UNASSIGNED: The high-dose dexamethasone suppression test is a common and usually benign endocrine procedure. We report a patient with ornithine transcarbamylase deficiency (OTCD) who developed hyperammonemic encephalopathy after a high-dose dexamethasone suppression test.
UNASSIGNED: A 46-year-old woman with a 1.3-cm right adrenal incidentaloma causing mild autonomous cortisol secretion underwent a high-dose dexamethasone suppression test for confirming adrenocorticotropic hormone independency. On the next day, she presented to the emergency room with confusion and somnolence. Her Glasgow Coma Scale score was 10 on arrival. The initial laboratory results showed ammonia, alanine transaminase, creatinine, and blood urea nitrogen levels of 289.51 (18.73-54.5) μg/dL, 21 (≤33) IU/L, 0.6 (0.6-1.1) mg/dL, and 13 (7-20) mg/dL, respectively. Electroencephalography showed triphasic morphology with no pathologies on brain imaging. Her husband told us that her brother and son had died in the neonatal period. On further review of medical records, we found that she was diagnosed as an OTCD carrier. We administered L-arginine, L-carnitine, rifaximin, and continuous renal replacement therapy. After 3 days, the serum ammonia level was 78.34 μg/dL with an increased Glasgow Coma Scale score of 15, and electroencephalography abnormalities disappeared.
UNASSIGNED: Liver diseases and urea cycle disorders are the leading causes of hyperammonemia. This causes encephalopathy and death if the ammonia levels are too high. X-linked OTCD urea cycle disorder affects men more severely as they have only the carrier X chromosome. Glucocorticoids can exacerbate this disorder because they increase protein substrates converted to ammonia.
UNASSIGNED: This case reminds that it may be particularly important to have a complete medical history when administering glucocorticoids.

OBJECTIVE: To review the evidence of uncommon but fatal adverse event of hyperammonemic encephalopathy by tyrosine kinase inhibitors (TKI) and the possible mechanisms underlying this condition and to describe the case of a patient that developed drug-induced hyperammonemic encephalopathy related to TKI.
METHODS: Literature search of different databases was performed for studies published from 1 January 1992 to 7 May 2023. The search terms utilized were hyperammonemic encephalopathy, TKI, apatinib, pazopanib, sunitinib, imatinib, sorafenib, regorafenib, trametinib, urea cycle regulation, sorafenib, carbamoyl-phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase 1, Mitogen activated protein kinases (MAPK) pathway and mTOR pathway, were used individually search or combined.
METHODS: Thirty-seven articles were included. The articles primarily focused in hyperammonemic encephalopathy case reports, management of hyperammonemic encephalopathy, urea cycle regulation, autophagy, mTOR and MAPK pathways, and TKI.
CONCLUSIONS: Eighteen cases of hyperammonemic encephalopathy were reported in the literature from various multitargeted TKI. The mechanism of this event is not well-understood but some authors have hypothesized vascular causes since some of TKI are antiangiogenic, however our literature review shows a possible relationship between the urea cycle and the molecular inhibition exerted by TKI. More preclinical evidence is required to unveil the biochemical mechanisms responsible involved in this process and clinical studies are necessary to shed light on the prevalence, risk factors, management and prevention of this adverse event. It is important to monitor neurological symptoms and to measure ammonia levels when manifestations are detected.

BACKGROUND: Sunitinib, a multi-targeted tyrosine kinase inhibitor (TKI), has been approved for the salvage treatment of gastrointestinal stromal tumors (GIST). Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use. Here, we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.
METHODS: A 66-year-old male with metastatic GIST was admitted because of reduced consciousness. Imatinib was administered as the first-line systemic therapy. He experienced repeated episodes of peritonitis due to tumor perforation, and surgery was performed. Progressive disease was confirmed based on increased liver metastasis, and sunitinib was initiated as a salvage treatment. However, 23 d after the third course of sunitinib, he presented to the emergency room with an episode of altered consciousness and behavioral changes. Based on the patient clinical history and examination findings, sunitinib-induced encephalopathy was suspected. Sunitinib was discontinued, and the patient was treated for hyperammonemia. The patient had a normal level of consciousness four days later, and the serum ammonia level gradually decreased. No further neurological symptoms were reported in subsequent follow-ups.
CONCLUSIONS: TKI-induced hyperammonemic encephalopathy is potentially life-threatening. Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.

Organophosphorus (OP) poisoning is the most common type of poisoning in India. Amongst the OP, monocrotophos poisoning has the highest lethality and need for mechanical ventilation. Monocrotophos is also implicated in causing OP-induced intermediate syndrome, the prevalence of which is 10-40% of all OP poisoning. The other neurological manifestations are delayed neuropathy and neuropsychiatric syndrome. We herein discuss a case of a 58-year-old male who presented with monocrotophos poisoning and intermediate syndrome. During the hospitalisation course, the patient developed hyperammonemic encephalopathy, resulting in difficulty in weaning from mechanical ventilation. After ruling out all possible causes of hyperammonemia, it was attributed to monocrotophos poisoning. The patient improved significantly after initiating lactulose and was successfully weaned off from the ventilator. This report highlights the high index of suspicion of hyperammonemic encephalopathy in monocrotophos toxicity, which can be easily missed due to other commoner neurological manifestations of organophosphorus poisoning.

Lithium, a medication commonly used to treat bipolar disorders, has a narrow therapeutic index, putting patients at risk of lithium toxicity. Such toxicity could entail neurological-related complications and could be precipitated by several factors. In this paper, the authors discuss a case of a middle-aged woman taking lithium for bipolar disorder who presented to the emergency department with altered mental status, tremors, generalized weakness, and dysarthria. Multiple differential diagnoses were considered during her hospitalization, which included an admission to the intensive care unit. This case highlights the variability of lithium toxicity presentations and its management challenges. Further research is needed to understand such manifestations, potential precipitating factors, differential diagnoses, and effective detection and management.

BACKGROUND: Acute hyperammonemic encephalopathy is associated with distinct brain MRI findings, namely, hyperintensity in T2-weighted sequences as well as restricted diffusion in diffusion-weighted imaging with accentuation in the insular cortex and cingulate gyrus. The pathophysiology and the histopathological correlates of these characteristic MRI findings are largely unknown.
METHODS: We present a 57-year-old male with a history of chronic alcohol abuse, liver cirrhosis and portal hypertension, and a clinical syndrome (variceal bleeding, depression of consciousness, seizures), elevated plasma ammonia levels, and characteristic brain MRI abnormalities suggestive of acute hyperammonemic encephalopathy. A postmortem histopathological examination revealed extensive hypoxic ischemic encephalopathy without evidence for metabolic encephalopathy. No episodes of prolonged cerebral hypoxemia were documented throughout the course of the disease. We conducted a review of the literature, which exhibited no reports of hyperammonemic encephalopathy in association with characteristic brain MRI findings and a consecutive histopathological examination.
CONCLUSIONS: This is the first report of a patient with acute hyperammonemic encephalopathy together with characteristic brain MRI findings and a histopathological correlation. Although characteristic MRI findings of acute hyperammonemic encephalopathy were present, a histopathological examination revealed only hypoxic pathology without signs of metabolic encephalopathy.

BACKGROUND: Valproic acid (VPA) is a prevalent antiseizure medication (ASM) used to treat epilepsy. Valproate-related hyperammonemic encephalopathy (VHE) is a type of encephalopathy that can occur during neurocritical situations. In VHE, the electroencephalogram (EEG) displays diffuse slow waves or periodic waves, and there is no generalized suppression pattern.
METHODS: We present a case of a 29-year-old female with a history of epilepsy who was admitted for convulsive status epilepticus (CSE), which was controlled by intravenous VPA, as well as oral VPA and phenytoin. The patient did not experience further convulsions but instead developed impaired consciousness. Continuous EEG monitoring revealed a generalized suppression pattern, and the patient was unresponsive. The patient\'s blood ammonia level was significantly elevated at 386.8 μmol/L, indicating VHE. Additionally, the patient\'s serum VPA level was 58.37 μg/ml (normal range: 50-100 μg/ml). After stopping VPA and phenytoin and transitioning to oxcarbazepine for anti-seizure and symptomatic treatment, the patient\'s EEG gradually returned to normal, and her consciousness was fully restored.
CONCLUSIONS: VHE can cause the EEG to display a generalized suppression pattern. It is crucial to recognize this specific situation and not to infer a poor prognosis based on this EEG pattern.

Multiple myeloma (MM) typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Only a few cases of hyperammonemic encephalopathy (HE) attributed to multiple myeloma have been reported. We report a case of a 68-year-old Hispanic female diagnosed with multiple myeloma and presented with altered mental status and elevated ammonia levels found to have HE. The pathology behind HE is associated with higher ammonia levels produced by myeloma cell lines in the absence of liver disease. Due to the wide range of differentials for altered mental status (AMS), HE often gets missed and causes delayed treatment and the associated higher mortality. The primary treatment is chemotherapy. Lactulose and rifaximin must be initiated; however, it is ineffective if solely used. In our case, chemotherapy was not considered a treatment option in light of the patient\'s pancytopenia and infection. Our case is unique, as despite adequately treating other commonly suspected causes of AMS such as infection, there was no expected improvement in the patient\'s clinical status noticed, eventually leading to intubation due to worsening AMS. Given the patient\'s history of multiple myeloma, non-compliance with chemotherapy before presentation, and elevated ammonia levels raised suspicion for HE. Clinicians are encouraged to acquaint themselves with HE as a differential for patients presenting with MM flare and AMS, specifically when other potential causes of AMS are ruled out and addressed.

Idiopathic hyperammonemic encephalopathy is a rare complication of chemotherapy, which has previously mainly been associated with L-asparaginase, cytarabine and 5-FU. We present a case following treatment with gemcitabine-cisplatin in a patient with cholangiocarcinoma. The etiology of chemotherapy-induced idiopathic hyperammonemic encephalopathy remains unclear and existing theories differ per chemotherapeutic agent. Physicians treating patients with gemcitabine-cisplatin should be aware of the possibility of this complication, especially because it is treatable when recognized early.

Acute hyperammonemic encephalopathy is rare and generally is not widely known; only a few pediatric cases were found in the literature. These lesions\' clinical presentation differs significantly so they can mimic other lesions. In this case report, we discuss a 5-year-old boy who presented with generalized seizures and was unconscious in an apyretic context, for which she had a cranial computed tomographic and magnetic resonance imaging, both objectified an acute hyperammonemic encephalopathy resulting from an enzyme deficiency. Magnetic resonance imaging revealed lesions throughout the cortex, with the perirolandic and occipital cortices spared. This distribution of cerebral signal abnormalities on magnetic resonance imaging with an abrupt and profound neurological disorder is secondary to hyperammonemic. The knowledge of the magnetic resonance imaging results of this entity is essential to accelerate the diagnosis, and treatment, also to prevent sequelae.