Whole-blood manganese levels and brain manganese accumulation in children receiving long-term home parenteral nutrition

Abstract

Recent reports attribute neurological and cerebral disorders to the accumulation of manganese (Mn) in the brain in patients receiving home parenteral nutrition (HPN). It is desirable to control the amount of Mn delivered to these patients, but a suitable method for monitoring an individual's Mn status and assessing Mn accumulation remains debatable. The aim of this study was to evaluate whether whole-blood manganese levels (WB-Mn) correlate with the accumulation of Mn in the brains of children who receive long-term HPN, using magnetic resonance imaging (MRI) of the brain. Six patients who had received HPN (duration of HPN, 18-137 months) were included in this study. The daily parenteral doses of Mn were calculated while on HPN. WB-Mn was measured and T1-weighted MRI of the brain was obtained for each patient with a 1.5-T MR imager. Twelve months after the withdrawal of Mn from HPN, measurements of WB-Mn and brain MRI were repeated in all patients except for one who was lost after initial examination. The same examinations were performed on an additional patient who had been successfully weaned off a 179 month course of HPN 20 months prior to the initial examination. The parenteral dose of Mn while receiving HPN ranged from 15.7 to 91.5 micro g/kg/day. Initially, MRI showed hyperintensity in the globus pallidus in all patients and in the anterior pituitary in one patient. WB-Mn was elevated in four patients, but was in the normal range in the remaining three. Following subsequent measurements 12 months later, WB-Mn was normal in all patients and MRI hyperintensity remained in the globus pallidus in one patient. One patient was lost after the initial examinations. WB-Mn does not necessarily correlate with the accumulation of Mn in the brain. Periodic MRI should be performed in patients receiving long-term NPN to monitor for excessive Mn accumulation in the brain.

Is manganese an essential supplement for parenteral nutrition?

“…Although chronic overexposure to Mn in parenteral nutrition patients has been recognized as a problem for some time now, there have been further reports of elevated Mn levels since Dickerson's review [4,7,11 ,[16][17][18][19][20][21]22 ,23 ] (Table 1). High Mn levels are particularly problematic in the paediatric setting [16,17,19,24] and in long-term HPN patients [18,[25][26][27]; however, hypermanganesemia has also been reported in acute care [7,20]. In addition to these clinical and laboratory findings, a recent analysis of post-mortem data [22 ] describes the cumulative effect of Mn supplementation in patients who received long-term parenteral nutrition for short bowel syndrome (SBS).…”

Manganese and Parenteral Nutrition

“…The neurodevelopmental consequences of this exposure were unfortunately not reported. 68 Our group has similarly documented increased T1-weighted signal intensity in the globus pallidus of children on prolonged Mn-supplemented parenteral nutrition. Figure 15.2 shows a representative T1-weighted MR image obtained from a 4 year-old child, who had been dependent since birth on parenteral nutrition.…”

“…,34,[59][60][61][62][66][67][68][69][70][71][72][73][74] Most of the case reports of Mn toxicity in adults reflect exposures to daily doses of 4500 mg per day of parenteral Mn 14,34,59,66,71,75. …”

Imaging Modalities for Manganese Toxicity

“…Since then, a wealth of human studies have shown that increased Mn exposure can result in significant signal changes in T1-weighted images of Mn-exposed workers. 9-21 Similar hyperintensities are found in patients with reduced hepatobiliary excretion of Mn, [22][23][24][25][26][27][28][29][30][31][32][33][34] in patients receiving total parenteral nutrition (TPN), [35][36][37][38][39][40][41] as well as in subjects addicted to the drug methcathinone (ephedrone). [42][43][44][45][46][47][48][49] In non-human primates, as well as in humans, Mn-induced signal changes are highest in the globus pallidus, adjacent basal ganglia regions, and the pituitary gland (see Figure 19.2), intermediate in the caudate and putamen, and lowest in other gray matter and white matter regions.…”