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Objective Headache after ventriculoperitoneal (VP) shunting is classically attributed to CSF over-drainage or shunt malfunction. We hypothesized that a subset of adults instead experience an occipital neuralgia-like pain syndrome (“Occipital Neuralgia”) from shunt hardware irritating the occipital nerves, and that these cases respond better to nerve-targeted treatments than to shunt revisions. Methods We retrospectively reviewed 2,223 adults who underwent first-time VP shunt placement between 2000 and 2025 at a tertiary center. Patients with post-shunt headache were identified and classified as Occipital Neuralgia if they had occipital-predominant, lancinating pain with focal tenderness over the valve or tract, short-term relief from diagnostic occipital nerve block, and no evidence of over-drainage, malfunction, or infection on work-up. Clinical features, management, and outcomes (nerve blocks, neuromodulation, shunt adjustments or revisions) were compared between Occipital Neuralgia and other post-shunt headaches. Results Among 2,223 adults who underwent VP shunt placement, 32 patients (1.44%) developed new, persistent post-shunt headaches not attributable to shunt malfunction, over-drainage, or infection. Of these, 24 patients (1.08% of the total cohort; 75% of chronic post-shunt headaches) met criteria for Occipital Neuralgia. These patients typically presented with occipital-predominant, lancinating pain, focal scalp tenderness over the shunt valve or tract, and absence of orthostatic features. Neuroimaging demonstrated normal or slit ventricles without signs of intracranial hypotension or other structural intracranial pathology. Most patients experienced substantial symptomatic improvement following nerve-targeted therapies, whereas shunt-directed interventions provided limited benefit once pressure-related causes were excluded. Conclusions Post-shunt occipital neuralgia is a recognizable, under-appreciated cause of headache after VP shunting. Early recognition of a focal occipital neuropathic phenotype and nerve-targeted therapy can yield meaningful relief and help avoid unwarranted shunt revisions. Prospective validation of diagnostic criteria and management pathways is needed.

Background and Objectives: Chronic headache after craniotomy is common and may include neuropathic subtypes (scar neuroma pain, occipital neuralgia). However, no large series has quantified these phenotypes. We conducted a single-center retrospective review (n = 5624 adult craniotomy patients) to estimate the prevalence of post-craniotomy neuropathic pain and to describe its characteristics. Materials and Methods: Institutional records were screened to identify craniotomy patients referred to a multidisciplinary pain clinic (n = 272). Eligible cases were reviewed in tiers: (1) exclusion of primary headache and noncranial pain; (2) identification of “probable neuropathic cranial pain” based on documented neuropathic features (lancinating/scalp pain, trigger tenderness, dermatomal distribution); and (3) subgroup categorization into occipital neuralgia-like, supraorbital/supratrochlear neuralgia-like, and scar-site neuropathic pain phenotypes. The supraorbital/supratrochlear subgroup was defined by frontal or frontotemporal postoperative pain in the supraorbital region, local tenderness or Tinel-like hypersensitivity over the supraorbital/supratrochlear course, and/or response to supraorbital–supratrochlear nerve block. Data extracted included demographics, timing (surgery to pain referral), pain characteristics, and treatments (blocks, radiofrequency, medications). Results: Of 5624 craniotomy patients, 272 (4.8%) had pain clinic encounters. The initial review identified 124 cases with chronic post-craniotomy headache requiring follow-up; after detailed chart classification, probable neuropathic cranial pain was present in 111 cases (2% of the cohort). Among the 111 probable neuropathic cranial pain cases, the dominant regional phenotype was occipital neuralgia-like pain. In addition, eight patients (7.2%) demonstrated a supraorbital/supratrochlear neuralgia-like phenotype, predominantly after frontal or frontotemporal craniotomies. Scar-site neuropathic pain frequently coexisted with both regional phenotypes, supporting a partially overlapping spectrum rather than mutually exclusive categories. The median time from surgery to pain referral was several months (≈12–18 months). Management commonly included occipital nerve blocks (±steroid); some patients received pulsed radiofrequency ablation of the occipital nerves, and most were trialed on neuropathic analgesics (gabapentinoids, SNRIs, etc., according to neuropathic pain guidelines). Conclusions: A clinically meaningful subset of post-craniotomy patients develops chronic neuropathic cranial pain, most commonly with occipital, supraorbital/supratrochlear, or scar-related features. Because most postoperative headaches are managed through neurosurgical follow-up and improve without pain clinic referral, the present cohort likely underestimates the true burden of neuropathic post-craniotomy pain while enriching for its most refractory neuralgic presentations. This is nevertheless the subgroup that must be recognized, discussed with patients, studied prospectively, and targeted in future prevention strategies.

The current standard of care for newly diagnosed glioblastoma multiforme (GBM) is resection followed by radiotherapy with concomitant and adjuvant temozolomide. Recent studies suggest that nearly half of the patients with early radiological deterioration post treatment do not suffer from tumor recurrence but from pseudoprogression. Similarly, a significant number of patients with brain metastases suffer from radiation necrosis following radiation treatments. Conventional MRI is currently unable to differentiate tumor progression from treatment-induced effects. The ability to clearly differentiate tumor from non-tumoral tissues is crucial for appropriate patient management. Ten patients with primary brain tumors and 10 patients with brain metastases were scanned by delayed contrast extravasation MRI prior to surgery. Enhancement subtraction maps calculated from high resolution MR images acquired up to 75 min after contrast administration were used for obtaining stereotactic biopsies. Histological assessment was then compared with the pre-surgical calculated maps. In addition, the application of our maps for prediction of progression was studied in a small cohort of 13 newly diagnosed GBM patients undergoing standard chemoradiation and followed up to 19.7 months post therapy. The maps showed two primary enhancement populations: the slow population where contrast clearance from the tissue was slower than contrast accumulation and the fast population where clearance was faster than accumulation. Comparison with histology confirmed the fast population to consist of morphologically active tumor and the slow population to consist of non-tumoral tissues. Our maps demonstrated significant correlation with perfusion-weighted MR data acquired simultaneously, although contradicting examples were shown. Preliminary results suggest that early changes in the fast volumes may serve as a predictor for time to progression. These preliminary results suggest that our high resolution MRI-based delayed enhancement subtraction maps may be applied for clear depiction of tumor and non-tumoral tissues in patients with primary brain tumors and patients with brain metastases.

Ultrasound in combination with the introduction of microbubbles into the vasculature effectively opens the blood brain barrier (BBB) to allow the passage of therapeutic agents. Increased permeability of the BBB is typically demonstrated with small-molecule agents (e.g., 1-nm gadolinium salts). Permeability to small-molecule agents, however, cannot reliably predict the transfer of remarkably larger molecules (e.g., monoclonal antibodies) required by numerous therapies. To overcome this issue, we developed a magnetic resonance imaging analysis based on the ΔR 2 * physical parameter that can be measured intraoperatively for efficient real-time treatment management. We demonstrate successful correlations between ΔR 2 * values and parenchymal concentrations of 3 differently sized (18 nm–44 nm) populations of liposomes in a rat model. Reaching an appropriate ΔR 2 * value during treatment can reflect the effective delivery of large therapeutic agents. This prediction power enables the achievement of desirable parenchymal drug concentrations, which is paramount to obtaining effective therapeutic outcomes. ΔR 2 * values from MRI analysis correlate with concentrations of liposomes in the size range of 18–44 nm in a rat model.

: On 28 February 2026, Israel entered direct large-scale hostilities with Iran under Operation Roaring Lion. The opening phase was characterized by repeated missile alerts, civilian protected-space instructions, and rapid reorganization of hospital activity into protected areas. We observed an apparent increase in strict spontaneous intracerebral hemorrhage admissions during March 2026 within our linked neurology/neurosurgery services dataset. The aim of this preliminary single-center study was to determine whether March 2026 was temporally associated with a higher proportional burden of strict spontaneous intracerebral hemorrhage admissions compared with March cohorts from the preceding decade and whether this pattern was also observed for acute ischemic stroke or non-traumatic subarachnoid hemorrhage. : We performed a retrospective observational cohort study of all unique March admissions captured within a linked neurology/neurosurgery services dataset from 2016 through 2026. Hospitalizations were deduplicated by admission number. March 2026 was treated as the first full March occurring after the onset of direct Israel-Iran hostilities on 28 February 2026. Strict spontaneous ICH was defined using diagnosis-text phenotyping that included intraparenchymal or intracerebral hemorrhage terminology while excluding trauma, subarachnoid hemorrhage, subdural hematoma, aneurysm, arteriovenous malformation, tumor-related hemorrhage, cavernoma, venous sinus thrombosis, dissection, and other clearly secondary etiologies. Comparator phenotypes included acute ischemic stroke and non-traumatic subarachnoid hemorrhage (SAH). : Across 3855 unique March admissions, 68 met criteria for strict spontaneous ICH. In March 2026, 9 of 223 admissions (4.0%) were classified as strict spontaneous ICH, compared with 59 of 3632 admissions (1.6%) across March 2016-2025, yielding a rate ratio of 2.48 (95% CI 1.25-4.94; = 0.015). Patients with strict spontaneous ICH in March 2026 were older (mean age 72.3 vs. 65.8 years), and 7 of 9 cases (77.8%) occurred in patients aged ≥70 years compared with 25 of 59 (42.4%) historically ( = 0.073). Acute ischemic stroke did not increase in March 2026 (7.6% vs. 9.4%; = 0.475), and non-traumatic SAH showed only a non-significant numerical increase (2.7% vs. 1.4%; = 0.147). Sensitivity analyses showed a directionally consistent but statistically non-significant increase when March 2026 was compared with March 2025 alone (4.0% vs. 1.2%; rate ratio 3.36, 95% CI 0.92-12.27; = 0.076) and with a rolling 3-year March baseline from 2023 through 2025 (4.0% vs. 2.1%; rate ratio 1.93, 95% CI 0.88-4.23; = 0.143). In-hospital mortality among strict spontaneous ICH patients was 1 of 9 (11.1%) in March 2026 versus 4 of 59 (6.8%) in March 2016-2025. : In this preliminary single-center neurology/neurosurgery services cohort, March 2026 showed a higher proportional burden of strict spontaneous intracerebral hemorrhage admissions than March cohorts from the preceding decade, while acute ischemic stroke did not increase. Sensitivity analyses using March 2025 alone and a rolling 3-year March baseline were directionally consistent but did not reach statistical significance. These findings should therefore be interpreted as a hypothesis-generating temporal association rather than evidence of causality or population-level incidence. Wartime-related psychological stress, sleep disruption, altered healthcare access, blood pressure dysregulation, and medication nonadherence are biologically plausible contributors, but individual-level blood pressure, medication exposure, body mass index, time-to-admission, direct stress exposure, and detailed outcome data were not available in the present dataset. Multicenter, hospital-wide, and registry-based validation with seasonal and systems-level sensitivity analyses is required.

Background Animal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We hypothesized that the metabolic stress induced by a KD combined with metformin would enhance radiation’s efficacy. We sought to assess the tolerability and feasibility of this approach. Methods A single-institution phase I clinical trial. Radiotherapy was either 60 or 35 Gy over 6 or 2 weeks, for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a Modified Atkins Diet (ModAD) supplemented with medium chain triglycerides (MCT). There were three cohorts: Dietary intervention alone, and dietary intervention combined with low-dose or high-dose metformin; all patients received radiotherapy. Factors associated with blood ketone levels were investigated using a mixed-model analysis. Results A total of 13 patients were accrued, median age 61 years, of whom six had newly diagnosed and seven with recurrent disease. All completed radiation therapy; five patients stopped the metabolic intervention early. Metformin 850 mg three-times daily was poorly tolerated. There were no serious adverse events. Ketone levels were associated with dietary factors (ketogenic ratio, p < 0.001), use of metformin (p = 0. 02) and low insulin levels (p = 0.002). Median progression free survival was ten and four months for newly diagnosed and recurrent disease, respectively. Conclusions The intervention was well tolerated. Higher serum ketone levels were associated with both dietary intake and metformin use. The recommended phase II dose is eight weeks of a ModAD combined with 850 mg metformin twice daily.

Introduction Breast cancer brain metastases (BCBM) are increasingly common due to improved systemic therapies prolonging survival. This study evaluates local control and factors influencing outcomes in patients with resected BCBM treated with postoperative stereotactic radiotherapy (SRT). Methods A retrospective review included single resected BCBM treated with postoperative SRT from 2010 to 2022. The median follow-up was 28 months (range, 14–43). Variables analyzed included tumor size, biology, surgical corridor inclusion, radiation dose, and timing of SRT. Multivariable analysis was conducted using Cox regression. Results 62 patients were analyzed in multivariable analysis, HER2-positive status was associated with improved local control (HR: 0.76, 95% CI: 0.36–0.88, p = 0.032), as was a higher biologically effective dose (BED > 40 Gy, HR: 0.65, 95% CI: 0.45–0.89, p = 0.028). In contrast, tumor size > 5 cm (HR: 2.1, 95% CI: 1.7–4.6, p = 0.021) and delayed initiation of SRT beyond 28 days post-surgery (HR: 2.7, 95% CI: 1.9–4.7, p = 0.015) were associated with worse outcomes. Age, cystic metastases, inclusion of surgical corridor, and tumor location were not significantly related to local control. Radiation necrosis occurred in 13% of patients, predominantly asymptomatic. Conclusion Postoperative SRT provides effective local control in resected BCBM. In multivariable analysis, HER2 positivity, higher BED, and timely SRT significantly influenced outcomes, while larger tumor size and delayed treatment were negative prognostic factors. Future research should optimize dosimetric strategies and integrate systemic therapy to improve local and intracranial control.

Background Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts. The aim of this study was to assess the expression of EphB6 in pituitary tumors. Methods and Results Human normal pituitaries and pituitary tumors were examined for EphB6 mRNA expression using real-time PCR and for EphB6 protein by immunohistochemistry and Western blotting. EphB6 was highly expressed in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) versus the normal pituitary and GH-secreting PitNETs. EphB6 mRNA expression was correlated with tumor size. Conclusions Our results suggest EphB6 aberrant expression in NF-PitNETs. Future studies are warranted to determine the role and significance of EphB6 in NF-PitNETs tumorigenesis.

One hundred and seventeen patients with cavernous sinus meningiomas had LINAC radiosurgery at our institution in the period 1993–2007. Six cases were lost and 9 had less than 1 year follow up. The remaining 102 patients were prospectively followed up at 1 y intervals with clinical, neuro-ophthalmological and MRI examinations. Patients’ age ranged between 31 and 86 years (mean 57). Seventy percent were females. The mean tumor volume was 7 cc. Thirty-three patients had previous microsurgery. Tumors were defined with high resolution MRI obtained 1–2 days before treatment and fused to stereotactic CT. Treatment was mostly delivered through a minimultileaf collimator and multiple dynamic arcs. The minimal dose to the tumor margin was 12–17.5 Gy (mean 13.5) encompassed by the 80% isodose shell. Radiation dose to the optic apparatus was kept below 10 Gy. Follow up ranged from 12 to 180 months (mean 67 months). Tumor control (lack of growth) was 98% (58% of the tumors reduced their volumes). Sixty-four patients presented with cranial nerve deficit. Thirty-nine percent improved or resolved following radiosurgery. Cranial neuropathy had significantly higher resolution rates when radiosurgery was performed early (<1 year) after its appearance (53% as opposed to 26%) even in patients with deficits post surgery. Complications were seen in five patients (1 with deafferentation pain, 1 with facial hypesthesia, 1 with visual loss and 2 with partial VI neuropathy). Radiosurgery had a high control rate for meningiomas of the cavernous sinus with few and mild complications. Cranial neuropathy can be solved by treatment, particularly those of recent onset.

Nonfunctioning pituitary adenomas (NFPAs) are the most common type of pituitary adenomas diagnosed in older patients. However, there are insufficient data regarding the clinical course, risk of regrowth, and long-term prognosis in elderly versus younger patients. This retrospective cohort study observed 105 adult patients with NFPAs diagnosed between 1995 and 2012. Patients were stratified into 3 age groups: 18 to 44 years (29 patients), 45 to 64 years (38 patients), and 65 years and over (38 patients). The impact of age on presenting symptoms, disease course, and outcome was analyzed. Adenoma size was larger in patients <45 years (mean, 2.9 ± 1.2 cm) compared to patients aged 45 to 64 years and those ≥65 years old (2.3 ± 0.9 and 2.5 ± 0.8 cm, respectively; P = .05), with transsphenoidal surgery being the treatment of choice in all 3 groups (83, 92, and 84%, not significant). After a mean follow-up of 6 years, there were higher recovery rates from hypopituitarism in patients <45 years old (58% vs. 27% and 24%; P = .04). Visual fields improved in most affected patients in each group following surgery (74, 94, and 86%), with a trend toward more full normalization in the youngest age group (58% vs. 44% and 41%; P = .09). There were no significant differences in the risk of remnant growth (29 to 39%), rates of radiation therapy, or need for repeated surgeries. There was no disease-related mortality. Elderly patients with NFPA have lower rates of recovery from hypopituitarism after treatment compared to younger patients, but the rates of regrowth and need for salvage surgery are similar.