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.

Impacts of Climate Change and Air Pollution on Neurologic Health, Disease, and Practice: A Scoping Review.

BACKGROUND AND OBJECTIVES: Although the international community collectively seeks to reduce global temperature rise to less than 1.5°C before 2100, irreversible environmental changes have already occurred, and as the planet warms, these changes will continue to occur. As we witness the effects of a warming planet on human health, it is imperative that neurologists anticipate how the epidemiology and incidence of neurologic disease may change. In this review, we organized our analysis around 3 key themes related to climate change and neurologic health: extreme weather events and temperature fluctuations, emerging neuroinfectious diseases, and pollutant impacts. Across each of these themes, we appraised and reviewed recent literature relevant to neurologic disease and practice. METHODS: Studies were identified using search terms relating to climate change, pollutants, and neurologic disease in PubMed, OVID MEDLINE, EMBASE, PsycInfo, and gray literature. Studies published between 1990 and 2022 were included if they pertained to human incidence or prevalence of disease, were in English, and were relevant to neurologic disease. RESULTS: We identified a total of 364 articles, grouped into the 3 key themes of our study: extreme weather events and temperature fluctuations (38 studies), emerging neuroinfectious diseases (37 studies), and pollutant impacts (289 studies). The included studies highlighted the relationships between neurologic symptom exacerbation and temperature variability, tick-borne infections and warming climates, and airborne pollutants and cerebrovascular disease incidence and severity. DISCUSSION: Temperature extremes and variability both associated with stroke incidence and severity, migraine headaches, hospitalization in patients with dementia, and multiple sclerosis exacerbations. Exposure to airborne pollutants, especially PM2.5 and nitrates, associated with stroke incidence and severity, headaches, dementia risk, Parkinson disease, and MS exacerbation. Climate change has demonstrably expanded favorable conditions for zoonotic diseases beyond traditional borders and poses the risk of disease in new, susceptible populations. Articles were biased toward resource-rich regions, suggesting a discordance between where research occurs and where changes are most acute. As such, 3 key priorities emerged for further study: neuroinfectious disease risk mitigation, understanding the pathophysiology of airborne pollutants on the nervous system, and methods to improve delivery of neurologic care in the face of climate-related disruptions.

The Efficacy and Use of a Pocket Card Algorithm in Status Epilepticus Treatment.

OBJECTIVE: To determine whether a pocket card treatment algorithm improves the early treatment of status epilepticus and to assess its utilization and retention in clinical practice. METHODS: Multidisciplinary care teams participated in video-recorded status epilepticus simulation sessions from 2015 to 2019. In this longitudinal cohort study, we examined the sessions recorded before and after introducing an internally developed, guideline-derived pocket card to determine differences in the adequacy or timeliness of rescue benzodiazepine. Simulation participants were queried 9 months later for submission of a differentiating identification number on each card to assess ongoing availability and utilization. RESULTS: Forty-four teams were included (22 before and 22 after the introduction of the pocket card). The time to rescue therapy was shorter for teams with the pocket card available (84 seconds [64-132]) compared with teams before introduction (144 seconds [100-162]) (U = 94; median difference = -46.9, 95% confidence interval [CI]: -75.9 to -21.9). The adequate dosing did not differ with card availability (odds ratio 1.48, 95% CI: 0.43-5.1). At the 9-month follow-up, 32 participants (65%) completed the survey, with 26 (81%) self-reporting having the pocket card available and 11 (34%) confirming ready access with the identification number. All identification numbers submitted corresponded to the hard copy laminated pocket card, and none to the electronic version. CONCLUSIONS: A pocket card is a feasible, effective, and worthwhile educational tool to improve the implementation of updated guidelines for the treatment of status epilepticus.

Myelin oligodendrocyte glycoprotein (MOG) antibodies in a patient with glioblastoma: Red flags for false positivity.

We present a patient with positive medium titer MOG-IgG and progressive neurological decline whose clinical and radiological phenotype were not consistent with a MOG-IgG associated disorder and ultimately received a diagnosis of glioblastoma after brain biopsy and died 4 weeks later. This represents an important topic with a high frequency of MOG-IgG testing in clinical practice. Due to this there are increasing reports of MOG-IgG positivity in atypical clinical phenotypes, raising the possibility of false positives, which can have important implications. It is important to highlight that judicious clinical evaluation is needed when interpreting MOG-IgG results in atypical settings.

Acute ischemic stroke and COVID-19.

Ischemic stroke may be a presenting feature of COVID-19. Its etiology remains unclear, but severe COVID-19 disease might increase the risk of large-artery strokes. More evidence is needed to substantiate the current reports and provide insights for optimal management.

Acute paraparesis and sensory loss following intravenous corticosteroid administration in a case of longitudinally extensive transverse myelitis caused by spinal dural arteriovenous fistula: case report and review of literature.

INTRODUCTION: The underlying causes of longitudinally extensive transverse myelitis (LETM) are broad and include inflammatory processes, compression and spinal dural arteriovenous fistula (SDAVF). Presenting symptoms of SDAVF are nonspecific and often go misdiagnosed. Acute clinical deterioration from SDAVF has been described following exertion or valsalva. However, deterioration has been recently recognized following steroid administration and may contribute to increased morbidity. CASE PRESENTATION: We describe a 63-year-old woman with a 2-year history of intermittent lower extremity numbness and back pain, lumbar stenosis, who presented with subacute worsening of symptoms following a course of oral steroids for an upper respiratory infection. Initial whole-spine imaging was concerning for LETM and lumbar puncture was concerning for an inflammatory process. The patient was treated with intravenous (IV) methylprednisolone, after which she developed acute onset bilateral lower extremity paraparesis with a sensory level. Angiogram confirmed the diagnosis of SDAVF and the patient was treated surgically. Post-operative course was complicated and subsequent clinical improvement has been slow with incomplete recovery to date. DISCUSSION: This case illustrates the nonspecific presentation of SDAVF and the difficulty of differentiating it from other causes of LETM. It demonstrates acute clinical deterioration of SDAVF following steroid administration, a recently recognized clinical entity. The most likely mechanism is hydrostatic steroid effect coupled with iatrogenic fluid co-administration causing increased venous congestion. Previous cases have demonstrated this effect to be transient and resolves after discontinuation of steroids. This case highlights a recent association of increased morbidity following steroid administration despite definitive treatment.

Mentored peer review of standardized manuscripts as a teaching tool for residents: a pilot randomized controlled multi-center study.

BACKGROUND: There is increasing need for peer reviewers as the scientific literature grows. Formal education in biostatistics and research methodology during residency training is lacking. In this pilot study, we addressed these issues by evaluating a novel method of teaching residents about biostatistics and research methodology using peer review of standardized manuscripts. We hypothesized that mentored peer review would improve resident knowledge and perception of these concepts more than non-mentored peer review, while improving review quality. METHODS: A partially blinded, randomized, controlled multi-center study was performed. Seventy-eight neurology residents from nine US neurology programs were randomized to receive mentoring from a local faculty member or not. Within a year, residents reviewed a baseline manuscript and four subsequent manuscripts, all with introduced errors designed to teach fundamental review concepts. In the mentored group, mentors discussed completed reviews with residents. Primary outcome measure was change in knowledge score between pre- and post-tests, measuring epidemiology and biostatistics knowledge. Secondary outcome measures included level of confidence in the use and interpretation of statistical concepts before and after intervention, and RQI score for baseline and final manuscripts. RESULTS: Sixty-four residents (82%) completed initial review with gradual decline in completion on subsequent reviews. Change in primary outcome, the difference between pre- and post-test knowledge scores, did not differ between mentored (-8.5%) and non-mentored (-13.9%) residents (p = 0.48). Significant differences in secondary outcomes (using 5-point Likert scale, 5 = strongly agree) included mentored residents reporting enhanced understanding of research methodology (3.69 vs 2.61; p = 0.001), understanding of manuscripts (3.73 vs 2.87; p = 0.006), and application of study results to clinical practice (3.65 vs 2.78; p = 0.005) compared to non-mentored residents. There was no difference between groups in level of interest in peer review (3.00 vs 3.09; p = 0.72) or the quality of manuscript review assessed by the Review Quality Instrument (RQI) (3.25 vs 3.06; p = 0.50). CONCLUSIONS: We used mentored peer review of standardized manuscripts to teach biostatistics and research methodology and introduce the peer review process to residents. Though knowledge level did not change, mentored residents had enhanced perception in their abilities to understand research methodology and manuscripts and apply study results to clinical practice.

MRI findings in cryptococcal meningitis of the non-HIV population.

OBJECTIVES: Cryptococcal meningitis is an opportunistic infection which can afflict immunocompetent and immunocompromised individuals. Imaging findings in the HIV population are well described; however, few studies have focused on the non-HIV population.The purpose of this study is to characterize clinical and magnetic resonance imaging (MRI) findings in the non-HIV population. METHODS: We performed a retrospective chart review of patients with positive CSF cryptococcal antigen (between 1997 and 2009) who were not HIV positive. Only patients with MRIs of the brain were included. Data collected included CSF findings, blood and CSF cryptococcal titers, and information regarding the use of immunosuppressant drugs. RESULTS: Nineteen patients fulfilled study criteria, and 74% of the patients had abnormal imaging.Ten patients were on immunosuppressants due to cancer, organ transplantation, or presumed vasculitis. Four patients had no known risk factors and 2 patients had idiopathic low CD4 counts.MRI findings in cryptococcal meningitis included leptomeningeal enhancement with or without a micronodular pattern, microcystic prominence involving the temporal lobes or basal ganglia, ventriculomegaly, and a brain abscess. Two patients had posterior fossa cysts at the foramen of Luschka. Five patients had a normal MRI. CONCLUSIONS: MRI findings in cryptococcal meningitis of the non-HIV population were more common in our series than previously recognized. In this patient population, leptomeningeal enhancement and intraventricular cystic lesions were more common than intraparenchymal findings.

Opinion & Special Articles: neurologist: specialized primary care provider vs consultant.

As per the Centers for Medicare and Medicaid Services (CMS) current proposal, many specialties including neurology are not eligible for the increase in Medicare reimbursements that will be allocated to other cognitive specialties, such as the 7% increase for family physicians, 5% for internists, and 4% for geriatric specialists.(1,2) Other specialties such as anesthesiology, radiology, and cardiology are scheduled for a 3%-4% decrease in reimbursement in order to pay for the increases outlined above. Current estimates show that neurologists provide a significant amount of primary care for complex patients and yet these services are not eligible for increased payments. It is estimated that up to 60% of neurologists' services to these complex patients are ineligible for increased payments.(3.)

Unusual headaches in the elderly.

Prevalence of headache lowers with age, and headaches of elderly adults tend to be different than those of the younger population. Secondary headaches, such as headaches associated with vascular disease, head trauma, and neoplasm, are more common. Also, certain headache types tend to be geriatric disorders, such as primary cough headache, hypnic headache, typical aura without headache, exploding head syndrome, and giant cell arteritis. This review provides an overview of some of the major and unusual geriatric headaches, both primary and secondary.

Acute treatment of basilar-type migraine with greater occipital nerve blockade.

Basilar-type migraine (BTM) precludes use of migraine-specific medications such as triptans and ergots based on concerns originating from the vascular theory of migraine, although data supporting this contraindication are lacking. Availability of effective treatments for acute BTM is limited. We report a case of BTM aborted with greater occipital nerve (GON) blockade given in the setting of prominent suboccipital tenderness. GON blockade may provide an additional option in acute management of BTM. It may be particularly useful when associated with prominent ipsilateral suboccipital tenderness.

Pitfalls in the electrodiagnostic studies of sacral plexopathies.

This retrospective review characterizes the electrodiagnostic (EDX) features and etiologies of sacral plexopathies (SPs) and discusses difficulties in their identification. The EDX findings of 171 clinically suspected SPs were reviewed using the following criteria: reduced/absent sensory nerve action potentials (SNAPs) of the sural or superficial peroneal nerve, denervation of plexus-innervated muscles, and the absence of paraspinal denervation. Sixty cases localized unequivocally to the sacral plexus. The majority were cancer-related, followed by traumatic, idiopathic, and iatrogenic causes. Final diagnoses in the remaining 111 cases were indeterminate. Lesions localized to either the plexus or L4-5, S1 roots in 52 cases, the plexus or sciatic nerve in 32 cases, and were equally compatible with an SP, sciatic neuropathy, or radiculopathy in 27 cases. Findings in the EDX evaluation of SPs are often complex and difficult to localize to a specific site due to multiple complicating factors. Frequently, SPs cannot be diagnosed definitively by EDX assessment alone.