Effect of Kencur (Kaempferia galanga L.) Ethanolic Extract Treatment on Cerebral Caspase-3 Expression in Traumatic Brain Injury Rat Models.

Background: Traumatic brain injury is one of the most common forms of trauma and causes significant morbidity and mortality. Kencur (Kaempferia galanga L.) ethanolic extract is known to contain substances that could theoretically inhibit unfavourable cellular processes, including oxidative stress and inflammation. This research aimed to study Kencur's anti-apoptosis activity through the inhibition of caspase-3. Methods: This is a true experimental post-test-only group design study, using male Wistar rats (Ratus novergicus) with weight-drop-induced traumatic brain injury. The subjects in this study were divided into four groups: two Control groups (Groups A and B) and two Therapy groups (Groups C and D). Groups C and D differed in the dose of Kencur ethanolic extract administered (600 mg/kgBW/day and 1,200 mg/kgBW/day, respectively). The Therapy groups were then subdivided into those receiving therapy for 24 h (C-24 and D-24) and those receiving therapy for 48 h (C-48 and D-48). Caspase-3 expression in brain tissue was evaluated at the end of the therapy using immunohistochemistry. All groups were subjected to a Kruskal-Wallis comparison test and the investigation continued with a Mann-Whitney U test to compare the two groups. Results: In traumatic brain injury rat models treated with Kaempferia galanga L. ethanolic extract at doses of 1,200 mg/kgBW/day within 48 h of therapy (D-48) compared to those who were not treated, there was a significant change in the cerebral expression of caspase-3 (P = 0.016). There was also a significant difference between the two doses of intervention (C-24 at 600 mg/kgBW/day and D-48 at 1,200 mg/kgBW/day; P = 0.016). Conclusion: With a minimum of 48 h of treatment split into two doses, Kencur (Kaempferia galanga L.) ethanolic extract can decrease caspase-3 expression in rats with traumatic brain injury.

Correlation between interleukin-6 expression in post-mortem core liver biopsy and degree of liver injury in patients with fatal COVID-19.

Excessive release of interleukin-6 (IL-6) during the progression of coronavirus disease 2019 (COVID-19) induces cytokine storms, resulting in multi-organ damages including liver injury, similar in nature with mechanism of viral hepatitis. Systemic IL-6 has been associated with the incidence of liver injury among COVID-19 patients; however, studies on IL-6 expression in the liver tissue are completely lacking. The aim of this study was to measure the IL-6 expression in the liver tissues and to determine its correlation with the degree of liver injury in fatal COVID-19 patients. Through this first cross-sectional study, IL-6 expression was measured through immunohistochemical staining and the degree of liver injury was identified based on level of serum alanine aminotransferase (ALT). The Spearman correlation test was used to identify the correlation between IL-6 expression and the degree of liver injury. A total of 47 deceased COVID-19 patients were included and IL-6 expression was observed in all post-mortem liver specimens, ranging from mild to strong expression. Liver injury at various degrees (mild to severe) was found in more than half (59.5%) of the cases. The Spearman correlation analysis suggested a statistically insignificant correlation between liver IL-6 expression and the degree of liver injury (r=0.152; p=0.309). In conclusion, even IL-6 expression was observed in all post-mortem liver specimens, there was an insignificant correlation between IL-6 expression in the liver tissue with the degree of liver injury among fatal COVID-19 patients, suggesting that IL-6 was not the only main factor contributing to liver damage in COVID-19 patients.

Unusual presentation of a neuroepithelial cyst: A case report.

Neuroepithelial cysts are benign, congenital, ependymal-lined cysts that constitute an infrequent cause of neurological symptoms among intracranial cystic lesions. We present Indonesian patient who underwent brain MRI depicting neuroepithelial cysts and pathological examination confirmed. Surgery was performed and yielded a satisfying result. Awareness of the entity and specific imaging features is key to making the diagnosis of neuroepithelial cyst and commencing appropriate treatment. This report is expected to aid in the diagnosis of neuroepithelial cysts, which are rare, and reduce the occurrence of misdiagnosis.

Clear-cell renal cell carcinoma and glioblastoma multiforme coexistence: Double primary malignancy, does it have a causal relationship?

Background: Multiple primary malignancies (MPMs), especially coexistence of renal cell carcinoma (RCC) and glioblastoma multiforme (GBM), are rare. The most likely clinical diagnosis in patient with tumor in another organ is metastatic brain tumor. Although GBM is the most common brain tumor, it is rarely coexistent with other malignancies. Case Description: A 64-year-old female presented with headache and dizziness, along with abdominal pain for 2 weeks before being admitted. The abdominal computed tomography (CT) scan showed a kidney tumor. The patient developed left hemiplegia, and the brain CT scan showed an intracranial tumor. The patient suggested for radical nephrectomy and craniotomy tumor removal. Histopathology of the kidney and brain tumor revealed two different features, which showed RCC and GBM. Immunohistochemistry result confirmed the diagnosis of GBM and IDH1 wild type; coexistent with clear cell RCC. Conclusion: The coexistence of carcinoma and glioma should be regarded as coincidental cases if it did not accomplish the criteria for tumor-to-tumor metastasis or proven to be a genetic syndrome. This case report provides an addition to the literature about double primary malignancy in a single patient. More studies are needed to confirm whether they have causal relationship or merely coincidental findings.

A case report of pilocytic astrocytoma mimicking meningioma on imaging.

Pilocytic astrocytoma (PA) is categorized as grade I gliomas with a good prognosis. Although PA mostly occurs in the cerebellum, it also can occur in the orbital and mostly presents as a cystic tumor with a mural nodule. PA often presents in the second decade of life, with 75% occurring under the age of 20 years. This case report describes a 10-year-old boy presented a left eye tumor for over 3 years. MRI examination showed unrestricted intraconal lesions in the optic nerve, visible from the optic canal to the anterior with well-defined borders. The excised tumor specimen depicted a nodular tumor tissue, measuring 35 × 28 × 20 mm, weighing 11 grams, solid with gray and white. The microscopic examination showed a classical biphasic pattern including combinations of loose glial tissue and compact pyloid tissue. Hispathology result revealed a pilocytic astrocytoma.

Apparent Diffusion Coefficient Values and Dynamic Contrast-Enhanced Magnetic Resonance Perfusion are Potential Predictors for Grading Meningiomas.

Purpose: Distinguishing between high-grade and low-grade meningiomas might be difficult but has high clinical value in deciding precise treatment and prognostic factors. Magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) values and dynamic contrast enhancement (DCE) may have a significant role in capturing such complexities. Methods: Data from our hospital database on meningioma patients from January 2020 to December 2021 were obtained. The MRI results of all patients were evaluated for mean ADC value and DCE parameters, including time-signal intensity curves (TIC), maximum signal intensity (SImax), time to maximum signal intensity (Tmax), maximum contrast enhancement ratio (MCER), and slope. Results: In this retrospective analysis, 33 individuals were included. Twenty-eight (84.8%) patients were pathologically diagnosed with low-grade meningioma and five (15.2%) patients with high-grade meningioma. There is a crossover between high- and low-grade meningiomas in conventional MRI. Tumor size, location, shape, necrotic/cystic changes, peritumoral edema, and enhancement patterns did not differ substantially between groups (p = 0.39, 0.23, 0.28, 0.57, 0.56, and 0.33, respectively). The mean ADC and Tmax values of high-grade meningiomas were substantially lower than those of low-grade meningiomas (p = 0.002 and 0.02, respectively). An optimal cut-off of 0.87 × 10-3 mm2s-1 for the mean ADC value (area under the curve [AUC] = 0.94, sensitivity = 80%, specificity = 92.8%) and 42 s for Tmax (AUC = 0.84, sensitivity = 80%, specificity = 89.3%) was suggested. High-grade meningiomas had significantly higher TIC, SImax, MCER, and slope than low-grade meningiomas (p = 0.004, < 0.001, 0.01, and 0.001, respectively). Type IV TIC had a sensitivity of 80% and specificity of 89.3% in distinguishing high-grade meningiomas from low-grade meningiomas. Optimal cut-offs of 940.2 for SImax (AUC = 0.98, sensitivity = 80%, specificity = 96.4%), 245% for MCER (AUC = 0.94, sensitivity = 80%, specificity = 85.7%), and 5% per second for slope (AUC = 0.97, sensitivity = 80%, specificity = 96.4%) were estimated. Conclusion: The ADC value and DCE-MRI parameters (TIC, SImax, Tmax, MCER, and slope) are potential predictors for separating high-grade from low-grade meningiomas.

Multiple spinal intramedullary cavernous angiomas with bleeding episode mimicking an intramedullary tumor.

Intramedullary cavernous angioma is a rare vascular malformation compared to cerebral cavernous malformation. The incidence of cavernous angioma is about 3 - 5% of all central nervous system lesions, 5 - 12% of all spinal vascular lesions, and 1% of all intramedullary lesions in pediatric patients. Although intramedullary cavernous angioma has the same histological picture as cerebral cavernous angioma, the natural history, and surgical approach are different from cerebral cavernous angioma. Due to its location in the eloquent area of the spinal medulla, a slight change in the size of the lesion can affect the neurological function of the patient. We describe a case of an intramedullary cavernous angioma with hemosiderin post bleeding, located in the cervical cord which was initially misdiagnosed as hemorrhagic ependymoma. On whole spine MR imaging we also found an intramedullary cavernous angioma in the lower thoracal cord at the T12 level with mild hemorrhage. Abdominal MRI showed cavernous angiomas in both kidneys. The patient underwent surgical treatment with removal of the lesion in the cervical cord and T12 level, with histopathologic findings consistent with cavernous angioma. No malignancy was detected. Post-surgery, the symptoms gradually improved. Symptomatic intramedullary cavernous angioma tends to bleed repeatedly and being unstable. Early diagnosis and surgical treatment can prevent rebleeding and more severe symptoms.

The Effect of Green Tea with EGCG Active Compound in Enhancing the Expression of M2 Microglia Marker (CD206).

Background: Stroke is a neurological deficit due to vascular disorders. Microglia are the first line of defense against brain injury. Anti-inflammatory cytokines activate M2 microglia, which upregulate CD206. EGCG is abundant in green tea, which has an anti-inflammatory effect. Objective: To know the effect of green tea with its active compound EGCG on CD206 expression. Settings and Design: True experimental trial design. Material and Methods: Rattus Novergicus were divided into six groups: a negative control group (Sham), a positive control group (P0), MCAO mice given 10 mg/kg BW EGCG (P1), 20 mg/kg BW EGCG (P2), 30 mg/kg BW EGCG (P3), and 30 mg/kg BW standardized green tea extract (P4). CD206 expression was measured using immunohistochemistry and scored according to the Allred scoring guidelines. Statistical Analysis Used: Descriptive test, Levine test, Kolmogorov-Smirnoff test, Independent sample t test, Pearson correlation test. Results: We discovered that there is a significant difference in CD206 expression between the Sham and P0 groups (P < 0.05). In addition, there are significant differences in expression between the sham group and the other two groups (P1 and P2) (P < 0.05). Furthermore, when we compared the P0 group with each treatment group, we found that CD206 expression between P0-P2, P0-P3, P0-P4 are significantly different. There is a significant correlation between green tea with its active compound EGCG and CD206 expression enhancement. The correlation is positive. Conclusions: Green tea with EGCG active compound increases CD206 expression as an M2 marker in the Rattus norvegicus with MCAO model.

Malignant struma ovarii: Case report of an unusual ovarian tumor with CT imaging.

Struma ovarii is categorised as a monodermal type of mature teratoma and consists primarily of thyroid tissue. It is an uncommon ovarian tumor, with non-specific clinical, and imaging findings. The majority of struma ovarii are benign and are typically associated with mature cystic teratomas. A small proportion of struma ovarii may undergo malignant transformation, with papillary carcinoma the most common type of malignancy. The criteria used to identify a malignant change in struma ovarii are identical to those used to evaluate the thyroid gland. Nevertheless, due to the rarity of struma ovarii, imaging diagnostic criteria, and subsequent management are not clearly defined. This case report describes a 41-year-old female patient who presented with rapid abdominal enlargement over a period of 1 month, accompanied by elevation of the tumor marker CA-125. Based on these clinically findings, ovarian cancer was suspected. The patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Histopathology results revealed a malignant struma ovarii.

Antioxidant Effect of Curcumin on the Prevention of Oxidative Damage to the Cochlea in an Ototoxic Rat Model Based on Malondialdehyde Expression

Abstract Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder. Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression. Methods The present research used 32 Rattus norvegicus, of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction. Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure. Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.

Antioxidant Effect of Curcumin on the Prevention of Oxidative Damage to the Cochlea in an Ototoxic Rat Model Based on Malondialdehyde Expression.

Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder. Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression. Methods The present research used 32 Rattus norvegicus , of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction. Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure. Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.

The aggressive progression of primary intracranial atypical teratoid/rhabdoid tumor after surgical resection: A case report.

INTRODUCTION AND IMPORTANCE: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive malignancy in children. Management of this aggressive tumor is associated with various diagnostic and therapeutic challenges. Maximum safe resection, followed by radiation therapy and multiagent chemotherapy, is the best course of treatment. This study aims to demonstrate the aggressive progression of the clinical presentation and radiographic features for an AT/RT after surgical resection. CASE PRESENTATION: We reported a case of a 7-years-old girl with recurrent tumor mass in the left parieto-occipital region after performing craniotomy surgical resection. The tumor mass aggressively grew within a month after surgery. CONCLUSION: AT/RT is a rare and highly progressive malignancy in the children population. This tumor aggressively grows after the first surgery. The INI-1 gene has been found as a diagnostic tumor marker in AT/RT. The characteristic of AT/RT is an absence of INI-1 staining in tumor cells. The treatment in AT/RT serves as palliative treatment, aiming to improve patient's quality of life. The poor prognosis is associated with MR imaging evidence of disseminated leptomeningeal tumor.

The effect of Camellia sinensis (green tea) with its active compound EGCG on neuronal cell necroptosis in Rattus norvegicus middle cerebral artery occlusion (MCAO) model.

OBJECTIVES: To determine the inhibition effect of epigallocatechin gallate (EGCG) and green tea extract on neuronal necroptosis based on necroptosis morphology. METHODS: In vivo study was performed on male Rattus norvegicus middle cerebral artery occlusion (MCAO) model divided into five groups, MCAO-control groups, EGCG 10 mg/kg BW/day, EGCG 20 mg/kg BW/day, EGCG 30 mg/kg BW/day, and green tea extract 30 mg/kg BW/day for 7 days treatment. MCAO model was made by modification method using Bulldog clamp. After 7 days of treatment, all R. norvegicus were sacrificed. After that, examination using Hematoxylin-Eosin stain was conducted to look at necroptosis morphology in each group. RESULTS: We found that there are significant differences between control group and the other three groups (EGCG 20 mg/kg BW/day, EGCG 30 mg/kg BW/day, and green tea extract (p<0.05). There is a significant correlation between the number of neuron cell necroptosis and both EGCG and green tea extract (p<0.05). The correlation is negative, which means both EGCG and green tea extract will decrease the number of neuron cell necroptosis. EGCG will decrease neuron cell necroptosis starting from the dose of 20 mg/kg BW/day. EGCG 30 mg/kg BW/day produces the best result compared to other doses. CONCLUSIONS: Camellia sinensis (green tea) with its active compound EGCG decreases neuronal necroptosis morphology in MCAO models.

Apoptosis-Inducing Factor, Protein Expression, and Apoptosis Changes with Glutamine in Podocytes Cells Exposed with Cisplatin.

Cisplatin is a well-known chemotherapeutic drug. It is one of the most effective anticancer agents and is widely used for the treatment of several types of tumors. However, side effects in normal tissues and organs, such as nephrotoxicity that induces apoptosis in epithelial cells in the kidney, limit the use of cisplatin. Glutamine is a substrate for the synthesis of glutathione as an antioxidant and promotes HSP70 release, protecting cells from apoptosis induced by different stimuli. In the present study, we investigated the protective effect of glutamine on cisplatin nephrotoxicity in the kidney. Mice were divided into three groups such as a group of control (P0), a group of intraperitoneal injection of a single dose cisplatin 20 mg/kg BW at 7th day (P1), and a group of intravenous glutamine injection 100 mg/kg BW at days 1-7 and given an intraperitoneal injection of single dose cisplatin 20 mg/kg BW at 7th day (P2). Measurement of AIF expression and apoptotic cells was carried out by immunohistochemical methods. The number of AIF expressions and apoptotic cells is expressed in the Allred score. AIF expression result is as follows: P0: 3.29 ± 0.79, P1: 5.32 ± 0.68, and P2: 4.49 ± 0.47. Apoptosis result is as follows: P0: 3.04 ± 0.70, P1: 5.26 ± 0.53, and P2: 4.44 ± 0.41. There is a decreased expression of AIF on intravenous glutamine administration, followed by a decrease in apoptosis in the podocyte. In conclusion, glutamine administration might represent the treatment of nephrotoxic-induced cisplatin.

Mediastinal Anaplastic Ependymoma

Ependymomas arise from ependymal cells and can grow at any site in the central nervous system (CNS), as well as in some locations outside of the CNS. The latter is rare, contributing to the frequent misdiagnoses of such cases. Herein, we present the case of a 54-year-old man with a history of lower limb weakness and numbness. Magnetic resonance imaging revealed an extradural, heterogeneously enhanced solid lesion with a regular and well-defined border in the posterior mediastinum. A post-resection histopathological examination revealed tumor-forming perivascular pseudo-rosettes that showed immunoreactivity against glial fibrillary acidic protein, epithelial membrane antigen, and vimentin, as well as a high Ki-67 labeling index. Based on pathological features, a diagnosis of anaplastic ependymoma was established.

The recurrent plexiform neurofibroma of the scalp in neurofibromatosis type 1: illustrative case.

BACKGROUND: Plexiform neurofibroma is a benign tumor of the peripheral nerves. It is an unusual variant of neurofibroma originating from all parts of the nerve. Plexiform neurofibroma is primarily pathognomonic and exhibits an unusual variant from neurofibromatosis type 1 (NF1). The possibility of malignancy and recurrence are the main reasons for long-term, close follow-up. OBSERVATIONS: The authors report a case of a 14-year-old girl with a recurrent plexiform neurofibroma derived from the peripheral nerves, which also presented with a typical sign of NF1 disease. The aim of the tumor resection is symptomatic relief. LESSONS: Accomplishing a good outcome can be related to good perioperative planning and a precise operative procedure. The result of anatomical pathology determines the prognosis of the patient. Clinical examination and radiological studies are needed to evaluate the recurrence of complications after surgical procedures.

Duraplasty using amniotic membrane versus temporal muscle fascia: A clinical comparative study.

In the field of neurosurgery, often the dura mater cannot be sutured, and consequently, it requires a duraplasty procedure using a dural fascial graft. Since 1890, various materials have been researched as dura mater substitutes. Amniotic membrane, for example, is suitable as a dural graft material and has been used in neurosurgery since 2012. However, there has been little research on human patient's dural healing after the use of amniotic membrane in their duraplasty procedure. To address this gap, a clinical experimental study was undertaken to evaluate the human dural healing of 16 patients who had undergone duraplasty in decompressive craniectomy surgery at Dr. Soetomo General Hospital, Surabaya. The amniotic membrane allograft, was sutured to cover the dural defect for eight randomly chosen patients (Group I). The fascial autograft from the temporal muscle had been applied for eight other patients (Group II). Between 10 and 20 weeks after surgery, the patients underwent cranioplasty and dural healing evaluation by cerebrospinal fluid (CSF) leakage testing through the edge of the dural defect. The fibrocyte infiltration around the edge of the dural defect was examined histologically. Statistical analysis, using an independent t-test, was performed with a confidence interval of 95%. The results of the clinical and histological analysis suggest that an amniotic membrane graft was able to provide watertight dural closure and adequate fibrocyte infiltration comparable with that provided by temporalis muscle fascia. This study shows that using an amniotic membrane in neurosurgery has a potential advantage over an alternative dural healing.

Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias.

PURPOSE: An International League Against Epilepsy (ILAE) consensus classification system for focal cortical dysplasias (FCDs) has been published in 2011 specifying clinicopathologic FCD variants. The aim of the present work was to microscopically assess interobserver agreement and intraobserver reproducibility for FCD categories among an international group of neuropathologists with different levels of experience and access to epilepsy surgery tissue. METHODS: Surgical FCD specimens covering a broad histopathology spectrum were retrieved from 22 patients with epilepsy. Three surgical nonepilepsy specimens served as controls. A total of 188 slides with routine or immunohistochemical stainings were digitalized with a slide scanner to allow Internet-based microscopy review. Nine experienced neuropathologists were invited to review these cases twice at a time gap of 3 months and different orders of case presentation. The 2011 ILAE FCD consensus classification served as instruction. Kappa analysis was calculated to estimate interobserver and intraobserver agreement levels. In a third evaluation round, 21 additional neuropathologists with different experience and access to epilepsy surgery reviewed the same case series. KEY FINDINGS: Interobserver agreement was good (κ = 0.6360), with 84% consensus of diagnoses during the first evaluation (21 of 25 cases). Kappa values increased to 0.6532 after reevaluation, and consensus was obtained in 24 (96%) of 25 cases. Overall intraobserver reproducibility was also good (κ = 0.7824, ranging from 0.4991 to 1.000). Fewest changes in the classification were made in the FCD type II group (2.2% of 225 original diagnoses), whereas the majority of changes occurred in FCD type III (13.7% of 225 original diagnoses). In the third evaluation round, interobserver agreement was reflected by the level of experience of each neuropathologist, with κ values ranging from moderate (0.5056; high level of experience >40 cases/year) to low (0.3265; low level of experience <10 cases/year). SIGNIFICANCE: Our study achieved a good and reliable interobserver agreement among the group of expert neuropathologists originally involved in the ILAE FCD consensus classification system. Intraobserver reproducibility in this group was even more robust. These results showed considerable improvement compared to a previous study evaluating the 2004 Palmini FCD classification. Agreement levels were lower in our second group of neuropathologists and were related to their level of access and experience with epilepsy surgery specimens. These results suggested that the more precise ILAE definition of FCD histopathology patterns improves operational procedures in the diagnosis of FCDs. On the other hand, microscopic assessment of FCD is a challenge and requires sustained experience and teaching. The virtual slide review system allowed testing of this hypothesis and reached a widespread group of participating colleagues from different centers all over the world. We propose to further use this tool as a teaching device and also to address other epilepsy-associated entities still difficult to classify such as hippocampal sclerosis, long-term epilepsy-associated tumors, or mild malformations of cortical development (mMCDs), which were not yet covered by current ILAE classification systems.