Blood marker for identifying epilepsy convulsion and application thereof

Abstract

The invention belongs to the field of biological medicine, and discloses a blood marker for identifying epilepsy convulsion and application thereof. The inventor finds that the LRG1 is obviously increased during epileptic convulsion, which indicates that the increase of the blood LRG1 is a blood marker during the acute attack stage of epileptic convulsion. The invention proposes and verifies that the LRG1 is the peripheral blood marker in the acute attack stage of epilepsy convulsion for the first time, and can be used as a clinical auxiliary diagnosis and treatment target.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of biological medicine, and particularly relates to a blood marker for identifying epilepsy convulsion and application thereof. BACKGROUND

[0002] Epilepsy, commonly known as seizures, is a chronic disease caused by sudden abnormal electrical discharges in the brain, leading to temporary brain dysfunction. It manifests as sudden, spontaneous, and recurrent disturbances in motor, sensory, mental, and consciousness functions. This definition encapsulates the complexity of epileptic symptoms and, more importantly, its two fundamental characteristics: recurrence and paroxysmal nature. Recurrence means that after the first seizure, there will definitely be a second, third, or even multiple seizures after a period of time. Even the most common convulsions, if they only occur once, do not possess recurrence and cannot be diagnosed as epilepsy. Paroxysmal nature refers to the sudden appearance and cessation of symptoms. Some patients may suddenly collapse and convulse while walking or eating, and then recover after a period of time. Epilepsy is divided into two main categories: idiopathic epilepsy and secondary (symptomatic) epilepsy. The former is also known as true, idiopathic, or cryptogenic epilepsy. Its true cause is unknown and remains unclear despite various modern diagnostic methods. In these patients, there are no structural changes or metabolic abnormalities in the brain that can explain the symptoms, but it is closely related to genetic factors. Secondary epilepsy: also known as symptomatic epilepsy. This refers to epilepsy with a identifiable cause. Common causes include various brain lesions and metabolic disorders, such as congenital diseases, prenatal and perinatal diseases (birth injury is a common cause of epilepsy in infancy), sequelae of febrile seizures, trauma, infection, poisoning, intracranial tumors, cerebrovascular diseases, and nutritional and metabolic diseases. Epilepsy is related to abnormal neuronal discharge. At rest, the firing frequency of a single pyramidal cell in the cerebral cortex is generally between 1 and 10 times per second. However, in an epileptic focus, the firing frequency of a group of pathological neurons can reach hundreds of times per second. The high-frequency repetitive firing of the epileptic focus cell group causes the neurons directly connected to its axons to generate large postsynaptic potentials, resulting in continuous propagation until inhibition (including the activity of inhibitory neurons around the epileptogenic focus, the reabsorption of excitatory substances by glial cells, and the participation of extra-lesional inhibitory mechanisms) terminates the seizure. Different forms of seizures result from different propagation pathways and extents. Epilepsy may involve only one area of ​​the cerebral cortex and not spread further, causing simple partial seizures; excitation in the precentral or postcentral gyrus may be conducted to adjacent neurons through an increase in extracellular potassium ions after discharge, causing Jackson's epilepsy; epilepsy often spreads from the cerebral cortex to the thalamus and midbrain reticular formation via descending projection fibers, causing loss of consciousness, and then spreads to the entire cerebral cortex via the diffuse thalamic projection system, producing secondary generalized tonic-clonic seizures. Based on the seizure pattern, it can be divided into grand mal seizures, petit mal seizures, psychomotor seizures, focal seizures, and complex partial seizures. Grand mal seizures, also known as generalized seizures, include generalized tonic-clonic seizures: half of them have a prodrome, such as dizziness, mental confusion, upper abdominal discomfort, visual and auditory disturbances, and olfactory disturbances.During a seizure (convulsive phase), some patients first emit a sharp cry, then lose consciousness and fall, experiencing generalized muscle rigidity, respiratory arrest, and possible head and eye deviation to one side. After several seconds, clonic convulsions occur, gradually increasing in intensity and lasting several seconds. During the clonic phase, breathing resumes, and white foam may appear at the mouth (blood-tinged foam if the tongue is bitten). Some patients experience urinary and fecal incontinence. After the convulsions, the whole body relaxes or enters a drowsy state (postictal phase), after which consciousness gradually returns. Alternatively, there may be sudden loss of consciousness, followed by tonic and then clonic spasms. It is often accompanied by screaming, cyanosis, urinary incontinence, tongue biting, white or blood-tinged foam at the mouth, and dilated pupils. The seizure usually stops spontaneously after tens of seconds or minutes, followed by a drowsy state. Upon awakening, there may be a short period of dizziness, irritability, and fatigue, with no recollection of the seizure. If the seizures are continuous and the patient remains in a coma, it is called status epilepticus, which is often life-threatening. Petit mal seizures, absence seizures: Sudden interruption of mental activity, loss of consciousness, possibly accompanied by myoclonus or automatisms. Each seizure lasts from a few seconds to more than ten seconds. The EEG shows 3 Hz spike-and-wave or sharp-and-slow-wave complexes. There may be brief (2-15 seconds) impairment or loss of consciousness without generalized convulsions. Multiple seizures may occur daily, sometimes accompanied by rhythmic blinking, head nodding, staring, or upper limb twitching. Psychomotor seizures may manifest as sudden onset, confusion, and irregular and uncoordinated movements (such as sucking, chewing, searching, shouting, running, struggling, etc.). The patient's actions are unmotivated, aimless, impulsive, and last for hours, sometimes even days. The patient has no memory of the seizure. Focal seizures, generally seen in patients with organic damage to the cerebral cortex, manifest as paroxysmal twitching or sensory abnormalities in one corner of the mouth, fingers, or toes, which may spread to one side of the body. When the seizure involves both sides of the body, it can manifest as a generalized tonic-clonic seizure. Complex partial seizures are characterized by impaired consciousness, with the patient unable to recall the seizure. They may manifest as staring and automatisms such as lip-smacking, chewing, groping, wandering, fidgeting, humming, muttering, or other symptoms and signs. Simple partial seizures involve tonic or clonic seizures of a specific area or one side of the body, or sensory abnormalities, lasting briefly with preserved consciousness. If the seizure spreads along the motor cortex to other limbs or the whole body, it may be accompanied by loss of consciousness, known as a Jacksonian seizure. Post-ictal paralysis of the affected limb may occur, known as Todd's paralysis. There are also complex partial seizures (psychomotor seizures): psychosensory, psychomotor, and mixed seizures. These often involve varying degrees of impaired consciousness and significant disturbances in thought, perception, emotion, and psychomotor function. Automatisms such as fugue states and somnambulism may occur. Sometimes, under the influence of hallucinations or delusions, violent behaviors such as harming others or self-harm may occur. Autonomic nervous system attacks (diencephalic): These may present as headache, abdominal pain, limb pain, syncope, or cardiovascular events.

[0003] The typical stages of epilepsy are divided into four phases: (1) Prodromal phase: Before loss of consciousness, patients experience dizziness, fear, chest tightness, palpitations, sensory abnormalities, mental abnormalities, nausea, and stomach discomfort. These symptoms may occur singly or in combination. The prodromal phase is usually short and has a low incidence rate, accounting for about 15%. (2) Tonic phase: The patient suddenly loses consciousness, falls to the ground, and experiences tonic contraction of all muscles, with the head tilted back, both upper limbs flexed and rigid, and both lower limbs extended and rigid. The mouth opens and then closes, and the patient may bite the lips, tongue, and cheeks. Due to the tonic contraction of the diaphragm and intercostal muscles, air is forced out of the lungs. At the same time, laryngeal spasm and pharyngeal stenosis cause a sharp cry known as epileptic cry. During this phase, the pupils dilate and blood pressure rises. Initially, the skin and conjunctiva become red, followed by respiratory arrest due to the tonic contraction of the respiratory muscles, and cyanosis of the lips and skin. This phase lasts for 10-20 seconds before entering the clonic phase. (3) Clonic phase: During this phase, rhythmic contractions occur throughout the body's muscles, often starting in the face. Due to the twitching of the masticatory muscles, the tongue and lips may be bitten. Fine tremors gradually appear in the extremities, with the amplitude gradually increasing and extending to the whole body, presenting as intermittent flexor spasms. The frequency gradually decreases, lasting 1-3 minutes, and finally stops abruptly after a strong spasm. During the attack, there is often an increased heart rate, elevated blood pressure, increased saliva and sweat secretion, coarse breathing sounds, foamy saliva flowing from the mouth, sometimes mixed with blood streaks, and blood-tinged foam spitting out of the mouth. The pupils are dilated, and there is urinary incontinence, or even fecal incontinence. At this time, the pupillary reflex and various deep and superficial reflexes disappear. (4) Recovery phase: During this phase, the patient is in a drowsy state, and wakes up after more than 10 minutes or continues to sleep for several hours. The heart rate, blood pressure, reflexes, and pupils tend to return to normal. The coma gradually lessens and the patient wakes up. Some patients show mental confusion, excitement, and restlessness before waking up, or even run around. After waking up, except for the prodromal symptoms, the patient has no memory of the attack. Symptoms include headache, fatigue, and muscle aches throughout the body.

[0004] The diagnosis of epilepsy begins with an accurate medical history and physical examination. The second is an electroencephalogram (EEG). In principle, an EEG during an epileptic seizure is the most valuable auxiliary examination. Regardless of the type of epilepsy, epileptiform discharges in the brain are present during seizures, but the routine scalp EEG used in clinical practice may not be able to record them all. Even with provocation tests and 24-hour continuous recording during the interictal period, the overall positive rate is only about 80% to 90%. In clinical diagnosis, it is necessary to combine medical history, physical examination and other aspects for comprehensive analysis. Epilepsy cannot be denied just because the EEG is negative. A positive EEG without clinical manifestations cannot be diagnosed. Typical clinical manifestations can generally lead to a diagnosis. The third diagnostic basis is imaging and laboratory tests. Epilepsy auxiliary examinations (1) EEG, BEAM, Holter (electroencephalography, brain topography, dynamic EEG monitoring): clear pathological waves, spikes, sharp waves, spike-slow waves or sharp-slow waves can be seen. (2) Secondary epilepsy should undergo further examinations such as head CT, head MRI, MRA, and DSA to detect the corresponding lesions.

[0005] Epilepsy treatment: With timely and appropriate treatment, about 80% of patients can be completely controlled and cured. Cure criteria: Epilepsy patients who have not had seizures after a certain period of regular and systematic drug treatment can usually reduce their medication until they stop taking it. If there are no seizures within 3 years after stopping medication, they are considered cured. Most people do not have seizures after systematic treatment, but not everyone does not have seizures. According to research and observation, 15% of clinically cured patients have seizures again within 10 years. Therefore, cured patients should not be blindly optimistic and should be vigilant about the possibility of seizures in the future. The most important thing is to pay attention to maintenance and prevent any inducing factors, such as absolutely quitting smoking and drinking, preventing excitement or anger, and excessive fatigue. In addition, try to watch less TV, play fewer video games, use less computers and mobile phones, and do not play chess or mahjong. (1) Choose safe, effective, inexpensive and easy-to-buy drugs according to the type of epileptic seizure. Phenobarbital, sodium valproate, carbamazepine, etc. are used for grand mal seizures. Phenytoin sodium, carbamazepine, etc. are used for complex partial seizures. Absence seizures: Clonazepam, diazepam. Status epilepticus: Dalmatian is the first choice for intravenous diazepam. (2) The drug dosage should start from the lower limit of the usual dosage and gradually increase until the seizures are well controlled without serious toxic side effects. Generally, it should not be changed or interrupted at will. After the epileptic seizures are completely controlled for 2-3 years and the EEG is normal, the dosage can be gradually reduced and the drug can be stopped. Antiepileptic drugs synthesized before the 1960s, such as phenytoin sodium, carbamazepine, ethosuximide, sodium valproate, etc., are generally called old antiepileptic drugs and are also first-line antiepileptic drugs. However, in some developed countries, due to some side effects of phenobarbital and phenytoin sodium, they have been listed as second-line antiepileptic drugs. Only carbamazepine and sodium valproate are listed as first-line antiepileptic drugs. New antiepileptic drugs such as gabapentin, lamotrigine, vigabatrin, topiramate, etc., the newest one is levetiracetam tablets from UCB. (3) For epilepsy with a clear cause, in addition to effectively controlling the seizures, the primary disease should be actively treated. (4) Drug-resistant epilepsy. Some secondary epilepsy. Special epilepsy syndromes can be treated surgically according to indications. Surgery requires good understanding and cooperation from the patient and their family. Surgery can be performed if the head does not involve dangerous or functional areas. Stereotactic surgery can be performed to destroy brain areas related to epileptic seizures, anterior corpus callosotomy or chronic cerebellar stimulation. (5) Treatment of status epilepticus: Active and effective control of convulsions: ① diazepam, ② sodium amobarbital, and management of complications: maintain airway patency, diuresis and dehydration to reduce cerebral edema, prevent acidosis, etc. (6) Traditional Chinese medicine treatment: Acorus tatarinowii: horse hoof incense: Uncaria rhynchophylla: morning glory seed: valerian: centipede: scorpion: silkworm: earthworm: cicada slough: antelope horn: bezoar.

[0006] The relationship between epileptic seizures and peripheral blood proteins Epilepsy patients exhibit related symptoms, and every symptom has a material basis, involving changes in gene expression and proteins. Proteins are the functional executors of genes, and research on protein structure, location, and protein-protein interactions will provide a direct foundation for elucidating the nature of life phenomena. Almost all physiological and pathological processes, as well as the effects of drugs and environmental factors, depend on proteins and cause changes in the proteome. Before any disease manifests any perceptible symptoms, certain proteins have certainly already changed. Therefore, identifying key and marker proteins for various diseases is of great significance for disease diagnosis, pathological research, and drug screening. Leucine-rich repeat (LRR) proteins are a family of proteins consisting of eight leucine-rich repeat sequences. Studies have shown that LRR proteins are transmembrane proteins that mainly participate in normal physiological activities as cell adhesion molecules or ligand-binding proteins.

[0007] Leucine-rich α2-glycoprotein 1 (LRG1) is a member of the leucine-rich repeat family and belongs to the LRR protein family. Previous studies have shown that LRG1 participates in important physiological and pathological processes, such as protein-protein interactions, signal transduction, and cell adhesion.

[0008] Currently, various proteins with leucine-rich repeat structures have been found in the nervous system. In some neurodegenerative diseases, decreased concentrations of LRG1 in cerebrospinal fluid (CSF) have been detected, and human LRG1 expression has been observed in the anatomically examined cerebral cortex. Previous studies have performed proteomic analysis on CSF samples from healthy individuals and patients with idiopathic normal pressure hydrocephalus (INPH), finding a specific increase in LRG1 expression in the CSF of INPH patients. Therefore, LRG1 has potential value in the clinical diagnosis of INPH. Abnormal LRG1 expression is associated with the development of various tumors, such as glioma, lung cancer, colon cancer, epithelial ovarian cancer, and hepatocellular carcinoma.

[0009] In studies of retinopathy caused by vascular remodeling, LRG1 was found to promote endothelial cell mitosis and angiogenesis. This hypothesis was further confirmed in in vitro human vascular endothelial cell (HUVEC) lumen formation assays. Providing recombinant human LRG1 as a medium resulted in a significant increase in lumen formation and branching, while anti-LRG1 antibodies significantly blocked lumen formation. Other studies have shown that the angiogenic activity of LRG1 is not limited to the eye and may play important roles in other major biological processes, including tumors and immune responses. The regulatory role of LRG1 on the TGF-β1 signaling pathway provides strong evidence for the function of LRG1. LRG1 is a very promising therapeutic target for controlling ocular angiogenesis and may play an important role in other diseases such as cancer and atherosclerosis.

[0010] The function of LRG1 may be related to its LRR structure. LRG is thought to regulate the function of other proteins, such as cytochrome C, by binding to them, thereby limiting the function of some proteins. Gliomas originate from glial cells and are the most common tumors of the central nervous system, accounting for 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors. Related experiments have shown that LRG1 plays an important role in promoting the proliferation, migration, and invasion of glioma cells, and these functions are achieved by mediating the transforming growth factor β1 (TGF-β1) signaling pathway. Furthermore, LRG1 can promote endothelial cell proliferation and angiogenesis through the TGF-β signaling pathway, suggesting that LRG1 may be involved in the occurrence and development of astrocytic malignancies. Previous studies have shown that inhibiting LRG1 expression suppresses the in vitro growth of glioma cells and delays the occurrence of gliomas in xenograft mouse models, providing evidence for the tropism of LRG1 on glioma pathological changes. LRG1 is associated with atherosclerosis and microcirculatory disturbances, and may serve as a biomarker of vascular injury in different vascular beds. LRG1 has the potential role in the early identification of vascular disease risk, but the pathological basis and mechanisms underlying these associations require further investigation. Altering LRG1 activity could be considered as a therapeutic potential in vascular diseases, particularly in minimally invasive surgery and endovascular revascularization. LRG1 expression is upregulated after myocardial infarction, and inhibiting post-infarction cardiac remodeling is a novel cardiovascular protective factor; therefore, LRG1 may become a therapeutic target for cardiovascular diseases. LRG1 gene deletion exacerbates post-infarction cardiac dysfunction and increases myocardial fibrosis. In LRG1-deficient mice, impaired smad1 / 5 / 8 pathways lead to reduced capillary density at the infarct margin, and LRG1 gene ablation further exacerbates the reduction in capillary density after myocardial infarction in cardiac remodeling models. Furthermore, our study indicates that elevated LRG1 levels in the blood of patients with cardiac and respiratory arrest following cardiopulmonary resuscitation may be associated with cerebral ischemia, brain injury, and vascular damage caused by cardiac and respiratory arrest. This is consistent with the mechanism of elevated LRG1 levels in the blood of patients with cerebral infarction and myocardial infarction.

[0011] On the other hand, LRG1, as an angiogenesis factor, may have considerable potential for the treatment of vascular diseases by regulating the smad1 / 5 / 8 pathway, but its specific regulatory mechanism is still unclear.

[0012] The inventor's prior Chinese patent application CN117110626A discloses that the average LRG1 level in the blood is higher in individuals with carotid artery disease than in normal individuals, and that the detachment of plaques from carotid vessels increases more significantly as the disease progresses. As a peripheral blood biomarker for dangerous carotid artery disease, it exhibits high sensitivity and specificity and can be used in conjunction with ultrasound results for the diagnosis of carotid artery disease. CN115856325A discloses that the level of peripheral blood LRG1 is closely related to lower limb arterial injury. By detecting the level of LRG1 in peripheral blood, lower limb arterial injury, especially lower limb arteriosclerosis or plaque, lower limb arterial stenosis, thrombosis, or occlusion, can be well predicted. It is particularly effective in predicting lower limb arteriosclerosis or plaque, lower limb arterial stenosis, thrombosis, or occlusion caused by hypertension, hyperlipidemia, or hyperglycemia. CN110261617A discloses that LRG1 can be used as a peripheral blood biomarker for cerebral hemorrhage. CN120405148A discloses that LRG1 is associated with nerve entrapment injury in the limbs.

[0013] In the current technology, no research has shown that LRG1 is associated with epilepsy. Summary of the Invention

[0014] The purpose of this invention is to overcome at least one deficiency of the prior art and to provide a blood marker for identifying epileptic seizures and its application.

[0015] The technical solution adopted in this invention is: The first aspect of the present invention provides: Application of LRG1 quantitative reagent in the preparation of diagnostic or auxiliary diagnostic reagents for epileptic seizures.

[0016] In some instances, the LRG1 quantification reagent is an ELISA reagent, an immunofluorescence reagent, or a mass spectrometry analysis reagent.

[0017] In some instances, the samples tested by the LRG1 quantitative reagent are peripheral blood.

[0018] A second aspect of the present invention provides: A diagnostic or auxiliary diagnostic system for epileptic seizures includes: The LRG1 quantification device is used to quantify the amount of LRG1 in a sample. An analytical device, based on LRG1 levels, determines the risk of epileptic seizures; The result output device is used to output the analysis results of the analysis device.

[0019] In some instances, the LRG1 quantification device is an ELISA detection device, an immunoblotting device, an immunofluorescence device, or a mass spectrometry device.

[0020] In some cases, high LRG1 levels indicate a high risk of epileptic seizures.

[0021] In some cases, high LRG1 levels refer to levels exceeding 5 ng / mL in peripheral blood samples.

[0022] In some instances, the sample is peripheral blood.

[0023] The beneficial effects of this invention are: The inventors' research found that LRG1 levels significantly increase during epileptic seizures, indicating that elevated blood LRG1 is a blood marker during acute epileptic seizures. This invention is the first to propose and verify that LRG1 is a peripheral blood marker during acute epileptic seizures, and can be used as an auxiliary diagnostic and therapeutic target in clinical practice. Detailed Implementation

[0024] The technical solution of the present invention will be further explained below with reference to experimental data.

[0025] Clinical Sample Screening and Collection: Thirty patients with acute and stable epileptic seizures over the past 8 years were collected. Gender and age were recorded. All patients underwent blood pressure, blood lipids, blood glucose, liver function, kidney function, coagulation parameters, ECG, and other examinations. All cases also underwent ultrasound, head CT, echocardiography, and electroencephalography. Sixty age- and gender-matched healthy individuals were selected as controls. Specimen Collection: 5 mL of venous blood was collected from patients meeting the inclusion criteria. After standing for 15 minutes, the blood was centrifuged at 3000 rpm for 15 minutes to extract serum. The serum was then placed in sterile cryovials and stored at -80°C for research.

[0026] Study of blood samples from case patients Serum separation. The examination method is as follows: serum and cells are separated using a high-speed centrifuge.

[0027] Main equipment, materials, and reagents: homogenizer, high-speed centrifuge, 3kDa ultrafiltration centrifuge tubes, ICP-MS. The water used in the experiment was 18.2 MΩ / cm ultrapure water. Sample pretreatment methods: 1) Fully automated biochemical analyzer (one each of Becman DXC800 and AU400), 0.01% electronic analytical balance (Shimadzu), ELISA reader, Roche electrochemiluminescence automated immunoassay analyzer (Elecsys 2010), specific protein analyzer (imported), purified water system (MEDICA60), electric thermostatic water bath (DK-600), low-temperature high-speed centrifuge (Sigma), ultra-low temperature freezer (Thermo Fisher Scientific), low-temperature freezer (HFC350, Germany), etc. The above equipment fully guarantees the implementation of this project. Reagent kit: Shenzhen-made ELISA LRG1 detection kit. Statistical methods: The t-test was used to compare the means of each group. SPSS statistical software was used, and P<0.05 was considered statistically significant.

[0028] result: Record gender, age, and blood pressure, blood lipids, blood glucose, liver function, kidney function, coagulation parameters, ECG, etc., were measured in all healthy individuals and patients. All cases were confirmed by combining medical history, physical examination, head CT scan, EEG, blood tests for electrolytes, and myocardial enzymes. Normal values ​​were determined by adding two standard deviations to the mean. The upper limit of normal cutoff for the Shenzhen-made LRG1 test kit (LRG1 Shenzhen) was 5 ng / ml. Over the past 8 years, the Shenzhen-made kit was used to test 30 cases each in the acute and stable phases of epileptic seizures. Results showed that in the acute phase, 29 of the 30 cases exceeded the cutoff, with 1 false negative, resulting in a sensitivity of 96.6%. Simultaneously, 60 age- and gender-matched healthy individuals were selected as controls. In these controls, normal values ​​were determined by adding two standard deviations to the mean. 12 cases exceeded the cutoff, resulting in a false positive rate of 20% and a specificity of 80%.

[0029] The changes in serum LRG during an acute epileptic seizure are shown in Table 1.

[0030] Table 1. Changes in peripheral blood LRG1 levels during epileptic seizures (X±SD, unit ng / ml) Number of patients LRG1 (Shenzhen) / ng / ml Normal 60 3.2±1.1 Epilepsy 30 50.8± 10.6 Compared with normal individuals, LRG1 levels were significantly elevated during epileptic seizures (P<0.001).

[0031] The sensitivity and specificity of LRG1 in diagnosing epileptic seizures are shown in Table 2.

[0032] Sensitivity = (Number of true positives / (Number of true positives + Number of false negatives)) * 100%, the percentage of patients correctly diagnosed. Specificity = (Number of true negatives / (Number of true negatives + Number of false positives)) * 100%, the percentage of individuals correctly identified as not being patients. False positive rate = Number of false positives / Number of negative results (gold standard) False negative rate = Number of false negatives / Number of gold standard positives.

[0033] The upper limit of normal cutoff value for the LRG detection kit produced in Shenzhen is 5 ng / ml. In a study of 30 cases of acute epileptic seizures, 29 cases showed elevated LRG levels, with 1 case showing a normal result and 1 false negative. Among 60 normal individuals (asymptomatic and without physical signs), 12 had blood LRG levels exceeding the cutoff value, resulting in a false positive rate of 20%, while 48 had normal LRG levels. The specificity was 80%.

[0034] Table 2. Sensitivity and specificity of LRG1 in diagnosing acute seizures in epilepsy (with 5 ng / ml as the cutoff value) Positive coincidence rate False positive Negative coincidence rate False negative Epilepsy 96.60% 20.00% 80.00% 3.40% The changes in LRG1 during the acute seizure period and the stable period (more than 1 year without seizures) are shown in Table 3.

[0035] Table 3. Changes in serum LRG1 levels during seizures and stable periods of epilepsy treatment. Number of cases LRG1 / ng / ml Normal 60 3.2±1.1 Epilepsy, acute stage 30 50.8± 10.6 Epilepsy, stable stage 30 4.5± 2.1 During the acute and stable phases of epileptic seizures, LRG was significantly reduced in the stable phase compared to the acute phase (P<0.001), and was comparable to normal levels (P>0.05).

[0036] The results of this invention show that LRG1 levels are significantly elevated during epileptic seizures, indicating that elevated blood LRG1 is a blood marker during acute epileptic seizures.

[0037] This invention is the first to propose and verify that LRG1 is a peripheral blood marker for acute epileptic seizures, and can be used as an auxiliary diagnostic and therapeutic target in clinical practice.

[0038] The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions without departing from the concept of the present invention are all within the protection scope of the present invention.

Claims

1. Application of LRG1 quantitative reagent in the preparation of diagnostic or auxiliary diagnostic reagents for epileptic seizures.

2. The application according to claim 1, characterized in that, The LRG1 quantitative reagents are ELISA reagents, immunofluorescence reagents, and mass spectrometry analysis reagents.

3. The application according to claim 1, characterized in that, The sample tested by the LRG1 quantitative reagent is peripheral blood.

4. A diagnostic or auxiliary diagnostic system for epileptic seizures, comprising: The LRG1 quantification device is used to quantify the amount of LRG1 in a sample. An analytical device, based on LRG1 levels, determines the risk of epileptic seizures; The result output device is used to output the analysis results of the analysis device.

5. The epileptic seizure diagnostic system according to claim 4, characterized in that, The LRG1 quantification device is an ELISA detection device, an immunoblotting device, an immunofluorescence device, or a mass spectrometry device.

6. The epileptic seizure diagnostic system according to claim 4, characterized in that, High levels of LRG1 indicate a high risk of epileptic seizures.

7. The epileptic seizure diagnostic system according to claim 6, characterized in that, High LRG1 content refers to its content in peripheral blood samples exceeding 5 ng / mL.

8. The epileptic seizure diagnostic system according to claim 4, characterized in that, The sample was peripheral blood.