Hopital Universitaire Habib Bourguiba

Levetiracetam (LEV) is frequently prioritized in epilepsy management due to its minimal drug-drug interactions and perceived metabolic neutrality. However, its potential involvement in severe electrolyte disturbances remains scarcely documented. We describe a 36-year-old male admitted for status epilepticus and initiated on a dose-escalated LEV regimen (2000 mg/day). The clinical course was complicated by the development of severe, recalcitrant hypokalemia (nadir 2.8 mmol/L). This electrolyte depletion proved remarkably refractory to intensive parenteral and enteral potassium chloride supplementation. A systematic diagnostic workup successfully excluded extrarenal losses, primary hyperaldosteronism, and renal tubular acidosis. Given the specific temporal alignment with drug intensification, LEV was substituted with phenobarbital. This intervention led to a rapid and sustained restoration of potassium homeostasis within seven days post-withdrawal. Causality was evaluated as highly probable (I5; C2S3). This case, corroborated by recent large-scale epidemiological findings, highlights LEV as a potential trigger for refractory potassium depletion in the adult population. Unlike other antiepileptics, LEV lacks carbonic anhydrase inhibition, suggesting alternative mechanisms such as iatrogenic transcellular shifts or interference with renal ion conductance. We emphasize the necessity of rigorous metabolic monitoring during LEV dose escalation and advocate for an update to official safety labeling to include this metabolic risk, ensuring earlier clinical detection and improved patient safety.

Spondylocostal dysostosis type 1 is caused by mutations in the DLL3 gene, which encodes a Notch1 ligand. These mutations lead to defective somitogenesis, resulting in a consistent pattern of abnormal vertebral segmentation. Disruptions in the Notch1 signaling pathways can potentially lead to extraskeletal anomalies, although specific associations with DLL3 mutations are less well-documented. We report a 23-week female fetus presenting with characteristic "pebble beach" sign and rib anomalies. Autopsy revealed pulmonary hypoplasia and a 4 mm fundic nodule bulging on both inner and outer gastric surfaces. Histological examination of the stomach walls revealed multifocal pancreatic heterotopia in the fundus and pylorus, invading the submucosa and/or the muscularis propria. Genetic analysis confirmed a novel homozygous likely pathogenic frameshift variant in DLL3 (NM_000435.3:c.183_184del, p.Arg61Serfs*39). This case report expands the DLL3 mutational spectrum in spondylocostal dysostosis type 1 and highlights associated pancreatic heterotopia.

Background and objectives: The fifth edition of the WHO Classification of Tumors of the Central Nervous System divides grade 4 diffuse glioma based on IDH1 mutation in grade 4 astrocytoma, IDH-mutant and glioblastoma, IDH-wild type tumors. This study aimed to evaluate the IDH1 status in grade 4 diffuse glioma as well as its correlation with clinicopathological features and patient survival. To our knowledge, no Tunisian studies on the molecular profile of diffuse glioma have yet been published. Methods: This is a retrospective study including all cases of adult, grade 4 diffuse glioma collected in the pathology department of Habib Bourguiba hospital. Results: A total of 67 patients were included in the final analysis. The expression of IDH1 was positive in 22 cases (32%). IDH1-positive tumors were classified as grade 4 astrocytoma, IDH1-mutant while, 45 IDH1-negative tumors were classified as glioblastoma, IDH1-wild type tumors (68%). IDH1 expression was correlated with younger age (≤ 40 years old), frontal location, complete surgical resection and well-defined borders. IDH1-positive tumors were associated significantly with better prognosis. The 1-year overall survival (OS) for grade 4 astrocytoma, IDH1-mutant was 86% compared with 8% in glioblastoma, IDH1-wild type (p=0.008). Conclusion: Our study investigated IDH1 expression in grade 4 diffuse glioma and proved that grade 4 astrocytoma, IDH1 positive tumors displayed different characteristics with a more favorable outcome compared to glioblastoma, IDH1 negative. Thus, evaluation of IDH1 mutation should be standardized routinely not only as diagnostic marker but also to refine the prognostic classification of these tumors.