Takakazu Kawamata

Background/Objectives: Observation is generally recommended for asymptomatic meningiomas, but evidence from incidental meningiomas is derived largely from heterogeneous intracranial locations and may not directly apply to tumors involving the anterior visual pathway. We investigated whether preoperative visual status remained associated with postoperative visual function after adjustment for baseline clinical and anatomical differences in this location-specific subgroup. Methods: We retrospectively reviewed 146 patients who underwent resection of skull base meningiomas contacting or compressing the optic nerve and/or chiasm. Preoperative visual status was categorized by comprehensive ophthalmologic evaluation as normal visual function or visual dysfunction. The primary outcome was postoperative normal visual function, defined as preservation of normal vision in patients with normal preoperative visual function and complete recovery in those with preoperative visual dysfunction. Multivariable logistic regression was performed, and propensity score matching was conducted using age, sex, tumor volume, tumor laterality, and optic canal involvement. Results: Propensity score matching yielded 48 matched pairs with adequate balance across all measured covariates (all standardized mean differences < 0.1). Postoperative normal visual function was preserved or achieved in 95.8% of patients with normal preoperative visual function versus 31.3% of those with preoperative visual dysfunction (exact McNemar p < 0.001). Favorable visual outcome occurred in 95.8% versus 77.1%, respectively (p = 0.0225). Conclusions: Among surgically treated patients, normal preoperative visual function remained strongly associated with postoperative normal visual function after adjustment for measured clinical and anatomical differences. These findings do not establish that earlier surgery improves visual outcomes or define an optimal surgical timing strategy, but suggest that preoperative visual status and tumor anatomy should be considered in individualized management decisions.

Context: Achieving durable prolactinoma remission while preserving safe pregnancy remains a central unmet goal of cabergoline therapy. Objective: To prospectively evaluate individualized-dose cabergoline therapy for safe pregnancy, remission, and dosing optimization. Methods: Women with 310 prolactinomas comprised 97 bromocriptine (Bc)-resistant, 93 Bc-intolerant, and 120 naïve patients, harboring 56 large macroprolactinomas (≥20 mm), 80 small macroprolactinomas (≥10 mm), and 174 microprolactinomas. Cabergoline dosing was individualized to maintain nadir prolactin within the lowest achievable normal range. In 129 macroprolactinomas and 19 microprolactinomas at risk of gestational enlargement, medical debulking prophylactically restored the optic–pituitary (O–P) distance to >5.0 mm before conception. Cabergoline was discontinued immediately after conception. Results: Treatment achieved 100% biochemical normalization; 84-100% prepregnancy tumor debulking; 365 uneventful pregnancies in 294 patients (95%); no symptomatic tumor enlargement during pregnancy; and 72% postpartum remission overall (naïve 82%, Bc-resistant 70%, Bc-intolerant 61%; microprolactinomas 73%, macroprolactinomas 72%). Responder frequency was subtype-specific across 0.25-9.0 mg/week doses with distinct ED50 values ranging from 0.66 in Bc-intolerant to 3.71 in Bc-resistant patients. AIC-based multivariate analysis identified nadir prolactin—markedly lower in nonvisible than residual prolactinomas—as the dominant determinant of tumor disappearance. No cardiac valvulopathy or impulse control disorders were observed on longitudinal follow-up. Conclusion: Despite marked ED50 heterogeneity, nadir prolactin-guided individualized-dose cabergoline therapy safely achieved durable remission with excellent pregnancy outcomes. These findings establish a clinically actionable, outcome-directed framework that prospectively integrates endocrine normalization, anatomical risk reduction, and tumor eradication, rendering durable remission and safe pregnancy realistically achievable therapeutic objectives in prolactinomas.

Postoperative cerebrospinal fluid (CSF) leakage remains one of the most challenging complications of transsphenoidal surgery (TSS). Numerous reconstruction techniques have been proposed, but none has been established as the gold standard. To address this issue, we standardized rigid sellar floor reconstruction using a hard buttress, based on the concept of counteracting the water-hammer effect of pulsatile CSF pressure. We retrospectively analyzed 1,168 consecutive TSS procedures for sellar lesions performed by a single surgeon between October 2004 and March 2024. Routine rigid reconstruction was implemented from January 2009 (Group B, n = 856) and compared with an earlier cohort without routine buttressing (Group A, n = 312). Reconstruction materials included autologous bone grafts, calcium phosphate cement, titanium mesh, and resorbable plates. Rigid reconstruction was performed in 885 cases, most commonly with autologous bone ( n = 781), which proved most reliable. Calcium phosphate cement occasionally caused inflammatory change or graft dislodgement, and titanium mesh complicated reoperations. Postoperative CSF leakage requiring reoperation was significantly reduced from 2.88% in Group A to 0.47% in Group B ( P = 0.002), despite a higher intraoperative leak rate in Group B (76.5% vs. 54.2%, P < 0.0001), particularly grade 3 leaks (30.4% vs. 11.2%, P < 0.0001). All postoperative leaks in Group B were attributable to inadequate buttressing. Rigid sellar floor reconstruction is a fundamental strategy—together with dural suturing and vascularized mucosal flaps—for safer and more extensive resections in modern TSS, supported by a physiological rationale based on the water-hammer effect.

Purpose Fat accumulation leads to obesity, which increases the risk of cardiovascular diseases. Recent studies have shown that adipose (pro)renin receptor ([P]RR) may play a role in fat accumulation, and we previously reported increased adipose (P)RR expression in growth hormone (GH) deficiency in mice; however, the association between human adipose (P)RR expression and GH deficiency remains unclear. Methods In this prospective study, abdominal subcutaneous adipose tissue was collected during pituitary surgery in patients with non-functioning hypothalamic-pituitary masses, and the associations between adipose (P)RR mRNA expression, determined using reverse transcription-polymerase chain reaction, and GH deficiency and other clinical parameters were investigated. Results Fifteen patients (5 craniopharyngioma, 4 non-functioning pituitary neuroendocrine tumor, 4 Rathke’s cleft cyst, and 2 other diseases) (mean age, 53 ± 17 years; male sex, 3 [20%]; and mean body mass index [BMI], 24.8 ± 4.3 kg/m²; GH deficiency, 8 [53%]) were included. Adipose (P)RR mRNA expression was significantly higher in patients with GH deficiency (P = 0.009) compared to those without, but was not significantly associated with other pituitary functions. Adipose (P)RR mRNA expression was significantly correlated with BMI (r = 0.526, P = 0.044) and body fat mass (r = 0.728, P = 0.026, n = 9). GH deficiency was significantly associated with (P)RR mRNA after adjustment for obesity (β = 2.257, 95% CI: 0.367–4.417, P = 0.023). Conclusion Adipose (P)RR expression may be increased in GH deficiency, suggesting the possible role of adipose (P)RR in fat accumulation in GH deficiency.

Background: Postoperative weight gain is a recognized complication of deep brain stimulation, but whether ablative surgery produces target‐dependent weight effects remains unknown. We investigated whether pallidothalamic tractotomy (PTT) causes greater weight gain than pallidotomy and explored spatial associations. Methods: We retrospectively analyzed 79 patients with focal, segmental, or generalized dystonia who underwent unilateral PTT (n = 41) or globus pallidus internus (GPi) lesioning (n = 38). Multivariable linear regression quantified the effect of target on weight and body mass index (BMI) changes, adjusting for age, sex, side, preoperative BMI, follow‐up duration, and Burke–Fahn–Marsden dystonia rating scale (BFMDRS) improvement. In a subset with postoperative magnetic resonance imaging (MRI), lesion overlap (N) maps and voxel‐wise mean BMI‐change maps were generated to explore anatomical associations. Results: PTT resulted in greater postoperative weight gain than GPi lesioning (+6.7 ± 7.5 kg vs. +1.1 ± 4.7 kg), with ≥10 kg gain in 29.3% versus 5.3% of patients. After covariate adjustment, PTT remained independently associated with greater weight gain (adjusted difference + 5.18 kg; 95% confidence interval [CI] +13 to +8.23) and BMI increase (+1.92 kg/m ² ; 95% CI +0.85 to +2.99). Lesion mapping localized PTT lesions to Forel's field H1. Weight‐gain hotspots mapped medial to the inferior border of the subthalamic nucleus, whereas GPi maps showed no consistent intranuclear hotspot. Conclusions: PTT was associated with greater postoperative weight gain than pallidotomy, independent of covariates. These findings suggest that lesion target influences postoperative body‐weight regulation, highlighting the potential risk of lesions extending into the caudal subthalamic region. © 2026 International Parkinson and Movement Disorder Society.

Objective: Prolactinomas are usually managed with cabergoline, and surgery is reserved for strictly selected cases. Based on our surgical experience, we observed no recurrence in women who conceived and delivered after surgical remission. We therefore evaluated surgical outcomes and indications in pregnancy-seeking women. Methods: We retrospectively reviewed 57 women who underwent surgery in 1998–2008 (median age 28.0 years) and identified predictors of remission and recurrence. Refined criteria (desiring pregnancy, enclosed-type tumor, and Knosp grade ≤ 2 with anticipated complete resection) were then applied to 135 women treated in 2009–2022 (median age 35.0 years). Results: In 1998–2008, remission was achieved in 73.8% of enclosed-type microadenomas and improved to 95.2% in the later period. Postoperative prolactin < 3 ng/mL predicted lower recurrence than 3–15 ng/mL (4.3% vs 50.0%, P = 0.0098). In 2009–2022, 25/135 (18.5%) underwent surgery. Of 32 women who met the refined criteria, 20 elected surgery, and all achieved remission without new deficits. Across both cohorts, 59 women of childbearing age achieved remission. Recurrence occurred in 6 of 30 women who did not conceive (20%) but in none of the 29 who conceived and delivered (0%, P = 0.0237). Conclusions: Pregnancy and delivery following surgical remission were associated with no recurrence, suggesting a potential cure in this subgroup. When performed by experienced pituitary surgeons, transsphenoidal surgery may offer a curative pathway for carefully selected women desiring pregnancy. These findings support further refinement of surgical candidacy in pregnancy-seeking women and warrant validation in larger cohorts.

Background: Cerebrospinal fluid placental alkaline phosphatase (CSF-PLAP) is useful in diagnosing intracranial germinomas. However, reports on CSF-PLAP in histological subtypes other than germinoma remain limited. The primary aim of this study was to retrospectively analyze cases with histological diagnoses in which CSF-PLAP levels were measured and evaluate the sensitivity and specificity of this test using the clinically applied cutoff value of 8 pg/mL. Methods: We retrospectively analyzed 134 patients with intracranial disease who underwent CSF-PLAP testing for diagnostic purposes and had confirmed histopathological diagnoses without receiving any adjuvant therapy before, or between CSF-PLAP measurement and surgery. The cases were categorized as true positive (TP), true negative (TN), false positive (FP), false negative, or clinical germinoma. Diagnostic accuracy was evaluated based on sensitivity, specificity, and statistical comparisons between groups. Results: Among the 134 analyzed cases, 30 were classified as TP, 99 as TN, and 5 as FP. Using the 8 pg/mL cutoff, CSF-PLAP testing demonstrated a sensitivity of 100% and a specificity of 95.2%. The mean CSF-PLAP level was significantly higher in the TP group than in the FP group, and the TP group participants were significantly younger than the FP group participants. No significant differences in CSF-PLAP levels or age were found between the TP and clinical germinoma groups, supporting their clinical equivalence. Conclusions: CSF-PLAP using an 8 pg/mL cutoff demonstrates high diagnostic accuracy for intracranial germinoma. Recognition of potential false-positive results and consideration of sampling site may further improve clinical interpretation of CSF-PLAP measurements.

Background: A major challenge in managing gliomas is the lack of reliable and clinically applicable biomarkers. Imaging alone is often insufficient to distinguish gliomas from primary central nervous system lymphoma (PCNSL), necessitating invasive biopsy. Soluble protein tyrosine phosphatase receptor type Z (sPTPRZ) in cerebrospinal fluid (CSF) has recently emerged as a promising candidate. We evaluated the diagnostic utility of CSF sPTPRZ in differentiating gliomas from PCNSL. Methods: We developed an anti-HNK-1 antibody-based ELISA for CSF sPTPRZ and analyzed 51 glioma, 15 PCNSL, and 20 control patients. Complementary assays included western blotting, immunohistochemistry, qPCR. sPTPRZ immunopurified from glioma CSF was used to determine HNK-1 epitope sites. RNA-seq data from the C-CAT database were used to identify PTPRZ gene fusions. Results: CSF sPTPRZ levels were significantly elevated in glioma patients compared with both controls and PCNSL, demonstrating robust discrimination between these entities (AUC = 0.910 vs controls; AUC = 0.805 vs PCNSL; P = .0010). PTPRZ expression was absent in PCNSL, consistent with low CSF sPTPRZ. Mass spectrometry localized the HNK-1 epitope to exon 12 of PTPRZ-long, absent in PTPRZ-MET fusion variants (2% of gliomas). These insights may explain low sPTPRZ levels in a subset of gliomas. Conclusion: CSF sPTPRZ detection with anti-HNK-1 antibody is a minimally invasive biomarker for glioma. It significantly improves diagnostic discrimination from PCNSL, and provides a molecular rationale for biomarker-negative glioma subsets with PTPRZ-MET fusions.

Objective: Intracranial arterial calcification (ICAC) has been suggested to influence the outcomes of mechanical thrombectomy (MT) for acute ischemic stroke. We conducted a systematic review and meta-analysis to evaluate MT outcomes in patients with acute ischemic stroke and large-vessel occlusions involving intracranial calcified arteries.Methods: This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Peer-reviewed studies were included if they evaluated intracranial arterial calcification (≥130 Hounsfield unit [HU] on noncontrast computed tomography) in patients undergoing MT within 24 h of acute ischemic stroke and reported modified Rankin Scale (mRS) score at 90 days or the final thrombolysis in cerebral infarction (TICI) grade. Four databases (PubMed, Cochrane Library, Web of Science, and Embase) were searched from inception to July 2025. Two reviewers independently screened and extracted the data and assessed their quality using the Newcastle–Ottawa Scale. Odds ratios (OR) were pooled using Mantel–Haenszel random-effects models, and heterogeneity was assessed using I2.Results: Among 968 records, 4 observational studies (n = 832; 2016–2024) met the inclusion criteria. All were adjusted for baseline factors using multivariable or propensity score models. The quality of the studies ranged from moderate to high. The ICAC definitions varied as follows: morphological (intimal vs. medial), location-based (symptomatic vs. asymptomatic), or volumetric assessments. Meta-analysis showed that ICAC—particularly in studies distinguishing intimal from medial calcification—was significantly associated with poor 90-day outcomes (mRS 3–6) (pooled OR 1.74; 95% CI 1.21–2.52; p <0.001; I2 = 49%). In a subanalysis focusing on calcification volume, increased volume alone was not consistently associated with worse functional outcomes or lower reperfusion success (pooled OR ≈ 1.19; 95% CI 0.78–1.80). Collectively, the lack of association in the volume-based analysis and the significant association observed in studies incorporating intimal–medial differentiation suggest that lesion morphology—particularly the presence of intimal calcification—may exert a greater influence on MT outcomes than calcification volume itself.Conclusion: ICAC, especially when intimal calcification is present, is independently associated with procedural complexity and poor functional outcomes after thrombectomy for acute ischemic stroke. The divergent findings between the volume subanalysis and the broader morphology-based analysis highlight that morphology-driven, rather than volume-driven, calcification better explains outcome variability. Recognition of ICAC on baseline imaging may aid in prognostication, guide device strategies, and anticipate adjunctive interventions. Standardized assessments and prospective validation studies are needed to optimize outcomes.