Search

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.

Background: The management of craniopharyngiomas is challenging due to their high rate of recurrence following resection. Excision of recurrent tumors poses further surgical challenges due to loss of arachnoidal planes and adherence to anatomical structures. The endoscopic endonasal approach (EEA) offers a favorable alternative to transcranial approaches for primary craniopharyngiomas. However, the safety and efficacy of EEA for recurrent tumors, specifically after a prior transcranial approach, needs further investigation. Methods: We performed a systematic review using PubMed to develop a database of cases of recurrent craniopharyngiomas previously treated with a transcranial approach. Results: Fifteen articles were included in this review with a total of 75 cases. There were 50 males and 25 females with a mean age of 38 years (range 2–80). One prior transcranial surgery was done in 80.0% of cases, while 8.0% had two and 12.0% had more than two prior surgeries. Radiotherapy after transcranial resection was given in 18 cases (24.0%). Following EEA, vision improved in 60.0% of cases, and vision worsened in 8.6% of the cases. Of cases, 64.4% had pre-existing anterior hypopituitarism, and 43.8% had diabetes insipidus prior to EEA. New anterior hypopituitarism and diabetes insipidus developed in 24.6% and 21.9% of cases, respectively following EEA. Gross total resection (GTR) was achieved in 64.0%, subtotal resection in 32.0%, and partial resection in 4.0% revision EEA cases. GTR rate was higher in cases with no prior radiotherapy compared to cases with prior radiotherapy (72.0% vs 39.0%, p = 0.0372). The recurrence rate was 17.5% overall but was significantly lower at 10.0% following GTR (p = 0.0019). The average follow-up length was 41.2 months (range, 1–182 months). Conclusion: The EEA can be utilized for resection of recurrent or residual craniopharyngiomas previously managed by a transcranial approach. [ABSTRACT FROM AUTHOR]

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.

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]

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.

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]

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

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.

Introduction Endoscopic endonasal approach (EEA) and keyhole transcranial approaches (TCAs) are being increasingly used in anterior skull base meningioma (ASBM) surgery. Objective We compare tumor resection rates and complication profiles of EEA and supraorbital keyhole approach (SOKHA) with conventional TCAs. Methods Fifty-four patients with ASBM (olfactory groove meningioma [OGM], n = 19 and planum sphenoidale/tuberculum sellae meningioma [PSM/TSM], n = 35) operated at a single center over 7 years were retrospectively analyzed. Results The overall rate of gross total resection (GTR) was higher in OGM (15/19, 78.9%) than PSM-TSM group (23/35, 65.7%, p = 0.37). GTR rate with OGM was 90% and 75% with TCA and EEA. Death (n = 1) following medical complication (TCA) and cerebrospinal fluid leak requiring re-exploration (n = 2, one each in TCA and EEA) accounted for the major complications in OGM. For the PSM/TSM group, the GTR rates were 73.3% (n = 11/15), 53.8% (n = 7/13), and 71.4% (n = 5/7) with TCA, EEA, and SOKHA, respectively. Seven patients (20%) of PSM-TSM developed major postoperative complications including four deaths (one each in TCA and SOKHA, and two in EEA groups) and three visual deteriorations. Direct and indirect vascular complications were common in lesser invasive approaches to PSM-TSM especially if the tumor has encased intracranial arteries. Conclusion No single approach is applicable to all ASBMs. TCA is still the best approach to obtain GTR but has tissue trauma-related problems. SOKHA may be a good alternative to TCA in selected PSM-TSMs, while EEA may be an alternate option in some OGMs. A meticulous patient selection is needed to derive reported results of EEA for PSM-TSM. [ABSTRACT FROM AUTHOR]

We report on the rationale and design of an ongoing National Institute of Mental Health (NIMH) sponsored R61-R33 project in major depressive disorder (MDD). Current treatments for MDD have significant limitations in efficacy and side effect burden. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. This project focuses on the adjunctive use of the transcranial photobiomodulation (tPBM) with near-infrared (NIR) light for the treatment of MDD. tPBM with NIR light penetrates robustly into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow (CBF). In the R61 phase, we will conduct target engagement studies to demonstrate dose-dependent effects of tPBM on the prefrontal cortex (PFC) CBF, using the increase in fMRI blood-oxygenation-level-dependent (BOLD) signal levels as our Go/No-go target engagement biomarker. In the R33 phase, we will conduct a randomized clinical trial of tPBM vs. sham in MDD to establish the target engagement and evaluate the association between changes in the biomarker (BOLD signal) and changes in clinical symptoms, while also collecting important information on antidepressant effects, safety, and tolerability. The study will be done in parallel at New York University/the Nathan Kline Institute (NYU/NKI) and at Massachusetts General Hospital (MGH). The importance of this study is threefold: 1. it targets MDD, a leading cause of disability worldwide, which lacks adequate treatments; 2. it evaluates tPBM, which has a well-established safety profile and has the potential to be safe in at-home administration; and 3. it uses fMRI BOLD changes as a target engagement biomarker. If effects are confirmed, the present study will both support short-term clinical development of an easy to scale device for the treatment of MDD, while also validating a biomarker for the development of future, novel modulation strategies. [ABSTRACT FROM AUTHOR]

Responsive neurostimulation (RNS) is a treatment option for patients with refractory epilepsy when surgical resection is not possible due to overlap of the irritative zone and eloquent cortex. Presurgical evaluations for RNS placement typically rely on invasive methods. This study investigated the potential of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to provide key presurgical information non-invasively. We hypothesized that these non-invasive methods may assist in optimizing RNS placement by providing useful information for seizure localization by MEG and eloquent cortex mapping by TMS. A retrospective chart review identified nine patients who underwent RNS placement (mean age = 20.4 years [ SD = 5.6], two-thirds were female). Characterization of the irritative zone using MEG was successful in eight of nine patients. Non-invasive mapping of relevant eloquent cortex was attempted in all patients. TMS was successful in eight of nine patients, and MEG was successful in two of six patients. Importantly, patients mapped with non-invasive modalities experienced an average seizure reduction of 77 % at their most recent clinic visit, compared to 75 % seizure reduction in those with invasive evaluations, indicating appropriate RNS placement. These data demonstrate that TMS and MEG can provide key information for RNS and may be feasible alternatives to invasive methods for assisting in decision making regarding RNS placement. Non-invasive methods for determining RNS placement have a high rate of success when data from multiple non-invasive modalities converge and can inform more accurate placement of intracranial electrodes prior to RNS placement or mitigate their need. • Non-invasive characterization of the irritative zone using magnetoencephalography (MEG) is possible. • Non-invasive mapping of eloquent cortex is possible using transcranial magnetic stimulation (TMS). • TMS and MEG can provide key information for responsive neurostimulator (RNS) placement. [ABSTRACT FROM AUTHOR]

Background: Despite the evolution of endoscopic techniques, large pituitary adenomas with unfavorable characteristics and irregular anatomical configurations continue to pose a challenge for the dexterity, skills, and patience of endoscopic surgeons. Transcranial surgery retains a significant role in these situations where the tumor access, hemostasis, and dissection around adjoining neurovascular tissues can be controlled efficaciously.Objective: In this report, we describe our experience with transcranial surgery for pituitary adenomas highlighting its safety and versatility in peripheral centers.Methods: We accessed the case files and imaging records of pituitary tumors operated between 2001 and 2019 at a private hospital in a major Indian city. The records were analyzed with emphasis on postoperative clinical course, visual, and endocrinological outcomes. The data was analyzed with respect to differences between transcranial and transsphenoidal procedures. Categorical variables were compared with Chi-square test/Fischer's exact test and difference in means evaluated with Welch's t-test.Results: A total of 178 procedures were performed in 173 patients with pituitary adenoma, who were the subjects of this study. Ninety-eight (56.7%) patients were treated by transsphenoidal excision whereas 80 (46.2%) underwent transcranial procedures (75 primary and five secondary). In the patients operated transcranially, we observed three deaths and nine patients suffered from significant morbidity. Visual outcomes were similar to the group operated transsphenoidally. However, incidence of panhypopituitarism was significantly higher in transcranial procedures; the extent of resection was poorer than transsphenoidal surgeries owing to more extensive nature of tumors.Conclusions: In low-volume centers, the endoscopic skills required for transsphenoidal resection of large and complex pituitary adenomas may be scarce. Transcranial surgery, dependent on familiar microsurgical techniques and equipment, may still be viable, safe, and an effective option. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: White matter hyperintensities (WMHs) have been observed with greater frequency in patients with migraine and are thought to be associated with impaired cognition and function. The relationship between WMHs and right-to-left shunt (RLS) in migraine patients is unknown. We performed a systematic review to determine if there is an association between RLS and WMHs in patients with migraine. Methods: A systematic search of the literature was performed in PubMed and Embase using a suitable keyword search strategy from inception up to 16th June 2021. All studies that included patients with migraine and studied RLS and WMHs were included. Results: A total of 8 non-randomized observational studies comprising 1125 patients with migraine were included; 576 had an RLS, compared to 549 patients with no RLS. The mean age of the study populations ranged from 28.4 to 43 years, while the average duration from migraine diagnosis ranged from 5.1 to 19 years. The proportion of female to male patients was consistently higher in all studies (60.0-94.4%). Amongst migraine patients with RLS, 338 patients (58.7%) had WMHs. In contrast, 256 (46.6%) of migraine patients without RLS had WMHs. RLS was significantly associated with the presence of WMHs in migraine patients (OR: 1.56, 95% CI: 1.05-2.34, p = 0.03). Conclusion: In migraine patients, RLS was significantly associated with the presence of WMHs. Longitudinal studies are warranted to establish RLS as a risk factor forWMHs in patients withmigraine, and to establish the significance of these changes. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson’s disease (PD) is the second most common, progressive, and debilitating neurodegenerative disease associated with aging and the most common movement disorder. Photobiomodulation (PBM), the use of non-thermal light for therapeutic purposes using laser or light emitting diodes (LED) is an emerging non-invasive treatment for a diverse range of neurological conditions. The main objectives of this clinical trial are to investigate the feasibility, safety, tolerability, and efficacy of a novel transcranial LED helmet device (the “PDNeuro”) in the alleviation of symptoms of PD. Methods and analysis: This is a 24-week, two-arm, triple-blinded randomized placebo-controlled clinical trial of a novel transcranial “PDNeuro” LED Helmet, comparing an active helmet to a sham helmet device. In a survey, 40 PD participants with Hoehn and Yahr Stage I–III during ON periods will be enrolled and randomly assigned into two groups. Both groups will be monitored weekly for the safety and tolerability of the “PDNeuro” LED Helmet. Clinical signs and symptoms assessed will include mobility, fine motor skills and cognition, with data collected at baseline, 12 weeks, and 24 weeks. Assessment tools include the TUG, UPDRS, and MoCA all validated for use in PD patients. Patient’s adherence to the device usage and participant drop out will be monitored weekly. At 12 weeks both placebo and treatment groups will crossover and placebo participants offered the treatment. The main indicator for clinical efficacy of the “PDneuro” Helmet is evidence of sustained improvements in motor and non-motor symptoms obtained from participant self-reported changes, carer reporting of changes and objective reassessment by the investigators. The outcomes will assist in a future larger randomized trial design. [ABSTRACT FROM AUTHOR]

An increase in the latency of a motor evoked potential might be as significant as a decrease in amplitude to predict a significant and clinically symptomatic neurological injury in spinal surgery for adolescent idiopathic scoliosis. The aim of the study was to investigate the impact of monitoring of latency of motor evoked potentials during spinal surgery for adolescent idiopathic scoliosis by describing intraoperative data. Preoperative recordings of 50 patients undergoing posterior spinal fusion for idiopathic scoliosis were studied. Latencies of appearance of the motor evoked potential curves on the right and left side were recorded for each group of muscles at several key moments during the procedure (basal, before the first implant, before and after corrective maneuvers). Mean latencies were approximately the same in each muscle group on the right and the left side, before and after correction. There was no significant increase in latency during surgery. Overall results showed that the measured latency did not differ significantly between the two age groups (p=0.07). Negative correlation between height and the means of latencies was recorded in the abductor pollicis brevis and abductor digiti minimi (r=0.4; p=0.009), rectus femoris (r=0.4; p=0.01), tibialis anterior (r=0.4; p=0.007), and abductor hallucis (r=0.5; p=0.0004). No significant correlation was found between age and intraoperative parameters. Intraoperative latency could be a reliable intraoperative monitoring criteria with low variability, that might be used to predict postoperative motor deficits in surgery for adolescent idiopathic scoliosis. [ABSTRACT FROM AUTHOR]

• C1(+)-C4(-) or C2(+)–C3(-) stimulation was performed to induce unilateral muscle responses. • This stimulation induced unilateral MEPs with a suprathreshold stimulation in 97% of patients. • This technique specifically activates the motor cortex with localized current distribution. Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses. The stimulation of C1(+)-C4(-) or C2(+)–C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed. The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 μV, respectively. The C1(+)–C4/C2(+)–C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses. Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery. [ABSTRACT FROM AUTHOR]

IntroductionParkinson’s disease (PD) is the second most common, progressive, and debilitating neurodegenerative disease associated with aging and the most common movement disorder. Photobiomodulation (PBM), the use of non-thermal light for therapeutic purposes using laser or light emitting diodes (LED) is an emerging non-invasive treatment for a diverse range of neurological conditions. The main objectives of this clinical trial are to investigate the feasibility, safety, tolerability, and efficacy of a novel transcranial LED helmet device (the “PDNeuro”) in the alleviation of symptoms of PD.Methods and analysisThis is a 24-week, two-arm, triple-blinded randomized placebo-controlled clinical trial of a novel transcranial “PDNeuro” LED Helmet, comparing an active helmet to a sham helmet device. In a survey, 40 PD participants with Hoehn and Yahr Stage I–III during ON periods will be enrolled and randomly assigned into two groups. Both groups will be monitored weekly for the safety and tolerability of the “PDNeuro” LED Helmet. Clinical signs and symptoms assessed will include mobility, fine motor skills and cognition, with data collected at baseline, 12 weeks, and 24 weeks. Assessment tools include the TUG, UPDRS, and MoCA all validated for use in PD patients. Patient’s adherence to the device usage and participant drop out will be monitored weekly. At 12 weeks both placebo and treatment groups will crossover and placebo participants offered the treatment. The main indicator for clinical efficacy of the “PDneuro” Helmet is evidence of sustained improvements in motor and non-motor symptoms obtained from participant self-reported changes, carer reporting of changes and objective reassessment by the investigators. The outcomes will assist in a future larger randomized trial design.Clinical Trial Registration[https://www.anzctr.org.au], identifier [12621001722886].