Predicting outcome of endovascular treatment in patients with acute ischemic stroke

Abstract

A computer-implemented method for predicting an outcome of an endovascular stroke treatment in a patient in need thereof before the patient is administered the treatment, the method comprising using an apparatus comprising: a stimulator for providing electrical stimulation to one or more pairs of stimulating electrodes for stimulating a nerve; a voltmeter connected to one or more pairs of recording electrodes for recording somatosensory evoked potentials (SEPs) resulting from the electrical stimulation provided to the nerve; and a processor. The computer-implemented method is performed by the processor by performing the steps of: a) comparing an absolute amplitude of a SEP maxima or minima ipsilateral to the stroke to a first predetermined amplitude threshold; and b) determining that an absolute amplitude of a SEP maxima or minima ipsilateral to the stroke site that exceeds the first predetermined amplitude threshold is indicative of a good outcome of the endovascular treatment, and / or determining that an absolute amplitude of a SEP maxima or minima ipsilateral to the stroke site that is below the first predetermined amplitude threshold is indicative of a poor outcome of the endovascular treatment. Additionally or alternatively, the computer-implemented method is performed by a processor by performing the steps of: a) comparing the latency of the SEP maximum or minimum ipsilateral to the stroke to a first predetermined latency threshold; and b) determining that a latency of the SEP maximum or minimum ipsilateral to the stroke site that is below the first predetermined latency threshold indicates a good outcome of the endovascular treatment.

Description

[Technical field]

[0001] The present invention relates to the field of medicine, in particular to the field of stroke. The present invention relates to a computer-implemented method and device for predicting the outcome of an endovascular stroke treatment in a patient in need thereof before the patient is administered the treatment. [Background technology]

[0002] Stroke is caused by a cerebral circulatory disturbance that temporarily or permanently alters the function of one or more parts of the brain. These changes result in focal symptoms in motor functions, such as paralysis of one half of the body (hemiplegia), facial paralysis, and weakness of one limb, sensory functions, such as loss of vision in one or both eyes and loss of balance, and cognitive functions, such as aphasia (loss of ability to produce or understand language) and disorientation, among others. In general, stroke symptoms vary depending on the brain area affected. In milder cases, the consequences may go unnoticed or be confused with minor health problems, such as headaches, and may not be a major limitation for the patient due to the anodyne nature of the symptoms. However, strokes often cause permanent neuronal damage or result in the death of the individual. In fact, according to the 2016 Global Burden Disease Study, stroke is the second leading cause of death (5.5 million deaths [95% UI 5.3-5.7], second only to ischemic heart disease). Stroke was also the second leading cause of disability-adjusted life years (DALYs) worldwide (116.4 million [11.4-121.4]).

[0003] Strokes can be divided into cerebral ischemia and cerebral hemorrhage according to the nature of the lesion, with a rate of 85% and 15% respectively. Ischemic strokes appear when blood flow is suddenly and immediately interrupted and the brain loses its blood supply, and frequently occur due to blockage of one of the arteries supplying the brain matter due to a blood clot. Blood loss leads to a decrease in the flow of glucose and oxygen to the brain, damaging brain cells. On the other hand, hemorrhagic strokes appear when a blood vessel in the brain ruptures, placing high pressure on brain cells, damaging them.

[0004] The outcome of acute ischemic stroke depends heavily on the time it takes to restore normal circulation of blood in the brain, as neurons are more sensitive to ischemia than other cells in the body due to their high dependency and availability on ATP. Therefore, the management of acute ischemic stroke is a major medical challenge. In the past 15 years, advances in acute ischemic stroke management with specific protocols have significantly reduced the morbidity and mortality associated with this disease. Therefore, once the diagnosis of acute ischemic stroke is confirmed by imaging techniques such as MR and / or CT on arrival at the hospital, etiological workup is performed in parallel with the therapeutic procedure by the stroke unit.

[0005] Intravenous administration of tissue plasminogen activator (tPA) is widely used as a first-line treatment for emergency ischemic stroke management due to its clot-busting capabilities. It has been demonstrated that its administration early after ischemic stroke improves patient survival and functional outcomes (SITS-MOST study). However, its use is limited by a narrow therapeutic window (today, the therapeutic time window is less than 4.5 hours, but this time may be extended to less than 6 hours depending on the results of ongoing clinical trials) and by important contraindications, including, among others, coagulopathy, recent surgery, stroke or head trauma within the past 3 months, or age 80 years or older. It is also associated with increased intracranial bleeding. Ultimately, only a limited percentage of patients presenting with ischemic stroke may be candidates for treatment with intravenous tPA. Furthermore, complete arterial recanalization with systemic thrombolysis and restoration of functional independence is achieved in less than 40% of patients, and this percentage is significantly reduced when the occlusion is in the proximal M1 segment of the middle cerebral artery (MCA) and internal carotid artery (ICA).

[0006] These limitations of intravenous tPA have led to the exploration of complementary or alternative endovascular therapies for acute ischemic stroke, particularly mechanical aspiration and mechanical thrombectomy. Unlike intravenous tPA, endovascular therapies use mechanical devices applied by angiography-guided catheterization to recanalize intracranial arteries occluded by thrombi. These could significantly shorten the duration of the procedure and improve recanalization rates and clinical outcomes. The latest generation of endovascular therapies has demonstrated the superiority of these new devices, with recanalization rates exceeding 68%.

[0007] Patient selection is usually performed according to several clinical and neuroimaging parameters, since not all patients can benefit from endovascular intervention. Among the clinical variables, particular attention is paid to age, baseline NIHSS score (National Institute of Health Stroke Scale: a tool used to objectively quantify the functional disability caused by stroke), systolic blood pressure, and hyperglycemia. Regarding neuroimaging parameters, computed tomography (CT) and magnetic resonance imaging (MRI) have proven useful in providing important information such as infarct core, degree of ischemic penumbra / collaterals, vascular occlusion, and thrombus, which help in the selection of the best candidates for endovascular treatment. However, achieving complete arterial recanalization by endovascular treatment is not always sufficient to achieve optimal clinical and functional recovery. Despite great advances in stroke treatment and the use of multivariate predictors based on clinical and neuroimaging criteria, the chance of significant disability or death 3 months after stroke onset is still 40% to 68%.

[0008] It is therefore clear that current patient selection parameters do not adequately capture the underlying processes leading to a good or bad stroke outcome, and that the outcome of endovascular interventions still does not reliably predict prognosis. Early knowledge of the outcome of endovascular interventions could provide valuable information regarding the best therapeutic approach for patients and avoid unnecessary risks such as intracranial hemorrhage. Therefore, there remains a need to more accurately predict the outcome of endovascular treatment in patients before and after treatment.

[0009] Known methods compare the somatosensory evoked potentials (SEPs) of the affected cerebral hemisphere with the healthy one, which has several drawbacks. First, there is a risk of errors in the measurement of bilateral SEPs, since small changes in the amplitude of SEPs can lead to large percentage differences between the hemispheres, which may lead to erroneous decisions if the values ​​in the healthy hemisphere are low. Also, since acute ischemic strokes are clearly lateralized, which is limited to cases where only one hemisphere is affected, the prediction results rely on an accurate analysis of the spread of ischemia. Given the importance of time management for the outcome of endovascular treatment, this is a further problem that these methods must address. Therefore, there is a need for more reliable methods to measure and accurately predict the outcome of endovascular treatment for patients before and after treatment that do not rely on the healthy hemisphere. Summary of the Invention

[0010] According to a first aspect of the present invention, there is provided a computer-implemented method for predicting an outcome of an endovascular stroke treatment in a patient in need thereof before the patient is administered the endovascular stroke treatment, the method comprising the use of an apparatus comprising: a stimulator for providing electrical stimulation to one or more pairs of stimulating electrodes for stimulating a nerve; a voltmeter connected to one or more pairs of recording electrodes for recording somatosensory evoked potentials (SEPs) resulting from the electrical stimulation provided to the nerve; and a processor. The computer-implemented method is performed by the processor by performing the steps of: a) comparing the absolute amplitude of the SEP maxima or minima ipsilateral to the stroke to a first predetermined amplitude threshold; and b) determining that an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site that exceeds the first predetermined amplitude threshold is indicative of a good outcome of the endovascular treatment, and / or determining that an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site that is below the first predetermined amplitude threshold is indicative of a poor outcome of the endovascular treatment. Additionally or alternatively, the computer-implemented method is performed by a processor by performing the steps of: a) comparing the latency of the SEP maximum or minimum ipsilateral to the stroke to a first predetermined latency threshold; and b) determining that a latency of the SEP maximum or minimum ipsilateral to the stroke site that is below the first predetermined latency threshold indicates a good outcome of the endovascular treatment.

[0011] In some preferred embodiments, a first predetermined amplitude threshold defines a noise threshold, and the computer-implemented method is performed by a processor by performing the steps of: a) determining that an absolute amplitude of the SEP maximum or minimum ipsilateral to the stroke site exceeds the first predetermined amplitude threshold indicates the presence of an SEP, and / or b) determining that an absolute amplitude of the SEP maximum or minimum ipsilateral to the stroke site falls below the first predetermined amplitude threshold indicates the absence of an SEP, optionally wherein the noise threshold is 0.1 μV.

[0012] In another preferred embodiment, the SEP is N 20component, the input voltage being the lowest voltage at which the finger visibly twitches, and the first predetermined amplitude threshold being an absolute threshold, between 0.1 μV and 0.75 μV, preferably between 0.25 μV and 0.55 μV, and more preferably between 0.3 μV and 0.4 μV.

[0013] In some embodiments, the computer-implemented method is performed by the processor by further performing the steps of: c) comparing the SEP amplitude of the maximal or minimal value ipsilateral to the stroke site to a second predefined amplitude threshold; and d) determining that the SEP amplitude of the maximal or minimal value ipsilateral to the stroke site below the second predefined amplitude threshold indicates a poor outcome of the endovascular treatment. 20 component, the input voltage being the lowest voltage at which the finger visibly twitches, and the second predetermined amplitude threshold being an absolute threshold, between 0.1 μV and 0.75 μV, preferably between 0.25 μV and 0.5 μV, and more preferably between 0.3 μV and 0.4 μV.

[0014] In some embodiments of the alternative embodiment of the first aspect of the present invention, the computer-implemented method is performed by the processor by further performing the steps of: c) comparing the latency of the SEP maximum or minimum ipsilateral to the stroke with a second predefined latency threshold; and d) determining that a latency of the SEP maximum or minimum ipsilateral to the stroke site that exceeds the second predefined latency threshold is indicative of a poor outcome of the endovascular treatment.

[0015] The SEP may be determined by stimulating the median nerve or the ulnar nerve. 20 Ingredients and P 25 The SEP may be selected from the group consisting of N 20 It is.

[0016] The SEP may be determined by stimulating the tibial nerve. 35 Ingredients and P 40 The components may be selected from:

[0017] In a preferred embodiment, the amplitude or latency of the SEP maxima or minima can be combined with a quantitative assessment of the severity of the stroke or one or more clinical variables of the patient. In a further preferred embodiment, the quantitative assessment is the NIHSS and / or the ASPECTS score and / or the collateral circulation status and / or the ischemic core and / or the TICI scale, and / or the clinical variables are selected from the patient's age, sex, stroke laterality, blood glucose level and mean arterial pressure.

[0018] According to a second aspect of the present invention there is provided an apparatus for predicting an outcome of an endovascular stroke treatment in a patient in need thereof prior to an endovascular stroke treatment being performed in the patient, the apparatus comprising: a stimulator for providing electrical stimulation to one or more pairs of stimulating electrodes for stimulating a nerve; a voltmeter connected to one or more pairs of recording electrodes for recording SEPs resulting from the electrical stimulation provided to the nerve; and a processor configured to compare an absolute amplitude of the SEP maximum or minimum with a predefined amplitude threshold, wherein an absolute amplitude of the SEP maximum or minimum exceeding the predefined amplitude threshold indicates a good outcome of the endovascular treatment and / or an absolute amplitude of the SEP maximum or minimum below a first predefined amplitude threshold indicates a bad outcome of the endovascular treatment; and / or a processor configured to compare a latency of the SEP maximum or minimum with a predefined latency threshold, wherein a latency of the SEP maximum or minimum ipsilateral to the stroke site below the first predefined latency threshold indicates a good outcome of the endovascular treatment.

[0019] To enable a better understanding of the present disclosure and to show how the same may be carried into effect, reference will now be made, by way of example only, to the accompanying schematic drawings in which: [Brief description of the drawings]

[0020] [Figure 1A] FIG. 1 shows a stimulation device for stimulating a patient with electrical pulses at the patient's wrist. [Figure 1B] FIG. 1 illustrates a transcranial recording device placed on a patient's scalp to measure somatosensory evoked potentials. [Figure 1C]FIG. 1 shows voltage measured over time by a transcranial recording device following stimulation of the median nerve. [Diagram 2] FIG. 1 shows a tibial SEP recording defined by two major local extrema of the negative curvature wave (N35) and the positive curvature wave (P40). [Diagram 3] Figure 1 shows ROC curves and AUC values ​​of different clinical variables of interest, alone or in combination, for outcome prognosis on day 7 before MT. A. NIHSS. B. N20 (pathological hemispheric log-transformed amplitude of N20). C. NIHSS+N20. D. NIHSS+ASPECTS. E. NIHSS+basic clinical variables (age, sex, laterality, blood glucose, and mean arterial pressure (MAP)). F. NIHSS+basic clinical variables+N20. [Figure 4] Figure 1 shows ROC curves and AUC values ​​of different clinical variables of interest, alone or in combination, for outcome prognosis 90 days before MT. A. N20 (pathological hemispheric log-transformed amplitude of N20). B. NIHSS+ASPECTS. C. NIHSS+baseline clinical variables (age, sex, laterality, blood glucose, and mean arterial pressure (MAP)). D. NIHSS+baseline clinical variables+N20. [Diagram 5] Figure 1 shows ROC curves and AUC values ​​of different clinical variables of interest, alone or in combination, for outcome prognosis 7 days after MT. A. TICI. B. N20 (pathological hemispheric log-transformed amplitude of N20). C. TICI+N20. [Figure 6] Figure 1 shows ROC curves and AUC values ​​of different clinical variables of interest, alone or in combination, for outcome prognosis at 90 days after MT. A. TICI. B. N20 (pathological hemispheric log-transformed amplitude of N20). C. TICI+N20. [Figure 7] 1 is a schematic diagram of an apparatus according to one or more embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] definition As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Additionally, the use of "or" means "and / or" unless specifically stated otherwise. Similarly, "comprise," "comprises," "comprising," "include," "includes," and "including" have the same meaning and are not intended to be limiting.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, exemplary methods, devices, and materials are described herein.

[0023] As used herein, the words or terms set forth below have the following definitions.

[0024] The term "modified Rankin scale" refers to a scale that measures the degree of impairment or dependency in daily living for people who have suffered a stroke or other cause of neurological disability.

[0025] The term "NIHSS" refers to the National Institutes of Health Stroke Scale, a systematic rating tool that provides a quantitative measurement of stroke-related neurological deficits. The higher the score, the more severe the stroke.

[0026] The term "ASPECTS" refers to the Alberta Stroke Program Early CT Score, a 10-point quantitative topographic CT scan score used in patients who have had a stroke, with higher values ​​indicating less severe ischemia.

[0027] The term "TICI" refers to the Thrombolysis in Cerebral Infarction scale, a tool for determining the response to thrombolytic therapy for ischemic stroke, with grade 0 indicating no perfusion and grade 3 indicating complete perfusion.

[0028] The term "good prognosis" is preferably understood as the probability of a good outcome of the endovascular treatment. A good outcome is understood as a modified Rankin scale of 0 to 2 at 90 days (after the endovascular treatment). The terms "prognosis" and "prediction" are used interchangeably in this application.

[0029] The term "poor prognosis" is preferably understood as the probability of a bad outcome of endovascular treatment. A bad outcome is understood as a modified Rankin Scale score of 3 or higher at 90 days after stroke onset.

[0030] The term "dramatic recovery" is preferably understood as an improvement of more than 10 in 24 hours or an NIHSS score of 0-1, as well as a modified Rankin scale of 0-2 at 90 days.

[0031] The term "potential" is preferably understood as the amplitude of a measured electrical signal, for example in the context of an SEP signal. Therefore, the term "amplitude" may be used instead.

[0032] The term "latency" is preferably understood as the time elapsed between a reference time and receiving a signal. The latency of an SEP may be absolute and is understood as the time between the SEP stimulation and the recording of the subject's SEP at the scalp. The latency of an SEP may be relative to the expected time of the SEP after the stimulation signal is provided.

[0033] The term "CTP" is preferably understood as computed tomography perfusion, in which a temporal sequence of images is taken during a rinse phase after intravenous administration of a bolus of iodized contrast agent to analyze the temporal density of the contrast agent and determine the perfusion of a particular area.

[0034] The term "Tmax" is preferably understood as the delay time between the start of the CT scan and the detection of the maximum intensity of the contrast bolus, which is preferably expressed in seconds.

[0035] The term "ROC" is preferably understood as a receiver operating characteristic curve, which describes the diagnostic ability of a binary classifier system with varying decision thresholds.

[0036] The term "AUC" is preferably understood as the area under the (ROC) curve, which represents the probability that a classifier ranks a randomly selected positive instance higher than a randomly selected negative instance. A less informative classifier will have an AUC of 0.5.

[0037] The term "quantitative SEP variable" is preferably understood as a SEP variable whose values ​​are continuously defined within a range of values. The term "continuous SEP variable" may alternatively be used.

[0038] The term "binary SEP variable" is preferably understood as a SEP variable whose values ​​are defined discretely, typically as "present" or "absent." The term "categorical SEP variable" may be used instead.

[0039] explanation The registration of evoked potentials (EPs) consists of stimulating a nerve and capturing the electrical response in the brain via electrodes placed on the scalp. Somatosensory EPs (SEPs) consist of stimulating a sensory or mixed peripheral nerve and measuring the response by electrodes specifically placed on the scalp.

[0040] SEPs are a useful, non-invasive means of assessing the proper functioning of the somatosensory system. These evoked potentials consist of a train of positive and negative waves generated by the successive excitation of neural structures located along the ascending somatosensory pathways (e.g., the posterior fascicular pathway).

[0041] To generate SEPs, it is usually necessary to apply a stimulus capable of depolarizing receptors that respond to various forms of mechanical stimulation (touch, vibration, tendon stretching...), which can be achieved for example by electrical stimulation. They are mainly evoked by bipolar transcutaneous electrical stimulation applied to the skin via the trajectories of the peripheral nerves of the upper limbs (e.g. the median nerve) or the peripheral nerves of the lower limbs (e.g. the posterior tibial nerve). Median nerve SEPs may start with a square wave or other wave electrical stimulation of 100 microseconds to 300 microseconds applied to the median nerve or the ulnar nerve at the wrist. The intensity (i.e. the amplitude of the electrical stimulation) is chosen to cause a visible thumb twitch, e.g. a thumb twitch of 1 cm to 2 cm, without causing pain to the patient. The electrical stimulation generates a depolarization cascade along the nerve until it reaches the brain. Along its path, several neurons and ganglia are involved, generating a positive to potential (P x ) and negative (N x ) (x values ​​refer to the latency of such deflection measured in ms from the stimulus time). x The SEP is considered as the minimum of the SEP amplitude, N x The SEP is taken as the local maximum of the amplitude of the SEP. The response can be measured by electrodes placed on the scalp.

[0042] In an upper extremity SEP, when such a stimulus is delivered, the nerve action potential travels up the sensory fibers to the shoulder and reaches a minimum in amplitude as it enters the spinal cord at the brachial plexus around vertebra C7. This minimum is formally known as P9. Then, during the process of conduction, the sensory fibers cross the cervical roots and enter the cervical spinal cord. The median nerve pathway then joins the posterior columns and sends out collateral branches to synapses in the mid-cervical spinal cord. This mid-cervical activity is called P 13Further conduction in the dorsal column passes through a synapse at the cervicomedullary junction and enters the lemniscus. 14 The amplitude minimum is generated at this level. As conduction ascends the ML and enters the upper midbrain and then the thalamus, a scalp maximum, N 18 After synapsing in the thalamus and crossing the internal capsule, the amplitude reaches a maximum value N 20 was recorded in the somatosensory cortex (parietal area) contralateral to the stimulated wrist and corresponds to the arrival of a nerve impulse to the primary somatosensory area. 25 N etc. 20 The generators of the components following N are not known in detail, but are thought to be cortical structures that receive afferents from the primary somatosensory cortex, such as the secondary somatosensory cortex and cortical association areas. 20 and P 25 Responses can be recorded by one or more measurement electrodes placed on the scalp near the top of the head. Recordings are optimally performed using electrodes placed 3 cm to 4 cm posterior to C3 or C4.

[0043] FIG. 1 shows an example of a median nerve SEP recording setup and upper limb SEP recording. FIG. 1A shows electrode placement on the wrist for electrical stimulation of the ulnar nerve of the upper limb. FIG. 1B shows electrode placement in the scalp for recording SEPs. FIG. 1C shows the SEP potential recorded by electrodes placed on the scalp after stimulation from the electrodes as shown in FIG. 1B. The potential amplitude is shown over time, with the stimulation time as the reference time, t=0 ms. SEP N 20 can be seen as a peak with a negative curvature (i.e., a local maximum) in the potential of the signal recorded 20 ms after the stimulus was delivered. In the particular example in Figure 1C, SEP N 20 appears 22 ms after the stimulus is delivered. Similarly, SEP P 25 can be seen as a peak (i.e., a minimum) with positive curvature in the potential of the signal recorded 25 ms after the stimulus. In the particular example in Figure 1C, SEP N 20appears 26 ms after the stimulus is delivered. The slight differences in the latency of each SEP relative to the reference time are responsive to physiological factors, as we will explain further below. The SEP amplitude is therefore understood as the potential maximum or minimum recorded from the scalp for the determined SEP event.

[0044] It should be noted that physiological differences between subjects, such as height, will affect the latency of SEPs. Thus, peripheral differences may be related to the P 14~16 and N 20 It can be eliminated by adjusting the central conducting time (CCT), defined as the interval between local extrema of the amplitude. 14~16 Measurements of N can be made at cervical levels (e.g., vertebra C6) and transcranial locations. CCT measures the N from when nerve conduction enters the spinal cord level. 20 This difference is defined as the interval between the onset of a response and the onset of a response for a given transcranially recorded SEP (N 20 This can also be resolved by measuring the difference in latency between the potential evoked at the ER and the absolute SEP latency values ​​measured. The difference in latency can be subtracted from the measured absolute SEP latency values ​​to account for peripheral abnormalities in the conduction of electrical signals to the brain.

[0045] In the lower limbs, a similar inference of the potentials ascending the posterior tibial nerve results in a variable deflection of the potential. The evoked potentials following electrical stimulation of the posterior tibial nerve have as their main component a maximum (N 35 ) followed by a large minimum with a latency of 40 ms (P 40 ), which is hypothesized to originate from cortical structures. 35 and P 40 is best recorded using an electrode 3 cm to 4 cm posterior to Cz, with a frontal or cranial reference placed at a high cervical level. The response produced in the popliteal fossa after tibial nerve stimulation is equivalent to that elicited at the elbow point in upper limb SEPs. This can determine whether the tibial nerve has been adequately stimulated and distinguish whether increases in absolute latencies are due to peripheral problems such as polyneuropathy.

[0046] Figure 2 shows an example of a SEP recording from a lower limb. The potential change is shown over time, with the stimulation time taken as the reference time t = 0 ms. SEP N 35 can be seen as the maximum potential of the signal recorded 35 ms after the stimulus was delivered. Similarly, the SEP P 40 can be seen as a local minimum in the potential of the signal recorded 45 ms after stimulation.

[0047] To obtain a response ipsilateral to the stroke site, it is necessary to stimulate nerves such as the median nerve and / or ulnar nerve contralateral to the stroke site, and vice versa. In some embodiments, bilateral nerves are stimulated to assess SEP responses on the sides of the brain ipsilateral and contralateral to the stroke site. Thus, healthy SEP responses are obtained from the ipsilateral median nerve, ulnar nerve, or tibial nerve, and impaired SEP responses are obtained from the contralateral median nerve, ulnar nerve, or tibial nerve.

[0048] A first aspect of the invention refers to the use of SEP as a marker for predicting outcome of endovascular stroke treatment. Data may be received that quantitatively indicates the SEP amplitude of a patient ipsilateral to the stroke site. The SEP is then used as follows: the absolute amplitude of the SEP maxima or minima ipsilateral to the stroke is compared to a first predefined amplitude threshold, and an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site that exceeds the first predefined amplitude threshold indicates a good outcome of the endovascular treatment, and / or an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site that is below the first predefined amplitude threshold indicates a poor outcome of the endovascular treatment.

[0049] Endovascular treatment can be planned or excluded based on the observed SEP values.

[0050] A patient's SEP ipsilateral to the stroke site before, during and after endovascular treatment has been shown to be a good indicator of whether endovascular treatment will result in good and / or bad outcomes for the patient (see Examples).

[0051] The SEP is defined by a specific latency (x) from the moment the potential is evoked and by the determined local extremum (either a maximum or minimum). x ) is a local maximum and has a positive curvature (P x However, in real-world situations, due to anatomical differences in neural pathways, certain patients may experience a neurological process of interest (e.g., N 20 In some cases, the latency associated with the arrival of a nerve impulse to the primary somatosensory area (N) may not have the expected latency. Therefore, a range of ±5 ms is defined within which the determined SEP may be found. For example, 20 It is believed that the potential can be recorded between 15 ms and 25 ms after it is triggered.

[0052] SEPs are non-invasive markers that can be rapidly applied to patients. The use of non-invasive markers to determine the outcome of endovascular treatment in patients suffering from acute ischemic stroke is essential in stroke units, since it effectively helps to allocate resources in a time-constraint driven field and avoids unnecessary risks resulting from invasive interventions on patients. It should be noted that since the recording of SEPs can be achieved within a short time from the arrival at the hospital, these decisions can be made as early as possible, before any neuroimaging technique that can provide an ASPECTS score to assess the degree of early ischemic changes in the middle cerebral artery territory. Furthermore, since SEPs can be recorded in a pre-hospital environment (e.g., ambulance), patients can be assessed before arriving at the hospital, with all the associated timing benefits from this rapid assessment. In other words, SEP values ​​(presence / absence, amplitude, or latency) can be rapidly determined in real time in a non-invasive manner, and the use of SEPs provides a more accurate indicator of the functional state of the brain than currently used clinical factors, allowing staff to make accurate and rapid decisions both pre-hospital and during hospitalization.

[0053] In some embodiments, the first predetermined amplitude threshold defines a noise threshold such that an absolute amplitude of a SEP maximum or minimum ipsilateral to the stroke site above the first predetermined amplitude threshold indicates the presence of an SEP and / or an absolute amplitude of a SEP maximum or minimum ipsilateral to the stroke site below the first predetermined amplitude threshold indicates the absence of an SEP. In these embodiments, the noise threshold is determined by the value of noise in the signal, where noise is defined as electrical noise in the signal and / or all signal values ​​that do not represent an SEP but are derived from recording and / or processing the signal. In a more preferred embodiment, the noise threshold is 0.1 μV.

[0054] In some embodiments, the SEP amplitude of the maximal or minimal value ipsilateral to the stroke site is compared to a first predetermined amplitude threshold. A SEP amplitude of the maximal or minimal value ipsilateral to the stroke site exceeding the first predetermined amplitude threshold indicates a good outcome of the endovascular treatment. The value of the first predetermined amplitude threshold depends on the input voltage applied to the patient, as well as the position and type of measurement electrodes used. However, the first amplitude threshold is preferably determined by measuring "healthy" SEP responses in one or more patients who are considered to have healthy brain function when twitches are visible at the SEP trigger points (e.g., fingers or toes visibly twitch), as shown in the examples, and selecting a threshold potential value for the setup corresponding to the first predetermined amplitude threshold. It should be noted that the SEP amplitude and the first predetermined amplitude threshold may be absolute amplitude values ​​or may be logarithmic so that logarithmic amplitude values ​​are taken.

[0055] In a preferred embodiment, the SEP is 20 component, the input voltage being the lowest voltage at which the finger visibly twitches, and the first predetermined amplitude threshold being an absolute threshold, between 0.1 μV and 0.75 μV, preferably between 0.25 μV and 0.5 μV, and more preferably between 0.3 μV and 0.4 μV.

[0056] In some embodiments, the use of SEPs includes comparing the SEP amplitude of the maximal or minimal value ipsilateral to the stroke site with a second predetermined amplitude threshold. A SEP amplitude of the maximal or minimal value ipsilateral to the stroke site below the second predetermined amplitude threshold indicates a poor outcome of the endovascular treatment. The value of the second predetermined amplitude threshold depends on the input voltage applied to the patient, as well as the position and type of measurement electrodes used. However, the second amplitude threshold is preferably determined by measuring "unhealthy" SEP responses in one or more patients considered to have unhealthy brain function when a twitch is visible at the SEP trigger point (e.g., a finger or toe visibly twitches), and selecting a threshold potential value for the setup corresponding to the second predetermined amplitude threshold. It should be noted that the SEP amplitude and the first predetermined amplitude threshold may be absolute amplitude values ​​or may be logarithmic so that a logarithmic amplitude value is taken.

[0057] In a preferred embodiment, the SEP is 20 component, the input voltage being the lowest voltage at which the finger visibly twitches, and the second predetermined amplitude threshold being an absolute threshold, between 0.1 μV and 0.75 μV, preferably between 0.25 μV and 0.5 μV, and more preferably between 0.3 μV and 0.4 μV.

[0058] It should be noted that the first and second predetermined amplitude thresholds can be used in combination or alone. Thus, the SEP amplitude value can be a marker for indicating that the endovascular treatment will have a good outcome (if it exceeds the first predetermined amplitude threshold), or a marker for indicating that the endovascular treatment will have a bad outcome (if it falls below the second predetermined amplitude threshold), or it can be a marker for both cases, where exceeding the first predetermined amplitude threshold is a marker for a good outcome and falling below the second predetermined amplitude threshold is a marker for a bad outcome. It should also be noted that the first and second predetermined amplitude thresholds may or may not be the same value.

[0059] An alternative embodiment of the first aspect of the present invention refers to the use of SEP as a marker for predicting the outcome of endovascular therapy. Data may be received that quantitatively indicates the SEP latency of a patient ipsilateral to the stroke site. The SEP is then used as follows: the latency of the SEP maximum or minimum ipsilateral to the stroke is compared to a first predefined latency threshold, where a SEP amplitude ipsilateral to the stroke site below the first predefined latency threshold indicates a good outcome of the endovascular therapy.

[0060] Since latency depends on the length of the pathway, strokes tend to induce longer pathways for SEPs because direct pathways are unavailable or the neurons involved are less responsive. Thus, having a latency below a first predefined latency value indicates that the ipsilateral site of the stroke is less damaged or at least closer to normal functional pathways, and can be used as a marker of good outcome of endovascular treatment instead of measuring SEP amplitude.

[0061] Note that the latency values ​​and thresholds may be modified to avoid the effect of "0" values. This effect arises from patients with no SEP present, who may be assigned a null or 0 latency. Since latency is inversely correlated with the probability of a good outcome, paradoxically, these patients are predicted by the regression algorithm to have the best outcome. In some embodiments, the latency registration signal is transformed by correcting its value to the absolute difference with the expected latency, i.e. L = Abs(L0-x) where L is the corrected latency, L0 is the originally measured latency, and x is the expected latency for a given SEP. In this way, a patient with a latency of 0 will actually be given a latency of x, which is greater than any of those with good (low) latencies.

[0062] In some embodiments, the use further comprises comparing the latency of the SEP maximum or minimum ipsilateral to the stroke to a second predetermined latency value, where a latency of the SEP maximum or minimum ipsilateral to the stroke site that exceeds the second predetermined latency threshold indicates a poor outcome of the endovascular treatment. By similar reasoning as before, having a latency that exceeds the second predetermined latency threshold indicates that the ipsilateral site of the stroke is more damaged or at least further away from normal functional pathways, and can be used as a marker of a poor outcome of the endovascular treatment.

[0063] It is also noted that in any of the preferred embodiments, the first and second predetermined latency thresholds may be used in combination or alone. Thus, the latency of the SEP maximum or minimum may be a marker that the endovascular treatment has a good outcome (if it is below the first predetermined latency threshold) or that the endovascular treatment will have a bad outcome (if it is above the second predetermined latency threshold), or it may be a marker for both cases, where being below the first predetermined latency threshold is a marker for a good outcome and being above the second predetermined latency threshold is a marker for a bad outcome. It is also noted that in any of the preferred embodiments, the first and second predetermined latency thresholds may be used in combination or alone.

[0064] In some embodiments, the SEP is determined by stimulating the median nerve and / or the ulnar nerve. 20 Ingredients and P 25 Preferably, SEP is selected from N 20 N 20 Ingredients and P 25 The components are local extrema of the SEP recording occurring at latencies of 20 ms and 25 ms, respectively, from the input. 20 is the local maximum peak, and P 25 is a local minimum peak.

[0065] In some embodiments, the SEP is determined by stimulating the tibial nerve. 35 Ingredients and P 40 The component is selected from N 35 Ingredients and P 40 The components are the peak components of the SEP recording occurring at latencies of 35 ms and 40 ms from the input, respectively. 35 is the local maximum peak, and P 40 is a local minimum peak.

[0066] In some embodiments, the amplitude and / or latency of the SEP maxima or minima are combined with a quantitative assessment of stroke severity or one or more clinical variables of the patient. Although the SEP has predictive power in itself, it can be further combined with current outcomes of endovascular treatment prediction systems, which typically include the use of a quantitative assessment of stroke severity and one or more clinical variables of the patient, thereby improving the accuracy of the prediction (see FIG. 3).

[0067] In some embodiments, the quantitative assessment is NIHSS and / or ASPECTS score and / or collateral circulation status and / or ischemia core and / or TICI scale. Clinical variables can be, but are not limited to, age, sex, stroke laterality, blood glucose level, and mean arterial pressure (MAP) level. SEP alone has better predictive ability of good outcome prognosis at 7 days after stroke than NIHSS scale and combination of NIHSS score and ASPECTS score, but NIHSS variables and NEP are not predictive. 20 Variables and NIHSS and baseline variables and N 20 Note that the combination of the NIHSS scale and the ASPECTS scale has a higher predictive ability than the NIHSS scale alone and the combination of the NIHSS and ASPECTS (see Figures 3-6).

[0068] N 20 is the log-transformed N 20When the values ​​are further used in a logistic regression model for predicting good functional outcome, they have been shown to add predictive power to currently used clinical variables (NIHSS, ASPECTS). This effect has been shown to be slightly more pronounced in the 90 day outcome than in the 7 day outcome (see Example 2.7).

[0069] It should be noted that the use of SEP as a marker to predict the outcome of endovascular stroke treatment according to any of the embodiments described herein may occur before, during, or after the endovascular stroke treatment is administered.

[0070] FIG. 7 shows a schematic diagram of a device 100 for predicting the outcome of endovascular stroke therapy through measurement of somatosensory evoked potentials (SEPs). The device 100 comprises a SEP module 105 including a processor 110, a memory 120, a stimulator 130, a voltmeter 140, a timer 150 and a user interface 155. The SEP module 105 is electrically connected to one or more pairs of stimulating electrodes 135 and one or more pairs of recording electrodes 145. The SEP module 105 may additionally comprise a communication module 160. The communication module 160 may be communicatively connected (i.e., wired or wireless) to an external display device 200 for displaying information recorded by the device 100. Alternatively, the SEP module 105 may comprise a display device integrated into the module.

[0071] The memory 120 stores instructions for the SEP measurement procedure for the processor 110. The procedure may be configured to measure any SEP, but preferably is configured to measure any SEP up to N 20The memory 120 further stores instructions for the processor 110 to control the stimulator 130 to provide a stimulation potential between one or more pairs of stimulation electrodes 135 during a SEP measurement procedure. The memory 120 further stores instructions for the processor 110 to control a timer 150, in particular to start the timer 150 when the stimulator 130 provides a stimulation potential. The memory 120 further stores instructions for the processor 110 to measure a voltage measured by the voltmeter 140 at multiple time instances after the stimulation potential is provided, and instructions for measuring the time recorded by the timer 150 for each voltage measurement. The memory may include one or more volatile or non-volatile memory devices, such as DRAM, SRAM, flash memory, read-only memory, ferroelectric RAM, hard disk drives, floppy disks, magnetic tapes, optical disks, etc., and may be provided within the SEP module 105, or may be partially or wholly external to the SEP module 105, or may be communicatively connected to the SEP module 105.

[0072] The processor 110 is configured to control the stimulator 130, the timer 150, and the voltmeter 140. The processor 110 is further configured to follow instructions of a SEP measurement procedure when it receives instructions from a user interface 155 indicating that the procedure should be started. The processor 110 may include one or more processing units, such as a microprocessor, GPU, CPU, multi-core processor, etc., and may be internal or external to the SEP module 105, or may be distributed among processors of different devices.

[0073] The stimulator 130 is electrically connected to the one or more pairs of stimulating electrodes 135 and is configured to provide one or more electrical stimuli to the one or more pairs of stimulating electrodes 135 (i.e., provide a potential between the one or more pairs of electrodes). The electrical stimuli include one or more electrical pulses. The pulses may include, for example, square wave or sinusoidal pulses and may, for example, be less than 1 ms in duration, preferably 0.1 ms to 0.3 ms in duration, more preferably 0.2 ms in duration. The electrical stimuli may be provided at any suitable frequency, for example 1 Hz to 10 Hz, more preferably 5 Hz to 6 Hz. The stimulator 130 is configured to provide electrical stimulation of sufficient intensity to cause a visible twitch of the finger or toe on which the one or more pairs of stimulating electrodes 135 are positioned. In some embodiments, the stimulator 130 may be configured to apply electrical stimulation of a fixed, predetermined intensity determined to provide the correct amount of stimulation to the finger or toe. In other embodiments, the stimulator 130 may be controlled by the processor 110 to provide stimulation over a range of predetermined electrical intensities. For example, a user may select an electrical intensity using the user interface 155, and the processor 110 may control the stimulator 130 to provide electrical stimulation at the selected electrical intensity. The stimulator 130 may be configured to provide electrical stimulation having a current intensity between 0 mA and 50 mA.

[0074] The voltmeter 140 is connected between one or more pairs of recording electrodes 145 and configured to measure the potential between the recording electrodes 145. The voltmeter may be any suitable voltmeter known in the art. The voltmeter 140 preferably has a time resolution of 5 ms or less, preferably 1 ms or less, more preferably 0.1 ms or less so that the amplitude peak of the SEP can be accurately determined. The voltage resolution of the voltmeter is preferably 0.1 μV or less.

[0075] The components of the SEP module 100 may be powered by an external power source via a power connection (not shown) or may include an internal power source, such as a battery, and the power source may be configured to power the display device 200, or the display device 200 may be powered by a separate external power source.

[0076] Timer 150 may be any suitable timer. The timer preferably has a time resolution at least as short as that of voltmeter 140 so that the voltage measurements can be accurately timed. Timer 150 may be included in voltmeter 140 or may be provided separately.

[0077] The one or more pairs of stimulation electrodes 135 are configured to be placed on the user's skin such that an exposed surface of each electrode contacts the user's skin. The one or more pairs of stimulation electrodes 135 may be provided on a substrate having an adhesive surface configured to removably adhere to the user's skin. The one or more pairs of stimulation electrodes 135 may be provided on an inner surface of a glove or sock at a location corresponding to the location of the desired nerve (e.g., the median nerve or the ulnar nerve) to be stimulated.

[0078] The one or more pairs of recording electrodes 145 are configured to be placed on the scalp of the user such that an exposed surface of each electrode contacts the skin of the user's scalp. The one or more pairs of stimulating electrodes 135 may be provided on a substrate having an adhesive surface configured to removably adhere to the skin of the user. The one or more pairs of recording electrodes 145 may be provided on an inner surface of the cap at locations on the cap corresponding to desired locations on the scalp for recording. In particular, the locations of the one or more pairs of recording electrodes 145 may be provided on the cap proximal to the bilateral somatosensory cortex, more specifically, at the locations of C3', C4' and / or Cz'.

[0079] The user interface 155 may be any suitable user interface for providing user input to the SEP module. The user interface may be, for example, a touch screen or other display device with a guided user interface (GUI), or may include one or more buttons, switches, levers, and the like. In some embodiments, the user interface 155 is also the display device 200. A user may select various variables for the SEP measurement procedure via the user interface 155. For example, the user may select the electrical intensity of the electrical stimulation, start and stop the measurement procedure, select the number of electrical stimulations to be provided during the procedure, etc.

[0080] The display device 200 may be any suitable display device for displaying results of a SEP measurement procedure or other information. The display device 200 may be, for example, a mobile device, a tablet, a computer, or a screen. The display device 200 may include a user interface 155 (e.g., a GUI) for controlling the SEP module 105.

[0081] The device 100 may be used for a SEP measurement procedure as follows: First, a user may place one or more pairs of stimulating electrodes 135 at desired locations on the patient. For example, the stimulating electrodes 135 may be placed proximal to a nerve (e.g., the median nerve or ulnar nerve) that, when stimulated, causes the patient's finger or toe to twitch. One or more pairs of recording electrodes 145 may be placed at desired locations on the patient's head to record SEPs. For example, a user may place one or more recording electrodes 145 at desired locations on the patient's head to record SEPs. 20One or more pairs of recording electrodes 145 may be placed at the C3', C4', and / or Cz' locations to record the SEP. The SEP module 105 may then be initiated. In some embodiments, the device 100 may include an impedance meter or ohmmeter (not shown) configured to measure the impedance of the one or more pairs of recording electrodes 145. The device 100 may be configured to measure the impedance before initiating the SEP measurement procedure and to alert the user (e.g., via the user interface 155 or the display device 200) that the impedance between the one or more pairs of recording electrodes 145 is not below a predetermined impedance threshold. The device 100 may be configured to initiate the SEP measurement procedure when the measured impedance falls below a predetermined impedance threshold, indicating that all of the corrective electrode pairs are in contact with the patient's skin. In some embodiments, the user may use the SEP module 105 in a preliminary procedure to select the correct electrical intensity for electrical stimulation, in particular the lowest electrical intensity that produces a visible twitch of the patient's fingers or toes. The user may adjust the electrical intensity via the user interface 155. In other embodiments, no preliminary procedure occurs and a preselected electrical intensity may be used in the SEP measurement procedure. A user may select other parameters for the procedure, such as the number of pulses, via the user interface 155 and initialize the measurement procedure via the user interface 155. The SEP module 105 then provides one or more electrical stimuli via the stimulator 130 and records the response measured at one or more pairs of recording electrodes 145 as a function of time. The response may be stored in the memory 120. The processor 110 is configured to calculate the voltage amplitude of a local maximum or minimum associated with the measured SEP potential as measured by the voltmeter (i.e., to determine whether the local maximum or minimum exists within an expected time window associated with the SEP (e.g., an expected time instance of the SEP ±5 ms)). If multiple electrical stimuli are provided, the processor 110 may calculate the average maximum or minimum voltage amplitude of the SEP. The maximum or minimum may be calculated by any suitable method, such as an interpolation of the measurements or a best-fit algorithm.Alternatively, the measured potential values ​​as a function of time may be displayed on the display device 200 and the user may manually input maximum or minimum amplitude values ​​(and optionally latency) via the user interface 155.

[0082] In some embodiments, the processor 110 is configured to compare the amplitude of the local maximum or minimum to a predefined threshold stored in the memory 120. The predefined threshold may, in some embodiments, define a noise threshold such that a maximum or minimum with an absolute value greater than the noise threshold indicates the presence of a measured SEP. For example, the noise threshold may be determined by determining the maximum or average voltmeter reading when no electrical stimulation is applied, and a voltage reading of that order is associated with noise present in the system and not any measured SEP signal. In some embodiments, the noise threshold may be 0.1 μV. The predefined threshold may be another threshold with optimal specificity and sensitivity as disclosed herein.

[0083] In some embodiments, the processor 110 is configured to determine a maximum or minimum latency associated with the measured SEP potential measured by the voltmeter. The latency may be associated with the time of electrical stimulation provided by the stimulating electrodes or may be associated with a maximum or minimum expected time after the electrical stimulation is provided. This latency may be compared to a predefined latency threshold stored in memory 120. If multiple electrical stimulations are provided, the processor 110 may calculate an average latency of the SEP maximum or minimum.

[0084] The processor 110 may be configured to output information regarding the SEP measurement procedure to the display device 200. The information may include one or more of a maximum or minimum measured voltage amplitude and a maximum or minimum measured latency associated with the SEP. The information may include whether the amplitude and / or latency is above or below a threshold. The information may include an indication of a good or poor expected patient outcome for the endovascular treatment. The information may include a probability value of optimal patient functional recovery from the endovascular treatment. The display device 200 displays the information to a user.

[0085] In some embodiments, memory 120 may include other clinical variables associated with the patient, including a quantitative assessment of the severity of the patient's stroke. Alternatively, a user may input these clinical variables via user interface 155. The variables may include the patient's NIHSS score, ASPECTS score, age, sex, stroke laterality, blood glucose level, and mean arterial pressure. Processor 110 may use the measured amplitude or latency of the measured SEP maximum or minimum in combination with one or more clinical variables to predict the outcome of an endovascular treatment using a composite model stored in memory 120.

[0086] The device 100 may be used to implement any use or method disclosed herein, as another aspect of the invention refers to a computer-implemented method for predicting the outcome of an endovascular stroke treatment in a patient in need thereof before the patient is administered an endovascular stroke treatment, the method comprising the use of the device 100, the computer-implemented method comprising: a) comparing the absolute amplitude of the maxima or minima of SEPs ipsilateral to the stroke to a first predefined amplitude threshold; b) determining that an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site exceeding a first predetermined amplitude threshold indicates a favorable outcome of the endovascular treatment; and / or and determining that absolute amplitudes of SEP maxima or minima ipsilateral to the stroke site below a first predetermined amplitude threshold are indicative of a poor outcome of the endovascular treatment.

[0087] Alternatively or additionally, the computer implemented method comprises: a) comparing the latency of a SEP maximum or minimum ipsilateral to the stroke to a first predetermined latency threshold; and b) determining that a latency of the SEP maximum or minimum ipsilateral to the stroke site below a first predetermined latency threshold indicates a favorable outcome of the endovascular treatment.

[0088] It will therefore be understood that any of the uses of the first aspect of the invention may be considered as such a method. EXAMPLES

[0089] 1.Methodology Patients: According to available data from experimental models, eligible patients were aged between 18 and 90 years, had occlusion of the anterior circulation (M1 or M2 segments of the middle cerebral artery) with or without significant stenosis or occlusion of the ipsilateral internal carotid artery diagnosed by CT angiography (CTA) or MR angiography, had pre-stroke functional independence as measured by a modified Rankin Scale score of 2 or less (0 means no symptoms, 6 indicates death), and had a baseline National Institutes of Health Stroke Scale (NIHSS) score of 6 or more, ranging from 0 to 42 (the higher the score, the more severe the stroke), and were treated within the first 8 hours after the onset of symptoms or after the last hour of an asymptomatic episode in patients with awake stroke or stroke of uncertain course. The main imaging exclusion criterion was evidence of an extensive ischemic core. Therefore, patients with an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) score of 5 or less on plain CT or a score of 4 or less on MR diffusion sequences were excluded from the study. These core cut-off points were selected according to the treatment effect of mechanical thrombectomy shown in the HERMES Collaborative Group meta-analysis (presented at the International Stroke Conference, Houston 2017). In addition, patients with a well-documented history of neuromuscular disease, stroke, or nervous system tumors, which may interfere with the assessment of PES, were also excluded.

[0090] Clinical and neuroimaging data: Clinical and anthropometric variables such as age, sex, location of intracranial occlusion, type of treatment, and the presence of cardiovascular risk factors such as arterial hypertension, diabetes, dyslipidemia, and obesity were registered. Stroke severity was assessed by the NIHSS at admission. Time variables from stroke onset to the various diagnostic and therapeutic interventions during the acute stroke phase were also recorded.

[0091] Baseline neuroimaging was either non-contrast head computed tomography (NCCT) with vascular computed tomography (CTA), multiparametric MRI (MRI), or perfusion computed tomography (CTP) if MRI was unavailable. Control non-contrast head computed tomography (NCCT) or MRI was performed at 24 hours to determine infarct volume and exclude intracranial hemorrhage or malignant edema. Vascular computed tomography (CTA), vascular MRI (MRA), or transcranial Doppler ultrasound (TCD) were used to confirm the durability of revascularization after 24 hours. Variables analyzed on control neuroimaging were the volume and location of the ischemic lesion, the presence of hemorrhagic transformation, and arterial status.

[0092] The CTP protocol was performed on a 64-detector scanner (APV General Electrics, GE Medical Systems; Milwaukee, WI, USA) and included CBF, CBV, MTT, and perfusion mapping (TMax). The amount of tissue with delays to TMax>2s, TMax>4s, TMax>6s, and TMax>8s was assessed to establish a gradient of hypoperfusion severity. Tissue with delays to TMax>6s was considered tissue at risk for ischemia.

[0093] The MRI protocol was performed using a Siemens Magneton Verio 3 Tesla machine with a 32-channel magnet. The acquired sequences were axial slice SWI / gradient echo (GRE), DWI, FLAIR (attenuated inversion recovery imaging), Angio-MR TOF, dMRA (dynamic post-contrast MR angiography), and a perfusion study performed immediately after the dynamic study.

[0094] All images were anonymized and stored in DICOM format. Investigators blinded to clinical outcomes and SEP monitoring assessed all neuroimaging studies. They performed first-pass cerebral perfusion (DSC: Dynamic Susceptibility Contrast) and perfusion maps, visual analysis of qualitative variables and quantitative analysis of post-processing variables. Post-processing of DWI and perfusion sequences was performed using the Olea Sphere platform. In addition, RAPID software (iSchemaView, Redwood City, CA) was used to calculate baseline and control ischemic lesion volumes in MRI DWI sequences and rCBF maps, as well as for automated assessment of the ASPECTS scale in NCCT and MRI DWI sequences. Pre-procedural imaging variables included the volume and location of the ischemic core and baseline hypoperfused tissue, severity of hypoperfusion, location of occlusion, and status of collateral circulation according to the Arterial Collateral Grading Scale (ACG) for Angio-CT or the ASITN / SIR Collateral Grading System scale if the neuroimaging performed was dMRI.

[0095] Conventional angiography assessed the location of arterial occlusion and the extent of recanalization according to modified TICI criteria, which define complete recanalization as TICI 2b, 2c, and 3. The time of femoral puncture (GP), the number of stentriever passes required to achieve revascularization, and the time of arterial recanalization were recorded. Baseline blood pressure and glucose levels were collected, followed by periodic (every 5 min) blood pressure. Conscious sedation was used whenever possible.

[0096] EP monitoring: Evoked potentials were recorded using the 10-channel electromyography system Medelec Synergy™ (Vyasys Healthcare) and the intraoperative monitoring system ISIS (Inomed Medizintechnik GmbH).

[0097] Initially, both MEP and SEP monitoring was planned, but the center's acute ischemic stroke protocol requires patients to be awake or semi-anesthetized, which would make MEP monitoring painful and would prevent patients from cooperating by being under strict rest during the endovascular procedure. Therefore, only SEPs were monitored.

[0098] Stimulation was applied using circular adhesive superficial electrodes (Ambu™ Neuroline 715) on the anterior surface of the carpal bones at a distance of 2 cm center-to-center. Supramaximal stimulation was defined as the intensity that caused a visually perceptible movement of the stimulated limb, with the median nerve considering the thumb movement. Waveform electric pulses of 0.2 ms duration were applied at a frequency of 5.7 Hz, repeated 30 to 150 times depending on the noise-signal ratio. SEPs were recorded in a referenced format according to the international 10-20 system from the locations C3' (right median nerve stimulation) and C4' (left median nerve stimulation), as well as a reference electrode at the Cz' electrode (2 cm behind Cz). Needle subdermal electrodes (Ambu™ Neuroline subdermal) were used if the patient was awake, and "corkscrew" electrodes (Ambu™ Neuroline corkscrew) were used if the patient was under general anesthesia during surgery. Signals were digitally filtered (5 Hz–200 Hz bandpass) and analyzed within a time window of 80 ms after stimulation. 30 to 150 trials were averaged to correct for noise. Target signals were generated from the N-stimulus ipsilateral to the stroke site. 20 Next, the presence of a N response was measured both ipsilaterally and contralaterally to the stroke site. 20 The amplitude (μV) and latency (ms) of the response were also measured. SEPs were analyzed at the time by the examiner and subsequently (>3 months after the stroke event) by a second investigator who was blinded to the clinical outcome and the SEP monitoring results.

[0099] SEP registration was initiated in the emergency area or angiography room before femoral punction was performed and continued throughout the endovascular procedure. SEP monitoring continued until the patient was transferred to the ICU or acute stroke unit to monitor neurological damage during reperfusion.

[0100] Statistical considerations: N for functional independence (mRS ≤ 2) after MT 20 The adjusted predictive value of was analyzed by binary logistic regression, and its predictive value for the total range of physical disability was analyzed by ordinal logistic regression.

[0101] Prognostic variables: The main prognostic variable was functional independence at 7 days after stroke or at discharge, defined as an mRS score ≦2, which shows a strong correlation with functional independence at 90 days (Davalos A et al. Lancet Neurol 2017). Other secondary prognostic variables were functional independence at 90 days as assessed by the mRS scale; severity of disability at 7 and 90 days according to the mRS scale; (dramatic) neurological improvement (defined as a (10)4-point reduction in the NIHSS scale compared to baseline); optimal revascularization (defined by a TICI scale score of 2b or 3 (stroke size on control CT or MR); and several baseline imaging variables, such as core, size of ischemic volume, and status of collateral circulation.

[0102] 2.Results A total of 228 patients were included. Five were excluded, three because the SEP registry could not be recovered for the analysis performed by the blinded investigator, one because a previous stroke was found in the neuroimaging study that could affect the SEP results, and the last one due to the presence of a bihemispheric acute ischemic stroke. Thus, the final sample size was 223 patients. The mean age was 69.9 years (SD 13.7), and 41.7% were women. At the time of inclusion, all patients, except for four, scored a modified Rankin Scale (mRS) score of 0–2. These four patients scored 3 on the mRS and were considered for endovascular treatment according to the criteria of the vascular neurologist. They had previous comorbidities not related to the blood vessels. 48% of the patients presented with stroke due to occlusion of the M1 segment of the middle cerebral artery (MCA), making it the most frequent type of stroke. Other types of occlusions were the internal carotid artery (ICA) in 19.3%, tandem MCA-ICA in 19.7%, and the M2 segment of the MCA. Regarding the type of treatment received, 113 patients (51.1%) had endovascular treatment after intravenous thrombolysis, and 108 patients (48.9%) had primary endovascular treatment. The median NIHSS score on arrival at the hospital was 18 points ([12-22] 95% CI), and the mean and median ASPECTS scores on neuroimaging before MT were 8. The mean time from symptom onset to arterial recanalization was 432 minutes, with a median of 340.5 ([240-522] 95% CI). Recanalization time could not be achieved in 26 patients, 23 because of lack of recanalization and 3 because of unknown symptom course.

[0103] 2.1 Neurophysiological variables The target neurophysiological variable was the N of SEPs. 20 Responses can be defined qualitatively (present / absent / valueless) and quantitatively (amplitude and latency). 20 In the contralateral side, 162 patients had N 20There were no cases with or without the presence of N 20 Responses were not assessable in 25% and 27% of patients with affected and healthy hemispheres, respectively, due to ambient radio frequency artifacts. 20 The mean and median amplitudes were lower in the affected hemisphere, but the latencies were similar between the two hemispheres (Table 1). 20 The mean time to documentation was 299.03 minutes (SD 267.6), whereas the median time was 252 minutes, with an interquartile range (IQR) of [149.7–363.7].

[0104] [Table 1]

[0105] Table 1: Baseline neurophysiological variables (analysis population). μV: microvolts; ms: milliseconds.

[0106] Neurophysiological outcome variables in the population under study Seventy-seven patients (34.6%) had a good functional outcome, defined as an mRS score ≤ 2 on day 7 after stroke. At 24 hours after stroke, 133 patients (59.6%) had neurological improvement (improvement of ≥ 4 points on the NIHSS scale) and 79 (35.4%) had dramatic neurological improvement (improvement of ≥ 10 points on the NIHSS scale or an NIHSS score of 0–1).

[0107] Beneficial N 20 Neurophysiological outcome variables in populations with N 20 Responses were not assessed at baseline (before MT) in 55 patients, reducing the population to 168. Baseline N = 1 for all primary and secondary clinical outcome variables in this study 20 A statistically significant difference between patients with and without was found (see Table 2). The p-value is used as a statistical significance indicator.

[0108] [Table 2]

[0109] Table 2: Measurable N 20 Primary and secondary clinical outcomes in the responding population. mRS variables at 90 days after stroke were 20 Among patients with and without IL-1, 101 and 56 were titratable, respectively.

[0110] 2.2 N on the 7th day before MT 20 Prognostic ability of response 2.2.1 Good prognostic function at day 7 (mRS ≤ 2) Post-mortem analysis A favorable functional outcome was observed in 77 patients (34.6%), who were younger, had poorer levels of blood glucose and diastolic arterial tone, lower initial scores on the NIHSS scale, and less ischemic tissue stretch (Table 3).

[0111] [Table 3]

[0112] Table 3: Baseline clinical and time-flow variables in patients with good (mRS ≤ 2) and poor (mRS > 2) functional outcome at 7 days. Optimal functional outcome was defined as a score ≤ 2 on the mRS scale. tPA: intravenous thrombolysis; MT: mechanical thrombectomy; LMCA: left middle cerebral artery; ICA: internal carotid artery. &U Mann-Whitney; * Chi-square.

[0113] Baseline N, characterized by latency (ms) and amplitude (mV) values, with good or poor functional outcome 7 days after stroke 20When correlating the responses quantitatively, it was found that patients with a good functional prognosis had significantly higher amplitude (2.7 vs. 1.1, p<0.001) values ​​than patients with a poor functional prognosis of the affected cerebral hemisphere. Similarly, it was found that patients with a good functional prognosis had significantly lower latency values ​​(corrected for zero value effects) than patients with a poor functional prognosis of the affected cerebral hemisphere (3.4 vs. 11.2, p<0.001). The ratios of amplitude and latency between pathological and healthy hemispheres were not statistically significant compared to the absolute amplitude and latency values ​​(Table 4). Therefore, relative values ​​(% of healthy hemisphere) are not necessary.

[0114] [Table 4]

[0115] Table 4: Post-hoc analysis: Baseline N according to optimal functional outcome at 7 days after stroke 20 Amplitude and latency of & Mann-Whitney U; ¶ Nonparametric tests for median comparison. # t-Student. Variable "N" in pathological cerebral hemispheres 20 In the case of "latency", N 20 The value "0" is not included when the "Discr." latency: N 20 To eliminate the effect of the "0" value for no response, a variable "discriminant latency" was also created. This was 20 It consists of the absolute difference from the normal latency of the response (20 ± 5 ms). 20 "Amplitude pathological cerebral hemisphere" includes N 20 Contains the value "0" if there was no response. X The variable "N 20 "Latent pathological cerebral hemisphere" includes N 20 The "0" latency value assigned to non-responding patients was omitted. Therefore, this variable was omitted for N 20 N of patients with a response 20 The mean latency of response is defined and other patients are excluded.

[0116] Baseline N measured by categorical 7-day functional outcome 20 When correlated with the response (present / absent), baseline N ipsilateral to the stroke 20 Of the 58 non-responders, 54 had poor clinical outcome (mRS>2). 20 Of the 110 patients who responded, 56 had a good clinical outcome. 20 The NCI was not assessable in 22.1% and 26% of patients with good and poor clinical outcomes, respectively (Table 5). Taking these results into account, the NCI was 20 Exclude patients with baseline N 20 The presence of N ipsilateral to the stroke had a sensitivity of 93% and a specificity of 50% for predicting optimal functional outcome 7 days after stroke, with positive and negative predictive values ​​of 51% and 93%, respectively (Table 6). 20 Measurement of response may provide a reliable method of determining which patients would not benefit from endovascular treatments such as mechanical thrombectomy.

[0117] [Table 5]

[0118] Table 5: Primary outcome variables: baseline N vs functional outcome at 7 days post-stroke 20 Ability to predict response.

[0119] [Table 6]

[0120] Table 6: N for predicting optimal functional outcome at 7 days after stroke 20 Precision of the response. CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value.

[0121] Univariate analysis Correlating the clinical variables considered in this study with optimal functional outcome at 7 days after stroke, N 20It was observed that variables related to the dichotomous N had a better ability to predict optimal functional outcome than other variables used in daily clinical practice, such as the NIHSS or ASPECTS scales (Table 7). 20 Amplitude (odds ratio (OR) = 14, area under the [ROC] curve (AUC) = 0.713) and log-transformed N 20 The predictive power of amplitude (OR=1.93, AUC=0.726) was noteworthy.

[0122] [Table 7]

[0123] Table 7: Univariate analysis. Predictive ability of clinical variables for optimal functional outcome after 7 days. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. rTPA: intravenous fibrinolysis. "Discr." Latency: N 20 The variable “discrimination latency” was also created to eliminate the effect of the “0” value for no response. 20 The variable "Amplitude N" consists of the absolute difference from the normal latency of the response (20 ± 5 ms). 20 "Pathological cerebral hemisphere" includes N 20 Contains the value "0" if there was no response.

[0124] Multivariate analysis Multivariate analysis was performed including all significant variables with p<0.1. In multivariate model A, N 20 In multivariate model B, the log-transformed amplitudes of N 20 Dichotomous (present / absent) amplitudes of were used. Multivariate analysis included both log-transformed (Model A) and dichotomous (Model B) N 20 The results showed that amplitude response behaved as an independent factor associated with good functional outcome at day 7 (OR 1.83; [1.35-2.57]; p<0.001 in model A, and OR 9.88 [3.08-44.58]; p=0.001 in model B) (Table 8).

[0125] [Table 8]

[0126] Table 8: Multivariate analysis: Clinical variables and optimal functional outcome 7 days after stroke. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0127] Logistic regression models were also constructed for various clinical variables of interest, either alone or in combination: baseline clinical variables (age, sex, laterality, blood glucose and mean arterial pressure (MAP), NIHSS, ASPECTS, and N 20 Response (see Table 9). N 20 The responses were included in several configurations: amplitude of the SEP using the variable in a quantitative manner (quantitative amplitude), the same amplitude but applying a logarithmic transformation to the values ​​(quantitative log-transformed amplitude), and amplitude using the variable in a binarized manner (i.e. indicating that the variable is either present or absent according to a threshold (binarized amplitude)). The model was designed as follows. Model 0a: NIHSS Model 0b: NIHSS + baseline variables Model 1a: Quantitative N 20 amplitude Model 1b: NIHSS Basic + Quantitative N 20 Amplitude + Baseline Variables Model 2a: Quantitative N 20 Logarithmic Transformation Magnitude Model 2b: NIHSS + quantitative N 20 Log-transformed amplitudes + baseline variables Model 3a: Binarized N 20 amplitude Model 3b: NIHSS + binary N 20 Amplitude + Baseline Variables Model 4: NIHSS+ASPECTS Model 5: NIHSS + Binarized N 20 amplitude

[0128] [Table 9]

[0129] Table 9: Logistic regression model for 7-day prediction before MT: number of patients and AUC values.

[0130] Quantitative N 20 The amplitude response alone (Model 1a) has a higher predictive ability for favorable functional outcome at 7 days after stroke than the NIHSS scale (Model 0a) (AUC 0.726 vs. 0.670) and the combination of the NIHSS and ASPECTS scales (Model 4) (AUC 0.719), clinical variables currently used to select candidates for endovascular therapy. Of note, the NIHSS scale can be assessed in a prehospital setting, whereas the ASPECTS scale is limited to the in-hospital setting, as it requires imaging of the brain, either CT or MRI. Furthermore, the NIHSS and the dichotomized N 20 Amplitude combination (Model 5); NIHSS and baseline variables and log-transformed quantitative N 20 Combination of amplitude variables (Model 2b), and NIHSS and baseline variables and dichotomized N 20 The combination of amplitude variables had AUCs of 0.784, 0.823, and 0.830, respectively, both higher than those of the NIHSS scale alone and the combination of NIHSS and ASPECTS (Model 4 - AUC 0.719) (see Figures 3A-F for the ROC curves of the models and Table 9 for the regression AUCs of the models). 20 It can be concluded that adding to the NIHSS and usual baseline variables significantly increases its predictive power.

[0131] Further analysis of Model 1a was performed to determine the current amplitude value that better determines the difference between good and bad outcome, i.e. the value that provides the best decision threshold. Several threshold cuts were made and for each, sensitivity, specificity, PPV and NPV were calculated (see ).

[0132] [Table 10]

[0133] Table 10: Pre-intervention classification performance on day 7 for various threshold cuts

[0134] N 20 Absolute N of the response 20 The classification index with an amplitude threshold of 0.375 μV had a sensitivity and NPV of 93%, a specificity and PPV of 52%, and a mean mean of 1.0. 20 Absolute N of the response 20 Classification indices with amplitude thresholds between 0.25 μV and 0.5 μV were observed to have sensitivity and NPV of 90%–92%, specificity of 49%–53%, and PPV value of 46%.

[0135] N 20 Optimal sensitivity and acceptable specificity for functional prognosis before endovascular stroke treatment on day 7 were obtained when the SEP absolute amplitude threshold was included between 0.25 μV and 0.5 μV. 20 The most suitable sensitivity and specificity are obtained when the absolute amplitude threshold of the SEP is included in the range of 0.37 μV to 0.38 μV.

[0136] 2.2.2 Functional outcome at 7 days (shift analysis) Post-mortem analysis N 20 Patients with N have an overall better functional prognosis in all categories of the mRS scale. 20 Fifty-one percent of responding patients had a score of 0–2 on the mRS scale 7 days after stroke, compared with baseline N 20 Of note, the proportion of patients with mRS scores of 4 and 5–6 was significantly higher in the N 20 was significantly lower in patients with genomic DNA (15.5% vs. 20.7%, 21.9% vs. 63.9%, respectively).

[0137] Univariate analysis When the clinical variables assessed in the study were related to functional outcomes according to the degree of total disability at day 7, N 20 Variables related to the binarization N 20It was observed that amplitude has a better ability to predict optimal functional outcome than other variables used in routine clinical practice, such as the NIHSS or ASPECTS scales (Table 11).

[0138] [Table 11]

[0139] Table 11: Univariate analysis. Predictive ability of clinical variables for 7-day functional outcome. OR coefficients and Brier coefficients (lower values ​​indicate higher predictive ability) are shown for the clinical variables of the study. Variables are ordered according to Brier coefficients. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. rTPA: intravenous fibrinolysis. #N to avoid the influence of the value "0" 20 The latency was corrected.

[0140] Multivariate analysis Similar multivariate analyses were performed including all significant variables with p<0.1 as in the favorable functional prognosis analysis, and model A (N 20 (including logarithmic transformation amplitude (μV) of ) and Model B (N 20 A multivariate analysis was designed to assess whether baseline variables associated with ordinal mRS at day 7 were age (older age associated with poorer outcome), baseline NIHSS (higher baseline severity associated with poorer outcome), blood glucose (higher values ​​associated with poorer outcome), ASPECTS (higher values ​​associated with better outcome), and baseline amplitude or N 20 The presence of a response (presence of a value is associated with a better outcome than absence of a value) was shown (Table 12).

[0141] [Table 12]

[0142] Table 12: Multivariate analysis: Clinical variables and functional outcome 7 days after stroke. *All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0143] 2.3 N on the 90th day before MT 20 Prognostic ability of response 2.3.1 Good functional outcome at 90 days (mRS ≤ 2) Post-mortem analysis The mRS was evaluated at 90 days for 204 patients. A good functional outcome was observed in 98 patients (48%). They were younger, had poorer blood glucose and diastolic arterial tone levels, lower initial scores on the NIHSS scale, and smaller ischemic tissue stretch (Table 13).

[0144] [Table 13]

[0145] Table 13: Baseline clinical and time-flow variables in patients with good (mRS ≦2) and poor (mRS>2) functional outcome at 90 days. Optimal functional outcome is defined as a score ≦2 on the mRS scale. tPA: intravenous thrombolysis; MT: mechanical thrombectomy; LMCA: left middle cerebral artery; ICA: internal carotid artery. &U Mann-Whitney; * Chi-square.

[0146] Similar to the 7-day prognosis analysis, patients with a good functional outcome at 90 days after stroke were found to have significantly higher amplitude values ​​(2.4 vs. 1.1, p<0.001) in the affected hemisphere than patients with a poor functional outcome at 90 days after stroke. Similarly, patients with a good functional outcome at 90 days after stroke were found to have significantly lower latency values ​​(corrected for zero value effects) in the affected hemisphere than patients with a poor functional outcome at 90 days after stroke (4.1 vs. 13.6, p<0.001) (Table 14). Similarly, relative values ​​(% of healthy hemisphere) are not necessary.

[0147] [Table 14]

[0148] Table 14: Post-hoc analysis: Baseline N according to optimal functional outcome at 90 days post-stroke 20 Amplitude and latency of & Mann-Whitney U; ¶ Nonparametric tests for median comparison. # t-Student. Variable "N" in pathological cerebral hemispheres 20 In the case of "latency", N 20 The value "0" is not included when the "Discr." latency: N 20 The variable “discrimination latency” was also created to eliminate the effect of the “0” value for no response. 20 It consists of the absolute difference from the normal latency of the response (20 ± 5 ms). 20 "Amplitude pathological cerebral hemisphere" includes N 20 Contains the value "0" if there was no response.

[0149] 90-day functional outcome measured by categorical baseline N 20 When correlated with the response (present / absent), baseline N ipsilateral to the stroke 20 Of the 56 non-responders, 48 ​​had poor clinical outcome (mRS>2). 20 Of the 101 patients who responded, 73 had a good clinical outcome. 20 The NCI was not evaluable in 17.3% and 28.3% of patients with good and poor clinical outcomes, respectively (Table 15). Taking these results into account, the NCI for non-evaluable outcomes was 20 Exclude patients with baseline N 20 The sensitivity and specificity of the presence of N ipsilateral to the stroke for predicting optimal functional outcome 7 days after stroke was 90.1% and 63.2%, respectively, with positive and negative predictive values ​​of 85.7% and 72.3%, respectively (Table 16). 20 Measurement of response may provide a reliable method of predicting outcome in patients undergoing endovascular treatments such as mechanical thrombectomy.

[0150] [Table 15]

[0151] Table 15: Functional outcome at 90 days after stroke by baseline category N 20 Ability to predict response.

[0152] [Table 16]

[0153] Table 16: N for predicting optimal functional outcome at 7 days after stroke 20 Precision of the response. CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value.

[0154] Univariate analysis When relating the clinical variables considered in this study to optimal functional outcome at 90 days after stroke, N 20 It was also observed that variables related to the dichotomous N had a better ability to predict optimal functional outcome than other variables used in daily clinical practice, such as the NIHSS or ASPECTS scales (Table 17). 20 Amplitude (OR=15.62) and log-transformed N 20 The predictive power of amplitude (OR=1.95) was noteworthy.

[0155] [Table 17]

[0156] Table 17: Predictive ability of clinical variables for optimal functional outcome at 90 days. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. # t-Student. Pathological cerebral hemisphere variable "N 20 In the case of "latency", N 20 does not include the value "0" in the absence of rTPA: intravenous fibrinolysis.

[0157] Multivariate analysis Multivariate analysis was performed. In multivariate model A, N20 All significant variables with p<0.1, including the amplitude of 20 An automated variable selection process (AIC) was used, including the dichotomous (present / absent) amplitude of . Multivariate analysis was performed with a dichotomous N 20 The amplitude response was shown to behave as an independent factor associated with good functional outcome at 90 days (OR 15.36; [5.50-49.87]; p<0.001 in models A and B) (Table 18).

[0158] [Table 18]

[0159] Table 18: Multivariate analysis: Clinical variables and functional outcome 90 days after stroke. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0160] Logistic regression models were also constructed for various clinical variables of interest, either alone or in combination: baseline clinical variables (age, sex, laterality, blood glucose and mean arterial pressure (MAP), NIHSS, ASPECTS, and N 20 Response (see Table 19). N 20 The responses were included in several configurations: the amplitude of the SEP using the variable in a quantitative manner (quantitative amplitude), the same amplitude but applying a logarithmic transformation to the values ​​(quantitative log-transformed amplitude), and the amplitude using the variable in a binarized manner (i.e., indicating that the variable is either present or absent according to a threshold (binarized amplitude)). The model was designed as follows. Model 0a: NIHSS Model 0b: NIHSS + baseline variables Model 1a: Quantitative N 20 amplitude Model 1b: NIHSS Basic + Quantitative N 20 Amplitude + Baseline Variables Model 2a: Quantitative N 20 Logarithmic Transformation Magnitude Model 2b: NIHSS Basic + Quantitative N 20 Log-transformed amplitudes + baseline variables Model 3a: Binarized N 20 amplitude Model 3b: Baseline NIHSS + dichotomized N 20 Amplitude + Baseline Variables Model 4: NIHSS Basic + ASPECTS

[0161] [Table 19]

[0162] Table 19: Logistic regression model of 90-day prediction before MT: number of patients and AUC values.

[0163] Quantitative N 20 Response alone (Model 1a) still has a higher predictive ability for favorable functional outcome at 90 days after stroke than the NIHSS scale (Model 0a) (AUC 0.736 vs. AUC 0.678) and the combination of the NIHSS and ASPECTS scales (Model 4) (AUC 0.697), clinical variables currently used to select candidates for endovascular therapy. Furthermore, the association between the NIHSS and baseline variables and N 20 The combination of variables has better predictive ability (AUC 0.851-Model 2b) (AUC 0.895-Model 3b) than the combination of NIHSS and ASPECTS (Model 4) (AUC 0.697) and the combination of NIHSS and baseline variables (AUC 0.793) (see Figures 4A-4D for the ROC curves of the models and Table 19 for the regression AUCs of the models).

[0164] Similar to the 7-day outcome analysis, N 20 Adding NIHSS and normal basic variables to the above, especially N 20 predictive ability improves significantly when is measured qualitatively or dichotomously (presence / absence) (Model 3b).

[0165] Further analysis of Model 1a was performed to determine the current amplitude value that better determines the difference between good and bad outcome, i.e. the value that provides the best decision threshold. Several threshold cuts were made and for each, sensitivity, specificity, PPV and NPV were calculated (see ).

[0166] [Table 20]

[0167] Table 20: Pre-intervention classification performance at 90 days for various threshold cuts

[0168] N 20 Absolute N of the response 20 The classification index between the amplitude threshold of 0.339 μV was observed to have a sensitivity of 90.1%, specificity of 64.5%, PPV of 65%, and NPV of 72.7%, with N 20 Absolute N of the response 20 Classification indices with amplitude thresholds between 0.25 μV and 0.5 μV were observed to have sensitivity between 86% and 88%, specificity between 62% and 64%, PPV values ​​between 65%, and NPV values ​​between 72% and 76%. 20 Optimal sensitivity and acceptable specificity for functional prognosis before endovascular stroke treatment at 90 days were obtained when the SEP absolute amplitude threshold was included between 0.25 μV and 0.5 μV. 20 The most suitable sensitivity and specificity are obtained when the absolute amplitude threshold of the SEP is included in the range of 0.33 μV to 0.35 μV.

[0169] 2.3.2 Functional outcome at 90 days (shift analysis) Post-mortem analysis N 20 Patients with N have an overall better functional prognosis in all categories of the mRS scale. 20 Seventy-two percent of responding patients had a score of 0–2 on the mRS scale 90 days after stroke, compared with baseline N 20 Of note, the proportion of patients with mRS scores of 4 and 5–6 was significantly higher in the N 20was significantly lower in patients with genomic DNA present (10.9% vs. 25% and 15.8% vs. 51.8%, respectively).

[0170] Univariate analysis When the clinical variables assessed in the study were related to functional outcomes according to the degree of total disability at 90 days, N 20 Variables related to the binarization N 20 It was observed that amplitude has a better ability to predict optimal functional outcome than other variables used in routine clinical practice, such as the NIHSS or ASPECTS scales (Table 21).

[0171] [Table 21]

[0172] Table 21: Univariate analysis. Predictive ability of clinical variables for functional outcome according to the degree of total disability at 90 days. OR coefficients and Brier coefficients (lower values ​​indicate higher predictive ability) are shown for the clinical variables of the study. Variables are ordered according to Brier coefficients. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. rTPA: intravenous fibrinolysis. #N to avoid the influence of the value "0" 20 The latency was corrected.

[0173] Multivariate analysis Similar multivariate analyses were performed, defining Models A and B as in Section 2.3.1. Multivariate analyses showed that baseline variables associated with ordinal mRS at day 90 were age (older age associated with poorer outcome), baseline NIHSS (higher baseline severity associated with poorer outcome), blood glucose (higher values ​​associated with poorer outcome), ASPECTS (higher values ​​associated with better outcome), and baseline amplitude or N 20 The presence of a response (presence of a value was associated with a better outcome than absence of a value, with presence associated with the best functional prognosis) (OR 6.67 model A and OR 7.14 model B) (see Table 22).

[0174] [Table 22]

[0175] Table 22: Multivariate analysis: Clinical variables and functional outcome according to degree of total disability 90 days after stroke. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. Baseline amplitudes are included in only one modality (quantitative, log-transformed, and categorical) depending on whether the Brier score is low or not. rTPA: intravenous fibrinolysis.

[0176] 2.4 Neuroimaging study of N on the 7th day before MT 20 Prognostic ability of response Finally, N by category 20 The performance of several models including the response (present / absent) and one or more neuroimaging tests was assessed. By itself, each assessment method has a different odds ratio (OR), predictive ability (AUC), and statistical significance (p), as seen in Table 23.

[0177] [Table 23]

[0178] Table 23 N 20 Univariate analysis of (categorical) and imaging variables. * Ungradable N 20 Patients with ≥ 10% CI were not considered. The ASPECTS scale was considered a continuous variable.

[0179] Category N 20 Response has better prognostic power than any other imaging variable in the study. This represented a significant improvement over the best neuroimaging predictor, ischemia core score (AUC 0.713 vs. 0.657).

[0180] In multivariate analysis, the univariate model showed a useful N 20Adjusted to include only patients with a response. Tmax>6 and HIR variables were excluded due to poor performance. Five models were adjusted. Model 0: Categorical N 20 Response(N 20 ) Model 1: Collateral circulation + N 20 Model 2: Core ischemic lesion + N 20 Model 3: ASPECTS scale score + N 20 Model 4: Collateral circulation status + Core ischemic damage + ASPECTS scale score + N 20

[0181] As mentioned above, N by category 20 Responses alone, collateral circulation, core ischemic lesions, and their combinations with ASPECTS scale score, both independently and together, have been used to construct these models. The ORs of each variable in each model and the AUC of each model are summarized in Table 24.

[0182] [Table 24]

[0183] Table 24: Multivariate analysis. N 20 Adjusted predictive ability of response (categorical) and imaging variables. * Ungradable N 20 Patients with Tmax > 6 and HIR were excluded.

[0184] Category N 20 The combination of response (absent / present) and neuroimaging tests provided better predictive power than current multimodal / advanced neuroimaging techniques. 20 The response combination provided the best predictive ability with an AUC of 0.813. 20 Note that response improved neuroimaging AUC by 0.12 points when included as a prognostic tool.

[0185] These results are categorical N 20 We show that Response not only provides better prognostic ability than known techniques, but also significantly improves the prognostic ability of these techniques (collateral circulation, ischemic core, and ASPECTS scale scores). The best prognostic ability was observed for all neuroimaging scores and categorical N 20 This is achieved by a combination of response variables.

[0186] 2.5 N on the 7th day after MT 20 Prognostic ability of response 2.5.1 Good functional outcome (mRS ≤ 2) at day 7 Post-mortem analysis In the post-treatment analysis, the following variables were examined: TICI scale at the end of mechanical thrombectomy, duration of ischemia (time from onset of symptoms to arterial recanalization), presence of complications during the procedure, and general complications after stroke (first 72 hours and after this time limit). Patients with a good functional outcome (mRS ≦2) had a higher rate of optimal arterial recanalization (TICI scale ≧2b) and fewer overall complications after stroke, both early (first 72 hours) and late (more than first 72 hours) (see Table 25).

[0187] [Table 25]

[0188] Table 25: Final clinical and time-flow variables in patients with good (mRS≦2) and poor (mRS>2) functional outcome at day 7. Optimal functional outcome is defined as a score on the mRS scale of 2 or less. TM: mechanical thrombectomy; TICI: thrombolysis in cerebral infarction. * Chi-square.

[0189] Univariate analysis Clinical variables considered to be relevant during and after mechanical thrombectomy were associated with optimal functional outcome at 7 days after stroke, and pathological hemispheric N at the end of the procedure. 20 Variables related to N, especially in absolute value20 It was observed that amplitude and latency of sigma-beta had a higher ability to predict optimal functional outcome than the rest of the variables studied (Table 26).

[0190] [Table 26]

[0191] Table 26: Univariate analysis. Predictive ability of post-MT clinical variables for optimal functional outcome at day 7. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0192] Multivariate analysis Multivariate analysis was performed. In multivariate model B, N 20 All significant variables with p<0.1 were included, including the (presence / absence) amplitude of 20 The quantitative log amplitude of CI, CI, and two variables that were significant at the univariate level but not at the multivariate level (medical complications during the first 72 hours and duration of ischemia). Multivariate analysis included categorical (binary) N 20 The response amplitude was shown to behave as an independent factor associated with better functional outcome at day 7 (Table 27).

[0193] [Table 27]

[0194] Table 27: Multivariate analysis. Predictive ability of clinical variables for 7-day optimal functional outcome after mechanical thrombectomy * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0195] Logistic regression models were also constructed for various clinical variables of interest, alone or in combination: final TICI scale, post-intervention N 20Amplitude (quantitative and log-transformed), and combinations of the two (see Figures 5A-C for model ROC curves and Table 28 for model regression AUC): Model 0a: Final TICI (scale determining the degree of arterial recanalization) Model 1: N after intervention 20 Amplitude (quantitative and logarithmic transformation) Model 2: Final TICI + N after intervention 20 Amplitude (quantitative and logarithmic transformation)

[0196] [Table 28]

[0197] Table 28: Logistic regression model for 7-day prediction after MT: number of patients and AUC values.

[0198] N 20 Amplitude alone (Model 1) still has a higher predictive ability for good functional outcome at 7 days after stroke than the TICI scale (Model 0) (AUC 0.823 vs. AUC 0.620). 20 The predictive ability of amplitude alone is slightly improved (AUC 0.829 vs. 0.823).

[0199] Further analysis of Model 1 was performed to determine the current amplitude value that better determines the difference between good and bad outcomes, i.e., the value that provides the best decision threshold. Several threshold cuts were made and for each, sensitivity, specificity, PPV and NPV were calculated (see Table 29).

[0200] [Table 29]

[0201] Table 29: Post-intervention classification performance on day 7 for various threshold cuts

[0202] N 20 Log transformation of response N 20Classifiers with amplitude thresholds of 0.25 μV to 0.5 μV were observed to have a sensitivity of 98% to 100% (95% CI 86% to 100%), specificity of 64%, PPV of 53% to 55%, and NPV of 96%.

[0203] N 20 Optimal sensitivity and acceptable specificity for functional outcome after endovascular stroke treatment on day 7 was obtained when the SEP absolute amplitude threshold was included between 0.25 µV and 0.5 µV.

[0204] 2.5.2 Functional outcome at day 7 (shift analysis) Post-mortem analysis N 20 Patients with N have an overall better functional prognosis in all categories. 20 None of the non-responders had mRS scores between 0 and 2 at 7 days after stroke. The proportion of patients with mRS scores of 5 and 6 (major addicts and achievers) was 1.2%. 20 The difference in the mean age for patients with ≥ 18 years was significantly higher in those without ≥ 18 years (17% vs. 4% and 11% vs. 0.4%, respectively).

[0205] Univariate analysis When the clinical variables assessed in this study were related to functional outcomes according to the degree of total disability at day 7, N 20 Variables related to the 20 It was observed that amplitude had a better ability to predict optimal functional outcome than either arterial recanalization itself (TICI scale) or post-procedure medical complications (Table 30).

[0206] [Table 30]

[0207] Table 30: Univariate analysis. Predictive ability of functional outcome according to the degree of all disability at 7 days after MT clinical variables. OR and Brier coefficient are shown (lower values ​​indicate higher predictive ability). Variables are ordered according to Brier coefficient. *All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. #N to avoid the influence of the value “0” 20 The latency was corrected.

[0208] Multivariate analysis Similar multivariate analyses were performed including all significant variables with p<0.1 as in the favorable functional prognosis analysis, and model A (N 20 (including logarithmic transformation amplitude (μV) of ) and Model B (N 20 A categorical (present / absent) amplitude (%) of was designed.

[0209] Multivariate analysis showed that baseline variables associated with ordinal mRS at day 7 were complications >72 hours after stroke (more complications, worse outcome) and N 20 The extent (log transformed) or presence (higher values ​​or greater presence associated with better outcome) of response was shown (Table 31).

[0210] [Table 31]

[0211] Table 31: Multivariate analysis: Clinical variables and functional outcome according to degree of total disability 7 days after stroke. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. Baseline amplitudes are included in only one modality (quantitative, log-transformed, and categorical) depending on whether the Brier score is low or not.

[0212] 2.6 N on the 90th day after MT 20 Prognostic ability of response 2.6.1 Good functional outcome at 90 days (mRS ≤ 2) Post-mortem analysis The mRS was evaluated at 90 days for 204 patients. A good functional outcome was observed in 98 patients (48%). They were younger, had poorer levels of blood glucose and diastolic arterial tone, lower initial scores on the NIHSS scale, and less stretch of ischemic tissue (Table 32).

[0213] [Table 32]

[0214] Table 32: Final clinical and time-flow variables in patients with good (mRS≦2) and poor (mRS>2) functional outcome 90 days after stroke. Optimal functional outcome is defined as a score on the mRS scale of 2 or less. MT: mechanical thrombectomy; TICI: thrombolysis in cerebral infarction. & Mann-Whitney U;¶Nonparametric test for median comparison; # t-Student. Variable "N" in pathological cerebral hemispheres 20 In the case of "latency", N 20 does not contain the value "0" when absent. * “Discr” latency: N 20 To avoid the effect of a "0" value in the absence of a response, a variable "discrimination latency" was also created. 20 The variable "Amplitude N" consists of the absolute difference from the normal latency of the response (20 ± 5 ms). 20 "Pathological cerebral hemisphere" includes N 20 Contains the value "0" if there was no response.

[0215] Univariate analysis When the relevant post-MT clinical variables considered in the study were associated with optimal functional outcome at 90 days after stroke, N 20 It was similarly observed that the relevant variables, especially latency and amplitude, both in absolute and dichotomized form, proved to be more capable of predicting optimal functional outcome than either the TICI score at the end of treatment or duration of ischemic time (Table 33). 20 Amplitude (OR=500) and log-transformed N 20 The predictive power of amplitude (OR=5.85) was notable.

[0216] [Table 33]

[0217] Table 33: Univariate analysis. Predictive ability of post-intervention clinical variables for optimal functional outcome at 90 days. All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. The variables are ordered from highest to lowest according to their predictive ability, expressed as the area under the curve (AUC). * “Discr” latency: N 20 To avoid the effect of a "0" value in the absence of a response, a variable "discrimination latency" was also created. 20 The variable "Amplitude N" consists of the absolute difference from the normal latency of the response (20 ± 5 ms). 20 In "Pathological Cerebral Hemisphere", the value "0" is N 20 Included if there was no response. ≠ The variable "N" of the pathological cerebral hemisphere 20 "Amplitude" and "logN 20 For "amplitude", the value "0" is N 20 Included if there was no response. # Nervous system: progressive stroke, malignant infarction, stroke recurrence, concurrent seizures, asymptomatic IH1 and IH2 hemorrhagic transformation, symptomatic intracranial hemorrhage, hyperperfusion syndrome, coma. Systemic: systemic hemorrhage, atrial fibrillation, hypertensive crisis, hypotension, chest pain, other cardiovascular complications, aspiration pneumonia, systemic infection, cardiopulmonary arrest, respiratory infection, peripheral embolism, acute urinary retention, anemia, hematological complications, angioedema, agitation. ± Arterial rupture with contrast extravasation, arterial dissection, distal embolism, subarachnoid hemorrhage, vasospasm requiring treatment, hemodynamic complications (hypertension, hypotension, bradycardia), device rupture, reocclusion, and femoral thrombosis.

[0218] Multivariate analysis Multivariate analysis was performed. In multivariate model A, all significant variables with p<0.1 were included. "Complications within 72 hours of stroke", which was significant in univariate analysis, was included in multivariate model B using an automated variable selection process (AIC). Multivariate analysis showed that in both models, the only post-treatment variables associated with functional outcome at 90 days were N in the stroke-affected hemisphere at the end of treatment. 20 The log-transformed amplitude of the response and complications >72 hours after stroke onset were shown (Table 34).

[0219] [Table 34]

[0220] Table 34: Multivariate analysis. Predictive ability of post-intervention clinical variables for optimal functional outcome at 90 days. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0221] Logistic regression models were also constructed for various clinical variables of interest, alone or in combination: final ICTI and post-intervention quantitative and transformed N 20 (See Figures 6A-6C for model ROC curves and Table 35 for model regression AUC): Model 0: Final TICI Model 1: N after intervention 20 Amplitude (quantitative and logarithmic transformation) Model 2: Final TICI and post-intervention N 20 Amplitude (quantitative and logarithmic transformation)

[0222] [Table 35]

[0223] Table 35: Logistic regression model of 90-day prediction after MT: number of patients and AUC values.

[0224] N 20 Response alone (Model 1) still has a higher predictive ability for good functional outcome at 90 days after stroke than the TICI scale (Model 0) (AUC 0.917 vs. AUC 0.626). Similar to the 7-day outcome analysis, N 20 Adding N to the TICI scale 20 predictive ability improves significantly when is measured qualitatively or dichotomously (presence / absence) (Model 2).

[0225] Further analysis of Model 1 was performed to determine the current amplitude value that better determines the difference between good and bad outcomes, i.e., the value that provides the best decision threshold. Several threshold cuts were made and for each, sensitivity, specificity, PPV and NPV were calculated (see Table 36).

[0226] [Table 36]

[0227] Table 36: Post-intervention classification performance at 90 days for various threshold cuts

[0228] N 20 Log transformation of response N 20 Classifiers with amplitude thresholds of 0.25 μV to 0.5 μV were observed to have sensitivities of 96% to 98%, specificities of 87% to 88%, PPVs of 82% to 84%, and NPVs of 91% to 93%.

[0229] N 20 Optimal sensitivity and acceptable specificity for functional outcome after endovascular stroke treatment at 90 days was obtained when the SEP absolute amplitude threshold was included between 0.25 μV and 0.5 μV.

[0230] 2.6.2 Functional outcome at 90 days (shift analysis) Post-mortem analysis N 20 Patients with N at the end of MT have an overall better functional prognosis in all categories of the mRS scale. 20 The only non-responder was one patient with an mRS score of 1 at 90 days after stroke. The proportion of patients with mRS scores of 5 and 6 (primary dependents and discharged patients) was 1. 20 The difference in scores was significantly higher in patients without HF (14.1% vs. 0%, and 45.3% vs. 4.4%, respectively).

[0231] Univariate analysis When the clinical variables assessed in this study were related to functional outcomes according to the degree of total disability at 90 days, N 20Variables related to, especially N 20 It was observed that latency and amplitude (logarithmic and qualitative transformation) had excellent predictive ability for functional outcome with respect to arterial recanalization itself (TICI scale) or post-procedural medical complications (Table 37).

[0232] [Table 37]

[0233] Table 37: Univariate analysis. Predictive ability of post-MT clinical variables for functional outcome according to the degree of total disability at 90 days. OR and Brier coefficient are shown (lower values ​​indicate higher predictive ability). Variables are ordered according to Brier coefficient. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke. #N to avoid the influence of the value “0” 20 The latency was corrected.

[0234] Multivariate analysis Similar multivariate analyses were performed by defining Models A and B as in Section 2.5.2. Multivariate analyses showed that baseline variables associated with ordinal mRS at day 90 were significantly associated with N after MT. 20 The log-transformed amplitude of the response (higher values ​​associated with better outcome) and post-stroke medical complications (both within 72 hours and beyond symptom onset) (more complications, worse progression) were shown to be significant predictors of stroke progression. Although not significant, duration of ischemia was retained in both models as an adjustment variable (see Table 38).

[0235] [Table 38]

[0236] Table 38: Multivariate analysis. Predictive ability of post-intervention clinical variables for functional outcome at 90 days. * All neurophysiological variables refer to the cerebral hemisphere affected by the stroke.

[0237] 2.7 Prognostic improvement of ASPECTS and NIHSS scales N 20 Further analysis was performed comparing how the responses could help improve the current standard of care in assessing patient outcomes for endovascular stroke treatment.

[0238] The ASPECTS scale (Alberta Stroke Program Early CT Score) is a 10-point quantitative topographic CT scan score used in patients with stroke, with higher values ​​indicating less severe ischemia. The NIHSS (National Institutes of Health Stroke Scale) is a systematic rating tool that quantitatively measures stroke-related neurological deficits. Higher values ​​indicate greater stroke severity.

[0239] For both 7-day and 90-day predictions, the predictors alone (raw) and log-transformed N 20 Several models were constructed comparing the good functional prognosis (mRS≦2) performance of these scales as a combination (adjusted) of the AUC and ROC of the eight possible models were compared (see Table 39).

[0240] [Table 39]

[0241] Table 39: Log-transformed N 20 Comparison of performance between the ASPECTS and NIHSS scales with and without values. In the equation, logBPA is the log-transformed N 20 Represents a value.

[0242] Results: For the prediction on day 7, NIHSS+N (A) was used instead of NIHSS alone (B). 20 (B) increases the AUC from 0.64 to 0.76, and ASPECTS+N instead of ASPECTS alone (C) 20 (D) increases the AUC from 0.67 to 0.78. For 90-day predictions, the results show that using NIHSS+N instead of NIHSS alone (E) increases the AUC from 0.67 to 0.78.20 (F) increased the AUC from 0.61 to 0.76 when using ASPECTS+N instead of ASPECTS alone (G). 20 Using (H) shows an increase in AUC from 0.68 to 0.78.

[0243] 3. Conclusion Currently, clinical algorithms for acute ischemic stroke due to large vessel occlusion are mainly based on clinical and neuroimaging predictors for stratifying patient candidates for endovascular treatment. However, the probability of significant functional disability or death 3 months after stroke still ranges from 40% to 67%. SEP serves as a neurophysiological marker and provides additional and varied data provided by the remaining predictors (NIHSS, blood pressure, hyperglycemia, ASPECTS, ischemic core, and collateral circulation status). It was observed that SEP intensity values ​​of 0.25μV to 0.5μV were the best thresholds to predict patient outcome with high sensitivity, according to the mRS scale system, before and after endovascular treatment in 7-day and 90-day outcome prediction. Furthermore, N 20 adds predictive power to currently used clinical variables (NIHSS, ASPECTS), with the effect being slightly more evident in the outcome at 90 days than at 7 days. Thus, SEP can be included in the diagnostic algorithm of acute ischemic stroke due to large vessel occlusion, not only to improve the indication for endovascular treatment but also to assess the progress of subsequent endovascular treatment.

Claims

1. 1. A computer-implemented method for predicting an outcome of an endovascular stroke treatment in a patient in need thereof before the treatment is administered to the patient, the method comprising: a stimulation device for providing electrical stimulation to one or more pairs of stimulation electrodes for stimulating a nerve; a voltmeter connected to one or more pairs of recording electrodes for recording somatosensory evoked potentials (SEPs) ipsilateral to the stroke site resulting from the electrical stimulation provided to the nerve; a processor; The computer-implemented method comprises: a) comparing the absolute amplitude of the SEP maxima or minima ipsilateral to the stroke with a first predetermined amplitude threshold; b) determining that an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site exceeding the first predetermined amplitude threshold indicates a favorable outcome of the endovascular treatment; and / or determining that an absolute amplitude of the SEP maxima or minima ipsilateral to the stroke site below the first predetermined amplitude threshold indicates a poor outcome of the endovascular treatment; and The SEP is N ２０ It is an ingredient, The computer-implemented method, wherein the first predetermined amplitude threshold is an absolute threshold and is between 0.25 μV and 0.75 μV.

2. 2. The computer-implemented method of claim 1, wherein the first predetermined amplitude threshold defines a noise threshold, and the computer-implemented method is implemented by the processor by performing the steps of determining that an absolute amplitude of a maximum or minimum of the SEP ipsilateral to the stroke site that exceeds the first predetermined amplitude threshold indicates the presence of the SEP, and / or determining that an absolute amplitude of a maximum or minimum of the SEP ipsilateral to the stroke site that is below the first predetermined amplitude threshold indicates the absence of the SEP, and optionally, the noise threshold is 0.1 μV.

3. 2. The computer-implemented method of claim 1, wherein the input voltage is the lowest voltage at which a finger visibly twitches, and the first predetermined amplitude threshold is between 0.25 μV and 0.5 μV.

4. The computer-implemented method comprises: a) comparing the SEP amplitude of the maximum or minimum ipsilateral to the stroke site with a second predetermined amplitude threshold; b) determining that a maximum or minimum SEP amplitude ipsilateral to the stroke site that is below the second predetermined amplitude threshold indicates a poor outcome of the endovascular treatment.

5. The SEP is ２０ 5. The computer-implemented method of claim 4, wherein the input voltage is the lowest voltage at which the finger visibly twitches, and the second predetermined amplitude threshold is an absolute threshold between 0.1 μV and 0.75 μV.

6. The computer-implemented method of any one of claims 1 to 3, wherein the SEP is determined by electrically stimulating the median nerve or the ulnar nerve.

7. The SEP is N ２０ Ingredients and P ２５ The computer-implemented method of claim 6 , wherein the component is selected from the group consisting of:

8. The SEP is determined by electrically stimulating the tibial nerve, and optionally, the SEP is determined by ３５ Ingredients and P ４０ The computer-implemented method of any one of claims 1 to 3, wherein the component is selected from the group consisting of:

9. 4. The computer-implemented method of claim 1, wherein the amplitude or latency of the SEP maxima or minima is combined with a quantitative assessment of the severity of the stroke or one or more clinical variables of the patient.

10. 9. The computer-implemented method of claim 8, wherein the quantitative assessment is the NIHSS and / or ASPECTS score and / or collateral circulation status and / or ischemic core and / or TICI scale, and / or the clinical variables are selected from the patient's age, sex, stroke laterality, blood glucose level and mean arterial pressure.

11. 1. An apparatus for predicting an outcome of an endovascular stroke treatment in a patient in need thereof before the treatment is performed in the patient, comprising: a stimulation device for providing electrical stimulation to one or more pairs of stimulation electrodes for stimulating a nerve; a voltmeter connected to one or more pairs of recording electrodes for recording SEPs ipsilateral to the stroke site resulting from the electrical stimulation provided to the nerve; a processor configured to compare the absolute amplitude of the SEP maxima or minima with a predetermined amplitude threshold, wherein an absolute amplitude of the SEP maxima or minima exceeding the predetermined amplitude threshold indicates a good outcome of the endovascular treatment, and / or an absolute amplitude of the SEP maxima or minima below a first predetermined amplitude threshold indicates a bad outcome of the endovascular treatment; The SEP is N ２０ It is an ingredient, The apparatus, wherein the first predetermined amplitude threshold is an absolute threshold and is between 0.25 μV and 0.75 μV.

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