Practical Considerations for Managing Pregnancy in Patients With Multiple Sclerosis: Dispelling the Myths.

Purpose of Review: Lack of consistent data and guidance have led to variations between clinicians in the management of pregnancy in women with multiple sclerosis (MS). Pregnant and/or lactating women are often excluded from clinical trials conducted in MS, and thus, the labeling for most disease-modifying therapies (DMTs) excludes use during pregnancy. This has led to heterogeneity in interpretation and labeling regarding the safety of DMTs during pregnancy and lactation and the required preconception washout periods. This review identifies key themes where there is conflicting information surrounding family planning and pregnancy in MS, focusing on the most common discussion points between physicians and patients during preconception planning, pregnancy, postpartum, and lactation. The goal was to inform the patient-physician conversation and provide best practice recommendations based on expert clinical expertise and experience. Recent Findings: We outline the latest evidence-based data for DMT use during pregnancy and lactation, the effect of MS on fertility and fertility treatments, the risk of adverse pregnancy and delivery outcomes, the risk of postpartum relapse, and immunization and clinical imaging safety during pregnancy and breastfeeding. Summary: Management of family planning and pregnancy in patients with MS requires the most current information. Health care providers should discuss family planning early and frequently with patients with MS, and partners where practicable. Because management of pregnant people with MS will often require a risk/benefit analysis of their needs, shared decision-making in family planning discussions is emphasized. Additional data are needed for specific and underrepresented populations with MS (e.g., single parents or those from the LGBTQ+ community) and those at risk of racial and socioeconomic disparities in care. Pregnancy registries and the design and conduct of clinical trials focused on pregnant and lactating patients should provide additional data to guide the ongoing management of patients with MS.

Disparities by Race in Pregnancy Care and Clinical Outcomes in Women With Multiple Sclerosis: A Diverse Multicenter Cohort

BACKGROUND AND OBJECTIVES: Racial disparities exist in both neurologic and obstetric populations, underscoring the importance of evaluating pregnancy outcomes in diverse women with multiple sclerosis (MS). The objective of this multicenter retrospective study was to compare pregnancy care and outcomes between Black and Hispanic (underrepresented) and White women with MS. METHODS: Demographic and clinical data were extracted from medical records of 9 US MS centers for women with MS/clinically isolated syndrome who delivered live births between 2010 and 2021. Sites identified at last 15 consecutive Black/Hispanic women and a matching number of White women. Socioeconomic factors, pregnancy, and MS care/outcomes were compared between groups (underrepresented and White and then Black and Hispanic) using Wilcoxon rank sum (U statistic and effect size r reported), χ2, t tests and logistic regressions as appropriate to data type. Multiple imputation by chained equation was used to account for missing data. RESULTS: Overall, 294 pregnancies resulting in live births were analyzed ( 81 Black, 67 Hispanic, and 146 White mothers). Relative to underrepresented women, White women lived in areas of higher median (interquartile range [IQR]) Child Opportunity Index (79 [45.8] vs 22 [45.8], U = 3,824, r = 0.56, p < 0.0001) and were more often employed (84.9% vs 75%, odds ratio [OR] 2.57, CI 1.46-4.50, p = 0.0008) and privately insured (93.8% vs 56.8%, OR 11.6, CI 5.5-24.5, p < 0.0001) and more received a 14-week ultrasound (98.6% vs 93.9%, OR 4.66, CI 0.99-21.96, p = 0.027). Mode of delivery was significantly different between the three groups (X2(10,294) = 20.38, p = 0.03); notably, Black women had the highest rates of emergency cesarean deliveries, and Hispanic women highest rates of uncomplicated vaginal deliveries. Babies born to underrepresented women had lower median (IQR) birthweights than babies born to White women (3,198 g [435.3 g] vs 3,275 g [412.5 g], U = 9,255, r = 0.12, p = 0.04) and shorter median (IQR) breastfeeding duration (4.5 [3.3] vs 6.0 [4.2] months, U = 8,184, r = 0.21, p = 0.003). While underrepresented women were younger than White women (mean [SD] 30.9 [4.8] vs 33.8 [4.0], t = 1.97, CI 1.96-3.98, p < 0.0001), their median (Q1-Q3, IQR) Expanded Disability Status Scale was higher (1.5 [1-2.5, 1.5] vs 1 [0-1.5, 1.5], U = 7,260, r = 0.29, p < 0.0001) before pregnancy. Finally, medical records were missing more key data for Black women (19.7% missing vs 8.9% missing, OR 2.54, CI 1.25-5.06, p = 0.008). DISCUSSION: In this geographically diverse multicenter cohort, underrepresented women entered pregnancy with higher disability and fewer health care resources. Pregnancy represents a pivotal window where structural factors affect maternal and fetal health and neurologic trajectories; it is a critical period to optimize care and health outcomes.

Rituximab and pregnancy: Late-onset neutropenia in a 2-month infant whose mother received rituximab 2 weeks prior to childbirth.

Late-onset neutropenia (LON) is a rare adverse event that has not been reported from in utero exposure. We describe a case of LON in an infant, whose mother had neuromyelitis optica and received rituximab in the third trimester due to re-emergence of CD19 B cells. The newborn was born without complications but 2 months later was found to have grade IV neutropenia. No etiology was identified. Neutropenia self-resolved within 1 week. This case emphasizes an unmet need for developing guidelines and protocols to manage in utero rituximab exposure.

Case report: Use of granulocyte-colony stimulating factor as an immunomodulatory therapy in a patient with neuromyelitis optica spectrum disorder and comorbid immunodeficiency.

Background: Autoimmune diseases can coexist with immunodeficiency. We describe a treatment approach in which granulocyte-colony stimulating factor (G-CSF) is used to restore immune competence without worsening autoimmunity. G-CSF is a polyfunctional cytokine that influences survival, proliferation, and differentiation of hematopoietic stem cells, and has immunomodulatory effects on the innate and adaptive immune systems. Objective: To report a case of neuromyelitis optica spectrum disorder (NMOSD) with comorbid immunodeficiency and frequent infections. Methods: Case report and review of literature. Results: A 23 years-old man presented with a focal onset seizure with impaired awareness at age 12. At age 18, he developed headaches, recurrent multifocal seizures, and non-convulsive status epilepticus. Brain magnetic resonance imaging (MRI) showed extensive T2 hyperintense and gadolinium-enhancing periventricular and corpus callosum lesions. Serum aquaporin 4 antibody was positive 1:10,000 (normal value <1.5 titer), hence he was diagnosed with NMOSD. As a complication, patient developed mucormycotic pneumonia with cavitation, requiring thoracotomy precluding use of immunosuppressants. Gene testing demonstrated a mutation in MT-ND4 gene encoding for NADH dehydrogenase 4 in mitochondrial complex 1. Eventually, he began a treatment with filgrastim, a G-CSF analog, in addition to intravenous immunoglobulins and prednisone. Patient's NMOSD has been in remission without relapses, or coexistent infections ever since. Conclusion: G-CSF is a polyfunctional cytokine with important immunomodulatory effects, which makes it an interesting therapeutic option when autoimmunity coexists with immunodeficiency and was used successfully in this case.

Differential Diagnosis of Tumor-like Brain Lesions.

Purpose of Review: Tumor-like brain lesions are rare and commonly suggest a neoplastic etiology. Failure to rapidly identify non-neoplastic causes can lead to increased morbidity and mortality. In this review, we describe 10 patients who presented with atypical, non-neoplastic tumor-like brain lesions in which brain biopsy was essential for a correct diagnosis and treatment. Recent Findings: There has been increasing recognition of autoimmune conditions affecting the nervous system, and many of those diseases can cause tumor-like brain lesions. Currently available reports of non-neoplastic tumor-like brain lesions are scarce. Most case series focus on tumefactive demyelinating lesions, and a comprehensive review including other neuroimmunological conditions such as CNS vasculitis, neurosarcoidosis, histiocytic and infectious etiologies is lacking. Summary: We review the literature on tumor-like brain lesions intending to increase the awareness and differential diagnosis of non-neoplastic brain tumor mimics. We advocate for earlier brain biopsies, which, in our case series, significantly changed diagnosis, management, and outcomes.

Corrigendum: Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARSCoV-2 Nucleocapsid protein.

[This corrects the article DOI: 10.3389/fimmu.2023.1155770.].

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

Introduction: Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents. Results: We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4+ T cell responses and diminished CD8+ memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8+ T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction. Discussion: We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.

Current Updates on the Diagnosis and Management of Multiple Sclerosis for the General Neurologist.

Multiple sclerosis (MS) is an immune-driven disease that affects the central nervous system and is characterized by acute-on-chronic demyelination attacks. It is a major cause of global neurological disability, and its prevalence has increased in the United States. Conceptual understandings of MS have evolved over time, including the identification of B cells as key factors in its pathophysiology. The foundation of MS management involves preventing flares so as to avoid long-term functional decline. Treatments may be categorized into low-, middle-, and high-efficacy medications based on their efficacy in relapse prevention. With 24 FDA-approved treatments for MS, individual therapy is chosen based on distinct mechanisms and potential side effects. This review provides a detailed update on the epidemiology, diagnosis, treatment advances, and major ongoing research investigations in MS.

Neuroimmunological Disorders: The Gender Effect.

Multiple sclerosis is a disease that tends to affect women during their childbearing years. Although relapse risk decreases during pregnancy, patients should still be optimized on disease-modifying therapy before and after pregnancy to minimize gaps in treatment. Exclusive breastfeeding may reduce the chances of disease relapse postpartum, and many disease-modifying therapies are considered to be safe while breastfeeding. Treatments for other neuroimmunologic disorders such as neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, neurosarcoidosis, and central nervous system vasculitis may require rituximab before and prednisone or intravenous immunoglobulin therapy during pregnancy.

Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.

OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients. METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021. RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients. INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.

Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era.

BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse. METHODS: Patients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported. RESULTS: One hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI. DISCUSSION: In this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

Therapeutic Approaches to the Neurologic Manifestations of COVID-19.

As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.

Peripartum disease activity in moderately and severely disabled women with multiple sclerosis.

Background: The effects of pregnancy on multiple sclerosis (MS) inflammatory activity are not well described in women with moderate to severe disabilities. Objective: To quantify the peripartum annualized relapse rate (ARR) in women with MS with an Expanded Disability Status Scale (EDSS) ≥ 3. Methods: We performed a retrospective cohort study of 85 pregnancies in 74 subjects with preconception EDSS ≥ 3. We quantified peripartum ARR and tested for risk factors predictive of peripartum relapses, postpartum brain magnetic resonance imaging activity (new T2 or gadolinium-enhancing lesions), and disability worsening. Results: There were 74 live births, with a 56% operative delivery rate. In subjects with relapsing-remitting MS, ARR decreased to 0.11 during the third trimester of pregnancy compared to 0.59 in the year preconception and increased to 1.22 in the 3 months postpartum. Women with a higher preconception EDSS had higher odds of postpartum relapses and clinically significant worsening of disability as compared to subjects with a lower EDSS. Conclusions: Moderately to severely disabled women with MS have a lower risk of relapse during pregnancy as compared to preconception, followed by a marked increase postpartum. Further studies are needed to identify ways to reduce peripartum inflammatory activity and disability progression in women with MS with moderate to severe disability.

Evolution of neurologic symptoms in non-hospitalized COVID-19 "long haulers".

OBJECTIVE: We characterized the evolution of neurologic symptoms and self-perceived recovery of non-hospitalized COVID-19 "long haulers" 6-9 months after their initial Neuro-COVID-19 clinic evaluation. METHODS: In this follow-up study on the first 100 patients, 50 SARS-CoV-2 laboratory-positive (SARS-CoV-2+ ), and 50 laboratory-negative (SARS-CoV-2- ), evaluated at our Neuro-COVID-19 clinic between May and November 2020, patients completed phone questionnaires on their neurologic symptoms, subjective impression of recovery and quality of life. RESULTS: Of 52 patients who completed the study (27 SARS-CoV-2+ , 25 SARS-CoV-2- ) a median 14.8 (range 11-18) months after symptom onset, mean age was 42.8 years, 73% were female, and 77% were vaccinated for SARS-CoV-2. Overall, there was no significant change in the frequency of most neurologic symptoms between first and follow-up evaluations, including "brain fog" (81 vs. 71%), numbness/tingling (69 vs. 65%), headache (67 vs. 54%), dizziness (50 vs. 54%), blurred vision (34 vs. 44%), tinnitus (33 vs. 42%), and fatigue (87 vs. 81%). However, dysgeusia and anosmia decreased overall (63 vs. 27%, 58 vs. 21%, both p < 0.001). Conversely, heart rate and blood pressure variation (35 vs. 56%, p = 0.01) and gastrointestinal symptoms (27 vs. 48%, p = 0.04) increased at follow-up. Patients reported improvements in their recovery, cognitive function, and fatigue, but quality of life measures remained lower than the US normative population (p < 0.001). SARS-CoV-2 vaccination did not have a positive or detrimental impact on cognitive function or fatigue. INTERPRETATION: Non-hospitalized COVID-19 "long haulers" continue to experience neurologic symptoms, fatigue, and compromised quality of life 14.8 months after initial infection.

Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients.

BACKGROUND: Persistent viral RNA shedding of SARS-CoV-2 following COVID-19 has increasingly been recognized, with limited understanding of its implications on outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively assessed for persistent viral shedding across Northwestern Medicine Healthcare (NMHC) patients between March and August 2020. We assessed for predictors of persistent viral shedding, in-hospital delirium, and six-month mortality using binary logistic regression. RESULTS: Of the 2,518 hospitalized patients with an RT-PCR-confirmed diagnosis of COVID-19, 959 underwent repeat SARS-CoV-2 RT-PCR at least fourteen days from initial positive testing. Of those, 405 (42.2%) patients were found to have persistent viral shedding. Persistent viral shedding was associated with male sex, increased BMI, diabetes mellitus, chronic kidney disease, and exposure to corticosteroids during initial COVID-19 hospitalization. Persistent viral shedding was independently associated with incidence of in-hospital delirium after adjusting for factors including severity of respiratory dysfunction (OR 2.45; 95% CI 1.75, 3.45). Even after adjusting for age, severity of respiratory dysfunction, and occurrence of in-hospital delirium, persistent viral shedding remained significantly associated with increased six-month mortality (OR 2.43; 95% CI 1.42, 4.29). CONCLUSIONS: Persistent viral shedding occurs frequently in hospitalized COVID-19 patients and is associated with in-hospital delirium and increased six-month mortality.

T cell responses to SARS-CoV-2 in people with and without neurologic symptoms of long COVID.

Many people experiencing long COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), suffer from debilitating neurologic symptoms (Neuro-PASC). However, whether virus-specific adaptive immunity is affected in Neuro-PASC patients remains poorly understood. We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated humoral and cellular responses toward SARS-CoV-2 Nucleocapsid protein at an average of 6 months post-infection compared to healthy COVID convalescents. Neuro-PASC patients also had enhanced virus-specific production of IL-6 from and diminished activation of CD8+ T cells. Furthermore, the severity of cognitive deficits or quality of life disturbances in Neuro-PASC patients were associated with a reduced diversity of effector molecule expression in T cells but elevated IFN-γ production to the C-terminal domain of Nucleocapsid protein. Proteomics analysis showed enhanced plasma immunoregulatory proteins and reduced pro-inflammatory and antiviral response proteins in Neuro-PASC patients compared with healthy COVID convalescents, which were also correlated with worse neurocognitive dysfunction. These data provide new insight into the pathogenesis of long COVID syndrome and a framework for the rational design of predictive biomarkers and therapeutic interventions.

Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers".

OBJECTIVE: Most SARS-CoV-2-infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non-hospitalized Covid-19 "long haulers". METHODS: This is a prospective study of the first 100 consecutive patients (50 SARS-CoV-2 laboratory-positive (SARS-CoV-2+ ) and 50 laboratory-negative (SARS-CoV-2- ) individuals) presenting to our Neuro-Covid-19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid-19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient-reported quality of life measures and standardized cognitive assessments. RESULTS: Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: "brain fog" (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS-CoV-2+ than SARS-CoV-2- patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS-CoV-2+ patients performed worse in attention and working memory cognitive tasks compared to a demographic-matched US population (T-score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01). INTERPRETATION: Non-hospitalized Covid-19 "long haulers" experience prominent and persistent "brain fog" and fatigue that affect their cognition and quality of life.

Treatment challenges in idiopathic extracranial ICA vasospasm case report and review of the literature.

Idiopathic extracranial internal carotid artery (ICA) vasospasm is a rare pathological phenomenon that may lead to stroke in young patients. We report a case of an 18 year-old female with recurrent extracranial ICA vasospasm since age thirteen. We summarize published data related to this condition including all twenty-three reported cases of extracranial ICA vasospasm. We describe the various proposed pathophysiological mechanisms underlying this disorder. Various treatment modalities have been attempted but there is no known long-term effective treatment.

The 'present-tense' experience of failure in the university: Reflections from an action research project.

This article reflects on insights from an action research project where we worked with students whose university experience was inhibited by the fear of failure. In contrast to the popular concept of 'learning from failure', which involves intellectualizing the experience and distancing ourselves from it, our findings demonstrate the importance of a 'present tense' focus on emotions and affects in order to understand the experience of failure for students. Doing so brings us face-to-face with the often painful experience of failure in the present moment which, we argue, is an important and valid part of the university experience. We conclude by reflecting on the kinds of spaces and skills that may be needed to work with this new understanding of failure and show that developing these is a crucial part of resisting neoliberalism and creating a more 'care-full' (Mountz et al., 2015) academy.