Diagnosis of Pediatric Stroke in Resource Limited Settings.

Global awareness of stroke as a significant cause of neurologic sequelae and death in children has increased over the years as more data in this field becomes available. However, most published literature on pediatric stroke have limited geographic representation. Data on childhood stroke from developing countries remains limited. Thus, this paper reviewed geographic/ethnic differences in pediatric stroke risk factors highlighting those reported in low- and middle-income countries, and proposes a childhood arterial ischemic stroke diagnostic algorithm for resource limited settings. Stroke risk factors include cardiac disorders, infectious diseases, cerebral arteriopathies, hematologic disorders, inflammatory diseases, thrombophilia and genetic conditions. Infection of the central nervous system particularly tuberculous meningitis, is a leading cause of pediatric arterial ischemic stroke in developing countries. Stroke should be considered in children with acute focal neurologic deficit especially in the presence of aforementioned risk factors. Cranial magnetic resonance imaging with angiography is the neuroimaging modality of choice but if unavailable, cranial computed tomography with angiography may be performed as an alternative. If both are not available, transcranial doppler together with neurologic exam may be used to screen children for arterial ischemic stroke. Etiological diagnosis follows with the aid of appropriate laboratory tests that are available in each level of care. International collaborative research on stroke risk factors that are prevalent in low and middle income countries will provide information for drafting of stroke care guidelines that are universal yet inclusive taking into consideration regional differences in available resources with the goal of reducing global stroke burden.

Hypoechogenicity of brainstem raphe in long-COVID syndrome-less common but independently associated with depressive symptoms: a cross-sectional study.

OBJECTIVE: Long coronavirus disease (Long-COVID) syndrome is a hitherto poorly understood phenomenon with a broad spectrum of symptoms, including depression and anxiety. Depressive symptoms have been associated with brainstem raphe (BR) alterations in transcranial sonography (TCS) that might reflect dysfunction of the serotonergic system. The primary aim was to investigate the connection of BR alterations with depressive and anxiety symptoms in patients with Long-COVID syndrome. METHODS: In a cross-sectional study design, we included outpatients fulfilling the criteria of Long-COVID syndrome. All patients were examined by TCS in the axial plane with focus on BR signal alterations. The Hospital Anxiety and Depression Scale (HADS) was used to test for symptoms of anxiety and depression. RESULTS: We included n = 70 patients with Long-COVID syndrome, of which 28.6% (n = 20) exhibited a reduced echogenicity of BR in the TCS examination. Patients with hypoechogenic BR had higher subscores for anxiety and depression compared to normoechogenic patients (HADS depression: median 8 versus 5.5, p = 0.006; HADS anxiety: median 9 versus 6.5, p = 0.006). After adjustment for reasonable confounders, only the odds ratio (OR) for relevant depressive symptoms was higher among Long-COVID patients with hypoechogenic raphe (adjusted OR 3.884, 95% CI 1.244-12.123). DISCUSSION: Hypoechogenic BR alterations are independently associated with depressive symptoms in Long-COVID patients but are not highly frequent. Future studies should investigate whether the hypoechogenicity of the BR is a direct consequence or whether it reflects a priori a higher susceptibility to depressive symptoms after COVID-19, thus enabling to identify COVID-19 patients at higher risk of developing Long-COVID depressive symptoms.

Cerebral Hemodynamic Reserve Abnormalities Detected Via Transcranial Doppler Ultrasound in Recovered COVID-19 Patients.

INTRODUCTION: SARS-CoV-2 infection can produce endothelial injury and microvascular damage, one cause of the multiorgan failure associated with COVID-19. Cerebrovascular endothelial damage increases the risk of stroke in COVID-19 patients, which makes prompt diagnosis important. Endothelial dysfunction can be evaluated by using transcranial Doppler ultrasound to study cerebral hemodynamic reserve, but there are few of these studies in patients with COVID-19, and the technique is not included in COVID-19 action and follow-up guidelines nationally or internationally. OBJECTIVE: Estimate baseline cerebral hemodynamic patterns, cerebral hemodynamic reserve, and breath-holding index in recovered COVID-19 patients. METHOD: We conducted an exploratory study in 51 people; 27 men and 24 women 20-78 years of age, divided into two groups. One group comprised 25 recovered COVID-19 patients, following clinical and epidemiological discharge, who suffered differing degrees of disease severity, and who had no neurological symptoms or disease at the time they were incorporated into the study. The second group comprised 26 people who had not been diagnosed with COVID-19 and who tested negative by RT-PCR at the time of study enrollment. Recovered patients were further divided into two groups: those who had been asymptomatic or had mild disease, and those who had severe or critical disease. We performed transcranial Doppler ultrasounds to obtain baseline and post-apnea tests of cerebral hemodynamic patterns to evaluate cerebral hemodynamic reserve and breath-holding indices. We characterized the recovered patient group and the control group through simple descriptive statistics (means and standard deviations). RESULTS: There were no measurable differences in baseline cerebral hemodynamics between the groups. However, cerebral hemodynamic reserve and breath-holding index were lower in those who had COVID-19 than among control participants (19.9% vs. 36.8% and 0.7 vs. 1.2 respectively). These variables were similar for patients who had asymptomatic or mild disease (19.9% vs.19.8%) and for those who had severe or critical disease (0.7 vs. 0.7). CONCLUSIONS: Patients recovered from SARS-CoV-2 infection showed decreased cerebral hemodynamic reserve and breath-holding index regardless of the disease's clinical severity or presence of neurological symptoms. These abnormalities may be associated with endothelial damage caused by COVID-19. It would be useful to include transcranial Doppler ultrasound in evaluation and follow-up protocols for patients with COVID-19.

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.

Transcranial Doppler in Acute COVID-19 Infection: Unexpected Associations.

BACKGROUND AND PURPOSE: Stroke may complicate coronavirus disease 2019 (COVID-19) infection based on clinical hypercoagulability. We investigated whether transcranial Doppler ultrasound has utility for identifying microemboli and clinically relevant cerebral blood flow velocities (CBFVs) in COVID-19. METHODS: We performed transcranial Doppler for a consecutive series of patients with confirmed or suspected COVID-19 infection admitted to 2 intensive care units at a large academic center including evaluation for microembolic signals. Variables specific to hypercoagulability and blood flow including transthoracic echocardiography were analyzed as a part of routine care. RESULTS: Twenty-six patients were included in this analysis, 16 with confirmed COVID-19 infection. Of those, 2 had acute ischemic stroke secondary to large vessel occlusion. Ten non-COVID stroke patients were included for comparison. Two COVID-negative patients had severe acute respiratory distress syndrome and stroke due to large vessel occlusion. In patients with COVID-19, relatively low CBFVs were observed diffusely at median hospital day 4 (interquartile range, 3-9) despite low hematocrit (29.5% [25.7%-31.6%]); CBFVs in comparable COVID-negative stroke patients were significantly higher compared with COVID-positive stroke patients. Microembolic signals were not detected in any patient. Median left ventricular ejection fraction was 60% (interquartile range, 60%-65%). CBFVs were correlated with arterial oxygen content, and C-reactive protein (Spearman ρ=0.28 [P=0.04]; 0.58 [P<0.001], respectively) but not with left ventricular ejection fraction (ρ=-0.18; P=0.42). CONCLUSIONS: In this cohort of critically ill patients with COVID-19 infection, we observed lower than expected CBFVs in setting of low arterial oxygen content and low hematocrit but not associated with suppression of cardiac output.

Transcranial Doppler Ultrasound Evidence of Active Cerebral Embolization in COVID-19.

OBJECTIVE: To report six consecutive patients with confirmed coronavirus disease-2019 (COVID-19) who underwent Transcranial Doppler (TCD) ultrasonography evaluation for cerebral microemboli in the setting of suspected or confirmed acute ischemic stroke. METHODS: Patient data were obtained from medical records from Northwestern Memorial Hospital, Chicago, IL between May and June 2020. All patients with confirmed COVID-19 who underwent clinical TCD ultrasonography for microemboli detection were included. RESULTS: A total of eight TCD studies were performed in six patients with COVID-19 (4 men and 2 women, median age 65±5), four with confirmed ischemic stroke and two with refractory encephalopathy. Microemboli were detected in three male patients, two patients had suffered a confirmed ischemic stroke and one who developed prolonged encephalopathy. Microemboli of varying intensity were identified in multiple vascular territories in two patients, and microemboli persisted despite therapeutic anticoagulation in a third patient. Of the three patients without evidence of microemboli on TCD ultrasonography, two patients had suffered a confirmed ischemic stroke, while one remained with refractory encephalopathy. CONCLUSIONS: TCD ultrasonography for microemboli detection identified three patients with confirmed COVID-19 with evidence of cerebral arterial microemboli, including one who was therapeutically anticoagulated. TCD ultrasonography provides a non-invasive method for evaluating cerebral microemboli in patients with COVID-19 and may be useful in assessing response to treatment in cases with suspected or confirmed disorders of hypercoagulability. Further studies investigating the prevalence of cerebral microemboli and associated risk factors are needed to characterize their pathogenic mechanism and guide therapeutic interventions in hospitalized COVID-19 patients.

Changes in Care Delivery for Children With Sickle Cell Anemia During the COVID-19 Pandemic.

BACKGROUND: Specialty care for children with sickle cell disease (SCD) may be disrupted during the coronavirus (COVID-19) pandemic. Our DISPLACE consortium includes 28 pediatric SCD centers. METHODS: In May 2020, we surveyed the consortium on the impact of COVID-19 on their practice focusing on transcranial Doppler ultrasound, chronic red cell transfusions, telehealth, and COVID-19 testing. OBSERVATION: Twenty-four DISPLACE providers completed the survey. Transcranial Doppler ultrasound screening decreased to 67% but chronic red cell transfusions remained at 96%. Most investigators (92%) used telehealth and 40% of providers had patients test positive for COVID-19. CONCLUSION: The COVID-19 pandemic has affected routine care and necessitated changes in practice in SCD.

Cerebral hemodynamic alterations in patients with Covid-19

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than in the healthy volunteers and it was statistically significant (P = 0.00). The mean vasomotor reactivity rates values were found to be lower in the Covid-19 group than the healthy group and was also statistically significant (P = 0.00). Conclusion: An increase in basal cerebral blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in the central nervous system and this can be evaluated as a result of endothelial dysfunction.

Powered Air Purifying Respirator (PAPR) restores the N95 face mask induced cerebral hemodynamic alterations among Healthcare Workers during COVID-19 Outbreak.

BACKGROUND AND AIM: COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes in cerebral hemodynamics among healthcare-workers using PPE. METHODS: Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask. RESULTS: A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone. CONCLUSION: Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.