Portable multi-focal visual evoked potential diagnostics for multiple sclerosis/optic neuritis patients.

PURPOSE: Multiple sclerosis (MS) is a neuro-inflammatory disease affecting the central nervous system (CNS), where the immune system targets and damages the protective myelin sheath surrounding nerve fibers, inhibiting axonal signal transmission. Demyelinating optic neuritis (ON), a common MS symptom, involves optic nerve damage. We've developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from the scalp using custom electroencephalography electrodes. METHODS: Subject vision is evaluated using a short 2.5-min full-field visual evoked potentials (ffVEP) test, followed by a 12.5-min multifocal VEP (mfVEP) test. The ffVEP evaluates the integrity of the visual pathway by analyzing the P100 component from each eye, while the mfVEP evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEPs. Key metrics from patients' ffVEP results were statistically evaluated against data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification. RESULTS: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging and Optical Coherence Tomography findings. CONCLUSION: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Spontaneous Intracranial Hemorrhages in a Community of Asian Americans: Case Series and Literature Review.

Background and objectives Several Asian populations abroad are reported to have a higher prevalence of spontaneous intracranial hemorrhages (sICH) and a greater proportion of all stroke types attributed to ICH compared to non-Asians. However, the causes are unknown, and few studies have examined the issue among Asian Americans. This report aims to highlight some less common, but not rare, clinical features that could bear on several pathophysiological factors, by presenting a selected case series of 13 Asian American patients admitted to a Boston-based healthcare system and hospital. Methods The selected cases were classified into six categories based on presumed sICH mechanisms including vasculopathy, hypertensive crises, moyamoya disease/syndrome, venous sinus thrombosis, brainstem hemorrhages, and arterial malformation/aneurysm. We also examined 5 years of medical records at our institution, a single healthcare system among several in a large urban area having its main hospital embedded in an Asian community, to arrive at stroke-type proportions, comparing our Asian to non-Asian population. ICH cases excluded trauma, coagulopathy, and hemorrhagic transformation. ICH patient counts were compared to acute ischemic stroke and subarachnoid hemorrhage across various ethnicities. Results Pathophysiology-biomarker correlations within each ICH stroke category were reviewed, some possibly having specificity for Asian populations. We found some evidence to support an increased proportion of sICH among all stroke types in our Asian American patients, relative to other ethnic groups. A higher apparent estimate of sICH incidence in Asian Americans vs. Caucasians was also uncovered. However, these did not reach statistical significance and so no conclusion on risk could be made from this preliminary study. Conclusions We review the extensive literature on epidemiology and genetic markers and affirm that an awareness of the potential increased risk of sICH in this expanding population is clinically prudent. An expanded epidemiologic study to refine ICH risk estimates in Asian Americans is planned.

A Survey of Burnout Among Neurocritical Care Practitioners.

BACKGROUND: Burnout is a growing problem among medical professionals, reaching a crisis proportion. It is defined by emotional exhaustion, cynicism, and career dissatisfaction and is triggered by a mismatch between the values of the person and the demands of the workplace. Burnout has not previously been examined thoroughly in the Neurocritical Care Society (NCS). The purpose of this study is to assess the prevalence, contributing factors, and potential interventions to reduce burnout within the NCS. METHODS: A cross-sectional study of burnout was conducted using a survey distributed to members of the NCS. The electronic survey included personal and professional characteristic questions and the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI). This validated measure assesses for emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). These subscales are scored as high, moderate, or low. Burnout (MBI) was defined as a high score in either EE or DP or a low score in PA. A Likert scale (0-6) was added to the MBI (which contained 22 questions) to provide summary data for the frequencies of each particular feeling. Categorical variables were compared using χ2 tests, and continuous variables were compared using t-tests. RESULTS: A total of 82% (204 of 248) of participants completed the entire questionnaire; 61% (124 of 204) were burned out by MBI criteria. A high score in EE was present in 46% (94 of 204), a high score in DP was present in 42% (85 of 204), and a low score in PA was present in 29% (60 of 204). The variables feeling burned out now, feeling burned out in the past, not having an effective/responsive supervisor, thinking about leaving one's job due to burnout, and leaving one's job due to burnout were significantly associated with burnout (MBI) (p < 0.05). Burnout (MBI) was also higher among respondents early in practice (currently training/post training 0-5 years) than among respondents post training 21 or more years. In addition, insufficient support staff contributed to burnout, whereas improved workplace autonomy was the most protective factor. CONCLUSIONS: Our study is the first to characterize burnout among a cross-section of physicians, pharmacists, nurses, and other practitioners in the NCS. A call to action and a genuine commitment by the hospital, organizational, local, and federal governmental leaders and society as a whole is essential to advocate for interventions to ameliorate burnout and care for our health care professionals.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis.

OBJECTIVE: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. DATA SOURCES: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. METHODS: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. PRIMARY ENDPOINT: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. DISCUSSION: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?'Protocol version 0.4 - 06/26/2023PROSPERO registration:CRD42021278869.

Portable Multi-focal Visual Evoked Potential Diagnostics for Multiple Sclerosis/Optic Neuritis patients.

Purpose: Multiple Sclerosis (MS) is a neuro-inflammatory disease of the Central Nervous System (CNS) in which the body's immune system attacks and destroys myelin sheath that protects nerve fibers and causes disruption in axonal signal transmission. Demyelinating Optic Neuritis (ON) is often a manifestation of MS and involves inflammation of the optic nerve. ON can cause vision loss, pain and discomfort in the eyes, and difficulties in color perception.In this study, we developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from near the O1, Oz, O2, O9 and O10 locations on the scalp (extended 10-20 system) using custom electroencephalography (EEG) electrodes. Methods: Each test session is constituted by a short 2.5-minute full-field visual evoked potentials (ffVEP) test, followed by a 12.5-minute multifocal VEP (mfVEP) test. The ffVEP test evaluates the integrity of the visual pathway by analyzing the P1 (also known as P100) component of responses from each eye, while the mfVEP test evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEP responses. The results of the ffVEP test for patients were evaluated against normative data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification. Results: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging (MRI) and Optical Coherence Tomography (OCT) findings. Conclusion: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

Neuroimmunological adverse events associated with immune checkpoint inhibitor: a retrospective, pharmacovigilance study using FAERS database.

PURPOSE: To investigate the characteristics and risk factors for neurologic adverse events (AEs) induced by immune checkpoint inhibitors (ICIs). METHODS: An observational, retrospective, and pharmacovigilance study based on the FAERS database collected between January 2014 and December 2019 was conducted. ICI-related AEs were defined as adverse reactions in patients using anti-PD-1 (nivolumab and pembrolizumab), anti-PD-L1 (atezolizumab, avelumab, and durvalumab), and anti-CTLA-4 (ipilimumab and tremelimumab). Neurologic AEs previously reported to be associated with ICI were evaluated in the disproportionality analysis using the reporting odds ratio (ROR). RESULTS: Among 50,406 ICI-related reports, 3619 (7.2%) neurological case was found: 1985 with anti-PD-1, 372 with anti-PD-L1, 366 with anti-CTLA-4, and 896 with the combination of ICIs. In comparison to non-ICI drug use, ICI use demonstrated higher risk for neurologic complication, including hypophysitis/hypopituitarism, myasthenia gravis, encephalitis/myelitis, meningitis, Guillain-Barre syndrome, vasculitis, and neuropathy. The risk of neurologic AEs associated with ICI combination therapy was as high as or even higher than ICI monotherapy, most significantly in hypophysitis/hypopituitarism. The proportion of serious neurological events and death related to combination therapy has been decreasing in recent years. Older age, male and female sex, and metastasis were not significant risk factors for the incidence of neurologic ICI-related AEs. Patients at older age, with melanoma or non-small cell lung cancer, or on dual ICI therapy may be at higher risk of fatal neurologic AEs. CONCLUSION: ICI use is associated with a higher risk of neurological complications, with dual ICI therapy posing a higher risk, while older age, sex, or metastasis were not. Patients at older age, with certain cancer types, or on dual ICI therapy may be at higher risk of fatal neurologic AEs.

Rapid Cognitive Decline Secondary to CSF Venous Fistula With Postoperative Rebound Intracranial Hypertension and a Hyperintense Paraspinal Vein Sign Seen Retrospectively.

A 56-year-old female with 2 prior Chiari decompressions presented with rapidly progressive cognitive decline. Brain magnetic resonance imaging, computed tomography myelogram, and prone digital subtraction myelography revealed signs of brain sag and left T9 perineural cysts but no cerebrospinal fluid leaks. Symptoms improved after multilevel blood patches but recurred. Lateral decubitus digital subtraction myelography revealed a spinal cerebrospinal fluid venous fistula (SCVF), which resolved after neurosurgeons ligated the nerve root. Rebound headaches with papilledema occurred on postoperative day 9 and then resolved 2 months after acetazolamide was started. A hyperintense paraspinal vein was seen retrospectively on T2-weighted magnetic resonance imaging with Dixon fat suppression sequencing. This case is unique in the acuity of cognitive decline secondary to SCVF. Acetazolamide at the time of treatment may potentially be used as prophylaxis for rebound intracranial hypertension. The hyperintense paraspinal vein may have utility in future diagnosis of SCVF.

Delay in Diagnosis of Basilar Artery Stroke.

BACKGROUND: Basilar artery stroke causes substantial morbidity and mortality. Although its unusual clinical presentation potentially contributes to a delay in diagnosis, this problem has not been systematically studied. We compared intervals between symptom onset, initial presentation, and diagnosis in stroke due to basilar artery (BA) versus left middle cerebral artery (LMCA) occlusion to determine the presence of and potential reasons for diagnostic delay in BA stroke. METHODS: We retrospectively identified 21 consecutive adult patients diagnosed with BA stroke between 2009 and 2011 from our hospital's prospective stroke registry. Patients were age-, sex-, and race-matched with 21 LMCA stroke patients from the same period. All subjects had confirmed clinical and radiographic diagnosis of stroke due to occlusion or stenosis of the BA, LMCA, or left internal carotid artery. Time to diagnosis was determined independently by two investigators through medical record review. The pre-specified primary outcome was latency from emergency department (ED) arrival to stroke diagnosis. RESULTS: Median time from ED arrival to diagnosis was 8 h 24 min (IQR: 2:43-26:32) for BA and 1 h 23 min (IQR: 0:41-1:45; p < 0.001) for LMCA. Median time from symptom onset to ED arrival was 7 h 44 min (IQR 1:23-21:30) for BA and 1 h 2 min (IQR 0:36-9:41; p = 0.06) for LMCA. Four of 21 (19 %) BA patients were diagnosed within a 4-h time frame to make intravenous thrombolysis possible compared to 13 of 21 (62 %) LMCA patients (p = 0.01). CONCLUSIONS: Our results suggest that both pre-hospital and in-hospital processes cause substantial, clinically significant delays in the diagnosis of BA stroke.