Predictors of hematologic response and survival with stem cell transplantation in AL amyloidosis: A 25-year longitudinal study.

High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow-up interval of 8 years, the median event-free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1 ng/mL, and serum creatinine >2.0 mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low-risk (0 factors), intermediate-risk (1 factor), and high-risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p < .001). The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.

Optimizing the operation of an electrodiagnostic laboratory during the COVID-19 pandemic: A 6-month single-center experience.

INTRODUCTION/AIMS: The initial surge of the coronavirus disease-2019 (COVID-19) pandemic in early 2020 led to widespread cancellation of elective medical procedures in the United States, including nonurgent outpatient and inpatient electrodiagnostic (EDx) studies. As certain regions later showed a downtrend in daily new cases, EDx laboratories have reopened under the guidance of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). In our reopening experience guided by the AANEM, we measured relevant outcomes to determine further workflow adaptations. We aimed to detail our experience and share the lessons learned. METHODS: We reviewed the clinical volumes, billing data, diagnosis distributions, and rates of COVID-19 exposure and transmission among patients and staff in our EDx laboratory during the first 6 months of reopening, starting on June 1, 2020. For context, we detailed the recent AANEM guidelines we adopted at our laboratory, supplemented by other consensus statements. RESULTS: We completed 816 outpatient studies from June 1 to December 1, 2020, reaching 97% of the total volume and 97% of total billing compared with the same time period in 2019. The average relative value units per study were similar. There were no major shifts in diagnosis distributions. We completed 10 of 12 requested inpatient studies during this period. There were no known COVID-19 transmissions between patients and staff. DISCUSSION: Our experience suggests that it is possible to safely operate an EDx laboratory under the guidance of the AANEM and other experts, with clinical volume and billing rates comparable to pre-pandemic baselines.

Posterior Reversible Encephalopathy Syndrome in Patients with Coronavirus Disease 2019: Two Cases and A Review of The Literature.

INTRODUCTION: Encephalopathy is a common complication of coronavirus disease 2019. Although the encephalopathy is idiopathic in many cases, there are several published reports of patients with posterior reversible encephalopathy syndrome in the setting of coronavirus disease 2019. OBJECTIVE: To describe the diverse presentations, risk factors, and outcomes of posterior reversible encephalopathy syndrome in patients with coronavirus disease 2019. METHODS: We assessed patients with coronavirus disease 2019 and a diagnosis of posterior reversible encephalopathy syndrome at our institution from April 1 to June 24, 2020. We performed a literature search to capture all known published cases of posterior reversible encephalopathy syndrome in patients with coronavirus disease 2019. RESULTS: There were 2 cases of posterior reversible encephalopathy syndrome in the setting of coronavirus 2019 at our institution during a 3-month period. One patient was treated with anakinra, an interleukin-1 inhibitor that may disrupt endothelial function. The second patient had an underlying human immunodeficiency virus infection. We found 13 total cases in our literature search, which reported modest blood pressure fluctuations and a range of risk factors for posterior reversible encephalopathy syndrome. One patient was treated with tocilizumab, an interleukin-6 inhibitor that may have effects on endothelial function. All patients had an improvement in their neurological symptoms. Interval imaging, when available, showed radiographic improvement of brain lesions. CONCLUSIONS: Risk factors for posterior reversible encephalopathy syndrome in patients with coronavirus disease 2019 may include underlying infection or immunomodulatory agents with endothelial effects in conjunction with modest blood pressure fluctuations. We found that the neurological prognosis for posterior reversible encephalopathy syndrome in the setting of coronavirus disease 2019 infection is favorable. Recognition of posterior reversible encephalopathy syndrome in this patient population is critical for prognostication and initiation of treatment, which may include cessation of potential offending agents and tight blood pressure control.

Neurological Complications of Leprosy.

Leprosy is a challenging international health concern. Despite tremendous efforts in reducing worldwide disease prevalence in the past decades, some countries remain endemic and are plagued by high levels of disability. The neurological complications of leprosy are varied and complex, with current research focused on evaluating tools for earlier diagnosis of neuropathy, especially in resource-limited countries. While treatment with multidrug therapy is highly effective, active research aims to simplify regimens to improve adherence, minimize adverse effects, and prevent antimicrobial resistance. Although promising progress has been made in the past decades, further efforts are needed to push the international community toward achieving worldwide elimination.

Laboratory Evaluation of Peripheral Neuropathy.

Peripheral neuropathy is a common neurological disorder, with high prevalence especially in the aged population. The general evaluative approach is to first identify the type of peripheral neuropathy prior to investigating for a possible underlying etiology, which is an increasingly important endeavor, as many causes of peripheral neuropathy are now recognized as treatable. To this end, laboratory testing plays an important adjunctive role to a detailed history and examination. This review will discuss possible diagnostic laboratory testing pathways for different types of peripheral neuropathy, with the goal of minimizing costs and false-positive results while maximizing the likelihood of identifying a potentially reversible etiology.

New Media, Technology and Neurology Education.

The use of technology in neurology education has revolutionized many aspects of medical teaching, addressing some important challenges of modern education such as information overload and the unique needs of millennial learners. However, it also has inherent problems, such as depersonalization and high development costs. Due to the heterogeneity of different applications, it is difficult to establish general principles to guide front line educators, but it may be possible to describe "minimum" best practice elements. In this article, we examine commonalities of some of the most successful uses of technology in neurology education. We suggest the following for effective application of technology: (1) match technology to predetermined educational objectives, (2) characterize learners in relationship to technology, (3) optimize how technological components fit into the learning environment, (4) monitor and manage learner engagement with technology, (5) perform cost analyses, and (6) explore opportunities for educational scholarship and research.

Using learning analytics to evaluate a video-based lecture series.

BACKGROUND: The video-based lecture (VBL), an important component of the flipped classroom (FC) and massive open online course (MOOC) approaches to medical education, has primarily been evaluated through direct learner feedback. Evaluation may be enhanced through learner analytics (LA) - analysis of quantitative audience usage data generated by video-sharing platforms. METHODS AND RESULTS: We applied LA to an experimental series of ten VBLs on electroencephalography (EEG) interpretation, uploaded to YouTube in the model of a publicly accessible MOOC. Trends in view count; total percentage of video viewed and audience retention (AR) (percentage of viewers watching at a time point compared to the initial total) were examined. The pattern of average AR decline was characterized using regression analysis, revealing a uniform linear decline in viewership for each video, with no evidence of an optimal VBL length. Segments with transient increases in AR corresponded to those focused on core concepts, indicative of content requiring more detailed evaluation. We propose a model for applying LA at four levels: global, series, video, and feedback. DISCUSSION AND CONCLUSIONS: LA may be a useful tool in evaluating a VBL series. Our proposed model combines analytics data and learner self-report for comprehensive evaluation.

Exacerbation of myasthenia gravis in a patient with melanoma treated with pembrolizumab.

INTRODUCTION: While anticancer immunotherapies have traditionally focused on activation of the immune system, there is recent interest in disinhibition of the natural antitumor immune response by targeting immune checkpoints such as cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). One humanized monoclonal antibody against PD-1, pembrolizumab, was recently approved for treatment of metastatic malignant melanoma. METHODS: We report exacerbation of myasthenia gravis (MG) after treatment with pembrolizumab and provide a brief literature review. RESULTS: We describe a 75-year-old man with stable MG who experienced myasthenic crisis in the setting of pembrolizumab treatment. A concurrent azathioprine taper was a possible although unlikely contributor given the short time interval between taper and exacerbation. CONCLUSIONS: As long-term data become available regarding the adverse immune effects of novel checkpoint inhibitors, clinicians should be mindful of their risks/benefits and of possible autoimmune disease exacerbation. Muscle Nerve 54: 157-161, 2016.

Meningitis Caused by Candida Dubliniensis in a Patient with Cirrhosis: A Case Report and Review of the Literature.

Candida species, including Candida dubliniensis, are a rare cause of meningitis. Herein, we report the second case of C. dubliniensis meningitis in a 49-year-old man with a history of hepatitis C virus-related cirrhosis, substance use disorder, and recent exposure to intravenous antibiotic therapy, presenting with confusion, abnormal gait, and urinary incontinence. Magnetic resonance imaging (MRI) of the brain showed marked hydrocephalus and leptomeningeal enhancement. Initial cerebrospinal fluid (CSF) studies were concerning for bacterial meningitis, although cultures were negative. Despite empiric treatment with broad-spectrum antibiotics, the patient's mental status declined. The diagnosis of C. dubliniensis meningitis was not made until the third lumbar puncture. The patient was treated with liposomal amphotericin B and flucytosine. Despite improvement of hydrocephalus on MRI of the brain and sterilization of CSF, the patient's mental status declined and he expired. This case highlights the difficulty in the diagnosis of C. dubliniensis meningitis as multiple lumbar punctures may be necessary. C. dubliniensis meningitis should be considered in the differential diagnosis for a patient with risk factors such as end-stage liver disease, human immunodeficiency virus infection, recent chemotherapy, substance use disorders, and recent broad-spectrum antibiotic use. A high index of suspicion is necessary as delay in initiation of therapy is associated with high mortality. The optimal treatment strategy has not been determined.

Computer-based teaching module design: principles derived from learning theories.

CONTEXT: The computer-based teaching module (CBTM), which has recently gained prominence in medical education, is a teaching format in which a multimedia program serves as a single source for knowledge acquisition rather than playing an adjunctive role as it does in computer-assisted learning (CAL). Despite empirical validation in the past decade, there is limited research into the optimisation of CBTM design. This review aims to summarise research in classic and modern multimedia-specific learning theories applied to computer learning, and to collapse the findings into a set of design principles to guide the development of CBTMs. METHODS: Scopus was searched for: (i) studies of classic cognitivism, constructivism and behaviourism theories (search terms: 'cognitive theory' OR 'constructivism theory' OR 'behaviourism theory' AND 'e-learning' OR 'web-based learning') and their sub-theories applied to computer learning, and (ii) recent studies of modern learning theories applied to computer learning (search terms: 'learning theory' AND 'e-learning' OR 'web-based learning') for articles published between 1990 and 2012. The first search identified 29 studies, dominated in topic by the cognitive load, elaboration and scaffolding theories. The second search identified 139 studies, with diverse topics in connectivism, discovery and technical scaffolding. Based on their relative representation in the literature, the applications of these theories were collapsed into a list of CBTM design principles. RESULTS: Ten principles were identified and categorised into three levels of design: the global level (managing objectives, framing, minimising technical load); the rhetoric level (optimising modality, making modality explicit, scaffolding, elaboration, spaced repeating), and the detail level (managing text, managing devices). CONCLUSIONS: This review examined the literature in the application of learning theories to CAL to develop a set of principles that guide CBTM design. Further research will enable educators to take advantage of this unique teaching format as it gains increasing importance in medical education.

Using Learning Analytics to Evaluate the Clinical Education Podcast Format.

Learning analytics has been rigorously applied to various forms of e-learning, but not to the evaluation of clinical education podcasts. We created a podcast series using the Anchor by Spotify platform, uploading an episode every 2 weeks starting on March 30, 2021. We examined analytics data using a censoring date of November 1, 2022. Based on 29,747 total plays, average audience retention declined 10%/minute until an inflection point at 2.5 minutes, followed by a steady decline of 1.8%/minute. With a maximum episode length of 17 minutes, we did not identify a limit on learner attention for short-form podcasts.

Social Work in Outpatient Neurology at a Safety-Net Hospital: A 200-Hour Profile.

Social work plays a critical role in preventive health and mitigation of healthcare disparities, but few studies focus on its role in multi-specialty clinics serving marginalized populations. We aimed to characterize the role of outpatient neurology social work at an urban, safety-net hospital. In December 2021, we introduced a dedicated social worker to a neurology clinic primarily caring for an underserved patient population. We logged and characterized the first 200 consecutive hours of patient encounters, classifying interventions based on a recently popularized 10-category scheme in social work literature derived from natural language processing and machine learning algorithms. We characterized 125 encounters with neurology patients referred to social work. The neurology social worker spent the greatest amount of time on care coordination (40%), followed by housing insecurity (14%) and applications and reporting (11%). Interventions that required the most time per case included housing (129 min), applications and reporting (120 min), care coordination (96 min). The majority of interventions were directly related to the patient's underlying neurologic disorder, highlighting the importance of a neurology-specific social worker. Embedding a social worker in a multi-specialty neurology clinic may address many of the root causes of neurologic health disparities.

Podcast-Based Medical Education and Content Alignment with National Education Bodies.

Introduction: Despite the rapid expansion of medical education podcasts in the past decade, there are few efforts to characterize the landscape of available content for specific medical specialties. We trialed a method of rigorous characterization for the field of neurology. Materials and Methods: Using a censoring date of July 25, 2022, we queried the top three podcast platforms for neurology education podcasts: Apple Podcasts, Spotify, and Google Podcasts. We characterized podcasts based on total number of episodes, episode release frequency, target audience, and affiliation type. We characterized individual episodes by length and primary content area as defined by the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Psychiatry and Neurology (ABPN). We compared content availability with content recommendations from these education bodies. Results: We identified 30 podcasts sharing 1772 episodes and totaling 46,287 min. The ACGME subspecialties most frequently covered were vascular neurology (5082 total min, 11%), neuroimmunology (4,406, 10%), and neuromuscular diseases (3,771, 8%). Subjects that were underrepresented included palliative neurology (89 min, 0.2%), neuropathology (95 min, 0.2%), and bioethics (171 min, 0.4%). The coverage of ABPN examination topics varied substantially from the content distribution for the examination. Discussion: The current landscape of neurology education podcasts features heterogeneous coverage of topics and varies considerably from recommended distribution of content by national education bodies. As podcasts have tremendous potential in supplementing neurology education, characterizing available content may help various stakeholders in the neurology education pipeline optimize the use of this e-learning modality. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01971-0.

Clinical Reasoning: A 23-Year-Old Man With Progressive Asymmetric Weakness and Numbness.

We report a case of a 23-year-old man who presented with progressive asymmetric weakness and numbness in his distal extremities over 4 months, with initial symptoms starting days after a coronavirus 2019 (COVID-19) vaccine booster. Initial neurologic examination was notable for distal weakness of both upper and lower extremities that was more pronounced on the left, complete areflexia, and decreased distal sensation to pinprick and vibration without loss of proprioception. Nerve conduction studies demonstrated a generalized, non-length-dependent, sensorimotor, demyelinating polyneuropathy, with conduction block seen in multiple compound muscle action potentials. Sensory nerve action potentials were normal in absolute terms but had asymmetric amplitudes.Based on the patient's nerve conduction studies, he was diagnosed with a specific immune-mediated neuromuscular disorder. He was started on intravenous immunoglobulin, but within days of the first infusions experienced a rare and potentially life-threatening complication. He received appropriate treatment and was started on alternative immunotherapy, after which his symptoms improved.Our case exemplifies the features of a specific subtype of a more common immune-mediated neuromuscular diagnosis with unique elements of history, examination, and nerve conduction studies that required interpretation in the clinical context. We also discuss a rare side effect of a commonly used immunotherapy and its risk factors and comment on the likelihood that this diagnosis may be related to a preceding COVID-19 vaccine booster.

Hereditary gelsolin amyloidosis: a rare cause of cranial, peripheral and autonomic neuropathies linked to D187N and Y447H substitutions.

INTRODUCTION: Hereditary gelsolin (AGel) amyloidosis is a systemic disease that is characterised by neurologic, ophthalmologic, dermatologic, and other organ involvements. We describe the clinical features with a focus on neurological manifestations in a cohort of patients with AGel amyloidosis referred to the Amyloidosis Centre in the United States. METHODS: Fifteen patients with AGel amyloidosis were included in the study between 2005 and 2022 with the permission of the Institutional Review Board. Data were collected from the prospectively maintained clinical database, electronic medical records and telephone interviews. RESULTS: Neurologic manifestations were featured in 15 patients: cranial neuropathy in 93%, peripheral and autonomic neuropathy in 57% and bilateral carpal tunnel syndrome in 73% of cases. A novel p.Y474H gelsolin variant featured a unique clinical phenotype that differed from the one associated with the most common variant of AGel amyloidosis. DISCUSSION: We report high rates of cranial and peripheral neuropathy, carpal tunnel syndrome and autonomic dysfunction in patients with systemic AGel amyloidosis. The awareness of these features will enable earlier diagnosis and timely screening for end-organ dysfunction. The characterisation of pathophysiology will assist the development of therapeutic options in AGel amyloidosis.

Using Technology Adoption Theories to Maximize the Uptake of E-learning in Medical Education.

Introduction: While the use of e-learning tools in medical education is guided by robust literature on their design and evaluation, there is sparse literature on strategies that maximize their adoption among trainees. Methods: In this scoping review, we searched Web of Science for studies on technology adoption theories as applied to education, using a final censoring date of August 1, 2021. Results: Based on our findings, we identified three representative theories: (1) technology acceptance model, (2) technology adoption life cycle, and (3) domestication theory. Discussion: We describe these theories in detail, examine their prior applications, and propose specific uses within medical e-learning.

Isolated High-Grade Malignancy of the Spinal Cord Presenting as Longitudinally Extensive Transverse Myelitis.

This article characterizes 2 cases of longitudinally extensive transverse myelitis (LETM) that did not respond to immunotherapy and were diagnosed by biopsy as primary central nervous system (CNS) malignancies. Diffuse H3 K27M-mutant glioma is a recently described entity with very few cases of isolated spinal disease described in adults. Primitive neuroectodermal tumor is similarly uncommon in the spinal cord. Malignancies should be considered in patients who fail to improve with immunomodulatory therapy. We believe the experiences of our center will raise awareness about that point, broaden the existing understanding of the diagnostic approach to LETM, and highlight the need for additional studies.

Two-Year Profile of Preventable Errors in Hospital-Based Neurology.

Background and Objectives: Medical errors are estimated to cause 7,000 deaths and cost 17-29 billion USD per year, but there is a lack of published real-world data on preventable errors, in particular in hospital-based neurology. We sought to characterize the profile of errors that occur on the inpatient neurology services at our institution to inform strategies on future error prevention. Methods: We reviewed all cases of preventable errors occurring on the inpatient neurology services from July 1, 2018, to June 30, 2020, logged in institutional error reporting systems and reviewed at departmental morbidity and mortality conferences (M&MC). Each case was characterized by primary category of error, level of harm as determined by the Agency for Healthcare Research & Quality Common Format Harm Scale version 1.2, primary intervention, and recurrence within 1 year, with a final censoring date of June 30, 2021. Results: Of 72 cases, 43 (60%) were attributed to errors in clinical decision making and 20 (28%) to systems or electronic health record-related errors. The majority of cases resulted in in-conference education on systems-based errors (29%) at departmental M&MCs followed by in-conference education on clinical neurology (25%). Among errors classified primarily as clinical, 28% were addressed via systems-based interventions including in-conference education on systems issues and changes in written protocol. In 23 cases (32%), a similar error recurred within 1 year of the presentation. In total, 7 cases (10%) resulted in a change in written protocol, none with recurrences. Discussion: Systems-based interventions may reduce both clinical and systems-based errors, and protocol changes are effective when feasible. Given the important goal of optimizing care for every patient, quality leaders should conduct continuous audits of preventable errors and quality improvement systems in their clinical areas.