Lingappa et al. reply


SIR–The letter by Squier and Mack raises very pertinent questions about the causal mechanisms of occlusion of mineralized lenticulostriate arteries following trauma. The latency of only about 24 hours between trauma and stroke suggests that the trauma may not be a cause, but a trigger for occlusion of predisposed vessels. The neonatal lenticulostriate vasculopathy may be a precursor of the mineralization of these arteries.[1]

The known associations in children include intrauterine infections, trisomies, and head injury itself. The association between infections (cytomegalovirus, echovirus, Epstein-Barr virus, and mycoplasma) and mineralization was also highlighted by a recent study from China.[2] A study in Cynomolgus monkeys using X-ray microanalysis of mineralized brain samples, demonstrated the presence of the calcium, phosphate, zinc, and iron in a mucopolysacharide matrix.[3, 4] The electron microscopy of the mineralized tissues revealed degenerative changes in the vessel walls, a severely thickened subendothelial basement membrane due to excessive collagen fibres, resulting in atrophy of endothelial cells.[5] The inflammatory cell infiltration and glial reaction were conspicuously absent at the mineralized areas.

This suggests that the unknown inciting factor (infection, inflammation, genetic, or other environmental factors) started a cascade of vessel wall endothelial changes, culminating in vascular wall mineralization. The intermediary steps have yet to be elucidated. The mineralized vessels (arterioles and venules) are highly susceptible to occlusion following minor trauma. The mechanisms underlying occlusion of arterioles following trauma are also poorly understood. Mineralizing angiopathy with basal ganglia stroke in infants after minor trauma is one syndrome that clearly implicates lenticulostriate calcification as the pathological substrate.[6]

Information on the platelet-derived growth factor receptor β gene (PDGF-Rβ) mutations being associated with idiopathic basal ganglia calcification is also very important in understanding this entity.[7]

Further pericyte dysfunction may predispose to breakage of the blood brain barrier and mineralization of lenticulostriate arteries. Whether the lenitculostirate mineralization is the end result of multiple different insults or a homogenous group is not yet clear. In our cohort there were no other family members similarly affected. It would be prudent to perform genetic studies evaluating PDGF-Rβ mutations in this cohort to understand the pathophysiology better. Suitable animal models are needed to elucidate the mechanisms of mineralization, as well as the mechanisms mediating the occlusion of mineralized vessels following trauma. This information might help in primary and secondary prevention of this form of stroke in infants and young children.