In-Hospital Neurologic Complications, Neuromonitoring, and Long-Term Neurologic Outcomes in Patients With Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although delirium is well described in patients with sepsis, there are limited data on other neurologic complications. We aimed to systematically review the prevalence, neuromonitoring tools, and neurocognitive outcomes in sepsis patients with neurologic complications. DATA SOURCES: MEDLINE and six other databases (Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov ) were searched through January 2023. STUDY SELECTION: Studies of adult patients with sepsis reported neurologic complications, use of neuromonitoring tools, neuropathology, and cognitive outcomes. DATA EXTRACTION: Two independent reviewers extracted the data. Random-effect meta-analyses were used to pool data. DATA SYNTHESIS: Seventy-four studies ( n = 146,855) were included. Neurologic complications were reported in 38 studies ( n = 142,193) including septic encephalopathy (36%, 95% CI, 27-46%; I 2 = 99%), ischemic stroke (5%, 95% CI, 2.1-11.5; I 2 = 99%), intracranial hemorrhage (2%, 95% CI, 1.0-4.4%; I 2 = 96%), seizures (1%, 95% CI, 0.2-7%; I 2 = 96%), posterior reversible encephalopathy syndrome (9%), and hypoxic-ischemic brain injury (7%). In the meta-regression analysis, pulmonary infection, sepsis induced by a gram-positive organism, higher sequential organ failure assessment score, acute physiology and chronic health evaluation II score at admission, and longer ICU length of stay were associated with higher risk of developing septic encephalopathy. Three studies ( n = 159) reported postmortem neuropathological findings, acute brain injury was noted in 47% of patients. Twenty-six studies ( n = 1,358) reported the use of neuromonitoring tools, electroencephalogram was the most used tool for seizure detection. Transcranial Doppler and near infrared spectroscopy were used for monitoring cerebral hemodynamic changes to detect early ischemia. Six studies reported cognitive outcomes ( n = 415) up to 12 months postdischarge and cognitive impairment (≥ one domain) was reported in 30%. CONCLUSIONS: In-hospital neurologic complications are common in patients with sepsis. However, the mechanism and timing of those sepsis-associated complications are poorly understood and there are limited data on standardized neuromonitoring in this population.

Intravascular Lymphoma as a Cause of Recurrent Strokes - Case Report and Review of the Literature.

Background: Intravascular lymphoma is an uncommon cause of ischemic strokes. Because of its rarity and atypical pattern, most diagnoses are made post-mortem. Case study: We present a case of a 68-year-old male with multiple cardiovascular risk factors and recent SARS-CoV-2 infection who presented with recurrent strokes. Because of his stroke risk factors, he was initially managed with a sequentially escalating antithrombotic regimen. A malignant process was low on the differential at this point given his lack of systemic symptoms. When he continued to have new strokes despite these measures, including a spinal cord infarct, a broad workup was sent including for hypercoagulable states, vasculitis, and intravascular lymphoma. Eventually, a skin biopsy of a cherry angioma returned positive for lymphoma cells. He was treated with methotrexate followed by chemotherapy and rituximab. Unfortunately, he did not improve and was made comfort measures only by his family. Conclusion: This case illustrates the importance of considering intravascular lymphoma as a potential etiology of recurrent strokes, as early diagnosis and treatment are important for preventing irreversible neurological damage.

Neurologic Complications in Patients With Left Ventricular Assist Devices.

Left ventricular assist device (LVAD) use has revolutionised the care of patients with advanced heart failure, allowing more patients to survive until heart transplantation and providing improved quality for patients unable to undergo transplantation. Despite these benefits, improvements in device technology, and better clinical care and experience, LVADs are associated with neurologic complications. This review provides information on the incidence, risk factors, and management of neurologic complications among LVAD patients. Although scant guidelines exist for the evaluation and management of neurologic complications in LVAD patients, a high index of suspicion can prompt early detection of neurologic complications which may improve overall neurologic outcomes. A better understanding of the implications of continuous circulatory flow on systemic and cerebral vasculature is necessary to reduce the common occurrence of neurologic complications in this population.

Physiological Monitoring in Patients with Acute Brain Injury: A Multimodal Approach.

Neurocritical care management of acute brain injury (ABI) is focused on identification, prevention, and management of secondary brain injury (SBI). Physiologic monitoring of the brain and other organ systems has a role to predict patient recovery or deterioration, guide individualized therapeutic interventions, and measure response to treatment, with the goal of improving patient outcomes. In this review, we detail how specific physiologic markers of brain injury and neuromonitoring tools are integrated and used in ABI patients to develop therapeutic approaches to prevent SBI.

Treating the body to prevent brain injury: lessons learned from the coronavirus disease 2019 pandemic.

PURPOSE OF REVIEW: We aim to provide the current evidence on utility and application of neuromonitoring tools including electroencephalography (EEG), transcranial Doppler (TCD), pupillometry, optic nerve sheath diameter (ONSD), cerebral near-infrared spectroscopy (cNIRS), somatosensory-evoked potentials (SSEPs), and invasive intracranial monitoring in COVID-19. We also provide recent evidence on management strategy of COVID-19-associated neurological complications. RECENT FINDINGS: Despite the common occurrence of neurological complications, we found limited use of standard neurologic monitoring in patients with COVID-19. No specific EEG pattern was identified in COVID-19. Frontal epileptic discharge was proposed to be a potential marker of COVID-19 encephalopathy. TCD, ONSD, and pupillometry can provide real-time data on intracranial pressure. Additionally, TCD may be useful for detection of acute large vessel occlusions, abnormal cerebral hemodynamics, cerebral emboli, and evolving cerebral edema at bedside. cNIRS was under-utilized in COVID-19 population and there are ongoing studies to investigate whether cerebral oxygenation could be a more useful parameter than peripheral oxygen saturation to guide clinical titration of permissive hypoxemia. Limited data exists on SSEPs and invasive intracranial monitoring. SUMMARY: Early recognition using standardized neuromonitoring and timely intervention is important to reduce morbidity and mortality. The management strategy for neurological complications is similar to those without COVID-19.

Cerebral Microvascular Injury in Patients with Left Ventricular Assist Device: a Neuropathological Study.

Strokes are common among patients with left ventricular devices (LVAD). We hypothesize that there is ongoing cerebral microvascular injury with LVAD support and aim to describe this among LVAD-implanted patients through post-mortem neuropathologic evaluation. We identified and reviewed medical records of LVAD patients who underwent brain autopsy between January 2006 and December 2019 at a tertiary center. Cerebral injury was defined as both gross and microscopic injuries within the intracranial space including cerebral infarct (CI), hypoxic-ischemic brain injury (HIBI), intracranial hemorrhage (ICH), and cerebral microvascular injury. Cerebral microvascular injury was defined as microscopic brain intraparenchymal or perivascular hemorrhage, perivascular hemosiderin deposition, and perivascular inflammation. Twenty-one patients (median age = 57 years, 67% male) had autopsy after LVAD support (median LVAD support = 51 days). The median time from death to autopsy was 19 h. All 21 patients had cerebral injuries and 19 (90%) patients had cerebral microvascular injuries. Fourteen patients (78%) harbored more than one type of cerebral injury. On gross examination, 8 patients (38%) had CI, and 6 patients (29%) had ICH. On microscopic exam, 12 patients (57%) had microscopic intraparenchymal hemorrhage, 3 patients (14%) had perivascular hemorrhage, 11 patients (43%) had perivascular hemosiderin deposition, 5 patients (24%) had meningeal hemorrhage, 13 patients had chronic perivascular inflammation (62%), and 2 patients had diffuse HIBI (10%). Among patients with LVAD, there is a high prevalence of subclinical microvascular injuries and cerebral microbleeds (CMBs), which may provide some insights to the cause of frequent cerebral injury in LVAD population.

Prevalence and Outcome of Acute Respiratory Distress Syndrome in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. DATA SOURCES: PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. DATA EXTRACTION: Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle-Ottawa Scale for cohort and case-control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). DATA SYNTHESIS: We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35-47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13-0.27, I2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2-5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64-0.75; I2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23-0.40; I2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. CONCLUSION: In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted.

Pathophysiology of Brain Injury and Neurological Outcome in Acute Respiratory Distress Syndrome: A Scoping Review of Preclinical to Clinical Studies.

Acute respiratory distress syndrome (ARDS) has been associated with secondary acute brain injury (ABI). However, there is sparse literature on the mechanism of lung-mediated brain injury and prevalence of ARDS-associated secondary ABI. We aimed to review and elucidate potential mechanisms of ARDS-mediated ABI from preclinical models and assess the prevalence of ABI and neurological outcome in ARDS with clinical studies. We conducted a systematic search of PubMed and five other databases reporting ABI and ARDS through July 6, 2020 and included studies with ABI and neurological outcome occurring after ARDS. We found 38 studies (10 preclinical studies with 143 animals; 28 clinical studies with 1175 patients) encompassing 9 animal studies (n = 143), 1 in vitro study, 12 studies on neurocognitive outcomes (n = 797), 2 clinical observational studies (n = 126), 1 neuroimaging study (n = 15), and 13 clinical case series/reports (n = 15). Six ARDS animal studies demonstrated evidence of neuroinflammation and neuronal damage within the hippocampus. Five animal studies demonstrated altered cerebral blood flow and increased intracranial pressure with the use of lung-protective mechanical ventilation. High frequency of ARDS-associated secondary ABI or poor neurological outcome was observed ranging 82-86% in clinical observational studies. Of the clinically reported ABIs (median age 49 years, 46% men), the most common injury was hemorrhagic stroke (25%), followed by hypoxic ischemic brain injury (22%), diffuse cerebral edema (11%), and ischemic stroke (8%). Cognitive impairment in patients with ARDS (n = 797) was observed in 87% (range 73-100%) at discharge, 36% (range 32-37%) at 6 months, and 30% (range 25-45%) at 1 year. Mechanisms of ARDS-associated secondary ABI include primary hypoxic ischemic injury from hypoxic respiratory failure, secondary injury, such as lung injury induced neuroinflammation, and increased intracranial pressure from ARDS lung-protective mechanical ventilation strategy. In summary, paucity of clinical data exists on the prevalence of ABI in patients with ARDS. Hemorrhagic stroke and hypoxic ischemic brain injury were commonly observed. Persistent cognitive impairment was highly prevalent in patients with ARDS.

Callosal Diffusion-Restriction in Patients with Intracranial Hemorrhage.

OBJECTIVE: We aim to report the incidence and clinical characteristics of patients who were found to have diffusion restricting lesions of the corpus callosum (CC) on Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) following intracranial hemorrhage (ICH). DESIGN/METHODS: A retrospective cross-sectional analysis was performed of medical records of all adult patients admitted to a single tertiary center with a primary diagnosis of ICH and received nicardipine infusion over a 2-year period. Patients without MRI brain available or patients who underwent digital subtraction angiography (DSA) prior to MRI were excluded. ICH and intraventricular hemorrhage (IVH) volumes and scores were calculated. MRI brain scans were evaluated for presence and locations of DWI lesions. RESULTS: Among 162 patients who met inclusion criteria, 6 patients (4%, median age 53, range 37-71, 100% male, 33% white) were found to have DWI lesions in the CC with a median ICH volume of 17ml (range 1-105ml). The ICH locations were lobar (n=3), deep (n=2) and cerebellum (n=1). All patients (100%) had intraventricular hemorrhage (IVH) with median IVH volume of 25ml (range 2.7-55ml). Four patients were on levetiracetam. No identifiable infections or metabolic abnormalities were found among these patients. All but one patient had normal DSA. Follow up MRI was only available in one patient and showed no reversibility at 14 days. CONCLUSION: Although rare, diffusion restricting corpus callosum lesions can be seen in patients with ICH, especially in patients with IVH. The etiology and clinical significance of these lesions remains unknown and warrant further research.

How Are We Monitoring Brain Injuries in Patients With Left Ventricular Assist Device? A Systematic Review of Literature.

Despite the common occurrence of brain injury in patients with left ventricular assist device (LVAD), optimal neuromonitoring methods are unknown. A systematic review of PubMed and six electronic databases from inception was conducted until June 5, 2019. Studies reporting methods of neuromonitoring while on LVAD were extracted. Of 5,190 records screened, 37 studies met the inclusion criteria. The neuromonitoring methods include Transcranial Doppler ultrasound for emboli monitoring (TCD-e) (n = 13) and cerebral autoregulation (n = 3), computed tomography and magnetic resonance imaging (n = 9), serum biomarkers (n = 7), carotid ultrasound (n = 3), and near-infrared spectroscopy (n = 2). Of 421 patients with TCD-e, thromboembolic events (TEs) were reported in 79 patients (20%) and microembolic signals (MES) were detected in 105 patients (27%). Ischemic stroke was more prevalent in patients with MES compared to patients without MES (43% vs.13%, p < 0.001). Carotid ultrasound for assessing carotid stenosis was unreliable after LVAD implantation. Elevated lactate dehydrogenase (LDH) levels were associated with TEs. Significant heterogeneity exists in timing, frequency, and types of neuromonitoring tools. TCD-e and serial LDH levels appeared to have potential for assessing the risk of ischemic stroke. Future prospective research incorporating protocolized TCD-e and LDH may assist in monitoring adverse events in patients with LVAD.

Cerebrovascular complications and vasculopathy in patients with herpes simplex virus central nervous system infection.

OBJECTIVE: Herpes simplex viruses (HSV) are neurotropic and known to cause central nervous system (CNS) infections. We aimed to describe the clinical and imaging features of cerebrovascular complications in patients with HSV CNS infections. METHODS: We reviewed records of patients with HSV infections by querying acyclovir use in a clinical registry of parenteral anti-infective therapy at a tertiary medical center from January 2010 until September 2018. One patient who met the inclusion criteria is subsequently added. Diagnostic criteria for HSV CNS infection were intrathecal presence of viral DNA with clinical signs of CNS involvement. RESULTS: Of 36 patients who met the criteria for HSV CNS infections, cerebrovascular complications occurred in 6 patients (17%). Two patients with HSV-1 encephalitis had cerebrovascular complications (1 ischemic stroke, 1 intraparenchymal hemorrhage). Four patients had HSV-2 infection without encephalitis had cerebrovascular complications (3 ischemic strokes, 1 cerebral vein thrombosis). All 3 patients with ischemic strokes without encephalitis had pattern of vasculitis on vessel imaging on MRI with segmental narrowing and vessel wall irregularities of large intracranial arteries with circumferential wall enhancement. CONCLUSION: Cerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis.

Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60.

BACKGROUND: The risk-benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown. OBJECTIVE: To evaluate clinical and patient-reported outcomes after stopping DMT in older MS patients. METHODS: Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regression modeled time to discontinuation and time to reinitiation of therapy. Pre- and post-discontinuation comparisons of Performance Scales (PS), Timed 25-Foot Walk, and Patient Health Questionnaire-9 (PHQ9) were analyzed using linear mixed models. RESULTS: A total of 600 patients were included, with 178 (29.7%) discontinuing. Discontinuers were 2.2 years older, had 3.2 years longer disease duration, and 1.6 years lesser treatment exposure. Providers initiated discontinuation more than patients (68.0%). Only one clinical relapse occurred in discontinuers. A proportion (10.7%) reinitiated DMT. Provider-initiated discontinuers restarted less often (hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.12-0.9). In discontinuers, relapsing-remitting patients had lower PS on average than primary progressive. Provider-initiated discontinuation was associated with lower PS than patient- initiated discontinuation. PHQ9 scores appeared higher in those stopping intravenous (IV) therapies than interferons. Lower PS and PHQ9 indicate better outcomes. CONCLUSION: Most patients over age 60, who discontinued DMT, remained off DMT. This study provides real-world data that may guide clinicians considering discontinuing DMT.