Pineoblastoma is a rare and highly aggressive embryonal tumor of the pineal region, predominantly affecting children and adolescents. It is classified as a CNS WHO grade 4 tumor and is characterized by a high risk of cerebrospinal fluid dissemination. Although leptomeningeal spread is a recognized feature of this tumor, spinal metastatic involvement at diagnosis remains uncommon and indicates high-risk disease. We report the case of a 16-year-old girl with no relevant past medical history who presented with a two-week history of sleep disturbances, right-sided strabismus, and projectile vomiting. Brain MRI demonstrated a heterogeneous pineal region mass measuring approximately 28 × 26 mm, associated with triventricular hydrocephalus. The patient underwent endoscopic ventriculocisternostomy and stereotactic biopsy. Histopathological and immunohistochemical findings confirmed the diagnosis of pineoblastoma. Staging spinal MRI revealed multiple dorsal spinal leptomeningeal nodules, consistent with CSF dissemination and spinal drop metastases. Given the rarity of pineoblastoma and the absence of a universally established pineoblastoma-specific therapeutic protocol, the case was discussed with an international pediatric neuro-oncology expert. Based on this expert recommendation, the patient was treated using a high-risk medulloblastoma-derived regimen. She received craniospinal irradiation with weekly vincristine, followed by adjuvant chemotherapy with cisplatin, cyclophosphamide, and vincristine according to an ACNS0332-based approach. At three months after completion of treatment, follow-up MRI showed complete regression of the spinal metastatic lesions and a small residual cystic lesion in the pineal region. Clinically, the patient showed marked improvement, particularly in oculomotor function. This case highlights the importance of systematic craniospinal staging at diagnosis in pineoblastoma and illustrates the potential value of early multidisciplinary and multimodal management in metastatic disease. At nine months of follow-up, the patient remained clinically stable, without evidence of spinal disease progression on serial imaging. However, this follow-up remains limited, and long-term clinical and radiological surveillance is essential because of the high risk of recurrence.

Treatment optimization through pharmacokinetic evaluation is needed to improve outcomes in tuberculous meningitis (TBM). Clinical assessment of drug penetration into the central nervous system (CNS) is limited to cerebrospinal fluid (CSF) sampling, which may not reflect drug exposures at the site-of-disease. We characterized the pharmacokinetics of antituberculosis drugs in CNS tissues using a rabbit model of TBM. Rabbits infected with Mycobacterium tuberculosis received human-equivalent doses of antituberculosis drugs after displaying signs of TBM. Blood was intensively sampled on day 1 and until euthanasia on day 3 when terminal plasma, CSF, and CNS tissues were collected. Total drug concentrations were quantified by LC-MS/MS and analyzed in NONMEM to estimate equilibration half-lives and CSF- and CNS tissue-to-plasma ratios. Across 5 experiments, 48 rabbits provided 600 plasma samples and 48 sets of terminal CSF/CNS tissue samples. Pyrazinamide and isoniazid showed high and consistent penetration, with CSF ratios of 0.98 and 0.85 and CNS tissue ratios ranging from 0.44 to 0.73 and 0.60-0.82, respectively. Linezolid demonstrated modest and uniform penetration (CSF ratio 0.39; CNS tissue ratios 0.15-0.44). Rifampicin showed the lowest overall penetration (CSF ratio 0.08; CNS tissue ratios 0.07-0.32). In contrast, the most lipophilic drugs, bedaquiline and rifabutin, showed low CSF ratios (0.01 and 0.42, respectively) compared with much higher CNS tissue ratios (1.11-6.34 and 1.23-6.78, respectively). CSF penetration in the rabbit TBM model closely mirrored reported human data, establishing its translational value. High relative CNS exposures of bedaquiline and rifabutin support their clinical evaluation for TBM treatment.

Cytotoxic lesions of the corpus callosum are increasingly recognized after aneurysmal subarachnoid hemorrhage, but their prognostic value for shunt-dependent chronic hydrocephalus remains uncertain. We conducted a two-center retrospective cohort study of consecutive patients with aneurysmal subarachnoid hemorrhage who underwent brain magnetic resonance imaging within 7 days of onset. Cytotoxic lesions of the corpus callosum were defined as diffusion restriction with corresponding apparent diffusion coefficient reduction and were classified as none, small-type, or large-type using prespecified morphological criteria. The primary outcome was shunt-dependent chronic hydrocephalus, and the secondary outcome was unfavorable functional outcome (modified Rankin Scale score 3-6 at discharge or at approximately day 60). Associations were evaluated using prespecified multivariable logistic regression. As a sensitivity analysis, binary intraventricular hemorrhage was replaced by the Graeb score to account for quantitative intraventricular hemorrhage burden. Among 230 patients, 68 (29.6%) had cytotoxic lesions of the corpus callosum (small-type, 44 [19.1%]; large-type, 24 [10.4%]), and 62 (27.0%) developed shunt-dependent chronic hydrocephalus. After adjustment, small-type cytotoxic lesions of the corpus callosum (vs none) were associated with shunt-dependent chronic hydrocephalus (adjusted odds ratio 2.99, 95% confidence interval 1.31-6.83; p = 0.009) and unfavorable functional outcome (adjusted odds ratio 4.85, 95% confidence interval 1.79-13.93; p = 0.002). For large-type cytotoxic lesions of the corpus callosum, point estimates for both outcomes were elevated, but the 95% confidence interval included 1.0. Modified Fisher grade and Graeb score differed significantly across cytotoxic lesion of the corpus callosum subtypes (both p < 0.001). Early cytotoxic lesion of the corpus callosum assessment, particularly identification of small-type lesions, was associated with shunt-dependent chronic hydrocephalus and unfavorable outcome after aneurysmal subarachnoid hemorrhage.

Intracranial germ cell tumors (IGCTs) are a group of malignant central nervous system (CNS) tumors primarily affecting children and adolescents, whose pathogenesis remains incompletely understood. The embryonic cell theory suggests that IGCTs may originate from pluripotent embryonic cells that escape normal migration and differentiation during embryonic development. Research indicates that DNA hypomethylation, abnormalities in the MAPK and/or PI3K signaling pathways, and chromosomal abnormalities play significant roles in the development and progression of IGCTs. Diagnosis relies on a comprehensive evaluation of clinical presentation, tumor markers, and imaging studies, ultimately confirmed by histopathology. In recent years, novel biomarkers in serum and cerebrospinal fluid, such as microRNAs (miRNAs) and circulating tumor DNA (ctDNA), have gained increasing attention for their diagnostic and prognostic value. Current treatment predominantly relies on surgery, radiotherapy, and chemotherapy, though the optimal radiation field and dose remain controversial. With a deepening understanding of molecular drivers and the tumor microenvironment, targeted therapy and immunotherapy are gradually being applied clinically. As the survival rate of patients with IGCTs improves, we are also confronted with new clinical challenges: how to minimize treatment-related long-term sequelae while maintaining excellent therapeutic outcomes, and improve the prognosis for refractory non-germinomatous germ cell tumors (NGGCTs). This review summarizes recent advances in genetic variation, diagnosis, and treatment of IGCTs, serving as a reference for exploring personalized therapeutic strategies, reducing treatment-related toxicity, and improving long-term prognosis.