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

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 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.

Evidence for sex differences in morphological abnormalities in type I Chiari malformation.

BACKGROUND AND PURPOSE: Relatively little is known about the influence of individual difference variables on the presentation of macro-level brain morphology in type I Chiari malformation (CMI). The goal of the present study is to examine how case-control differences in Chiari are affected by patient sex. MATERIALS AND METHODS: Patient-provided magnetic resonance images were acquired through the Chiari 1000 database. Twenty-four morphometric measurements were taken using mid-sagittal images of 104 participants (26 male CMI, 26 female CMI, 26 male controls, and 26 female controls) using internally developed and validated custom software, Morphpro. Case-control comparisons were conducted separately by sex using healthy controls matched by age and body mass index. Probability-based t-tests, effect sizes (Cohen's d), and confidence intervals were used to compare case-control differences separately by sex. RESULTS: Male and female case-control comparisons yielded largely the same trends of CMI-related morphometric abnormalities. Both groups yielded reductions in posterior cranial fossa (PCF) structure heights. However, there was evidence for greater PCF structure height reductions in male CMI patients as measured by Cohen's d. CONCLUSIONS: Case-control differences indicated strong consistency in the morphometric abnormalities of CMI malformation in males and females. However, despite the higher prevalence rates of CMI in females, the results from the present study suggest that male morphometric abnormalities may be greater in magnitude. These findings also provide insight into the inconsistent findings from previous morphometric studies of CMI and emphasize the importance of controlling for individual differences when conducting case-control comparisons in CMI.

Type I Chiari malformation, RBANS performance, and brain morphology: Connecting the dots on cognition and macrolevel brain structure.

BACKGROUND: Idiopathic descent of cerebellar tonsils into the cervical spine in Chiari malformation Type I (CMI) is typically associated with occipital headache. Accumulating evidence from experimental studies suggests cognitive effects of CMI. The aim of the current study was to examine the relationship between cognition and CMI using a battery of standardized neuropsychological and symptom inventory instruments. METHOD: Eighteen untreated adults with CMI, and 18 gender, age, and education matched healthy controls completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and standardized measures of pain, mood, and disability. Morphometric measurements of key neural and osseous elements were also obtained from structural brain magnetic resonance images, for correlation with symptom outcomes. RESULTS: CMI patients exhibited deficits in RBANS attention, immediate memory, delayed memory, and total score. After controlling for pain and associated affective disturbance, the significant group effect for RBANS attention remained. CMI patients also presented seven morphometric differences comprising the cerebellum and posterior cranial fossa compartment that differed from healthy controls, some of which were associated with self-reported pain and disability. Notably, group differences in tonsillar position were associated with self-reported pain, disability, and delayed memory. CONCLUSION: Adult CMI is associated with domain-specific cognitive change, detectable using a standard clinical instrument. The extent of cognitive impairment is independent of pain or affective symptomatology and may be related to the key pathognomonic feature of the condition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).