Valproate is widely used because of broad spectrum of action, but it can produce an encephalopathy resulting from hyperammonemia even at the therapeutic range of valproate and is called as valproate-induced encephalopathy (VHE). Delay in recognition of VHE can result in the development of potentially life-threatening complications. Fortunately, it is reversible with discontinuing valproate. A 65-year-old man became progressively lethargic with impaired gait and poor cognitive function while taking valproate as alternative to zonisamide. Routine investigations of admission profiles were performed but revealed no abnormalities. Next, we checked serum ammonia level to identify other possible causes and detected hyperammonemia despite the therapeutic range of valproate in the absence of any abnormalities in liver enzymes. On cessation of valproate, he has achieved dramatic clinical improvement including the reversal of hyperammonemia. We confirmed the diagnosis of VHE. This emphasizes the importance of rapid diagnosis and proper management of VHE in order to prevent the neurological damage and minimize complications.
Aged ; Ammonia ; Gait ; Humans ; Hyperammonemia ; Isoxazoles ; Liver ; Valproic Acid

Seventeen dogs were treated with L-ornithin-L-aspartate (LOLA; experimental group). Three dogs were treated with lactulose recognized therapy (control group). Following LOLA administration, 15 dogs experienced a significant decrease in ammonia level (p < 0.05) and showed clinical signs of improvement. However, there were no clinical signs of improvement in two dogs, even though the ammonia level decreased. Conversely, the clinical signs of the control group also improved and the ammonia level decreased, although these changes were not significant (p > 0.05). These results suggest that LOLA is an effective drug to treat hyperammonemia in veterinary medicine.
Ammonia ; Animals ; Dogs* ; Dipeptides* ; Hepatic Encephalopathy* ; Hyperammonemia ; Lactulose ; Veterinary Medicine

Neonatal hyperammonemia is a disorder of ammonia metabolism that occurs in the neonatal period. It is a clinical syndrome characterized by abnormal accumulation of ammonia in the blood and dysfunction of the central nervous system. Due to its low incidence and lack of specificity in clinical manifestations, it is easy to cause misdiagnosis and missed diagnosis. In order to further standardize the diagnosis and treatment of neonatal hyperammonemia, the Youth Commission, Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association formulated the expert consensus based on clinical evidence in China and overseas and combined with clinical practice experience,and put forward 18 recommendations for the diagnosis and treatment of neonatal hyperaminemia.
Humans ; Infant, Newborn ; Ammonia ; China ; Consensus ; Hyperammonemia/therapy*

Cardiomyopathies ; diagnosis ; therapy ; Carnitine ; deficiency ; Female ; Humans ; Hyperammonemia ; diagnosis ; therapy ; Infant ; Muscular Diseases ; diagnosis ; therapy

PURPOSE: The serum ammonia level was postulated as a surrogate marker for severe neurotoxicity in glufosinate ammonium (GLA) poisoning. The aim of this study is to evaluate whether the level of serum ammonia can predict delayed neurologic complications in patients with GLA poisoning presented with alert mentality. METHODS: Thirty-six GLA-poisoned patients presented to our emergency department with alert mentality initially were analyzed retrospectively. The baseline characteristics, laboratory findings, ammonia level (initial and second ammonia level, frequency of hyperammonemia, and difference of ammonia level), and clinical outcomes were compared between non-neurologic (n=16) and neurologic complication groups (n=20). RESULTS: Neurologic complications occurred in 20 patients (55.6%) with 14.3 hours (median) of latent period. The initial ammonia level and frequency of initial hyperammonemia did not show any difference between the two groups. However, the difference of ammonia level between the 2nd and 1st samples was an independent predictor of delayed neurologic complication (adjusted odds ratio; 1.184 (95% confidence interval (CI); 1.01-1.387, p=0.037)). The area under the curve and cut-off point of the difference of ammonia level for the prediction of delayed neurologic complication was 0.936 (95% CI; 0.756-0.992) and 15.4 umol/L respectively. CONCLUSION: The difference of ammonia level rather than the initial ammonia level could be used to predict delayed neurologic complication in GLA-poisoned patients presented with alert mentality.
Ammonia* ; Ammonium Compounds* ; Biomarkers ; Emergency Service, Hospital ; Humans ; Hyperammonemia ; Odds Ratio ; Poisoning* ; Retrospective Studies

BACKGROUND: Differential diagnosis between a generalized tonic-clonic seizure and syncope may be difficult due to similar clinical features. The need for a biological marker to distinguish a seizure from syncope has been emphasized from past studies. Transient hyperammonemia could be an indicator of recent convulsive seizure. The purpose of this study is to review the use of plasma ammonia level in the differential diagnosis of seizure and syncope. METHODS: Adult patients who were admitted to the Department of Neurology at Gangnam Severance Hospital with final diagnosis of a generalized tonic-clonic seizure or syncope were eligible for this study. Plasma ammonia levels were checked within 8 hr after an insult. RESULTS: Among the patients with a loss of consciousness who underwent analysis of plasma ammonia level, diagnoses were made with a seizure (n=65) and syncope (n=38). The seizure group had 70.29+/-70.86 micromol/L and the syncope group had 28.37+/-10.27 micromol/L of ammonia level, respectively. The seizure group presented with a significantly increased plasma ammonia (p<0.05) compared to the syncope group. The cut-off value with the reliable diagnostic level was defined as 36 micromol/L (=61.308 microg/dL) with a sensitivity of 0.65 and specificity of 0.80 by receiver operating characteristic (ROC) curve analysis. CONCLUSIONS: Plasma ammonia measurement during acute post-ictal period may be a useful test for the identification and the differential diagnosis of seizures and syncope.
Adult ; Ammonia ; Biomarkers ; Diagnosis, Differential ; Humans ; Hyperammonemia ; Neurology ; Plasma ; ROC Curve ; Seizures ; Sensitivity and Specificity ; Syncope ; Unconsciousness

5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used in the treatment of a variety of solid tumors. Common adverse effects of fluorouracil chemotherapy include diarrhea, mucositis and myelosuppression. However, neurologic toxicities including hyperammonemic encephalopathy are rare and not well recognized. Transient hyperammonemic encephalopathy related to continuous infusion of high-dose 5-FU has rarely been reported. We report four cases of transient hyperammonemic encephalopathy in patients receiving continuous infusion of 5-FU. The mentality of all patients was altered during or just after the infusion of 5-FU. There were no focal neurological signs, laboratory excluding hyperammonemia or radiological abnormalities. After patients received adequate hydration and repeated lactulose enema, the mental status completely recovered within one or two days, and serum ammonium level subsequently returned to normal. In conclusion, we suggest that a transient hyperammonemic encephalopathy should be considered in differential diagnosis of patients receiving continuous 5-FU infusion with altered mentality.
Ammonium Compounds ; Diagnosis, Differential ; Diarrhea ; Drug Therapy ; Enema ; Fluorouracil* ; Humans ; Hyperammonemia ; Lactulose ; Mucositis

OBJECTIVETo establish an accurate new rat model of hyperammonemia-induced liver injury for use in studies of the molecular mechanisms underlying acute liver failure (ALF).

METHODSTwenty-six Sprague-Dawley rats were administered D-galactosamine (400 mg/kg) and endotoxin (50 mug/kg) via intraperitoneal injection to induce ALF and sacrificed at 12 h post-injection (ALF-12 group, n = 10) or 24 h post-injection (ALF-24 group, n = 16). Ten rats administered physiological saline served as the control group. In addition, 20 rats were given serial oral administrations of 10% NH4Cl solution (10 ml/kg, every 8 hrs) to establish the hyperammonemia-induced liver injury model; an additional 20 rats were prepared in parallel to serve as the ALF control group (n = 10; D-galactosamine at 800 mg/kg every 6 d for 30 days) and the physiological saline control group (n = 10). Serum samples were collected from each mouse and used to detect markers of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetal protein (AFP), and gamma-glutamyltransferase (GGT), as well as blood ammonia (BA) level and prothrombin time activity (PT-A). Affects on liver histology was assessed by hematoxylin and eosin staining of resected liver tissues, and on apoptosis by TUNEL assay and calculating the apoptotic index (AI).

RESULTSALF rats showed elevated levels of ALT (1202.51+/-282.00 U/L), AST (1560.14+/-298.98 U/L), and BA (165.9+/-23.6 mumol/L) as early as 6 hrs after model establishment; these levels peaked at 12 hrs after model establishment (ALT: 774.40+/-207.65 U/L; AST: 967.60+/-121.94 U/L; BA: 143.4+/-18.1 mumol/L; P less than 0.05). No significant variations were detected in the levels of AFP (except for the ALF-24 group) or GGT. Liver tissues of the ALF-12 and ALF-24 groups showed large or diffuse hemorrhagic necroses with sinusoidal congestion or spotty bleeding, as well as increased AI. Hyperammonemia-induced liver injury rats showed elevated levels of ALT and BA as early as 6 hrs after model establishment. Similar to the ALF rats, AFP and GGT were unaffected and AI increased. However, in contrast to the ALF rats, the liver tissues of the hyperammonemia-induced liver injury rats showed no signs of hepatocyte swelling, necrosis, or inflammatory cell invasion.

CONCLUSIONALF rats and hyperammonemia-induced liver injury rats have elevated BA and marked hepatocyte necrosis. Given that reducing the level of ammonemia can improve the animal's biochemistry indexes, it is likely that hyperammonemia plays a role in acute liver injury or ALF consequent to repeated injury. The pathogenic mechanisms of repeated injury may involve promotion of hepatocyte apoptosis in conjunction with inhibition of cellular regeneration.

OBJECTIVETo study the CPS-II mechanism underlying the pathological process of elevated blood ammonia leading to liver injury.

METHODSAn in vitro hyperammonemia hepatocyte cell model was constructed by exposure to various concentrations of NH4Cl. The subsequent changes to cellular morphology were observed by microscopy. to cell apoptosis were determined by flow cytometry, and to mRNA and protein expression of CPS-II were examined by real-time PCR and western blotting, respectively.

RESULTSExposure to NH₄Cl led to dose-dependent morphological damage, apoptosis and necrosis of the hepatocytes. The apoptosis rate was significantly higher for the high-dose group than for the control (no exposure) group (24.7% ± 2.39% vs. 4.1% ± 0.78%, q =8.06, P less than 0.05). Expression of the CPS-II mRNA was significantly elevated in response to NH₄Cl exposure (vs. the control group; F=191.881, P < 0.05).The CPS-II mRNA expression level increased with increasing NH₄Cl concentration (grey values: 1.040 ± 0.045, 1.641 ± 0.123, 2.285 ± 0.167 and 3.347 ± 0.124, respectively). The CPS-II protein expression level was also significantly enhanced in response to the NH₄Cl exposures (CPS-II protein and internal GAPDH grey value ratios: 0.099 ± 0.0130, 0.143 ± 0.025, 0.161 ± 0.036 and 0.223 ± 0.042, respectively; t=3.825, 3.968 and 6.908, P less than 0.05).

CONCLUSIONCPS-II mRNA and protein expression levels become elevated with increase in the NH₄Cl concentrations, suggesting that in addition to the urea cycle, CPS-II may play an important role in the ammonia metabolism under the condition of hyperammonemia.

Cardiomyopathies ; diagnosis ; Carnitine ; deficiency ; Humans ; Hyperammonemia ; diagnosis ; Infant, Newborn ; Male ; Muscular Diseases ; diagnosis