We made an observation of an increased T2 signal of the cerebellum in fetuses with the Chiari Type II malformation and myelomeningocele, and wondered whether this reflected a real change in the diffusion properties of the cerebellum. Our article describes that we did indeed find a difference when comparing this group with normal fetuses, supporting the hypothesis that this malformation is associated with abnormalities of cerebellar structures beyond those described classically. We presume the underlying mechanism relates to altered CSF flow dynamics, due to impaired venous drainage as a result of obstruction at the foramen magnum. This results in CSF pooling in the posterior fossa, increased extracellular CSF, and hence, measured mean diffusivity. The underlying theory of altered CSF flow and resultant cerebellar tonsillar herniation in open neural tube defects was demonstrated in sheep models and, more recently, was proven in humans, where reversal of tonsillar herniation and subsequent decreased rates of obstructive hydrocephalus necessitating ventriculoperitoneal shunting were shown post in utero closure of the spinal defect at 21–25 weeks’ gestation.¹

However, whether our simplistic explanation accounts for our findings is uncertain. One could argue our findings reflect microstructural damage, as a result of compressive effects, or maldevelopment of the deep cerebellar tracts, similar to those of the supratentorial compartment, where lack of inductive pressure on the adjacent mesenchyme can result in focal developmental anomalies.²  Alternatively, maldevelopment may result from defective expression of a gene related to rhombomeric segmentation, as has been shown in other types of posterior fossa malformations, such as the Dandy-Walker malformation, where altered FOXC1 expression appears to be at least in part responsible for the spectrum of abnormalities demonstrated.³

If our proposed theory is correct, we would expect reversal or improvement of these findings post closure of the surgical defect. Unfortunately, given the small number of patients at our institutions opting to continue pregnancy, and an even smaller number who have proceeded to antenatal surgery, we have been unable to confirm our hypothesis. However, further

investigation of deep matter tract integrity, by way of diffusion tractography of specific cerebellar tracts, particularly projectional corticocerebellar fibers, and if/how they are altered at birth post antenatal surgery, would be helpful to further elucidate mechanisms that result in altered brain stem and cerebellar function post birth. Such findings, particularly if reflective of later neuromotor and cognitive development, may further contribute to justification for antenatal surgery, which is not currently universal practice.

Results of such studies may also assist in clarifying the role of ultra-early posterior fossa decompression surgery, suggested by one author on the basis of improvement of posterior fossa CSF spaces.⁴ However, we understand this practice is controversial,⁵ particularly given that cerebellar atrophy and structural brain stem abnormalities are thought to be already well established at birth. This is not surprising if our findings are indeed reflective of early changes.

Clearly, however, this is a subject warranting further research. Cross-institutional collaboration would also be beneficial given the numbers of subjects required to arrive at robust scientific conclusions—necessary if such findings are used to assist in clinical decision making, particularly when guiding antenatal care.

References

1. Adzick NS, Thom EA, Spong CY, et al. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011;364:993–1004, 10.1056/NEJMoa1014379
2. McLone DG, Naidich TP. Developmental morphology of the subarachnoid space, brain vasculature, and contiguous structures, and the cause of the Chiari II malformation. AJNR Am J Neuroradiol 1992;13:463–82.
3. Aldinger KA, Lehmann OJ, Hudgins L, et al. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet 2009;41:1037–42, 10.1038/ng.422
4. Salman MS. Posterior fossa decompression and the cerebellum in Chiari type II malformation: a preliminary MRI study. Childs Nerv Syst 2011;27:457–62, 10.1007/s00381-010-1359-8
5. Vinchon M. Comment on Salman M: Posterior fossa decompression and the cerebellum in Chiari type II malformation: a preliminary MRI study. Childs Nerv Syst 2011;27:463–64, 10.1007/s00381-010-1361-1

 

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