Coexistence of mastoid, frontal and vertebral hemangiomas in a patient with diabetic neuropathy: Possible correlation between diabetic angiopathy and intraosseous neoangiogenesis.

Bony hemangiomas are benign vascular lesions with an expansive growth; usually they tend to obliterate the entire bony cavity. They are typical lesion of the spinal bones, but they can rarely arise within other bones of the neurocranium. Diabetic microangiopathy is a condition characterized by the development of aberrant vessel tangles anastomosed to each other due to dysregulated neoangiogenesis. We report the case of a 56-year-old woman, suffering from type 2 diabetes mellitus, admitted to the neurology department due to a reported worsening of paresthesias and dysesthesias of the upper and lower limbs. She performed a contrast-enhanced brain CT scan that showed the presence, at the level of the right mastoid process, of an hypervascular angioma. A subsequent MRI study of the brain and spine showed the presence of multiple bone angiomas, at the level of the right frontal theca and C7, Th3, and Th7 vertebral bodies. Due to the absence of further symptoms and clinical and radiological signs of intracranial compression, the patient did not perform surgery. A radiological follow-up was advised. Although possible pathophysiological correlations between diabetes and vertebral hemangiomas are mentioned in literature, vascular lesions of this type involving vertebrae and skull base simultaneously can be discovered in a patient with chronic diabetic disease. As long as these lesions remain asymptomatic, surgical treatment is not indicated, and the patient is followed over time with radiological follow-up.

Cables1 links Slit/Robo and Wnt/Frizzled signaling in commissural axon guidance.

During neural circuit formation, axons navigate from one intermediate target to the next, until they reach their final target. At intermediate targets, axons switch from being attracted to being repelled by changing the guidance receptors on the growth cone surface. For smooth navigation of the intermediate target and the continuation of their journey, the switch in receptor expression has to be orchestrated in a precisely timed manner. As an alternative to changes in expression, receptor function could be regulated by phosphorylation of receptors or components of signaling pathways. We identified Cables1 as a linker between floor-plate exit of commissural axons, regulated by Slit/Robo signaling, and the rostral turn of post-crossing axons, regulated by Wnt/Frizzled signaling. Cables1 localizes ß-catenin, phosphorylated at tyrosine 489 by Abelson kinase, to the distal axon, which in turn is necessary for the correct navigation of post-crossing commissural axons in the developing chicken spinal cord.

The Nogo-66 Receptors NgR1 and NgR3 Are Required for Commissural Axon Pathfinding.

Nogo-66 receptors (NgR1-3) are glycosylphosphatidyl inositol-linked proteins that belong to the leucine-rich repeat superfamily. Through binding to myelin-associated inhibitors, NgRs contribute to the inhibition of axonal regeneration after spinal cord injury. Their role in limiting synaptic plasticity and axonal outgrowth in the adult CNS has been described previously, but not much is known about their role during the development of the nervous system. Here, we show that NgR1 and NgR3 mRNAs are expressed during spinal cord development of the chicken embryo. In particular, they are expressed in the dI1 subpopulation of commissural neurons during the time when their axons navigate toward and across the floorplate, the ventral midline of the spinal cord. To assess a potential role of NgR1 and NgR3 in axon guidance, we downregulated them using in ovo RNAi and analyzed the trajectory of commissural axons by tracing them in open-book preparations of spinal cords. Our results show that loss of either NgR1 or NgR3 causes axons to stall in the midline area and to interfere with the rostral turn of postcrossing axons. In addition, we also show that NgR1, but not NgR3, requires neuronal PlexinA2 for the regulation of commissural axon guidance.SIGNIFICANCE STATEMENT Over the last decades, many studies have focused on the role of NgRs, particularly NgR1, in axonal regeneration in the injured adult CNS. Here, we show a physiological role of NgRs in guiding commissural axons during early development of the chicken spinal cord in vivo Both NgR1 and NgR3 are required for midline crossing and subsequent turning of postcrossing axons into the longitudinal axis of the spinal cord. NgR1, but not NgR3, forms a receptor complex with PlexinA2 during axon guidance. Overall, these findings provide a link between neural regenerative mechanisms and developmental processes.