Recurrent atypical meningiomas: combining surgery and radiosurgery in one effective multimodal treatment

OBJECTIVE: Owing to their rarity and proteiform pathologic features, the clinical behavior of atypical meningiomas is not yet well characterized. Though the extent of resection is believed to be a key determinant of prognosis, limited data exist regarding optimal management of patients with recurrent disease. METHODS: In this 20-year retrospective case series, we reviewed the medical records of 46 patients with recurrent atypical meningiomas (185 lesions, 89 of which were local, 78 marginal, and 18 distant recurrences); treatment was radiosurgery (n = 60), surgery (n = 56), or both (n = 8). The median follow-up period was 53 months. Outcome measures were length of overall survival and disease-free intervals and prognostic factors for survival. RESULTS: Overall, the median progression-free survival was 26 months at the first recurrence and 100 months thereafter (the sum of the later intervals). Multivariate analysis showed that no treatment-related factors influenced prognosis, whereas recurrence at the skull base was a significant tumor-related factor limiting further treatment. Irrespective of treatment type, the recurrence-free interval was increasingly shorter during the clinical course, with a higher occurrence of marginal and distant lesions migrating to the midline and to the skull base. In sporadic cases, disease-free intervals were longer after wide craniotomy, tumor and dural resection with tumor-free margin. CONCLUSIONS: The disease-free interval was substantially similar after surgery and radiosurgery for treating recurrent disease in patients with atypical meningiomas. Surgery is the mainstay for prolonging survival, while radiosurgery can be an adjuvant strategy to gain time for clinical observation and planning aggressive surgical treatment

The Immunohistochemical Loss of H3K27me3 in Intracranial Meningiomas Predicts Shorter Progression-Free Survival after Stereotactic Radiosurgery

The immunohistochemical loss of histone H3 trimethylated in lysine 27 (H3K27me3) was recently shown to predict recurrence of meningiomas after surgery. However, its association with tumor progression after stereotactic radiosurgery (SRS) is unexplored. To investigate whether H3K27 methylation status may predict progression-free survival (PFS) after SRS, we assessed H3K27me3 immunoexpression in thirty-nine treatment naïve, intracranial, meningiomas, treated with surgery and subsequent SRS for residual (twenty-three cases) or recurrent (sixteen cases) disease. H3K27me3 immunostaining was lost in seven meningiomas, retained in twenty-seven and inconclusive in five. Six of the seven meningiomas (86%) with H3K27me3 loss had tumor progression after SRS, compared to nine of twenty-seven (33%) with H3K27me3 retention (p = 0.0143). In addition, patients harboring a meningioma with H3K27me3 loss had significantly shorter PFS after SRS (range: 10-81 months; median: 34 months), compared to patients featuring a meningioma with retained H3K27me3 (range: 9-143 months; median: 62 months) (p = 0.0036). Nonetheless, tumor sagittal location was the only significant prognostic variable at multivariate analysis for PFS after SRS (p = 0.0142). These findings suggest a previously unreported role of H3K27me3 as a predictor of meningioma progression after SRS for recurrent or residual disease. Modulation of H3K27 methylation status may represent a novel therapeutic strategy to induce radiosensitization of meningiomas

Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data

Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data. Methods: A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review. Results: The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature. Conclusion: We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years

A role for leukocyte-endothelial adhesion mechanisms in epilepsy

The mechanisms involved in the pathogenesis of epilepsy, a chronic neurological disorder that affects approximately 1 percent of the world population, are not well understood1–3. Using a mouse model of epilepsy, we show that seizures induce elevated expression of vascular cell adhesion molecules and enhanced leukocyte rolling and arrest in brain vessels mediated by the leukocyte mucin P-selectin glycoprotein ligand-1 (PSGL-1) and leukocyte integrins α4β1 and αLβ2. Inhibition of leukocyte-vascular interactions either with blocking antibodies, or in mice genetically deficient in functional PSGL-1, dramatically reduced seizures. Treatment with blocking antibodies following acute seizures prevented the development of epilepsy. Neutrophil depletion also inhibited acute seizure induction and chronic spontaneous recurrent seizures. Blood-brain barrier (BBB) leakage, which is known to enhance neuronal excitability, was induced by acute seizure activity but was prevented by blockade of leukocyte-vascular adhesion, suggesting a pathogenetic link between leukocyte-vascular interactions, BBB damage and seizure generation. Consistent with potential leukocyte involvement in the human, leukocytes were more abundant in brains of epileptics than of controls. Our results suggest leukocyte-endothelial interaction as a potential target for the prevention and treatment of epilepsy

Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data

IntroductionMagnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an “incisionless” treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data.MethodsA retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018–December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review.ResultsThe CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature.ConclusionWe confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years

Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part II: adjuvant radiobiological tools

Stereotactic radiosurgery (SRS) is currently a well-established, minimally invasive treatment for many primary and secondary tumors, especially deep-sited lesions for which traditional neurosurgical procedures were poorly satisfactory or not effective at all. The initial evolution of SRS was cautious, relying on more than 30 years of experimental and clinical work that preceded its introduction into the worldwide medical community. This path enabled a brilliant present, and the continuous pace of technological advancement holds promise for a brighter future. Part II of this review article will cover the impact of multimodal adjuvant technologies on SRS, and their input to the crucial role played by neurosurgeons, radiation oncologists and medical physicists in the management and care of fragile neuro-oncological patients