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Fluorescence imaging (FI) employing near‐infrared (NIR) light within the range of ~750–1350 nm enables biomedical imaging several millimeters beneath the tissue surface. More recent investigations into the short‐wave IR (SWIR) transparency windows between ~1550–1870 and 2100–2300 nm highlight their superior capabilities. This research presents a comparison of IR‐FI of PbS quantum dots, emitting at 990, 1310, and 1580 nm, through the mouse scalp skin, skull, and brain. The SWIR fluorescence is the most effectively transmitted signal, showing particularly significant enhancement when passing through the skull, which causes high light scattering. For the analysis of the imaging results and light propagation through the organs, their spectra of attenuation, absorption, and scattering coefficients are measured. In view of biomedical imaging, attenuation due to light scattering is a more destructive factor. Hence, the spatial resolution and imaging contrast can be improved by operating in SWIR due to decreased light scattering. [ABSTRACT FROM AUTHOR]

Transcranial Doppler (TCD) ultrasound is a crucial non-invasive tool for assessing cerebral blood flow and is widely used to diagnose and monitor cerebrovascular diseases. This paper reaffirms the importance of TCD, details examination methods and precautions, and provides a guide for practitioners. TCD evaluates the blood flow velocity to assess stenosis, occlusion, and hemodynamic changes. Distinguishing between increased blood flow volume and decreased vessel diameter based solely on velocity is challenging, necessitating a comprehensive approach to integrating clinical findings and hemodynamic changes. The reliability of TCD results depends on the skill of the examiner and requires standardized procedures and continuous training. Advances in automation and artificial intelligence promise enhanced accuracy and reliability. Future research should focus on validating and clinically applying these technologies. This paper is a review of the clinical significance of TCD, methods, and precautions, offering a valuable guide for practitioners and highlighting the potential benefits of ongoing advancements in TCD for the diagnosis and treatment of cerebrovascular diseases.

Near infrared (NIR) light has been shown to provide beneficial treatment of traumatic brain injury (TBI) and other neurological problems. This concept has spawned a plethora of commercial entities and practitioners utilizing panels of light emitting diodes (LEDs) and promising to treat patients with TBI and other disorders, who are desperate for some treatment for their untreatable conditions. Unfortunately, an LED intended to deliver photonic energy to the human brain does not necessarily do what an LED pointed at a mouse brain does. There is a problem of scale. Extensive prior research has shown that infrared light from a 0.5-watt LED will not penetrate the scalp and skull of a human. Both the properties of NIR light and the manner in which it interacts with tissue are examined. Based on these principles, the shortcomings of current approaches to treating neurological disorders with NIR light are explored. Claims of clinical benefit from low-level LEDbased devices are explored and the proof of concept challenged. To date, that proof is thin with marginal benefits which are largely transient. Extensive research has shown fluence at the level of the target tissue which falls within the range of 0.9J/cm2 to 15J/cm2 is most effective in activating the biological processes at the cellular level which underlie direct photobiomodulation. If low-level infrared light from LED devices is not penetrating the scalp and skull, then these devices certainly are not delivering that level of fluence to the neurons of the subjacent brain. Alternative mechanisms, such as remote photobiomodulation, which may underlie the small and transient benefits for TBI symptoms reported for low-power LED-based NIR studies are presented. Actionable recommendations for the field are offered. [ABSTRACT FROM AUTHOR]

The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation. The NaviTH system consists of a 360-element, 700 kHz transmitter–receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps. The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm. The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. This is the first study in humans demonstrating noninvasive modulation of insula subregions to affect pain ratings, brain physiology related to pain (the contact heat–evoked potential), and also metrics of autonomic/cardiovascular activity including heart-rate variability. The insula is an intriguing target for pain modulation. Unfortunately, it lies deep to the cortex making spatially specific noninvasive access difficult. Here, we leverage the high spatial resolution and deep penetration depth of low-intensity focused ultrasound (LIFU) to nonsurgically modulate the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact heat–evoked potentials, as well as autonomic measures including heart-rate variability (HRV). In a within-subjects, repeated-measures, pseudo-randomized trial design, 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, electrodermal, electrocardiography and EEG recording. Low-intensity focused ultrasound was delivered to the AI (anterior short gyrus), PI (posterior longus gyrus), or under an inert Sham condition. The primary outcome measure was pain rating. Low-intensity focused ultrasound to both AI and PI similarly reduced pain ratings but had differential effects on EEG activity. Low-intensity focused ultrasound to PI affected earlier EEG amplitudes, whereas LIFU to AI affected later EEG amplitudes. Only LIFU to the AI affected HRV as indexed by an increase in SD of N-N intervals and mean HRV low-frequency power. Taken together, LIFU is an effective noninvasive method to individually target subregions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus. [ABSTRACT FROM AUTHOR]

Background: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer's disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT), or transcranial laser therapy, has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of transcranial photobiomodulation (tPBMT) on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (>9-year-old) dogs with moderate (16-33) to severe (>33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient's head, 3 times per week for one month and 2 times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30-and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD. [Open Vet J 2024; 14(5.000): 1167-1171]

As the coronavirus disease 2019 (COVID-19) pandemic spread to the United States in 2020, there was an impetus toward postponing or ceasing nonurgent transsphenoidal pituitary surgeries to prevent the spread of the virus. Some centers encouraged transcranial approaches for patients with declining neurologic function. However, no large-scale data exist evaluating the effects that this situation had on national pituitary practice patterns. Pituitary surgeries in the National Inpatient Sample were identified from 2017 to 2020. Surgeries in 2020 were compared with the 3 years previously to determine any differences in demographics, surgical trends/approaches, and perioperative outcomes. In 2020, there was a decline in overall pituitary surgeries (34.2 vs. 36.3%; odds ratio (OR), 0.88; P < 0.001) yet transsphenoidal approaches represented a higher proportion of interventions (69.0 vs. 64.9%; P < 0.001). Neurosurgical complications were higher (51.9 vs. 47.4%; OR, 1.13; P < 0.001) and patients were less likely to be discharged home (86.4 vs. 88.5%; OR, 0.84; P < 0.001). This finding was especially true in April 2020 during the first peak in COVID-19 cases, when transcranial approaches and odds of mortality/complications were highest. In 2020, transsphenoidal surgery remained the preferred approach for pituitary tumor resection despite initial recommendations against the approach to prevent COVID-19 spread. Pituitary surgeries had a higher risk of periprocedural complications despite accounting for preoperative comorbidities, COVID-19 infection status, and surgical approach, suggesting that an overwhelmed hospital system can negatively influence surgical outcomes in noninfected patients. [ABSTRACT FROM AUTHOR]

Aim: We aimed to describe the neurosonological findings related to cerebral hemodynamics acquired using transcranial Doppler and to determine the frequency of elevated ICP by optic nerve sheath diameter (ONSD) measurement in patients with severe coronavirus disease (COVID-19) hospitalized in the intensive care unit of a national referral hospital in Peru. Methods: We included a retrospective cohort of adult patients hospitalized with severe COVID-19 and acute respiratory failure within the first 7 days of mechanical ventilation under deep sedoanalgesia, with or without neuromuscular blockade who underwent ocular ultrasound and transcranial Doppler. We determine the frequency of elevated ICP bymeasuring the diameter of the optic nerve sheath, choosing as best cut-off value a diameter equal to or >5.8mm. We also determine the frequency of sonographic patterns obtained by transcranial Doppler. Through insonation of the middle cerebral artery. Likewise, we evaluated the associations of clinical, mechanical ventilator, and arterial blood gas variables with ONSD =5.8mm and pulsatility index (PI) =1.1. We also evaluated the associations of hemodynamic findings and ONSD with mortality the effect size was estimated using Poisson regression models with robust variance. Results: This study included 142 patients. The mean age was 51.39 ± 13.3 years, and 78.9% of patients were male. Vasopressors were used in 45.1% of patients, and mean arterial pressure was 81.87 ± 10.64 mmHg. The mean partial pressure of carbon dioxide (PaCO2) was elevated (54.08 ± 16.01 mmHg). Elevated intracranial pressure was seen in 83.1% of patients, as estimated based on ONSD =5.8mm. A mortality rate of 16.2% was reported. In the multivariate analysis, age was associated with elevated ONSD (risk ratio [RR] = 1.07). PaCO2 was a protective factor (RR = 0.64) in the cases of PI = 1.1. In the mortality analysis, the mean velocity was a risk factor for mortality (RR = 1.15). Conclusions: A high rate of intracranial hypertension was reported, with ONSD measurement being themost reliablemethod for estimation. The increase in ICP measured by ONSD in patients with severe COVID-19 on mechanical ventilation is not associated to hypercapnia or elevated intrathoracic pressures derived from protective mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer's disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT) or transcranial laser therapy has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of tPBMT on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (>9-year-old) dogs with moderate (16-33) to severe (>33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient's head, three times per week for one month and two times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30- and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD. [ABSTRACT FROM AUTHOR]

Transcranial histotripsy has shown promise as a non-invasive neurosurgical tool, as it has the ability to treat a wide range of locations in the brain without overheating the skull. One important effect of histotripsy in the brain is the blood–brain barrier (BBB) opening (BBBO) at the ablation site, but there is a knowledge gap concerning the extent of histotripsy-induced BBBO. Here we describe induction of BBBO by transcranial histotripsy and use of magnetic resonance imaging (MRI) and histology to quantify changes in BBBO at the periphery of the histotripsy ablation zone over time in the healthy mouse brain. An eight-element, 1 MHz histotripsy transducer with a focal distance of 32.5 mm was used to treat the brains of 23 healthy female BL6 mice. T1-gadolinium (T1-Gd) MR images were acquired immediately following histotripsy treatment and during each of the subsequent 4 wk to quantify the size and intensity of BBB leakage. The T1-Gd MRI results revealed that the hyperintense BBBO volume increased over the first week and subsided gradually over the following 3 wk. Histology revealed complete loss of tight junction proteins and blood vessels in the center of the ablation region immediately after histotripsy, partial recovery in the periphery of the ablation zone 1 wk following histotripsy and near-complete recovery of tight junction complex after 4 wk. These results provide the first evidence of transcranial histotripsy-induced BBBO and repair at the periphery of the ablation zone. [ABSTRACT FROM AUTHOR]

Near infrared (NIR) light has been shown to provide beneficial treatment of traumatic brain injury (TBI) and other neurological problems. This concept has spawned a plethora of commercial entities and practitioners utilizing panels of light emitting diodes (LEDs) and promising to treat patients with TBI and other disorders, who are desperate for some treatment for their untreatable conditions. Unfortunately, an LED intended to deliver photonic energy to the human brain does not necessarily do what an LED pointed at a mouse brain does. There is a problem of scale. Extensive prior research has shown that infrared light from a 0.5-watt LED will not penetrate the scalp and skull of a human. Both the properties of NIR light and the manner in which it interacts with tissue are examined. Based on these principles, the shortcomings of current approaches to treating neurological disorders with NIR light are explored. Claims of clinical benefit from low-level LED-based devices are explored and the proof of concept challenged. To date, that proof is thin with marginal benefits which are largely transient. Extensive research has shown fluence at the level of the target tissue which falls within the range of 0.9 J/cm2 to 15 J/cm2 is most effective in activating the biological processes at the cellular level which underlie direct photobiomodulation. If low-level infrared light from LED devices is not penetrating the scalp and skull, then these devices certainly are not delivering that level of fluence to the neurons of the subjacent brain. Alternative mechanisms, such as remote photobiomodulation, which may underlie the small and transient benefits for TBI symptoms reported for low-power LED-based NIR studies are presented. Actionable recommendations for the field are offered.

Objective To explore the application value of transcranialcerebral vessel Doppler (TVD) ultrasonography in the diagnoses and postoperative evaluations of type Ⅰ Chiari malformation in children. Methods From March 2018 to December 2021, the relevant clinical data were retrospectively reviewed for 27 children with type Ⅰ Chiari malformation. Based upon age, they were assigned into two groups of preschool (aged 1-6 year, n=15) and school-age (aged 7-16 year, n=12). TVD was detected at pre-operation, 24 h post-operation and 1 month post-operation. Posterior cerebral artery (PCA), bilateral vertebral artery (VA) and basilar artery (BA) in posterior cranial fossa were selected as target vessels. Peak systolic velocity (PSV), end-diastolic velocity (EVD) and pulsative index (PI) of the corresponding target vessels were monitored. Hemodynamic profiles of posterior cranial fossa were compared in different age groups at pre-operation versus post-operation. The accuracy of diagnosis was compared with magnetic resonance imaging (MRI) at pre-operation and the consistency of efficacy compared with Tator evaluation post-operation. Results PSV of bilateral PCA post-operation spiked in preschool group as compared with that pre-operation [left (44.25±13.06) vs. (66.76±14.45) cm/s, t=5.148, P=0.023; right (45.12±13.41) cm/s vs. (65.33±10.12) cm/s, t=5.389, P=0.021) and PI declined [left (1.18±0.42) vs. (0.91±0.18), t=4.545, P=0.033; right (1.24±0.48) vs. (0.92±0.13), t=4.776, P=0.028), bilateral VA PSV [left (43.50±11.99) vs. (70.94±7.56) cm/s, t=7.042, P=0.008; right (44.56±8.45) vs. (68.82±9.02) cm/s, t=6.833, P=0.009], preoperative EVD rose [left (19.01±9.22) vs. (27.18±8.53) cm/s, t=4.587, P=0.032; right (18.28±5.77) vs. (28.32±7.26) cm/s, t=4.683, P=0.030]and preoperative bilateral PI dropped [left (1.12±0.45) vs. (0.86±0.19), t=4.712, P=0.029; right (1.31±0.46) vs. (0.84±0.31) cm/s, t=5.277, P=0.022], BA PSV [(48.75±16.57) vs. (69.17±11.86) cm/s, t=5.413, P=0.019], preoperative EVD increased [(27.73±7.34) vs. (27.18±8.53) cm/s, t=4.738, P=0.027) and preoperative PI decreased [(1.13±0.55) vs. (0.90±0.28), t=4.721, P=0.030]; PSV of bilateral VA after surgery in school-age group was higher than that pre-operation [left (48.16±18.47) vs. (53.77±24.73)cm/s, t=4.187, P=0.045; right [(45.72±18.53) vs. (56.31±19.82) cm/s, t=3.872, P=0.036)], BA PSV [(48.50±11.44) vs. (58.17±18.86) cm/s, t=5.108, P=0.024], preoperative EVD increased [(18.63±9.91) vs. (23.19±10.63) cm/s, t=4.763, P=0.029]and preoperative PI declined [(1.06±0.42) vs. (0.92±0.25), t=4.572, P=0.032]. Preoperative TVD detection rate of 27 cases was lower than that of MRI (χ²=5.511, P=0.019). At 1 month after Tator efficacy evaluation, there were improvements (n=19, 70.4%) and non-improvements (n=8, 29.6%). TVD ultrasonic monitoring parameters improved (n=22, 81.5%) and stagnated (n=5, 18.5%). There was consistency between TVD ultrasound and Tator efficacy evaluation [χ²=0.911, P=0.340]. Conclusions MRI is a gold diagnostic standard for Chiari type Ⅰ malformation in children. However, TVD ultrasound has some accuracy and auxiliary effects. It can effectively depict the hemodynamic changes of posterior fossa artery and indirectly and non-invasively assess intracranial pressures. Thus it enables clinicians to make a timely diagnosis, offer a proper treatment and make an accurate assessment of outcomes. [ABSTRACT FROM AUTHOR]

The neurological complications following cardiovascular surgery can significantly affect the prognosis of patients. As a convenient and non-invasive intraoperative neurological monitoring method, transcranial Doppler ultrasonography (TCD) can provide real-time assessment of cerebral hemodynamics and microemboli signals, guide the development of neuroprotective strategies, and reduce the brain injury events. This review systematically summarizes the basic methods and technical performance of TCD monitoring, its clinical application in cardiovascular surgery, as well as the main limitations and future trends of this technology, in order to improve perioperative safety. [ABSTRACT FROM AUTHOR]

Background: Sphenoorbital meningiomas (SOM) harbor intrinsic features that render their surgical management and the reconstruction of the resulting bony defect overtly challenging. Methods: A 70‐year‐old woman, harboring a long‐standing left frontotemporal bony swelling conservatively managed, presented with progressive left proptosis. Radiological features were consistent with an en plaque SOM. A one‐step multiportal transcranial and endoscopic transorbital approach (TOA) with custom bone three‐dimensional (3D) printing reconstruction using polymethylmethacrylate (PMMA) was scheduled. Results: Postoperative functional and aesthetic results were excellent, with proptosis and calvarian deformity resolution. Tumor subtotal resection was achieved. Histopathological diagnosis confirmed a transitional meningioma (WHO grade I). Conclusions: The endoscopic TOA, isolated or as part of a multiportal strategy, has entered the surgical armamentarium for the treatment of SOMs. A customized PMMA cranioplasty can be considered a possible option for the reconstruction of large bony defects in a one‐step fashion. [ABSTRACT FROM AUTHOR]

Background: The generation of transcranial ultrasound is usually based on the piezoelectric effect, so it is necessary to attach transducers around the skull. However, the skull will cause serious attenuation and scattering of ultrasound, which makes it particularly difficult for transcranial ultrasound imaging and modulation. Purpose: In transcranial ultrasound imaging, there is significant attenuation and scattering of ultrasound waves by the skull bone. To mitigate this influence and enable precise imaging and high‐efficient transcranial ultrasound for specific patients (such as stroke patients who already require craniotomy as part of their surgical care), this paper proposes to use EMAT to excite metal plates placed inside the skull based on the excellent penetration characteristics of EM waves into the skull, generating ultrasound signals, which can completely avoid the influence of skull on ultrasound transmission. Methods: Based on an efficient wireless transcranial ultrasound experimental platform, we first verified that the skull would not affect the propagation of electromagnetic waves generated by EMAT. In addition, the distribution of the transcranial sound field generated by EMAT was measured. Results: EMAT can generate 1.0 MHz ultrasound by wireless excitation of a 0.1 mm thick copper plate through an adult skull with a thickness of ∼1 cm, and the frequency and amplitude of the generated ultrasound are not affected by the skull. The results indicated that the electromagnetic waves successfully penetrated the skull, with a recorded strength of approximately 2 mV. We also found that the ultrasound signals generated by the EMAT probe through the skull remained unaffected, measuring around 2 mV. In addition, the measurement of the transcranial sound field distribution (80*50 mm2) generated by EMAT shows that compared with the traditional extracranial ultrasound generation method, the sound field distribution generated by the wireless excitation of the intracranial copper plate based on EAMT is no longer affected by the uneven and irregular skull. Conclusion: Our experiments involved validating the penetration capabilities of electromagnetic waves utilizing the EMAT probe through a 7 (5+2) mm thick organic glass plate and a real human skull ranging from 8 to 15 mm in thickness. The efficient and wireless transcranial ultrasound excitation proposed in this paper may be possible for transcranial ultrasound imaging and therapy. [ABSTRACT FROM AUTHOR]

Parkinson's disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson's disease and their care givers. Parkinson's disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome–gut–brain axis is also important in Parkinson's disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson's disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson's disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson's disease and may potentially slow its progression. [ABSTRACT FROM AUTHOR]

Cardiovascular surgery has a high risk of neurological complications, which can increase the burden of disease. Perioperative real-time monitoring of neurological function in cardiovascular surgery can assist clinicians to detect neurological abnormalities as early as possible, intervene and reduce the risk of neurological complications in time. The main monitoring indicators include cerebral oxygen saturation (ScO2), EEG, cerebral blood flow (CBF), etc. In this paper, the common perioperative neuromonitoring techniques and their research advances in cardiovascular surgery are reviewed to provide theoretical basis for reducing neurological complications and improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

AimWe aimed to describe the neurosonological findings related to cerebral hemodynamics acquired using transcranial Doppler and to determine the frequency of elevated ICP by optic nerve sheath diameter (ONSD) measurement in patients with severe coronavirus disease (COVID-19) hospitalized in the intensive care unit of a national referral hospital in Peru.MethodsWe included a retrospective cohort of adult patients hospitalized with severe COVID-19 and acute respiratory failure within the first 7 days of mechanical ventilation under deep sedoanalgesia, with or without neuromuscular blockade who underwent ocular ultrasound and transcranial Doppler. We determine the frequency of elevated ICP by measuring the diameter of the optic nerve sheath, choosing as best cut-off value a diameter equal to or >5.8 mm. We also determine the frequency of sonographic patterns obtained by transcranial Doppler. Through insonation of the middle cerebral artery. Likewise, we evaluated the associations of clinical, mechanical ventilator, and arterial blood gas variables with ONSD ≥5.8 mm and pulsatility index (PI) ≥1.1. We also evaluated the associations of hemodynamic findings and ONSD with mortality the effect size was estimated using Poisson regression models with robust variance.ResultsThis study included 142 patients. The mean age was 51.39 ± 13.3 years, and 78.9% of patients were male. Vasopressors were used in 45.1% of patients, and mean arterial pressure was 81.87 ± 10.64 mmHg. The mean partial pressure of carbon dioxide (PaCO2) was elevated (54.08 ± 16.01 mmHg). Elevated intracranial pressure was seen in 83.1% of patients, as estimated based on ONSD ≥5.8 mm. A mortality rate of 16.2% was reported. In the multivariate analysis, age was associated with elevated ONSD (risk ratio [RR] = 1.07). PaCO2 was a protective factor (RR = 0.64) in the cases of PI ≥ 1.1. In the mortality analysis, the mean velocity was a risk factor for mortality (RR = 1.15).ConclusionsA high rate of intracranial hypertension was reported, with ONSD measurement being the most reliable method for estimation. The increase in ICP measured by ONSD in patients with severe COVID-19 on mechanical ventilation is not associated to hypercapnia or elevated intrathoracic pressures derived from protective mechanical ventilation.

Introduction  The management of recurrent craniopharyngioma is complex with limited data to guide decision-making. Some reports suggest reoperation should be avoided due to an increased complication profile, while others have demonstrated that safe reoperation can be performed. For other types of skull base lesions, maximal safe resection followed by adjuvant therapy has replaced radical gross total resection due to the favorable morbidity profiles. Methods  Seventy-one patients underwent resection over a 9-year period for craniopharyngioma and were retrospectively reviewed. Patients were separated into primary resection and reoperation cohorts and stratified by surgical approach (endonasal vs. cranial) and survival analyses were performed based on cohort and surgical approach. Results  Fifty patients underwent primary resection, while 21 underwent reoperation for recurrence. Fifty endonasal transsphenoidal surgeries and 21 craniotomies were performed. Surgical approaches were similarly distributed across cohorts. Subtotal resection was achieved in 83% of all cases. There were no differences in extent of resection, visual outcomes, subsequent neuroendocrine function, and complications across cohorts and surgical approaches. The median time to recurrence was 87 months overall, and there were no differences by cohort and approach. The 5-year survival rate was 81.1% after reoperation versus 93.2% after primary resection. Conclusion  Compared with primary resection, reoperation for craniopharyngioma recurrence is associated with similar functional and survival outcomes in light of individualized surgical approaches. Maximal safe resection followed by adjuvant radiotherapy for residual tumor likely preserves vision and endocrine function without sacrificing overall patient survival.

While noninvasive brain stimulation is convenient and cost effective, its utility is limited by the substantial distance between scalp electrodes and their intended neural targets in the head. The tympanic membrane, or eardrum, is a thin flap of skin deep in an orifice of the head that may serve as a port for improved efficiency of noninvasive stimulation. Here we chose the cochlea as a target because it resides in the densest bone of the skull and is adjacent to many deep-brain-stimulation structures. We also tested the hypothesis that noninvasive electric stimulation of the cochlea may restore neural activities that are missing in acoustic stimulation. We placed an electrode in the ear canal or on the tympanic membrane in 25 human adults (10 females) and compared their stimulation efficiency by characterizing the electrically-evoked auditory sensation. Relative to ear canal stimulation, tympanic membrane stimulation was four times more likely to produce an auditory percept, required eight times lower electric current to reach the threshold and produced two-to-four times more linear suprathreshold responses. We further measured tinnitus suppression in 14 of the 25 subjects who had chronic tinnitus. Compared with ear canal stimulation, tympanic membrane stimulation doubled both the probability (22% vs. 55%) and the amount (-15% vs. -34%) of tinnitus suppression. These findings extended previous work comparing evoked perception and tinnitus suppression between electrodes placed in the ear canal and on the scalp. Together, the previous and present results suggest that the efficiency of conventional scalp-based noninvasive electric stimulation can be improved by at least one order of magnitude via tympanic membrane stimulation. This increased efficiency is most likely due to the shortened distance between the electrode placed on the tympanic membrane and the targeted cochlea. The present findings have implications for the management of tinnitus by offering a potential alternative to interventions using invasive electrical stimulation such as cochlear implantation, or other non-invasive transcranial electrical stimulation methods.

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days—a good outcome was defined as a modified Rankin scale (mRS) score of 0–2, while a poor outcome was defined as an mRS score of 3–6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28–48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38–18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700–0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4–99.0) vs. 57.7 (45.3–76.3), p = 0.004] and MFV index [1.24 (0.98–1.57) vs.1.0 (0.87–1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81–33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

Background: Giant (with a diameter of at least 40 mm and a volume of at least 10 cm³ ) pituitary adenomas (GPAs) are intricate tumors that pose considerable difficulty for surgical removal. While endoscopic transsphenoidal surgery (ETS) is a commonly employed technique for these destructive tumors, its effectiveness may be restricted in cases where invasion into multiple compartments is present, leading to limited resection. Methods: A retrospective review was conducted on the clinical records of 94 patients diagnosed with GPAs who had undergone surgical resection from 2014 to 2022. An analysis was conducted on the outcomes of the surgical and clinical procedures. Results: In this group, the average size of the tumor before surgery was 44.6 ± 5.6 mm (range, 40–73 mm), and the volume was 25. 5± 16.6 cm³ (range, 10– 20.67 cm³ ). Of the total number of patients, 72 (76.6%) underwent a single ETS, 12 (12.8%) opted for transcranial surgery (TCS), and 10 (10.6%) chose a combined method. Gross total resection (GTR) was successfully performed in 49 (68.1%), 3 (25.0%), and 8 (80.0%) patients who underwent each surgical approach. Seventyfour (78.7%) patients had improved vision, 20 (21.3%) were unchanged, and none had deterioration. Twenty-two patients (23.4%) experienced a total of 43 complications, which comprised hormonal insufficiency (11/94, 11.7%), diabetic insipidus (6/88, 6.8%), electrolyte disorders (7/94, 7.4%), cerebrospinal fluid leakage (5/94, 5.3%), meningitis (8/94, 8.5%), and hydrocephalus (6/94, 6.4%). The GTR, subtotal resection (STR), and partial resection (PTR) rates were 63.8% (60/94), 21.3% (20/94), and 14.9% (14/94), respectively. Throughout the follow-up duration, 18.1% (17/94) of patients required reoperation and/or adjuvant radiation treatment as a result of tumor regrowth or inadequate biochemical remission of functioning GPAs. Conclusion: ETS remains the optimal surgical option for most GPAs and generally offers safe and efficient tumor resection. However, a combined approach with TCS remains a requirement in cases that are not suitable for treatment with a single ETS. To achieve optimal tumor removal and minimize the occurrence of surgical complications, a flexible combination of ETS and TCS is recommended based on the characteristics of the tumor. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) of deep brain structures through transcranial infrared irradiation might be an effective treatment for Parkinson's disease (PD). However, the mechanisms underlying this intervention should be elucidated to optimize the therapeutic outcome and maximize therapeutic efficacy. The present study aimed at investigating the oxidative stress-related parameters of malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) and the enzymatic activities of sodium–potassium-ATPase (Na+, K+-ATPase), Acetylcholinesterase (AChE), and monoamine oxidase (MAO) and monoamine levels (dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the midbrain and striatum of reserpine-induced PD in an animal model treated with PBM. Furthermore, the locomotor behavior of the animals has been determined by the open field test. Animals were divided into three groups; the control group, the PD-induced model group, and the PD-induced model treated with the PBM group. Non-invasive treatment of animals for 14 days with 100 mW, 830 nm laser has demonstrated successful attainment in the recovery of oxidative stress, and enzymatic activities impairments induced by reserpine (0.2 mg/kg) in both midbrain and striatum of adult male Wistar rats. PBM also improved the decrease in DA, NE, and 5-HT in the investigated brain regions. On a behavioral level, animals showed improvement in their locomotion activity. These findings have shed more light on some mechanisms underlying the treatment potential of PBM and displayed the safety, easiness, and efficacy of PBM treatment as an alternative to pharmacological treatment for PD. [ABSTRACT FROM AUTHOR]

Cerebral venous sinus thrombosis (CVST) may impair dynamic cerebral autoregulation (dCA) of the middle cerebral artery (MCA). However, most studies have focused on dCA of the MCA; a few studies are based on the posterior cerebral artery (PCA) during silent reading and neurovascular coupling (NVC). This study explored the effects of CVST on dCA of the MCA and PCA during silent reading and NVC. From January 2021 to August 2022, 60 CVST patients and 30 controls were enrolled in this study. Non-invasive continuous beat-to-beat blood pressure, cerebral blood flow velocity and other associated information on the MCA and PCA during silent reading were collected using a transcranial Doppler. NVC assessment was performed by opening and closing the eyes periodically based on voice prompts, and eye-opening visual stimulation was achieved by silently reading Chinese tourism materials. Visual stimulation signals can selectively activate Brodmann's areas 17, 18, and 19 of the occipital when reading silently with open eyes, prompting them to release neurotransmitters and dilate PCA. dCA was determined by transfer function analysis. In dCA of the PCA during silent reading, the CVST group's very low frequency phase was lower than that of the control group (p = 0.047). In NVC, the difference in the indexes of the cerebrovascular conductance and visually evoked flow response of the CVST group were lower than those of the control group (p = 0.017 and p = 0.019, respectively). Compared with the control group, dCA and NVC of the PCA during silent reading were impaired in CVST patients. [ABSTRACT FROM AUTHOR]

PurposeThe mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20-30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement.MethodsWe prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO.ResultsAmong nine participants, primary cancers were breast (n = 6), upper gastrointestinal (n = 2), and thyroid (n = 1). A positive bubble study was identified in 2/9 (22.2%) participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging.ConclusionIn this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

Background: Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects. Objective: Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates. Methods: Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first. While the animals performed the task, we recorded intracranial EEG from occipital screws. The ultrasound was delivered into the deep brain targets daily for a period of more than 6 months. Results: The brief stimulation induced effects on choice behavior that persisted up to 15 minutes and were specific to the sonicated target. Stimulation of the left/right LGN increased the proportion of rightward/leftward choices. These effects were accompanied by an increase in gamma activity over visual cortex. The contralateral effect on choice behavior and the increase in gamma, compared to sham stimulation, suggest that the stimulation excited the target neural circuits. There were no detrimental effects on the animals' discrimination performance over the months-long course of the stimulation. Conclusion: This study demonstrates that brief, 30-s ultrasonic stimulation induces neuroplastic effects specifically in the target deep brain circuits, and that the stimulation can be applied daily without detrimental effects. These findings encourage repeated applications of transcranial ultrasound to malfunctioning deep brain circuits in humans with the goal of providing a durable therapeutic reset.

Background The primary aim of this study was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise in humans at 3- and 6-months poststroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or nonresponder. We tested whether physical activity, aerobic fitness, and exercise mean arterial blood pressure differed between groups. Methods and Results Transcranial Doppler ultrasound measured MCAv during a 90-second baseline followed by a 6-minute moderate intensity exercise bout. Heart rate, mean arterial blood pressure, and end-tidal CO2 were additional variables of interest. The MCAv dynamic response variables included the following: baseline, time delay, amplitude, and time constant. Linear mixed model revealed no significant differences in our selected outcomes between 3- and 6-months poststroke. Individuals characterized as responders demonstrated a faster time delay, higher amplitude, and reported higher levels of physical activity and aerobic fitness when compared with the nonresponders. No between-group differences were identified for baseline, time constant, or exercise mean arterial blood pressure. In the nonresponders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near baseline values, while the responders showed an exponential rise until steady state was reached. Conclusions The MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported statin use and regular participation in exercise.

BackgroundIntracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism.MethodsThis prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks.ResultsAmongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes.ConclusionsDespite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes.Trial registrationClinicalTrials.gov: NCT02121028.

Summary: Background: Parkinson's disease is a progressive neurological disease with limited treatment options. Animal models and a proof-of-concept case series have suggested that photobiomodulation may be an effective adjunct treatment for the symptoms of Parkinson's disease. The aim was to determine the safety and feasibility of transcranial photobiomodulation (tPBM) to reduce the motor signs of Parkinson's disease. Methods: In this double-blind, randomised, sham-controlled feasibility trial, patients (aged 59–85 years) with idiopathic Parkinson's disease were treated with a tPBM helmet for 12 weeks (72 treatments with either active or sham therapy; stage 1). Treatment was delivered in the participants' homes, monitored by internet video conferencing (Zoom). Stage 1 was followed by 12 weeks of no treatment for those on active therapy (active-to-no-treatment group), and 12 weeks of active treatment for those on sham (sham-to-active group), for participants who chose to continue (stage 2). The active helmet device delivered red and infrared light to the head for 24 min, 6 days per week. The primary endpoints were safety and motor signs, as assessed by a modified Movement Disorders Society revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III)-motor scale. This trial is registered with ANZCTR, ACTRN 12621001722886. Findings: Between Dec 6, 2021, and Aug 12, 2022, 20 participants were randomly allocated to each of the two groups (10 females plus 10 males per group). All participants in the active group and 18 in the sham group completed 12 weeks of treatment. 14 participants in the sham group chose to continue to active treatment and 12 completed the full 12 weeks of active treatment. Treatment was well tolerated and feasible to deliver, with only minor, temporary adverse events. Of the nine suspected adverse events that were identified, two minor reactions may have been attributable to the device in the sham-to-active group during the active treatment weeks of the trial. One participant experienced temporary leg weakness. A second participant reported decreased fine motor function in the right hand. Both participants continued the trial. The mean modified MDS-UPDRS-III scores for the sham-to-active group at baseline, after 12 weeks of sham treatment, and after 12 weeks of active treatment were 26.8 (sd 14.6), 20.4 (sd 12.8), and 12.2 (sd 8.9), respectively, and for the active-to-no-treatment group these values were 21.3 (sd 9.4), 16.5 (sd 9.4), and 15.3 (sd 10.8), respectively. There was no significant difference between groups at any assessment point. The mean difference between groups at baseline was 5.5 (95% confidence interval (CI) −2.4 to 13.4), after stage 1 was 3.9 (95% CI −3.5 to 11.3 and after stage 2 was −3.1 (95% CI 2.7 to −10.6). Interpretation: Our findings add to the evidence base to suggest that tPBM is a safe, tolerable, and feasible non-pharmaceutical adjunct therapy for Parkinson's disease. While future work is needed our results lay the foundations for an adequately powered randomised placebo-controlled clinical trial. Funding: SYMBYX Pty Ltd.

Photoacoustic imaging through skull bone causes strong attenuation and distortion of the acoustic wavefront, which diminishes image contrast and resolution. As a result, transcranial photoacoustic measurements in humans have been challenging to demonstrate. In this study, we investigated the acoustic transmission through the human skull to design an ultrasound sensor suitable for transcranial PA imaging and sensing. We measured the frequency dependent losses of human cranial bones ex vivo, compared the performance of a range of piezoelectric and optical ultrasound sensors, and imaged skull phantoms using a PA tomograph based on a planar Fabry–Perot sensor. All transcranial photoacoustic measurements show the typical effects of frequency and thickness dependent attenuation and aberration associated with acoustic propagation through bone. The performance of plano-concave optical resonator ultrasound sensors was found to be highly suitable for transcranial photoacoustic measurements.

Currently, there is a knowledge gap in our understanding of the magnetic resonance imaging (MRI) characteristics of brain tumors treated with histotripsy to evaluate treatment response as well as treatment-related injuries. Our aim was to bridge this gap by investigating and correlating MRI with histological analysis after histotripsy treatment of mouse brain with and without brain tumors and evaluating the evolution of the histotripsy ablation zone on MRI over time. An eight-element, 1 MHz histotripsy transducer with a focal distance of 32.5 mm was used to treat orthotopic glioma-bearing mice and normal mice. The tumor burden at the time of treatment was ∼5 mm3. T2, T2*, T1 and T1-gadolinium (Gd) MR images and histology of the brain were acquired on days 0, 2 and 7 for tumor-bearing mice and days 0, 2, 7, 14, 21 and 28 post-histotripsy for normal mice. T2 and T2* sequences most accurately correlated with histotripsy treatment zone. The treatment-induced blood products, T1 along with T2, revealed blood product evolution from oxygenated, de-oxygenated blood and methemoglobin to hemosiderin. And T1-Gd revealed the state of the blood–brain barrier arising from the tumor or histotripsy ablation. Histotripsy leads to minor localized bleeding, which resolves within the first 7 d as evident on hematoxylin and eosin staining. By day 14, the ablation zone could be distinguished only by the macrophage-laden hemosiderin, which resides around the ablation zone, rendering the treated zone hypo-intense on all MR sequences. These results provide a library of radiological features on MRI sequences correlated to histology, thus allowing for non-invasive evaluation of histotripsy treatment effects in in vivo experiments. [ABSTRACT FROM AUTHOR]

Objective To investigate sex difference of dynamic cerebral autoregulation (dCA) in different body positions. Methods A total of 130 healthy adults (65 males and 65 females) who underwent physical examination in Xuanwu Hospital Capital Medical University from August 2021 to November 2022 were included. Non-invasive continuous blood pressure monitor and transcranial Doppler ultrasonography (TCD) were used to monitor beat-to-beat blood pressure and middle cerebral artery (MCA) cerebral blood flow velocity (CBFV), respectively. Transfer function analysis (TFA) was used to compare and analyze the dCA parameters (absolute gain value and percentage gain, phase, coherence) in the range of very low frequency (0.02-0.07 Hz), low frequency (0.07-0.20 Hz) and high frequency (0.20-0.50 Hz) of different positions and sex. Results The phase in very low frequency and low frequency were significantly lower in the standing position than in the supine position [(57.37 ± 12.45)° vs. (66.72 ± 16.64)°, t = -6.428, P = 0.000; (36.82 ± 11.59)° vs. (43.02 ± 11.51)°, t = - 6.052, P = 0.000], while the coherence in very low frequency and low frequency were significantly higher in the standing position than in the supine position (0.73 ± 0.06 vs. 0.66 ± 0.06, t = - 8.947, P = 0.000; 0.76 ± 0.06 vs. 0.73 ± 0.07, t = - 2.693, P = 0.007). In both supine and standing positions, absolute gain value of male in the low frequency [(0.91 ±0.23) cm/(s⋅mm Hg) vs. (1.04±0.23)cm/(s⋅mm Hg), t = 3.075, P = 0.003; (0.84±0.19)cm/(s⋅mm Hg) vs. (0.95 ±0.21)cm/(s⋅mm Hg), t = 3.102, P = 0.002] and high frequency [(0.94 ± 0.25) cm/(s⋅mm Hg) vs. (1.11 ± 0.27) cm/(s⋅mm Hg), t = 3.740, P = 0.000; (0.91 ±0.21) cm/(s-mm Hg) vs. (1.05 ±0.23) cm/(s⋅mm Hg), t = 3.747, P = 0.000] was lower than those of female, while the phase in the low frequency was higher than that of female [(45.25 ± 10.21)° vs. (40.81 ± 12.37)°, t = - 2.239, P = 0.027; (38.90 ± 12.25)° vs. (34.74 ± 10.57)°, t = - 2.072, P = 0.040]. Conclusions Postural changes can also affect the cerebral autoregulation, and dCA can be improved in the supine position; there is no significant difference in dCA between male and female in the very low frequency, but there is a certain difference between the sex in the low frequency and high frequency. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation method that has been used to alter cognition in hundreds of experiments. During tDCS, a low-amplitude current is delivered via scalp electrodes to create a weak electric field in the brain. The weak electric field causes membrane polarization in cortical neurons directly under the scalp electrodes. It is generally assumed that this mechanism causes the observed effects of tDCS on cognition. However, it was recently shown that some tDCS effects are not caused by the electric field in the brain but rather via co-stimulation of cranial and cervical nerves in the scalp that also have neuromodulatory effects that can influence cognition. This peripheral nerve co-stimulation mechanism is not controlled for in tDCS experiments that use the standard sham condition. In light of this new evidence, results from previous tDCS experiments could be reinterpreted in terms of a peripheral nerve co-stimulation mechanism. Here, we selected six publications that reported tDCS effects on cognition and attributed the effects to the electric field in the brain directly under the electrode. We then posed the question: given the known neuromodulatory effects of cranial and cervical nerve stimulation, could the reported results also be understood in terms of tDCS peripheral nerve co-stimulation? We present our re-interpretation of these results as a way to stimulate debate within the neuromodulation field and as a food-for-thought for researchers designing new tDCS experiments. [ABSTRACT FROM AUTHOR]

The leptomeningeal collateral status is an independent predictor of stroke outcome. By means of optical coherent tomography angiography to compare two mouse strains with different extent of native leptomeningeal collateralization, we determined the spatiotemporal dynamics of collateral flow and downstream hemodynamics following ischemic stroke. A robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, with continued expansion over the course of seven days. In contrast, little collateral recruitment was seen in Balb/C mice during- and one day after MCAO, which coincided with a greater infarct size and worse functional outcome compared to C57BL/6, despite a slight improvement of cortical perfusion seven days after MCAO. Both strains of mice experienced a reduction of blood flow in the penetrating arterioles (PA) by more than 90% 30-min after dMCAO, although the decrease of PA flow was greater and the recovery was less in the Balb/C mice. Further, Balb/C mice also displayed a prolonged greater heterogeneity of capillary transit time after dMCAO in the MCA territory compared to C57BL/6 mice. Our data suggest that the extent of native leptomeningeal collaterals affects downstream hemodynamics with a long lasting impact in the microvascular bed after cortical stroke.

RationaleIntracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke with the highest rate of recurrence, despite aggressive medical management. Diverse mechanisms may be responsible for ICAD-related cerebral ischemia, with potential therapeutic implications. Here we present the rationale, design and methods of the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. The aim of MyRIAD is to determine the mechanisms of stroke in ICAD through physiologic imaging biomarkers that evaluate impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, artery to artery embolism, and their interaction.Methods and designThis is a prospective observational study of patients with recently symptomatic (

Cerebral Blood Flow Velocity waveforms acquired via Transcranial Doppler (TCD) can provide evidence for cerebrovascular occlusion and stenosis. Thrombolysis in Brain Ischemia (TIBI) flow grades are widely used for this purpose, but require subjective assessment by expert evaluators to be reliable. In this work we seek to determine whether TCD morphology can be objectively assessed using an unsupervised machine learning approach to waveform categorization. TCD beat waveforms were recorded at multiple depths from the Middle Cerebral Arteries of 106 subjects; 33 with Large Vessel Occlusion (LVO). From each waveform, three morphological features were extracted, quantifying onset of maximal velocity, systolic canopy length, and the number/prominence of peaks/troughs. Spectral clustering identified groups implicit in the resultant three-dimensional feature space, with gap statistic criteria establishing the optimal cluster number. We found that gap statistic disparity was maximized at four clusters, referred to as flow types I, II, III, and IV. Types I and II were primarily composed of control subject waveforms, whereas types III and IV derived mainly from LVO patients. Cluster morphologies for types I and IV aligned clearly with Normal and Blunted TIBI flows, respectively. Types II and III represented commonly observed flow-types not delineated by TIBI, which nonetheless deviate from normal and blunted flows. We conclude that important morphological variability exists beyond that currently quantified by TIBI in populations experiencing or at-risk for acute ischemic stroke, and posit that the observed flow-types provide the foundation for objective methods of real-time automated flow type classification.

Sickle cell disease (SCD) is characterized by deoxygenation-induced polymerization of hemoglobin in red blood cells, leading to hemolytic anemia, vaso-occlusion, and the development of multiple clinical complications. To characterize the clinical burden associated with differences in hemoglobin concentration and hemolysis measures, a systematic literature review of MEDLINE, EMBASE, and related meta-analyses was undertaken. For quantitative analyses related to hemoglobin concentration, pooled results were analyzed using random effects models to control for within-and between-study variability. To derive risk ratios associated with hemoglobin concentration change, we combined ratios of means from select studies, which reported hazard and odds ratios in meta-analyses for hemoglobin concentration-related outcomes and changes between groups. Forty-one studies were identified for inclusion based on relating hemoglobin concentration to clinical outcomes. Meta-analyses demonstrated that mean hemoglobin concentration was significantly lower in patients with cerebrovascular disease (0.4 g/dL), increased transcranial Doppler velocity in cerebral arteries (0.6 g/dL), albuminuria (0.6 g/dL), elevated estimated pulmonary artery systolic pressure (0.9 g/dL), and in patients that subsequently died (0.6 g/dL). In a risk reduction meta-analysis, modeled increased hemoglobin concentrations of 1 g/dL or greater resulted in decreased risk of negative clinical outcomes of 41% to 64%. In conclusion, chronic anemia is associated with worse clinical outcomes in individuals with SCD and even modest increases in hemoglobin concentration may be beneficial in this patient population. This systematic review has been registered on Prospero (Registration number CRD42018096860; https://www.crd.york.ac.uk/prospero/).

Sleep is a critical part of our daily routine. It impacts every organ and system of our body, from the brain to the heart and from cellular metabolism to immune function. A consistent daily schedule of quality of sleep makes a world of difference to our health and well-being. Despite its importance, so many individuals have trouble sleeping well. Poor quality sleep has such a detrimental impact on many aspects of our lives; it affects our thinking, learning, memory, and movements. Further, and most poignantly, poor quality sleep over time increases the risk of developing a serious medical condition, including neurodegenerative disease. In this review, we focus on a potentially new non-pharmacological treatment that improves the quality of sleep. This treatment, called photobiomodulation, involves the application of very specific wavelengths of light to body tissues. In animal models, these wavelengths, when applied at night, have been reported to stimulate the removal of fluid and toxic waste-products from the brain; that is, they improve the brain’s inbuilt house-keeping function. We suggest that transcranial nocturnal photobiomodulation, by improving brain function at night, will help improve the health and well-being of many individuals, by enhancing the quality of their sleep.

In recent years, the endoscopic endonasal approach (EEA) for craniopharyngiomas has proven to be a safe option for extensive tumor resection, with minimal or no manipulation of the optic nerves and excellent visualization of the superior hypophyseal branches when compared to the Transcranial Approach (TCA). However, there is an ongoing debate regarding the criteria for selecting different approaches. To explore the current results of EEA and discuss its role in the management of craniopharyngiomas, we performed MEDLINE, Embase, and LILACS searches from 2012 to 2022. Baseline characteristics, the extent of resection, and clinical outcomes were evaluated. Statistical analysis was performed through an X2 and Fisher exact test, and a comparison between quantitative variables through a Kruskal–Wallis and verified with post hoc Bonferroni. The tumor volume was similar in both groups (EEA 11.92 cm3, -TCA 13.23 cm3). The mean follow-up in months was 39.9 for EEA and 43.94 for TCA, p = 0.76). The EEA group presented a higher visual improvement rate (41.96% vs. 25% for TCA, p < 0.0001, OR 7.7). Permanent DI was less frequent with EEA (29.20% vs. 67.40% for TCA, p < 0.0001, OR 0.2). CSF Leaks occurred more frequently with EEA (9.94% vs. 0.70% for TCA, p < 0.0001, OR 15.8). Recurrence rates were lower in the EEA group (EEA 15.50% vs. for TCA 21.20%, p = 0.04, OR 0.7). Our results demonstrate that, in selected cases, EEA for resection of craniopharyngiomas is associated with better results regarding visual preservation and extent of tumor resection. Postoperative CSF leak rates associated with EEA have improved compared to the historical series. The decision-making process should consider each person's characteristics; however, it is noticeable that recent data regarding EEA justify its widespread application as a first-line approach in centers of excellence for skull base surgery. [ABSTRACT FROM AUTHOR]

Objective: Although there is widespread acceptance of the concept of brain death/death by neurologic criteria (BD/DNC), there is marked variability in the use of ancillary tests worldwide. Transcranial Doppler (TCD) is a useful ancillary test for brain death confirmation because it is safe, noninvasive, and done at the bedside. However, it is considered less sensitive than Single Photon Emission Computed Tomography (SPECT) Tc‐HMPAO (99 m). This study aims to test the yield of brain perfusion SPECT testing after a TCD has demonstrated some level of intracranial blood flow among patients fulfilling clinical criteria for BD/DNC. Methods: This was a single‐center retrospective cohort study of all the patients fulfilling clinical criteria for BD/DNC who underwent brain perfusion SPECT after an intracerebral circulatory arrest was not confirmed by TCD between July 2016 and January 2022. Results: TCD was an initial ancillary test performed in 252 patients (99.6%) fulfilling clinical criteria for BD/DNC. A complete circulatory arrest was demonstrated in 228 (90.5%) patients. Brain perfusion SPECT was performed in the remaining 24 patients. The absence of cerebral perfusion consistent with BD/DNC was found in 21 cases (87.5%). BD/DN could not be confirmed in three patients (12.5%). Conclusions: SPECT testing has a high diagnostic yield when TCD fails to confirm a suspected diagnosis of BD/DNC. Combining these two modalities may be an optimal strategy for BD/DNC diagnosis when this is required by local regulations or when confounding factors interfere with the performance of a complete clinical assessment. [ABSTRACT FROM AUTHOR]

Single-element low-intensity focused ultrasound (LIFU) is an emerging form of human neuromodulation. Current coupling methods are impractical for clinical bedside use. Here, we evaluate commercially available high-viscosity gel polymer matrices as couplants for human LIFU neuromodulation applications. We first empirically tested the acoustic transmission of three densities at 500 kHz and then subjected the gel with the least acoustic attenuation to further tests of the effect of thickness, frequency, de-gassing and production variability. The highest-density gel had the lowest acoustic attenuation (3.3%) with low lateral (<0.5 mm) and axial (<2 mm) beam distortion. Different thicknesses of the gel up to 10 mm did not appreciably affect results. The gel polymers exhibited frequency-dependent attenuation at 1 and 3 MHz up to 86.6%, as well as significant beam distortion >4 mm. Poor de-gassing methods also increased pressure attenuation at 500 kHz up to 59.6%. Standardized methods of making these gels should be established to reduce variability. Commercially available de-gassed, high-density gel matrices are a low-cost, easily malleable, low-attenuation and distortion medium for the coupling of single-element LIFU transducers for human neuromodulation applications at 500 kHz. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease and the world's primary cause of dementia, a condition characterized by significant progressive declines in memory and intellectual capacities. While dementia is the main symptom of Alzheimer's, the disease presents with many other debilitating symptoms, and currently, there is no known treatment exists to stop its irreversible progression or cure the disease. Photobiomodulation has emerged as a very promising treatment for improving brain function, using light in the range from red to the near-infrared spectrum depending on the application, tissue penetration, and density of the target area. The goal of this comprehensive review is to discuss the most recent achievements in and mechanisms of AD pathogenesis with respect to neurodegeneration. It also provides an overview of the mechanisms of photobiomodulation associated with AD pathology and the benefits of transcranial near-infrared light treatment as a potential therapeutic solution. This review also discusses the older reports and hypotheses associated with the development of AD, as well as some other approved AD drugs. [ABSTRACT FROM AUTHOR]

Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects. Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates. Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first. While the animals performed the task, we recorded intracranial EEG from occipital screws. The ultrasound was delivered into the deep brain targets daily for a period of more than 6 months. The brief stimulation induced effects on choice behavior that persisted up to 15 minutes and were specific to the sonicated target. Stimulation of the left/right LGN increased the proportion of rightward/leftward choices. These effects were accompanied by an increase in gamma activity over visual cortex. The contralateral effect on choice behavior and the increase in gamma, compared to sham stimulation, suggest that the stimulation excited the target neural circuits. There were no detrimental effects on the animals' discrimination performance over the months-long course of the stimulation. This study demonstrates that brief, 30-s ultrasonic stimulation induces neuroplastic effects specifically in the target deep brain circuits, and that the stimulation can be applied daily without detrimental effects. These findings encourage repeated applications of transcranial ultrasound to malfunctioning deep brain circuits in humans with the goal of providing a durable therapeutic reset. • Transcranial ultrasound induces sustained modulation of deep brain circuits in task-performing non-human primates. • The deep brain stimulation elicits a contralateral bias in visual choice behavior. • The stimulation increases gamma and decreases alpha and beta activity in visual cortex. • The stimulation is applied safely over the course of several months. [ABSTRACT FROM AUTHOR]

Emerging evidence is increasingly supporting the use of transcranial photobiomodulation (tPBM) to improve symptoms of neurodegenerative diseases, including Parkinson's disease (PD). The objective of this study was to analyse the safety and efficacy of tPBM for PD motor symptoms. The study was a triple blind, randomized placebo-controlled trial with 40 idiopathic PD patients receiving either active tPBM (635 nm plus 810 nm LEDs) or sham tPBM for 24 min per day (56.88J), six days per week, for 12 weeks. The primary outcome measures were treatment safety and a 37-item MDS-UPDRS-III (motor domain) assessed at baseline and 12 weeks. Individual MDS-UPDRS-III items were clustered into sub-score domains (facial, upper-limb, lower-limb, gait, and tremor). The treatment produced no safety concerns or adverse events, apart from occasional temporary and minor dizziness. There was no significant difference in total MDS-UPDRS-III scores between groups, presumably due to the placebo effect. Additional analyses demonstrated that facial and lower-limb sub-scores significantly improved with active treatment, while gait and lower-limb sub-scores significantly improved with sham treatment. Approximately 70% of participants responded to active treatment (≥5 decrease in MDS-UPDRS-III score) and improved in all sub-scores, while sham responders improved in lower-limb sub-scores only. tPBM appears to be a safe treatment and improved several PD motor symptoms in patients that responded to treatment. tPBM is proving to be increasingly attractive as a possible non-pharmaceutical adjunct therapy. [ABSTRACT FROM AUTHOR]

Context. Pituitary adenomas are benign tumors, usually found in men in their 3rd and 5th decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations include important endocrinological disturbances and visual impairment. Objective. This study aimed to determine the most suitable neurosurgical approach regarding the dimensions, extensions and invasiveness of tumor extensions. Design. This was a systematic review of the literature from 2002-2022, focused on clinical outcome, especially endocrinological state according to the surgical approach. Subjects and Methods. We performed an advanced search on Web of Science and PubMed databases on October 10th, 2022. The literature showed 300 studies in the last 20 years, and after we applied the inclusion and exclusion criteria’s, 19 studies were fully read and analyzed. Results. Postoperative complications were reviewed in each surgical approach group, including visual impairment, new endocrinological disturbances, diabetes insipidus and cerebrospinal fluid leakage. Analyze of the endocrinological findings did not determined differences in transcranial groups from transsphenoidal groups. Overall complications were identified in the transcranial cohorts, while cerebrospinal fluid leakage still represent the main problem in transsphenoidal groups. The majority of studies found included extended endoscopic transsphenoidal approach, which shows results of great potential. Conclusions. For the surgical treatment of pituitary adenoma, transsphenoidal procedure with or without extended approaches is preferred, but they’re cases when a craniotomy is mandatory for a feasible gross tumor resection. Combined “above and below” simultaneous procedure or a two-staged intervention is recommended for giant pituitary adenoma, to maximize tumor resection and lower the risk of cerebrospinal fluid leakage [ABSTRACT FROM AUTHOR]

Background and Aim: Transcranial endoscopic surgeries are mainly limited to intraventricular lesions. This study aims to elaborate on the various benefits of transcranial endoscopic surgeries in extraventricular regions of the brain. Methods and Materials/Patients: It is a retrospective study of transcranial extraventricular endoscopic surgeries (TEESs) operated between June 2022 to May 2023. The authors described the surgeries done for brain lesions other than intraventricular lesions as extraventricular surgeries. Access to the intracranial region was obtained through the transcranial approach. The transnasal rigid endoscope was used for the surgeries. The surgery was performed as either pure endoscopic surgery or endoscopic-assisted microscopic surgery. Results: The authors have performed 6 microvascular decompressions using an endoscope. Three pineal tumors, 3 craniopharyngiomas, 1 cerebellopontine angle epidermoid cyst, and 1 petrous neurenteric cyst were excised using an endoscope by transcranial approach. One internal carotid artery bifurcation aneurysm was clipped using an endoscope. All patients improved in the postoperative period. Surgeries were done using the 0-degree and 30-degree endoscopes. The endoscopic eye was able to reach the deep-seated area of surgical interest and authors were able to visualize the structures in a wide panoramic view with good illumination and magnification. There was no misinterpretation of structures. Conclusion: Endoscope can reach the deep-seated extraventricular areas of the brain with a narrow corridor, giving good illumination and magnification at the site of surgery. An endoscope can reach beyond the obstructing anatomical structure and visualize the area behind it. It is used as a complimentary to microscope to access the microscopic invisible areas. It has increased the ease of doing surgery, decreased tissue dissection, decreased complications, and improved surgical results. TEES improves the hand-eye coordination of surgeons in transcranial surgeries and it will help in adapting to exoscope easily

Over 50% of patients who rapidly ascend to extreme altitudes develop various symptoms known as acute mountain sickness (AMS), which rarely can be life threatening. It is unclear why some patients are more susceptible to AMS than others. Our objective was to determine whether patent foramen ovale (PFO) is a risk factor for AMS. Subjects who had hiked to altitudes above 10,000' (∼3,000 meters) on the John Muir Trail in California were recruited. Participants completed a questionnaire and 2-physician adjudication was performed in regard to AMS status. A transcranial Doppler with agitated saline contrast injection was performed to evaluate the presence or absence of PFO. The primary outcome was the development of AMS. From 2016 to 2018, 137 hikers were recruited into the study. There was a higher prevalence of PFO in hikers with AMS 15 of 24 (63%) compared with hikers without AMS 44 of 113 (39%); p = 0.034. In the multivariate model, the presence of a PFO significantly increased the risk for developing AMS: odds ratio 4.15, 95% confidence intervals 1.14 to 15.05; p = 0.030. In conclusion, hikers with a PFO had significantly higher risk of developing AMS relative to hikers without a PFO. Clinicians should consider PFO a risk factor in patients who plan to hike to high altitudes.

The low cost, simple, noninvasive, and continuous measurement of cerebral blood flow velocity (CBFV) by transcranial Doppler is becoming a common clinical tool for the assessment of cerebral hemodynamics. CBFV monitoring can also help with noninvasive estimation of intracranial pressure and evaluation of mild traumatic brain injury. Reliable CBFV waveform analysis depends heavily on its accurate beat-to-beat delineation. However, CBFV is inherently contaminated with various types of noise/artifacts and has a wide range of possible pathological waveform morphologies. Thus, pulse onset detection is in general a challenging task for CBFV signal. In this paper, we conducted a comprehensive comparative analysis of three popular pulse onset detection methods using a large annotated dataset of 92,794 CBFV pulses-collected from 108 subarachnoid hemorrhage patients admitted to UCLA Medical Center. We compared these methods not only in terms of their accuracy and computational complexity, but also for their sensitivity to the selection of their parameters values. The results of this comprehensive study revealed that using optimal values of the parameters obtained from sensitivity analysis, one method can achieve the highest accuracy for CBFV pulse onset detection with true positive rate (TPR) of 97.06% and positive predictivity value (PPV) of 96.48%, when error threshold is set to just less than 10 ms. We conclude that the high accuracy and low computational complexity of this method (average running time of 4ms/pulse) makes it a reliable algorithm for CBFV pulse onset detection.