Mouse Models in Circadian Rhythm and Melatonin Research.

This contribution reviews the role of inbred and transgenic mouse strains for deciphering the mammalian melatoninergic and circadian system. It focusses on the pineal organ as melatonin factory and two major targets of the melatoninergic system, the suprachiasmatic nuclei (SCN) and the hypophysial pars tuberalis (PT). Mammalian pinealocytes sharing molecular characteristics with true pineal and retinal photoreceptors synthesize and secrete melatonin into the blood and cerebrospinal fluid night by night. Notably, neuron-like connections exist between the deep pinealocytes and the habenular/pretectal region suggesting direct pineal-brain communication. Control of melatonin biosynthesis in rodents involves transcriptional regulation including phosphorylation of CREB and upregulation of mPer1. In the SCN, melatonin acts upon MT1 and MT2 receptors. Melatonin is not necessary to maintain the rhythm of the SCN molecular clockwork, but it has distinct effects on the synchronization of the circadian rhythm by light, facilitates re-entrainment of the circadian system to phase advances in the level of the SCN molecular clockwork by acting upon MT2 receptors and plays a stabilizing role in the circadian system as evidenced from locomotor activity recordings. While the effects in the SCN are subtle, melatonin is essential for PT functions. Via the MT1 receptor it drives the PT-intrinsic molecular clockwork and the retrograde and anterograde output pathways controlling seasonal rhythmicity. Although inbred and transgenic mice do not show seasonal reproduction, the pathways from the PT are fully intact if the animals are melatonin proficient. Thus, only melatonin-proficient strains are suited to investigate the circadian and melatoninergic systems.

[Surgery for Pineal Region Tumors: Concept and Technical Aspects of Occipital Transtentorial Approach].

This article describes the concept and technical aspects of the occipital transtentorial approach(OTA)for tumor extraction in the pineal region, based on the author's experience and literature review. Awareness of the successful completion of each surgical step is essential. Preoperative preparation and imaging evaluations, with particular attention to the veins and venous sinuses, are especially important. It is also helpful to perform a complete dura incision and inversion up to the edge of confluence, superior sagittal sinus, and transverse sinus. Subsequently, it is necessary to understand the usefulness of adequate dissection in the vicinity of the corpus callosum and internal occipital vein(IOV)so that the occipital lobe can be moved without difficulty. Furthermore, development of the IOV with adequate tentoriotomy facilitates contralateral work. Finally, complete understanding of each step during the bilateral, ambient cistern and cerebellomesencephalic fissure dissection process, where the cerebellar vermis can be moved without difficulty, is necessary for a safe OTA to pineal region tumor extraction.

Dual sources of melatonin and evidence for different primary functions.

This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin, herein referred to as Source #1, is the pineal gland. In this organ, melatonin production is circadian with maximal synthesis and release into the blood and cerebrospinal fluid occurring during the night. Of the total amount of melatonin produced in mammals, we speculate that less than 5% is synthesized by the pineal gland. The melatonin rhythm has the primary function of influencing the circadian clock at the level of the suprachiasmatic nucleus (the CSF melatonin) and the clockwork in all peripheral organs (the blood melatonin) via receptor-mediated actions. A second source of melatonin (Source # 2) is from multiple tissues throughout the body, probably being synthesized in the mitochondria of these cells. This constitutes the bulk of the melatonin produced in mammals and is concerned with metabolic regulation. This review emphasizes the action of melatonin from peripheral sources in determining re-dox homeostasis, but it has other critical metabolic effects as well. Extrapineal melatonin synthesis does not exhibit a circadian rhythm and it is not released into the blood but acts locally in its cell of origin and possibly in a paracrine matter on adjacent cells. The factors that control/influence melatonin synthesis at extrapineal sites are unknown. We propose that the concentration of melatonin in these cells is determined by the subcellular redox state and that melatonin synthesis may be inducible under stressful conditions as in plant cells.

Melatonin in energy control: Circadian time-giver and homeostatic monitor.

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical-scavenging, and anti-inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time-giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity.

Optic nerve sheath diameter correlates with both success and failure of hydrocephalus treatment in pediatric patients with pineal region lesions.

BACKGROUND: Pineal region lesions in children are heterogenous pathologies often symptomatic due to occlusive hydrocephalus and thus elevated intracranial pressure (ICP). MRI-derived parameters to assess hydrocephalus are the optic nerve sheath diameter (ONSD) as a surrogate for ICP and the frontal occipital horn ratio (FOHR), representing ventricle volume. As elevated ICP may not always be associated with clinical signs, the adjunct of ONSD could help decision making in patients undergoing treatment. The goal of this study is to assess the available magnetic resonance imaging (MRI) of patients with pineal region lesions undergoing surgical treatment with respect to pre- and postoperative ONSD and FOHR as an indicator for hydrocephalus. METHODS: Retrospective data analysis was performed in all patients operated for pineal region lesions at a tertiary care center between 2010 and 2023. Only patients with pre- and postoperative MRI were selected for inclusion. Clinical data and ONSD at multiple time points, as well as FOHR were analyzed. Imaging parameter changes were correlated with clinical signs of hydrocephalus before and after surgical treatment. RESULTS: Thirty-three patients with forty operative cases met the inclusion criteria. Age at diagnosis was 10.9 ± 4.6 years (1-17 years). Hydrocephalus was seen in 80% of operative cases preoperatively (n = 32/40). Presence of hydrocephalus was associated with significantly elevated preoperative ONSD (p = 0.006). There was a significant decrease in ONSD immediately (p < 0.001) and at 3 months (p < 0.001) postoperatively. FOHR showed a slightly less pronounced decrease (immediately p = 0.006, 3 months p = 0.003). In patients without hydrocephalus, no significant changes in ONSD were observed (p = 0.369). In 6/6 patients with clinical hydrocephalus treatment failure, ONSD increased, but in 3/6 ONSD was the only discernible MRI change with unchanged FOHR. CONCLUSIONS: ONSD measurements may have utility in evaluating intracranial hypertension due to hydrocephalus in patients with pineal region tumors. ONSD changes appear to have value in assessing hydrocephalus treatment failure.

Effect of Melatonin on Herpesvirus Type 1 Replication.

Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation, which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by immunofluorescence, indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.

Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

Homeobox gene-encoded transcription factors in development and mature circadian function of the rodent pineal gland.

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene-encoded transcription factors in developmental and circadian mature neuroendocrine function.

Constant light and pinealectomy disrupt daily rhythm in song production and negatively impact reproductive performance in zebra finches.

We assessed the circadian clock control of singing and reproductive performance in zebra finches. Experiment 1 examined changes in body mass, testis size, and plasma corticosterone and testosterone levels in male birds exposed to constant light (LL, 100 lx) and constant darkness (DD, 0.5 lx), with controls on 12L:12D (L = 100 lx, D = 0.5 lx). There was a significant increase in the body mass and testis size under LL and a decrease in testis size under the DD. Using a similar design, experiment 2 assessed the persistence of the circadian rhythm in singing along with activity-rest pattern in cohort I birds that were entrained to 12L:12D and subsequently released in DD or LL, and in cohort II birds that were entrained to 12L:12D and following pinealectomy were released in DD. Both activity and singing patterns were synchronized with the light phase under 12L:12D, free-ran with a circadian period under DD, and were arrhythmic under the LL. There was an overall decreased and increased effect on singing under DD and LL, respectively, albeit with differences in various song parameters. The pinealectomy disrupted both activity and singing rhythms but did not affect singing or the overall song features. Pinealectomized bird pairs also exhibited a significant reduction in their nest-building and breeding efforts, resulting in a compromised reproductive performance. These results suggest a circadian clock control of singing and more importantly demonstrate a role of the pineal clock in breeding behaviors, leading to a compromised reproductive performance in diurnal zebra finches.

Autonomic dysfunction in patients with tectal plate compression: A systematic review.

INTRODUCTION: Pineal region lesions can result in tectal plate compression, hydrocephalus, and associated symptoms including headache, Parinaud's Syndrome, and epileptic phenomena. No studies have looked at the relationship between these lesions and the autonomic nervous system. METHODS: To evaluate the clinical presentation of pineal lesions secondary to tectal plate compression with a focus on autonomic dysfunction, a systematic review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Case reports and prospective and retrospective studies on patients with pineal or tectal region lesions were included. RESULTS: Of 73 identified studies, 43 underwent full text screening. 26 studies (n=363 patients; age range 0-69 years) were included. 47.1% of patients were male (n=171). Obstructive hydrocephalus was identified in 119 patients (32.8%). The most common symptom was headache (n=228, 62.8%), followed by epileptic phenomena (n=76, 20.9%). Vision related symptoms were identified in 88 patients (24.2%). 251 patients (69.1%) had symptoms associated with autonomic dysfunction including dizziness, nausea, pupillary dysfunction, photophobia and fatigue. Of the 200 (55%) patients who underwent surgery, 135 patients (67.5%) had improved or resolved symptoms post-operatively, including 120 patients with improved autonomic dysfunction symptoms. CONCLUSIONS: Though these lesions are most characterized by Parinaud's syndrome and hydrocephalus, this review suggests dysfunction of the autonomic nervous system may be at play and require consideration at initial presentation and treatment.

The first pineoblastoma case report of a patient with Sotos syndrome harboring NSD1 germline mutation.

Germline mutations of NSD1 are associated with Sotos syndrome, characterized by distinctive facial features, overgrowth, and developmental delay. Approximately 3% of individuals with Sotos syndrome develop tumors. In this study, we describe an infant in pineoblastoma with facial anomalies, learning disability and mild autism at 1 years diagnosed as Sotos syndrome owing to carrying a novel mutation de novo germline NSD1 likely pathogenic variant. This patient expands both the mutation and phenotype spectrum of the Sotos Syndrome and provides new clinical insights into the potential mechanism of underlying pinealoblastoma pathology.

Circadian patterns and photoperiodic modulation of clock gene expression and neuroendocrine hormone secretion in the marine teleost Larimichthys crocea.

The light/dark cycle, known as the photoperiod, plays a crucial role in influencing various physiological activities in fish, such as growth, feeding and reproduction. However, the underlying mechanisms of this influence are not fully understood. This study focuses on exploring the impact of different light regimes (LD: 12 h of light and 12 h of darkness; LL: 24 h of light and 0 h of darkness; DD: 0 h of light and 24 h of darkness) on the expression of clock genes (LcClocka, LcClockb, LcBmal, LcPer1, LcPer2) and the secretion of hormones (melatonin, GnRH, NPY) in the large yellow croaker, Larimichthys crocea. Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assays were utilized to assess how photoperiod variations affect clock gene expression and hormone secretion. The results indicate that changes in photoperiod can disrupt the rhythmic patterns of clock genes, leading to phase shifts and decreased expression. Particularly under LL conditions, the pineal LcClocka, LcBmal and LcPer1 genes lose their rhythmicity, while LcClockb and LcPer2 genes exhibit phase shifts, highlighting the importance of dark phase entrainment for maintaining rhythmicity. Additionally, altered photoperiod affects the neuroendocrine system of L. crocea. In comparison to the LD condition, LL and DD treatments showed a phase delay of GnRH secretion and an acceleration of NPY synthesis. These findings provide valuable insights into the regulatory patterns of circadian rhythms in fish and may contribute to optimizing the light environment in the L. crocea farming industry.

[Neurosurgical treatment of tumors of the pineal region - literature review and overview of cases at OMIII]. / A pineális régió tumorainak idegsebészeti ellátása ­ irodalmi áttekintés és az OMIII beteganyagának vizsgálata.

Pineal region tumors account for less than 1% of adult supratentorial tumors. Their treatment requires a multimodality approach. Previously, the treatment of choice was direct surgery, which is associated with high surgical risk. Advances in minimally invasive techniques and onco-radiotherapy offer a safe and multimodal personalized therapy. The aim of our study was to describe the practice of our Institute based on combined endoscopic and radiotherapy techniques. We performed a retrospective clinical study. We processed data from 23 adult patients who underwent endoscopic third ventricle fenestration and pineal tumor biopsy between 2014 and 2023. Descriptive statistics, t-test, Fisher's exact test and Kaplan-Meier analysis were performed. Clinical improvement with endoscopic intervention was achieved in 78.3% of cases. Significant increase in preoperative performance status was observed in the postoperative period (p=2.755e-5), and radiotherapy resulted in regression or stable disease. Our results suggest a safe treatment with good clinical outcome and an excellent alternative to direct surgery.

Role of Melatonin in Viral, Bacterial and Parasitic Infections.

In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night's darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role. Circulating MLT may stimulate both innate and acquired immune responses through its circadian action and by activating high-affinity receptors on immunocompetent cells. Extra-pineal MLT may have antioxidant and anti-inflammatory effects that dampen the innate immune response. These two seemingly divergent roles may be considered to be two sides of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effects of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility of integrating the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite of the fact that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

[Microsurgical ventriculostomy of the third ventricle with access through a burrhole in the treatment of midly located deep-seated brain tumors]. / Mikrokhirurgicheskaya ventrikulostomiya III zheludochka s dostupom cherez frezevoe otverstie v lechenii sredinno raspolozhennykh glubinnykh opukholei golovnogo mozga.

BACKGROUND: Currently, endoscopic third ventriculostomy and simultaneous biopsy of deep midline brain tumors are a generally accepted option in neurooncology. Nevertheless, effectiveness of this surgery and diagnostic accuracy of biopsy are not without drawbacks. An alternative to endoscopic surgery may be simultaneous microsurgical third ventriculostomy and biopsy of deep midline tumors. OBJECTIVE: To evaluate effectiveness and safety of burr hole microsurgical third ventriculostomy in the treatment of deep midline brain tumors. MATERIAL AND METHODS: We used transcortical (25 cases) and transcallosal (8 cases) approaches for microsurgical third ventriculostomy. RESULTS: Initially scheduled biopsy was performed in 19 cases, partial resection in 6 cases, subtotal resection in 4 cases and total resection in 4 cases. All patients underwent microsurgical third ventriculostomy. In 12 cases, stenting of stoma was performed in addition to ventriculostomy. Biopsy was informative in all cases. Postoperative follow-up period ranged from 3 to 44 months (mean 29 months). There was no postoperative hydrocephalus and need for shunting procedure. CONCLUSION: Burr hole microsurgery may be an alternative to endoscopic surgery for the treatment of pineal, periaqueductal and third ventricular tumors.

The role of melatonin deficiency induced by pinealectomy on motor activity and anxiety responses in young adult, middle-aged and old rats.

BACKGROUND: Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate their inherited life "clock." The present study aimed to explore the impact of plasma melatonin deficiency on anxiety responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock proteins (Hsp) 70 and 90 in the frontal cortex (FC) and the hippocampus in young adult, middle-aged and elderly rats with pinealectomy. RESULTS: Melatonin deficiency induced at different life stages did not affect the lifespan of rats. Pinealectomy abolished the circadian rhythm of motor activity, measured for 48 h in the actimeter, in young adult but not in middle-aged rats. Pinealectomy reduced the motor activity of the young adult rats during the dark phase and impaired the diurnal activity variations of old rats. The same generations (3- and 18 month-old rats with pinealectomy) had lower anxiety levels than the matched sham groups, measured in three tests: elevated-plus maze, light-dark test, and novelty-suppressed feeding test. While the activity of the HPA axis remained intact in young adult and middle-aged rats with melatonin deficiency, a high baseline corticosterone level and blunted stress-induced mechanism of its release were detected in the oldest rats. Age-associated reduced Hsp 70 and 90 levels in the FC but not in the hippocampus were detected. Pinealectomy diminished the expression of Hsp 70 in the FC of middle-aged rats compared to the matched sham rats. CONCLUSIONS: Our results suggest that while melatonin hormonal dysfunction impaired the motor activity in the actimeter and emotional behavior in young adult and elderly rats, the underlying pathogenic mechanism in these generations might be different and needs further verification.

Papillary Tumors of Pineal Region: A Single-Center Experience in Management of 11 Cases.

BACKGROUND: Papillary tumors of pineal region (PTPR) comprise a very rare subset of pineal region tumors that have been recently described. Literature on the management and outcome of PTPR is scarce owing to the rarity of these tumors. To address this lacuna, we analyzed our experience in management of PTPR. METHODS: We retrospectively analyzed the outcome of 11 patients with histopathologically proven PTPR who underwent surgical excision at our center. RESULTS: Mean patient age was 33.3 years (range, 12-45 years), and male-to-female ratio was 1.75:1. Headache was the most common presentation followed by visual disturbances, altered sensorium, Perinaud syndrome, and seizures. Cerebrospinal fluid diversion was required in 6 patients. Krause approach was the most common approach used for tumor excision (9/11 cases). There was no perioperative mortality. Two patients were lost to follow-up. In the remaining 9 patients, the average follow-up period was 45 months (range, 12-79 months). On first postoperative magnetic resonance imaging, 8 patients showed no evidence of residual tumor (gross total resection), while 1 patient had small residual tumor (near-total resection) that remained stable during follow-up. Four patients underwent adjuvant chemoradiotherapy. None of the patients developed recurrence during follow-up. CONCLUSIONS: PTPR are a rare subgroup of pineal region tumors with distinct cells of origin but presentation similar to other pineal region tumors. Surgical resection constitutes the mainstay of management, and the extent of resection appears to be the most important determinant of prognosis. The role of adjuvant therapy still needs to be determined.

Simultaneous Single-Trajectory Endoscopic Biopsy and Third Ventriculostomy in Pineal Region Tumors: A Systematic Review and Single Arm Meta-Analysis.

OBJECTIVE: To assess the efficacy and surgical outcomes of the simultaneous single-trajectory endoscopic biopsy and third ventriculostomy (ETV) in pineal region tumors. METHODS: A systematic review and meta-analysis adhering to Cochrane Standards and PRISMA framework were conducted. PubMed, Embase, and Web Of Science databases were searched until December 2023. Outcomes included rate of histopathologic diagnosis success, ETV success, complications, required VPS, and mortality. RESULTS: Seventeen studies (N = 388) met inclusion criteria. Histopathologic diagnosis success rate was 90% for general population (95% CI: 86%-95%; I2 = 42%) and 94% for pediatric patients (95% CI: 89%-98%; I2 = 19%). ETV Success rate was 93% (95% CI: 88%-97%; I2 = 60%). An estimated risk of postoperative ETV complications was found to be 16% for the general population (95% CI: 5%-28%; I2 = 90%) and 5% for pediatric patients (95% CI: 0%-13%; I2 = 51%). The risk of requiring VPS was estimated as 2% (95% CI: 0%-4%; I2 = 39%) and for the pediatric population it was 7% (95% CI: 0%-16%; I2 = 69%). Mortality risk was found to be 1% (95% CI: 0%-3%; I2 = 0%). CONCLUSIONS: Simultaneous endoscopic biopsy and ETV demonstrated high diagnostic and therapeutic success rates. The procedure's safety profile, with low mortality and complications, supports its role in treating hydrocephalus associated to pineal region tumors. Subgroup analyses revealed higher diagnostic success rates and required VPS in the pediatric population, whilst it had lower complication rates.