Clinical criteria for filum terminale resection in occult tethered cord syndrome.

OBJECTIVE: Tethered cord syndrome (TCS) comprises three symptom categories: back/leg pain, bowel/bladder, and neurological complaints. MRI typically reveals a low-lying conus medullaris, filum terminale (FT) pathology, or lumbosacral abnormalities. FT resection is established in TCS but not in radiologically occult TCS (OTCS). This study aims to identify patients with OTCS who are likely to benefit from FT resection. METHODS: The authors recruited 149 patients with OTCS (31 pediatric, 118 adult) treated with FT resection-including only cases with progressive TCS, negative spine MRI, and no concurrent neurological/urological conditions. A comprehensive questionnaire collected patient self-reported symptoms and clinical findings at the preoperative and at 3- and 12-month follow-up examinations. Based on questionnaire data, the authors extracted a 15-item symptoms and findings scale to represent the three TCS symptom categories, assigning 1 point for each item present. RESULTS: OTCS presents without radicular/segmental sensorimotor findings, but with leg/back pain and conus dysfunction, in addition to leg fatigue and spasticity; the latter indicating an upper motoneuron pathology. The 15-item scale showed clinical improvement in 89% of patients at the 3-month follow-up and 68% at the 12-month follow-up. Multivariate analysis of the scale revealed that it accurately predicts outcome of FT resection in 82% of cases. Patients with a preoperative score exceeding 6 points are most likely to benefit from surgery. CONCLUSIONS: By applying the study's inclusion criteria and incorporating the novel 15-item scale, surgeons can effectively select candidates for FT resection in patients with OTCS. The observed outcomes in these selected patients are comparable to those achieved in degenerative spine surgery.

Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.

In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability-as measured by Oswestry Head and Neck Pain Scale and social isolation-as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity.

Cognition in Chiari Malformation Type I: an Update of a Systematic Review.

Chiari malformation has been classified as a group of posterior cranial fossa disorders characterized by hindbrain herniation. Chiari malformation type I (CM-I) is the most common subtype, ranging from asymptomatic patients to those with severe disorders. Research about clinical manifestations or medical treatments is still growing, but cognitive functioning has been less explored. The aim of this systematic review is to update the literature search about cognitive deficits in CM-I patients. A literature search was performed through the following electronic databases: MEDLINE, PsychINFO, Pubmed, Cochrane Library, Scopus, and Web of Science. The date last searched was February 1, 2023. The inclusion criteria were as follows: (a) include pediatric or adult participants with a CM-I diagnosis, (b) include cognitive or neuropsychological assessment with standardized tests, (c) be published in English or Spanish, and (d) be empirical studies. Articles that did not report empirical data, textbooks and conference abstracts were excluded. After the screening, twenty-eight articles were included in this systematic review. From those, twenty-one articles were focused on adult samples and seven included pediatric patients. There is a great heterogeneity in the recruited samples, followed methodology and administered neurocognitive protocols. Cognitive functioning appears to be affected in CM-I patients, at least some aspects of attention, executive functions, visuospatial abilities, episodic memory, or processing speed. However, these results require careful interpretation due to the methodological limitations of the studies. Although it is difficult to draw a clear profile of cognitive deficits related to CM-I, the literature suggests that cognitive dysfunction may be a symptom of CM-I. This suggest that clinicians should include cognitive assessment in their diagnostic procedures used for CM-I. In summary, further research is needed to determine a well-defined cognitive profile related to CM-I, favoring a multidisciplinary approach of this disorder.

Revisiting the factor structure of the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2): Evidence for a bifactor model in individuals with Chiari malformation.

The Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2; Dworkin et al., 2009) is intended to measure the multidimensional qualities of pain (i.e., continuous, intermittent, neuropathic, and affective) as well as total pain. Using structural equation modeling, we evaluated the fit of four competing measurement models of the SF-MPQ-2-an oblique 4-factor model, a 1-factor model, a higher-order model, and a bifactor model-in 552 adults diagnosed with Chiari malformation, a chronic health condition whose primary symptoms include head and neck pain. Results revealed the strongest support for the bifactor model, suggesting that SF-MPQ-2 item responses are due to both a general pain factor and a specific pain factor that is orthogonal to the general pain factor. Additional bifactor analyses of the SF-MPQ-2's model-based reliability and dimensionality revealed that most of the SF-MPQ-2's reliable variance is explained by a general pain factor, and that the instrument can be modeled unidimensionally and scored as a general pain measure. Results also indicated that the general and affective pain factors in the bifactor model uniquely predicted pain-related external criteria (e.g., depression, anxiety, and stress); however, the continuous, intermittent, and neuropathic factors did not.

Association between resistance to cerebrospinal fluid flow and cardiac-induced brain tissue motion for Chiari malformation type I.

PURPOSE: Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. METHODS: Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. RESULTS: The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10-10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. CONCLUSION: This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.

The Relationship Between Imbalance Symptom and Cardiac Pulsation Induced Mechanical Strain in the Brainstem and Cerebellum for Chiari Malformation Type I.

Chiari malformation Type I (CMI) is known to have an altered biomechanical environment for the brainstem and cerebellum; however, it is unclear whether these altered biomechanics play a role in the development of CMI symptoms. We hypothesized that CMI subjects have a higher cardiac-induced strain in specific neurological tracts pertaining to balance, and postural control. We measured displacement over the cardiac cycle using displacement encoding with stimulated echoes magnetic resonance imaging in the cerebellum, brainstem, and spinal cord in 37 CMI subjects and 25 controls. Based on these measurements, we computed strain, translation, and rotation in tracts related to balance. The global strain on all tracts was small (<1%) for CMI subject and controls. Strain was found to be nearly doubled in three tracts for CMI subjects compared to controls (p < 0.03). The maximum translation and rotation were ∼150 µm and ∼1 deg, respectively and 1.5-2 times greater in CMI compared to controls in four tracts (p < 0.005). There was no significant difference between strain, translation, and rotation on the analyzed tracts in CMI subjects with imbalance compared to those without imbalance. A moderate correlation was found between cerebellar tonsillar position and strain on three tracts. The lack of statistically significant difference between strain in CMI subjects with and without imbalance could imply that the magnitude of the observed cardiac-induced strain was too small to cause substantial damage to the tissue (<1%). Activities such as coughing, or Valsalva may produce a greater strain.

Pain and Depression Account for More Than One Half of the Neck Disability Variance Among Adult Women with Chiari I.

OBJECTIVE: We sought to quantify the neck-related disability in adult women with Chiari malformation type I and identify the significantly related variables. METHODS: A total of 70 variables were selected from the self-report history questionnaires (12 variables; n = 474), standardized scales (15 variables; n = 474), and morphometric data (43 variables; n = 293-474) of adult women with Chiari malformation type I. The variables were tested independently to identify those with a significant relationship to the Neck Disability Index (NDI; P < 0.00071) and those that might be associated with the NDI (P < 0.05). A forward selection regression model was constructed to identify the variables contributing unique variance to the NDI. In addition, a mediation analysis was performed to determine whether depression mediated the relationship between pain and disability. RESULTS: Overall, 79.5% of the patients had scored at a moderate level of disability or higher. Independent testing identified 16 significant variables, including symptom duration, tonsillar position, and measures of psychological distress. The short-form McGill pain questionnaire-2 (r = 0.69; P < 0.00001) and CES-D scale for depression (r = 0.56; P < 0.00001) exhibited the highest correlations with the NDI. The forward selection regression model produced an R2 of 0.6178. Pain and depression accounted for more than one half of the NDI variance. CONCLUSIONS: We found that high levels of disability are common among adult women with Chiari malformation type I, independent of surgical status. Pain and depression were the primary factors related to this disability. Depression mediated the relationship between pain intensity and disability at a modest level (5%). Patients who had experienced symptoms for >2 years before diagnosis had had, on average, 77% higher NDI scores, highlighting the importance of a timely diagnosis.

The importance of precise plane selection for female adult Chiari Type I malformation midsagittal morphometrics.

INTRODUCTION: Morphometric assessment of Chiari malformation type I (CMI) is typically performed on a midsagittal MRI. However, errors arising from an imprecise selection of the midsagittal plane are unknown. We define absolute parasagittal error as the absolute difference between morphometric measurements at the midsagittal and parasagittal planes. Our objective was to determine the absolute parasagittal error at various lateral distances for morphometric parameters commonly used in CMI research. METHODS: Sagittal T1-weighted MRI scans of 30 CMI adult female subjects were included. Image sets were evaluated to assess 14 CMI morphometric parameters in the midsagittal plane and four parasagittal planes located 1 and 2 mm lateral (left and right). Comparisons between measurements at the midsagittal and parasagittal planes were conducted to determine the mean individual absolute and mean group parasagittal errors for all 14 parameters. RESULTS: The mean individual absolute parasagittal error was > 1 unit (1 mm for lengths and 1 degree for angles) for 9/14 parameters within a lateral distance of 2 mm. No significant group parasagittal errors were seen in 14/14 parameters, including tonsillar position within a lateral distance of 2 mm. CONCLUSION: Our results show that the absolute errors for imprecise midsagittal plane selection may impact the clinical assessment of an individual patient. However, the impact on group measurements, such as in a research setting, will be minimal.

Influence of Pain on Cognitive Dysfunction and Emotion Dysregulation in Chiari Malformation Type I.

It has been well demonstrated that the cerebellum is associated with cognitive and affective processing as well as the traditionally conceptualized motor function. In the present chapter, we explore the behavioral and neurobiological implications of a common congenital cerebellar condition, Chiari malformation Type I, on cognitive and affective processing. We also emphasize the associations between Chiari-related chronic pain, cognitive dysfunction, and emotion dysregulation. Based on our review of the literature, we argue that chronic pain can account for a substantial amount of the cognitive dysfunction and emotion dysregulation in Chiari malformation Type I. Yet, there also exists aspects of Chiari-related cognitive dysfunction and emotion dysregulation that appear to be at least partially independent of chronic pain and more directly associated with abnormalities in cerebrospinal fluid flow dynamics and cerebro-cerebellar communication pathways.

Factors Associated With Patient-Reported Postsurgical Symptom Improvement in Adult Females with Chiari Malformation Type I: A Report from the Chiari1000 Dataset.

OBJECTIVE: The goal of this study was to assess if a broad array of factors is predictive of patient-reported surgical impact on symptoms. METHODS: Sixty-five presurgical factors were selected from the self-report history questionnaires (12 variables, N = 653), standardized scales (14 variables, N = 494-581), and morphometric measurements from magnetic resonance imaging (39 variables, N = 137) data of adult women in the Chiari1000 dataset. The factors were tested independently to identify those that were either significantly different in terms of, or significantly related to, patient-reported surgical impact on symptoms (P < 0.05). These results were then used to build a forward selection regression model. RESULTS: Overall, 74.4% of the patients reported either some level of improvement or complete resolution of symptoms. Independent testing identified 12 significant factors, including having a family member diagnosed with Chiari malformation type I (CMI), Ehlers-Danlos syndrome, migraines, duration of symptoms >2 years, multiple surgeries, symptom severity, depression, anxiety, stress, and loneliness. Depression showed the highest correlation (r = 0.36; P < 0.00001) with a negative outcome. The regression model produced an R2 = 0.346 and identified 5 factors with significant unique variance. CONCLUSIONS: The regression model accounted for more than a third of the surgical impact variance. Having a family member diagnosed with CMI contributed the largest unique variance to the model, suggesting that hereditary CMI may represent a unique subset of patients with poorer outcomes. Independent testing showed that psychological factors, such as depression and anxiety, were significant negative predictors, indicating that presurgical screening and treatment for these psychological conditions may improve outcomes.

A new hypothesis for the pathophysiology of symptomatic adult Chiari malformation Type I.

Chiari malformation Type I (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum. The pathophysiology of CMI is not well elucidated; however, the prevailing theory focuses on the underdevelopment of the posterior cranial fossa which results in tonsillar herniation. Symptoms are believed to be due to the herniation causing resistance to the natural flow of cerebrospinal fluid (CSF) and exerting a mass effect on nearby neural tissue. However, asymptomatic cases vastly outnumber symptomatic ones and it is not known why some people become symptomatic. Recently, it has been proposed that CMI symptoms are primarily due to instability of either the atlanto-axial (AA) or the atlanto-occipital (AO) joint and the cerebellar tonsils herniate to prevent mechanical pinching. However, only a small percentage of patients exhibit clinical instability and these theories do not account for asymptomatic herniations. We propose that the pathophysiology of adult CMI involves a combination of craniocervical abnormalities which leads to tonsillar herniation and reduced compliance of the cervical spinal canal. Specifically, abnormal AO and/or AA joint morphology leads to chronic cervical instability, often subclinical, in a large portion of CMI patients. This in turn causes overwork of the suboccipital muscles as they try to compensate for the instability. Over time, the repeated, involuntary activation of these muscles leads to mechanical overload of the myodural bridge complex, altering the mechanical properties of the dura it merges with. As a result, the dura becomes stiffer, reducing the overall compliance of the cervical region. This lower compliance, combined with CSF resistance at the same level, leads to intracranial pressure peaks during the cardiac cycle (pulse pressure) that are amplified during activities such as coughing, sneezing, and physical exertion. This increase in pulse pressure reduces the compliance of the cervical subarachnoid space which increases the CSF wave speed in the spinal canal, and further increases pulse pressure in a feedback loop. Finally, the abnormal pressure environment induces greater neural tissue motion and strain, causing microstructural damage to the cerebellum, brainstem, and cervical spinal cord, and leading to symptoms. This hypothesis explains how the combination of craniocervical bony abnormalities, anatomic CSF restriction, and reduced compliance leads to symptoms in adult CMI.

Adult Age Differences in Self-Reported Pain and Anterior CSF Space in Chiari Malformation.

Chiari malformation type I (CMI) is a neural disorder with sensory, cognitive, and motor defects, as well as headaches. Radiologically, the cerebellar tonsils extend below the foramen magnum. To date, the relationships among adult age, brain morphometry, surgical status, and symptom severity in CMI are unknown. The objective of this study was to better understand the relationships among these variables using causal modeling techniques. Adult CMI patients (80% female) who either had (n = 150) or had not (n = 151) undergone posterior fossa decompression surgery were assessed using morphometric measures derived from magnetic resonance images (MRI). MRI-based morphometry showed that the area of the CSF pocket anterior to the cervico-medullary junction (anterior CSF space) correlated with age at the time of MRI (r = - .21). Also, self-reported pain increased with age (r = .11) and decreased with anterior CSF space (r = - .18). Age differences in self-reported pain were mediated by anterior CSF space in the cervical spine area-and this effect was particularly salient for non-decompressed CMI patients. As CMI patients age, the anterior CSF space decreases, and this is associated with increased pain-especially for non-decompressed CMI patients. It is recommended that further consideration of age-related decreases in anterior CSF space in CMI patients be given in future research.

Are Two-Dimensional Morphometric Measures Reflective of Disease Severity in Adult Chiari I Malformation?

BACKGROUND: Two-dimensional (2D) morphometric measures have been previously used to diagnose Chiari I malformation (CMI) and distinguish patients from healthy subjects. There is, however, a paucity of literature regarding whether morphometric differences exist across the range of CMI disease severity. We evaluated whether 2D morphometrics demonstrate significant changes across standardized grades of CMI severity in adults. METHODS: This retrospective observational study comprised 76 patients with symptomatic CMI with or without syringomyelia. Patients matched for age, sex, and body mass index were selected from each of the 3 severity grades of the Chiari Severity Index (CSI). The study used 17 2D craniocervical and posterior fossa morphometric variables that were previously found to differentiate patients with CMI from healthy subjects. The measurements were performed on midsagittal T1-weighted magnetic resonance imaging sequences using 2 custom in-house software tools, MorphPro and CerePro, and compared across CSI grades. RESULTS: Analysis of variance showed that none of the 17 morphometric variables were significantly different across the 3 CSI grades (P > 0.003). Bayes factor 10 scores ranged from 0.11 to 0.82. Of variables, 9 had Bayes factor 10 scores between 0.10 and 0.30, while 8 had scores between 0.30 and 1. None of the Bayes factor 10 scores provided support for the alternative hypothesis that the morphometric measures differed across the CSI grades. CONCLUSIONS: Our study indicated that 2D morphometrics are not reflective of CMI disease severity as indicated by the CSI grading system. The findings of our study support the need for further investigation into whether non-2D morphometric variables can be used as markers of disease severity.

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

PURPOSE: Incidental cerebellar tonsillar ectopia (ICTE) that meets the radiographic criterion for Chiari malformation type I (CMI) is an increasingly common finding in the clinical setting, but its significance is unclear. The present study examined posterior cranial fossa (PCF) morphometrics and a broad range of health instruments of pediatric ICTE cases and matched controls extracted from the Adolescent Brain Cognitive Development (ABCD) dataset. METHODS: One-hundred-six subjects with ICTE and 106 matched controls without ICTE were identified from 11,411 anatomical MRI of healthy screened pediatric subjects from the ABCD project. Subjects were matched by sex, age, body mass index, race, and ethnicity. Twenty-two brain morphometrics and 22 health instruments were compared between the two groups to identify unrecognized CMI symptoms and assess the general health impact of ICTE. RESULTS: Twelve and 15 measures were significantly different between the ICTE and control groups for females and males, respectively. Notably, for females, the anterior CSF space was significantly smaller (p = 0.00005) for the ICTE group than controls. For males, the clivus bone length was significantly shorter (p = 0.0002) for the ICTE group compared to controls. No significant differences were found among the 22 health instruments between the two groups. CONCLUSION: This study demonstrated that pediatric ICTE subjects have similar PCF morphometrics to adult CMI. ICTE alone did not appear to cause any unrecognized CMI symptoms and had no impact on the subjects' current mental, physical, or behavioral health. Still, given their cranial and brain morphology, these cases may be at risk for adult-onset symptomatic CMI.

Functional connectivity abnormalities in Type I Chiari: associations with cognition and pain.

There is initial evidence of microstructural abnormalities in the fibre-tract pathways of the cerebellum and cerebrum of individuals diagnosed with Type I Chiari malformation. However, it is unclear whether abnormal white matter architecture and macro-level morphological deviations that have been observed in Chiari translate to differences in functional connectivity. Furthermore, common symptoms of Chiari include pain and cognitive deficits, but the relationship between these symptoms and functional connectivity has not been explored in this population. Eighteen Type I Chiari patients and 18 age-, sex- and education-matched controls underwent resting-state functional MRI to measure functional connectivity. Participants also completed a neuropsychological battery and completed self-report measures of chronic pain. Group differences in functional connectivity were identified. Subsequently, pathways of significant difference were re-analyzed after controlling for the effects of attention performance and self-reported chronic pain. Chiari patients exhibited functional hypoconnectivity between areas of the cerebellum and cerebrum. Controlling for attention eliminated all deficits with the exception of that from the posterior cerebellar pathway. Similarly, controlling for pain also eliminated deficits except for those from the posterior cerebellar pathway and vermis VII. Patterns of Chiari hyperconnectivity were also found between regions of the cerebellum and cerebrum in Chiari patients. Hyperconnectivity in all regions was eliminated after controlling for attention except between left lobule VIII and the left postcentral gyrus and between vermis IX and the precuneus. Similarly, hyperconnectivity was eliminated after controlling for pain except between the default mode network and globus pallidus, left lobule VIII and the left postcentral gyrus, and Vermis IX and the precuneus. Evidence of both hyper- and hypoconnectivity were identified in Chiari, which is posited to support the hypothesis that the effect of increased pain in Chiari draws on neural resources, requiring an upregulation in inhibitory control mechanisms and resulting in cognitive dysfunction. Areas of hypoconnectivity in Chiari patients also suggest disruption in functional pathways, and potential mechanisms are discussed.

Cerebellar and Brainstem Displacement Measured with DENSE MRI in Chiari Malformation Following Posterior Fossa Decompression Surgery.

Background Posterior fossa decompression (PFD) surgery is a treatment for Chiari malformation type I (CMI). The goals of surgery are to reduce cerebellar tonsillar crowding and restore posterior cerebral spinal fluid flow, but regional tissue biomechanics may also change. MRI-based displacement encoding with stimulated echoes (DENSE) can be used to assess neural tissue displacement. Purpose To assess neural tissue displacement by using DENSE MRI in participants with CMI before and after PFD surgery and examine associations between tissue displacement and symptoms. Materials and Methods In a prospective, HIPAA-compliant study of patients with CMI, midsagittal DENSE MRI was performed before and after PFD surgery between January 2017 and June 2020. Peak tissue displacement over the cardiac cycle was quantified in the cerebellum and brainstem, averaged over each structure, and compared before and after surgery. Paired t tests and nonparametric Wilcoxon signed-rank tests were used to identify surgical changes in displacement, and Spearman correlations were determined between tissue displacement and presurgery symptoms. Results Twenty-three participants were included (mean age ± standard deviation, 37 years ± 10; 19 women). Spatially averaged (mean) peak tissue displacement demonstrated reductions of 46% (79/171 µm) within the cerebellum and 22% (46/210 µm) within the brainstem after surgery (P < .001). Maximum peak displacement, calculated within a circular 30-mm2 area, decreased by 64% (274/427 µm) in the cerebellum and 33% (100/300 µm) in the brainstem (P < .001). No significant associations were identified between tissue displacement and CMI symptoms (r < .74 and P > .012 for all; Bonferroni-corrected P = .0002). Conclusion Neural tissue displacement was reduced after posterior fossa decompression surgery, indicating that surgical intervention changes brain tissue biomechanics. For participants with Chiari malformation type I, no relationship was identified between presurgery tissue displacement and presurgical symptoms. © RSNA, 2021 Online supplemental material is available for this article.

Impact of Surgical Status, Loneliness, and Disability on Interleukin 6, C-Reactive Protein, Cortisol, and Estrogen in Females with Symptomatic Type I Chiari Malformation.

Chiari malformation type I (CMI) provides an opportunity for examining possible moderators of allostatic load. CMI patients who had (n = 43) and had not (n = 19) undergone decompression surgery completed questionnaires regarding pain, disability, and loneliness, and provided serum samples for IL-6, CRP, estrogen, and free estradiol assays, and saliva samples to assess diurnal cortisol curves. ANOVAs examining surgical status (decompressed versus non-decompressed), loneliness (high vs. low), and disability (high vs. low) as independent variables and biomarker variables as dependent factors found that loneliness was associated with higher levels of cortisol, F(1, 37) = 4.91, p = .04, η2P = .11, and lower levels of estrogen, F(1, 36) = 7.29, p = .01, η2P = .17, but only in decompressed patients. Results highlight the possible impact of loneliness on biological stress responses and the need to intervene to reduce loneliness in patients with symptomatic CMI.

Association Between Resistance to Cerebrospinal Fluid Flow Near the Foramen Magnum and Cough-Associated Headache in Adult Chiari Malformation Type I.

Cough-associated headaches (CAHs) are thought to be distinctive for Chiari malformation type I (CMI) patients and have been shown to be related to the motion of cerebrospinal fluid (CSF) near the foramen magnum (FM). We used computational fluid dynamics (CFD) to compute patient-specific resistance to CSF motion in the spinal canal for CMI patients to determine its accuracy in predicting CAH. Fifty-one symptomatic CMI patients with cerebellar tonsillar position (CTP) ≥ 5 mm were included in this study. The patients were divided into two groups based on their symptoms (CAH and non-CAH) by review of the neurosurgical records. CFD was utilized to simulate CSF motion, and the integrated longitudinal impedance (ILI) was calculated for all patients. A receiver operating characteristic (ROC) curve was evaluated for its accuracy in predicting CAH. The ILI for CMI patients with CAH (776 dyn/cm5, 288-1444 dyn/cm5; median, interquartile range) was significantly larger compared to non-CAH (285 dyn/cm5, 187-450 dyn/cm5; p = 0.001). The ILI was more accurate in predicting CAH in CMI patients than the CTP when the comparison was made using the area under the ROC curve (AUC) (0.77 and 0.70, for ILI and CTP, respectively). ILI ≥ 750 dyn/cm5 had a sensitivity of 50% and a specificity of 95% in predicting CAH. ILI is a parameter that is used to assess CSF blockage in the spinal canal and can predict patients with and without CAH with greater accuracy than CTP.

Regional Brain Tissue Displacement and Strain is Elevated in Subjects with Chiari Malformation Type I Compared to Healthy Controls: A Study Using DENSE MRI.

While the degree of cerebellar tonsillar descent is considered the primary radiologic marker of Chiari malformation type I (CMI), biomechanical forces acting on the brain tissue in CMI subjects are less studied and poorly understood. In this study, regional brain tissue displacement and principal strains in 43 CMI subjects and 25 controls were quantified using a magnetic resonance imaging (MRI) methodology known as displacement encoding with stimulated echoes (DENSE). Measurements from MRI were obtained for seven different brain regions-the brainstem, cerebellum, cingulate gyrus, corpus callosum, frontal lobe, occipital lobe, and parietal lobe. Mean displacements in the cerebellum and brainstem were found to be 106 and 64% higher, respectively, for CMI subjects than controls (p < .001). Mean compression and extension strains in the cerebellum were 52 and 50% higher, respectively, in CMI subjects (p < .001). Brainstem mean extension strain was 41% higher in CMI subjects (p < .001), but no significant difference in compression strain was observed. The other brain structures revealed no significant differences between CMI and controls. These findings demonstrate that brain tissue displacement and strain in the cerebellum and brainstem might represent two new biomarkers to distinguish between CMI subjects and controls.