Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson's disease: a first retrospective analysis.

BACKGROUND: Transcranial Pulse Stimulation (TPS) has been recently introduced as a novel ultrasound neuromodulation therapy with the potential to stimulate the human brain in a focal and targeted manner. Here, we present a first retrospective analysis of TPS as an add-on therapy for Parkinson's disease (PD), focusing on feasibility, safety, and clinical effects. We also discuss the placebo response in non-invasive brain stimulation studies as an important context. METHODS: This retrospective clinical data analysis included 20 PD patients who received ten sessions of TPS intervention focused on the individual motor network. Safety evaluations were conducted throughout the intervention period. We analyzed changes in motor symptoms before and after TPS treatment using Unified Parkinson's Disease Rating Scale part III (UPDRS-III). RESULTS: We found significant improvement in UPDRS-III scores after treatment compared to baseline (pre-TPS: 16.70 ± 8.85, post-TPS: 12.95 ± 8.55; p < 0.001; Cohen's d = 1.38). Adverse events monitoring revealed no major side effects. CONCLUSION: These preliminary findings suggest that TPS can further improve motor symptoms in PD patients already on optimized standard therapy. Findings have to be evaluated in context with the current literature on placebo effects.

Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial.

Transcranial pulse stimulation has been proven effective to improve cognition, memory and depressive symptoms of Alzheimer's disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of transcranial pulse stimulation on the right temporoparietal junction, which is a key node for social cognition for autism spectrum disorder, and to examine the association between transcranial pulse stimulation and executive and social functions. This double-blinded, randomized, sham-controlled trial included 32 participants (27 males), aged 12-17 years with autism spectrum disorder. All eligible participants were randomized into either the verum or sham transcranial pulse stimulation group, on a 1:1 ratio, based on the Childhood Autism Rating Scale screening score. Sixteen participants received six verum transcranial pulse stimulation sessions (energy level: 0.2-0.25 mJ/mm2; pulse frequency: 2.5-4.0 Hz, 800 pulse/session) in 2 weeks on alternate days. The remaining 16 participants received sham transcranial pulse stimulation. The primary outcome measure included Childhood Autism Rating Scale score changes, evaluated by parents, from baseline to 3-month follow-ups. Secondary outcomes included a self-reported questionnaire responded to by parents and cognitive tests responded to by participants. A licensed mental health professional evaluated clinical global impression severity, improvement, efficacy and total score. Results revealed significant interactions in Childhood Autism Rating Scale and other secondary outcomes. Significant group and time effects were found in most secondary outcomes. Additionally, significant differences were found between the transcranial pulse stimulation and sham transcranial pulse stimulation groups in Childhood Autism Rating Scale and clinical global impression improvement and total score immediately after 2 weeks of transcranial pulse stimulation intervention (all P < 0.05), and effects were sustainable at 1- and 3-month follow-up, compared with baseline. The effect size of Childhood Autism Rating Scale (d = 0.83-0.95) and clinical global impression improvement (d = 4.12-4.37) were large to medium immediately after intervention and sustained at 1-month post-stimulation; however, the effects were reduced to small at 3-month post-stimulation (d = 2.31). These findings indicated that transcranial pulse stimulation over right temporoparietal junction was effective to reduce the core symptoms of autism spectrum disorder, as evidenced by a 24% reduction in the total Childhood Autism Rating Scale score in the verum transcranial pulse stimulation group. Additionally, the clinical global impression total score was reduced by 53.7% in the verum transcranial pulse stimulation group at a 3-month follow-up, compared with the baseline. Participants in the verum transcranial pulse stimulation group had shown substantial improvement at 1- and 3-month follow-ups, compared with baseline, although some of the neuropsychological test results were deemed statistically insignificant. Future replication of this study should include a larger sample derived from multi-nations to determine transcranial pulse stimulation as an alternative top-on treatment option in neuropsychiatry.

Evaluating the efficacy and safety of transcranial pulse stimulation on adolescents with attention deficit hyperactivity disorder: Study protocol of a pilot randomized, double-blind, sham-controlled trial.

Background: Traditional treatment alone might not effectively control the severity of attention deficit hyperactivity disorder (ADHD) symptoms. Transcranial pulse stimulation (TPS) is a non-invasive brain stimulation (NIBS) technology used on older adults with mild neurocognitive disorders and adults with major depressive disorder. However, there has been no study conducted on young adolescents with ADHD. This will be the first nationwide study evaluating the efficacy and safety of TPS in the treatment of ADHD among young adolescents in Hong Kong. Methods: This study proposes a double-blinded, randomized, sham-controlled trial including TPS as an intervention group and a sham TPS group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 1-month (T3) and 3-month follow-ups (T4). Recruitment: A total of 30 subjects aged between 12 and 17 years, diagnosed with attention deficit hyperactivity disorder (ADHD), will be recruited in this study. All subjects will be computer randomized into either the intervention group or the sham TPS group on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the ADHD symptoms and executive functions will also be conducted on all participants. The 1- and 3-month follow-up periods will be used to assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyze data. Missing data were managed by multiple imputations. The level of significance will be set to p < 0.05. Significance of the study: Results emerging from this study will generate new knowledge to ascertain whether TPS can be used as a top-on treatment for ADHD. Clinical trial registration: clinicaltrails.gov, identifier: NCT05422274.

Lapses of the Heart: Frequency and Subjective Salience of Impressions Reported by Patients after Cardiac Arrest.

After cardiac arrest (CA), some patients report impressions with highly realistic features, often referred to as near-death experience (NDE). The frequency of such episodes seems to be variable, with various types of content. In a prospective study, we subjected 126 CA cases treated at the Department of Emergency Medicine of the Medical University of Vienna under carefully controlled conditions to a structured interview. We included all patients admitted due to CA, whose communicative abilities were restored and who agreed to participate in the study. The questionnaire inquired as to living conditions, attitudes towards issues of life and death, and last recollections before and first impressions after the CA. The majority of the subjects (91 = 76%) replied to inquiries concerning impressions during CA with "nothing" or "blackout", but 20 (16%) gave a detailed account. A German version of the Greyson questionnaire specifically addressing NDE phenomena (included towards the end of the interview) resulted in ≥7 points in five patients (4%). Three patients reported a meeting with deceased relatives (one with 6 Greyson points), one an out-of-body episode, and one having been sucked into a colorful tunnel. Eleven of these twenty cases had their cardiopulmonary resuscitation (CPR) started within the first min of CA, a higher fraction than cases without experience. Reported experience after CA was of high significance for the patients; many of them changed their point of view on issues of life and death.

Ultrasound Neuromodulation as a New Brain Therapy.

Within the last decade, ultrasound has been "rediscovered" as a technique for brain therapies. Modern technologies allow focusing ultrasound through the human skull for highly focal tissue ablation, clinical neuromodulatory brain stimulation, and targeted focal blood-brain-barrier opening. This article gives an overview on the state-of-the-art of the most recent application: ultrasound neuromodulation as a new brain therapy. Although research centers have existed for decades, the first treatment centers were not established until 2020, and clinical applications are spreading rapidly.

Effects of Transcranial Pulse Stimulation (TPS) on Adults with Symptoms of Depression-A Pilot Randomized Controlled Trial.

Transcranial pulse stimulation (TPS) is a recent development in non-invasive brain stimulations (NIBS) that has been proven to be effective in terms of significantly improving Alzheimer patients' cognition, memory, and execution functions. Nonetheless, there is, currently, no trial evaluating the efficacy of TPS on adults with major depression disorder (MDD) nationwide. In this single-blinded, randomized controlled trial, a 2-week TPS treatment comprising six 30 min TPS sessions were administered to participants. Participants were randomized into either the TPS group or the Waitlist Control (WC) group, stratified by gender and age according to a 1:1 ratio. Our primary outcome was evaluated by the Hamilton depression rating scale-17 (HDRS-17). We recruited 30 participants that were aged between 18 and 54 years, predominantly female (73%), and ethnic Chinese from 1 August to 31 October 2021. Moreover, there was a significant group x time interaction (F(1, 28) = 18.8, p < 0.001). Further, when compared with the WC group, there was a significant reduction in the depressive symptom severity in the TPS group (mean difference = -6.60, p = 0.02, and Cohen's d = -0.93). The results showed a significant intervention effect; in addition, the effect was large and sustainable at the 3-month follow-up. In this trial, it was found that TPS is effective in reducing depressive symptoms among adults with MDD.

Evaluating the Safety and Efficacy of Transcranial Pulse Stimulation on Autism Spectrum Disorder: A Double-Blinded, Randomized, Sham-Controlled Trial Protocol.

Autistic spectrum disorder (ASD) is a common developmental disorder in children. The latest non-intrusive brain stimulation (NIBS) technology-transcranial pulse stimulation (TPS)-has been proven effective in older adults with mild neurocognitive disorders and adults with major depressive disorder. Nonetheless, there is so far no robust randomized controlled trial (RCT) conducted on adolescents with ASD nationwide. This study proposes a two-armed (verum TPS group vs. sham TPS group), double-blinded, randomized, sham-controlled trial. Both groups will be measured at four timepoints, namely, baseline (T1), 2 weeks immediately after post-TPS intervention (T2), and at the 1-month (T3) and 3-month (T4) follow-ups. Thirty-four subjects, aged between 12 and 17, diagnosed with ASD will be recruited in this study. All subjects will be computerized randomised into the verum TPS group or the sham TPS group on a 1:1 ratio. All subjects will undertake functional MRI (fMRI) before and after the 2-weeks TPS interventions, which will be completed in 2 weeks' time. This will be the first RCT evaluating the efficacy of TPS adolescents with ASD in Hong Kong. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05408793.

Safety of Clinical Ultrasound Neuromodulation.

Transcranial ultrasound holds much potential as a safe, non-invasive modality for navigated neuromodulation, with low-intensity focused ultrasound (FUS) and transcranial pulse stimulation (TPS) representing the two main modalities. While neuroscientific and preclinical applications have received much interest, clinical applications are still relatively scarce. For safety considerations, the current literature is largely based on guidelines for ultrasound imaging that uses various physical parameters to describe the ultrasound pulse form and expected bioeffects. However, the safety situation for neuromodulation is inherently different. This article provides an overview of relevant ultrasound parameters with a focus on bioeffects relevant for safe clinical applications. Further, a retrospective analysis of safety data for clinical TPS applications in patients is presented.

Melodic Intonation Therapy for aphasia: A multi-level meta-analysis of randomized controlled trials and individual participant data.

Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post-stroke aphasia. Our meta-analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies-overall 129 participants-met all eligibility criteria. Multi-level mixed- and random-effects models served to separately meta-analyze randomized controlled trial (RCT) and non-RCT data. RCT evidence on validated outcomes revealed a small-to-moderate standardized effect in noncommunicative language expression for MIT-with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non-RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non-Communicative Language Expression measures). Effect size for non-RCT data decreased with number of months post-stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.

Avoid or seek light - a randomized crossover fMRI study investigating opposing treatment strategies for photophobia in migraine.

BACKGROUND: Photophobia, the aberrantly increased sensitivity to light, is a common symptom in migraine patients and light discomfort is frequently found as a trigger for migraine attacks. In behavioral studies, planned exposure to light was found to reduce headache in migraine patients with photophobia, potentially by increasing habituation to this migraine trigger. Here, we aimed to elucidate neurophysiological mechanisms of light exposure versus light deprivation in migraine patients using functional magnetic resonance imaging (fMRI). METHODS: Ten migraine patients (9 female, age = 28.70 ± 8.18 years) and 11 healthy controls (9 female, age = 23.73 ± 2.24 years) spent one hour on 7 consecutive days exposed to flashing light (Flash) or darkness (Dark) using a crossover design with a wash-out period of 3 months. Study participants kept a diary including items on interictal and ictal photophobia, presence and severity of headache 7 days before, during and 7 days after the interventions. One week before and one day after both interventions, fMRI using flickering light in a block design was applied. Functional activation was analyzed at whole-brain level and habituation of the visual cortex (V1) was modeled with the initial amplitude estimate and the corrected habituation slope. RESULTS: Mean interictal photophobia decreased after both interventions, but differences relative to the baseline did not survive correction for multiple comparisons. At baseline, flickering light induced activation in V1 was higher in the patients compared to the controls, but activation normalized after the Flash and the Dark interventions. V1 habituation indices correlated with headache frequency, headache severity and ictal photophobia. In the Flash condition, the individual change of headache frequency relative to the baseline corresponded almost perfectly to the change of the habituation slope compared to the baseline. CONCLUSIONS: On average, light exposure did not lead to symptom relief, potentially due to the short duration of the intervention and the high variability of the patients' responses to the intervention. However, the strong relationship between visual cortex habituation and headache symptoms and its modulation by light exposure might shed light on the neurophysiological basis of exposure treatment effects. TRIAL REGISTRATION: NCT05369910 (05/06/2022, retrospectively registered).

Rapid screening for neglect following stroke: A systematic search and European Academy of Neurology recommendations.

BACKGROUND AND PURPOSE: Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments. METHODS: Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations. RESULTS: A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible. CONCLUSIONS: This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.

Prehospital triage optimization of patients with large vessel occlusion by Austrian Prehospital Stroke Scale.

OBJECTIVES: The Austrian Prehospital Stroke Scale (APSS) score was developed to predict large vessel occlusion (LVO) and improve prehospital transportation triage. Its accuracy has been previously analyzed retrospectively. We now aimed to investigate the accuracy, as well as the impact of the implementation of a triage strategy using this score on treatment times and outcome in a prospective study. MATHERIAL & METHODS: Prospective diagnostic test accuracy and before-after interventional study. EMS prospectively evaluated APSS in patients suspected of stroke. Accuracy was compared with other LVO scores. Patients with APSS ≥4 points were brought directly to the comprehensive stroke center. Treatment time frames, neurological, and radiological outcome before and after the APSS implementation were compared. RESULTS: A total of 307 patients with suspected stroke were included from October 2018 to February 2020. Treatable LVO was present in 79 (26%). Sensitivity of APSS to detect those was 90%, specificity 79%, positive predictive value 66%, negative predictive value 95%, and area under the curve 0.87 (95% CI 0.83-0.91). This was similar to in-hospital NIHSS (AUC 0.89 95% CI 0.89-0.92, p = .06) and superior to CPSS (AUC 0.83 95% CI 0.78-0.87, p = .01). Implementation of APSS triage increased direct transportation rate for LVO patients (21% before vs. 52% after; p < .001) with a significant time benefit (alert to groin puncture time benefit: 51 min (95% CI 28-74; p < .001). Neurological and radiological outcome did not differ significantly. CONCLUSIONS: Austrian Prehospital Stroke Scale triage showed an accuracy comparable with in-hospital NIHSS, and lead to a significant optimization of prehospital workflows in patients with potential LVO.

Functional Specificity of TPS Brain Stimulation Effects in Patients with Alzheimer's Disease: A Follow-up fMRI Analysis.

INTRODUCTION: Transcranial pulse stimulation (TPS) has been recently introduced as a novel clinical brain stimulation technique based on highly focused ultrasound pressure pulses. In a first pilot study on clinical effects of navigated and focused ultrasound neuromodulation, a dichotomy of functional effects was found: patients with Alzheimer's disease improved cognition and language but deteriorated with visuo-constructive functions. METHODS: We analyzed changes in functional connectivity measured with functional magnetic resonance imaging (fMRI) using graph analysis of a visuo-constructive network in 18 patients with Alzheimer's disease. We calculated the network's global efficiency and tested for correlation with visuo-constructive test scores to explain this dichotomy. RESULTS: Important visuo-constructive network nodes were not stimulated in the pilot setting and correspondingly global efficiency of a visuo-constructive network was decreased after TPS therapy, compatible with a natural progress of the disease. A correlation between visuo-constructive scores and changes in global efficiency was found. CONCLUSION: Results argue for a high functional specificity of ultrasound-based neuromodulation with TPS.

Over the last decade, there has been growing interest in ultrasound-based non-invasive brain stimulation techniques in neuroscience and as a potential therapy for disorders of the brain. Transcranial pulse stimulation (TPS) has been introduced as an innovative neuromodulation technique, applying ultrashort pressure pulses through the skull into neural tissue with 3D navigation in real time. In the first clinical pilot study, patients suffering from Alzheimer's disease showed an increase in memory and language functions for up to 3 months after TPS therapy. However, visuo-constructive capacities (e.g., copying a geometrical figure) worsened. Notably, brain areas relevant for such processes had been left out during stimulation. This begged the question whether the brain areas that were targeted for brain stimulation as well as functional changes could explain this diverse response pattern. We therefore analyzed functional magnetic resonance data from patients. Specifically, we compared graph theoretical functional connectivity measures in a visuo-constructive network before and after TPS therapy. We found a decrease in connectivity in a central network node, which also correlated with visuo-constructive test scores. This deterioration is likely associated with normal disease progression. Together with the already reported improvement in global cognitive functions, these results argue for a functional specific effect of TPS.

Effects of Transcranial Pulse Stimulation (TPS) on Young Adults With Symptom of Depression: A Pilot Randomised Controlled Trial Protocol.

Background: Since the emergence of the COVID-19 pandemic, there have been lots of published work examining the association between COVID-19 and mental health, particularly, anxiety and depression in the general populations and disease subpopulations globally. Depression is a debilitating disorder affecting individuals' level of bio-psychological-social functioning across different age groups. Since almost all studies were cross-sectional studies, there seems to be a lack of robust, large-scale, and technological-based interventional studies to restore the general public's optimal psychosocial wellbeing amidst the COVID-19 pandemic. Transcranial pulse stimulation (TPS) is a relatively new non-intrusive brain stimulation (NIBS) technology, and only a paucity of studies was conducted related to the TPS treatment on older adults with mild neurocognitive disorders. However, there is by far no study conducted on young adults with major depressive disorder nationwide. This gives us the impetus to execute the first nationwide study evaluating the efficacy of TPS on the treatment of depression among young adults in Hong Kong. Methods: This study proposes a two-armed single-blinded randomised controlled trial including TPS as an intervention group and a waitlist control group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 3- month follow-up (T3). Recruitment: A total of 30 community-dwelling subjects who are aged 18 and above and diagnosed with major depressive disorder (MDD) will be recruited in this study. All subjects will be computer randomised into either the intervention group or the waitlist control group, balanced by gender and age on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the psychological outcomes (i.e., depression, cognition, anhedonia, and instrumental activities of daily living) will also be conducted on all participants. A 3-month follow-up period will be usedto assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyse data. Missing data were managed by multiple mutations. The level of significance will be set to p < 0.05. Significance of the Study: Results of this study will be used to inform health policy to determine whether TPS could be considered as a top treatment option for MDD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05006365.

Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment.

INTRODUCTION: Ultrasound-based brain stimulation is a novel, non-invasive therapeutic approach to precisely target regions of interest. Data from a first clinical trial of patients with Alzheimer's disease (AD) receiving 2-4 weeks transcranial pulse stimulation (TPS) have shown memory and cognitive improvements for up to 3 months, despite ongoing state-of-the-art treatment. Importantly, depressive symptoms also improved. METHODS: We analyzed changes in Beck Depression Inventory (BDI-II) and functional connectivity (FC) changes with functional magnetic resonance imaging in 18 AD patients. RESULTS: We found significant improvement in BDI-II after TPS therapy. FC analysis showed a normalization of the FC between the salience network (right anterior insula) and the ventromedial network (left frontal orbital cortex). DISCUSSION: Stimulation of areas related to depression (including extended dorsolateral prefrontal cortex) appears to alleviate depressive symptoms and induces FC changes in AD patients. TPS may be a novel add-on therapy for depression in AD and as a neuropsychiatric diagnosis.

Human Ultrasound Neuromodulation: State of the Art.

The first human applications of ultrasound in medicine date back to 1939, when Reimar Pohlmann (Berlin, Germany) published data on therapy of neuralgia with ultrasound [...].

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain.

BACKGROUND: With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior. METHODS: Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed. RESULTS: Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area. CONCLUSIONS: TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: A follow-up study.

INTRODUCTION: Ultrasound for the brain is a revolutionary therapeutic concept. The first clinical data indicate that 2-4 weeks of therapy with transcranial pulse stimulation (TPS) improve functional networks and cognitive performance of Alzheimer's disease (AD) patients for up to 3 months. No data currently exist on possible benefits concerning brain morphology, namely the cortical atrophy characteristic of AD. METHODS: We performed a pre-/post-therapy analysis of cortical thickness in a group of N = 17 AD patients. RESULTS: We found a significant correlation between neuropsychological improvement and cortical thickness increase in AD-critical brain areas. DISCUSSION: AD patients who benefit from TPS appear to manifest reduced cortical atrophy within the default mode network in particular, whose memory-related subsystems are believed to be disrupted in AD. TPS may therefore hold promise as a new add-on therapy for AD.

Design and Derivation of the Austrian Prehospital Stroke Scale (APSS) to Predict Severe Stroke with Large Vessel Occlusion.

Objectives: Prediction of large vessel occlusion (LVO) is highly relevant for accurate prehospital transportation triage. The Austrian Prehospital Stroke Scale (APSS) score for LVO prediction was developed using critical synthesis of previously published LVO-scores. The aim of this study was to investigate the accuracy of the APSS and compare it to other LVO-scores. Methods: APSS consists of 5 items: "facial palsy," "motor arm," "language," "motor leg" and "gaze deviation." The score ranges from 0 to 9 points. Data from 741 consecutive stroke patients with acute vessel imaging admitted to an independent comprehensive stroke center was used to test the predictive performance of the APSS in context of other LVO-scores (CPSS, FAST-ED, G-FAST, sNIHSS-EMS and RACE). Results: In the prediction of treatable LVO the APSS showed the highest area under the curve (0.834) with significant difference to CPSS (p = 0.010) and G-FAST (p = 0.006) and showed highest sensitivity (69%) as compared to other LVO scores. Specificity (85%), positive predictive value (75%), negative predictive value (81%) and accuracy (79%) were comparable to other LVO scores. Receiver operating curve analysis revealed an optimal cutoff for LVO prediction at APSS equal to 4 points. Conclusions: The easy assessable 5-item APSS score tended to outperform other LVO scores. Real-life prospective evaluation in prehospital setting is ongoing.

Transcranial Ultrasound Innovations Ready for Broad Clinical Application.

Brain diseases are one of the most important problems in our rapidly ageing society. Currently, there are not many effective medications and surgical options are limited due to invasiveness and non-invasive brain stimulation techniques cannot be well targeted and cannot access deep brain areas. A novel therapy is transcranial ultrasound which allows a variety of treatments without opening of the skull. Recent technological developments generated three revolutionary options including 1) targeted non-invasive surgery, 2) highly targeted drug, antibody, or gene therapy via local opening of the blood-brain barrier, and 3) highly targeted brain stimulation to improve pathological brain functions. This progress report summarizes the current state of the art for clinical application and the results of recent patient investigations.