A Novel Virtual-Based Comprehensive Clinical Approach to Headache Care.

One major innovation, a result of the coronavirus pandemic, has been the proliferation of telemedicine. Telehealth can help solve the access problems that plague headache medicine, allowing patients in areas with no headache expertise to consult and work with a headache specialist. This is a retrospective chart review of patients seen by Neura Health, a comprehensive app-based telehealth headache center. Patients are seen by a specialist and, in addition to any medical recommendations, are given care plans individualized to their condition and recommendations at the end of their clinical appointments. The primary outcome of this study is a decrease in monthly headache days after 90 days; secondary outcomes include disability as determined by MIDAS score, depression determined by PHQ-9, patients' utilization of emergency department or urgent care resources, as well as their global impression of improvement. The deidentified outcomes of consecutive patients of Neura Health were evaluated from March 2022-March 2023. Subjects were excluded if they did not complete all forms, or if they did not receive a clinical or coaching follow-up appointment within 90 days. A total of 186 consecutive patients at Neura Health were identified during the review period. The median decrease in monthly headache days was 55.0% after a 90 day period, headache severity was decreased by 16.7%, global impression of improvement increased by 60.9%, disability decreased by 38.7%, depression decreased by 12.5% and ER/urgent care visits were decreased by 66.1%. A comprehensive, telehealth-based virtual headache-care model significantly decreased migraine frequency, severity and disability, and is able to decrease ER or urgent care visits.

Non-invasive monitoring of cyclodialysis cleft using anterior segment optical coherence tomography and its role in informing clinical treatment decisions.

PURPOSE: Anterior segment optical coherence tomography (AS-OCT) is an emerging imaging modality with an expanding role in glaucoma diagnosis and management. We present a series of two cases of iatrogenic cyclodialysis cleft and their conservative management being directly informed by non-invasive AS-OCT monitoring. OBSERVATIONS: Retrospective case series. A 51 year-old male and a 29 year-old male each underwent gonioscopy-assisted transluminal trabeculotomy for uncontrolled glaucoma with a cyclodialysis cleft being diagnosed postoperatively and then monitored using serial AS-OCT images. In both cases, conservative medical management was initially employed. Worsening hypotony maculopathy and decreasing best corrected visual acuity were evident in both cases at times when gonioscopy yielded inadequate visualization to meaningfully inform treatment decisions. Escalation to more invasive therapies was therefore considered. AS-OCT imaging revealed consistent anatomical improvement at each follow-up and ultimately both clefts closed without treatment escalation. CONCLUSIONS AND IMPORTANCE: AS-OCT played a critical role in the diagnosis and directly informed the conservative management of both of these cases. This non-invasive imaging modality may allow for deferral of invasive treatment escalation in some cases of cyclodialysis cleft.

Heartrate variability biofeedback for migraine using a smartphone application and sensor: A randomized controlled trial.

INTRODUCTION: Although hand temperature and electromyograph biofeedback have evidence for migraine prevention, to date, no study has evaluated heartrate variability (HRV) biofeedback for migraine. METHODS: 2-arm randomized trial comparing an 8-week app-based HRV biofeedback (HeartMath) to waitlist control. Feasibility/acceptability outcomes included number and duration of sessions, satisfaction, barriers and adverse events. Primary clinical outcome was Migraine-Specific Quality of Life Questionnaire (MSQv2). RESULTS: There were 52 participants (26/arm). On average, participants randomized to the Hearthmath group completed 29 sessions (SD = 29, range: 2-86) with an average length of 6:43 min over 36 days (SD = 27, range: 0, 88) before discontinuing. 9/29 reported technology barriers. 43% said that they were likely to recommend Heartmath to others. Average MSQv2 decreases were not significant between the Heartmath and waitlist control (estimate = 0.3, 95% CI = -3.1 - 3.6). High users of Heartmath reported a reduction in MSQv2 at day 30 (-12.3 points, p = 0.010) while low users did not (p = 0.765). DISCUSSION: App-based HRV biofeedback was feasible and acceptable on a time-limited basis for people with migraine. Changes in the primary clinical outcome did not differ between biofeedback and control; however, high users of the app reported more benefit than low users.

Remote electrical neuromodulation for acute treatment of migraine in adolescents.

OBJECTIVES: Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well-tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism. The REN device (Nerivio® , Theranica Bio-Electronics Ltd., Israel) is a FDA-authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine. DESIGN AND METHODS: This was an open-label, single-arm, multicenter study in adolescents (ages 12-17 years) with migraine. Participants underwent a 4-week run-in phase. Eligible participants continued to an 8-week treatment phase with the device. Pain severity, associated symptoms, and functional disability were recorded at treatment initiation, and 2 and 24 hours post-treatment. The primary endpoints of this study were related to the safety and tolerability of REN. The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment and the proportion of participants who achieved pain freedom at 2 hours. The presented results reflect an interim analysis with subsequent stopping of the rest of the study. RESULTS: Sixty participants were enrolled for the study; of these, 14 failed to meet the run-in criteria and 1 was lost to follow-up. Forty-five participants performed at least one treatment, of which 39 participants completed a test treatment with REN. One device-related adverse event (2%) was reported in which a temporary feeling of pain in the arm was felt. Pain relief and pain-free at 2 hours were achieved by 71% (28/39) and 35% (14/39) participants, respectively. At 2 hours, 69% (23/33) participants experienced improvement in functional ability. CONCLUSIONS: REN may offer a safe and effective non-pharmacological alternative for acute treatment in adolescents.

Introducing the National Headache Fellowship Opportunities Website.

OBJECTIVE: To build a national Headache Medicine fellowship opportunities website that promotes a unified application timeline and a more transparent application process. BACKGROUND: In July 2019, the Consortium of Academic Headache Program Directors unanimously accepted the recommendations of the American Academy of Neurology Fellowship Application Timing Position Statement. To implement the unified application timeline, the American Headache Society agreed to host a fellowship opportunities website with information on the application process and resources for each fellowship program. METHODS: We designed a main landing page that features the unified timeline for applications and offers. The page also features icons for all participating US fellowship programs (identified using the United Council for Neurologic Subspecialties certification database). The icons serve as links to each fellowship program's individual webpage. We sent an electronic form to each fellowship program director, asking them to submit program information to be included on each fellowship program's individual webpage. Key contents on each program webpage include an image of the program, brief program description, names of applicants who have filled positions, and open positions. Each institution webpage also includes an electronic form that allows applicants to directly send their name, contact, and a brief message to the program director. RESULTS: We launched the website on May 15, 2020. As of June 19, 2020, the website featured 24 participating headache fellowship programs, including 5 pediatric programs and 19 adult training programs, from all regions of the US. CONCLUSION: The website serves as a central resource for Headache Medicine fellowship applicants and promotes a unified application timeline and a more transparent application process.

The state of the headache fellowship application process and attitudes toward the match.

OBJECTIVE: To examine the current headache medicine fellowship application process and to propose recommendations for a more unified, systematic, and transparent process. METHODS: We identified 42 headache fellowship programs using the United Council for Neurologic Subspecialties certification database. After an initial contact via e-mail, we conducted individual telephone interviews with program directors. Qualitative data coding allowed identification of emerging themes. Quantitative data were summarized with descriptive statistics. RESULTS: Forty (95%) program directors (34 adult, 6 pediatric) responded. Emerging themes included the following. (1) There are benefits and disadvantages to having a match. (2) If the match were reinstated, programs would participate only if all programs participated. (3) There should be consequences for programs that do not participate. If the match were reinstated, 37.5% of program directors responded that their program would participate without conditions; 37.5% would participate only if every program were required to participate. Fifteen percent would not participate, and 10% were not sure if they would participate. Forty percent supported sanctions against programs that did not participate in the match. CONCLUSION: The fellowship match potentially makes the process more systematic for both programs and applicants; however, it does not currently appear to be a feasible option for the field of headache medicine. Until the number of applicants exceeds the number of programs, we recommend instituting a universal timeline for applications and offers.

Smartphone-based migraine behavioral therapy: a single-arm study with assessment of mental health predictors.

Progressive muscle relaxation (PMR) is an under-utilized Level A evidence-based treatment for migraine prevention. We studied the feasibility and acceptability of smartphone application (app)-based PMR for migraine in a neurology setting, explored whether app-based PMR might reduce headache (HA) days, and examined potential predictors of app and/or PMR use. In this single-arm pilot study, adults with ICHD3 migraine, 4+ HA days/month, a smartphone, and no prior behavioral migraine therapy in the past year were asked to complete a daily HA diary and do PMR for 20 min/day for 90 days. Outcomes were: adherence to PMR (no. and duration of audio plays) and frequency of diary use. Predictors in the models were baseline demographics, HA-specific variables, baseline PROMIS (patient-reported outcomes measurement information system) depression and anxiety scores, presence of overlapping pain conditions studied and app satisfaction scores at time of enrollment. Fifty-one patients enrolled (94% female). Mean age was 39 ± 13 years. The majority (63%) had severe migraine disability at baseline (MIDAS). PMR was played 22 ± 21 days on average. Mean/session duration was 11 ± 7 min. About half (47%) of uses were 1+ time/week and 35% of uses were 2+ times/week. There was a decline in use/week. On average, high users (PMR 2+ days/week in the first month) had 4 fewer days of reported HAs in month 2 vs. month 1, whereas low PMR users (PMR < 2 days/week in the first month) had only 2 fewer HA days in month 2. PROMIS depression score was negatively associated with the log odds of using the diary at least once (vs. no activity) in a week (OR = 0.70, 95% CI = [0.55, 0.85]) and of doing the PMR at least once in a week (OR = 0.77, 95% CI = [0.68, 0.91]). PROMIS anxiety was positively associated with using the diary at least once every week (OR = 1.33, 95% CI = [1.09, 1.73]) and with doing the PMR at least once every week (OR = 1.14 [95% CI = [1.02, 1.31]). In conclusion, about half of participants used smartphone-based PMR intervention based upon a brief, initial introduction to the app. App use was associated with reduction in HA days. Higher depression scores were negatively associated with diary and PMR use, whereas higher anxiety scores were positively associated.

Diagnosis and Treatment of Primary Headache Disorders in Older Adults.

OBJECTIVES: To provide a unique perspective on geriatric headache and a number of novel treatment options that are not well known outside of the headache literature. DESIGN: Review of the most current and relevant headache literature for practitioners specializing in geriatric care. RESULTS: Evaluation and management of headache disorders in older adults requires an understanding of the underlying pathophysiology and how it relates to age-related physiological changes. To treat headache disorders in general, the appropriate diagnosis must first be established, and treatment of headaches in elderly adults poses unique challenges, including potential polypharmacy, medical comorbidities, and physiological changes associated with aging. CONCLUSION: The purpose of this review is to provide a guide to and perspective on the challenges inherent in treating headaches in older adults. J Am Geriatr Soc 66:2408-2416, 2018.

Factors Related to Migraine Patients' Decisions to Initiate Behavioral Migraine Treatment Following a Headache Specialist's Recommendation: A Prospective Observational Study.

Objective: To evaluate the frequency with which migraine patients initiated behavioral migraine treatment following a headache specialist recommendation and the predictors for initiating behavioral migraine treatment. Methods: We conducted a prospective cohort study of consecutive patients diagnosed with migraine to examine whether the patients initiated behavioral migraine treatment following a provider recommendation. The primary outcome was scheduling the initial visit for behavioral migraine treatment. Patients who initiated behavioral migraine treatment were compared with those who did not (demographics, migraine characteristics, and locus of control) with analysis of variance and chi-square tests. Results: Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment. Fifty-three (76.8%) patients referred for behavioral treatment were reached by phone. The mean duration from time of referral to follow-up was 76 (median 76, SD = 45) days. Thirty (56.6%) patients initiated behavioral migraine treatment. There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, health care utilization visits, Migraine Disability Assessment Screen, and locus of control (P > 0.05). Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not. Time constraints were the most common barrier cited for not initiating behavioral migraine treatment. Conclusions: Less than one-third of eligible patients were referred for behavioral treatment, and only about half initiated behavioral migraine treatment. Future research should further assess patients' decisions regarding behavioral treatment initiation and methods for behavioral treatment delivery to overcome barriers to initiating behavioral migraine treatment.

The Use and Method of Action of Intravenous Lidocaine and Its Metabolite in Headache Disorders.

BACKGROUND: Lidocaine, an amide anesthetic, has been used in the treatment of a wide variety of pain disorders for over 75 years. In addition to pain control, lidocaine is an anti-arrhythmic agent and has anti-inflammatory properties. Lidocaine's unique properties, including nonlinear pharmacokinetics, have limited its modern-day use. OBJECTIVE: The purpose of this review is to offer a better understanding of the properties of this unique treatment, which we hope will allow more practitioners to offer this to their patients. METHODS: An analysis of the history, pharmacokinetics, and relevant uses of lidocaine in headache medicine based on a synthesis of the medical literature and clinical experience. RESULTS: Lidocaine is an amide anesthetic that inhibits voltage gated sodium channels, and lidocaine metabolism occurs exclusively in the liver. One lidocaine metabolite has its own unique properties and may be an active form of the drug. CONCLUSION: Open label and retrospective studies have investigated the use of lidocaine in many headache disorders, primarily via injection or infusion. Further research into the active metabolite of lidocaine may allow for its use as a novel nonopiate treatment of chronic pain.

Visual and Refractive Outcomes in Manual versus Femtosecond Laser-Assisted Cataract Surgery: A Single-Center Retrospective Cohort Analysis of 1838 Eyes.

PURPOSE: Femtosecond laser-assisted cataract surgery (FLACS) has emerged as an alternative to manual cataract surgery (MCS) for corneal incision and capsulorhexis creation, as well as nuclear fragmentation. This study compares postoperative refractive and visual outcomes in eyes receiving MCS or FLACS. DESIGN: Single-center, comparative, retrospective cohort analysis. PARTICIPANTS: Consecutive eyes receiving FLACS and MCS from July 1, 2012, to July 31, 2015, at a single tertiary care center. METHODS: Demographic data, ocular history, preoperative measurements and biometry, and postoperative surgical results were retrospectively obtained and statistically analyzed using a generalized linear mixed model adjusting for differences in baseline characteristics and within-patient correlation. A 2-tailed P value <0.05 was considered statistically significant throughout the study. MAIN OUTCOME MEASURES: Percentage of eyes achieving absolute error (AE) ≤0.5 diopters (D). Secondary outcomes included percentage of eyes with AE ≤0.25 D and ≤1.0 D, and percentage of distance-targeted eyes achieving uncorrected distance visual acuity (UDVA) of 20/20 or better, 20/25 or better, and 20/30 or better. RESULTS: A total of 883 eyes received MCS and 955 received FLACS among 1089 patients. Some 82.6% of FLACS eyes and 78.8% of MCS eyes had ≤0.5 D of AE at 3 weeks, representing an adjusted odds ratio (OR) of 1.28 (95% confidence interval [CI], 0.98-1.66) of FLACS relative to MCS being within target. Some 97.1% of FLACS and 97.2% of MCS eyes had ≤1.0 D of AE (OR, 0.96; 95% CI, 0.57-1.60) and 49.3% of FLACS and 46.3% of MCS eyes, ≤0.25 D of AE (OR, 1.13; 95% CI, 0.91-1.39). Factors predictive of a favorable refractive outcome included axial length between 22 and 24.8 mm, receiving a toric intraocular lens, less preoperative cylinder, and greater preoperative average keratometry. There was no significant difference in the percentage of patients targeted for distance who achieved UDVA of 20/20 or better (P = 0.30), 20/25 or better (P = 0.06), or 20/30 or better (P = 0.66) vision. CONCLUSIONS: Postoperatively, there was no statistically significant difference found between eyes undergoing FLACS and eyes undergoing MCS with respect to refractive and visual outcomes.

Inadvertent Cyclodialysis Cleft and Hypotony Following Ab-Interno Trabeculotomy Using the Trabectome Device Requiring Surgical Repair.

PURPOSE: To report the first case of inadvertent cyclodialysis cleft and hypotony requiring surgical repair following ab-interno trabeculotomy (AIT) using the Trabectome device, and the postoperative clinical results following direct suture cyclopexy. METHODS: A 55-year-old man with hypotonous maculopathy secondary to cyclodialysis cleft inadvertently created 3 years earlier during AIT using the Trabectome device was referred for repair. Direct suture cyclopexy was performed and topical homatropine and dexamethasone drops were prescribed postoperatively. RESULTS: Gonioscopic examination revealed complete cleft closure on postoperative day 1 confirmed by anterior segment optical coherence tomography. At 11 weeks postoperatively, visual acuity had improved from 20/400 to 20/40, with resolution of preoperative macular folds on fundoscopic examination. At 9 months postoperatively, visual acuity had further improved to 20/20 with intraocular pressure stable at 9 mm Hg maintained on travoprost and brimonidine. CONCLUSIONS: Inadvertent cyclodialysis cleft from a malpositioned AIT and resultant hypotony is rare and in this case was successfully treated by direct suture cyclopexy.

Prospective Comparative Analysis of 4 Different Intraocular Pressure Measurement Techniques and Their Effects on Pressure Readings.

PURPOSE: To compare intraocular pressure (IOP) measurement using the Goldmann applanation tonometry (GAT) without fluorescein, with fluorescein strips, with fluorescein droplets, and IOP measurement with Tono-Pen Avia (TPA). PATIENTS AND METHODS: This was a prospective comparative clinical analysis. It was performed in clinical practice. The study population consisted of 40 volunteer patients, 1 eye per patient. All patients who were 18 years and older having routine ophthalmological examination were eligible to participate. Active corneal abrasions and/or ulcers, previous glaucoma surgery, or prostheses interfering with GAT measurement were excluded. GAT IOP was measured first without fluorescein, then with fluorescein strip, then with fluorescein droplet, and finally with the TPA device. The main outcome measure was central corneal IOP. RESULTS: Mean±SD IOP measurements for GAT without fluorescein, with fluorescein strip, with fluorescein droplet, and for TPA groups were 12.65±3.01, 14.70±2.82, 15.78±2.64, and 16.33±3.08 mm Hg, respectively. Repeated-measures analysis of variance corrected with the Greenhouse-Geisser estimate ([Latin Small Letter Open E]=0.732) showed that measuring technique had a significant effect on IOP measurements (F2.20,85.59=34.66, P<0.001). The pairwise post hoc testing showed statistically significant mean differences (P≤0.001) between all techniques except when GAT with fluorescein droplet was compared with TPA (P=0.222). The Bland-Altman analyses showed 95% limits of agreement maximum potential discrepancies in measurement ranging from 5.89 mm Hg in the GAT with fluorescein strip versus droplet compared with 11.83 mm Hg in the GAT with fluorescein strip versus TPA comparison. CONCLUSIONS: IOP measurement technique significantly impacted the values obtained. The ophthalmologist should ensure consistent measurement technique to minimize variability when following patients.

Distal coronary embolization following acute myocardial infarction increases early infarct size and late left ventricular wall thinning in a porcine model.

BACKGROUND: Distal coronary embolization (DCE) of thrombotic material occurs frequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size and myocardial function remains unsettled. The aims of this study were to evaluate the effects of DCE sufficient to cause no-reflow on infarct size, cardiac function and ventricular remodeling in a porcine acute myocardial infarction model. METHODS AND RESULTS: Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion and injection of either microthrombi (prepared from autologous porcine blood) sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size (CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences in infarct size, ventricular volume or ejection fraction between the two groups, although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning (percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03) were significantly increased in the DCE group. CONCLUSIONS: DCE increased early infarct size, but without affecting later infarct size, cardiac function or ventricular volumes. The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.

Electron microscopic evaluation of a gold glaucoma micro shunt after explantation.

UNLABELLED: We present a case of an explanted gold glaucoma micro shunt (GMS Plus) and the subsequent light and electron microscopic analyses. The shunt was implanted in a patient with medically refractive glaucoma. The intraocular pressure (IOP) was stable at 12 mm Hg 6 months postoperatively but spiked to 26 mm Hg 6 months later; membranous growth was visible on the implant gonioscopically. A second gold micro shunt was placed 2 years after the first. The IOP was 7 mm Hg 1 week postoperatively but increased to 23 mm Hg 3 weeks later; similar membranous growth was visible on this implant. One of the shunts was explanted, and light and scanning electron microscopic analyses revealed encapsulation around the shunt exterior and connective tissue invasion of the microstructure. This represents the first electron microscopic analysis of an explanted gold glaucoma micro shunt and the first unequivocal images of the fibrotic pseudo-capsule traversing its microchannels and fenestrations. FINANCIAL DISCLOSURE: Dr. Ahmed is a consultant to and has received research grants from Solx, Inc. No other author has a financial or proprietary interest in any material or method mentioned.

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

OBJECTIVE: Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. METHODS AND RESULTS: Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. CONCLUSIONS: These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals.

Unexpected calcification after direct intravascular injection of autologous bone marrow-derived cells in a chronic total occlusion model.

AIMS: Patients with symptomatic chronic total occlusions (CTO) remain a therapeutic challenge. Enhancement of intraluminal neovascularisation by pro-angiogenic therapies has been proposed as a new strategy to improve percutaneous revascularisation. The aim of this study was to investigate the effects of intraluminal injection of bone marrow-derived cells (BMC) into experimental CTO. METHODS AND RESULTS: CTO were created in the femoral arteries of 43 New Zealand White rabbits using the thrombin injection model. At 12 weeks following CTO creation, 33 rabbits were injected with either cultured BMC (n=19) or control DMEM alone (n=14) directly into the CTO. Ten rabbits were used for cell tracking (seven BMC and three control). BMC labelled with fluorescent Qdot® nanocrystals were identified in the CTO up to one week after injection. Animals were sacrificed at three to five weeks post-treatment and arterial samples were excised for micro-CT imaging and histologic morphometric analysis. There was a significant but modest increase in neovascularisation in BMC-treated arteries compared to controls (7.47±4.75% vs. 4.35±2.97%, p<0.05). However, unexpected intravascular calcification was only detected within the CTO in BMC cell treated arteries. Western blot for conditioned medium from BMC showed up-regulation of osteogenic proteins (BMP-2 and -7). CONCLUSIONS: Although direct delivery of BMC into CTO increases neovascularisation, undesirable vascular calcification will limit this therapeutic approach.