Metabolic encephalopathy caused by nitrous oxide ('laughing gas') induced hyperammonaemia.

A 26-year-old man presented at the emergency department with confusion and decreased consciousness after several days of vomiting. In the preceding 6 months, he had used a 2-litre tank of nitrous oxide (N2O) weekly. His metabolic encephalopathy was caused by hyperammonaemia which probably resulted from interference of N2O-induced vitamin B12 deficiency with ammonia degradation. A catabolic state might have contributed to the hyperammonaemia in this case. After treatment with vitamin B12 and lactulose, both his consciousness and hyperammonaemia improved. He reported no residual complaints after 3 months of follow-up. Since N2O is increasingly used as a recreational drug, we recommend considering hyperammonaemia as a cause of metabolic encephalopathy in cases of N2O use and altered mental status.

Cephalosporin-related neurotoxicity: Metabolic encephalopathy or non-convulsive status epilepticus?

Metabolic encephalopathy and Non-Convulsive Status Epilepticus (NCSE) have been reported with cephalosporin use, particularly cefepime. We aimed to analyze the clinical and EEG findings in patients with cephalosporin-related neurotoxicity (CRN) at our hospital identified via the hospital EEG database, and to critically review CRN case reports in the literature. A Medline search was performed to identify CRN cases where a representative sample of EEG was provided. EEGs were analyzed using published criteria differentiating NCSE from triphasic waves (TW). Eleven patients at our hospital were identified with CRN (9 cefepime, 2 ceftriaxone): all had an encephalopathy with decreased consciousness and/or confusion. One patient had clinical seizures and 6 had multifocal myoclonus. All patients had abnormal EEGs, all with moderate to severe generalized slowing and 10 also with TW. Recovery was related to cephalosporin withdrawal rather than antiepileptic therapy. Analysis of 37 EEG samples of CRN patients reported in the literature as NCSE (30) or TW (7) revealed that most did not meet criteria for NCSE, with 33 showing TW, 1 showing generalised epileptiform discharges and 3 being uninterpretable. CRN usually produces a toxic encephalopathy rather than NCSE, and is commonly associated with triphasic waves on EEG. In most patients anti-epileptic and/or sedative drugs do not hasten clinical improvement.

Baclofen Neurotoxicity: A Metabolic Encephalopathy Susceptible to Exacerbation by Benzodiazepine Therapy.

PURPOSE: Baclofen has been reported to cause both a metabolic encephalopathy and nonconvulsive status epilepticus. Baclofen is typically used in the management of muscle spasticity but is being increasingly used to manage alcohol withdrawal and opiate dependency. Given the increasing use of baclofen we describe the clinical and electrographical features of baclofen neurotoxicity seen at our institution. METHODS: The clinical and EEG features of patients with an encephalopathy in the setting of baclofen therapy were analyzed. Patients were identified via our hospital EEG database. RESULTS: Fourteen patients were identified having presented with an acute confusional state without identifiable cause other than baclofen use. Five patients took a deliberate overdose, three of whom were baclofen naive, two patients presented after medication prescription error, and seven patients were on stable doses (30-140 mg daily). All patients presented with an encephalopathy, one patient was reported to have clinical seizures, and seven had multifocal myoclonus. EEGs were abnormal in all patients and showed moderate to severe generalized slowing. Generalized triphasic waves occurring at 1 to 2 Hz, sometimes with an anterior to posterior phase lag, were present in 10 patients (71%), and intermittent generalized suppression of the background was seen in three patients. Three patients received small doses of intravenous benzodiazepines, resulting in a marked depression of consciousness and respiration. All patients recovered within 48 hours of baclofen discontinuation. CONCLUSIONS: Baclofen toxicity can produce an acute encephalopathy even at modest doses, with the EEG showing generalized slowing and triphasic waves consistent with a toxic encephalopathy. Management consists of supportive care and cessation of baclofen. Patients with baclofen neurotoxicity exhibit a marked vulnerability to the depressant effects of benzodiazepines.

[Valproate-induced hyperammonemic encephalopathy]. / Encefalopatia hiperamonemica inducida por acido valproico.

TITLE: Encefalopatia hiperamonemica inducida por acido valproico.

Encephalopathy following melphalan administration.

OBJECTIVE: To describe a rare case of encephalopathy following melphalan administration. Presentation and intervention:: A 59-year-old female with multiple myeloma developed encephalopathy following administration of melphalan. After ruling out other aetiologies, we hypothesized elevated cytokines from systemic inflammatory response to melphalan as the likely aetiology. The TNF-alpha level was found to be significantly elevated. Plasmapharesis was performed which reduced the level of cytokines, and also improved the patient's neurological status. CONCLUSION: Melphalan administration, especially in renally impaired patients, may lead to development of encephalopathy. Based on our case report, we suggest that elevated levels of cytokines could be the underlying mechanism of worsening mental status.

Further Concerns About Glutamine: A Case Report on Hyperammonemic Encephalopathy.

OBJECTIVE: We report a case of a woman with hyperammonemic encephalopathy following glutamine supplementation. DESIGN: Case report. INTERVENTIONS: Plasma amino acid analysis suggestive of a urea cycle defect and initiation of a treatment with lactulose and the two ammonia scavenger drugs sodium benzoate and phenylacetate. Together with a restricted protein intake ammonia and glutamine plasma levels decreased with subsequent improvement of the neurological status. MEASUREMENTS AND MAIN RESULTS: Massive catabolism and exogenous glutamine administration may have contributed to hyperammonemia and hyperglutaminemia in this patient. CONCLUSION: This case adds further concerns regarding glutamine administration to critically ill patients and implies the importance of monitoring ammonia and glutamine serum levels in such patients.

Encefalopatía metabólica secundaria a intoxicación por vitamina D / Metabolic encephalopathy secondary to vitamin d intoxication

La asociación entre la deficiencia de vitamina D y un mayor riesgo de diversas enfermedades, entre ellas cardiovasculares y autoinmunes, ha aumentado en los últimos años el uso de suplementos para la normalización de los valores plasmáticos de esta vitamina. Desde entonces se ha descrito un mayor número de casos de intoxicación iatrogénica por vitamina D. Presentamos una enferma de 81 años con encefalopatía metabólica e insuficiencia renal secundarias a una intoxicación por vitamina D. Los suplementos orales con calcio y vitamina D se le prescribieron después de sufrir una fractura vertebral osteoporótica. La enferma mejoró clínica y analíticamente tras hidratación y diuréticos. Es importante destacar la hipercalcemia como causa de encefalopatía metabólica y considerar la intoxicación por vitamina D como etiología poco frecuente pero posible de hipercalcemia e insuficiencia renal reversibles (AU)

The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure (AU)

[FOLFIRINOX-induced hyperammonemic encephalopathy in a patient with pancreatic cancer].

Hyperammonemic encephalopathy is a rare adverse event of chemotherapies based on high-dose 5-fluorouracil. We present a woman in her 70s with metastatic pancreatic adenocarcinoma who underwent FOLFIRINOX therapy. She developed acute onset disturbance of consciousness after completing the first 5-fluorouracil infusion cycle (2400 mg/m(2)/46h). We suspected hyperammonemic encephalopathy induced by 5-fluorouracil and administered branched-chain amino acids solutions and she recovered within a few hours of treatment. Brain computed tomography and magnetic resonance imaging revealed no abnormal findings. She subsequently received chemotherapy with gemcitabine and developed no further hyperammonemia. To the best of our knowledge, this is the first report of FOLFIRINOX-induced hyperammonemic encephalopathy in a patient with pancreatic cancer.

Acute ethanol-induced changes in edema and metabolite concentrations in rat brain.

The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy ((1)H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema.

[Metabolic encephalopathy secondary to vitamin D intoxication]. / Encefalopatía metabólica secundaria a intoxicación por vitamina D.

The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

La asociación entre la deficiencia de vitamina D y un mayor riesgo de diversas enfermedades, entre ellas cardiovasculares y autoinmunes, ha aumentado en los últimos años el uso de suplementos para la normalización de los valores plasmáticos de esta vitamina. Desde entonces se ha descrito un mayor número de casos de intoxicación iatrogénica por vitamina D. Presentamos una enferma de 81 años con encefalopatía metabólica e insuficiencia renal secundarias a una intoxicación por vitamina D. Los suplementos orales con calcio y vitamina D se le prescribieron después de sufrir una fractura vertebral osteoporótica. La enferma mejoró clínica y analíticamente tras hidratación y diuréticos. Es importante destacar la hipercalcemia como causa de encefalopatía metabólica y considerar la intoxicación por vitamina D como etiología poco frecuente pero posible de hipercalcemia e insuficiencia renal reversibles.

Methylene blue encephalopathy: a case report and review of published cases.

Methylene blue is a cationic thiazine dye useful in staining parathyroid glands during surgical resection. There have been a number of reports of altered neurologic status postoperatively in patients who are taking antidepressant medications when they received methylene blue for their surgery. We present a case report and review 30 additional cases that have been reported in the literature. It has been suggested that in susceptible individuals an interaction occurs between methylene blue and serotonergic agents that precipitates serotonin syndrome. Because people with hyperparathyroidism commonly experience depression as part of their illness, anesthesia practitioners should exercise increased vigilance when administering methylene blue to these patients.

[Dynamics of initial manifestations of experimental diabetic encephalopathy].

We established that alloxan diabetes leads to early development of diabetic encephalopathy on the background of marked hyperglycemia. Initial manifestations of experimental diabetic encephalopathy are based on fast progressing loss of neurons and glial cells in the structures of primary somatosensory cortex (field Par 1) and hippocampus (field CAl) between 4th and 17th day after alloxan administration. This is accompanied by accumulation oflipofuscin in neocortex neurons. Manifestations of diabetic encephalopathy on diencephalic level is registered only 10 days after alloxan administration, specifically in paraventricular nucleus where decrease in the number of neurocytes is observed between 10th and 17th day after diabetes induction. Initial manifestations of experimental diabetic encephalopathy correspond to progressing inhibition of orientation and exploratory behavior in animals and decrease of their capacity for conditioning.

Can the tyrosine kinase inhibitors trigger metabolic encephalopathy in cirrhotic patients?

BACKGROUND: Sorafenib is the standard treatment of advanced hepatocarcinoma (HCC) in cirrhotic patients with preserved liver function. It shares many adverse effects with other tyrosine-kinase (TK) inhibitors and antiangiogenic drugs. TK inhibitors could have a direct toxicity on CNS, both by interfering with TK-related pathways and by inhibiting angiogenesis. AIMS: The aim of this study was to investigate whether sorafenib administration can be associated to metabolic encephalopathy in patients with cirrhosis. METHODS: We retrospectively reviewed medical records of all cirrhotic patients treated with sorafenib for HCC afferent at our Department from January 2009 to December 2011. RESULTS: Among 62 patients, we identified 10 patients with clinically significant cognitive impairment. Seven of these were clearly diagnosed with overt hepatic encephalopathy (HE), one with brain metastases and two with drug-related toxic-metabolic encephalopathy. These last two cases were characterized by severe cognitive impairment, mood alteration and memory deficit. Clinical exam, blood tests and brain CT excluded organic causes of encephalopathy and precipitating factors of HE. Sorafenib discontinuation was associated with complete reversal of the syndrome, which recurred on drug re-administration in one case. CONCLUSIONS: Our study suggests that sorafenib may be a precipitating factor of metabolic encephalopathy in cirrhotic patients with advanced HCC. This neurological syndrome appears to be not responsive to the conventional treatment for HE, but it is fully reversible by drug discontinuation. It can be speculated that the potential direct neuronal action of sorafenib may represent a trigger for the onset of metabolic encephalopathy in a subset of cirrhotic patients.

Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid.

The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 µmol/g) or saline (11 h interval between injections) and 60 min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I-III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II-III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.

Metabolic and toxic myelopathies.

The myelopathies discussed in this article have an underlying metabolic or toxic etiology. They have many clinical, electrophysiologic, and neuropathologic similarities. Preferential involvement of the dorsal columns and/or corticospinal tracts is commonly seen. Variable degrees of peripheral nerve and/or optic nerve involvement may be present. In the presence of clinical or electrophysiologic evidence of peripheral nerve involvement, the term myeloneuropathy is commonly used. The metabolic and toxic myelopathies discussed here are divided into three categories: disorders due to an identified nutrient deficiency such as the subacute combined degeneration of cobalamin/vitamin B12 or copper deficiency, disorders that have a geographical predilection and are due to a suspected toxin such as lathyrism, and disorders due to a possible toxin but without a geographical predilection such as hepatic myelopathy (Table 1).