Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that manganese (Mn) deficiency in rats results in reduced activity of manganese superoxide dismutase (MnSOD) and increased levels of mitochondrial lipid peroxidation. These findings suggested to us that the Mn-deficient rat may be especially susceptible to the toxic effects of ethanol, as the metabolism of this compound results in production of superoxide anion. Offspring from Mn-sufficient and Mn-deficient adult rats were given either 20% (wt/vol) ethanol or distilled-deionized water as their drinking fluid for 14 d. Response to ethanol feeding was different between Mn-sufficient and deficient rats as evidenced by severe reductions in caloric intake and body weight observed in the Mn-deficient rats. Furthermore, after 14 d of ethanol feeding, these rats were extremely lethargic and in poor physical condition. Although Mn-sufficient rats responded similarly to the deficient rats during the first 6 d of ethanol feeding, they increased their caloric intake and body weight during the remainder of the experimental period. MnSOD activity in the ethanol-fed Mn-sufficient and Mn-deficient rats was similar, thus the alcohol-induced toxicity observed in the deficient rats was not due to reduced MnSOD activity. Iron-induced lipid peroxidation may be one of the mechanisms leading to the toxicity observed, as ethanol feeding resulted in liver Fe levels that were 30% higher than those in Mn-deficient rats that were not fed ethanol.
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PMID:Manganese deficiency: effects on susceptibility to ethanol toxicity in rats. 398 Dec 64

Chronic acquired hepatocerebral degeneration (CAHD) is a heterogeneous disorder that can occur with a primary neurologic, hepatic, or combined presentation. Little has been added to the understanding of this disorder since the detailed, early clinical and pathological descriptions. The spectrum of clinical presentations can be neuropsychiatric (apathy, lethargy, excessive somnolence), a movement disorder (ataxia, tremor, chorea, parkinsonism, myoclonus, dystonia), or both. Cortical laminar necrosis and polymicrocavitation in the cortex and basal ganglia are combined with cerebral and cerebellar atrophy. Microscopically, Alzheimer type II astrocytes and cytoplasmic glycogen granules are characteristic. Recent neuroradiological observations in patients with liver failure have shown a specific magnetic resonance (MR) imaging appearance with a hyperintense T1 signal in the pallidum, putamen, and, rarely, mesencephalon. Using clues from a similar MR appearance in patients receiving total parenteral nutrition as well as animals given parenteral manganese, and the knowledge that manganese is cleared by the hepatobiliary system, deposition of manganese in the brain is postulated in patients with CAHD. In this review we describe three cases of CAHD with detailed clinical and radiological documentation and discuss the aforementioned pathogenetic mechanisms.
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PMID:Chronic acquired hepatocerebral degeneration: case reports and new insights. 886 9

We describe the case of a 50-year-old man with a fatal intoxication after accidental massive oral ingestion of manganese. The patient presented with lethargy, diffuse abdominal pain, vomiting, and profuse diarrhea after ingesting Epsom salts (magnesium sulfate heptahydrate) during a liver cleansing diet. Despite intensive care management with intubation, prone position ventilation, continuous venovenous hemofiltration, and multiple transfusions, he progressed to refractory shock with multiple organ dysfunction resulting in death within 72 h. Similar patients arrived at several hospitals with identical epidemiology (all had ingested the same salt obtained in the same place). Clinical and forensic investigations (X-ray diffraction) discovered that the supplier had mistakenly prepared the salts with hydrated manganese sulfate instead of magnesium sulfate heptahydrate. The results enabled the other patients to be successfully treated for hydrated manganese sulfate intoxication with life support in the intensive care unit and chelation therapy (EDTA). We describe the clinical presentation of acute manganese poisoning and alert professionals to the risk of an increasingly popular diet. This case demonstrates the importance of collaboration between clinicians, pathologists, and forensic scientists to resolve a difficult-to-diagnose case.
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PMID:Fatal manganese intoxication due to an error in the elaboration of Epsom salts for a liver cleansing diet. 2288 74

Lethargy is a frequent and important clinical feature of anaemia; however, it does not absolutely correlate with the severity of anaemia. Manganese is efficiently absorbed through the gastrointestinal tract via divalent metal transporter 1 (DMT1), which is also responsible for iron transport. DMT1 is upregulated in iron deficiency (ID). Increased manganese concentrations are reported in ID anaemia (IDA) in various species. Manganese is neurotoxic and therefore may contribute to lethargy observed in some anaemic patients. In addition, anaemia and ID are common in human inflammatory bowel disease. Little is known about how anaemia influences manganese metabolism in veterinary patients and how common is anaemia in dogs with chronic enteropathy (CE). If elevated manganese concentrations are found, then potentially neurotoxicity may be contributing to morbidity in these cases. The objectives of this study were to investigate the hypothesis that whole blood manganese concentrations would be increased in dogs with anaemia, particularly in dogs with confirmed IDA, and that anaemia would be common in canine CE. Medical records from 2012-2016 were reviewed for dogs with CE that were anaemic, as well as dogs with confirmed IDA, where a sample suitable for manganese analysis was held in an archive. Manganese concentration was measured in whole blood from: 11 anaemic dogs with CE, 6 dogs with IDA, 9 non-anaemic ill controls, and 12 healthy controls. Mann-Whitney U and Kruskal-Wallis tests with post-test Dunn's multiple comparisons tests were performed, with P<0.05 considered significant. The prevalence of anaemia in canine CE was 20.6% (33/160). Manganese concentrations were significantly different between all groups (P=0.0001) and higher in non-anaemic than anaemic dogs (P=0.0078). Manganese concentrations were also higher in healthy compared to ill controls (P<0.0001), anaemic dogs with CE (P=0.0056) and to dogs with IDA (P=0.0001). No differences were observed between anaemic dogs with CE, IDA and ill controls. Although anaemia was frequently observed in canine CE, the hypothesis that dogs with anaemia would have increased manganese concentrations, possibly contributing to a lethargic state was not supported. Further research is warranted to understand the influence of anaemia on whole blood manganese.
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PMID:Investigation of manganese homeostasis in dogs with anaemia and chronic enteropathy. 2929 96

Manganese accumulation in the central nervous system creates clinical symptoms of cognitive dysfunction, behavioral changes, and movement disorders resembling Parkinson's disease. Radiographic features of this rare clinical entity include symmetric T1 hyperintensities in the bilateral globus pallidi, with corresponding hypointensities on T2-weighted images. Total parenteral nutrition (TPN) is an increasingly used potentially lifesaving therapy for patients who cannot tolerate enteral nutrition. However, when used over a period of several weeks to months, its associated risks and complications carry significant morbidity and mortality. One of the more rare complications of TPN use is manganese toxicity. We provided care for a 38-year-old female on chronic TPN who presented to the hospital with Parkinsonian features, confusion, falls, and lethargy. MRI brain showed T1 hyperintensities in the bilateral globus pallidi, which were attributed to manganese toxicity from chronic TPN use. Supporting evidence for this rare entity included decreased signal intensity in the bilateral globus pallidi on T2-weighted images and T1 hyperintensities in the substantia nigra. With antifungal treatment and permanent cessation of TPN, her mentation and neurological symptoms began to improve within a week. Repeat MRI brain performed one month after discontinuation of TPN revealed improvement of the T1 hyperintensities in the bilateral globus pallidi. Our objective in presenting this case is to highlight manganese neurotoxicity as a rare complication of TPN in a patient without known hepatic dysfunction and to emphasize the importance of routinely monitoring patients for the possible adverse effects of chronic TPN. Our case is among the handful of published cases in which a patient without known liver dysfunction, which is the primary organ responsible for manganese elimination from the body, developed manganese neurotoxicity.
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PMID:Manganese Neurotoxicity as a Complication of Chronic Total Parenteral Nutrition. 3237 76