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Background: Manganese (Mn) is included in current premixed multiple trace element (TE) additives for home parenteral nutrition (HPN). However, there is a risk of oversupplementation of Mn due to contamination from PN additives. Oversupplementation can produce Mn toxicity with neurologic symptoms and abnormalities on brain magnetic resonance imaging (MRI). In 2009, we reported that whole-blood Mn levels were above the upper limit of normal in 16 HPN patients, with 81% having MRI findings. Subsequently, we removed Mn supplementation from all our HPN patients. We present a 5-year follow-up here., Methods: This is a prospective cohort study on 11 of the surviving 16 patients on HPN. All patients had Mn removed from PN and had yearly monitoring of blood Mn levels. Eight patients had a repeat MRI to evaluate for resolution of basal ganglia deposits. Patient demography, clinical history, and bloodwork were recorded., Results: Five of 6 patients who initially had elevated Mn levels had normal levels on follow-up. All patients who had Mn levels measured serially had a decrease in levels; the mean percent decrease of Mn was 38.1% (range, 10.1%-53.8%). Two patients had elevated Mn despite the absence of supplementation. Six of 8 patients who had repeat MRIs had complete resolution abnormalities., Conclusions: Removal of Mn as an additive in HPN solutions resulted in resolution of MRI abnormalities in most patients. Over 5 years, all patients except for 1 maintained normal blood Mn levels. Therefore, Mn levels should be monitored and supplementation be individualized., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: Long-term parenteral nutrition (PN) can be associated with micronutrient deficiency or toxicity depending on supplementation. Recently, hypermanganesemia and potential neurological toxicity were reported. The aim of this study was to assess the effect of manganese supplementation in a sample of patients on long-term PN receiving manganese (Mn) as part of a multi-trace element (TE) supplement., Methods: A convenience sample of 16 patients underwent clinical and blood biochemical measurements as well as magnetic resonance imaging (MRI) of the brain. Descriptive statistics were performed., Results: The mean daily Mn supplementation was 7.28 ± 0.97 µmol/d (400 ± 53 µg/d), which was within the American Medical Association Nutrition Advisory Group guidelines of 2.73-14.56 μmol/d (150-800 µg/d) but exceeded the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) 2002 recommendations of 1.09-1.82 µmol/d (60-100 µg/d). The mean whole blood Mn level was 1.38 ± 0.29 times the upper limit of normal (ULN), and 8 of 14 patients with blood measurements had Mn levels above ULN. On MRI, 81% of patients had high signals on T1-weighted images assumed to be Mn deposits in their basal ganglia. Two patients with positive MRI (15%) had a clinical diagnosis of Parkinson disease. Multiple neuropsychiatric complaints were reported, including depression (66%), lack of concentration (42%), memory disturbances (17%), and gait instability (8%)., Conclusion: These results suggest that Mn status is elevated in these patients. Manganese supplementation should be used with caution in patients receiving long-term PN, and attention should be paid to the Mn content of multi-TE supplements.

Background and Methods: The administration of trace elements is thought to be needed in patients receiving long-term parenteral nutrition. Recently, manganese intoxication or deposition was documented in such patients. We report two cases of manganese intoxication during intermittent parenteral nutrition including manganese. Manganese had been administered for 4 years at a frequency of one or two times per week in one case and for 5 years at a frequency of one or two times per month in the other case. Both cases showed mild symptoms with headache and dizziness. One case had mild hepatic dysfunction and the other did not. The whole-blood manganese level increased in one case, but not in the other case. T1-weighted magnetic resonance images revealed symmetrical high-intensity areas in basal ganglia and thalamus in both cases. After the administration of manganese was stopped, these symptoms all disappeared and the magnetic resonance images abnormalities gradually improved in both patients. Mild long-term manganese intoxication is thus considered to occur regardless of the frequency of using a manganese supplement., Conclusions: Patients should be carefully monitored when receiving long-term parenteral nutrition including manganese, even when the manganese dose is small and the frequency of receiving a manganese supplement is low.

Background: Extrapyramidal syndrome and alterations in brain magnetic resonance images are described in patients undergoing long-term home parenteral nutrition (HPN) and in cholestatic patients. These abnormalities have been correlated to basal ganglia manganese (Mn) accumulation., Methods: A longitudinal 1-year study was conducted on 15 patients undergoing HPN (median duration, 3.8 years; range, 1.7-10; median Mn parenteral supplementation, 0.1 mg/d). Whole-blood, plasma, intra-erythrocytes, and urinary Mn concentrations were measured and brain magnetic resonance was performed at the beginning (time 0) and after 1 year of Mn intravenous supplementation withdrawal (time 1). No patients showed psychosis, extrapyramidal syndrome, or cholestasis., Results: At time zero, 10 of 15 patients (67%) showed paramagnetic accumulation on cerebral magnetic resonance images; at time 1 there was a reduction of cerebral Mn accumulation. In all patients, blood-Mn levels were significantly reduced after 1 year of Mn intravenous supplementation withdrawal., Conclusions: Patients receiving long-term HPN showed an elevated incidence of alterations in brain magnetic resonance images with a median Mn intravenous supplementation of 0.1 mg/d. Mn supplementation withdrawal significantly decreased metal levels in blood and brain storage. We noticed that the intra-erythrocyte Mn level was a good index of Mn status.

Background: Manganese is one of the trace elements that is routinely administered to total parenteral nutrition (TPN) patients. The recommended daily IV dosage ranges from 100 to 800 MICROg. We have used 500 microg daily. Recent reports have suggested neurologic symptoms seen in some patients receiving home parenteral nutrition (HPN) may be due to hypermanganesemia. Therefore, HPN patients and some short-term inpatients receiving TPN were studied to ascertain the relationship between dose and blood levels., Methods: Red blood cell manganese levels were obtained by atomic absorptiometry., Results: The levels in 36 hospitalized, short-term patients obtained within 48 hours of initiating TPN were all normal. The 30 patients receiving TPN from 3 to 30 days had levels that ranged from 4.8 to 28 microg/L (normal, 11 to 23 microg/L). Two patients had abnormal levels, at days 14 and 18. Fifteen of the 21 patients receiving inpatient TPN or HPN for 36 to 5075 days had elevated Mn levels. Only one patient with hypermanganesemia, an inpatient, had abnormal biochemical liver tests (bilirubin and alkaline phosphatase). One of the patients with a high level had some vestibular symptoms attributed to aminoglycoside use and had increased signal density in the globus pallidus on T1-weighted images on magnetic resonance imaging (MRI). A second patient with Mn levels twice normal had no neurologic symptoms, but had similar MRI findings. A third had some basal ganglia symptoms, confirmed by a neurologic evaluation, seizures, and very high Mn levels. The MRI showed no signal enhancement, but motion artifacts limited the study technically., Conclusions: Hypermanganesemia is seen in HPN patients receiving 500 microg manganese daily and may have resulted in some neurologic damage in three patients. Hypermanganesemia is sometimes seen after a short course of TPN in inpatients, as early as 14 days. Patients should be monitored for hypermanganesemia if they receive Mn in their TPN for >30 days. A 500 microg/d dose of Mn is probably excessive, and 100 microg/d should probably never be exceeded. Mn should be eliminated from the solution if the Mn level is elevated and should not be readministered unless the level returns to normal or subnormal. Mn should not be supplemented if the patient has liver disease with an elevated bilirubin.

Background: Hypermanganesemia and cholestatic liver disease are both recognized complications of long-term IV nutrition. Manganese is primarily excreted in bile, and recent studies have indicated that manganese toxicity may play a role in the pathogenesis of IV nutrition-associated cholestasis., Methods: Whole blood and plasma manganese concentrations were measured in patients receiving long-term home IV nutrition (HIN, n = 30). Whole blood manganese concentrations also were measured in patients with chronic liver disease (CLD, n = 10) and control subjects (n = 10)., Results: Whole blood manganese concentrations of all CLD patients were within the reference interval (73 to 210 nmol/L) and were not different from those of the control group (151 +/- 44 nmol/L, CLD vs 155 +/- 35 nmol/L, control; not significant), despite the presence of cholestasis. In contrast, whole blood manganese concentration was increased (>210 nmol/L) in 26 patients, and plasma manganese concentration increased (>23 nmol/L) in 23 of the patients receiving HIN. None of the patients exhibited neurologic signs of manganese toxicity. There was no correlation between whole blood manganese concentrations and markers of cholestasis, IV manganese intake, or duration of HIN. However, plasma manganese concentration correlated both with average weekly IV manganese intake (r = .44, p = .02) and with gamma-glutamyl transferase (r = .43, p = .02) and alkaline phosphatase activities (r = .55, p = .003)., Conclusions: Cholestatic liver disease does not appear to contribute to increased whole blood manganese concentrations in patients not receiving HIN. Plasma manganese concentrations in patients receiving HIN reflect recent manganese exposure and impaired excretion where cholestasis is present. The lack of relationship between plasma and whole blood manganese concentrations suggests that factors other than manganese intake and excretion affect intracellular concentrations.

Background: Neurologic and radiologic disorders have been reported in patients receiving long-term parenteral nutrition (PN). On the basis of elevated serum manganese levels, some of these abnormalities have been attributed to manganese intoxication. Alterations of the basal ganglia signal intensity on T1-weighted magnetic resonance images (MRIs) have been previously reported, but the precise nature of these alterations remains controversial although the deposition of manganese has been suggested in patients with chronic hepatic encephalopathy due to liver failure., Methods: We report the case of a patient who was receiving PN and exhibited a chronic cholestasis. Neurologic disorders appeared after several months of PN, when a hypersignal in the basal ganglia and white matter was found on T1-weighted MRIs of the brain in association with elevated serum and manganese levels., Results: Elevated autopsic concentrations of manganese were found in the radiologic abnormal cerebral areas., Conclusions: Our observation is the first demonstration of a relationship between high intracerebral manganese levels, radiologic abnormalities, and neurologic disorders during long-term PN. Moreover, serum manganese levels are not a good indicator of cerebral levels. In fact, in our patient, serum manganese levels returned to normal, whereas those of cerebral manganese remained increased.

Background: Manganese deposition was suspected in a pediatric patient who received long-term total parenteral nutrition. T1-weighted magnetic resonance images revealed high intensity areas in the globus pallidus. This study was designed to clarify if these abnormal findings were related to manganese deposition and clinical neurological manifestations., Methods: Whole-blood manganese concentrations were measured during manganese supplementation to total parenteral nutrition and after 5 months without manganese. Magnetic resonance images were also examined on each occasion and compared with the blood level of manganese., Results: The whole-blood manganese level during supplementation was 135 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was 20 micrograms/L after a manganese-free period of 5 months. Accompanied with normalization of manganese level, abnormal high intensity lesions in the globus pallidus on T1-weighted images also disappeared. No neurological manifestation related to the high manganese level was recognized., Conclusions: It is probable that the high manganese level was elicited by manganese supplementation to total parenteral nutrition. This high manganese condition was confirmed by the measurement of whole-blood manganese level, which was associated with the abnormal high intensity lesions on T1-weighted magnetic resonance images.

Manganese is vital in human nutrition. When oral intake is precluded, the recommended parenteral supplementation is 0.15 to 0.8 mg/day. Manganese is excreted primarily in the bile; during cholestasis, serum manganese levels may rise, and manganese toxicity ensue. Neuropsychiatric symptoms are prominent. Phenothiazine-derivative drugs may potentiate manganese toxicity. Serum or whole blood manganese levels should guide manganese therapy in jaundiced patients.

Manganese is excreted primarily via the bile. The objective of this study was to determine if plasma Mn concentrations were elevated in infants and children fed intravenously who developed cholestatic liver disease. An additional aim was to determine the Mn content of intravenous solutions. The study included nine subjects with normal liver function (group A) and five subjects who developed cholestatic liver disease while fed intravenously (group B). Serum total bilirubin in group B had been elevated for 1 wk to 5 months prior to entry into this study. Mean plasma Mn for group A was 0.79 +/- 0.18 ng/ml, which was similar to that for adult controls. The mean for group B was 3.06 +/- 2.07 ng Mn/ml which was significantly higher (p less than 0.005). Plasma Mn was correlated positively with serum total bilirubin (r = 0.874, p less than 0.001). In four group B subjects studied longitudinally, plasma Mn declined. This decline was associated with a decline in serum total bilirubin in one subject and both a decline in serum total bilirubin and a reduction in, or a cessation of, supplemental intravenous Mn in two subjects. In the fourth subject, hepatic dysfunction remained severe, but plasma Mn declined to a near normal value after discontinuing supplemental intravenous Mn. The mean Mn contamination in the final intravenous infusate was 5.1 +/- 2.1 micrograms Mn/1. In conclusion, it is recommended that plasma Mn concentrations be monitored in patients fed intravenously who have evidence of cholestatic liver disease. If monitoring is not feasible, Mn supplements should be withheld.