A Nail in the Brain.

Transorbital penetrating brain injuries (TOPI) are rare. We report a case of industrial injury that resulted in perforating eye injury and intracranial foreign body by a nail gun. A 30-year-old man accidentally fired a nail gun onto his left eye at his construction workplace while handling the malfunctioned equipment and sustained a perforating injury of the left eye with intracranial foreign body. The misfired nail was lodged in his frontal lobe of the brain. He also suffered laceration wounds of the lateral canthus of the left eye and fractures of the left orbital floor and roof. He underwent emergency bicoronal craniotomy and removal of intracranial foreign body, followed by left eye examination under anaesthesia as well as scleral toilet and suturing. The nail was successfully removed. He recovered well with no neurological deficit and was discharged on postoperative day 5 with a Glasgow Coma Scale score of 15; however, his left eye vision remained no perception of light. Work-related eye injuries can be debilitating and are largely preventable.

What are COVID-19 Patient Preferences for and Experiences with Virtual Care? Findings From a Scoping Review.

Virtual care became a routine method for healthcare delivery during the coronavirus disease 2019 (COVID-19) pandemic. Patient preferences are central to delivering patient-centered and high-quality care. The pandemic challenged healthcare organizations and providers to quickly deliver safe healthcare to COVID-19 patients. This resulted in varied implementation of virtual healthcare services. With an increased focus on remote COVID-19 monitoring, little research has examined patient experiences with virtual care. This scoping review examined patient experiences and preferences with virtual care among community-based self-isolating COVID-19 patients. We identified a paucity of literature related to patient experiences and preferences regarding virtual care. Few articles focused on patient experiences and preferences as a primary outcome. Our research suggests that (1) patients view virtual care positively and to be feasible to use; (2) patient access to technology impacts patient satisfaction and experiences; and (3) to enhance the patient experience, healthcare organizations and providers need to support patient use of technology and resolve technology-related issues. When planning virtual care modalities, purposeful consideration of patient experiences and preferences is needed to deliver quality patient-centered care.

A new approach to digital health? Virtual COVID-19 care: A scoping review.

Aims: The use of virtual care enabled by digital technologies has increased, prompted by public health restrictions in response to COVID-19. Non-hospitalized persons in the acute phase of COVID-19 illness may have unique health needs while self-isolating in the community. This scoping review aimed to explore the nature of care, the use of digital technologies, and patient outcomes arising from virtual care among community-based self-isolating COVID-19 patients. Methods: Literature searches for peer-reviewed articles were conducted in four bibliographic databases: CINAHL, Medline, Embase and Cochrane Database of Systematic Reviews between January and February 2022, followed by hand-searching reference lists of included articles. Two levels of screening using defined eligibility criteria among two independent reviewers were completed. Results: Of the 773 articles retrieved, 19 were included. Results indicate that virtual care can be safe while enabling timely detection of clinical deterioration to improve the illness trajectory. COVID-19 virtual care was delivered by single health professionals or by multidisciplinary teams using a range of low-technology methods such as telephone to higher technology methods like wearable technology that transmitted physiological data to the care teams for real-time or asynchronous monitoring. Conclusion: The review described the varied nature of virtual care including its design, implementation, and evaluation. Further research is needed for continued exploration on how to leverage digital health assets for the delivery of appropriate and safe virtual COVID-19 community care, which can support patient recovery, control transmission, and prevent intensifying the burden on the health care system, especially during surges.

Telestroke consultation can accurately diagnose ischemic stroke mimics.

INTRODUCTION: Telestroke (TS) networks are standard in many areas of the US. Despite TS systems having approximately 33% mimic rates, it is unknown if TS can accurately diagnose patients with acute ischemic stroke (AIS) versus stroke mimics. METHODS: We performed a retrospective review of consecutive TS consults to 27 TS sites in six states during 2018. Clinical information and diagnosis were extracted from discharge records and compared to those from the TS consult. Discharge diagnoses were verified and coded into 12 categories. Cases without a clear discharge diagnosis and intracerebral haemorrhage were excluded. We report agreement and a Cohen's kappa between TS and discharge diagnoses for the category of AIS/transient ischemic attack (TIA) versus stroke mimic. RESULTS: We included 404 cases in the analysis (mean age 66 years; 54% women). Of these, 225 had a TS diagnosis of AIS/TIA; 102 (45%) received intravenous tissue plasminogen activator. Our study demonstrated a high diagnostic agreement for AIS/TIA (88%) with a kappa of 0.75 for stroke and mimics. Of the 179 patients diagnosed with a stroke mimic on TS, 27 (15%) were diagnosed with AIS/TA by discharge. TS mimic diagnosis had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 90%; TS diagnosis of stroke/TIA had PPV 90%, NPV 85%. DISCUSSION: We found excellent correlation between TS and discharge diagnoses for patients with both stroke and stroke mimics. This suggests that TS systems can accurately assess a wider variety of patients with acute neurologic syndromes other than AIS.

Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson’s Disease in a Taiwanese Population: An 11-Year Follow-Up Study

Objective@#aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. @*Methods@#aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. @*Results@#aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. @*Conclusion@#aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than 280 distinct pathogenic mutations have been reported to date. CADASIL was once considered a very rare disease with an estimated prevalence of 1.3–4.1 per 100,000 adults. However, recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The disease severity and age at onset vary significantly even among individuals who carry the same NOTCH3 mutations. It is still unclear whether a significant genotype–phenotype correlation is present in CADASIL. The accumulation of granular osmiophilic material in the vasculature is a characteristic feature of CADASIL. However, the exact pathogenesis of CADASIL remains largely unclear despite various laboratory and clinical observations being made. Major hypotheses proposed so far have included aberrant NOTCH3 signaling, toxic aggregation, and abnormal matrisomes. Several characteristic features have been observed in the brain magnetic resonance images of patients with CADASIL, including subcortical lacunar lesions and white matter hyperintensities in the anterior temporal lobe or external capsule, which were useful in differentiating CADASIL from sporadic stroke in patients. The number of lacunes and the degree of brain atrophy were useful in predicting the clinical outcomes of patients with CADASIL. Several promising blood biomarkers have also recently been discovered for CADASIL, which require further research for validation.

Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown. @*Materials and Methods@#We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed. @*Results@#Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions. @*Conclusion@#Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

How Has COVID-19 Changed the Way We Do Virtual Care? A Scoping Review Protocol.

The coronavirus disease (COVID-19) pandemic created worldwide interest and use of virtual care to support public health measures and reduce the spread of infection. While some forms of virtual care have been used prior to COVID-19 such as telemedicine, little is known about other virtual modalities such as video conferencing, wearables and other digital technologies. The COVID-19 pandemic has presented an opportunity to question the efficacy and safety of virtual care, especially in terms of patient outcomes among those self-isolating. The purpose of this scoping review is to examine the safety of virtual care among active COVID-19 patients in the community and examine the types and dose of virtual care. Finally, this review will examine what patient outcomes are identified from interventions delivered virtually to treat COVID-19. We followed a systematic process guided by the PRISMA checklist for scoping reviews with a comprehensive search strategy across four bibliographic databases and handsearching reference lists. We undertook a blinded, two-stage screening process with eligibility criteria. All citations and screening were managed using the DistillerSR software. Data were extracted using a data extraction tool developed for this project. The conclusions from this review will offer greater understanding for how virtual care can be used among community-based COVID-19 patients.

Commentary: Access to Virtual Care Matters: The Problem with Giving to Some and Not All.

Expedited in the midst of the COVID-19 pandemic, virtualization of healthcare is becoming an inevitable norm. While this conveys hope for improving health systems performance, inequitable access could result in consequences that intensify health disparities and increase the burden on the health system. Nurse leaders are optimally positioned to tactfully influence policy directions on virtual care and shape a comprehensive research agenda that includes virtual nursing care in all domains of practice. With virtual care advancing into the mainstream, it is time to mind the health equity gap and co-design virtualized care that ensures the needs of all are met.

Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course.

The coronavirus disease 2019 pandemic has changed the way we engage patient care, with a move toward telemedicine-based health care encounters. Teleneurology is now being rapidly embraced by neurologists in clinics and hospitals nationwide but for many, this paradigm of care is unfamiliar. Exposure to telemedicine in neurology training programs is scarce despite previous calls to expand teleneurology education. Programs that provide a teleneurology curriculum have demonstrated increased proficiency, accuracy, and post-training utilization among their trainees. With the current changes in health care, broad incorporation of teleneurology education in resident and fellow training after this pandemic dissipates will only serve to improve trainee preparedness for independent practice.

Less Experienced Telestroke Consultants Are More Likely to Go On-Camera, but Less Likely to Give tPA.

BACKGROUND: Stroke telemedicine (telestroke) increases tPA availability and administration. However, the effective use of telestroke requires training, which is not a standard component of vascular neurology training. As a result, many providers learn telestroke skills "on the job" after finishing their training. AIMS: We sought to explore if providers with more telestroke experience would be more efficient in the utilization of telemedicine, compared to providers with less experience. METHODS: We prospectively collected data on telestrokes between July 2014 and July 2017 at a Comprehensive Stroke Center. Telestrokes are initiated on the telephone and typically, but not always, followed by an on-camera consult. Decision to do a phone-only versus on-camera consult is at the provider's discretion. RESULTS: There were 1,029 telestrokes, of which 807 were on-camera (74%). Of the 8 telestroke providers, 4 had less experience, having just finished stroke fellowship, and 4 had more experience (mean = 7.8 years of telestroke experience at the beginning of the study). Providers with less experience were more likely to go on camera than providers with more experience (79% vs. 67% of consults, p = 0.021), but were less likely to give tPA when on-camera (25% vs. 33%, p = 0.023). The absolute rate of tPA administration, combining phone and camera administration, or the frequency of technical difficulties were not different. CONCLUSIONS: Telestroke consultants with less experience do not triage as many cases by phone and are less likely to administer tPA on-camera, suggesting their use of telemedicine is not optimized. This supports the introduction of telestroke didactics during vascular neurology training.

Subclinical Cerebrovascular Disease: Epidemiology and Treatment.

PURPOSE OF REVIEW: Subclinical cerebrovascular disease (sCVD) is highly prevalent in older adults. The main neuroimaging findings of sCVD include white matter hyperintensities and silent brain infarcts on T2-weighted MRI and cerebral microbleeds on gradient echo or susceptibility-weighted MRI. In this paper, we will review the epidemiology of sCVD, the current evidence for best medical management, and future directions for sCVD research. RECENT FINDINGS: Numerous epidemiologic studies show that sCVD, in particular WMH, is an important risk factor for the development of dementia, stroke, worse outcomes after stroke, gait instability, late-life depression, and death. Effective treatment of sCVD could have major consequences for the brain health of a substantial portion of older Americans. Despite the link between sCVD and many vascular risk factors, such as hypertension or hyperlipidemia, the optimal medical treatment of sCVD remains uncertain. Given the clinical equipoise about the risk versus benefit of aggressive medical management for sCVD, clinical trials to examine pragmatic, evidence-based approaches to management of sCVD are needed. Such a trial could provide much needed guidance on how to manage a common clinical scenario facing internists and neurologists in practice.

Prevalence and predictors of exclusive breastfeeding among immigrant and Canadian-born Chinese women.

Breastfeeding is the optimal method for infant feeding, yet migrant women may be at risk for suboptimal exclusivity rates. In a cohort of immigrant and Canadian-born Chinese women, our objectives were to (a) describe patterns and prevalence of exclusive breastfeeding at 1, 3, and 6 months postpartum; (b) identify risk and protective factors associated with exclusivity; and (c) examine potentially differential importance of these factors across this 6-month period. This was a prospective study of 565 immigrants and Canadian-born Chinese women (Toronto, Canada). Exclusive breastfeeding was measured at 1, 3, and 6 months postpartum. Predictors comprised fixed (demographics, history of depression, immigrant status, prenatal breastfeeding classes, in-hospital formula supplementation, baseline social support, and baseline acculturative stress) and time-dependent (depression, anxiety, fatigue, and breastfeeding problems) variables. Descriptive statistics, logistic regression, and generalized linear mixed models, respectively, were undertaken to address the objectives. Patterns of breastfeeding practices included exclusive breastfeeding in all time points (26.8%) or none (32.9%) and moving from exclusive to nonexclusive (20.3%) or nonexclusive to exclusive breastfeeding (15.2%). Women less likely to breastfeed exclusively at 1, 3, or 6 months were those whose infants received in-hospital formula supplementation. Exclusivity attrition was higher between 3 and 6 months than 1-3 months. Immigrant status and in-hospital formula supplementation had a significant impact on exclusivity earlier in the postpartum period while breastfeeding problems were associated with decreased exclusivity across time. Proactive preventive efforts are need to maintain breastfeeding exclusivity especially between 3 and 6 months if women are to meet international breastfeeding recommendations.

Outcomes in adults with cerebral venous sinus thrombosis: A retrospective cohort study.

Most patients with cerebral venous sinus thrombosis (CVST) treated with anticoagulation have good outcomes. We examined which factors were associated with poor outcomes after treatment. We retrospectively reviewed patients ≥18 years old who were diagnosed with CVST between 1997 and 2015. Good (modified Rankin score [mRS] ≤2) and poor outcomes were dichotomized. Demographic, historical, clinical, imaging, and treatment characteristics were compared. Eighty-nine patients received treatment for CVST (52.8% males, 74.2% Caucasian). Sixty-eight (76.4%) had good outcomes and 21 (23.6%) had poor outcomes. Poor outcome was associated with systemic or central nervous system (CNS) infection (p = 0.002), lower use of heparin-only therapy than interventional-only treatments (p = 0.003), and increased use of craniectomy (p = 0.002). Good outcomes were associated with migrainous headache on presentation (p = 0.01) and involvement of superficial cortical vessels only (p = 0.02). No prothrombotic or imaging findings correlated with poor outcome. Multivariable analysis showed that any clinical risk factor (p = 0.02) and headache (p = 0.02) predicted improved outcome whereas systemic or CNS infection (p = 0.02) and craniectomy (p = 0.02) predicted poor outcome. A published risk score showed a moderate ability to predict good outcome but not poor outcome. Overall sensitivity (23.8%), specificity (75.0%), and positive (24.0%) and negative (77.0%) predictive value suggested moderate prediction of good outcome and limited prediction of poor outcome. Rates of poor outcomes in CVST were comparable with previous investigations (23.6%), but prediction of poor outcome remains challenging in patients with CVST. Our results suggested that systemic infection and craniectomy were the most robust predictors of poor outcome.

Construction and Validation of a Mammalian Expression Vector for in Utero Electroporation Study of miR-3099 in the Mouse Neocortex

@#Introduction: MiR-3099 was reported to play a role in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development. To further explore its potential regulatory effects on embryonic brain development, this study aims to construct and validate an expression vector of miR-3099 for future gain-of-function and loss-of-function studies. Methods: pCAG-eGFP vector was modified to include IRES2 and miR-3099 with 150bp upstream and downstream genomic sequences. The newly constructed vector, pCAG-miR-3099-IRES2-eGFP, consists of CAG promoter. The in vitro expression level of miR-3099 was measured using stem-loop RT-qPCR after it was transfected into 293FT cell. Later, the vector was electroporated into the embryonic brain at E15.5. Three days later, the E18.5 embryonic brain was harvested and cryopreserved. Immunohistochemistry was performed by using antibody against eGFP to validate the in utero expression of the transgene in the neocortex of the brain. Results: Our finding showed that, the expression level of miR-3099 was significantly upregulated (p<0.001) in cells transfected with miR-3099 vector as compared to both negative and empty plasmid control groups. In addition, the expression of eGFP was noted in the brain section indicating that the vectors with or without miR-3099 transgene were successfully transfected into and expressed in the neocortex upon electroporation. Conclusion: The bicistronic expression vector of miR-3099 which was driven by the CAG promoter was successfully constructed, validated and sufficiently delivered to brain cells via the in utero electroporation approach. The regulatory roles of miR-3099 in embryonic brain development can be manipulated using similar approach.

Determinants of the impact of blood pressure variability on neurological outcome after acute ischaemic stroke.

INTRODUCTION: Increased blood pressure variability (BPV) is detrimental after acute ischaemic stroke, but the interaction between BPV and neuroimaging factors that directly influence stroke outcome has not been explored. METHODS: We retrospectively reviewed inpatients from 2007 to 2014 with acute anterior circulation ischaemic stroke, CT perfusion and angiography at hospital admission, and a modified Rankin Scale (mRS) 30-365 days after stroke onset. BPV indices included SD, coefficient of variation and successive variation of the systolic blood pressure between 0 and 120 hours after admission. Ordinal logistic regression models were fitted to mRS with predictor variables of BPV indices. Models were further stratified by CT perfusion volumetric measurements, proximal vessel occlusion and collateral score. RESULTS: 110 patients met the inclusion criteria. The likelihood of a 1-point rise in the mRS increased with every 10 mm Hg increase in BPV (OR for the 3 BPV indices ranged from 2.27 to 5.54), which was more pronounced in patients with larger ischaemic core volumes (OR 8.37 to 18.0) and larger hypoperfused volumes (OR 6.02 to 15.4). This association also held true for patients with larger mismatch volume, proximal vessel occlusion and good collateral vessels. CONCLUSIONS: These results indicate that increased BPV is associated with worse neurological outcome after stroke, particularly in patients with a large lesion core volume, concurrent viable ischaemic penumbra, proximal vessel occlusion and good collaterals. This subset of patients, who are often not candidates for or fail acute stroke therapies such as intravenous tissue plasminogen activator or endovascular thrombectomy, may benefit from interventions aimed at reducing BPV.

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

Identification of the PROM1 Mutation p.R373C in a Korean Patient With Autosomal Dominant Stargardt-like Macular Dystrophy

Stargardt-like macular dystrophy 4 (STGD4) is a rare macular dystrophy characterized by bull's eye atrophy of the macula and the underlying retinal pigment epithelium. Patients with STGD4 show decreased central vision, which often progresses to severe vision loss. The PROM1 gene encodes prominin-1, which is a 5-transmembrane glycoprotein also known as CD133 and is involved in photoreceptor disk morphogenesis. PROM1 mutations have been identified as genetic causes for STGD4 and other retinal degenerations such as retinitis pigmentosa. We report a case of STGD4 with a PROM1 p.R373C mutation in a Korean patient. Ophthalmic examinations of a 38-yr old man complaining of decreased visual acuity revealed bilateral atrophic macular lesions consistent with STGD4. Targeted exome sequencing of known inherited retinal degeneration genes revealed a heterozygous missense mutation c.1117C>T (p.R373C) of PROM1, which was confirmed by Sanger sequencing. To the best of our knowledge, this is the first case of a PROM1 mutation causing STGD4 in Koreans.

Increased Blood Pressure Variability Is Associated with Worse Neurologic Outcome in Acute Anterior Circulation Ischemic Stroke.

Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0-24, 0-72, and 0-120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population.