Evidence of Neural Microstructure Abnormalities in Type I Chiari Malformation: Associations Among Fiber Tract Integrity, Pain, and Cognitive Dysfunction

Abstract

Background Previous case–control investigations of type I Chiari malformation (CMI) have reported cognitive deficits and microstructural white matter abnormalities, as measured by diffusion tensor imaging (DTI). CMI is also typically associated with pain, including occipital headache, but the relationship between pain symptoms and microstructure is not known. Methods Eighteen female CMI patients and 18 adult age- and education-matched control participants underwent DTI, were tested using digit symbol coding and digit span tasks, and completed a self-report measure of chronic pain. Tissue microstructure indices were used to examine microstructural abnormalities in CMI as compared with healthy controls. Group differences in DTI parameters were then reassessed after controlling for self-reported pain. Finally, DTI parameters were correlated with performance on the digit symbol coding and digit span tasks within each group. Results CMI patients exhibited greater fractional anisotropy (FA), lower radial diffusivity, and lower mean diffusivity in multiple brain regions compared with controls in diffuse white matter regions. Group differences no longer existed after controlling for self-reported pain. A significant correlation between FA and the Repeatable Battery for the Assessment of Neuropsychological Status coding performance was observed for controls but not for the CMI group. Conclusions Diffuse microstructural abnormalities appear to be a feature of CMI, manifesting predominantly as greater FA and less diffusivity on DTI sequences. These white matter changes are associated with the subjective pain experience of CMI patients and may reflect reactivity to neuroinflammatory responses. However, this hypothesis will require further deliberate testing in future studies.

Imaging and health metrics in incidental cerebellar tonsillar ectopia: findings from the Adolescent Brain Cognitive Development Study (ABCD)

“…Pediatric ICTE subjects were also found to have a ~3mm shortening of the distance from the McRae line to these hindbrain structures, implying a similar type of hindbrain sagging as seen in adult CMI. However, the clivus bone in adult CMI has also been found to be signi cantly shorter compared to controls, with a larger reduction in men than women (5.4 vs. 3 mm, respectively) [29,31,37]. In the present study, the differences in clivus length between ICTE and controls were not as dramatic (1.15 and 2.15 mm, for females and males, respectively), with only the male difference reaching statistical signi cance.…”

“…The present pediatric results were compared with adult CMI PCF morphometrics reported previously [31,36,37]. Speci cally, Houston et al looked at >115 adult female CMI subjects compared to matched controls and found 14 signi cant differences they grouped as PCF structure heights, clivus angulation, and odontoid process irregularities [31,36].…”

“…All ABCD participants were screened for major health and neurological issues, ensuring that all subjects were healthy, and thus, all subjects found with TP > 5mm were strictly incidental. In addition, the size of the ABCD repository enabled the selection of a carefully matched control group by race, ethnicity, gender, age, BMI, all factors that can affect morphometric evaluation [37]. Finally, 22 morphometrics measures were selected representing cranial, tissue, PCF lengths, areas, and angles that together comprise an extensive assessment of the PCF morphometrics.…”

“…Houston et al found that in adults (females and males), the distances from the fastigium, pons, and corpus callosum to the McRae line were ~3mm shorter in CMI subjects compared to controls, meaning the entire hindbrain sits lower [31,37]. Pediatric ICTE subjects were also found to have a ~3mm shortening of the distance from the McRae line to these hindbrain structures, implying a similar type of hindbrain sagging as seen in adult CMI.…”

“…Speci cally, Houston et al looked at >115 adult female CMI subjects compared to matched controls and found 14 signi cant differences they grouped as PCF structure heights, clivus angulation, and odontoid process irregularities [31,36]. In a smaller follow-up study, Houston et al examined the same PCF morphometrics in 26 male symptomatic CMI subjects and matched controls and found largely similar results as with females, but that the male differences were larger in magnitude [37]. In a study using many of the same subjects as Houston et al, Biswas et al found that adult female CMI subjects exhibited larger cerebellum (in the PCF space) and reduced CSF spaces below the FM [36].…”