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BMJ Open May 2024Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve...
Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.
INTRODUCTION
Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).
METHODS AND ANALYSIS
The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 μs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events.
ETHICS AND DISSEMINATION
This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.
TRIAL REGISTRATION NUMBER
ChiCTR2300073950.
Topics: Humans; Vagus Nerve Stimulation; Consciousness Disorders; China; Transcutaneous Electric Nerve Stimulation; Consciousness; Randomized Controlled Trials as Topic; Adult; Multicenter Studies as Topic; Recovery of Function; Female; Treatment Outcome; Male
PubMed: 38821572
DOI: 10.1136/bmjopen-2024-083888 -
Stroke and Vascular Neurology May 2024
PubMed: 38821556
DOI: 10.1136/svn-2024-003166 -
Stroke and Vascular Neurology May 2024Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery...
BACKGROUND
Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals.
METHODS
We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups.
RESULTS
Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform.
CONCLUSIONS
Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.
PubMed: 38821555
DOI: 10.1136/svn-2023-002831 -
Stroke and Vascular Neurology May 2024Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH),...
BACKGROUND AND OBJECTIVES
Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed the detailed neurological indications for LAAC and outcomes after LAAC in high ICH risk patients.
METHODS
Study population included consecutive patients with NVAF who underwent LAAC in a single hospital network between January 2015 and October 2021 because of prior ICH or the presence of high ICH risk imaging markers on brain MRI (cerebral microbleeds (CMBs)). Primary safety and efficacy outcome measures were the occurrence of ICH and thromboembolic events, respectively, after LAAC.
RESULTS
Among 146 patients with NVAF who underwent LAAC for high ICH risk, 122 had a history of ICH, while 24 presented with high ICH risk imaging markers only. Mean age was 75.7±7.61, 42 (28.8%) were women. Mean CHADS-VASc score was 5.23±1.52. Of 122 patients with ICH history, 58 (47.5%) had intraparenchymal haemorrhage (IPH), 40 (32.8%) had traumatic ICH (T-ICH) and 18 (14.7%) had non-traumatic subdural haemorrhage. Of 85 patients with brain MRIs including necessary sequences, 43 (50.6%) were related to cerebral amyloid angiopathy and 37 (43.5%) to hypertensive microangiopathy. While 70% of patients were discharged on oral anticoagulants (OAC), 92% were not taking OAC at 1 year. Over 2.12 years mean follow-up, one patient had recurrent non-traumatic IPH (incidence rate (IR) 0.32 per 100 patient-years), five had T-ICH (IR 1.61 per 100 patient-years) and six had an ischaemic stroke (IR 1.94 per 100 patient-years).
CONCLUSIONS
Among patients with NVAF at high ICH risk, LAAC demonstrated a low risk of recurrent ICH or ischaemic stroke compared with previously published data. LAAC in high ICH risk populations should be considered in clinical practice per FDA approval and recent guidelines.
PubMed: 38821554
DOI: 10.1136/svn-2024-003142 -
Annals of Indian Academy of Neurology May 2024Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke.
BACKGROUND
Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke.
OBJECTIVES
To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke.
MATERIALS AND METHODS
In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0-2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents.
RESULTS
A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0-2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628).
CONCLUSION
The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.
PubMed: 38819417
DOI: 10.4103/aian.aian_59_24 -
Annals of Indian Academy of Neurology May 2024Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer...
BACKGROUND
Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer functional outcomes. However, recent randomized controlled trials (RCTs) indicate that EVT for large vessel occlusion (LVO) strokes improves functional outcomes compared to medical management alone, despite higher hemorrhagic transformation rates, with no corresponding increase in symptomatic intracerebral hemorrhage (sICH) rates. The real-world outcomes of this intervention in Indian patients remain underexplored.
OBJECTIVES
To evaluate the real-world outcomes of EVT for large core acute ischemic strokes with LVO in an Indian population.
METHODS
We conducted a single-center, retrospective observational study using a 7 years prospective database of EVT in anterior circulation stroke patients. Patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3-5 were included. Clinical and radiologic data were analyzed, with the primary endpoint being 90-day modified Rankin scale (mRS) scores. Safety outcomes included rates of sICH and mortality. Descriptive statistical analysis was done using Microsoft Excel.
RESULTS
The study included 25 patients who met the inclusion criteria. Mean age of patients was 52.9 ± 14.3 years, and there were 13 (52%) males. Median ASPECTS was 5 (interquartile range 4-5). Successful recanalization, classified by modified Thrombolysis in Cerebral Infarction score, was 92%. Good functional recovery, that is, 90-day mRS 0-3, was achieved in nine (36%) patients. Safety outcomes: sICH was seen in four (16%) and mortality was reported in nine (36%) patients.
CONCLUSIONS
Our results reaffirm findings from RCTs, provide updated real-world evidence, and suggest that EVT is a viable option to be considered in selected patients with large core ischemic infarcts.
PubMed: 38819415
DOI: 10.4103/aian.aian_53_24 -
Annals of Indian Academy of Neurology May 2024
PubMed: 38819413
DOI: 10.4103/aian.aian_50_24 -
Neural Regeneration Research Feb 2025JOURNAL/nrgr/04.03/01300535-202502000-00028/figure1/v/2024-05-28T214302Z/r/image-tiff Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are...
JOURNAL/nrgr/04.03/01300535-202502000-00028/figure1/v/2024-05-28T214302Z/r/image-tiff Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases. However, conventional topical drug delivery often results in a burst release of the drug, leading to transient retention (inefficacy) and undesirable diffusion (toxicity) in vivo. Therefore, a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke. Matrix metalloproteinase-2 (MMP-2) is gradually upregulated after cerebral ischemia. Herein, vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG (TIMP) and customizable peptide amphiphilic (PA) molecules to construct nanofiber hydrogel PA-TIMP-QK. PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro. The results indicated that PA-TIMP-QK promoted neuronal survival, restored local blood circulation, reduced blood-brain barrier permeability, and restored motor function. These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
PubMed: 38819063
DOI: 10.4103/NRR.NRR-D-23-01322 -
Neural Regeneration Research Feb 2025JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of...
Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke.
JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer's disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
PubMed: 38819062
DOI: 10.4103/NRR.NRR-D-23-01263 -
Neural Regeneration Research Feb 2025
PubMed: 38819055
DOI: 10.4103/NRR.NRR-D-24-00127