Longitudinally Extensive Transverse Myelitis in a Patient With Systemic Lupus Erythematosus, Recent Influenza Infection, and Nutritional Deficiencies in the Setting of Chronic Alcohol Use.

Longitudinally extensive transverse myelitis (LETM) is traditionally classified as an inflammatory disorder of the spinal cord spanning three or more vertebral segments. The differential diagnosis for TM is vast and can include infectious, nutritional, and can even be idiopathic in some reported cases. However, autoimmune etiologies such as systemic lupus erythematosus (SLE) can rarely present with neurological manifestations such as LETM. In this case report, we present a 33-year-old female with a prior history of SLE who developed an LETM in the setting of possible provoking factors such as nutritional deficiencies and a recent viral illness. In this case report, we highlight her clinical course, recovery, and working differential diagnosis after laboratory testing and neurological imaging. Finally, we discuss the different treatments that ultimately lead to her successful recovery after her prolonged clinical course.

Efficacy of refrigerated gel packs for therapeutic hypothermia in neonatal retrieval: a retrospective cohort study.

OBJECTIVE: To determine the efficacy of refrigerated gel packs in achieving and maintaining target temperature in neonates receiving therapeutic hypothermia (TH) for hypoxic ischaemic encephalopathy during neonatal retrieval. DESIGN: Retrospective cohort study. SETTING: Paediatric Infant Perinatal Emergency Retrieval, Victoria, Australia. PATIENTS: 200 neonates treated with TH during retrieval between 1 January 2015 and 31 December 2020. INTERVENTIONS: Active cooling with refrigerated gel packs or passive cooling. MAIN OUTCOME MEASURES: The primary outcomes were the proportion of neonates who achieved therapeutic cooling rectal temperature (33-34°C) within 6 hours of birth and maintained target temperature range once TH was achieved. Secondary outcomes included need for respiratory support, inotropes, anticonvulsant therapy, sedation and survival at 7 days of life. RESULTS: 200 neonates received TH. Median gestational age was 39 weeks and median birth weight 3300 g. 120 (60%) were actively cooled with refrigerated gel packs and the remainder passively cooled. 121 neonates (61%) reached target temperature within 6 hours and 14 (7%) after 6 hours of birth. Of those who achieved target temperature, 38% were maintained in therapeutic cooling range for the remainder of the retrieval. CONCLUSIONS: Achieving and maintaining TH during neonatal retrieval with gel packs is challenging. Target temperature was not maintained in most neonates in this study. These findings support existing evidence favouring the use of servo-controlled cooling devices to optimise TH in the retrieval setting.

The Uniform Determination of Death Act is Not Changing. Will Physicians Continue to Misdiagnose Brain Death?

Efforts to revise the Uniform Determination of Death Act in order to align law with medical practice have failed. Medical practice must now align with the law. People who are not dead under the law that defines death should not be declared dead. There is no compelling reason to continue the practice of declaring legally living persons to be dead.

Bickerstaff Brainstem Encephalitis Presenting With Negative Anti-GM1 and Anti-GQ1B Antibodies.

A woman in her 60s initially presented with rapid-onset left-sided hemiparesis with later development of slurred speech and left-sided facial droop. Despite ruling out common causes, her condition rapidly progressed with the development of bilateral proximal weakness, ophthalmoplegia, ataxia, and pyramidal signs eventually leading to a cardiorespiratory arrest. Extensive investigations, including computerised tomography (CT), magnetic resonance imaging (MRI), and lumbar puncture (LP), were negative for infectious or vascular aetiologies. Nerve conduction studies (NCS) revealed severe peripheral nerve damage, and despite a provisional diagnosis of Guillain-Barré Syndrome (GBS), the clinical picture aligned more with Bickerstaff Brainstem Encephalitis (BBE) given the central nervous system (CNS) involvement, despite negative anti-GM1 and anti-GQ1b autoantibodies. Treatment involved ventilatory support, immunoglobulins, and steroids. This case report describes a rare and challenging presentation of BBE and reminds clinicians to have a systematic approach to a patient presenting with rapid onset neurological symptoms and that BBE is a clinical diagnosis.

Chronic cerebrospinal fluid leak can cause amyotrophic lateral sclerosis mimic.

Chronic cerebrospinal fluid leak with spinal cord compression can mimic the symptoms of ALS, with a snake-eyes appearance on MRI.

Case-Based Specialty Training for Medical Students to Elicit Social Determinants of Health.

Introduction: Without explicit education and training on how social determinants of health (SDoH) impact patient care and health outcomes, medical schools are failing to effectively equip future physicians to serve their patients. We created this workshop on health equity with a focus on SDoH to help students more effectively communicate with diverse populations. Methods: Third-year medical students and faculty were provided with class guides, learning objectives, role-play vignettes containing clerkship-specific history and physical exams, schedules, and discussion questions during a 2-hour session centered on SDoH. The workshop's impact was measured through mixed-methods analysis of surveys. Results: Based on pre- and postsurvey results from 87 participants, medical students strongly agreed that (1) SDoH factor more into a patient's health outcomes than the clinical encounter (pre: 67%, post: 87%), (2) it is their duty to gather information about SDoH (pre: 86%, post: 97%), (3) neighborhood safety is one of the key SDoH (pre: 88%, post: 97%), (4) they understood the impact of upstream interventions (pre: 35%, post: 93%), (5) they could efficiently screen all patients for SDoH at every medical encounter (pre: 27%, post: 86%), and (6) they could find preliminary resources to quickly assist patients in need of help regarding particular SDoH (pre: 26%, post: 85%). Discussion: This was the first iteration of this workshop; challenges involved piloting the content, time restraints, and organizational structure of the workshop design. Future directions include making SDoH curricula an integral part of undergraduate medical education and diverse clinical environments.

High risk and low prevalence diseases: Cavernous sinus thrombosis.

INTRODUCTION: Cavernous sinus thrombosis (CST) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of CST, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: CST is a potentially deadly thrombophlebitic disease involving the cavernous sinuses. The most common underlying etiology is sinusitis or other facial infection several days prior to development of CST, though other causes include maxillofacial trauma or surgery, thrombophilia, dehydration, or medications. Staphylococcus aureus, streptococcal species, oral anaerobic species, and gram-negative bacilli are the most frequent bacterial etiologies. The most prevalent presenting signs and symptoms are fever, headache, and ocular manifestations (chemosis, periorbital edema, ptosis, ophthalmoplegia, vision changes). Cranial nerve (CN) VI is the most commonly affected CN, resulting in lateral rectus palsy. Other CNs that may be affected include III, IV, and V. The disease may also affect the pulmonary and central nervous systems. Laboratory testing typically reveals elevated inflammatory markers, and blood cultures are positive in up to 70% of cases. Computed tomography of the head and orbits with intravenous contrast delayed phase imaging is recommended in the ED setting, though magnetic resonance venography demonstrates the highest sensitivity. Management includes resuscitation, antibiotics, and anticoagulation with specialist consultation. CONCLUSION: An understanding of CST can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Developing education in environmental health and medicine focusing on neurology: Initiatives in Sweden (the UPRISE model), France, and Turkey.

BACKGROUND: The role of environmental factors in neurological disorders constitutes a topic of increasing importance. Teaching in European universities should expand and update this field gaining future health professionals including adjacent disciplines. AIM: To describe recent efforts to create courses that cover crucial interdisciplinary content that we believe should be included in modern education, and to adapt modern pedagogic strategies. METHODS: In collaboration with RISE (Rencontres Internationales Santé Environnement), elective courses focused on Environmental Health and Medicine (EHM) were developed, in France, Sweden, and Turkey. The courses combined classic teaching methods and new pedagogic and digital solutions to create environment-related health awareness and facilitate future interprofessional collaboration in this field. RESULTS: UPRISE is an innovative elective course introduced in 2020 in Sweden's Uppsala University with the participation of lecturers from several countries and aim to recruit students from different universities. A total of 45, mainly female students (68%), participated in the course. In Strasbourg, France, a novel course on environmental medicine was held in 2019-2023 and examined 90 students, of which more than half were female. Nine graduate nurse students in Turkey attended ten seminar series focused on EHM. Overall, students expressed satisfaction with the courses. CONCLUSIONS: This European project for courses in higher education arising from RISE was met with appreciation and challenges from academic institutions. However, due to considerable efforts to introduce the EHM concept, a unique compulsory course for all medical students in the second year of training started in 2023 in all French medical faculties. In 2023, UPRISE was integrated into ENLIGHT, the European University Network to promote equitable quality of Life, sustainability, and Global engagement through Higher education Transformation.

Brain 3T magnetic resonance imaging in neonates: features and incidental findings from a research cohort enriched for preterm birth.

BACKGROUND AND OBJECTIVES: The survival rate and patterns of brain injury after very preterm birth are evolving with changes in clinical practices. Additionally, incidental findings can present legal, ethical and practical considerations. Here, we report MRI features and incidental findings from a large, contemporary research cohort of very preterm infants and term controls. METHODS: 288 infants had 3T MRI at term-equivalent age: 187 infants born <32 weeks without major parenchymal lesions, and 101 term-born controls. T1-weighted, T2-weighted and susceptibility-weighted imaging were used to classify white and grey matter injury according to a structured system, and incidental findings described. RESULTS: Preterm infants: 34 (18%) had white matter injury and 4 (2%) had grey matter injury. 51 (27%) infants had evidence of intracranial haemorrhage and 34 (18%) had punctate white matter lesions (PWMLs). Incidental findings were detected in 12 (6%) preterm infants. Term infants: no term infants had white or grey matter injury. Incidental findings were detected in 35 (35%); these included intracranial haemorrhage in 22 (22%), periventricular pseudocysts in 5 (5%) and PWMLs in 4 (4%) infants. From the whole cohort, 10 (3%) infants required referral to specialist services. CONCLUSIONS: One-fifth of very preterm infants without major parenchymal lesions have white or grey matter abnormalities at term-equivalent age. Incidental findings are seen in 6% of preterm and 35% of term infants. Overall, 3% of infants undergoing MRI for research require follow-up due to incidental findings. These data should help inform consent procedures for research and assist service planning for centres using 3T neonatal brain MRI for clinical purposes.

Long-read sequencing identifies an SVA_D retrotransposon insertion deep within the intron of ATP7A as a novel cause of occipital horn syndrome.

BACKGROUND: SINE-VNTR-Alu (SVA) retrotransposons move from one genomic location to another in a 'copy-and-paste' manner. They continue to move actively and cause monogenic diseases through various mechanisms. Currently, disease-causing SVA retrotransposons are classified into human-specific young SVA_E or SVA_F subfamilies. In this study, we identified an evolutionarily old SVA_D retrotransposon as a novel cause of occipital horn syndrome (OHS). OHS is an X-linked, copper metabolism disorder caused by dysfunction of the copper transporter, ATP7A. METHODS: We investigated a 16-year-old boy with OHS whose pathogenic variant could not be detected via routine molecular genetic analyses. RESULTS: A 2.8 kb insertion was detected deep within the intron of the patient's ATP7A gene. This insertion caused aberrant mRNA splicing activated by a new donor splice site located within it. Long-read circular consensus sequencing enabled us to accurately read the entire insertion sequence, which contained highly repetitive and GC-rich segments. Consequently, the insertion was identified as an SVA_D retrotransposon. Antisense oligonucleotides (AOs) targeting the new splice site restored the expression of normal transcripts and functional ATP7A proteins. AO treatment alleviated excessive accumulation of copper in patient fibroblasts in a dose-dependent manner. Pedigree analysis revealed that the retrotransposon had moved into the OHS-causing position two generations ago. CONCLUSION: This is the first report of a human monogenic disease caused by the SVA_D retrotransposon. The fact that the evolutionarily old SVA_D is still actively transposed, leading to increased copy numbers may make a notable impact on rare genetic disease research.

Atypical presentation of biotinidase deficiency: masquerading neuromyelitis optica spectrum disorder.

Biotinidase deficiency (BTD) is a treatable, inherited metabolic disorder commonly characterised by alopecia, dermatitis, seizures and developmental delay. It can also manifest as optic neuritis and myelitis; however, these are infrequently described in the literature. We report three cases who presented with quadriplegia and vision loss, initially managed as neuromyelitis optica spectrum disorder (NMOSD), based on neuroimaging findings. Two of them initially responded to immune therapy but relapsed after a few months, while one case showed no clinical improvement with immune therapy. The clinical presentation and neuroimaging findings in all three cases were consistent with NMOSD, leading to a delayed diagnosis of BTD. Antiaquaporin4 and antimyelin oligodendrocyte glycoprotein antibodies were negative in all patients. Urine organic acids reported raised markers of biotinidase or holocarboxylase synthase deficiency. Two of them had a dramatic response to biotin supplementation, showing significant improvement in motor function and vision.

Emergency medicine updates: Transient ischemic attack.

INTRODUCTION: Transient ischemic attack (TIA) is a condition commonly evaluated for in the emergency department (ED). Therefore, it is important for emergency clinicians to be aware of the current evidence regarding the diagnosis and management of this disease. OBJECTIVE: This paper evaluates key evidence-based updates concerning TIA for the emergency clinician. DISCUSSION: TIA is a harbinger of ischemic stroke and can result from a variety of pathologic causes. While prior definitions incorporated symptoms resolving within 24 h, modern definitions recommend a tissue-based definition utilizing advanced imaging to evaluate for neurologic injury and the etiology. In the ED, emergent evaluation includes assessing for current signs and symptoms of neurologic dysfunction, appropriate imaging to investigate for minor stroke or stroke risk, and arranging appropriate disposition and follow up to mitigate risk of subsequent ischemic stroke. Imaging should include evaluation of great vessels and intracranial arteries, as well as advanced cerebral imaging to evaluate for minor or subclinical stroke. Non-contrast computed tomography (CT) has limited utility for this situation; it can rule out hemorrhage or a large mass causing symptoms but should not be relied on for any definitive diagnosis. Noninvasive imaging of the cervical vessels can also be used (CT angiography or Doppler ultrasound). Treatment includes antithrombotic medications if there are no contraindications. Dual antiplatelet therapy may reduce the risk of recurrent ischemic events in higher risk patients, while anticoagulation is recommended in patients with a cardioembolic source. A variety of scoring systems or tools are available that seek to predict stroke risk after a TIA. The Canadian TIA risk score appears to have the best diagnostic accuracy. However, these scores should not be used in isolation. Disposition may include admission, management in an ED-based observation unit with rapid diagnostic protocol, or expedited follow-up in a specialty clinic. CONCLUSIONS: An understanding of literature updates concerning TIA can improve the ED care of patients with TIA.

Validation of an abbreviated Big Five personality inventory at large population scale: Psychometric structure and associations with common psychiatric and neurological disorders.

BACKGROUND: The five-factor model of personality, as quantified using instruments such as the Big Five Inventory, consists of broad personality domains including Extraversion, Agreeableness, Conscientiousness, Neuroticism (emotional instability), and Openness. Such instruments typically include >40 items. However, instruments with many items can be unwieldly and a cause of measurement error in clinical and cohort studies where multiple scales are sequenced. Conversely, established 5- and 10-item versions of the Big Five Inventory have poor reliability. Here, we developed and validated an abbreviated 18-item Big Five Inventory that balances efficiency, reliability and sensitivity. METHOD: We analysed three datasets (N = 59,797, N = 21,177, and N = 87,983) from individuals who participated in the online Great British Intelligence Test (GBIT) study, a collaborative citizen science project with BBC2 Horizon. We applied factor analyses (FA), predictive normative modelling, and one-sample t-tests to validate the 18-item version of the Big Five and to investigate its associations with psychiatric and neurological conditions. RESULTS: The 18-item version of the Big Five Inventory had higher validity and retest reliability compared to the other previously shortened versions in the literature, with comparable demographic associations to the full Big Five Inventory. It exhibited strong (i.e. large effect size) associations with psychiatric conditions, and moderate (small-medium) associations with neurological conditions. Neuroticism (emotional instability) was substantially higher in all psychiatric conditions, whereas Conscientiousness, Openness and Extraversion showed differential associations across conditions. CONCLUSION: The newly validated 18-item version of the Big Five provides a convenient means of measuring personality traits that is suitable for deployment in a range of studies. It retains psychometric structure, retest reliability and clinical-group sensitivity, as compared to the full original scale.

Reframing the clinical phenotype and management of cryptococcal meningitis.

Cryptococcal meningitis is an important global health problem, resulting from infection with the yeast Cryptococcus, especially Cryptococcus neoformans and Cryptococcus gattii, which cause a spectrum of disease ranging from pulmonary and skin lesions to life-threatening central nervous system involvement. The diagnosis and management of cryptococcal meningitis have substantially changed in recent years. Cryptococcal meningitis often occurs in people living with advanced HIV infection, though in high-income countries with robust HIV detection and treatment programmes, it increasingly occurs in other groups, notably solid-organ transplant recipients, other immunosuppressed patients and even immunocompetent hosts. This review outlines the clinical presentation, management and prognosis of cryptococcal meningitis, including its salient differences in people living with HIV compared with HIV-negative patients. We discuss the importance of managing raised intracranial pressure and highlight the advantages of improved multidisciplinary team working involving neurologists, infectious disease specialists and neurosurgeons.

Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study.

OBJECTIVES: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA). DESIGN AND SETTING: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study. PARTICIPANTS: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort). OUTCOMES: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model. RESULTS: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080). CONCLUSION: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Gender Disparities in the Academic Performance of Neurology Residents in Portugal.

Implicit bias has been linked to gender disparities in medical careers, impacting not only access to leadership positions but also early career opportunities. We aimed to evaluate if there were differences in the assessment of Neurology residents according to gender. We collected publicly available grades and rankings of two major evaluations that residents are submitted to, one at the beginning and another at the end of the neurology residency program, the National Board Exam and neurology examination, respectively. The National Board Examination is a multiple-choice gender-blinded evaluation, while the neurology examination is an oral gender-unblinded evaluation. We found that 36.5% of women and 21.6% of men were in the first quartile of the National Board Examination ranking, which reflects a similar representation among top classifications when assessed through a gender-blinded examination. On the other hand, the percentage of men who were in the top classification of NE, a gender-unblinded evaluation, was more than twice as high compared to women (37.8% vs 18.3%, p < 0.05). The findings of the present study may imply that there could be a disparity in women's career progression among neurology residents in Portugal, although the recruitment seems balanced between genders.

The prominent role of Charcot and the French neurological tradition in Latin America.

The establishment of neurology schools in Latin America during the late-nineteenth and early-twentieth centuries profoundly influenced the French neurology school. In the latter half of the nineteenth century, the neurology department at the Salpêtrière Hospital in Paris held a preeminent position as the global hub of neurology. Professor Jean-Martin Charcot, widely acclaimed as the father of modern neurology, was the most revered neurology professor of the nineteenth century. Many physicians from diverse countries across South America (notably Argentina, Uruguay, Peru, Brazil, and Colombia), the Caribbean (Cuba), and Mexico pursued specialized training in neurology under Charcot's tutelage, and even after his passing in 1893, they continued their training with his numerous disciples. As a result, nearly two centuries after the birth of Charcot, his enduring contributions to the field of neurology remain vibrantly influential, particularly in Latin America.