Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children with sickle cell disease: Results from a long-term natural history study in Italy in the era of multimodal therapy.

BACKGROUND: Stroke and cerebral vasculopathy are leading causes of morbidity and mortality in patients with sickle cell disease (SCD). Transcranial Doppler (TCD) is a reliable and validated predictor of stroke risk. Children with conditional or abnormal TCD are at an increased risk for stroke, which can be mitigated by red blood cell transfusion or hydroxyurea. Elucidating the relationship between cerebral hemodynamics and hemolytic anemia can help identify novel therapeutic approaches to reduce stroke risk and transfusion dependence. METHODS: This long-term, real-world study was designed to evaluate the prevalence of TCD imaging (TCDi)-assessed flow velocities in children and to interrogate their relationship with markers of anemia and hemolysis. RESULTS: In total, 155 children (median follow-up 79.8 months, 1358.44 patient-years) had 583 evaluable TCDi results. Only patients with HbSS or HbSß0 had abnormal (1.6%) or conditional (10.9%) TCDi. Children with abnormal or conditional TCDi had lower hemoglobin (Hb) and higher hemolysis markers. A linear correlation was detected between TCD velocity and Hb: an Hb increase of 1 g/dL corresponded to decreases in velocity in the internal carotid and middle cerebral arteries (6.137 cm/s and 7.243 cm/s). Moreover, patients with Hb >9 g/dL presented a lower risk of TCDi-associated events. CONCLUSION: These results support the need to optimize disease-modifying treatments that increase Hb and reduce hemolysis for stroke prevention in young children with SCD.

A Deep Learning Framework for Deriving Noninvasive Intracranial Pressure Waveforms from Transcranial Doppler.

Increased intracranial pressure (ICP) causes disability and mortality in the neurointensive care population. Current methods for monitoring ICP are invasive. We designed a deep learning framework using a domain adversarial neural network to estimate noninvasive ICP, from blood pressure, electrocardiogram, and cerebral blood flow velocity. Our model had a mean of median absolute error of 3.88 ± 3.26 mmHg for the domain adversarial neural network, and 3.94 ± 1.71 mmHg for the domain adversarial transformers. Compared with nonlinear approaches, such as support vector regression, this was 26.7% and 25.7% lower. Our proposed framework provides more accurate noninvasive ICP estimates than currently available. ANN NEUROL 2023;94:196-202.

Brain-derived neurotrophic factor and neuroimaging in pediatric patients with sickle cell disease.

BACKGROUND: The risk of neurological complications is increased in children with sickle cell disease (SCD), such as silent cerebral infarction (SCI) and stroke. Brain-Derived Neurotrophic Factor (BDNF) is a nerve growth factor associated with elevated transcranial Doppler (TCD) velocities and increased risk of stroke in SCD patients. So, we assessed the BDNF level in children with SCD and its relation to neurological complication as silent stroke. METHODS: A comparative cross-sectional study was conducted on 40 patients with SCD, recruited from the Hematology Unit, Pediatric Department, Menoufia University Hospital, and 40 healthy children as controls. Laboratory investigations including BDNF were done. TCD was done for all patients and Magnetic Resonance Imaging (MRI) was done on high-risk patients. RESULTS: BDNF levels were significantly higher in children with SCD than in controls with a significant relation to TCD findings. There was a statistically significant diagnostic ability of BDNF in the prediction of SCD complications as its sensitivity was 89.5%, specificity (95% CI) was 80% with a cut-off point >0.69, AUC = 0.702, and p = 0.004). CONCLUSION: Serum BDNF levels were higher in sickle disease patients who had abnormal transcranial Doppler. BDNF had a significant diagnostic ability in the detection of SCD complications. IMPACT: Silent stroke is a very serious complication in children with sickle cell disease, so regular follow up should be every six months. BDNF is considered a potential biomarker for stroke risk prediction in patients unable to receive TCD.

Non-association of stroke risk with intracranial hemodynamic steal in patients with symptomatic internal carotid artery occlusions.

OBJECTIVES: Paradoxical intracranial hemodynamic steal (IHS) is known in patients having persistent proximal arterial occlusions and is linked with early neurological worsening. However, stroke risk specific to symptomatic internal carotid artery occlusions (SICAO) having paradoxical IHS is unknown. Therefore, we aimed to investigate the association of paradoxical IHS in SICAO patients with stroke recurrence during a one-year follow-up. MATERIALS AND METHODS: We prospectively enrolled adult patients having SICAO with a recent history of ischemic events. Steal magnitude (SM) to classify patients in IHS and non-IHS categories was evaluated by a breath-holding test using bilateral transcranial doppler (TCD). Patients were prescribed optimal medical therapy and followed up for one year for any ischemic stroke/TIA/cardiovascular death. RESULTS: 36 SICAO patients, mean age of 56 years, were assessed using TCD at median 22.5 days (Interquartile range, IQR= 9-42), and 11 (30.6%) had paradoxical IHS with median SM 12% (IQR= 6%-18%). On follow-up, 7 (19.4%) patients had event recurrence and its association with IHS was non-significant (IHS vs non-IHS, 18.2% vs 20%; Log-rank statistics=0.006; P=0.940). On Cox regression analysis, event recurrence was independently associated with the presence of significant contralateral stenosis only (regression coefficient= 2.237; P= 0.012; 95% CI= 1.63-53.89). CONCLUSIONS: IHS prevalence among SICAO is high. However, paradoxical IHS was not associated with an increased risk of stroke in SICAO. Therefore, the presence of paradoxical IHS in SICAO may be considered a transit state and does not necessarily imply an increased risk of stroke.

Transcranial Doppler and computed tomography angiography for detecting cerebral vasospasm post-aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm is a life-threatening complication following aneurysmal subarachnoid hemorrhage (aSAH). While digital subtraction angiography (DSA) is the current gold standard for detection, the diagnostic performance of computed tomography angiography (CTA) and transcranial Doppler (TCD) remains controversial. We aimed to summarize the available evidence and provide recommendations for their use based on GRADE criteria. A literature search was conducted for studies comparing CTA or TCD to DSA for adults ≥ 18 years with aSAH for radiographic vasospasm detection. The DerSimonian-Laird random-effects model was used to pool sensitivity and specificity and their 95% confidence intervals (CI) and derive positive and negative pooled likelihood ratios (LR + /LR -). Out of 2070 studies, seven studies (1646 arterial segments) met inclusion criteria and were meta-analyzed. Compared to the gold standard (DSA), CTA had a pooled sensitivity of 82% (95%CI, 68-91%) and a specificity of 97% (95%CI, 93-98%), while TCD had lower sensitivity 38% (95%CI, 19-62%) and specificity of 91% (95%CI, 87-94%). Only the LR + for CTA (27.3) reached clinical significance to rule in diagnosis. LR - for CTA (0.19) and TCD (0.68) approached clinical significance (< 0.1) to rule out diagnosis. CTA showed higher LR + and lower LR - than TCD for diagnosing radiographic vasospasm, thereby achieving a strong recommendation for its use in ruling in or out vasospasm, based on the high quality of evidence. TCDs had very low LR + and a reasonably low LR - , thereby achieving a weak recommendation against its use in ruling in vasospasm and weak recommendation for its use in ruling out vasospasm.

Diagnostic Value of Micro-Bubble Transcranial Doppler Combined with Contrast Transthoracic Echocardiography in Cryptogenic Stroke Patients with Patent Foramen Ovale.

Background: In recent years, increasing attention has been paid to cryptogenic stroke (CS) caused by the patent foramen ovale (PFO). Objective: This study aims to evaluate the value of microbubble transcranial Doppler (MB-TCD) combined with contrast transthoracic echocardiography (cTTE) in the diagnosis of cryptogenic stroke patients with PFO. Materials and Method: From January 2014 to January 2019, patients who suffered from CS were recruited and divided into the cTTE group and MB-TCD combined with cTTE group. All patients were further checked by transesophageal echocardiography (TEE). Results: A total of 130 patients accepted cTTE examination, and 109 patients accepted MB-TCD combined with cTTE. In the group, 52 of the 54 positive patients were finally confirmed by TEE with PFO, and 12 of the 76 negative patients were finally confirmed by TEE with PFO. In combined group, 50 patients were negative on both two examination (Negative group), 54 were positive on both two examination (Positive group) and finally confirmed by TEE indeed with patent foramen ovale (PFO), while remaining five (5) patients were positive only on MB-TCD (Suspected group). After checked by TEE, three (3) of five patients with MB-TCD positive were confirmed by TEE indeed with PFO. The sensitivity, specificity, positive likelihood ratio (+LR), and Youden's index of cTEE in diagnostic of cryptogenic stroke patients with PFO were 81.25%, 96.97%, 26.82 and 0.78, respectively, and these for MB-TCD combined with cTTE were 100%, 96.15%, 25.97 and 0.96, respectively. MB-TCD medium can sensitively discover PFO in cryptogenic stroke patients with 100% sensitivity and a missdiagnosis rate of 0. Conclusion: The combination of MB-TCD and cTTE can improve the sensitivity and specificity of PFO diagnosis in cryptogenic stroke patients. MB-TCD medium also had high sensitivity and specificity.

An exploratory study to identify neonatal arterial ischemic stroke: A single-center study.

BACKGROUND: Neonatal arterial ischemic stroke (NAIS) presents as seizures, including convulsions, subtle seizures, and apnea, and most patients experience neurological sequelae. Diagnosis is often delayed owing to low test sensitivity. The present study aimed to identify the early clinical diagnostic factors for NAIS in neonates with seizures. METHODS: The present study included 54 patients born at ≥36 weeks of gestation during the last 15 years who presented to the neonatal intensive care unit with neonatal seizures and underwent brain magnetic resonance imaging (MRI), 6 of whom were diagnosed with NAIS. Maternal background, clinical characteristics, and transcranial pulsed Doppler sonography results were retrospectively reviewed. RESULTS: Of the 24 patients who presented with convulsions or subtle seizures, 3 (13%) were diagnosed with NAIS and 3 of 30 patients (10%) presented with apnea. Maternal premature ventricular contraction complications were higher in the NAIS group than in the non-NAIS group (p = 0.01). NAIS group showed lower mean middle cerebral artery (MCA) resistance index (RI) was lower the non-NAIS group (p = 0.009), while the left-right RI difference (p = 0.019), mean MCA blood velocity (MnV; p = 0.04), and left-right MnV difference (p < 0.001) in cerebral blood flow velocities (CBFVs) were higher in the NAIS group. CONCLUSIONS: Our results revealed that maternal arrhythmia may be a diagnostic factor for NAIS in neonates with seizures. Early brain MRI is essential in neonates with seizures and findings of low MCA-RI, high MCA-MnV, or high left-right difference in CBFVs to distinguish between NAIS and non-NAIS.

Adjunct Methods for the Detection of Patent Foramen Ovale: The Contribution of Transcranial Doppler and the Valsalva Manoeuvre.

A patent foramen ovale (PFO) is present in 25% of the population. In some patients, especially those without traditional stroke risk factors and with no immediately apparent cause, a cryptogenic stroke may be caused by an embolus passing through the PFO to the systemic circulation. The identification, or indeed exclusion, of a PFO is sought in these patients, most commonly using contrast-enhanced transthoracic or transoesophageal echocardiography. Another method for detecting a PFO is transcranial Doppler, which allows the detection of PFO possibly without the need for an echo laboratory, and with arguably improved sensitivity. This review will focus on transcranial Doppler detection of PFO, with a brief summary of echocardiographic techniques and the use of ultrasound contrast agents, and the role of provocations to increase diagnostic accuracy, specifically the Valsalva manoeuvre. We discuss the phases alongside the direct and indirect signs of an adequate Valsalva manoeuvre.

Prevalence of Patent Foramen Ovale in North Indian Cryptogenic Young Strokes.

Background: : Strokes of the undetermined cause or cryptogenic strokes (CS) account for 30-40% of ischemic strokes. Paradoxical embolism secondary to patent foramen ovale (PFO) may be associated with CS. Transcranial Doppler (TCD) with bubble contrast is a noninvasive bedside tool for diagnosis of right-to-left shunt (RLS) with high sensitivity and specificity. Data on the prevalence of PFO in CS in India are lacking. We determined the prevalence of RLS likely secondary to PFO in cryptogenic young strokes of the north Indian population using TCD with bubble contrast. Patients and Methods: : In this hospital-based prospective cross-sectional study, TCD with bubble contrast was performed in 57 young (age 15 > 45 years) CS and 50 healthy controls for the detection of RLS. The risk of paradoxical embolism (RoPE) score was calculated from various variables such as age, presence of cortical stroke on neuroimaging, and absence of vascular risk factors. Results: : 57 young CS and 50 healthy controls were recruited. TCD with bubble contrast was positive in 31% cases vs 6% in controls (P = 0.001). All patients with TCD positive for RLS had superficial cortical infarcts (P = 0.03). The median RoPE score of our patients was 9 (range: 7-10). Conclusions: : There is a high prevalence of RLS likely secondary to PFO in cryptogenic young strokes in north India. TCD with bubble contrast is an excellent bedside tool for the detection of RLS.

Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.

BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. RESULTS: One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). CONCLUSIONS: Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.

Transcranial Doppler for stratification of high-risk morphology of patent foramen ovale in patients with cryptogenic stroke.

Microbubble testing using transcranial Doppler (TCD) is an important screening tool for diagnosing paradoxical cerebral embolism with high-risk PFO. However, little is known about the association between the microbubble test by TCD and the features of high-risk PFO evaluated by transesophageal echocardiography (TEE). We studied 101 consecutive patients at Showa University, from April 2019 to October 2020, who underwent both TCD and TEE with a sufficient Valsalva maneuver and who were strongly suspected by neurologists as cryptogenic stroke. According to the appearance of microbubbles as high-intensity transient signals (HITS), the TCD grade was stratified into three categories based on the criteria (A: none, no HITS, B: small; 1-10 HITS, and C: large; > 10 HITS, or an uncountable number of HITS). Among patients with RLS through the PFO in TEE, high-risk morphological features of PFO for cerebral embolism were evaluated as follows: (1) tunnel height, (2) tunnel length, (3) total excursion distance of the atrial septum into the right and left atrium, (4) existence of Eustachian valve or Chiari network, (5) angle of PFO from the inferior vena cava, and (6) large shunt (20 or more microbubbles). Of 101 patients (TCD grade; Group A = 49, Group B = 26, Group C = 26), RLS through PFO was detected in 37 patients (grade A = 8, grade B = 6, grade C = 23) by TEE. Among PFO-positive patients, tunnel height, length, total excursion distance into the right and left atria, angle of PFO from the inferior vena cava, and frequency of large shunt in TEE were significantly larger in grade C than in grade A and B (p < 0.05). Additionally, grade C patients had significantly more forms of high-risk PFOs than those in grades A and B when the six features of high-risk PFO were compared. A multivariate logistic regression demonstrated that the tunnel length of PFO and the presence of large shunt in TEE were independently associated with large HITS in TCD (odds ratio: 1.18 and 49.5, 95% confidence interval 1.043-1.337 and 10.05-244.3, p = 0.0086 and p < 0.0001, respectively). In conclusion, the existence of a large HITS detected by TCD may have a screening advantage in predicting the high-risk morphologies of PFO that can cause paradoxical cerebral embolism.

Impact of Stellate Ganglion Block in the Management of Cerebral Vasospasm: A Prospective Interventional Study.

Background: Stellate ganglion block (SGB) causes blockage of sympathetic nerve activity, which may lead to intracerebral vessel dilatation and relieve cerebral vasospasm in patients of aneurysmal subarachnoid hemorrhage (aSAH). Objective: The aim of this study was to evaluate the efficacy and safety of SGB to relieve cerebral vasospasm on clinicoradiological parameters. Materials and Methods: We prospectively included 20 patients with clinical and angiographic evidence of vasospasm post aneurysmal clipping. Cerebral blood flow velocity and Lindegaard ratio were assessed using transcranial Doppler (TCD). Location of vasospasm, vessel diameter, vasospasm severity, parenchymal filling time, and venous sinus filling time were assessed on digital subtraction angiography (DSA). Patients received ultrasound-guided SGB with 10 mL of 0.5% bupivacaine on the ipsilateral side of the vasospasm. After 30 minutes, the neurological status, TCD, and DSA parameters were reevaluated. Results: After SGB, there was statistically significant reduction in the middle cerebral artery (MCA) peak systolic velocity (P = 0.005), mean flow velocity (P = 0.025), and Lindegaard ratio (P = 0.022) on TCD. We observed significant dilatation in the mean vessel diameter measured at the mid-M1 segment of MCA (P = 0.003) and mid-A1 segment of ACA (P = 0.002) on DSA. The mean parenchymal filling time and mean venous sinus filling time decreased nonsignificantly after SGB (P = 0.163/0.104). Neurological improvement was observed in five (25%) patients. Conclusion: SGB has positive clinicoradiological influence in the management of cerebral vasospasm of large vessels. However, its effect on cerebral microvasculature is limited and needs a larger database for further analysis.

Safety and efficacy of a novel robotic transcranial doppler system in subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) secondary to vasospasm is a determinate of outcomes following non-traumatic subarachnoid hemorrhage (SAH). SAH patients are monitored using transcranial doppler (TCD) to measure cerebral blood flow velocities (CBFv). However, the accuracy and precision of manually acquired TCD can be operator dependent. The NovaGuide robotic TCD system attempts to standardize acquisition. This investigation evaluated the safety and efficacy of the NovaGuide system in SAH patients in a Neuro ICU. We retrospectively identified 48 NovaGuide scans conducted on SAH patients. Mean and maximum middle cerebral artery (MCA) CBFv were obtained from the NovaGuide and the level of agreement between CBFv and computed tomography angiography (CTA) for vasospasm was determined. Safety of NovaGuide acquisition of CBFv was evaluated based on number of complications with central venous lines (CVL) and external ventricular drains (EVD). There was significant agreement between the NovaGuide and CTA (Cohen's Kappa = 0.74) when maximum MCA CBFv ≥ 120 cm/s was the threshold for vasospasm. 27/48 scans were carried out with CVLs and EVDs present without negative outcomes. The lack of adverse events associated with EVDs/CVLs and the strong congruence between maximal MCA CBFv and CTA illustrates the diagnostic utility of the NovaGuide.

Transcranial Doppler findings in a population with clinical probable reversible cerebral vasoconstriction syndrome.

OBJECTIVE: To describe transcranial Doppler (TCD) findings in a population with clinical probable RCVS. Exploratory objectives included the study of clinical characteristics of probable RCVS patients with and without spasm detected by TCD. METHODS: Cross-sectional cohort study of patients with thunderclap headache (TCH) without subarachnoid hemorrhage (SAH) of our neurology and headache center between 2010 and 2019, selecting patients with clinical diagnosis of probable RCVS (negative angiography study) by ICHD-3 criteria and with at least two TCD studies. RESULTS: From 114 TCH patients, 36/114 had probable RCVS by ICHD-3 criteria and had at least two TCD studies available. The mean age at RCVS onset was 42.9years (21-72years); 29/36 (80.6%) were female, 7/28 (25%) had cardiovascular risk factors and 20/36 (55.6%) had history of migraine. Most common triggers were stressful emotion, drugs, valsalva maneuvers and sexual activity. Five/36 (13.9%) had complications and 3/36 (8.3%) had late recurrence. Initial TCD was performed on average of 16 (6-26) days after headache onset. Twenty-nine had vasospasm on TCD, presenting mean flow velocity of MCA (VMCA) of 135.7±17.0cm/s and mean maximum VMCA of 138.3±17.2. Vasospasm was mild in 21/29 patients (72.4%) and moderate in 8/29 (27.6%). Complete VMCA normalization occurred on average 41 (30-70) days after headache onset and 24 (11-47) days after initial TCD. The group of patients with vasospasm detected by TCD had more female patients (26/29, 89.7% vs. 3/7, 42.8%, P=0.016), and more TCH attacks (mean of 3.6 vs. 2.14, P=0.049). CONCLUSION: TCD may be a useful tool in the identification of vasospasm in patients with probable RCVS, supporting the diagnosis of RCVS in patients presenting with recurrent TCH without SAH.

Cerebral microemboli during extracorporeal life support: a single-centre cohort study.

OBJECTIVES: The aim of this study was to investigate the load and composition of cerebral microemboli in adult patients undergoing venoarterial extracorporeal life support (ECLS). METHODS: Adult ECLS patients were investigated for the presence of cerebral microemboli and compared to critically ill, pressure-controlled ventilated controls and healthy volunteers. Cerebral microemboli were detected in both middle cerebral arteries for 30 min using transcranial Doppler ultrasound. Neurological outcome (ischaemic stroke, global brain ischaemia, intracerebral haemorrhage, seizure, metabolic encephalopathy, sensorimotor sequelae and neuropsychiatric disorders) was additionally evaluated. RESULTS: Twenty ECLS patients (cannulations: 15 femoro-femoral, 4 femoro-subclavian, 1 femoro-aortic), 20 critically ill controls and 20 healthy volunteers were analysed. ECLS patients had statistically significantly more cerebral microemboli than critically ill controls {123 (43-547) [median (interquartile range)] vs 35 (16-74), difference: 88 [95% confidence interval (CI) 19-320], P = 0.023} and healthy volunteers [11 (5-12), difference: 112 (95% CI 45-351), P < 0.0001]. In ECLS patients, 96.5% (7346/7613) of cerebral microemboli were of gaseous composition, while solid cerebral microemboli [1 (0-5)] were detected in 12 out of 20 patients. ECLS patients had more neurological complications than critically ill controls (12/20 vs 3/20, P = 0.003). In ECLS patients, a high microembolic rate (>100/30 min) tended to be associated with neurological complications including ischaemic stroke, neuropsychiatric disorders, sensorimotor sequelae and non-convulsive status epilepticus (odds ratio 4.5, 95% CI 0.46-66.62; P = 0.559). CONCLUSIONS: Our results indicate that adult ECLS patients are continuously exposed to many gaseous and, frequently, to few solid cerebral microemboli. Prolonged cerebral microemboli formation may contribute to neurological morbidity related to ECLS treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02020759, https://clinicaltrials.gov/ct2/show/NCT02020759?term=erdoes&rank=1.

Effects of 2D-Shear Wave Elastography on Brain-Derived Neurotrophic Factor (BDNF) in the Brains of Neonatal Mice and Exploration of the Mechanism.

BACKGROUND The aim of this study was to explore the effect and duration of 2-dimensional shear wave elastography (2D-SWE) irradiation on the expression of brain-derived neurotrophic factor (BDNF) in the brains of neonatal mice and to preliminarily investigate whether its mechanism is neuronal apoptosis. MATERIAL AND METHODS Neonatal mice (within 48 hours of birth) were subjected to 2D-SWE irradiation of the brain for 10 minutes (group S1), 20 minutes (group S2), and 30 minutes (group S3). The mice were sacrificed immediately after irradiation or 24 hours after irradiation. Brains were collected for real-time polymerase chain reaction (RT-PCR) and western blot experiments to determine the expression of BDNF in each group. TdT-mediated dUTP nick-end labeling (TUNEL) was performed to observe neuronal apoptosis in the brain. RESULTS The results of PCR and western blots from the brains of neonatal mice that were sacrificed immediately after irradiation show that S1, S2, and S3 were significantly different from those in the control group. The PCR and western blot results of brain tissues from neonatal mice sacrificed at 24 hours after irradiation showed that there was no significant difference between the S1, S2, S3, and control groups. The results of TUNEL experiments showed that there was no statistically significant difference in the number of apoptotic neurons between the S1, S2, S3, and control groups. CONCLUSIONS 2D-SWE irradiation of neonatal mice for more than 10 minutes downregulated the expression of BDNF. This effect disappeared within 24 hours after the irradiation, and the 2D-SWE scan seemed not to induce neuronal apoptosis.

Cardiac-Neurovascular Adverse Effects Responsible to Contrast Transcranial Doppler: A Case Report.

Introduction and Case Presentation: A 44-year-old female patient suffered migraines and underwent contrast-enhanced transcranial Doppler (c-TCD). During the rapid injection of contrast agent, she suffered chest tightness, palpitation, decreased consciousness, perimouth numbness, and headache, respectively. Meanwhile, "curtain" pattern of air embolic signals lasted up to 115 seconds in her decreased right middle cerebral artery accompanied with arrhythmia. The microair embolic signals lasted as long as 340 seconds. The patient's symptoms were relieved in 30 minutes. The aforementioned symptoms and signs occurred, lasted, then disappeared coinciding in time with changes of microbubbles. The woman was later found to have ventricular septal defect. Discussion: The adverse effects to cardiac-neurovascular system of c-TCD are reported for the first time, which arouse attention to safety of the procedure.

Safety of thrombolytic therapy with rt-PA and transcranial color Doppler ultrasound (TCCS) combined with microbubbles: a histopathologic study on rabbit brain tissues.

OBJECTIVE: To evaluate effect of thrombolytic therapy with rt-PA (recombinant tissue plasminogen activator) and transcranial color Doppler ultrasound (TCCS) combined with microbubbles on histology of brain tissue. METHODS: New Zealand rabbits were subjected to TCCS based thrombolytic therapy, in 8 groups depending on dose of rt-PA, exposure duration of TCCS and presence of attenuation by skull bone window, 2 animals/group: (1) skull+1/2 rt-PA+TCCS+MBs, 10 min, (2) skull+rt-PA+TCCS+MBs, 10 min, (3) skull+1/2 rt-PA+TCCS+MBs, 20 min, (4) skull+rt-PA+TCCS+MBs, 20 min, (5) skull+1/2 rt-PA+TCCS+MBs, 30 min, (6) skull+rt-PA+TCCS+MBs, 30 min, (7) 1/2 rt-PA+TCCS+MBs, 10 min, (8) 1/2 rt-PA+TCCS+MBs, 20 min. The brain tissues were harvested after therapies and submitted for microscopic, electronic microscope and immunohistochemical examination. The histological changes were scored. RESULTS: TCCS caused exposure duration dependent brain tissue damage. With attenuation by bone window, TCCS based therapies for 10-20 min caused minimal tissue damage. However, significant tissue damage was observed upon TCCS for 30 min in presence of skull bone window, presenting as hemorrhage, misdistribution of organelles, demyelination of nerve fibers, and thinning of basement membrane in blood-brain barrier, which was milder than that after 20 min of exposure to TCCS in absence of bone window. Dose of rt-PA did not affect brain histology in all groups. CONCLUSION: Short treatment of brain tissue with TCCS through a bone window is relative safe. And skull bone window protected brain tissue from TCCS induced damage.

The value of transcranial Doppler imaging in children with tuberculous meningitis.

PURPOSE: Transcranial Doppler imaging (TCDI) is potentially a valuable investigational tool in children with tuberculous meningitis (TBM), a condition often complicated by pathology relevant to Doppler imaging such as raised intracranial pressure (ICP) and cerebral vasculopathies. METHODS: Serial TCDI was performed on 20 TBM children with the aim of investigating cerebrovascular haemodynamics and the relationship between pulsatility index (PI) and ICP. RESULTS: We observed a poor correlation between ICP and PI in children with communicating hydrocephalus (p = 0.72). No decline in PI was noted following 7 days of medical therapy for communicating hydrocephalus (p = 0.78) despite a concomitant decline in ICP. Conversely, a decline in PI was noted in all four children with non-communicating hydrocephalus who underwent cerebrospinal fluid diversion. High blood flow velocities (BFV) in all the basal cerebral arteries were observed in 14 children (70 %). The high BFV persisted for 7 days suggesting stenosis due to vasculitis rather than functional vasospasm. Complete middle cerebral artery (MCA) occlusion, subnormal mean MCA velocities (<40 cm/s) and PIs (<0.4) correlated with radiologically proven large cerebral infarcts. CONCLUSIONS: TCDI-derived PI is not a reliable indicator of raised ICP in children with tuberculous hydrocephalus. This may be attributed to individual variation of tuberculous vascular disease, possibly compromising cerebral vascular compliance and resistance. Basal artery stenosis secondary to vasculitis is observed during the acute stage of TBM in the majority of children.