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.

Evaluation of viscoelastic coagulation monitoring parameters and fibrinogen concentrations in healthy dogs undergoing stifle arthroscopy and tibial plateau leveling osteotomy.

OBJECTIVE: Evaluation of viscoelastic parameters along with Hct percentages, platelet numbers, and fibrinogen concentrations in healthy dogs undergoing elective stifle arthroscopy and tibial plateau leveling osteotomy (TPLO). These results determine if dogs are in a normal, hypocoagulable, or hypercoagulable state at 4 different time points. ANIMALS: Prospective study of 37 client-owned dogs enrolled between February 2, 2022, and November 10, 2022. METHODS: All dogs received a standardized anesthetic protocol. Patients enrolled in the study underwent stifle arthroscopy using a 3-portal technique with a TPLO performed by board-certified surgeons. Viscoelastic testing, Hct percentage, fibrinogen concentration, and platelet numbers were measured preoperatively, immediately postoperatively, 24 hours postoperatively, and 14 days postoperatively. RESULTS: Stifle arthroscopy and TPLO surgery was not associated with significant effects on viscoelastic coagulation monitoring and fibrinogen concentrations in healthy dogs when comparing the time points. CLINICAL RELEVANCE: Humans have a high risk of thrombotic events when undergoing elective orthopedic surgery and are often placed on prophylactic antithrombotic medication prior to surgery. Viscoelastic coagulation monitoring in dogs undergoing similar orthopedic procedures has been evaluated in veterinary medicine, but the effects on platelets and fibrinogen concentrations from similar orthopedic procedures and uniform anesthesia protocols have not been documented. Cranial cruciate ligament insufficiency is the most common orthopedic injury in dogs. Treatment requires elective surgical correction for the best results and improved long-term prognosis. The findings of this study suggest that similar preoperative prophylactic antithrombotic intervention is not needed for canine patients.

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.

Adjusting for Congenital Heart Surgery Risk Using Administrative Data.

BACKGROUND: Congenital heart surgery (CHS) encompasses a heterogeneous population of patients and surgeries. Risk standardization models that adjust for patient and procedural characteristics can allow for collective study of these disparate patients and procedures. OBJECTIVES: We sought to develop a risk-adjustment model for CHS using the newly developed Risk Stratification for Congenital Heart Surgery for ICD-10 Administrative Data (RACHS-2) methodology. METHODS: Within the Kids' Inpatient Database 2019, we identified all CHSs that could be assigned a RACHS-2 score. Hierarchical logistic regression (clustered on hospital) was used to identify patient and procedural characteristics associated with in-hospital mortality. Model validation was performed using data from 24 State Inpatient Databases during 2017. RESULTS: Of 5,902,538 total weighted hospital discharges in the Kids' Inpatient Database 2019, 22,310 pediatric cardiac surgeries were identified and assigned a RACHS-2 score. In-hospital mortality occurred in 543 (2.4%) of cases. Using only RACHS-2, the mortality mode had a C-statistic of 0.81 that improved to 0.83 with the addition of age. A final multivariable model inclusive of RACHS-2, age, payer, and presence of a complex chronic condition outside of congenital heart disease further improved model discrimination to 0.87 (P < 0.001). Discrimination in the validation cohort was also very good with a C-statistic of 0.83. CONCLUSIONS: We created and validated a risk-adjustment model for CHS that accounts for patient and procedural characteristics associated with in-hospital mortality available in administrative data, including the newly developed RACHS-2. Our risk model will be critical for use in health services research and quality improvement initiatives.

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.

Questionable utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment in individuals with comorbid PTSD and SUD.

Posttraumatic stress disorder (PTSD) is frequently comorbid with substance use disorder (SUD) in individuals seeking treatment for substance use. Further, SUD and PTSD are individually associated with cognitive impairment (CI) and poor treatment outcomes. Despite the frequent use of the Montreal Cognitive Assessment (MoCA) as a screening tool for CI, the validity of the MoCA has not been established in individuals with comorbid SUD-PTSD. We assessed the criterion validity of the MoCA in 128 participants seeking inpatient medically-assisted detoxification using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as a reference for CI. The correlation between the RBANS and MoCA was weaker in those with SUD-PTSD (r = .32) relative to SUD alone (r = .56). Receiver operating characteristic (ROC) curves demonstrated that the MoCA had moderate-to-high ability to discriminate CI in individuals with SUD alone, with an area under the ROC curve of .82 (95% CI .69-.92) and optimal cutoff score of ≤23. However, in individuals with comorbid SUD-PTSD, the ROC analysis was not significant. Results suggest that PTSD, when comorbid with SUD, reduces the criterion-related validity of the MoCA. We recommend exercising caution when classifying CI in individuals with SUD-PTSD using the MoCA and suggest reducing the cutoff score to ≤23 in order to limit the rate of false-positive CI diagnoses in SUD-PTSD populations.

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.

StARD9 is a novel lysosomal kinesin required for membrane tubulation, cholesterol transport and Purkinje cell survival.

The pathological accumulation of cholesterol is a signature feature of Niemann-Pick type C (NPC) disease, in which excessive lipid levels induce Purkinje cell death in the cerebellum. NPC1 encodes a lysosomal cholesterol-binding protein, and mutations in NPC1 drive cholesterol accumulation in late endosomes and lysosomes (LE/Ls). However, the fundamental role of NPC proteins in LE/L cholesterol transport remains unclear. Here, we demonstrate that NPC1 mutations impair the projection of cholesterol-containing membrane tubules from the surface of LE/Ls. A proteomic survey of purified LE/Ls identified StARD9 as a novel lysosomal kinesin responsible for LE/L tubulation. StARD9 contains an N-terminal kinesin domain, a C-terminal StART domain, and a dileucine signal shared with other lysosome-associated membrane proteins. Depletion of StARD9 disrupts LE/L tubulation, paralyzes bidirectional LE/L motility and induces accumulation of cholesterol in LE/Ls. Finally, a novel StARD9 knock-out mouse recapitulates the progressive loss of Purkinje cells in the cerebellum. Together, these studies identify StARD9 as a microtubule motor protein responsible for LE/L tubulation and provide support for a novel model of LE/L cholesterol transport that becomes impaired in NPC disease.

The effect of adding an open distal anastomosis to proximal aneurysm repairs in bicuspid aortopathy.

OBJECTIVES: To determine the role of adding open distal anastomosis to proximal aortic aneurysm repairs in bicuspid aortic valve (BAV) patients. METHODS: Retrospective review was performed of 1132 patients at our Aortic Center between 2005 and 2019. Inclusion criteria were all patients diagnosed with a BAV who underwent proximal aortic aneurysm repair with open or clamped distal anastomosis. Exclusion criteria were patients without a BAV, age < 18 years, aortic arch diameter ≥ 4.5 cm, type A aortic dissection, previous ascending aortic replacement, ruptured aneurysm, and endocarditis. Propensity score matching in a 2:1 ratio (220 clamped: 121 open repairs) on 18 variables was performed. RESULTS: Median follow-up time was 45.6 months (range 7.2-143.4 months). In the matched groups, no significant differences were observed between the respective open and clamped distal anastomosis groups for Kaplan Meier 10-year survival (86.9% vs. 92.9%; p = 0.05) and landmark survival analysis after 1 year (90.6%; vs. 93.3%; p = 0.39). Overall incidence of aortic arch-related reintervention was low (n = 3 total events). In-hospital complications were not significantly different in the open with respect to the clamped repair group, including in-hospital mortality (2.5% vs. 0.5%; p = 0.13) and stroke (0% vs. 0.9%; p = 0.54). In multivariable analysis, open distal anastomosis repair was not associated with long-term mortality (Hazard Ratio (HR) 1.98; p = 0.06). CONCLUSION: We found no significant inter-group differences in survival, reintervention, or in-hospital complication rates, with low rates of mortality, and aortic arch-related reintervention, suggesting adding open distal anastomosis may not provide benefit in BAV patients undergoing proximal aortic aneurysm repairs.

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.

Threats to public figures and association with approach, as a proxy for violence: The importance of grievance.

The adoption of the term grievance-fuelled violence reflects the fact that similarities exist between those committing violent acts in the context of grievance in different settings, so potentially allowing the application of insights gained in the study of one group to be applied to others. Given the low base rate of violence against public figures, studies in the field of violence against those in the public eye have tended to use, as a proxy for violence, attempts by the individuals concerned to achieve unwarranted and unwanted proximity to the subject of their attention, given that approach is a necessary prerequisite for most forms of attack. In such studies, one factor that has frequently been considered is whether the making of threats is associated with a subsequent approach. The results have been varied, with no correlation found in some, a negative correlation in others, and a positive correlation in at least one. Such studies have been retrospective, using case files prepared for other purposes, and samples of cases have been selected according to their victims' sector of employment - for instance, politicians, celebrities, judiciary, and the corporate world. This study of a sample of 126 threat assessment cases, using a prospective methodology, looks at the associations between the making of threats and subsequent approach from a different angle - that of a standardised and validated classification of underlying motivation. It finds that particular types and forms of threat are significantly associated with subsequent approach in cases that are fuelled by grievance, but not in those with the motivation of seeking a relationship. Furthermore, when a sample with a mixture of motivational categories was examined in the manner of previous studies, such associations with threat were not apparent. These results refine the existing understanding of the significance of threats in public-facing cases. Future research projects in this area might usefully incorporate the consideration of underlying motivation, in particular grievance.

Anatomic structures of the canine middle ear visible during endoscopic examination through a ventral or lateral approach.

OBJECTIVE: To describe the anatomic structures of the canine middle ear visible during endoscopic examination through ventral and lateral surgical approaches. SAMPLE: 5 cadaveric canine heads representing 4 breeds. PROCEDURES: A descriptive study was performed. For each head, a lateral approach was performed on one side and a ventral approach was performed on the opposite side. Images were obtained with a 2.7-mm, 30° telescope. RESULTS: Captured images were reviewed, and anatomic structures visualized through the lateral and ventral approaches were identified. The optimal approach, telescope position, and light post orientation to identify each anatomic structure were subjectively determined. CLINICAL RELEVANCE: Middle ear evaluation with a telescope was technically straightforward and allowed identification of middle ear structures not typically visible with an open surgical approach. Findings may serve as an anatomic reference guide for future video-assisted surgical procedures of the middle ear. A better understanding of the location of anatomic structures in the middle ear may help to prevent unnecessary damage to fragile middle ear structures, such as nerves or blood vessels, during surgical procedures.

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.

Risk Stratification for Congenital Heart Surgery for ICD-10 Administrative Data (RACHS-2).

BACKGROUND: As the cardiac community strives to improve outcomes, accurate methods of risk stratification are imperative. Since adoption of International Classification of Disease-10th Revision (ICD-10) in 2015, there is no published method for congenital heart surgery risk stratification for administrative data. OBJECTIVES: This study sought to develop an empirically derived, publicly available Risk Stratification for Congenital Heart Surgery (RACHS-2) tool for ICD-10 administrative data. METHODS: The RACHS-2 stratification system was iteratively and empirically refined in a training dataset of Pediatric Health Information Systems claims to optimize sensitivity and specificity compared with corresponding locally held Society of Thoracic Surgeons-Congenital Heart Surgery (STS-CHS) clinical registry data. The tool was validated in a second administrative data source: New York State Medicaid claims. Logistic regression was used to compare the ability of RACHS-2 in administrative data to predict operative mortality vs STAT Mortality Categories in registry data. RESULTS: The RACHS-2 system captured 99.6% of total congenital heart surgery registry cases, with 1.0% false positives. RACHS-2 predicted operative mortality in both training and validation administrative datasets similarly to STAT Mortality Categories in registry data. C-statistics for models for operative mortality in training and validation administrative datasets-adjusted for RACHS-2-were 0.76 and 0.84 (95% CI: 0.72-0.80 and 0.80-0.89); C-statistics for models for operative mortality-adjusted for STAT Mortality Categories-in corresponding clinical registry data were 0.75 and 0.84 (95% CI: 0.71-0.79 and 0.79-0.89). CONCLUSIONS: RACHS-2 is a risk stratification system for pediatric cardiac surgery for ICD-10 administrative data, validated in 2 administrative-registry-linked datasets. Statistical code is publicly available upon request.

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.