level remained elevated for 3 weeks after admission. She gradually became alert and free from seizures after admission, but a peculiar constellation of behavioral changes were manifested: oral tendencies (biting anything
338
Case Report / Epilepsy & Behavior 12 (2008) 337–339
Fig. 1. This electroencephalogram obtained on the second day of admission shows diffuse slowing with synchronized periodic sharp waves or trochaic waves, which are compatible with hepatic encephalopathy.
Fig. 2. (A) MRI FLAIR images obtained on admission reveal slightly high signal intensity in the bilateral temporo-occipital lobes (arrows). (B) MRI FLAIR images taken 12 days after admission show more extended high-signal-intensity areas. (C) MRI FLAIR images taken 78 days after admission reveal bilateral temporo-occipital lobe atrophy without cortical high-signal areas.
she saw or touched); groping movements (extending her hands to grasp the examiner’s clothes); jargon (ceaseless incomprehensible speech); and partial cortical blindness. MRI FLAIR images taken 12 days after admission revealed that the high-signal-intensity areas in the bilateral temporo-occipital lobes were more extended and slightly edematous (Fig. 2B). Additional blood tests revealed no hypothyroidism, and titers of anti-thyroid, anti-nuclear, anti-SS-A, anti-SS-B, and anti-neuronal (anti-Hu, antiYo, anti-Li) antibodies were not elevated. The serum level of sodium was maintained in the normal range after admis-
sion. Serum levels of lactate and pyruvate were normal. Cerebrospinal fluid (CSF) analysis revealed no elevation of protein or white blood cells. Herpes simplex virus (HSV) polymerase chain reaction was negative, and the IgG antibody and IgM antibody titers from the enzymelinked immunosorbent assay against HSV did not show a rise in a paired sample of CSF. We started a 3-day course of intravenous methylprednisolone 1000 mg daily on the 23rd day after admission, followed by intravenous dexamethasone 12 mg daily. Her speech improved and contained less jargon, but she occa-
Case Report / Epilepsy & Behavior 12 (2008) 337–339
sionally uttered sexual expressions to the men around her. Her visuognosis also improved. Oral prednisolone 50 mg daily followed dexamethasone and was tapered 10 weeks later. MRI FLAIR images taken 78 days after admission revealed bilateral temporo-occipital lobe atrophy without cortical hyperintense areas (Fig. 2C). The signs of Klu¨ver–Bucy syndrome disappeared except for mild oral tendencies and partial cortical blindness a year after onset. 3. Discussion Before developing Klu¨ver–Bucy syndrome, our patient had repetitive generalized epilepsy including an episode of status epilepticus. Severe hepatic encephalopathy was presumed to cause the status epilepticus, as has been reported [3]. Complete or partial forms of Klu¨ver–Bucy syndrome have been reported in association with epilepsy without structural lesions [4,5]; however, development of the syndrome after resolution of seizures, and improvement of the syndrome along with evolution of the temporo-occipital lesions suggest that the structural damage caused by the bilateral cortical lesions produced the syndrome in our patient. Herpes encephalitis is the most frequently reported etiology of Klu¨ver–Bucy syndrome [6], and the MRI findings in our patient resembled those of bilateral herpes encephalitis; however, the lack of CSF pleocytosis, the negative polymerase chain reaction for HSV DNA, and the lack of an increase in CSF HSV titers do not support that possibility. Paraneoplastic syndrome, Hashimoto’s encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were other possible causes, but all were judged not to be involved in our patient on the basis of laboratory results and clinical course. It is also known that transient magnetic resonance signal changes characterized by focally increased T2 signal intensity with mild swelling can occur following status epilepticus [7]. The mechanisms are believed to be hypermetabolic neural necrosis and an excitotoxic mechanism mediated by both NMDA and non-NMDA receptors [8]. In these cases, the lesion sites are restricted to the epileptogenic areas, but the lesions in our patient were located in wide areas of the bilateral temporo-occipital cortices. Acute hepatic encephalopathy with evidence of cortical lesions on MRI has been reported. Kinoshita et al [9] described two children with Reye’s syndrome whose T2weighted MRI scans revealed a diffuse cortical laminar
339
high signal with cerebral edema in the acute stage and, in addition, cortical white matter changes in the chronic stage. Arnold et al. [10] described a patient with acute hepatic encephalopathy whose MRI scan revealed widespread cortical signal changes and cerebral edema. The causes of these cortical lesions were speculated to be mitochondrial insult to the cortex [9] or the toxic effects of ammonia [10]. Hepatic encephalopathy may have accounted for the cortical lesions in our patient; however, we have found no published report of a person manifesting Klu¨ver–Bucy syndrome caused by structural temporal lesions in association with hepatic encephalopathy. In conclusion, the probable cause of the temporo-occipital lesions revealed by MRI in our patient was cortical damage related mainly to status epilepticus, and coexisting severe hepatic encephalopathy may have contributed somewhat to development of the lesions. The efficacy of corticosteroids in the treatment of Klu¨ver–Bucy syndrome and cortical lesions in our patient suggest that the inflammation provoked under epilepsy-induced metabolic changes and the hyperammonemia constitute a part of the disease process. References [1] Klu¨ver H, Bucy PC. An analysis of certain effects of bilateral temporal lobectomy in the rhesus monkey, with special reference to ‘‘psychic blindness’’. J Psychol 1938;5:33–54. [2] Klu¨ver H, Bucy PC. Preliminary analysis of functions of the temporal lobes in monkeys. Arch Neurol Psychiatry 1939;42:979–1000. [3] Tanaka H, Ueda H, Kida Y, et al. Hepatic encephalopathy with status epilepticus: a case report. World J Gastroenterol 2006;12:1793–4. [4] Varon D, Pritchard PB III, Wagner MT, Topping K. Transient Klu¨ver–Bucy syndrome following complex partial status epilepticus. Epilepsy Behav 2003;4:348–51. [5] Janszky J, Fogarasi A, Magalova V, et al. Hyperorality in epileptic seizures: periictal incomplete Klu¨ver–Bucy syndrome. Epilepsia 2005;46:1235–40. [6] Jha S, Patel R. Klu¨ver–Bucy syndrome: an experience with six cases. Neurology India 2004;52:369–71. [7] Kim JA, Chung JI, Yoon PH, et al. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. Am J Neuroradiol 2001;22:1149–60. [8] Donaire A, Carreno M, Go´mez B, et al. Cortical laminar necrosis related to prolonged focal status epilepticus. J Neurol Neurosurg Psychiatry 2006;77:104–6. [9] Kinoshita T, Takahashi S, Ishii K, et al. Reye’s syndrome with cortical laminar necrosis: MRI. Neuroradiol 1996;38:269–72. [10] Arnold SM, Ells T, Sprier J, Schumacher M. Acute hepatic encephalopathy with diffuse cortical lesions. Neuroradiology 2001;43:551–4.