Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family.

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families.

Extra-axial desmoplastic/nodular medulloblastoma in adult mimicking cerebellar metastasis: reappraisal of this rare presentation with literature review.

Introduction and importance: Medulloblastomas are the most common malignant intra-axial brain tumour in paediatric patients and represent 35-40% of posterior fossa tumour types in children between 3 and 9 years of age. Medulloblastomas may also be found in adulthood. These tumours are classified into two groups according to its molecular characteristics and histological type. The desmoplastic/nodular subtype is the second common subtype after the classic one. Only three cases of desmoplastic/nodular extra-axial medelloblastoma have been previously reported in the literature originating from to the cerebellopontine angle. Case presentation: The authors report a new case of an extra-axial desmoplastic/nodular cerebellar medulloblastoma originating outside the cerebellopontine angle and mimicking a solitary cerebellar metastasis in a 49-year-old female patient who presented for a raised intracranial pressure and cerebellar syndrome. Clinical discussion: Medulloblastoma is a malignant embryonal intra-axial tumour of the cerebellum or posterior brain stem that occurs mainly in children. Medulloblastomas may also be found in adulthood. Desmoplastic/nodular medulloblastoma is the second most common type of all medulloblastomas. The intra-axial form is always predominant. Only three cases of extra-axial desmoplastic/nodular medulloblastoma have been reported in the literature. The authors will go through the literature to dissect this rare entity. Conclusion: Although considered a common paediatric intra-axial tumour, there are increasing numbers of solitary cases reporting an extra-axial presentation in different locations of the posterior cerebral fossa even in adulthood. These rare and unusual presentations and locations may mislead the correct diagnosis and delay treatment.

Early postoperative intra-axial dissemination of a pediatric extradural and complicated hydatid cyst.

Hydatid disease is very common around the Mediterranean basin and endemic in some parts of the world. Cerebral involvement remains rare, represents only about 2% of all hydatid localizations and mainly affects the pediatric population. Extradural hydatid cyst is very rare or even exceptional when it is associated with or followed by intracerebral disseminations. Here, the authors report a new exceptional case of an early multiple intra-axial hydatid dissemination in a 5-year-old North African male patient from a rural area who underwent surgery 3 months after a primary osteolytic extradural and complicated hydatid cyst with good clinical and radiological outcomes.

A case of pediatric primary osteolytic extradural and complicated hydatid cyst revealed by a skull vault swelling.

Hydatidosis is a parasitic infestation whose etiological agent is the larva of the cestode Echinococcus granulosus. It is a zoonosis, and the human being behaves as an accidental intermediate host in the parasitic cycle with pediatric predominance. The most frequent clinical presentation is hepatic, followed by pulmonary, with cerebral hydatidosis being extremely rare. Imaging is characteristic, generally dealing with single cystic lesion, usually unilocular and less frequently multilocular, located mainly intraaxially. Extradural hydatid cyst, whether primary or secondary, remains very rare or even exceptional. The primary disease remains extremely rare, and its clinical picture is related to the number, size, and location of the lesions. Infection within these cerebral hydatid cysts remains an extremely rare occurrence, and only few cases were reported previously in the literature. The authors report the nosological review of the clinical, imaging, surgical, and histopathological records of a pediatric primary osteolytic extradural and complicated hydatid cyst in a 5-year-old North African male patient coming from a rural area who presented for progressive onset of a painless left parieto-occipital soft swelling without any neurological disorder with good outcomes after surgery. The authors report this case due the fact that it had not been documented before in the pediatric population and to the success of the specialized treatment.

A chronic subdural hematoma complicating an arachnoid cyst in a juvenile boxer: a rare case report with comprehensive literature review.

Introduction and importance: Arachnoid cyst (AC) is the most frequently founded lesion reported in adolescent patients suffering from chronic subdural haematoma (CSDH). Association between these two distinct clinical entities is known for a long time. However, in the literature there are numerous clinical cases that reflect this relationship and few large series that analyze them in detail. Paediatric population is more rarely affected with this association. Case presentation: The authors report the case of AC of incidental discovery complicated with CSDH in 15-year-old male recreational boxer presented with progressive onset of holocranial drug-resistant throbbing headache with favourable clinical course after conservative treatment. Clinical discussion: ACs are a well-known predisposing cause for CSDH after head trauma. In all cases of CSDH in children, the diagnosis of ruptured AC should be considered. Rupture may be spontaneous or following even mild head trauma with rupture of bridging veins causing subdural bleeding as it was seen in our patient who was practicing a full-contact free-sparring sport like boxing sustaining repeated and direct mild head traumas. MRI is recommended to detect small cysts in adolescents with CSDH. The management of these patients remains controversial. Conclusion: This is a rare reported case of CSDH complicating an AC in a juvenile recreational male boxer. This association remains extremely rare in children and adolescents, as evidenced by the rare cases reported in the literature.

Shotgun Proteomic-Based Approach with a Q-Exactive Hybrid Quadrupole-Orbitrap High-Resolution Mass Spectrometer for Protein Adductomics on a 3D Human Brain Tumor Neurospheroid Culture Model: The Identification of Adduct Formation in Calmodulin-Dependent Protein Kinase-2 and Annexin-A1 Induced by Pesticide Mixture.

Pesticides are increasingly used in combinations in crop protection, resulting in enhanced toxicities for various organisms. Although protein adductomics is challenging, it remains a powerful bioanalytical tool to check environmental exposure and characterize xenobiotic adducts as putative toxicity biomarkers with high accuracy, facilitated by recent advances in proteomic methodologies and a mass spectrometry high-throughput technique. The present study aims to predict the potential neurotoxicity effect of imidacloprid and λ-cyhalothrin insecticides on human neural cells. Our protocol consisted first of 3D in vitro developing neurospheroids derived from human brain tumors and then treatment by pesticide mixture. Furthermore, we adopted a bottom-up proteomic-based approach using nanoflow ultraperformance liquid chromatography coupled with a high-resolution mass spectrometer for protein-adduct analysis with prediction of altered sites. Two proteins were selected, namely, calcium-calmodulin-dependent protein kinase-II (CaMK2) and annexin-A1 (ANXA1), as key targets endowed with primordial roles. De novo sequencing revealed several adduct formations in the active site of 82-ANXA1 and 228-CaMK2 as a result of neurotoxicity, predicted by the added mass shifts for the structure of electrophilic precursors. To the best of our knowledge, our study is the first to adopt a proteomic-based approach to investigate in depth pesticide molecular interactions and their potential to adduct proteins which play a crucial role in the neurotoxicity mechanism.

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography-Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors.

Pesticides are widely used, resulting in continuing human exposure with potential health impacts. Some exposures related to agricultural works have been associated with neurological disorders. Since the 2000s, the hypothesis of the role of pesticides in the occurrence of central nervous system (CNS) tumors has been better documented in the literature. However, the etiology of childhood brain cancers still remains largely unknown. The major objective of this work was to assess the potential role of pesticide exposure as a risk factor for CNS tumors based on questionnaires and statistical analysis of information collected from patients hospitalized in the Neurosurgery Department of the Habib Bourguiba Hospital Medium in Sfax, Tunisia, during the period from January 1, 2022, to May 31, 2023. It also aimed to develop a simple and rapid analytical method by the gas chromatography-mass spectrometry technique for the research traces of pesticide metabolites in some collected human brain tumor tissues in order to more emphasize our hypothesis for such a correlation between pesticide exposure and brain tumor development. Patients with a history of high-risk exposure were selected to conduct further analysis. Chemometric methods were adapted to discern intrinsic variation between pathological and control groups and ascertain effective separation with the identification of differentially expressed metabolites accountable for such variations. Three samples revealed traces of pesticide metabolites that were mostly detected at an early age. The histopathological diagnosis was medulloblastoma for a 10-year-old child and high-grade gliomas for 27- and 35-year-old adults. The bivariate analyses (odds ratio >1 and P value <5%) confirmed the great probability of developing cancer by an exposure case. The Cox proportional hazards model revealed the risk of carcinogenicity beyond the age of 50 as a long-term effect of pesticide toxicity. Our study supports the correlation between pesticide exposure and the risk of development of human brain tumors, suggesting that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased childhood brain tumor risk. This hypothesis was enhanced in identifying traces of metabolites from the carbamate insecticide class known for their neurotoxicity and others from pyridazinone, organochlorines (OCs), triazole fungicide, and N-nitroso compounds known for their carcinogenicity. The 2D-OXYBLOT analysis confirmed the neurotoxicity effect of insecticides to induce oxidative damage in CNS cells. Aldicarb was implicated in brain carcinogenicity confirmed by the identification of oxime metabolites in a stress degradation study. Revealing "aziridine" metabolites from the OC class may better emphasize the theory of detecting traces of pesticide metabolites at an early age. Overall, our findings lead to the recommendation of limiting the residential use of pesticides and the support of public health policies serving this objective that we need to be vigilant in the postmarketing surveillance of human health impacts.

Differential Proteome Profiling Analysis under Pesticide Stress by the Use of a Nano-UHPLC-MS/MS Untargeted Proteomic-Based Approach on a 3D-Developed Neurospheroid Model: Identification of Protein Interactions, Prognostic Biomarkers, and Potential Therapeutic Targets in Human IDH Mutant High-Grade Gliomas.

High-grade gliomas represent the most common group of infiltrative primary brain tumors in adults associated with high invasiveness, agressivity, and resistance to therapy, which highlights the need to develop potent drugs with novel mechanisms of action. The aim of this study is to reveal changes in proteome profiles under stressful conditions to identify prognostic biomarkers and altered apoptogenic pathways involved in the anticancer action of human isocitrate dehydrogenase (IDH) mutant high-grade gliomas. Our protocol consists first of a 3D in vitro developing neurospheroid model and then treatment by a pesticide mixture at relevant concentrations. Furthermore, we adopted an untargeted proteomic-based approach with high-resolution mass spectrometry for a comparative analysis of the differentially expressed proteins between treated and nontreated spheroids. Our analysis revealed that the majority of altered proteins were key members in glioma pathogenesis, implicated in the cellular metabolism, biological regulation, binding, and catalytic and structural activity and linked to many cascading regulatory pathways. Our finding revealed that grade-IV astrocytomas promote the downstream of the mitogen-activated-protein-kinases/extracellular-signal-regulated kinase (MAPK1/ERK2) pathway involving massive calcium influx. The gonadotrophin-releasing-hormone signaling enhances MAKP activity and may serve as a negative feedback compensating regulator. Thus, our study can pave the way for effective new therapeutic and diagnostic strategies to improve the overall survival.

Post-traumatic chronic-encapsulated and calcified intracerebral hematoma mimicking a supratentorial hemangioblastoma: a case report and literature review.

Chronic-encapsulated intracerebral hematomas are a rare type of hematoma. They tend to be mistaken for abscesses or tumors. The etiology of these hematomas is not yet clear, although they have mainly been linked to arteriovenous malformations, cavernomas, and head trauma. Surgical evacuation is effective in improving neurological symptoms with a good prognosis. However, the lesion may be difficult to diagnose. Case presentation: Here, the authors report a case of a chronic-encapsulated and calcified intracerebral hematoma following recurrent mild head injuries mimicking a supratentorial hemangioblastoma in a healthy 26-year-old female patient presented with progressive raised intracranial pressure and left body heaviness with good outcomes after en bloc surgical resection. Clinical discussion: The chronic-encapsulated intracerebral hematoma was first described by Hirsh et al. in 1981. Their etiology is not yet clear, although they have mainly been linked to arteriovenous malformations, cavernomas, and head trauma. Pathologically, they are characterized by the presence of a fibrous capsule composed of an outer collagen layer and an inner granulated layer. Radiologically, they appear as cystic lesions with a homogeneous high signal on T1-weighted and T2-weighted images associated with a lower signal ring sign and ring enhancement after gadolinium administration that may suggest hemangioblastoma. Conclusion: Although chronic parenchymal hematomas remain a rare phenomenon, it has become increasingly logical to consider this entity in differential diagnoses with other lesions. In cases with recurrent head trauma, a detailed investigation will aid in making the diagnosis of such a rare pathology.

Safety assessment of fish oil green extraction and in vivo acute toxicity evaluation.

Sardine co-products can represent an interesting source of bioactive compounds, such as polyunsaturated fatty acids and in particular omega-3. This study aimed to investigate extraction of oil from sardine co-products by enzymatic hydrolysis using two proteases: commercial Alcalase and protease Bb from a local fungal strain (P2) of Beauveria bassiana, which overproduces proteases. Despite a higher degree of hydrolysis (41.34%) than Alcalase (24.28%), protease Bb allowed the extraction of approximately the same oil content. Resulting oil from both processes had the same fatty acid profile. Interestingly, the all-produced oil displayed an attractive w6/w3 ratio, an indicator of nutritional quality, of the order of 0.16. The safety of the generated oils was also assessed by treating two groups of Wistar rats with the fish oil administered by oral gavage at the doses (30 mg/kg and 300 mg/kg body weight) for 14 days using olive oil as a vehicle. Compared to controls used, both treated groups showed no statistically significant differences. Consequently, the acute oral toxicity evaluated by hematological, biochemical, and histological studies showed the safety of the oil generated using B. bassiana protease.

Isolated pediatric retroclival epidural hematoma following a minor blunt head trauma: a case report with review of the literature.

Post-traumatic clival hematomas are a rare entity and almost exclusive to the pediatric population. Those of retroclival location are exceptionally rare. This entity was first described in 1941 by Coleman and Thomson, and since then, less than 30 cases have been reported in the literature. Clinically, these hematomas are usually silent and slow, but clinical state worsening may be sudden and rapidly fatal by the onset of obstructive hydrocephalus in the absence of prompt treatment. Here, the authors report a new case of pediatric post traumatic retroclival epidural hematoma following a minor blunt head trauma in a 03-year-old male patient with good outcomes. The authors will proceed with a review of the literature regarding the pathophysiology and mechanisms of occurrence of such post-traumatic injury.

Infrequent delayed controlateral remote cerebellar hemorrhage after supratentorial craniotomy in adult patient: a case report.

Remote cerebellar hemorrhage as a rare complication of supratentorial surgery was already first described in the 1970s by Yasargil. Its incidence ranges from 0.2% to 0.4% after supratentorial craniotomies. Although its incidence is low, the volume of reports with remote cerebellar hemorrhage in the literature has been growing in recent times. The authors report here a new case of a controlateral remote cerebellar hemorrhage after 24 hours of supratentorial craniotomy for a solitary brain metastasis of a pulmonary adenocarcinoma in a 59 year-old male patient with unbalanced high blood pressure. Supratentorial craniotomy, Remote cerebellar hemorrhage, CT scan.

A postoperative brain abscess due to Propionibacterium acnes in an immunocompetent adult with incidental discovery.

Introduction: and importance: Propionibacterium acnes (P. acnes) is an anaerobic, lipophilic, Gram-positive bacteria of the commensal skin flora. It may also be present on the mouth's mucosa, nose, urogenital tract, and large bowel. P. acnes is an unusual and rare agent of intracerebral abscess although in recent years some publications suggest that its frequency in brain surgery is increasing. Case presentation: The authors report a case of an incidental cerebral abscess during follow-up imaging in a 63-year-old male patient operated on twice for cerebral meningioma the last of which was 3 months ago without placement of any surgical implant with uneventful postoperative course. Clinical discussion: P. acnes is still an sunder-appreciated cause of post-neurosurgical infection. Time between neurosurgery and infection is variable ranging from few months to many years. Its culture time is long, with currently an average time to positivity of six days (2-15 days), justifying prolonged cultures. Conclusion: Intracranial infections by P. acnes are not quite frequent. We emphasize the need to send samples for culture of anaerobes in this type of complications before giving a negative result.

Papillary thyroid carcinoma associated with glioblastoma in a neurofibromatosis 1 patient: An unusual and rare combination of multiple primary malignancies.

Introduction: and importance: Papillary Thyroid carcinoma (PTC) is the most common endocrine malignancy and accounts for 1-2% of all cancer cases. Second malignancies in women diagnosed with thyroid cancer are of concern given the young average age at diagnosis. The concurrent occurrence of thyroid cancer and malignant brain tumor such as glioblastoma (GBM) was rarely seen and reported. However, the simultaneous association of these 2 conditions, namely PTC and GBM, in a neurofibromatosis type 1 (NF1) patient, has never been reported before in the literature. Case presentation: The authors report the first case of an extremely rare association combining papillary thyroid carcinoma, glioblastoma, and a neurofibromatosis 1 in a 34-year-old female patient with primary generalized tonic-clonic seizures. Clinical discussion: NF1 can be associated with PTC and GBM independently. In this current case, NF1 was accompanied by both PTC and GBM. With the exception of the present case, to our knowledge, there has been no previous case report in the literature in which these 3 entities were associated. The reason for the rarity of this combination of these neoplasms in patients with NF1 remains not clear, but it may be explained by the low incidence of combined occurrence of PTC and GBM. Conclusion: This is the first reported extremely rare coexistence of GBM and PTC in a female NF1 patient. Further genetic investigations could improve our understanding of this combination and change our therapeutic approaches.

Primary adult unilateral thalamic pilocytic astrocytoma with von Recklinghausen's disease mimicking lymphoma: A case report.

Thalamic astrocytomas are rare central nervous system tumors that account for 1%-1.5% of all brain tumors. Their Clinical features depend on anatomical involvement. For these tumors, gross total resection is so difficult due to their deep location and also the infiltration of the optic pathway or brain stem. Unilateral adult thalamic locations are rarely described in the literature. Their radiological features often suggest lymphoma. The authors report here a new case of a primary unilateral thalamic pilocytic astrocytoma mimicking lymphoma diagnosed after a stereotactic core biopsy in a 62-year-old male patient with von Recklinghausen's disease and which is responsible for Dejerine-Roussy syndrome. The authors will proceed with a comprehensive review of literature regarding this rare entity.

Pediatric synchronous multifocal and disseminated cerebrospinal classic medulloblastoma revealed by bilateral decreased visual acuity: a case report.

Medulloblastoma (MB) is a rapidly growing malignant solid tumor that arises from stem cells located in the subependymal germinal matrix or outer granular layer of the cerebellum. It represents 15 to 30% of pediatric brain tumors and less than 1% of primary brain tumors. The reason for the high incidence of MB in children compared to adults is the embryonic origin of the tumor. In typical cases, MB manifests as a solitary lesion in the fourth ventricle or in the cerebellar parenchyma; cases of synchronous multifocal and disseminated MB are quite rare in patients without familial tumor syndromes. To date, only 7 cases in adults and a single pediatric case with Gorlin syndrome have been described previously. Here, the authors report a new case of synchronous multifocal classic cerebrospinal histologically confirmed MB in a 10-year-old male patient revealed by bilateral decreased visual acuity without any other localizing neurological signs. The authors will proceed with a review of the current literature regarding this rare entity.

Spontaneous rapid regression of a juvenile primary aneurysmal bone cyst of the skull: A case report and literature review.

Aneurysmal bone cyst (ABC) is a benign lesion that often starts off the metaphysis of long bones and which, as it grows, may blow out bone. Only 3%-6% of cases are located in the skull. Spontaneous recovery has been reported. These cases occur more often in adults and in pelvic locations. Spontaneous regression at the skull level remains a very rare entity and few cases were described in the literature. Here, the authors report another case of spontaneous rapid regression of ABC of the skull in a 7-year-old boy revealed by gradually increasing painless hard swelling in the right frontal bone region with rapid spontaneous regression within 15 days. The authors will also proceed with an overview concerning this rare entity.

A giant partial thrombosed aneurysm of the internal cavernous carotid artery mimicking a meningioma of the lesser wing of the sphenoid bone.

Giant intracranial aneurysms are defined as those with diameters of 25 mm or more and represent about 5% of all intracranial aneurysms. These aneurysms typically manifest during the fifth to seventh decades of life. Due to their size, giant aneurysms are responsible for intracranial mass effect rather than hemorrhage. Clinical symptoms depend on aneurysm's location. Radiological features are not common for aneurysms of the internal cavernous carotid artery. Differential diagnosis includes pituitary adenoma, meningioma, craniopharyngioma, hamartoma, glioma, teratoma, and even granuloma. Here, the authors report a case of a 63-year-old female patient with a giant partial thrombosed aneurysm of the internal cavernous carotid artery mimicking a meningioma of the lesser wing of the sphenoid bone who presented for visual defect, and raised intracranial pressure. The authors will proceed with a literature review investigating this entity as well its ability of mimicking meningioma.

A case of adult cerebellar liponeurocytoma with atypical radiological features and long survival with literature review.

Cerebellar liponeurocytoma or lipomatous medulloblastoma is a rare oncological entity. Knowledge regarding the management and outcomes of these rare tumors are still evolving. Very few cases have been described previously in the literature. The authors report a case of a middle-aged woman operated on twice, 8 years apart, with uneventful postoperative follow-ups. Radiological characteristics were revealed atypically on the computed tomography scan and magnetic resonance imaging. Histopathological study supported a cerebellar liponeurocytoma with classic immunohistochemical features. Through this report, the authors aim to describe atypical radiological and histopathological features of this rare entity with good outcome by going through a comprehensive review of the existing literature.

A rare case of pediatric primary central nervous system differentiating neuroblastoma: an unusual and rare intracranial primitive neuroectodermal tumor (a case report).

Neuroblastoma represents the most common solid extracranial tumor in children under 5, accounting for 8% to 10% of all childhood cancers. Primary central nervous system (CNS) neuroblastomas are a very rare location and only few cases are available in the literature. It was first described in 1973 by Hart and Earl as supratentorial primitive neuroectodermal tumors. Clinical presentation is highly variable and depends on the initial location of the tumor. Regarding imaging, primary brain neuroblastoma shows no pathognomonic appearance on brain computed tomography (CT) whether or not enhanced or magnetic resonance imaging (MRI). There were no standard guidelines available for the adjuvant treatment in case of primary CNS neuroblastoma. Surgery remains the main and the first tool toward these lesions. Radiotherapy associated or not to chemotherapy is offered based on patient´s age. Here, the authors report a new pediatric case of primitive central nervous system neuroblastoma revealed by an intracranial hypertension syndrome and confirmed by both histopathological and immunohistochemistry study after a gross total surgical excision. The postoperative course was uneventful and the child had good recovery.