Clinical/Scientific Notes N. Kumar, MD B.F. Boeve, MD C.T. Cowl, MD, MS J.W. Ellison, MD, PhD P.S. Kamath, MD K.L. Swanson, DO HYPERMANGANESEMIA, HEREDITARY HEMOR- RHAGIC TELANGIECTASIA, BRAIN ABSCESS: THE HEPATIC CONNECTION Hypermanganesemia related pallidal T1-hyperintensity is a rare manifestation of hereditary hemorrhagic telangi- ectasia (HHT). 1 Levodopa-unresponsive parkinsonism has been described in HHT. 1 We report a patient who presented with brain abscess–related seizures and was diagnosed with the HHT-juvenile polyposis overlap syndrome with hypermanganesemia. This report high- lights the multifactorial pathogenesis of hypermanga- nesemia in HHT. Case report. A 35-year-old man was referred for em- bolization of pulmonary arteriovenous malformations (AVMs) which were detected on a chest CT done to investigate the cause of a left frontoparietal abscess. A month earlier he presented with recurrent gen- eralized tonic-clonic seizures. Brain MRI showed a ring-enhancing left frontoparietal mass with edema (figure, A and B). Biopsy revealed purulent fluid which grew Streptococcus viridans and anaerobic Gram-negative rods. He had a past history of epi- staxis, left eye hemorrhage, gum bleeds, iron defi- ciency anemia, and lower gastrointestinal bleeding. Endoscopy revealed multiple telangiectasia involving the gastroduodenal mucosa and colonic polyps. A co- lectomy revealed multiple tubulovillous adenomas. His family history was positive for epistaxis in his mother. His examination was unremarkable except for oral telangiectasia. Hepatic function assessed by liver enzymes was normal. Multiple AVMs were seen on a pulmonary angio- gram. The larger ones were treated with coil embolization. An abdominal CT showed hepatic tel- angiectasia and prominent vessels. Early opacifica- tion of the left portal vein provided evidence of arterial-portal shunting. The suspicion of HHT-polyposis overlap syn- drome was confirmed by analysis of the SMAD4 gene. He was noted to be heterozygous for a single base substitution, c.1081CT, in exon 8 of the SMAD4 gene. Follow-up MRI done 5 months later showed im- provement in the brain abscess. Also noted all along was increased MRI signal on the T1-weighted sequences from the globus pallidus to the substantia nigra (figure). Since this finding suggests possible manganese deposi- tion, serum manganese was obtained and was elevated at 2.6 ng/mL (normal: 0.4 – 0.85 ng/mL). A review of his occupational history revealed that he used potassium permanganate as a reagent to test water purity. He ad- mitted to occasional hand staining. He was given to nail-biting and did not use any protection while using reagents. Discussion. HHT is an autosomal dominant dis- ease characterized by vascular telangiectasias and AVMs. The majority of the cases are caused by mu- tations in the endoglin (ENG) or activin receptor- like kinase (ALK1, ACVRL1) genes that encode members of the transforming growth factor (TGF)- signaling pathway. HHT can also be caused by SMAD4 mutations. The latter group usually also have gastrointestinal polyposis. 2 HHT can be associated with a variety of neuro- logic complications. 3 Hemorrhage or seizures are presenting manifestations of cerebral AVMs. Pulmo- nary AVMs present with a brain abscess or cerebro- vascular disease via paradoxical embolism. Ingested manganese enters the portal circulation and is elimi- nated almost exclusively by the liver via biliary excre- tion. If the hepatic excretion mechanism is overwhelmed, manganese accumulates in the body. Shunting between the portal and hepatic veins occurs in HHT and was the cause of ingested manganese bypassing hepatic clearing mechanisms, accumulat- ing in the blood and striatum. Increased pallidal T1-signal due to manganese has been described in liver failure and in welders. Similar basal ganglia lesions with hypermanganesemia have been rarely reported in HHT. 1,4 One of these cases also had levodopa-resistant manganese-induced parkinsonism. 1 Two additional factors were likely operative in our patient’s hypermanganesemia. Iron and manga- nese utilize the same gastrointestinal mucosal carrier. Patients with iron deficiency have increased man- ganese absorption. Iron deficiency promotes man- ganese uptake in the brain. 5 His occupational exposure to potassium permanganate may have had an additional role. Chronic enteral poisoning 1118 Neurology 71 September 30, 2008