Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.

BACKGROUND: Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology. OBJECTIVE: The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study. METHODS: The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18 years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41-61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39-57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (n = 229) and dual-therapy groups. RESULTS: The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30-30) to 15 (12-30) [p < 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12-30) to 8 (3-22) [p < 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25-30) to 15 (8-25) from onabot monotherapy and decreased from 25 (15-30) to 12 (4-25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (p < 0.0001). CONCLUSION: Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action.

Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk.

OBJECTIVE: To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. BACKGROUND: CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. METHODS: We conducted a case-control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18-55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 µg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n = 635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. RESULTS: Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p = 0.011). Stroke risk was higher with ≥30-µg EE doses compared to those using a <30-µg dose (OR, 1.52; CI 1.02, 2.26; p = 0.040). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p = 0.003). Compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32, 4.2; p = 0.004). CONCLUSIONS: Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 µg EE are preferred. Shared decision-making should include discussions about ischemic stroke risks in patients with migraine, even those without aura.

Single-centre study surveying neurology trainees' and faculty's perceptions of the impact of the COVID-19 pandemic on residents' medical education.

OBJECTIVE: To assess perceptions of our neurology residents and faculty regarding training experience and medical education during the early COVID-19 pandemic. METHODS: We distributed two online, voluntary and anonymous surveys to trainees and teaching faculty of our Neurology Department at Henry Ford Hospital. Surveys inquired about trainees' stress, well-being, clinical experience and satisfaction with medical education and available support resources during the first wave of the COVID-19 pandemic in Michigan (mid-March to June 2020). RESULTS: A total of 17/31 trainees and 25/42 faculty responded to the surveys. Eight (47%) trainees reported high stress levels. Nine (57%) were redeployed to cover COVID-19 units. Compared with non-redeployed trainees, redeployed residents reported augmented medical knowledge (89% vs 38%, p=0.05). There was no difference in the two groups regarding overall satisfaction with residency experience, stress levels and didactics attendance. Twenty-one (84%) faculty felt that the redeployment interfered with trainees education but was appropriate, while 10 (59%) trainees described a positive experience overall. Both trainees and faculty believed the pandemic positively impacted trainees' experience by increasing maturity level, teamwork, empathy, and medical knowledge, while both agreed that increased stress and anxiety levels were negative outcomes of the pandemic. Twelve (70%) trainees and 13 (52%) faculty were interested in pursuing more virtual didactics in the future. CONCLUSION: Our findings provide an objective assessment of residents' experience during the COVID-19 pandemic and can guide teaching programmes in their medical education response in the face of future global crises.

Paradoxical embolic strokes in a liver transplant recipient with atrial septal defect undergoing therapeutic plasma exchange.

Therapeutic plasma exchange (TPE) is a technique used to separate blood components into layers based on their density difference, thus removing plasma and exchanging it with replacement fluids. A variety of adverse reactions has been described during TPE. Thrombotic events, especially strokes, are extremely rare complications of TPE. Our patient was a 55-year-old female with history of decompensated nonalcoholic steatohepatitis (NASH) liver cirrhosis. She underwent an orthotopic liver transplant (OLT) that was complicated with asystole during reperfusion. Cardiac workup revealed a new atrial septal defect (ASD) with left to right flow. Within the first 5 days after surgery, she developed refractory and persistent hyperbilirubinemia, with total bilirubin levels as high as 42 mg/dL. Our plasmapheresis service was consulted to initiate TPE. Towards the end of the first and only session of TPE, the patient developed hypoxia and left-sided hemiplegia. Stroke response was initiated, and the patient was intubated. MRI done 24 hours after the incident showed multiple acute small embolic infarcts scattered within the bilateral cerebral and cerebellar hemispheres. Bilateral lower and upper extremities venous duplex studies were positive for acute left internal jugular (IJ) vein thrombosis. Patient was treated with anticoagulation and the IJ catheter was removed. Patient also had closure of her ASD. On last follow up, she was doing well with complete reversal of neurologic deficits and stable liver function. Our patient had an uncommon complication of TPE. Her thrombosis manifested with multiple embolic strokes that would not have happened without an ASD with left to right flow.

Use of positive airway pressure in mild cognitive impairment to delay progression to dementia.

STUDY OBJECTIVES: The aim was to assess the relationship between continuous positive airway pressure (CPAP) therapy and cognitive function in patients with mild cognitive impairment (MCI) and obstructive sleep apnea (OSA). METHODS: This was a retrospective chart review of patients with MCI and OSA. CPAP therapy compliance was defined as average use of CPAP therapy for at least 4 hours per night. Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards regression were done to compare the compliance groups in terms of progression to dementia, defined as a Clinical Dementia Rating of 1 or greater. Linear mixed models were used to assess the relationships between CPAP therapy compliance and neurological cognitive function outcomes over time. RESULTS: Ninety-six patients were included with mean age at MCI diagnosis of 70.4 years, mean apnea-hypopnea index of 25.9 events/h, and mean duration of neurology follow-up of 2.8 years. Forty-two were CPAP compliant, 30 were noncompliant, and 24 had no CPAP use. No overall difference between the groups was detected for progression to dementia (P = .928, log-rank test). Patients with amnestic MCI had better CPAP use (P = .016) and shorter progression time to dementia (P = .042), but this difference was not significant after adjusting for age, education, and race (P = .32). CONCLUSIONS: CPAP use in patients with MCI and OSA was not associated with delay in progression to dementia or cognitive decline.

Brain metastasis in bone and soft tissue cancers: a review of incidence, interventions, and outcomes.

Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing's sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20-30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma), some at 24-36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma), and a few after 36 months (chondrosarcoma and liposarcoma). Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing's sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas). Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.