Transcranial doppler velocity in iron-deficient Nigerian children with sickle cell anemia.

Oral iron supplementation in iron deficient children with sickle cell anemia and normal transcranial Doppler ultrasound (TCD) velocities does not reduce arterial flow in the middle cerebral artery.

Role of transcranial Doppler in assessment of cerebral blood flow in full term neonates with extreme unconjugated hyperbilirubinemia.

PURPOSE: To evaluate the difference in cerebral blood flow in neonates with and without extreme unconjugated hyperbilirubinemia. METHODS: Transcranial Doppler parameters of 26 full term newborns with extreme unconjugated hyperbilirubinemia (UCH) were compared to 13 postnatal age and sex matched normal healthy neonates serving as controls. Resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV) were measured in the middle cerebral, internal carotid and posterior cerebral arteries on both sides by transcranial color Doppler ultrasound. RESULTS: An increase in cerebral blood flow (decreased RI, PI and increased PSV) was observed in the extreme unconjugated hyperbilirubinemia (UCH) group. There was positive correlation between total serum bilirubin level and peak systolic velocity and vice versa with resistivity and pulsatility indices. Eight neonates developed clinical features of acute bilirubin encephalopathy and showed significantly increased peak systolic velocity in the right middle cerebral artery compared to those with normal outcome. Resistivity index and pulsatility index were lower in patients managed by exchange transfusion compared to those managed with phototherapy. CONCLUSION: An increase in cerebral blood flow was observed in neonates with UCH compared to those without hyperbilirubinemia. By assessing the cerebral blood flow velocity, resistivity index (RI), and pulsatility index (PI) of particular intracranial arteries, the transcranial Doppler can identify the at-risk neonates, for development of neurological affliction in extreme unconjugated hyperbilirubinemia.

Cerebrovascular reactivity during visual stimulation: Does hypnotizability matter?

Hypnotizability is a trait associated with several physiological correlates including cardiovascular control. The present study aimed to investigate the posterior cerebral artery flow velocity (PCAv) in basal closed eyes (B) and during visual stimulation (VS) conditions in med-highs and med-lows. Twenty-four healthy volunteers were submitted to the hypnotic assessment through the Stanford Hypnotic Susceptibility Scale, form A which classified 13 low-to-medium (med-lows) and 10 high-to-medium (med-highs) hypnotizable participants. One subject scoring 6 out of 12 was excluded from the comparisons between groups. Arterial blood pressure, heart rate, and partial pressure of end-tidal CO2 were monitored during both B and VS conditions. Simultaneously, PCAv was assessed by transcranial Doppler. Cerebrovascular Reactivity (CVR) was computed as a percentage of the PCAv change occurring during VS with respect to B (ΔPCAv). During VS both groups increased their PCAv (mean ± SD: 7.9 ± 5.2 %) significantly with no significant group difference. However, among med-highs, CVR was negatively correlated with hypnotizability scores. Thus, higher hypnotizability may be associated with lower metabolic demand in response to VS only within med-highs hypnotizable participants.

Cerebral hemodynamics in children with sickle cell disease in India: An observational cohort study.

India has the second highest number of cases of sickle cell disease (SCD) and affects the most socioeconomically disadvantaged communities living in a horizontal belt from Gujarat to Odisha state. Despite high prevalence, information about cerebral hemodynamics among children with SCD in India remains scarcely described. We performed transcranial Doppler (TCD) to assess cerebral hemodynamics among Indian children with SCD and evaluated their association with clinical and hematological parameters. Children aged 3-18years, diagnosed with SCD living in Raipur in Chhattisgarh and Ahmedabad in Gujarat state were recruited. TCD was performed to obtain flow velocities from middle cerebral (MCA), intracranial internal carotid (ICA) and basilar artery. Associations were evaluated between timed-average-mean-maximum velocities (TAMMV) and various clinical and hematological parameters. Our prospective study included 62 consecutive children with known SCD. Mean ± SD age of the study population was 9.8 ± 3.9 years and 31 (50%) were male. Mean ± SD hemoglobin was 8.64 ± 1.34 Gm/dL while the mean HbSS ± SD was 70.25 ± 15.27%. While 6 (9.6%) children had suffered from stroke during previous 2 years, 7 (11%) demonstrated abnormal TAMMV. Higher HbSS level along with history of iron chelation therapy, blood transfusion and/or stroke showed a trend towards having higher TAMMV. Stroke and cerebral hemodynamic alterations are common among Indian children with SCD. Larger studies with detailed neuroimaging and genetic evaluations are needed for better understanding, characterization, risk stratification as well as optimization of the timing of blood transfusion to reduce physical disabilities among Indian children with SCD.

Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia.

Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSß0thalassemia), exposed to chronic transfusions (n = 12) or hydroxyurea (n = 32), median age 19.2 years (range 18.0-31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5-54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0-15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76-0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2-64), abnormal pediatric exam (P = 0.00084), and elevated transcranial Doppler ultrasound velocities (P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.

Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways. OBJECTIVE: We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal. METHODS: In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 °C at the target and <3 °C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS. RESULTS: We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound. CONCLUSION: Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.

Can cervical vascular ultrasound combined with transcranial Doppler ultrasound accurately diagnose cerebral infarction?: A protocol for a systematic review and meta-analysis.

BACKGROUND: The purpose of this study is to investigate the impact of cervical vascular ultrasound (CVU) combined transcranial Doppler ultrasound (TDU) in the diagnosis of cerebral infarction (CI). METHODS: The following electronic databases will be sought from PUBMED, EMBASE, Cochrane Library, PSYCINFO, Web of Science, Allied and Complementary Medicine Database, WANGFANG, VIP database, and China National Knowledge Infrastructure. The search period will cover from the initial indexing to March 1, 2020 without restrictions of language and publication status. All case-controlled studies which identifying the impact of CVU combined TDU in the diagnosis of CI will be considered. Two authors will independently perform the whole process of study selection, data extraction, and quality assessment, respectively. If any disagreements occur between two authors, we will invite a third experienced author to help solve them through discussion. Quality Assessment of Diagnostic Accuracy Studies tool will be used to check study quality, and RevMan V.5.3 software and Stata V.12.0 software will be utilized to carry out statistical analysis. RESULTS: This study will summarize the most recent evidence that focusing on the impact of CVU combined TDU in the diagnosis of CI. CONCLUSION: This study will provide helpful evidence to determine whether CVU combined TDU is an accurate diagnosis tool for CI or not. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020171367.

Impact of transcranial Doppler sonography for detecting ischemic stroke: A protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to explore the impact of transcranial Doppler sonography (TDS) for detecting ischemic stroke (IS). METHODS: PUBMED, EMBASE, Cochrane Library, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge In-frastructure will be utilized to examine case-controlled studies that used TDS for detecting IS. All electronic databases will be searched from inception to March 20, 2020. All study selection, data extraction, and study quality assessment will be carried out by 2 independent reviewers. All study quality will be assessed by Quality Assessment of Diagnostic Accuracy Studies tool, and statistical analysis will be performed by RevMan V.5.3 software and Stata V.12.0 software. RESULTS: This study will explore the impact of TDS for detecting IS through sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. CONCLUSION: This study expects to find out whether TDS can be utilized for IS detection.Systematic review registration: INPLASY202040155.

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep.

BACKGROUND: Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI). OBJECTIVE: To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI. METHODS: Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS. RESULTS: No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS. CONCLUSIONS: The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

Comparative effectiveness of Ginkgo injections for treating vertebrobasilar insufficiency: A systematic review and network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: This study sought to assess the clinical effectiveness of Ginkgo injections (GIs) combined with conventional drugs for vertebrobasilar insufficiency (VBI). METHODS: Randomized controlled trials (RCTs) that assessed the adjunctive effects of GIs for patients with VBI were retrieved from several English and Chinese databases from inception to December 2018. The Cochrane risk of bias method was used to evaluate the methodological quality of the eligible trials. The data were analysed by Stata 13.0 and WinBUGS 1.4.3 software. RESULTS: A total of 20 RCTs that included 1710 patients were included. All RCTs had an unclear risk of bias or a high risk of bias. The network meta-analysis (NMA) showed that the use of four kinds of GIs, especially Ginkgo leaf extract and dipyridamole injections (GDs), as adjunctive therapies with drugs for VBI increased the total effectiveness rate. Ginkgo biloba leaf extract injections (EGbs) combined with conventional drugs were more effective than only conventional drugs for improving the results of transcranial Doppler ultrasonography (TCD). Shuxuening injections (SXNs) seemed superior for improving blood viscosity-related indicators. Adverse events were mentioned in nine trials, and there was no difference between the GI group and the control group for the incidence rate of adverse events. WHAT IS NEW AND CONCLUSIONS: GIs showed significant benefits as an add-on therapy for VBI, as GIs increased the total effectiveness rate and improved the results of TCD examinations. Due to the limited sample size and quality of the included trials, the results of this review still need to be tested in larger, rigorous studies in the future.

Effects of GB34 acupuncture on hyperventilation-induced carbon dioxide reactivity and cerebral blood flow velocity in the anterior and middle cerebral arteries of normal subjects.

OBJECTIVES: To determine whether acupuncture at GB34 affects cerebral blood flow (CBF) via the anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs). METHODS: This study included 10 healthy young male volunteers. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The changes in hyperventilation-induced carbon dioxide (CO2) reactivity and modified blood flow velocity at 40 mm Hg (CV40) were observed for both ACAs and MCAs before and after GB34 acupuncture treatment. Blood pressure and heart rate were also measured before and after GB34 acupuncture treatment. RESULTS: The CO2 reactivity of the ipsilateral MCA significantly increased after GB34 acupuncture treatment, compared with that at baseline (P=0.007). In contrast, the CO2 reactivity of both ACAs and the contralateral MCA remained unchanged. The CV40 of both ACAs and MCAs did not change after GB34 acupuncture treatment and neither did the mean arterial blood pressure and heart rate. CONCLUSIONS: GB34 acupuncture treatment increased CO2 reactivity specifically in the ipsilateral MCA, but had no effect on either the ACAs or the contralateral MCA. These data suggest that GB34 acupuncture treatment improves the vasodilatory potential of the cerebral vasculature to compensate for fluctuations caused by changes in external conditions and could potentially be useful for the treatment of disorders of the ipsilateral MCA circulation.

Acquired epileptiform opercular syndrome evaluated with real-time transcranial Doppler ultrasound-video-electroencephalogram before and after treatment: a case report.

BACKGROUND: Acquired epileptiform opercular syndrome (AEOS) with electrical status epilepticus during sleep (ESES) may be recurrent and intractable. The real-time transcranial Doppler ultrasound-sleep-deprived video electroencephalogram (TCD-SDvEEG) can be used to observe the relationships among hemodynamic, electrophysiological, and clinical factors in a patient during therapy. This study reported the case of a healthy 5-year-old boy with AEOS. CASE PRESENTATION: The patient had initial seizures during sleep at the age of 1 year, with the left mouth pouting, left eye blinking and drooling for several seconds, and, sometimes, the left upper-limb flexion and head version to the left, lasting for 1-2 min. The combined antiepileptic drug regimens, including valproate, lamotrigine, and clonazepam, failed in the present case. Therefore, the add-on high-dose methylprednisolone therapy was provided. Also, the serial TCD-SDvEEG was used to monitor the dynamic changes before and after add-on steroid treatment. The results showed less than 15% variation in the range of blood flow fluctuation with spikes during non-rapid eye movement sleep after treatment. This was similar to the outcomes in healthy children and also accorded with the clinical improvements such as seizure control, drooling control, and language ability melioration. However, 95% of spike-wave index (SWI) was still maintained. The improvements in cerebral hemodynamics and clinical manifestations were faster and earlier than the SWI progression. CONCLUSIONS: The real-time TCD-SDvEEG was highly sensitive in detecting therapeutic changes. The findings might facilitate the understanding of the mechanisms underlying neurovascular coupling in patients with AEOS accompanied by ESES.

Imaging Diagnosis of Transient Ischemic Attack in Clinic and Traditional Chinese Medicine.

Neuroimaging plays a pivotal role in Transient Ischemic Attack (TIA). Generally, clinicians focus on the specific changes in morphology and function, but the diagnosis of TIA often depends on imaging evidence. Whereas Traditional Chinese Medicine (TCM) is concerned with the performance of clinical symptoms, they began to use imaging methods to diagnose TIA. CT and MRI are the recommended modality to diagnose TIA and image ischemic lesions. In addition, Transcranial Doppler sonography (TCD) and Digital Subtraction Angiography (DSA) are two acceptable alternatives for diagnosing TIA patients. This article elaborates the update of imaging modalities in clinic and the development of imaging modalities in TCM. Besides, multiple joint imaging technologies also will be evaluated whether enhanced diagnostic yields availably.

A novel rescue therapy for cerebral vasospasm: Cisternal Nimodipine application via stereotactic catheter ventriculocisternostomy.

Delayed Cerebral Infarction (DCI) due to Cerebral Vasospasm (CVS) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Despite established risk factors CVS and DCI are unpredictable at the individual patient level. Efficient treatments are lacking. We report a novel rescue therapy for DCI: Access to the basal cisterns by stereotactic catheter ventriculocisternostomy (STX-VCS) and direct cisternal application of the spasmolytic agent Nimodipine. On the basis of individual treatment decisions three aSAH patients who developed CVS underwent STX-VCS. Continuous lavage with Nimodipine was performed. CVS was assessed by daily transcranial doppler ultrasonography. Neurological outcome at 3 months was assessed by modified Rankin scale. STX-VCS was performed without complications in all patients. CVS rapidly resolved upon cisternal application of Nimodipine. CVS recurred in two patients upon interruption of Nimodpine application and resolved upon restart of Nimodipine. DCI did not occur in all three cases. STX-VCS and cisternal Nimodipine application is a novel rescue therapy for CVS treatment and DCI-prevention in patients with aSAH.

EEG of patients in coma after traumatic brain injury reflects physical parameters of auditory stimulation but not its emotional content.

PRIMARY OBJECTIVE: We aimed to investigate the origin of EEG response of patients in coma and after moderate TBI to emotional stimulation, whether they distinguish emotional content or only react to the physical features of an audio signal. RESEARCH DESIGN: We registered EEG during continuous pleasant and unpleasant non-verbal stimulation and in rest. A total of 69 subjects participated in our study: healthy adults, conscious patients after moderate TBI and patients in coma after severe TBI. We analysed the distances between the stimuli according to EEG data and applied correlation analysis to the distances, acoustic parameters of stimuli, subjects' emotional assessment of the stimuli, GCS score and Doppler ultrasound data. MAIN OUTCOMES AND RESULTS: The EEG response to the stimulation in patients in coma mostly reflects the physical parameters of the stimuli, and correlated with Doppler ultrasound data. The EEG of healthy adults reflects their psychological assessment of the stimuli. Patients after moderate TBI differentiate unpleasant stimuli well and pleasant stimuli poorly, they mainly consider pitch to cope with this task like healthy adults do. CONCLUSIONS: The reactivity to the acoustic features of emotional stimulation in patients in coma should be investigated further as a marker of patients' recovery. ABBREVIATIONS: TBI: traumatic brain injurym; TBI: moderate TBI; MCA: middle cerebral artery; GCS: Glasgow Coma Scale; M: mean; SD: standard deviation.

Pathological Laughter as a Symptom of Middle Cerebral Artery Stroke.

BACKGROUND: Pathological laughter is defined as uncontrollable and inappropriate laughter unrelated to an emotion or a mood. This symptom can reveal a stroke. CASE REPORT: We described the case of a 57-year-old patient who presented to the emergency department 2 h after a sudden onset of left hemiparesis preceded by pathological laughter. The left motor weakness was very discrete and underestimated because of severe behavioral changes, that is, laughter, joviality, and motor restlessness. Despite abnormal brain imaging results, symptoms were considered as atypical to evoke a stroke. The patient did not receive intravenous thrombolysis. Brain magnetic resonance imaging performed 2 days after admission confirmed the diagnosis of stroke. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians are at the forefront of stroke management. They should be aware that the initial symptom of a stroke can be atypical and lead to misunderstanding the diagnosis. Because the treatment of stroke requires the fastest care, it is important for emergency physicians to know that sudden behavioral troubles and pathological laughter can reveal strokes.

Towards optimal visual presentation design for hybrid EEG-fTCD brain-computer interfaces.

OBJECTIVE: In this paper, we introduce a novel hybrid brain-computer interface (BCI) system that measures electrical brain activity as well as cerebral blood velocity using electroencephalography (EEG) and functional transcranial Doppler ultrasound (fTCD) respectively in response to flickering mental rotation (MR) and flickering word generation (WG) cognitive tasks as well as a fixation cross that represents the baseline. This work extends our previous approach, in which we showed that motor imagery induces simultaneous changes in EEG and fTCD to enable task discrimination; and hence, provides a design approach for a hybrid BCI. Here, we show that instead of using motor imagery, the proposed visual stimulation technique enables the design of an EEG-fTCD based BCI with higher accuracy. APPROACH: Features based on the power spectrum of EEG and fTCD signals were calculated. Mutual information and support vector machines were used for feature selection and classification purposes. MAIN RESULTS: EEG-fTCD combination outperformed EEG by 4.05% accuracy for MR versus baseline problem and by 5.81% accuracy for WG versus baseline problem. An average accuracy of 92.38% was achieved for MR versus WG problem using the hybrid combination. Average transmission rates of 4.39, 3.92, and 5.60 bits min-1 were obtained for MR versus baseline, WG versus baseline, and MR versus WG problems respectively. SIGNIFICANCE: In terms of accuracy, the current visual presentation outperforms the motor imagery visual presentation we designed before for the EEG-fTCD system by 10% accuracy for task versus task problem. Moreover, the proposed system outperforms the state of the art hybrid EEG-fNIRS BCIs in terms of accuracy and/or information transfer rate. Even though there are still limitations of the proposed system, such promising results show that the proposed hybrid system is a feasible candidate for real-time BCIs.