Normal dopamine transporter single photon‐emission CT scan in corticobasal degeneration

Herrero Hernandez et al. reported postural tremor in one patient with polycythaemia vera which was tentatively attributed to manganese deposits in the basal ganglia and improved after therapy with a chelating agent. Herein we report a patient with polycythaemia vera who developed persistent parkinsonism and in whom MRI showed features consistent with manganism. In 1998 a 47-year-old man employee began to complain of headache and arterial hypertension that led to the diagnosis of polycythaemia vera, which were treated with repeated blood-lettings. The next year he began to complain of dysesthesia to the feet, nocturnal leg cramps, and unsteady gait. His wife reported that he was slightly confused. The neurological examination showed masked face, monotonous voice, rigidity of the neck and of the right upper arm, slightly ataxic gait with forward bent of the trunk and diffusely brisk tendon reflexes. The blood examination revealed an increase of the hematocrit (50.2%), and transferrin (504 mg/dL; NV 290-390 mg/dL) and a decrease of the sideremia (33 lg/dL; NV 50-150 lg/dL). The serum magnesium, copper and ammonium were within normal range. Serum or urine manganese was not assessed. Hepatic biopsy was negative for increased hepatic copper content. Cranial CT was negative. T1 weighted MR imaging revealed a symmetric hyperintensity of the basal ganglia, cerebral peduncles, red nucleus, quadrigeminal bodies, superior cerebellar peduncles, and dentate nuclei. He started levodopa therapy (100 mg/die) which was unsuccessful and interrupted few months later. Seven years later the clinical condition was substantially stable and the score of the Unified Parkinson’s Disease Rating Scale subscale 3 was 16. A control MRI showed progression of the T1 symmetric hyperintensity in the cerebral peduncels and evidence of the same signal change also in occipital white matter (Fig. 1). There was only a mild diffuse cerebellar atrophy. SPECT examination, obtained by injection of 111-185 MBq of [I]FP-CIT, showed only a mild decrease of dopamine transporter (DAT) density in the right putamen. Manganese level was finally assessed in blood and urine and it was within normal limits. The diagnosis of manganism in our patient was based on the clinical features, exclusion of Parkinson’s disease and Wilson’s disease, and on presence of the typical MRI appearance of symmetric hyperintensity in T1-weighted images of the basal ganglia and other brain structures caused by the paramagnetic properties of manganese. Although a direct demonstration of increased manganese in the serum of our patient was not available, the normal manganese levels observed at follow-up do not exclude the diagnosis since it is well known that, serum or urine levels correlate with actual, but not previous, levels of exposure. Manganese intoxication is usually caused by professional exposure as it typically occurs in miners, welders, and workers in steel industry, but it can also be observed in acute or chronic hepatic diseases and anemia. In particular, increased level of serum manganese is observed in anemia since sideropenia increases the intestinal absorption of manganese. We speculate that in our patient, the increased hematocrit and the frequent blood-lettings associated with polycythaemia vera could have determined manganese intoxication though sideropenia. Persistent parkinsonism is observed in chronic manganese exposure. Although polycythaemia secondary to central hypoventilation can be observed in patients with Parkinson’s disease, in 1977 Herishanu and Rosenberg described occurrence of L-dopa responsive parkinsonisms in three patients with polycythaemia vera, but did not suspect a role for manganism. Ours appears to be the first case of persistent parkinsonism in a patient with polycythaemia vera in whom manganism was documented by MRI and L-dopa was ineffective. Inefficacy of the L-dopa therapy is common in patients with manganese intoxication and is in agreement with the DATscan results in our patient showing only a mildly decreased uptake in the right putamen, despite having the disease for 7 years. This indirectly supports a presumable predominant post-synaptic site of damage of the nigro-striatal pathway in manganism as supported by the normal 6[F]fluorodopa uptake observed with position emission tomography in patients with manganese intoxication. However, our DATscan findings appear to be substantially at variance with the marked symmetric decrease of the 6[F]fluorodopa uptake recently reported in a further patient with parkinsonism due to manganism. However, the latter developed manganism on a background of chronic alcoholic hepatic disease, and it has been pointed out that different exposure mechanisms and factors related to the host metabolism might explain the heterogeneity of the nigro-striatal damage and its clinical expression observed in patients with manganism. Chelating agents have been recommended in patients with chronic manganese exposure, but they were not provided to our patient. In conclusion our observation indicates that permanent extrapyramidal signs with striatal and extra-striatal manganese deposition can complicate polycythaemia vera, probably through increase of the intestinal manganese absorption secondary to sideropenia. Published online 29 September 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mds.22319