A case of manganese induced parkinsonism in hereditary haemorrhagic telangiectasia

Abstract

A 44 year old right handed woman complained of difficulty in moving. She and her relatives had skin telangiectasia or recurrent epistaxis. On neurological examination, she had a mask-like facies and bradykinesia in both extremities. Laboratory examinations showed iron deficiency anaemia and mild liver dysfunction with raised serum manganese. On T1 weighted cranial magnetic resonance imaging there were hyperintense areas in the globus pallidus bilaterally, suggesting manganese deposition. Abdominal angiography confirmed multiple portalsystemic shunts in the liver, and a needle biopsy of the liver showed diffuse dilatation of the sinusoids with fatty change. Levodopa did not improve the bradykinesia. This appears to be a case of hereditary haemorrhagic telangiectasia with manganese induced parkinsonism, which may be a new type of neurological disorder in such patients.H ereditary haemorrhagic telangiectasia, or Rendu-OslerWeber disease, was first reported by Rendu in 1896 as a systemic vascular disorder with idiopathic epistaxis and skin telangiectasia.1 It is now known to be caused by an abnormality of transforming growth factor β binding proteins, and the patients show hereditary systemic vascular disorders in an autosomal dominant fashion with a high penetrance of 97% by the age of 50 years.2 Recurrent epistaxis or bleeding in the gastrointestinal tract during adolescence is the first symptom of the disease. In the fourth or fifth decade of life, chronic anaemia after recurrent haemorrhage, congestive heart failure caused by pulmonary arteriovenous fistulae, or liver dysfunction associated with portal-systemic shunting become evident, depending on the amount and localisation of the vascular abnormalities.From the viewpoint of neurologists, the disease is interesting for its variety of complications in the central nervous system-paradoxical brain embolism or brain abscess in cases of pulmonary arteriovenous fistula (right to left shunt type, 61%); intracerebral haemorrhage or epilepsy in cases with arteriovenous malformations of the brain (parenchymal AVM type, 36%); and hepatic coma with progression of portalsystemic shunt (porto-systemic shunt type, 3%). In this study we present a patient with hereditary haemorrhagic telangiectasia with manganese induced parkinsonism. We propose that parkinsonism is a new neurological complication in this disease. CASE REPORTA 44 year old right handed woman consulted the neurological clinic because of difficulty in moving. This was especially marked during fine finger movements or in agility exercises. The symptom was insidious and had progressed over 12 months. She was a housewife and had never been exposed to manganese or its compounds. She did not smoke or drink. At the age of 40 years, duodenal ulcer and iron deficiency anaemia were diagnosed. There were no similar symptoms among her relatives. However, the patient, her father, and her younger brother all had skin or mucosal telangiectasia, and her son had experienced recurrent epistaxis, suggesting an autosomal dominant v...

Neuroimaging of Rapidly Progressive Dementias, Part 2: Prion, Inflammatory, Neoplastic, and Other Etiologies

“…T1-weighted hyperintensity within the basal ganglia implies deposition of metals such as iron or manganese. 76 This finding on MR imaging has been reported in the globus pallidus of individuals exposed to manganese from their occupation as miners who developed cognitive impairment. 77 The imaging findings in many other exposures are not well-established, and clinical suspicion and appropriate laboratory investigations remain the cornerstone of evaluation of these forms of progressive dementia.…”

Basal ganglia hyperintensity on T1‐weighted MRI in rendu–osler–weber disease

“…There have been only two other cases, to the best of our knowledge, of ROW so far reported in the literature with hyperintense basal ganglia on T1W MRI associated with hypermanganesemia and accompanied by multiple hepatic intrahepatic shunts (2,3). Since Mn is primarily metabolized in the liver, impaired clearance due to liver dysfunction or intrahepatic shunting could lead to Mn overload despite normal Mn intake (3).…”

“…It is worth noting that radiologic manifestations may precede any clinical symptoms (3,9). Mn-induced parkinsonism differs from idiopathic Parkinson's disease (PD) in that there is a rapid progression of the motor symptoms and early gait and postural impairment with focal dystonia, there is an absence of resting tremor, and finally it is restrictive to L-dopa therapy, which is the mainstay of treatment for idiopathic PD (11).…”

“…Histopathologically, gliosis and mineralization of the globus pallidus without depletion of neurons have been reported. The major neurologic symptom of Mn accumulation in the brain with high signal basal ganglia is parkinsonism associated with variable combinations of behavioral and cognitive dysfunction (3,9).…”

“…It has been reported in only two other case reports in the literature that in patients with ROW and documented intrahepatic portosystemic shunts manganese, a paramagnetic metal, escapes to the systemic circulation and accumulates at high doses in the brain, becoming neurotoxic (2,3). The purpose of this study was to describe the magnetic resonance imaging (MRI) findings of brain changes in ROW disease with or without obvious hepatic involvement.…”