A diagnostic system for predicting postoperative outcomes in patients with medically untreatable epilepsy (MIE) caused by focal cortical dysplasia (FCD).
A molecular biology-based diagnostic system analyzes CD44 expression patterns in brain tissue to predict postoperative outcomes in focal cortical dysplasia-induced epilepsy, addressing the limitations of current technologies by providing personalized and effective treatment strategies.
Patent Information
- Application Number
- DE202024106663
- Authority / Receiving Office
- DE · DE
- Patent Type
- Utility models
- Current Assignee / Owner
- Filing Date
- 2024-11-19
- Publication Date
- 2025-01-09
- Estimated Expiration
- 2034-11-30
AI Technical Summary
Current diagnostic and prognostic technologies for predicting surgical outcomes in patients with focal cortical dysplasia-induced drug-resistant epilepsy are inadequate, lacking insights into underlying molecular mechanisms, leading to inconsistent long-term seizure control and treatment inefficiencies.
A diagnostic system utilizing molecular biology techniques to analyze CD44 expression patterns in brain tissue samples, involving protein isolation, electrophoresis, membrane transfer, and specialized solution applications to detect specific CD44 variants associated with different postoperative outcomes.
Provides a cost-effective and personalized approach to predict postoperative outcomes, improving treatment strategies and patient care by identifying CD44 variants linked to various surgical results, thereby enhancing surgical planning and seizure management.
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Abstract
Description
FIELD OF THE INVENTION
[0001] The present disclosure relates to a medical diagnostic system for predicting postoperative outcome, in particular to a diagnostic system for predicting postoperative outcome in patients with medically refractory epilepsy (MIE) caused by focal cortical dysplasia (FCD). BACKGROUND OF THE INVENTION
[0002] Focal cortical dysplasia (FCD) is a common cause of drug-resistant epilepsy (DRE), characterized by abnormal development of the cerebral cortical layers. In patients with FCD-induced DRE, surgical resection of the lesion (SRL) is often the preferred treatment. However, a significant number of patients continue to experience seizures after surgery, and even initially seizure-free patients may experience relapses over time.
[0003] The causes of drug resistance, surgical failure, and inconsistent long-term seizure control in FCD patients are still not fully understood. Current diagnostic and prognostic techniques, which rely primarily on imaging and electrophysiology, do not provide insights into the underlying molecular mechanisms. This lack of understanding hinders the development of effective treatments and accurate prognostic tools.
[0004] Recent research has shown that CD44 and its variants, which are expressed at significant levels in the brain, play a crucial role in various brain diseases. However, their potential role in FCD and postoperative sequelae remains largely unexplored.
[0005] In light of the foregoing discussion, it is clear that there is a need for a system that fills the above-mentioned gap. The present invention provides a cost-effective diagnostic system for predicting surgical outcomes in drug-resistant epilepsy associated with focal cortical dysplasia, potentially improving patient care through more personalized treatment strategies and optimized postoperative care. SUMMARY OF THE INVENTION
[0006] The present disclosure relates to a diagnostic system for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE) caused by focal cortical dysplasia (FCD). The proposed system uses three solutions for predicting postoperative outcomes, two of which are probing solutions and one of which is a detection solution. The proposed system is based on simple molecular biology and is cost-effective, operating with minimal facilities for detecting the CD44 pattern to predict postoperative outcomes. The tissue sample is provided to the system, where complete protein isolation is performed using an isolation module, and the tissue is subsequently analyzed for the CD44 pattern. The diagnostic system comprises two solutions that detect CD44 variants in different outcome classes.The CD44 variant pattern is detected by a specially prepared BCIP-NBT solution.
[0007] This disclosure is intended to provide a diagnostic system for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE) due to focal cortical dysplasia (FCD).The system includes: a sampling unit for collecting tissue samples from FCD patients who have undergone surgery; a protein isolation unit for extracting total protein from the collected tissue samples; an electrophoresis unit for performing SDS-PAGE on the extracted proteins; a transfer unit for transferring the separated proteins to a nitrocellulose (NC) membrane; a first testing unit for applying solution A to the NC membrane; a second testing unit for applying solution B to the NC membrane; a detection unit for applying solution C to identify CD44 expression patterns on the NC membrane; and an analysis unit for interpreting the CD44 expression patterns to predict postoperative outcomes in FCD patients.
[0008] In one embodiment, the system uses two test solutions, namely solutions A and B, and one detection solution, namely solution C, wherein the solutions help to detect specific CD44 variants associated with different postoperative outcome classes.
[0009] In one embodiment, Solution C comprises a BCIP-NBT solution specifically formulated to detect CD44 variant patterns.
[0010] In one embodiment, the system further comprises a data storage unit for maintaining a database of CD44 expression patterns correlated with known postoperative outcomes in FCD patients.
[0011] In one embodiment, the system further comprises a reporting unit for generating detailed reports on predicted postoperative outcomes based on the analyzed CD44 expression patterns.
[0012] In one embodiment, the sampling unit comprises special tools for the safe collection and preservation of brain tissue samples during FCD surgery.
[0013] In one embodiment, the system further comprises a quality control unit to ensure the integrity and purity of extracted proteins prior to SDS-PAGE analysis.
[0014] In one embodiment, the electrophoresis unit is configured to separate proteins based on their molecular weight, optimized for the range of CD44 variant sizes.
[0015] In one embodiment, the system further comprises a user interface unit that enables medical professionals to display analysis results.
[0016] One objective of the present disclosure is to provide a diagnostic system for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE) due to focal cortical dysplasia (FCD).
[0017] Another objective of the present disclosure is to provide a cost-effective molecular biology-based diagnostic system.
[0018] Another objective of the present disclosure is to focus on the role of the CD44 receptor in patients with FCD-MIE after surgery.
[0019] Another goal of the present disclosure is a diagnostic system that analyzes the expression and splicing patterns of CD44 receptors, thereby providing insights into the molecular mechanisms underlying seizure recurrence after surgery.
[0020] Another objective of the present disclosure is to provide a diagnostic system that is cost-effective and improves accessibility for patients and healthcare providers.
[0021] To further clarify the advantages and features of the present disclosure, a more detailed description of the invention will be given with reference to specific embodiments thereof illustrated in the accompanying drawings. It should be noted that these drawings represent only typical embodiments of the invention and are therefore not to be considered limiting its scope. The invention will be described and explained in additional detail and in greater detail with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE CHARACTERS
[0022] These and other features, aspects, and advantages of the present disclosure will be better understood when the following detailed description is read with reference to the accompanying drawings, in which like characters represent like parts throughout. Fig. 1 shows a block diagram of a diagnostic system for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE) caused by focal cortical dysplasia (FCD), according to an embodiment of the present disclosure; and Fig. 2 shows a diagram illustrating the detection of the CD44 pattern using the proposed system according to an embodiment of the present disclosure.
[0023] Furthermore, those skilled in the art will appreciate that elements in the drawings are shown for convenience and may not necessarily be drawn to scale. For example, the flowcharts illustrate the method by key steps to enhance understanding of aspects of the present disclosure. Moreover, with respect to device construction, one or more components of the device may have been represented in the drawings by conventional symbols, and the drawings may show only those specific details relevant to understanding embodiments of the present disclosure in order not to clutter the drawings with details that would be readily apparent to those skilled in the art who would benefit from the description herein. DETAILED DESCRIPTION:
[0024] To facilitate an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and described in specific language. It is to be understood, however, that this is not intended to limit the scope of the invention, as such changes and further modifications to the illustrated system and such further applications of the principles of the invention as illustrated therein are contemplated as would normally occur to one skilled in the art to which the invention pertains.
[0025] It will be understood by one skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting thereof.
[0026] References in this specification to "one aspect," "another aspect," or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Therefore, occurrences of the phrase "in one embodiment," "in another embodiment," and similar language throughout this specification may or may not all refer to the same embodiment.
[0027] The terms "comprises," "comprising," or other variations thereof are intended to cover non-exclusive inclusion, such that a process or method comprising a list of steps not only includes those steps, but may also include other steps not expressly listed or inherent in such process or method. Likewise, one or more devices or subsystems or elements or structures or components preceded by "comprises...a" does not preclude, without further limitation, the existence of other devices or other subsystems or other elements or other structures or other components or additional devices or additional subsystems or additional elements or additional structures or additional components.
[0028] Unless defined otherwise, 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 invention belongs. The system, methods, and examples provided herein are for illustrative purposes only and should not be considered limiting.
[0029] Embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings.
[0030] Fig. 1 shows a block diagram of a diagnostic system (100) for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE) caused by focal cortical dysplasia (FCD), according to an embodiment of the present disclosure.
[0031] According to Fig. 1, the system (100) comprises a sampling unit (102) for taking tissue samples from FCD patients who have undergone surgery.
[0032] In one embodiment, a protein isolation unit (104) extracts the total protein from the collected tissue samples.
[0033] In one embodiment, an electrophoresis unit (106) performs SDS-PAGE on the extracted proteins.
[0034] In one embodiment, a transfer unit (108) transfers separated proteins to a nitrocellulose membrane (NC).
[0035] In one embodiment, a first testing unit (110) applies solution A to the NC membrane.
[0036] In one embodiment, a second testing unit (112) applies solution B to the NC membrane.
[0037] In one embodiment, a recognition unit (114) applies solution C to identify CD44 expression patterns on the NC membrane.
[0038] In one embodiment, an analysis unit (116) interprets CD44 expression patterns to predict postoperative outcomes in FCD patients.
[0039] In one embodiment, the system (100) uses two test solutions, namely solutions A and B, and one detection solution, namely solution C, wherein the solutions help to detect specific CD44 variants associated with different postoperative outcome classes.
[0040] In one embodiment, Solution C comprises a BCIP-NBT solution specifically formulated to detect CD44 variant patterns.
[0041] In one embodiment, the system (100) further comprises a data storage unit (118) for maintaining a database of CD44 expression patterns correlated with known postoperative outcomes in FCD patients.
[0042] In one embodiment, the system (100) further comprises a reporting unit (120) for generating detailed reports on predicted postoperative outcomes based on the analyzed CD44 expression patterns.
[0043] In one embodiment, the sampling unit (102) comprises special tools for the safe collection and preservation of brain tissue samples during FCD surgery.
[0044] In one embodiment, the system (100) further comprises a quality control unit (122) to ensure the integrity and purity of extracted proteins prior to SDS-PAGE analysis.
[0045] In one embodiment, the electrophoresis unit (106) is configured to separate proteins based on their molecular weight, optimized for the range of CD44 variant sizes.
[0046] In one embodiment, the system (100) further comprises a user interface unit (124) that enables medical professionals to display analysis results.
[0047] The present invention relates to a system for predicting postoperative outcomes in patients with medically intractable epilepsy (MIE) caused by focal cortical dysplasia (FCD). The proposed system provides a unique expression pattern of CD44 variants across different ILAE outcome classes, which provides information on the consistency of the postoperative outcome and further treatment. The proposed system utilizes brain tissue samples (~450) that exhibited a distinct expression pattern of CD44 variants across different outcome classes (ILAE class 1-6).
[0048] Fig. 2 shows a diagram illustrating the detection of the CD44 pattern using the proposed system according to an embodiment of the present disclosure.
[0049] The present invention provides a comprehensive system for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE) caused by focal cortical dysplasia (FCD). This system integrates multiple components for analyzing CD44 expression patterns in patient tissue samples. It includes units for sample collection, protein isolation, electrophoresis, membrane transfer, sequential probing with specialized solutions, and pattern recognition. The core of the system lies in its ability to detect and interpret specific CD44 variants associated with various postoperative outcome classes. By leveraging molecular biology techniques, this system offers a novel approach to understanding and predicting FCD treatment outcomes and could revolutionize patient care and treatment planning in the field of epilepsy treatment.
[0050] According to Fig.2, the proposed system uses three solutions to detect the CD44 pattern: two are test solutions and one is a detection solution.
[0051] After protein isolation, the removed brain tissue is subjected to SDS-PAGE and transferred to NC elements via a transfer unit. The NC membrane is exposed to Solution A and Solution B, followed by Solution C, through multiple test units to detect the CD44 pattern.
[0052] The proposed system is based on simple molecular biology, is cost-effective, and can be operated with minimal facilities. The proposed system is novel in FCD-MIE diagnosis for predicting postoperative outcomes and uses three solutions.
[0053] The drawings and the foregoing description provide examples of embodiments. Those skilled in the art will recognize that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be separated into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, orders of the processes described herein may be changed and are not limited to the manner described herein. Furthermore, the actions of any flowchart need not be implemented in the order shown; nor do all actions necessarily need to be performed. Also, those actions that are not dependent on other actions may be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples.Numerous variations, whether explicitly stated in the specification or not, such as differences in structure, dimensions, and use of materials, are possible. The scope of the embodiments is at least as broad as indicated in the following claims.
[0054] Advantages, other benefits, and solutions to problems have been described above with reference to specific embodiments. However, the advantages, benefits, solutions to problems, and any components that may cause an advantage or solution to occur or become more apparent are not to be construed as a critical, required, or essential feature or component of any or all of the claims. REFERENCE 100 A diagnostic system for predicting postoperative outcomes in patients with medically intractable epilepsy (MIE) caused by focal cortical dysplasia (FCD) Causes 102 sampling unit 104 Protein Isolation Unit 106 electrophoresis unit 108 Transfer unit 110 First key unit 112 Second key unit 114 Detection unit 116 Analysis Unit 118 Data storage unit 120 Reporting Unit 122 Quality Control Unit 124 User interface unit 202 tissue samples from the patient 204 Complete protein isolation 206 SDS PAGE 208 Transfer to NC membrane 210 Tested with Solution A 212 Tested with Solution B 214 Detection of the CD44 pattern with solution C
Claims
[1] A diagnostic system for predicting postoperative outcomes in patients with medically refractory epilepsy (MIE), the system comprising: a sampling unit for collecting tissue samples from FCD patients who have undergone surgery; a protein isolation unit for extracting total protein from the collected tissue samples; an electrophoresis unit for performing SDS-PAGE of the extracted proteins; a transfer unit for transferring separated proteins to a nitrocellulose membrane (NC); a first test unit for applying solution A to the NC membrane; a second test unit for applying solution B to the NC membrane; a detection unit for applying solution C to identify CD44 expression patterns on the NC membrane; and an analysis unit for interpreting CD44 expression patterns to predict postoperative outcomes in FCD patients. [2] The system of claim 1, wherein the system uses two test solutions, namely solutions A and B, and one detection solution, namely solution C, wherein the solutions aid in the detection of specific CD44 variants associated with different postoperative outcome classes. [3] The system of claim 1, wherein solution C comprises a BCIP-NBT solution specifically formulated to detect CD44 variant patterns. [4] The system of claim 1, further comprising a data storage unit for maintaining a database of CD44 expression patterns correlated with known postoperative outcomes in FCD patients. [5] The system according to claim 1 further comprises a reporting unit for preparing detailed reports on predicted postoperative outcomes based on the analyzed CD44 expression patterns. [6] The system of claim 1, wherein the sampling unit comprises special tools for the safe collection and preservation of brain tissue samples during FCD surgery. [7] The system of claim 1, further comprising a quality control unit for ensuring the integrity and purity of extracted proteins prior to SDS-PAGE analysis. [8] The system of claim 1, wherein the electrophoresis unit is configured to separate proteins based on their molecular weight optimized for the range of CD44 variant sizes. [9] The system according to claim 1 further comprises a user interface unit that enables medical professionals to display analysis results.