External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Patients' experiences with methylcobalamin injections in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with no definitive treatment. Vitamin B12 is not a Food and Drug Administration-approved treatment in the United States, although it has been prescribed off-label as ultra-high-dose methylcobalamin, which has been shown to be safe and effective in slowing functional decline in patients with ALS. This study evaluates the impact of Vitamin B12 injections on the quality of life of five patients. METHODS: Semi-structured interviews were conducted with the patients and caregivers. The data was carefully read, coded, and organized into themes and sub-themes by two independent researchers. RESULTS: The study found four themes and 11 subthemes from the data, including initial circumstances, administration of the injection, subjective experience with Vitamin B12, and outcomes and expectations. All participants recognized some benefits from Vitamin B12 injections, specifically increased energy, reduced fatigue, and improved balance. However, some patients had difficulty monitoring its specific effect due to the progressive nature of the disease. DISCUSSION: The flexibility offered by this intervention is beneficial for patients with declining mobility and strength who wish to adapt their treatment to their schedule. This work is a modest call to fill the existing gap in the literature and push for more randomized controlled trials investigating and clarifying the effects of Vitamin B12 injections on disease progression, muscle function, and quality of life in a small but diverse pool of patients with ALS.

Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.

OBJECTIVES: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment. METHODS: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention. RESULTS: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02). DISCUSSION: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence. It is a retrospective cohort study.

Long term quality of life follow-up and functional impairment study in patients with Hirayama disease.

Hirayama Disease (HD) is a focal motor neuron disorder generally affecting young adults with a male predominance who experience weakness and atrophy in distal upper extremity muscles in an asymmetric or unilateral pattern. Progression is insidious though significant weakness occurs during a progressive phase of the disease over 2-5 years. The long-term outcome of HD is not as well-known and, thus, this study presents self-reported outcomes from HD patients years after a diagnosis. Thirty HD patients reported quality of life (QOL) and other functional outcome measures after a mean of just over 11 years from diagnosis. Variables that predicted better or worse outcome were analyzed. Overall, QOL was affected by HD though most patients were functional with limitations. No clear attributes of patients or their disease predicted outcome.

HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP): Case based discussion of risk factors, clinical, and therapeutic considerations.

HTLV-1 is a retrovirus virus that infects CD4+ T cells. Most people with HTLV-1 infection remain asymptomatic but some may develop conditions such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma. HAM/TSP is characterized by progressive spasticity and weakness of the lower extremities, as well as loss of bladder control and sensory disturbances. The risk of developing HAM/TSP is associated with the duration of infection and the proviral load. There is currently no cure for the disease but medications can help manage symptoms and slow the progression of the disease. This is the case of a 66-year-old female who presented with nonspecific symptoms of weakness and spasticity in a hospital in Connecticut and was subsequently diagnosed with HAM/TSP. The patient's diagnosis highlights the importance of considering diseases previously confined to specific endemic regions in a globalized world where increased emigration and population mixing can occur. Early identification and management of such cases is essential for optimizing patient outcomes and quality of life.

Virology, ecology, epidemiology, pathology, and treatment of eastern equine encephalitis.

Eastern equine encephalitis (EEE) was one of the first-recognized neuroinvasive arboviral diseases in North America, and it remains the most lethal. Although EEE is known to have periodic spikes in infection rates, there is increasing evidence that it may be undergoing a change in its prevalence and its public health burden. Numerous factors shape the scope of EEE in humans, and there are important similarities with other emergent viral diseases that have surfaced or strengthened in recent years. Because environmental and ecological conditions that broadly influence the epidemiology of arboviral diseases also are changing, and the frequency, severity, and scope of outbreaks are expected to worsen, an expanded understanding of EEE will have untold importance in coming years. Here we review the factors shaping EEE transmission cycles and the conditions leading to outbreaks in humans from an updated, multidomain perspective. We also provide special consideration of factors shaping the virology, host-vector-environment relationships, and mechanisms of pathology and treatment as a reference for broadening audiences.

Financial Literacy Among Medical Trainees and Faculty: A Pilot Study.

INTRODUCTION: Medical education systems are trained to produce efficient, thorough clinicians. These programs provide limited training on personal finances. The current socioeconomic climate for medical trainees includes increasing education debt and stagnating reimbursement. We conducted a survey-based cross-sectional pilot study at an academic institution targeted at residents, fellows, and attendings of all medical specialties. Our aim was to understand baseline levels of financial literacy at different training and career stages, which can inform targeted interventions to improve this crucial aspect of physician well-being. METHODS: A survey was devised with the assistance of a certified financial planner. This survey was distributed at an academic institution targeting residents, fellows, and attendings. The survey was anonymous, and no identifying data were collected. Two reminders were sent to subjects to complete the survey. RESULTS: A total of 50 physicians completed the survey in 2021. There were eight responses from interns, 14 responses from residents (post-graduate year 2 or later), 14 responses from fellows, and nine responses from attendings. The majority of our respondents reported not having any particular financial education, and over 70% of respondents reported that their graduate education had not provided them with the tools needed for personal financial success. CONCLUSION: Financial education and financial literacy are important topics that need to be further incorporated into the medical education pathway. Physicians are not well equipped in this realm, and further training is necessary. This study provides pilot data that highlight important aspects of physician knowledge and practices in regard to finances.

"Hot nose" sign in brain death.

Background: Brain death testing is a rigorous process in which meticulous examination is crucial. In certain cases, ancillary testing is required. Case Description: A 30-year-old male presented to the emergency room after a motor vehicle accident and was found to have subarachnoid hemorrhage and subdural hematoma. The examination was notable for the absence of brainstem responses. A nuclear medicine brain scan was completed which showed carotid arterial activity up to the level of the skull base with no intracranial arterial activity above with a "hot nose" sign consistent with brain death. Conclusion: The "hot nose" sign has been described in brain-dead patients and is postulated to occur due to increased flow to the nose through the external carotid artery.

Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions.

OBJECTIVES: Plasmapheresis (PLEX) and intravenous immunoglobulin (IVIg) are commonly used to treat autoimmune neuromuscular disorders, including myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and other autoimmune neurological disorders. The side effect profiles of these therapies vary, and concern has been raised regarding the safety of PLEX in the elderly population. In this study, we have examined the pattern of PLEX and IVIg use for autoimmune neurological disorders at a single facility and in a national database, focusing on the complications in elderly patients. METHODS: We performed a retrospective chart review of adult patients at our institution receiving PLEX or IVIg for any autoimmune neuromuscular or neuro-immunological disease. Next, we analyzed the National Inpatient Sample database to confirm the trend in IVIg and PLEX use from 2012 to 2018 for a set of neuromuscular and neuro-immunological primary diagnoses. RESULTS: IVIg was overall favored over PLEX. The adverse effects were similar among elderly patients (age ≥65 years) compared with younger patients (<65 years) in our institution, even after adequate matching of patients based on age, sex, and medical history. We examined the National Inpatient Sample dataset and noted increasingly higher frequency of IVIg use, consistent with the findings from our institution or facility. CONCLUSIONS: Both PLEX and IVIg are safe therapeutic choices in adult patients with autoimmune neuromuscular disorders and other neuro-immunological diseases and can be safely administered in the appropriate clinical setting.

The Impact of COVID-19 on Families With Pediatric Muscular Dystrophy Patients.

The coronavirus disease 2019 (COVID-19) pandemic resulted in unprecedented changes in daily activities and healthcare services. In the United States, stay-at-home orders and social distancing measures were put, and school closures impacted many students. The psychological impact of the COVID-19 pandemic has been shown to have wide-ranging and long-term effects. With school closures and limitations in in-person visits and provider care, we hypothesized that the patients with pediatric muscular dystrophies and neuromuscular conditions were more vulnerable to the restriction posed by this pandemic. This survey-based study examined the psychosocial impact of this pandemic on pediatric patients with neuromuscular disorders and caregiver burden through chart review and self-reports via survey administration using a validated tool (COVID-19 Exposure and Family Impact Scales {CEFIS}). The majority of families reported that they had a stay-at-home order (91.7%), schools/childcare centers were closed (87.5%), their children's education was disrupted (83.3%), and they were unable to visit or care for a family member (58.3%). Parents/caregivers felt that the COVID-19 pandemic made parenting a little bit worse (mean = 2.6 ± 0.96) and made it more difficult to care for the elderly or those with disabilities in the family (mean = 2.6 ± 0.95) and for their child with a neuromuscular disability (mean = 2.6 ± 0.91). Our data highlights the significant impact of the COVID-19 pandemic on the lives of families and caregivers of pediatric patients with muscular dystrophies.

Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. METHODS: We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. RESULTS: Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60-187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07), male sex (OR, 0.44; 95% CI, 0.24-0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29-0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. CONCLUSION: Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.

Imaging biomarkers in the idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are a group of acquired muscle diseases with muscle inflammation, weakness, and other extra-muscular manifestations. IIMs can significantly impact the quality of life, and management of IIMs often requires a multi-disciplinary approach. Imaging biomarkers have become an integral part of the management of IIMs. Magnetic resonance imaging (MRI), muscle ultrasound, electrical impedance myography (EIM), and positron emission tomography (PET) are the most widely used imaging technologies in IIMs. They can help make the diagnosis and assess the burden of muscle damage and treatment response. MRI is the most widely used imaging biomarker of IIMs and can assess a large volume of muscle tissue but is limited by availability and cost. Muscle ultrasound and EIM are easy to administer and can even be performed in the clinical setting, but they need further validation. These technologies may complement muscle strength testing and laboratory studies and provide an objective assessment of muscle health in IIMs. Furthermore, this is a rapidly progressing field, and new advances are going to equip care providers with a better objective assessment of IIMS and eventually improve patient management. This review discusses the current state and future direction of imaging biomarkers in IIMs.

Neurologic Complications of Babesiosis, United States, 2011-2021.

Babesiosis is a globally distributed parasitic infection caused by intraerythrocytic protozoa. The full spectrum of neurologic symptoms, the underlying neuropathophysiology, and neurologic risk factors are poorly understood. Our study sought to describe the type and frequency of neurologic complications of babesiosis in a group of hospitalized patients and assess risk factors that might predispose patients to neurologic complications. We reviewed medical records of adult patients who were admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, during January 2011-October 2021 with laboratory-confirmed babesiosis. More than half of the 163 patients experienced >1 neurologic symptoms during their hospital admissions. The most frequent symptoms were headache, confusion/delirium, and impaired consciousness. Neurologic symptoms were associated with high-grade parasitemia, renal failure, and history of diabetes mellitus. Clinicians working in endemic areas should recognize the range of symptoms associated with babesiosis, including neurologic.

Hemorrhagic Conversion of Acute Ischemic Stroke.

Stroke is a leading cause of morbidity and mortality worldwide; a serious complication of ischemic stroke is hemorrhagic transformation. Current treatment of acute ischemic stroke includes endovascular thrombectomy and thrombolytic therapy. Both of these treatment options are linked with increased risks of hemorrhagic conversion. The diagnosis and timely management of patients with hemorrhagic conversion is critically important to patient outcomes. This review aims to discuss hemorrhagic conversion of acute ischemic stroke including discussion of the pathophysiology, review of risk factors, imaging considerations, and treatment of patients with hemorrhagic conversion.

Neurological sequelae of vaccines.

IMPORTANCE: Vaccines are a safe and efficacious way to prevent a variety of infectious diseases. Over the course of their existence, vaccines have prevented immeasurable morbidity and mortality in humans. Typical symptoms of systemic immune activation are common after vaccines and may include local soreness, myalgias, nausea, and malaise. In the vast majority of cases, the severity of the infectious disease outweighs the risk of mild adverse reactions to vaccines. Rarely, vaccines may be associated with neurological sequela that ranges in severity from headache to transverse myelitis, acute disseminated encephalomyelitis, and Guillain-Barre syndrome (GBS). Often, a causal link cannot be confirmed, and it remains unclear if disease onset is directly related to a recent vaccination. OBSERVATIONS: This review serves to summarize reported neurologic sequelae of commonly used vaccines. It will also serve to discuss potential pathogenesis. It is important to note that many adverse events or reactions to vaccines are self-reported into databases, and causal proof cannot be obtained. CONCLUSIONS AND RELEVANCE: Recognition of reported adverse effects of vaccines plays an important role in public health and education. Early identification of these symptoms can allow for rapid diagnosis and potential treatment. Vaccines are a safe option for prevention of infectious diseases.

A Case of West Nile Encephalitis: Neuroimaging Findings and Clinico-Radiological Mismatch.

West Nile Virus, an arthropod-borne RNA virus, may result in severe neurological disease. West Nile neuroinvasive disease is characterized by meningitis, encephalitis, and possible acute flaccid paralysis. Classically, signal intensity abnormalities on T2-weighted magnetic resonance images are associated with poor outcomes. Herein, we present a case of previous West Nile encephalitis with diffuse leukoencephalopathy on imaging that demonstrates a favorable clinical outcome with limited neurologic sequelae. A 53-year-old male presented to the hospital with one month of headaches, dizziness, generalized weakness, and a seizure. His initial neurologic exam was notable for wide-based gait and imbalance. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse bilateral white matter signal hyperintensities without contrast enhancement, suggestive of leukoencephalopathy. His lumbar puncture revealed lymphocytic pleocytosis and infectious studies demonstrated positive West Nile Virus immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) and serum with negative immunoglobulin M (IgM) in both CSF and serum, suggestive of previous infection. A diagnosis of sequelae of West Nile neuroinvasive disease was made. He was started on anti-seizure medications without further seizures. At his subsequent nine-month follow-up visit, he remained asymptomatic without weakness, headaches, or confusion. Repeat MRI demonstrated interval improvement of white matter signal change. This case report highlights that West Nile neuroinvasive disease may present with profound white matter changes on MRI with limited clinical symptoms and long-term neurologic sequelae. Further research is needed to identify imaging correlation with symptom severity in this disease.

Myasthenia Gravis in the Setting of Immune Checkpoint Inhibitor Therapy: Practical Considerations and Opinion-Based Approach to Acute Management.

Use of immune checkpoint inhibitors (ICI) is increasing in patients with oncologic disease. Three classes of checkpoint inhibitors exist: anti-PD1 (nivolumab, pembrolizumab), anti-CTLA4 (ipilimumab), and anti-PDL1 (atezolizumab, avelumab, durvalumab). ICI therapy has been used in multiple malignancies including renal cell cancer, non-small-cell lung cancer, and melanoma. These therapies have led to improved oncologic treatment and outcomes in patients but can lead to immune-related or inflammatory adverse effects. Neuromuscular system side effects, particularly at the neuromuscular junction, have been observed, including myasthenia gravis (MG). This narrative review serves to summarize key available information regarding myasthenia gravis in the setting of immune checkpoint inhibitor use including the molecular targets of checkpoint inhibitors, the clinical manifestations of MG in patients with checkpoint inhibitor therapy, and potential treatment options. Studies have shown that the use of checkpoint inhibitor therapy can trigger MG, and that patients with ICI-related MG can have more severe disease. Recognition and understanding of the range of neurologic complications, including neuromuscular disorders, which can be seen with ICI therapy is a critical step toward developing better treatment algorithms and improved clinical outcomes. Future investigations which include deep mechanistic studies to further our understanding of the immunopathologic triggers and predictive markers of ICI-related MG will be important to address the current knowledge gaps.

Characteristics and outcomes of postpartum cerebral venous sinus thrombosis: A subgroup analysis of the ACTION-CVT study.

BACKGROUND AND PURPOSE: There is a relative paucity of data regarding long-term outcomes and treatment-related complications in women of childbearing age with cerebral venous sinus thrombosis (CVST). We sought to determine whether outcomes differ in women of childbearing age with versus without postpartum CVST. METHODS: We retrospectively analysed 373 non-pregnant females of childbearing age (18-45 years) included in the multicenter observational Anticoagulation in the Treatment of Cerebral Venous Thrombosis study (ACTION-CVT). Comparisons were made between postpartum (first 12 weeks from delivery, n=38 [10.2%]) versus non-postpartum women (n=335 [89.8%]). The primary outcomes of interest were one-year risk of all-cause death, venous thromboembolism (VTE) recurrence, and major hemorrhage (i.e., new or worsening intracranial hemorrhage or major extracranial hemorrhage). Secondary outcomes were the discharge disposition and modified Rankin Scale (mRS) score at discharge and 90 days. RESULTS: Postpartum status was associated with greater risk of seizures (42.1% versus 20.9%, p=0.003), venous infarction (47.4% versus 29.5%, p=0.025), intracranial hemorrhage (55.3% versus 36.1%, p=0.022), and requirement for neurosurgical treatment (13.2% versus 3.6%, p=0.021). There was no significant association with one year all cause death (N=373 HR=1.35, 95%-CI=0.15-11.87, p=0.784), VTE recurrence (N=373, HR=1.27, 95%-CI=0.45-3.59, p=0.648), major hemorrhage (N=373, HR=1.36, 95%-CI=0.46-4.0, p=0.581) as well as excellent (mRS[0-1]: OR=1.58, 95%-CI=0.4-7.1, p=0.554) and good (mRS[0-2]: OR=0.92, 95%-CI=0.2-4.27, p=0.918) 90-day mRS. Results were similar after adjustment for potential confounders. CONCLUSIONS: Although CVST in the 12-week postpartum period was more frequently associated with early complications, 90-day functional disability and one-year outcomes were similar to women with CVST unrelated to pregnancy.