Osaka Neurological Institute

Quantification of dopaminergic neurons in the substantia nigra pars compacta (SNc) of animal models is important for understanding the pathogenesis of Parkinson's disease (PD). However, conventional manual cell counting method requires the time and effort, and has limited reproducibility due to inter- and intra-examiner variability. Here, we demonstrate that a commercially available convolutional neural network-based artificial intelligence (AI) counting method (TruAI, OLYMPUS, Tokyo, Japan) enables robust and reproducible quantification of TH-positive dopaminergic neurons in mouse, marmoset, and human SNc samples when compared with conventional manual counting. AI-based counting showed a strong correlation with manual counting across mouse, marmoset, and human samples. Good agreement between AI-based and manual counting was observed in mouse and marmoset samples, supporting the applicability of this approach for cross-species quantification of dopaminergic neurons. In the mouse model treated with α-syn preformed fibrils (PFFs), AI-based counting detected a significant reduction in TH-positive neurons consistent with expert manual counting. Non-experts exhibited greater intra-examiner variability than an expert, indicating that the reliability of manual counting depends on experience. Overall, AI-based quantification provides a robust and objective approach for TH-positive cell counting and may improve reproducibility in dopaminergic neuron analysis, particularly for non-expert users and cross-species studies of PD.

Abstract We introduce the term "combat dementia" as a novel neurocognitive phenotype that emerges in military personnel as a consequence of prolonged and continuous exposure to combat environments. In a prospective cohort (2014–2025; n = 297), neuropsychological testing (MoCA), cognitive event-related potentials, quantitative EEG, and multidisciplinary clinical evaluation were performed. Three phenotypes of cognitive impairment were distinguished for clinical analysis: (A) post-traumatic brain injury (TBI) with MRI/CT-verified macrostructural changes (classical organic variant); (B) without TBI and PTSD, with no macrostructural alterations on MRI/CT, but with persistent network-level microstructural pathology verified by specific neurophysiological markers (persistent variant, i.e., "combat dementia"); (C) associated with PTSD/cumulative psychotrauma, without neuroimaging evidence of macrostructural lesions or neurophysiological indicators of stable microstructural pathology, but with predominantly functional changes verified by neurophysiological markers and potentially reversible dynamics (transitional/borderline variant). Three distinct trajectories of cognitive decline were identified: macrostructural organic (A), microstructural persistent (B), and transitional/borderline (C). Phenotype C, occupying an intermediate position between A and B, illustrates a possible transformation from functional network-level alterations to stable microstructural pathology, thereby explaining the increased risk of dementia in cases of chronic PTSD. Key predictors of accelerated decline included age and continuous frontline exposure exceeding 14 months, which was associated with nearly a threefold increase in the risk of progression to more severe stages of cognitive impairment. Summarized longitudinal observations (6/12 months; subgroups of 3–10 years) confirm the stability of phenotype B and its distinction from phenotypes A and C; an extended analysis will be presented in subsequent publications. Recognition of combat dementia as an independent clinical entity is critically important for the development of new screening strategies, rehabilitation programs, and nosological classification of cognitive disorders in military populations. The findings delineate a novel domain in neuropsychiatry, with implications not only for Ukraine but also for the international community in shaping humanitarian and social policy, as well as rehabilitation systems and military medical expertise.

This case report describes the use of pharmacologic vasodilation with intra-arterial isosorbide dinitrate to facilitate endovascular treatment of a foramen magnum dural arteriovenous fistula in a man in his 40s. The fistula was supplied by the posterior meningeal artery arising from the right vertebral artery and the hypoglossal branch of the ascending pharyngeal artery (APA). Catheterization of the APA was challenging due to its tortuous course and small caliber. To address this, 2 mg of isosorbide dinitrate was administered intra-arterially, resulting in effective vasodilation and allowing smooth microcatheter navigation. Embolization was then successfully performed using 12.5% n-butyl-2-cyanoacrylate, leading to a significant reduction in shunt flow. Follow-up angiography at three months confirmed complete obliteration of the fistula, and the patient remained neurologically intact, with no perioperative or delayed complications. This case highlights the potential utility of intra-arterial vasodilators, such as isosorbide dinitrate, in overcoming anatomical challenges during transarterial embolization and suggests their broader applicability in complex neuroendovascular procedures.

Background and purposeMeningiomas often contain a pial supply, and devascularization through preoperative transarterial embolization (TAE) is useful. However, the efficacy indicators of TAE for meningiomas with pial feeders remain unclear owing to their challenging quantification. Therefore, we propose a practical and quantitative intratumoral cerebral blood volume (CBV) from the pial supply, called pial-nCBV. This study aimed to identify the efficacy indicators of TAE against meningiomas in pial feeders using pial-nCBV.Materials and methodsBetween 2015 and 2021, 25 patients who underwent preoperative TAE and perfusion magnetic resonance imaging (MRI) for meningiomas with pial feeders were included in the study. We set 5 mm diameter round Region Of Interests as many as possible within the tumor at the border with the brain parenchyma, and calculated the intratumoral CBV from pial supply. The reduction rate was defined as primary outcome, termed Δ pial-nCBV. Additionally, we collected data on the injection behavior of the n-Butyl-Cyanoacrylate (n-BCA), including intratumoral embolization (IE) and feeder occlusion. We then analyzed the association between each variable and Δ pial-nCBV.ResultsThe median Δ pial-nCBV was 25%. The n-BCA was applied in 22 (88%) cases, of which nine (36%) cases were injected into pial feeders. The use of n-BCA (p = .037), treatment with pial feeders (p = .002), and IE in meningeal feeders (p = .049) were associated with an increase in Δ pial-nCBV.ConclusionWe proposed a practical indicator, pial-nCBV, and increasing Δ pial-nCBV was associated with treating pial feeder using n-BCA.

Neoplastic cerebral aneurysms (NCAs) are rare. This study reported a case of an NCA secondary to a poorly differentiated carcinoma of the parotid gland. An 84-year-old Japanese woman undergoing treatment for parotid gland cancer was admitted to our hospital with headache and progressive loss of consciousness. Based on computed tomography (CT) and CT angiography (CTA), a diagnosis of subarachnoid hemorrhage due to rupture of a left posterior inferior cerebellar artery aneurysm was made, and emergency aneurysmectomy was performed. Pathological examination of the resected aneurysm showed an NCA secondary to parotid carcinoma. After the aneurysmectomy, her condition stabilized; however, 33 days later, the patient developed an intracerebral hemorrhage, and a new aneurysm was confirmed in the right middle cerebral artery. To the best of our knowledge, there have been no previous reports on cases of NCAs secondary to parotid carcinoma. The pathology and clinical course strongly suggest that NCAs derived from malignant tumors may have an aggressive course.

Background: Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke (IS) in several animal models. This phase II clinical trial aimed to test the safety and tolerability of intravenous (IV) AM administration in acute IS (AIS) patients within 24 hours of onset. Methods: The AdrenoMedullin For Ischemic Stroke study is an investigator-initiated, randomized, double-blind, phase II trial. Patients with non-cardioembolic IS within 24 hours after stroke onset and baseline NIH Stroke Scale (NIHSS) score ≥1 were randomly allocated to the intermittent IV AM (I-AM group) (30 μg/kg in total for 7 days, n=20) or placebo group (n=10) in the first cohort and a combination of continuous (the first 3 days) and intermittent (the following 4 days) IV AM (C/I-AM group) (56 μg/kg in total for 7 days, n=20) or placebo group (n=10) in the second cohort. The primary endpoint was serious adverse events related to the protocol treatment and secondary efficacy endpoints were favorable outcomes (mRS 0-2 at 90 days) and good outcomes (mRS 0-3 at 90 days). Results: The population of 60 patients had a median age of 75 years, 21 patients (35%) were female, and the median NIHSS score was 3. The primary endpoint did not occur in all groups. In the secondary efficacy endpoints, the rates of favorable outcome (75.0% vs. 68.9%, adjusted odds ratio [aOR], 1.45; 95% confidential interval [CI], 0.32-6.53) and good outcome (90.0% vs. 73.7%, aOR 3.86; 95% CI, 0.67-22.11) in the I-AM group were not statistically different from those in the placebo group. The rates of good outcomes in the C/I-AM group were comparable with those in the placebo group (85.0% vs. 73.7%, aOR 1.56; 95% CI, 0.72-3.39). Conclusions: Treatment with IV AM within 24 hours of AIS onset is safe. Intermittent IV AM may contribute to improved AIS prognosis. The efficacy and safety of AM will need confirmation in the next phase of clinical trials.

Due to the heterogeneous definitions of tumor regrowth and various tumor volume distributions, the nature of small remnants after vestibular schwannoma (VS) surgery and the appropriate timing of adjuvant stereotactic radiosurgery for these remnants remain unclear. In this study, the growth potential of small remnants (< 1 cm3) after VS surgery was compared with that of treatment-naïve (TN) small VSs. This retrospective single-center study included 44 patients with VS remnants following subtotal resection (STR) of a large VS (remnant group) and 75 patients with TN VS (< 1 cm3; TN group). A 20% change in tumor volume over the imaging interval indicated radiographic progression or regression. Tumor progression-free survival (TPFS) rates were estimated using the Kaplan-Meier method. In the remnant group, the mean preoperative tumor volume was 13.8 ± 9.0 cm3 and the mean tumor resection rate was 95% ± 5%. The mean tumor volume at the start of the observation period did not differ significantly between the two groups (remnant vs TN: 0.41 ± 0.29 vs 0.34 ± 0.28 cm3, p = 0.171). The median periods until tumor progression was detected were 15.1 (range 4.9-76.2) months and 44.7 (range 12.6-93.2) months in the TN and remnant groups, respectively. In the remnant group, the TPFS rates were 74% and 70% at 3 and 5 years after the surgery, respectively, compared with 59% and 47% in the TN group. The log-rank test demonstrated a significant difference (p = 0.008) in the TPFS rates between the two groups. Furthermore, 42 patients each from the remnant and TN groups were matched based on tumor volume. TPFS was significantly longer in the remnant group than in the TN group (3-year rates, 77% vs 62%; 5-year rates, 73% vs 51%; p = 0.02). In the remnant group, 18% of the tumor remnants demonstrated regression during follow-up, compared with 9% in the TN group, but this intergroup difference was not significant (p = 0.25). This study demonstrated that the growth potential of small VS remnants was lower than that of TN tumors. Observing for small remnants may be appropriate after STR of a large VS. Given the risk of tumor regrowth, careful observation using MRI should be mandatory during follow-up.

ObjectivesThe objective of this work is to evaluate the additional oncological benefit of photodynamic diagnosis (PDD) using blue‐light cystoscopy in transurethral resection (TURBT) for primary non‐muscle‐invasive bladder cancer (NMIBC) based on the International Bladder Cancer Group (IBCG)‐defined progression and the subsequent pathological pathways.Patients and MethodsWe reviewed 1578 consecutive primary NMIBC patients undergoing white‐light TURBT (WL‐TURBT) or PDD‐TURBT during 2006–2020. One‐to‐one propensity score‐matching was performed using multivariable logistic regression to obtain balanced groups. IBCG‐defined progression of NMIBC included stage‐up and grade‐up as well as conventional definitions such as the development of muscle‐invasive BC or metastatic disease. Nine oncological endpoints were evaluated. Sankey diagrams were generated to visualize follow‐up pathological pathways after the initial TURBT.ResultsComparison of event‐free survival between the matched groups revealed that PDD use decreased the bladder cancer recurrence risk and IBCG‐defined progression risk, whereas no significant difference was noted in conventionally defined progression. This was attributable to a reduced risk of stage‐up, from Ta to T1, and grade‐up. Sankey diagrams of the matched groups showed that patients with primary Ta low‐grade tumour and first‐recurrence Ta low‐grade tumour did not have bladder recurrence or progression, while some of those in the WL‐TURBT group developed recurrence after treatment.ConclusionsThe multiple survival analysis demonstrated that the risk of IBCG‐defined progression was significantly decreased by PDD use in NMIBC patients. Sankey diagrams revealed possible differences in pathological pathways after the initial TURBT between the two groups, demonstrating that repeated recurrence could be prevented by PDD use.

Hearing preservation after large vestibular schwannoma (VS) removal is challenging and the long-term outcomes of postoperatively preserved hearing have not been elucidated. We aimed to clarify long-term outcomes of hearing preservation after the retrosigmoid large VS removal and to recommend a strategy for treating large VS. Hearing preservation with total/nearly total (T/NT) tumor removal was accomplished in six of 129 patients who underwent retrosigmoid large VS (≥3 cm) removal. We evaluated the long-term outcomes of these six patients. Preoperative hearing of these six patients was 15-68 dB by pure tone audiometry (PTA) (Class I: 2, II: 3, and III: 1 by the Gardner-Robertson (GR) classification). Postoperatively, magnetic resonance imaging (MRI) with gadolinium administration confirmed T/NT removal, the preserved hearing was 36-88 dB (Class II: 4 and III: 2), and no facial palsy occurred. After long-term follow-up (8-16 [median: 11.5] years), five patients maintained hearing of 46-75 dB (Class II: 1 and III: 4) while one lost hearing. Three patients showed small tumor recurrence on MRI; two recurrences were controlled by gamma knife (GK) and one showed minimal change only by observation. Hearing preserved after T/NT removal of large VS is maintained for a long time (>10 years), though tumor recurrence on MRI is somewhat common. Detecting small recurrence early, and regular MRI follow-up contributes to the long-term maintenance of hearing. Hearing preservation with tumor removal is a challenging yet worthwhile strategy in large VS patients with preoperative hearing.