The Immediate Effects of Immersive Virtual Reality on Autonomic Nervous System Function in Patients with Disorders of Consciousness after Severe Acquired Brain Injury: A Pilot Study.

Disorders of Consciousness (DoCs) after severe acquired brain injury involve substantial impairment of cognition and physical functioning, requiring comprehensive rehabilitation and support. Technological interventions, such as immersive Virtual Reality (VR), have shown promising results in promoting neural activity and enhancing cognitive and motor recovery. VR can induce physical sensations that may activate the Autonomic Nervous System (ANS) and induce ANS-regulated responses. This study aimed to investigate the effects of immersive VR on the ANS in patients with DoCs through the analysis of the electrodermal activity (EDA). EDA was measured with a wearable device during a single immersive VR session consisting of static and dynamic videos depicting naturalistic environments. A pilot case-control study was conducted with 12 healthy participants and 12 individuals with DoCs. Results showed higher EDA values in patients than in healthy participants (p = 0.035), suggesting stronger autonomic activation during immersive VR exposure, while healthy subjects, in turn, showed a decrease in EDA values. Our results revealed a significant interaction between conditions and groups (p = 0.003), with patients showing significantly increased EDA values from the baseline compared to dynamic video observation (p = 0.014) and final rest (p = 0.007). These results suggest that immersive VR can elicit sympathetic arousal in patients with DoCs. This study highlights the potential of immersive VR as a tool to strengthen autonomic responses in patients with impaired consciousness.

Anticoagulation in acute ischemic stroke patients with mechanical heart valves: To bridge or not with heparin. The ESTREM study.

INTRODUCTION: The best therapeutic strategy for patients with mechanical heart valves (MHVs) having acute ischemic stroke during treatment with vitamin K antagonists (VKAs) remain unclear. Being so, we compared the outcomes for: (i) full dose heparin along with VKA (bridging therapy group) and (ii) restarting VKA without heparin (nonbridging group). PATIENTS AND METHODS: For this multicenter observational cohort study, data on consecutive acute ischemic stroke patients with MHV was retrospectively collected from prospective registries. Propensity score matching (PSM) was adopted to adjust for any treatment allocation confounders. The primary outcome was the composite of stroke, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding at 90 days. RESULTS: Overall, 255 out of 603 patients (41.3%) received bridging therapy: 36 (14.1%) had combined outcome, compared with 28 (8.0%) in the nonbridging group (adjusted OR 1.83; 95% CI 1.05-3.18; p = 0.03). Within the bridging group, 13 patients (5.1%) compared to 12 (3.4%) in the nonbridging group had an ischemic outcome (adjusted OR 1.71; 95% CI 0.84-3.47; p = 0.2); major bleedings were recorded in 23 (9.0%) in the bridging group and 16 (4.6%) in the nonbridging group (adjusted OR 1.88; 95% CI 0.95-3.73; p = 0.07). After PSM, 36 (14.2%) of the 254 bridging patients had combined outcome, compared with 23 (9.1%) of 254 patients in the nonbridging group (OR 1.66; 95% CI 0.95-2.85; p = 0.07). CONCLUSION: Acute ischemic stroke patients with MHV undergoing bridging therapy had a marginally higher risk of ischemic or hemorrhagic events, compared to nonbridging patients.

Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness.

Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions. We aimed to summarize the role of these essential metals in TBI and its possible link with consciousness alterations. We found that TBI alters many neuronal molecular mechanisms involving essential metals, causing neurodegeneration, neural apoptosis, synaptic dysfunction, oxidative stress, and inflammation. This final pattern resembles that described for Alzheimer's disease (AD) and other neurological and psychiatric diseases. Furthermore, we found that amantadine, zolpidem, and transcranial direct current stimulation (tDCS)-the most used treatments for DoC recovery-seem to have an effect on essential metals-related pathways and that Zn might be a promising new therapeutic approach. This review summarizes the neurophysiology of essential metals in the brain structures of consciousness and focuses on the mechanisms underlying their imbalance following TBI, suggesting their possible role in DoC. The scenario supports further studies aimed at getting a deeper insight into metals' role in DoC, in order to evaluate metal-based drugs, such as metal complexes and metal chelating agents, as potential therapeutic options.

Timing of Antithrombotic Secondary Prevention in Patients with Intracranial Hemorrhage after Stroke Thrombolysis and Thrombectomy.

In patients with acute ischemic stroke, hemorrhagic transformation (HT) of infarcted tissue frequently occurs after reperfusion treatment. We aimed to assess whether HT and its severity influences the start of secondary prevention therapy and increases the risk of stroke recurrence. In this retrospective dual-center study, we recruited ischemic stroke patients treated with thrombolysis, thrombectomy or both. Our primary outcome was the time between revascularization and the start of any secondary prevention therapy. The secondary outcome was ischemic stroke recurrence within three months. We compared patients with vs. without HT and no (n = 653), minor (n = 158) and major (n = 51) HT patients using propensity score matching. The delay in the start of antithrombotics or anticoagulants was median 24 h in no HT, 26 h in minor HT and 39 h in major HT. No and minor HT patients had similar rates of any stroke recurrence (3.4% (all ischemic) vs. 2.5% (1.6% ischemic plus 0.9% hemorrhagic)). Major HT patients had a higher stroke recurrence at 7.8% (3.9% ischemic, 3.9% hemorrhagic), but this difference did not reach significance. A total of 22% of major HT patients did not start any antithrombotic treatment during the three-month follow-up. In conclusion, the presence of HT influences the timing of secondary prevention in ischemic stroke patients undergoing reperfusion treatments. Minor HT did not delay the start of antithrombotics or anticoagulants compared to no HT, with no significant difference in safety outcomes. Major HT patients remain a clinical challenge with both a delayed or lacking start of treatment. In this group, we did not see a higher rate of ischemic recurrence; however, this may have been censored by elevated early mortality. While not reaching statistical significance, hemorrhagic recurrence was somewhat more common in this group, warranting further study using larger datasets.

Actigraphic Sensors Describe Stroke Severity in the Acute Phase: Implementing Multi-Parametric Monitoring in Stroke Unit.

Actigraphy is a tool used to describe limb motor activity. Some actigraphic parameters, namely Motor Activity (MA) and Asymmetry Index (AR), correlate with stroke severity. However, a long-lasting actigraphic monitoring was never performed previously. We hypothesized that MA and AR can describe different clinical conditions during the evolution of the acute phase of stroke. We conducted a multicenter study and enrolled 69 stroke patients. NIHSS was assessed every hour and upper limbs' motor activity was continuously recorded. We calculated MA and AR in the first hour after admission, after a significant clinical change (NIHSS ± 4) or at discharge. In a control group of 17 subjects, we calculated MA and AR normative values. We defined the best model to predict clinical status with multiple linear regression and identified actigraphic cut-off values to discriminate minor from major stroke (NIHSS ≥ 5) and NIHSS 5-9 from NIHSS ≥ 10. The AR cut-off value to discriminate between minor and major stroke (namely NIHSS ≥ 5) is 27% (sensitivity = 83%, specificity = 76% (AUC 0.86 p < 0.001), PPV = 89%, NPV = 42%). However, the combination of AR and MA of the non-paretic arm is the best model to predict NIHSS score (R2: 0.482, F: 54.13), discriminating minor from major stroke (sensitivity = 89%, specificity = 82%, PPV = 92%, NPV = 75%). The AR cut-off value of 53% identifies very severe stroke patients (NIHSS ≥ 10) (sensitivity = 82%, specificity = 74% (AUC 0.86 p < 0.001), PPV = 73%, NPV = 82%). Actigraphic parameters can reliably describe the overall severity of stroke patients with motor symptoms, supporting the addition of a wearable actigraphic system to the multi-parametric monitoring in stroke units.

Discomfort and Pain Related to Protective Mask-Wearing during COVID-19 Pandemic.

The SARS-CoV-2 pandemic made the use of facemasks mandatory to prevent contact with the virus. Recent studies have revealed that intensive use of facemasks significantly exacerbated pre-existing headaches and triggered de novo headaches. In our experience, some subjects also complain of symptoms of neuropathic pain in the head/facial regions. Until now, the relationship between neuropathic pain and facemasks has not been documented. The aim of the study is to investigate the occurrence of neuropathic pain related to facemask use. It is a cross-sectional survey using a questionnaire, developed following a commonly accepted outcome research methodology. Participants, both health care and non-health care workers, responded to items included in the questionnaire about the type of facemasks, time and manner of wearing them, side effects such as skin lesions, symptoms of neuropathic pain, etc.

Dual anti-platelet therapy for secondary prevention in intracranial atherosclerotic disease: a network meta-analysis.

Background: Intracranial arterial stenosis (ICAS) is a non-marginal cause of stroke/transient ischemic attacks (TIAs) and is associated with high stroke recurrence rate. Some studies have investigated the best secondary prevention ranging from antithrombotic therapy to endovascular treatment (ET). However, no direct comparison between all the possible treatments is currently available especially between single and dual anti-platelet therapies (SAPT and DAPT). Aim: To establish whether DAPT is more effective than SAPT in preventing the recurrence of ICAS-related stroke, by means of a network meta-analysis (NMA). Design: Systematic review and NMA in accordance to PRISMA guidelines. Data sources and methods: We performed a systematic review of trials investigating secondary prevention (SAPT or DAPT, anticoagulant treatment or ET) in patients with symptomatic ICAS available in MEDLINE, Scopus and Web of Science from January 1989 to May 2021. We defined our primary efficacy outcome as the recurrence of ischemic stroke/TIA. We analysed the extracted data with Bayesian NMA approach. Results: We identified 815 studies and included 5 trials in the NMA. Sequence generation was adequate in all the selected studies while the allocation concealment method was described in one study. All the included studies reported the pre-specified primary outcomes, and outcome assessment was blinded in all the studies. We used the fixed-effect approach as the heterogeneity was not significant (p > 0.1) according to the Cochran's Q statistic. DAPT was superior to SAPT and DAPT + ET in preventing stroke/TIA recurrence [respectively, odds ratio (OR), 0.59; confidence interval (CI), 0.39-0.9; and OR, 0.49, CI, 0.26-0.88], while no difference was found between DAPT and oral anticoagulant therapy (OAC). DAPT was safer than OAC (OR, 0.48; CI, 0.26-0.89) and DAPT + ET (OR, 0.50; CI, 0.35-0.71), while no difference was found between DAPT and SAPT. Conclusion: DAPT is more effective than SAPT for secondary stroke prevention in patients with symptomatic ICAS, without increasing the risk of haemorrhage. Registration: Prospero/CRD42019140033.

Virtual Reality and Lower Limb Rehabilitation: Effects on Motor and Cognitive Outcome-A Crossover Pilot Study.

The effectiveness of virtual reality (VR) in the motor and cognitive rehabilitation of patients with severe acquired brain injury (sABI) is unclear. This randomized, controlled, crossover, single-blinded, pilot study investigates the cognitive and motor effects of lower limb robotic therapy with and without VR visual feedback in a group of patients with ABI. A total of 23 patients with ABI were randomized into two groups: one group (VR-NVR) underwent a 2-week rehabilitation for the lower limbs training with a robotic device (Omego®) with VR feedback, followed by 2 weeks without VR; the other group (NVR-VR) performed the protocol in the opposite order. Patients were evaluated at baseline, after two and four weeks of treatment using the Level of Cognitive Functioning scale (LCF), Disability Rating Scale (DRS), and Motricity Index for Lower Limb (MI-LL) in the most affected limb. At the end of the intervention, both groups significantly improved in all the outcomes. A significant difference was found between VR treatment versus non-VR treatment for LCF (p = 0.024) and for DRS (p = 0.043) after the second week, while no significant differences were found in the group NVR-VR at T1. Our study indicates how the combination of robotic treatment with VR is effective in enhancing the recovery of cognitive function in patients with ABI, also improving disability and muscular function. Further, VR seems to enhance the early recovery process of motor and cognitive functions.

Connectivity modulations induced by reach&grasp movements: a multidimensional approach.

Reach&grasp requires highly coordinated activation of different brain areas. We investigated whether reach&grasp kinematics is associated to EEG-based networks changes. We enrolled 10 healthy subjects. We analyzed the reach&grasp kinematics of 15 reach&grasp movements performed with each upper limb. Simultaneously, we obtained a 64-channel EEG, synchronized with the reach&grasp movement time points. We elaborated EEG signals with EEGLAB 12 in order to obtain event related synchronization/desynchronization (ERS/ERD) and lagged linear coherence between Brodmann areas. Finally, we evaluated network topology via sLORETA software, measuring network local and global efficiency (clustering and path length) and the overall balance (small-worldness). We observed a widespread ERD in α and ß bands during reach&grasp, especially in the centro-parietal regions of the hemisphere contralateral to the movement. Regarding functional connectivity, we observed an α lagged linear coherence reduction among Brodmann areas contralateral to the arm involved in the reach&grasp movement. Interestingly, left arm movement determined widespread changes of α lagged linear coherence, specifically among right occipital regions, insular cortex and somatosensory cortex, while the right arm movement exerted a restricted contralateral sensory-motor cortex modulation. Finally, no change between rest and movement was found for clustering, path length and small-worldness. Through a synchronized acquisition, we explored the cortical correlates of the reach&grasp movement. Despite EEG perturbations, suggesting that the non-dominant reach&grasp network has a complex architecture probably linked to the necessity of a higher visual control, the pivotal topological measures of network local and global efficiency remained unaffected.

COVID-19 and hospital restrictions: physical disconnection and digital re-connection in disorders of consciousness.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic forced hospitals to adopt tighter restrictions, the most impacting is no access to visitors. Disorder of consciousness (DOC) due to severe acquired brain injury is a condition needing neurorehabilitation and the role of relatives is essential, hence besides physical "disconnection" digital "re-connection" is crucial. We aimed to assess whether digital communication benefits in patients with DOC, considering the sensorial and emotional deprivation due to the COVID-19 emergency lock-down.Methods: For eleven consecutive patients with DOC admitted to our Intensive Neurorehabilitation Care (mean age: 45; females: 9), two observers registered neurobehavioral changes during a video-calls with their relatives. Heart-rate variability was measured before and during the calls. The video-call was performed by using two displays of different sizes: tablet (T-video-call) and large screen (LS-Video-call).Results: The video-calls impacted on the patients' vigilance and in the relationship with relatives. Moreover, positively impacted on their relatives. The current results showed significant greater impact on patients during the LS-video-call than when they are exposed to T-video-call.Conclusions: During the COVID-19 pandemic, besides the physical disconnection to stop the contagion spread, a "digital re-connection" is needed for all and especially for fragile population groups as patients with DOC.

Actigraphic Measurement of the Upper Limbs for the Prediction of Ischemic Stroke Prognosis: An Observational Study.

BACKGROUND: It is often challenging to formulate a reliable prognosis for patients with acute ischemic stroke. The most accepted prognostic factors may not be sufficient to predict the recovery process. In this view, describing the evolution of motor deficits over time via sensors might be useful for strengthening the prognostic model. Our aim was to assess whether an actigraphic-based parameter (Asymmetry Rate Index for the 24 h period (AR2_24 h)) obtained in the acute stroke phase could be a predictor of a 90 d prognosis. METHODS: In this observational study, we recorded and analyzed the 24 h upper limb movement asymmetry of 20 consecutive patients with acute ischemic stroke during their stay in a stroke unit. We recorded the motor activity of both arms using two programmable actigraphic systems positioned on patients' wrists. We clinically evaluated the stroke patients by NIHSS in the acute phase and then assessed them across 90 days using the modified Rankin Scale (mRS). RESULTS: We found that the AR2_24 h parameter positively correlates with the 90 d mRS (r = 0.69, p < 0.001). Moreover, we found that an AR2_24 h > 32% predicts a poorer outcome (90 d mRS > 2), with sensitivity = 100% and specificity = 89%. CONCLUSIONS: Sensor-based parameters might provide useful information for predicting ischemic stroke prognosis in the acute phase.

Exoskeleton-assisted gait in chronic stroke: An EMG and functional near-infrared spectroscopy study of muscle activation patterns and prefrontal cortex activity.

OBJECTIVES: Gait impairment dramatically affects stroke patients' functional independence. The Ekso™ is a wearable powered exoskeleton able to improve over-ground gait abilities, but the relationship between the cortical gait control mechanisms and lower limbs kinematics is still unclear. Our aims are: to assess whether the Ekso™ induces an attention-demanding process with prefrontal cortex activation during a gait task; to describe the relationship between the gait-induced muscle activation pattern and the prefrontal cortex activity. METHODS: We enrolled 22 chronic stroke patients and 15 matched controls. We registered prefrontal cortex (PFC) activity with functional Near-Infrared Spectroscopy (fNIRS) and muscle activation with surface-electromyography (sEMG) during an over-ground gait task, performed with and without the Ekso™. RESULTS: We observed prefrontal cortex activation during normal gait and a higher activation during Ekso-assisted walking among stroke patients. Furthermore, we found that muscle hypo-activation and co-activation of non-paretic limb are associated to a high prefrontal metabolism. CONCLUSIONS: Among stroke patients, over-ground gait is an attention-demanding task. Prefrontal activity is modulated both by Ekso-assisted tasks and muscle activation patterns of non-paretic lower limb. Further studies are needed to elucidate if other Ekso™ settings induce different cortical and peripheral effects. SIGNIFICANCE: This is the first study exploring the relationship between central and peripheral mechanisms during an Ekso-assisted gait task.

Actigraphic measurement of the upper limbs movements in acute stroke patients.

BACKGROUND: Stroke units provide patients with a multiparametric monitoring of vital functions, while no instruments are actually available for a continuous monitoring of patients motor performance. Our aim was to develop an actigraphic index able both to identify the paretic limb and continuously monitor the motor performance of stroke patients in the stroke unit environment. METHODS: Twenty consecutive acute stroke patients (mean age 69.2 years SD 10.1, 8 males and 12 females) and 17 bed-restrained patients (mean age 70.5 years SD 7.3, 7 males and 10 females) hospitalized for orthopedic diseases of the lower limbs, but not experiencing neurological symptoms, were enrolled. This last group represented our control group. The motor activity of arms was recorded for 24 h using two programmable actigraphic systems showing off as wrist-worn watches. The firmware segmented the acquisition in epochs of 1 minute and for each epoch calculates two motor activity indices: MAe1 (Epoch-related Motor Activity index) and MAe2 (Epoch-related Motor Activity index 2). MAe1 is defined as the standard deviation of the acceleration module and MAe2 as the module of the standard deviation of acceleration components. To describe the 24 h motor performance of each limb, we calculated the mean value of MAe1 and MAe2 (respectively MA1_24h and MA2_24h). Then we obtained two Asymmetry Rate Indices: AR1_24h and AR2_24h to show the motor activity prevalence. AR1_24h refers to the asymmetry index between the values of MAe1 of both arms and AR2_24h to MAe2 values. The stroke patients were clinically evaluated by NIHSS at the beginning (NIHSST0) and at the end (NIHSST1) of the 24 h actigraphic recordings. RESULTS: Both MA1_24h and MA2_24h indices were smaller in the paretic than in the unaffected arm (respectively p = 0.004 and p = 0.004). AR2_24h showed a better capability (95% of paretic arms correctly identified, Phi Coefficient: 0.903) to discriminate the laterality of the clinical deficit than AR1_24h (85% of paretic arms correctly identified, Phi Coefficient: 0,698). We also found that AR1_24h did not differ between the two groups of patients while AR2_24h was greater in stroke patients than in controls and positively correlated with NIHSS total scores (r: 0.714, p < 0.001 for NIHSS, IC95%: 0.42-0.90) and with the sub-score relative to the paretic upper limb (r: 0.812, p < 0.001, IC95%: 0.62-0.96). CONCLUSIONS: Our data show that actigraphic monitoring of upper limbs can detect the laterality of the motor deficit and measure the clinical severity. These findings suggest that the above described actigraphic system could implement the existing multiparametric monitoring in stroke units.

Exploring Risk of Falls and Dynamic Unbalance in Cerebellar Ataxia by Inertial Sensor Assessment.

BACKGROUND: Patients suffering from cerebellar ataxia have extremely variable gait kinematic features. We investigated whether and how wearable inertial sensors can describe the gait kinematic features among ataxic patients. METHODS: We enrolled 17 patients and 16 matched control subjects. We acquired data by means of an inertial sensor attached to an ergonomic belt around pelvis, which was connected to a portable computer via Bluetooth. Recordings of all the patients were obtained during overground walking. From the accelerometric data, we obtained the harmonic ratio (HR), i.e., a measure of the acceleration patterns, smoothness and rhythm, and the step length coefficient of variation (CV), which evaluates the variability of the gait cycle. RESULTS: Compared to controls, patients had a lower HR, meaning a less harmonic and rhythmic acceleration pattern of the trunk, and a higher step length CV, indicating a more variable step length. Both HR and step length CV showed a high effect size in distinguishing patients and controls (p < 0.001 and p = 0.011, respectively). A positive correlation was found between the step length CV and both the number of falls (R = 0.672; p = 0.003) and the clinical severity (ICARS: R = 0.494; p = 0.044; SARA: R = 0.680; p = 0.003). CONCLUSION: These findings demonstrate that the use of inertial sensors is effective in evaluating gait and balance impairment among ataxic patients.

Upper limb joint kinematics using wearable magnetic and inertial measurement units: an anatomical calibration procedure based on bony landmark identification.

The estimate of a consistent and clinically meaningful joint kinematics using wearable inertial and magnetic sensors requires a sensor-to-segment coordinate system calibration. State-of-the-art calibration procedures for the upper limb are based on functional movements and/or pre-determined postures, which are difficult to implement in subjects that have impaired mobility or are bedridden in acute units. The aim of this study was to develop and validate an alternative calibration procedure based on the direct identification of palpable anatomical landmarks (ALs) for an inertial and magnetic sensor-based upper limb movement analysis protocol. The proposed calibration procedure provides an estimate of three-dimensional shoulder/elbow angular kinematics and the linear trajectory of the wrist according to the standards proposed by the International Society of Biomechanics. The validity of the method was assessed against a camera-based optoelectronic system during uniaxial joint rotations and a reach-to-grasp task. Joint angular kinematics was found as characterised by a low-biased range of motion (<-2.6°), a low root mean square deviation (RMSD) (<4.4°) and a high waveform similarity coefficient (R2 > 0.995) with respect to the gold standard. Except for the cranio-caudal direction, the linear trajectory of the wrist was characterised by a low-biased range of motion (<11 mm) together with a low RMSD (8 mm) and high waveform similarity (R2 > 0.968). The proposed method enabled the estimation of reliable joint kinematics without requiring any active involvement of the patient during the calibration procedure, complying with the metrological standards and requirements of clinical movement analysis.

Acute cerebellar stroke and middle cerebral artery stroke exert distinctive modifications on functional cortical connectivity: A comparative study via EEG graph theory.

OBJECTIVE: We tested whether acute cerebellar stroke may determine changes in brain network architecture as defined by cortical sources of EEG rhythms. METHODS: Graph parameters of 41 consecutive stroke patients (<5 days from the event) were studied using eLORETA EEG sources. Network rearrangements of stroke patients were investigated in delta, alpha 2, beta 2 and gamma bands in comparison with healthy subjects. RESULTS: The delta network remodeling was similar in cerebellar and middle cerebral artery strokes, with a reduction of small-worldness. Beta 2 and gamma small-worldness, in the right hemisphere of patients with cerebellar stroke, increase respect to healthy subjects, while alpha 2 small-worldness increases only among patients with a middle cerebral artery stroke. CONCLUSIONS: The network remodeling characteristics are independent on the size of the ischemic lesion. In the early post-acute stages cerebellar stroke differs from the middle cerebral artery one because it does not cause alpha 2 network remodeling while it determines a high frequency network reorganization in beta 2 and gamma bands with an increase of small-worldness characteristics. SIGNIFICANCE: These findings demonstrate changes in the balance of local segregation and global integration induced by cerebellar acute stroke in high EEG frequency bands. They need to be integrated with appropriate follow-up to explore whether further network changes are attained during post-stroke outcome stabilization.

Symptomatic intracranial atherosclerotic disease: an ultrasound 2-year follow-up pilot study.

INTRODUCTION: The objective of this single-center pilot study was to assess if symptomatic intracranial atherosclerotic disease (ICAD) ultrasound features change through the 2 years after acute ischemic stroke or TIA, being ICAD a relevant cause of acute ischemic stroke or TIA, linked to high rates of recurrent stroke. METHODS: We consecutively enrolled 48 patients with acute ischemic stroke or TIA with symptomatic ICAD detected by transcranial color-coded duplex sonography (TCCS) and confirmed by MR-angiography and/or CT-angiography. We set a neurosonological and clinical follow-up at 3, 6, 12, and 24 months (T0, T1, T2, T3, and T4). RESULTS: We observed that the hemodynamic effect of the stenosis changed during the 2-year follow-up, as revealed by the modifications of Peak Systolic Velocity (PSV) (Friedman-ANOVA test, p < 0.001). The pairwise post-hoc analysis showed a statistically significant difference between PSV at T0 and PSV at T3 (p = 0.005) and between PSV at T0 and PSV at T4 (p < 0.001) being PSV at T3 and T4 lower than PSV at T0. Seven patients had a new event in the first 12 months. CONCLUSIONS: The high rate of recurrent stroke or death among ICAD patients seems to be independent of progressive arterial narrowing. A wide multicenter follow-up study is needed in order to identify the factors that, alongside the hemodynamic features, contribute to the high risk of recurrent stroke among patient with symptomatic ICAD.