Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group

Background and aim: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. Methods: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. Results: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p &lt; 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P &lt; 0.001). Conclusion: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas “in-situ thrombosis” seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.</p

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

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

Antiepileptic drug pregnancy registries: do the latest findings concur?

The risk of antiepileptic drug (AED) exposure to the developing fetus is of global concern. Every year, 25,000 children are born to women with epilepsy (WWE) in the USA alone. Most pregnant WWE require AEDs and, therefore, scientifically derived evidence from large studies is essential to help determine the best management. AED pregnancy registries were initiated in the early 1990s to assess pregnancy outcomes in WWE, with the aims of obtaining accurate information about AED-related teratogenesis and evaluating the risks of the newer AEDs in a timely manner. The registries have had varied methodologies, which has been, in part, dictated by the healthcare system in which they are used. Countries with nationalized healthcare systems permit population-based data gathering, whereas in areas where medical care is privatized, a more focused prospective approach is taken. Furthermore, pharmaceutical companies have supported several registries aimed at determining the risk of exposure to a single compound. Therefore, each registry has different rules for enrollment, inclusion/exclusion criteria, length and detail of follow-up, and predetermined publication criteria. Owing to these differences and because a few subjects enroll in more than one registry, the registries do not lend themselves to a meta-analytic approach. This article will summarize the major concurrent and differing findings of the current registries from the perspective of their direct impact on managing WWE during pregnancy. We will discuss registries based in the USA, UK, Australia, Finland, Sweden and from the European and International Registry of AEDs in Pregnancy (EURAP)

Demyelinating syndrome Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune, inflammatory, demyelinating, and degenerative disorder of the central nervous system and one of the most common causes of disability in young adults. It is estimated that there are about 2.5 million people living with MS worldwide, with the onset typically occurring between the ages of 20 and 40 with a mean age of 30. MS was initially described as a disease of white matter, but people now know that it is characterized by inflammation, demyelination of white and gray matter, as well as axonal injury. The clinical course of the disease varies greatly and is completely unpredictable. The pharmacologic treatment of MS is threefold and involves treatment of acute attacks, disease-modifying drugs, and symptomatic therapies. The life span of a patient with MS is slightly less than the general population. MS requires a multidisciplinary approach to promote positive patient outcomes

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

Fingolimod is a S1P 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. 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. 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

'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

Dolichoectasia and multifocal simultaneous intracranial haemorrhages

Dolichoectasia is found primarily in aged individual with atherosclerotic disease. It presents with brain stem compression and stroke, which could be ischaemic or haemorrhagic. Even if severe atherosclerosis is thought to play a pivotal role, new evidence suggest that the internal elastic laminae is disrupted, intracranially and extracranially, so multiorganic involvement with various clinical presentations can occur. We present a rare association of multiorganic dolichoectasia debuting with multiple intracranial haemorrhages. A 79-year-old woman presented with altered mental status and left hemiplegia. The work up demonstrated brain arteries dolichoectasia and an abdominal aortic aneurysm with multiple site intraparenchymal haemorrhages. In this case, the presentation of multiple site dolichoectasia and multiple haemorrhages is probably linked to a systemic “media disease” that affected the media of small, medium and large arteries rather than a coincidental finding