Advancing toward precision migraine treatment: Predicting responses to preventive medications with machine learning models based on patient and migraine features.

OBJECTIVE: To develop machine learning models using patient and migraine features that can predict treatment responses to commonly used migraine preventive medications. BACKGROUND: Currently, there is no accurate way to predict response to migraine preventive medications, and the standard trial-and-error approach is inefficient. METHODS: In this cohort study, we analyzed data from the Mayo Clinic Headache database prospectively collected from 2001 to December 2023. Adult patients with migraine completed questionnaires during their initial headache consultation to record detailed clinical features and then at each follow-up to track preventive medication changes and monthly headache days. We included patients treated with at least one of the following migraine preventive medications: topiramate, beta-blockers (propranolol, metoprolol, atenolol, nadolol, timolol), tricyclic antidepressants (amitriptyline, nortriptyline), verapamil, gabapentin, onabotulinumtoxinA, and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab, eptinezumab). We pre-trained a deep neural network, "TabNet," using 145 variables, then employed TabNet-embedded data to construct prediction models for each medication to predict binary outcomes (responder vs. non-responder). A treatment responder was defined as having at least a 30% reduction in monthly headache days from baseline. All model performances were evaluated, and metrics were reported in the held-out test set (train 85%, test 15%). SHapley Additive exPlanations (SHAP) were conducted to determine variable importance. RESULTS: Our final analysis included 4260 patients. The responder rate for each medication ranged from 28.7% to 34.9%, and the mean time to treatment outcome for each medication ranged from 151.3 to 209.5 days. The CGRP mAb prediction model achieved a high area under the receiver operating characteristics curve (AUC) of 0.825 (95% confidence interval [CI] 0.726, 0.920) and an accuracy of 0.80 (95% CI 0.70, 0.88). The AUCs of prediction models for beta-blockers, tricyclic antidepressants, topiramate, verapamil, gabapentin, and onabotulinumtoxinA were: 0.664 (95% CI 0.579, 0.745), 0.611 (95% CI 0.562, 0.682), 0.605 (95% CI 0.520, 0.688), 0.673 (95% CI 0.569, 0.724), 0.628 (0.533, 0.661), and 0.581 (95% CI 0.550, 0.632), respectively. Baseline monthly headache days, age, body mass index (BMI), duration of migraine attacks, responses to previous medication trials, cranial autonomic symptoms, family history of headache, and migraine attack triggers were among the most important variables across all models. A variable could have different contributions; for example, lower BMI predicts responsiveness to CGRP mAbs and beta-blockers, while higher BMI predicts responsiveness to onabotulinumtoxinA, topiramate, and gabapentin. CONCLUSION: We developed an accurate prediction model for CGRP mAbs treatment response, leveraging detailed migraine features gathered from a headache questionnaire before starting treatment. Employing the same methods, the model performances for other medications were less impressive, though similar to the machine learning models reported in the literature for other diseases. This may be due to CGRP mAbs being migraine-specific. Incorporating medical comorbidities, genomic, and imaging factors might enhance the model performance. We demonstrated that migraine characteristics are important in predicting treatment responses and identified the most crucial predictors for each of the seven types of preventive medications. Our results suggest that precision migraine treatment is feasible.

Orthostatic Headache After Suboccipital Craniectomy Without CSF Leak: Two Case Reports.

OBJECTIVE: To review the clinical and radiographic characteristics of orthostatic headache following suboccipital craniectomy without CSF leak after encountering 2 such patients. BACKGROUND: Orthostatic headache may occur without CSF leak, suggesting alternative mechanisms for postural head pain in some patients. METHODS: Patients who were referred for orthostatic headache and suspected CSF leak within 1 year after suboccipital craniectomy but who had negative post-operative head and spine MRI, normal radioisotope cisternography, and normal or elevated CSF opening pressure were identified and their medical records reviewed. RESULTS: Two patients satisfied all inclusion criteria. One underwent suboccipital craniectomy for treatment of Chiari malformation type I in adolescence; the same surgical approach was used to resect a posterior fossa meningioma in the second. Both patients had non-orthostatic headache before surgery and newly developed orthostatic headache later. Delay from surgery to orthostatic headache onset was variable (2-9 months). Headaches were predominantly occipital and pressure-like, worsened by upright posture, bending forward, and exertion. MRI consistently showed adequate decompression of the posterior fossa. Epidural blood patches were unhelpful in the one patient in whom they were performed. CONCLUSIONS: Orthostatic headaches may develop after suboccipital craniectomy in the absence of CSF leak. Possible mechanisms include (1) scarring of the dura in the posterior fossa that leads to compensatory increased distensibility of lumbar dura and (2) sensitization of mechanosensitive dural nociceptors from altered skull-dura apposition.

A unique case of penetrating neck and cervical spine trauma resulting in vertebral artery transection and internal carotid artery laceration.

OBJECTIVES: Describe the presentation and treatment of a patient who suffered a penetrating cervical trauma resulting in occlusion of the vertebral and internal carotid arteries. METHODS: The electronic medical record was used to collect information pertaining to the patient's clinical history. RESULTS: A 20-year-old male suffered a unique penetrating neck injury resulting in simultaneous injuries to the internal carotid and vertebral arteries as demonstrated by pre-operative angiography. Combined endovascular and open surgical approaches were utilized to successfully manage the vascular injuries prior to foreign body extraction. CONCLUSION: Complex penetrating cervical trauma is best managed with a multidisciplinary and multimodality approach. In appropriately selected patients, pre-operative angiography is a critical diagnostic modality that can prevent life-threatening hemorrhage following foreign body extraction.

Sense of Belonging Among Medical Students, Residents, and Fellows: Associations With Burnout, Recruitment Retention, and Learning Environment.

PURPOSE: This study examines sense of belonging (belongingness) in a large population of medical students, residents, and fellows and associations with learner burnout, organizational recruitment retention indicators, and potentially modifiable learning environment factors. METHOD: All medical students, residents, and fellows at Mayo Clinic sites were surveyed between October and November 2020 with items measuring sense of belonging in 3 contexts (school or program, organization, and surrounding community), burnout (2 Maslach Burnout Inventory items), recruitment retention indicators (likelihood of recommending the organization and accepting a job offer), potentially modifiable learning environment factors, and demographic factors (age, gender, race and ethnicity, LGBTQ+ identification, disability, and socioeconomic background). RESULTS: Of 2,257 learners surveyed, 1,261 (56%) responded. The number of learners reporting a somewhat or very strong sense of belonging was highest in the school or program (994 of 1,227 [81%]) followed by the organization (957 of 1,222 [78%]) and surrounding community (728 of 1,203 [61%]). In adjusted analyses, learners with very strong organization belongingness had lower odds of burnout (odds ratio [OR], 0.05; 95% CI, 0.02-0.12) and higher odds of being likely to recommend the organization (OR, 505.23; 95% CI, 121.54-2,100.18) and accept a job offer (OR, 38.68; 95% CI, 15.72-95.15; all P < .001). School or program and community belongingness were also strongly associated with these outcomes. In multivariable analyses, social support remained associated with higher odds of belongingness in school or program, organization, and surrounding community, favorable ratings of faculty relationships and leadership representation with higher odds of school or program and organization belongingness, and favorable ratings of diversity, equity, and inclusion learning climate with higher odds of community belongingness. CONCLUSIONS: Belongingness among medical students, residents, and fellows varies across contexts, strongly correlates with learner burnout and organizational recruitment retention indicators, and is associated with multiple potentially modifiable learning environment factors.

Long term outcomes of occipital nerve stimulation.

Background: Occipital nerve stimulation (ONS) has been investigated as a potential treatment for disabling headaches and has shown promise for disorders such as chronic migraine and cluster headache. Long term outcomes stratified by headache subtype have had limited exploration, and literature on outcomes of this neuromodulatory intervention spanning 2 or more years is scarce. Measures: We performed a narrative review on long term outcomes with ONS for treatment of headache disorders. We surveyed the available literature for studies that have outcomes for 24 months or greater to see if there is a habituation in response over time. Review of the literature revealed evidence in treatment of occipital neuralgia, chronic migraine, cluster headache, cervicogenic headache, short lasting unilateral neuralgiform headache attacks (SUNHA) and paroxysmal hemicrania. While the term "response" varied per individual study, a total of 17 studies showed outcomes in ONS with long term sustained responses (as defined per this review) in the majority of patients with specific headache types 177/311 (56%). Only 7 studies in total (3 cluster, 1 occipital neuralgia, 1 cervicogenic headache, 1 SUNHA, 1 paroxysmal hemicrania) provided both short-term and long-term responses up to 24 months to ONS. In cluster headache, the majority of patients (64%) were long term responders (as defined per this review) and only a minority of patients 12/62 (19%) had loss of efficacy (e.g., habituation). There was a high number 313/439 (71%) of adverse events per total number of patients in the studies including lead migration, requirements of revision surgery, allergy to surgical materials, infection and intolerable paresthesias. Conclusions: With the evidence available, the response to ONS was sustained in the majority of patients with cluster headache with low rates of loss of efficacy in this patient population. There was a high percent of adverse events per number of patients in long term follow-up and likely related to the off-label use of leads typically used for spinal cord stimulation. Further longitudinal assessments of outcomes in occipital nerve stimulation with devices labelled for use in peripheral nerve stimulation are needed to evaluate the extent of habituation to treatment in headache.

Clinical and Imaging Outcomes of Surgically Repaired Cerebrospinal Fluid-Venous Fistulas Identified by Lateral Decubitus Digital Subtraction Myelography.

OBJECTIVE: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP). METHODS: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes. RESULTS: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias. CONCLUSIONS: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects.

A community-based study of demographics, medical and psychiatric conditions, and gender dysphoria/incongruence treatment in transgender/gender diverse individuals.

BACKGROUND: Current understanding about health care in the gender diverse population is limited by the lack of community-based, longitudinal data, especially in the USA. We sought to characterize a community-based cohort of transgender individuals including demographics, gender identities, social characteristics, psychiatric and medical conditions, and medical therapy for gender dysphoria/incongruence. PATIENTS AND METHODS: We performed a retrospective chart review of gender diverse residents of Olmsted County, Minnesota, who sought gender-specific healthcare from January 1, 1974, through December 31, 2015, using an infrastructure that links medical records of Olmsted County residents from multiple institutions. RESULTS: The number of patients seeking gender-specific healthcare increased from 1 to 2 per 5-year interval during the 1970s-1990s to 41 from 2011 to 2015 (n = 82). Forty-nine (59.8%) were assigned male sex at birth (AMAB), 31 (37.8%) were assigned female (AFAB), and 2 (2.4%) were intersex. Gender identities evolved over time in 16.3% and 16.1% of patients AMAB and AFAB, respectively, and at most recent follow-up, 8.2% and 12.9% of patients AMAB and AFAB, respectively, were non-binary. Depression affected 78%, followed by anxiety (62.2%), personality disorder (22%), and post-traumatic stress disorder (14.6%). 58.5% experienced suicidal ideation, 22% attempted suicide, and 36.6% were victims of abuse. The most prevalent medical conditions and cardiovascular (CV) risk factors included obesity (42.7%), tobacco use (40.2%), fracture [34.1% (86.2% traumatic)], hypertension (25.6%), hyperlipidemia (25.6%), and hypertriglyceridemia (15.9%). 67.3% of patients AMAB used feminizing and 48.4% of patients AFAB used masculinizing hormone therapy. When compared to US CDC National Health Statistics, there was a significantly greater prevalence of depression and anxiety but no difference in the prevalence of obesity, hypertension, hypercholesterolemia, type 2 diabetes, or stroke. CONCLUSION: Transgender and gender diverse individuals represent a population who express various gender identities and are seeking gender-specific healthcare at increasing rates. Psychiatric illness is highly prevalent compared to the US population but there is no difference in the prevalence of CV risk factors including obesity, type 2 diabetes, hypertension, and dyslipidemia.