Wipplinger, Tamara M

Abstract Background Imaging-based glioma monitoring is confounded by treatment-related changes. D-2-hydroxyglutarate (D-2-HG), produced by the isocitrate dehydrogenase (IDH) mutation, is detectable in cerebrospinal fluid (CSF), which can be sampled from cranial or lumbar compartments. We evaluated CSF D-2-HG as a serially accessible biomarker for IDH-mutant gliomas, including the optimal compartment for longitudinal sampling. Methods Lumbar and cranial CSF samples were collected from patients with IDH-mutant gliomas or IDH-wild-type central nervous system pathologies via surgical field collection, lumbar punctures, and CSF access devices. CSF D-2-HG was quantified via our CLIA-certified gas chromatography mass spectrometry assay. Results D-2-HG was significantly higher in cranial than lumbar CSF from IDH-mutant glioma patients. Consistent with low D-2-HG abundance in lumbar CSF, lumbar samples could not discriminate IDH-mutant gliomas from IDH-wild-type lesions. In contrast, cranial CSF D-2-HG was significantly higher in IDH-mutant gliomas than wild-type lesions, providing an adequate baseline for initial evaluations of monitoring capabilities. Across 75 samples from 7 consecutive patients with grade 4 IDH-mutant astrocytomas, serial cranial CSF D-2-HG decreased with cytoreduction, remained unchanged with stable disease, and increased with disease progression, but not pseudoprogression. Conclusions Serial cranial CSF D-2-HG shows promise as a monitoring biomarker for IDH-mutant gliomas.

BACKGROUND AND OBJECTIVES: Brainstem cavernous malformations (BSCM) can result in spontaneous intracerebral hemorrhage (ICH), often resulting in significant morbidity. We aimed to assess the functional outcome and identify predictors of functional neurological outcome after single and multiple symptomatic hemorrhages. METHODS: As part of an international multicenter collaboration, institutional databases from 3 different tertiary referral centers included BSCM patients with complete baseline characteristics, MRI Data set, ≥1 ICH, and ≥1 follow-up examination followed at our institutions between 2003 and 2023. Functional neurological outcome was obtained using the modified Rankin Scale at diagnosis, before and after each ICH, and last follow-up. Patients were excluded after surgical removal of the lesion and/or loss of follow-up. RESULTS: A total of 383 patients (41.47 ± 15.51 age; 220 [57.4%] female) were included and followed for an average of 63.16 ± 85.75 months. Functional neurological outcome deteriorated in 47.2% ( P = .010) after the second ICH and in 46.5% ( P = .007) after the third ICH. Moreover, the functional neurological status was impaired in 22.3% ( P < .001) of patients at last available follow-up compared with the time of BSCM diagnosis. CONCLUSION: In our study, we observed that the chance of full recovery might decrease with each ICH. We observed a significantly associated neurological deterioration after each ICH compared with initial ICH.

OBJECTIVE Stereotactic radiosurgery (SRS) offers excellent tumor control for pituitary adenoma (PA); however, treatment failure occasionally necessitates salvage surgery. Comprehensive studies on salvage surgical outcomes for recurrent PA after SRS remain scarce. This study aimed to elucidate the outcomes of salvage endonasal transsphenoidal surgery (sETS) for progressive PA failing SRS. METHODS This retrospective, two institution–based cohort study analyzed data from patients who underwent sETS for progressive PA failing SRS. Progression-free survival (PFS), disease-specific survival (DSS), and neurological and endocrinological outcomes in the sETS group were analyzed and compared with those in the primary ETS (pETS) group after propensity score matching using the following variables: age at surgery, maximum tumor diameter, highest Knosp–Steiner classification, and tumor type. RESULTS Thirteen sETS patients (8 males [62%], median age at surgery of 56 years) with 5 nonfunctioning (39%), 6 corticotropic (46%), and 2 other functioning (15%) PAs who received median (range) follow-up of 125 ( 23–169) months were included. None of the patients experienced new neurological deficits or death after sETS. The median (range) tumor resection rate was 90% (80%–100%). The 5-year PFS and DSS rates were 55% and 77%, respectively. All 4 patients (31%) who experienced recurrence after sETS had corticotropic tumors. In the matched cohort analysis between the sETS group with 12 patients and the pETS group with 12 patients, no significant differences were observed in surgical outcomes. PFS rates were marginally higher in the sETS group than in the pETS group (80% vs 49% at 3 years, p = 0.216, log-rank test), and DSS was similar between the two groups (p = 0.543, log-rank test). CONCLUSIONS The authors’ results indicate that ETS can be safely performed as a salvage treatment after failed SRS with low complication rates and satisfactory tumor control in treatment-resistant PA.