Clinical Reasoning: A 62-Year-Old Woman With Transient Vision Loss.

Transient visual loss (TVL) is a common complaint in the emergency department, with numerous possible etiologies. Prompt evaluation and management of TVL can potentially prevent progression to permanent visual loss. In this case, a 62-year-old woman presented with acute, painless, unilateral TVL. Two weeks before presentation, the patient reported bitemporal headaches and paresthesia of the distal extremities. A review of systems revealed chronic fatigue, cough, diffuse arthralgias, and decreased appetite for the previous 6 months. This case highlights the diagnostic approach to patients with TVL. Some common and rare causes associated with this clinical manifestation are briefly reviewed.

Obstetric and Gynecologic Disorders and the Nervous System.

OBJECTIVE: This article discusses obstetric and gynecologic associations with common neurologic disorders. LATEST DEVELOPMENTS: Neurologic complications of obstetric and gynecologic disorders can arise throughout the lifespan. Caution should be exercised when prescribing fingolimod and natalizumab to patients with multiple sclerosis who are of childbearing potential because of the risk of disease rebound when they are discontinued. OnabotulinumtoxinA is considered safe in pregnancy and lactation based on long-term observational data. Hypertensive disorders of pregnancy are associated with higher subsequent cerebrovascular risk, likely via multiple mechanisms. ESSENTIAL POINTS: Neurologic disorders may present in a variety of obstetric and gynecologic contexts, with meaningful implications for recognition and treatment. These interactions must be considered when treating women with neurologic conditions.

Chronic pruritus in multiple sclerosis and clinical correlates.

BACKGROUND: To date, little is known about the prevalence of itch in multiple sclerosis (MS) and its characteristics. OBJECTIVES: In this cross-sectional study, we assessed the prevalence, intensity and characteristics of chronic pruritus in MS patients and its effect on quality-of-life and association with MS symptoms, clinical signs, comorbidities and MRI findings. METHODS: MS patients presenting to an outpatient neurology clinic were asked about their current symptoms. Those who experienced chronic pruritus were administered the Standardized Itch Questionnaire and Itch Quality of Life forms. All patients' medical records were reviewed. Patients with any medical conditions associated with chronic itch were excluded. RESULTS: Seventy-seven total MS patients were included, and 27 (35%) reported pruritus. The average itch NRS severity was 5.42 (range 0-10). The most affected body parts were the extremities, face or scalp, and trunk. Itch was characterized as acute (74%), paroxysmal (59%) and tingling (55%). Heat (52%) was the most common aggravating factor, while cold temperatures had no effect. Compared with MS patients without itch, itch patients reported more fatigue (77% vs 44%, p = 0.004), heat sensitivity (48% vs 20%, p = 0.0177), cognitive impairment (62% vs 26%, p = 0.0029) and depression or anxiety (48% vs 16%, p = 0.0063). Additionally, itch patients had more T2 hyperintensities in the posterior cervical cord and anterior pons/ventromedial medulla (74.1% vs 46.0%, p = 0.018 and 29.6% vs 8.0%, p = 0.020, respectively). Finally, T2 hyperintensities in the anterior pons/ventromedial medulla were strongly associated with itch localized to the face or scalp (OR 11.3, 95% CI 1.6-78.6, p = 0.025). CONCLUSION: MS patients experience paroxysmal neuropathic pruritus that is most frequently localized to the extremities, face or scalp. Patients with itch were more likely to have MS-related comorbidities and demyelinating lesions in the spinal cord or brainstem.

Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide-a report by the HSS International Study Group.

INTRODUCTION: Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease. OBJECTIVES: The aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type. METHODS: The Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients. RESULTS: This atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis. CONCLUSION: The HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points • The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality. • All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease. • The HSS International Study Group reference atlas  classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA). • The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

Development of an Equity, Diversity, Inclusion, and Anti-racism Pledge as the Foundation for Action in an Academic Department of Neurology.

Racial inequities as illustrated by the health disparities in COVID19 infections and deaths, the recent killings of Black men and women by law enforcement, and the widening socioeconomic inequality and have brought systemic racism into a national conversation. These unprecedented times may have deleterious consequences, increasing stress, and trauma for many members of the neurology workforce. The Equity, Diversity, Inclusion and Anti-Racism Committee within our Department of Neurology provides infrastructure and guidance to foster a culture of belonging and addresses the well-being of faculty, staff, and trainees. Here, we present the creation and implementation of our Equity, Diversity, Inclusion, and Anti-Racism (EDIA) Pledge which was central to our committee's response to these unprecedented times. We outline the process of developing this unique EDIA Pledge and provide a roadmap for approaching these important topics through a CME Neurology Grand Rounds aimed at fostering a diverse, inclusive, equitable and antiracist work environment. Through the lived experiences of 4 faculty members, we identify the impact of bias and microaggressions, and encourage allyship and personal development for cultural intelligence. We hope these efforts will inspire Neurology departments and other academic institutions across the globe to make a similar pledge.

Increased multiple sclerosis disease activity in patients transitioned from fingolimod to dimethyl fumarate: a case series.

BACKGROUND: Fingolimod is a S1P1 receptor modulator that prevents activated lymphocyte egress from lymphoid tissues causing lymphopenia, mainly affecting CD4+ T lymphocytes. Withdrawal from fingolimod can be followed by severe disease reactivation, and this coincides with return of autoreactive lymphocytes into circulation. The CD8+ T cytotoxic population returns prior to the regulatory CD4+ T lymphocytes leading to a state of dysregulation, which may contribute to the rebound and severity of clinical relapses. On the other hand, dimethyl fumarate (DMF) preferentially reduces CD8+ T lymphocytes, has the same efficacy as fingolimod, and therefore, was expected to be a suitable oral alternative to reduce the rebound associated with fingolimod withdrawal. CASE PRESENTATION: We present six patients with relapsing-remitting MS who developed an unexpected increase in disease activity after transitioning from fingolimod to DMF. All patients were clinically and radiologically stable on fingolimod for at least 1 year. The switch in therapy was due to significantly low CD4+ T lymphocyte count ≤65 cells/ul (normal range 490-1740 cells/ul), after discussing the results with the patients and the potential risk for opportunistic infections including cryptococcal infections. DMF was introduced following a washout period of 5 to 11 weeks to allow reconstitution of the immune system and for the absolute lymphocyte count to reach ≥500 cells/ul. Every patient who experienced a relapse had several enhancing lesions in the brain and/or spinal cord between 12 to 23 weeks after cessation of fingolimod and 1 to 18 weeks after starting DMF. All relapses were treated with intravenous methylprednisolone with good clinical responses. CONCLUSION: The anticipated beneficial response of DMF treatment to mitigate rebound after fingolimod therapy cessation was not observed. Our patients experienced rebound disease despite being on treatment with DMF. Additional studies are necessary to understand which treatments are most effective to transition to after discontinuing fingolimod.

A critical analysis of 57 cases of Hughes-Stovin syndrome (HSS). A report by the HSS International Study Group (HSSISG).

BACKGROUND: Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment. METHODS: We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death. RESULTS: At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers. CONCLUSIONS: HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.

Development of SARS-CoV-2 IgM and IgG antibodies in a relapsing multiple sclerosis patient on ofatumumab.

We report the case of a MS patient on subcutaneous ofatumumab who became infected with SARS-CoV-2 and remained asymptomatic while developing antiviral IgM and IgG antibodies. The patient was B-cell depleted with normal serum immunoglobulin levels. Anti-SARS-CoV-2 IgG antibodies remained positive three months after the initial infection. These findings suggest that a MS patient treated with ofatumumab may be able to mount an effective humoral response to SARS-CoV-2 infection and probably to COVID-19 vaccines as well. Further research will be necessary to evaluate the humoral response of MS patients on ofatumumab to SARS-CoV-2 infection and COVID-19 vaccines.

Cognitive outcomes following laser interstitial therapy for mesiotemporal epilepsies.

OBJECTIVE: To provide a review of cognitive outcomes across a full neuropsychological profile in patients who underwent laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). METHODS: We examined cognitive outcomes following LiTT for mTLE by reviewing a consecutive series of 26 patients who underwent dominant or nondominant hemisphere procedures. Each patient's pre- and postsurgical performance was examined for clinically significant change (>1SD improvement or decline on standardized scores), with a neuropsychologic battery that included measures of language, memory, executive functioning, and processing speed. RESULTS: Presurgical performance was largely consistent with previous research, where patients suffering from dominant hemisphere epilepsies demonstrated deficits in verbal learning and memory, whereas patients with nondominant hemisphere scored lower on visually mediated tests. Case-by-case review comparing presurgical to postsurgical scores revealed clinically significant improvement in both dominant and nondominant patients in learning and memory and other aspects of cognition such as processing speed and executive functioning. Of the few patients who did experience clinically significant decline following LiTT, a greater proportion had undergone dominant hemisphere procedures. CONCLUSIONS: Compared with the outcome literature of dominant open anterior temporal lobectomies (ATLs), where postsurgical decline has been documented in up to 40%-60% of cases, our LiTT case series exhibited a much lower incidence of postoperative language or verbal memory decline. Moreover, promising rates of postoperative improvements were also observed across multiple cognitive domains. Future studies exploring cognitive outcomes following LiTT should include comprehensive neuropsychological findings, rather than only select domains, as clinically significant change can occur in areas other than those typically associated with mesiotemporal structures.

'Wargaming with the chiefs': A novel pre-mortem exercise to enhance communication and well-being among 'top gun' chief residents.

Pilots who complete the 'TOPGUN' program return to their squadrons as elite leaders and instructors. Physicians from all specialties who are selected to become Chief residents can also be viewed as 'Top Guns', as they are the 'cream of the crop'; having been chosen to be the leaders and role-models for all the other residents in their programs. Yet, unlike Top Gun pilots, Chief residents are arguably only minimally prepared for this new role. Wargaming involves generating every possible bad outcome and brainstorming contingencies for these possible outcomes. We developed an exercise for the incoming Chiefs (ICs) and outgoing Chiefs (OCs) in four specialties: Family Medicine, Internal Medicine, Neurosurgery, and Neurology. Following this exercise, 100% of the Chiefs in all four programs indicated that this activity was beneficial and the majority agreed that wargaming improved communication and their own feelings of well-being. Based on our trainees' feedback, it appears that wargaming is a simple, fun, and highly-interactive exercise which increases perceived control among ICs and allows OCs the chance to reflect and share their knowledge and experience with the new Chiefs. This activity also seems to enhance communication and feelings of well-being among both incoming and outgoing Chief residents.

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.

Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis.

BACKGROUND AND OBJECTIVE: Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics. METHODS: Data were obtained for 1033 self-identified Hispanics with MS from four MS-based registries from four academic institutions across the United States January 2016-April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom. RESULTS: Genetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = -0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96-0.99; P = 7.80 × 10-03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35-4.10; P = 2.60 × 10-03). Younger age of onset was found to be associated with a higher proportion NA (Beta: -5.58; P = 3.49 × 10-02) and African ancestry (Beta: -10.07; P = 1.39 × 10-03). INTERPRETATION: Ethnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.

Neuroleptic Malignant Syndrome Associated with Refractory Acute Disseminated Encephalomyelitis.

We present the case of a young man who was transferred to our hospital with worsening acute disseminated encephalomyelitis (ADEM) despite treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. He developed neuroleptic malignant syndrome (NMS) without the use of dopamine-modulating drugs. His progressive clinical improvement started after treatment with intravenous cyclophosphamide and methylprednisolone. In our patient, acute demyelination with severe bilateral inflammation of the basal ganglia could have caused a state of central dopamine depletion, creating proper conditions for the development of NMS. Significant clinical improvement of our case after treatment with intravenous cyclophosphamide and steroids provides further evidence for a possible role of the inflammatory lesions in the pathogenesis of NMS in association with ADEM.

Clinical Expression of Multiple Sclerosis in Hispanic Whites of Primarily Caribbean Ancestry.

OBJECTIVE: The clinical characteristics of multiple sclerosis (MS) are not well defined in Hispanic populations. We hypothesized that disease presentation in Hispanic white (HW) patients will be different from non-Hispanic white (NHW) patients given their ancestral background and reported lower disease prevalence. This study was undertaken to compare HW of primarily Caribbean ancestry to NHW on clinical characteristics of MS. METHODS: We assessed 312 HW and 312 NHW patients with definite MS for clinical disease characteristics obtained through consented review of medical records. In order to assess the relationship between age-related phenotypes and ethnicity, linear regression was used. Logistic regression was used to assess the relationship between ethnicity and descriptors of disease presentation and severity as well as presence of neurological symptoms. RESULTS: We observed a significantly younger age at diagnosis (p = 1.38E-02) and age at exam (p = 2.36E-05) in HW. However, age at first symptom did not differ significantly between the two groups. Furthermore, within HW, the mean age at first symptom and age at diagnosis was significantly younger in those born in the United States (p < 1.00E-03 for both). Interestingly, we noted an increase in ambulatory disability in HW patients, primarily among those with relapsing disease (p = 4.18E-03). CONCLUSIONS: We found several differences in age-related phenotypes and disease severity between HW of primarily Caribbean origin and NHW patients. To our knowledge, this is the largest study to date that examined the clinical characteristics of MS in Hispanic patients of largely Caribbean origin.

Multiple sclerosis and the cerebellum.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease that has unpredictable symptomatology and severity. Cerebellar manifestations in MS can be present at any time of the clinical course. Early cerebellar findings are a predictor of disability and disease progression. Most patients have cerebellar manifestations once they enter the progressive stages of the disease. Of the cerebellar findings, tremor is by far the most common.

Multiple sclerosis and the spinal cord.

Many clinical manifestations of multiple sclerosis (MS) may be attributed to spinal cord disease. MS may have classic presentation or a more complex presentation. MS is mainly a relapsing remitting disease, but there is also an insidious form that is progressive, known as primary progressive MS (PPMS). PPMS may not be identified for extended periods of time and should be on the differential of chronic myelopathies. Early diagnosis of MS rests on awareness of a clinically isolated syndrome and the required magnetic resonance imaging criteria. Early diagnosis results in early institution of treatment and a superior response.