Motor overflow and mirror dystonia.

Motor overflow is an unintentional muscle contraction which accompanies, but is anatomically distinct from the primary dystonic movement. This phenomenological nosology has not been systematically studied in focal hand dystonia (FHD). We conducted a prospective, case-control study to characterize motor overflow and mirror dystonia in patients with FHD. We compared the performance of 30 patients with FHD and 40 healthy controls on a variety of motor tasks, such as writing, drawing a spiral, straight line and a sine wave, repetitive wrist flexion-extension, finger tapping, hand grasping, hand pronation-supination, and a finger-to-nose task with each hand. The assessments were videotaped, the edited video segments were randomized, and an independent investigator who was "blind" to the subject's diagnosis rated the ipsilateral and contralateral overflow and mirror dystonia twice, 6 months apart. Using the mean of the two ratings, ipsilateral overflow was identified in 8.5 +/- 2.1 (28%) patients and in 1.5 +/- 0.7 (4%) controls (p < 0.001), contralateral overflow in 2.5 +/- 0.7 (8%) patients and in 1.5 +/- 0.7 (4%) of controls (p = 0.138), and mirror movement in 20.0 +/- 0.0 (67%) of patients and in 15.5 +/- 4.9 (39%) of controls (p = 0.001). There was a statistically significant correlation of dystonia and overflow score (Pearson's r 0.713, p < 0.001). The relatively high frequency of ipsilateral overflow and mirror dystonia in patients with FHD has both pathophysiological and therapeutic implications. In this study, the severity of dystonia was significantly correlated with motor overflow in multiple tasks.

Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier.

Iron homeostasis in the mammalian brain is an important and poorly understood subject. Transferrin-bound iron enters the endothelial cells of the blood-brain barrier from the systemic circulation, and iron subsequently dissociates from transferrin to enter brain parenchyma by an unknown mechanism. In recent years, several iron transporters, including the iron importer DMT1 (Ireg1, MTP, DCT1) and the iron exporter ferroportin (SLC11A3, Ireg, MTP1) have been cloned and characterized. To better understand brain iron homeostasis, we have characterized the distribution of ferroportin, the presumed intestinal iron exporter, and have evaluated its potential role in regulation of iron homeostasis in the central nervous system. We discovered using in situ hybridization and immunohistochemistry that ferroportin is expressed in the endothelial cells of the blood-brain barrier, in neurons, oligodendrocytes, astrocytes, and the choroid plexus and ependymal cells. In addition, we discovered using techniques of immunoelectron microscopy and biochemical purification of synaptic vesicles that ferroportin is associated with synaptic vesicles. In the blood-brain barrier, it is likely that ferroportin serves as a molecular transporter of iron on the abluminal membrane of polarized endothelial cells. The role of ferroportin in synaptic vesicles is unknown, but its presence at that site may prove to be of great importance in neuronal iron toxicity. The widespread representation of ferroportin at sites such as the blood-brain barrier and synaptic vesicles raises the possibility that trafficking of elemental iron may be instrumental in the distribution of iron in the central nervous system.