History of Treatment of Pineal Tumors.

Objective To investigate the value of endoscopic biopsy and third ventriculostomy in the diagnosis and treatment of pineal germ cell tumors. Methods Endoscopic biopsy and third ventricuiostomy were performed in 20 patients with pineal tumors to relieve obstructive hydrocephalus and determine the nature of the neoplasms. Results CT and magnetic resonance imaging confirmed successful third ventriculostomy and biopsy in the 20 cases with total relief of obstructive hydrocephalus. The diagnoses of germ cell tumors were established in all this cases. Conclusions Endoscopic biopsy and third ventriculostomy are effective and safe neuroendoscopic procedures in minimally invasive management of pineal region germ cell tumors. Key words: Neuroendoscopy; Pineal germ cell tumors; Third ventriculostomy; Endoscopic biopsy

Background: The pineal gland, a small, pinecone-shaped organ deep within the brain, is responsible for producing melatonin. The gland consists of pineal parenchymal cells and glial cells that can form neoplasms. Pineal region neoplasms can also arise from germ cells and adjacent structures. This review focuses on detection of serum and cerebrospinal fluid (CSF) biomarkers of germ cell tumors and pineal parenchymal cell tumors, as these types comprise most neoplasms specific to the pineal region. Methods: For this review, we searched PubMed using the following keywords: biomarkers, germ cell tumor, germinoma, melatonin, pineal, pineal gland, pineal neoplasm, pinealoma, pineal parenchymal cell tumor, pineal region, and pineal tumor. We limited our search to full-text English articles and identified other relevant sources from the reference lists of identified articles. Results: Serum and CSF biomarker assays have a role in cases of suspected pineal germ cell or parenchymal neoplasms. Biomarkers including alpha-fetoprotein, beta-human chorionic gonadotropin, and placental alkaline phosphatase inform diagnosis and treatment and are important for monitoring germ cell tumor response to treatment. No biomarkers are currently available that inform diagnosis or treatment of pineal parenchymal tumors, although melatonin assays may have a role in monitoring response to treatment. Conclusion: Serum and CSF biomarkers in conjunction with clinical and radiographic evidence of a pineal region mass can inform the decision whether to undertake stereotactic biopsy or surgical excision or whether to proceed straight to medical treatment.

The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase (Aanat) transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up-regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice. Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis.

BackgroundCultural traditions attribute to pineal gland an important role for spiritual experiences. Mediumship and spirit possession are cultural phenomena found worldwide which have been described as having dissociative and psychotic‐like characteristics, but with nonpathological aspects. A sympathetic activation pattern in response to spirit possession has been reported in some studies, but empirical data on pineal gland is scarce in this context.MethodsWe aimed to investigate pineal gland and pituitary volumes, as well as urinary 6‐sulfatoxymelatonin levels in 16 alleged mediums (Medium Group‐MG) compared with 16 healthy nonmedium controls (Control Group) (Experiment 1). Furthermore, we aimed to evaluate urinary 6‐sulfatoxymelatonin and stress reactivity in GM (n = 10) under different physiological conditions (Experiment 2).ResultsIn Experiment 1, MG presented higher scores of anomalous experiences, but there were no between‐group differences regarding mental health or subjective sleep quality. Similar pineal gland and pituitary volumes were observed between groups. There were no between‐group differences in urinary 6‐sulfatoxymelatonin collected under equivalent baseline conditions. In Experiment 2, the rise of anxiety and heart rate in response to mediumistic experience was intermediate between a nonstressful control task (reading) and a stressful control task (Trier Social Stress Test—TSST). No significant differences were observed in 6‐sulfatoxymelatonin urinary levels between the three conditions. The pattern of stress reactivity during the TSST was normal, but with an attenuated salivary cortisol response.ConclusionThe normal neuroimaging and stress reactivity findings in MG contrast with the abnormal results usually observed in subjects with psychotic and dissociative disorders.

Central nervous system disease is globally common with dysfunction of the brain and spinal cord, which significantly affects the quality of life, such as sleep disturbances. Pineal gland is pivotal in regulating sleep cycles and circadian rhythms. And melatonin, secreted by pineal gland, promotes neurodevelopment and maintains neurohomeostasis, which is also pivotal in the modulation of central nervous system disorders. In recent years, studies have found that patients with central nervous system damage often have degeneration of the pineal gland, characterized by a decrease in pineal gland volume, reduced melatonin secretion, and even parenchymal calcification. An increasing number of Alzheimer's disease patients have been observed to exhibit pineal gland calcification. Research suggests that sleep disturbances accompanying central nervous system disorders can be attributed to the degeneration of pineal gland function, indicating a potential contribution of gland calcification to central nervous system diseases. Here, we review the recent research on pineal gland calculi and discuss the potential relationship between pineal gland calcification and various central nervous system diseases, contributing to a deeper understanding of the intricate mechanisms underlying neurological disorders.

Objective To explore the significance of surgical resection for the pineal region tumor,the extent of tumor resection,the surgical approaches and treatment measures of hydrocephalus.Methods Twentythree patients diagnosed of pineal region cancer were recruited for this study.Thirteen patients received ventriculo-peritoneal shunt(V-P),during which 7 cases received intraoperative end-plate colostomy.Two of the 13 cases received a second V-P procedure.Another 13 cases received operation by corpus callosum- septum-Dome Room-the third ventricle approach to remove the tumor; Eight cases underwent the tumor resection by suboccipital supratentorial approach (Poppen approach )and 2 cases underwent the tumor resection by the infratentorial cerebellar approach( Krause approach).Results Total tumor resection was performed in 11 cases,subtotal or major total resection in 8 cases and partial resection in 4 cases.Nine cases underwent postoperative radiotherapy alone,8 receiving radiotherapy plus chemotherapy,and 6 cases receiving neither radiotherapy nor chemotherapy.Two cases died during treatment.Conclusion Though it is not practicable to completely remove the germ cell tumor in patients with relatively large tumors,cerebrospinal fluid circulation pathways should be reestablished,including ventriculo-peritoneal shunt,colostomy from the end of the third ventricle to the end plate.If tumors are not too large,they would be easy to be removed.The effects on the surrounding brain tissue would not be much significant.If the connection of Ⅲ,V ventricles were normal,the patient may not need shunt or colostomy.Radiotherapy and chemotherapy can be given to this kind of patients after the surgery.To improve the efficacy,other types of tumors,expecially the benign tumors,should be totally removed. Key words: Brain tumor; Pineal region; Surgery

The avian pineal gland, apart from the hypothalamic master clock (suprachiasmatic nuclei, SCN) and retina, functions as an independent circadian oscillator, receiving external photic cues that it translates into the rhythmical synthesis of melatonin, a biochemical signal of darkness. Functional similarity to the mammalian SCN makes the avian pineal gland a convenient model for studies on biological clock mechanisms in general. Pineal melatonin is produced not only in a light-dependent manner but also remains under the control of the endogenous oscillator, while the possible involvement of melatonin in maintaining cyclic expression of the avian clock genes remains to be elucidated. The aim of the present study was to characterize the diurnal profiles of main clock genes transcription in the pineal glands of chickens exposed to continuous light (LL) and supplemented with exogenous melatonin. We hypothesized that rearing chickens from the day of hatch under LL conditions would evoke a functional pinealectomy, influencing, in turn, pineal clock function. To verify this hypothesis, we examined the diurnal transcriptional profiles of selected clock genes as well as the essential parameters of pineal gland function: transcription of the genes encoding arylalkylamine N-acetyltransferase (Aanat), a key enzyme in melatonin biosynthesis, and the melatonin receptor (Mel1c), along with the blood melatonin level. Chickens hatched in summer or winter were maintained under LD 16:8 and 8:16, corresponding to the respective photoperiods, as the seasonal control groups. Another set of chickens was kept in parallel under LL conditions and some were supplemented with melatonin to check the ability of exogenous hormone to antagonize the effects evoked by continuous light. Twelve-day-old chickens were sacrificed every 3 h over a 24-h period and the mRNAs of selected clock genes, Bmal1, Cry1, Per3, E4bp4, together with those of Aanat and Mel1c, were quantified in the isolated pineal glands. Our results indicate that the profiles of clock gene transcription are not dependent on the duration of the light phase, while LL conditions decrease the amplitude of diurnal changes, but do not abolish them entirely. Melatonin supplied in drinking water to the birds kept in LL seems to desynchronize transcription of the majority of clock genes in the summer, while in the winter, it restores the pattern, but not the diurnal rhythmicity. Rhythmic expression of Bmal1 appears to provide a direct link between the circadian clock and the melatonin output pathway, while the availability of cyclic melatonin is clearly involved in the canonical transcription pattern of Per3 in the chicken pineal gland. Regardless of the experimental conditions, a negative correlation was identified between the transcription of genes involved in melatonin biosynthesis (Aanat) and melatonin signal perception (Mel1c receptor).

Pineal organs of poikilotherm animals have photoreceptor cells with cone type structures of disk membranes of the outer segment. In the lamprey, Lampetra japonica, photoreceptors responded to light at 6 X 10(-4) lux as a threshold with hyperpolarization, which modulated the spike discharge of the ganglion cells. Electrophysiological data and high performance liquid chromatography analysis of visual pigments of the pineal suggested the presence of several types of photoreceptor cells. Actually, two different immuno-reactivities were observed in photoreceptors by using antibodies against rod specific protein and cone specific protein. Light information of the environment perceived by the pineal organ is transmitted to the central nervous system and contributes to the control of the locomotor activity rhythm of the lamprey.

Psychoactive drugs, pineal gland and affective disorders

THE existence of an active substance in the pineal gland capable of inhibiting gonadotropic hormones is supported by most authors who have studied this problem. On the other hand, nothing has been revealed concerning the mechanism which causes this inhibition. The existence of a direct interaction between the pineal-inhibiting factor and gonadotropic hormones does not seem likely. In connexion with investigations carried out on anti-androgenic fractions of bovine pineal gland, one of us claimed that the antigonadotropic function of the pineal gland was exerted at the level of the subcortical centres inhibited by it1.

The pineal gland plays an important role in biological rhythms, circadian and circannual variations, which are key aspects in several headache disorders. Melatonin, the main pineal secreting hormone, has been extensively studied in primary and secondary headache disorders. Altered melatonin secretion occurs in many headache syndromes. Experimental data show pineal gland and melatonin both interfere in headache animal models, decreasing trigeminal activation. Melatonin has been shown to regulate CGRP and control its release. Melatonin has been used successfully as a treatment for migraine, cluster headaches and other headaches. There is a rationale for including the pineal gland as a relevant brain structure in the mechanisms of headache pathophysiology, and melatonin as a treatment option in primary headache.

Pineal Gland and Regulatory Function

Suprasellar Germinomas: 2 Case Reports and Literature Review

Although pinealectomy or blinding resulted in loss of the clarity of the free-running rhythm of locomotor activity and body temperature and reduced the peak level of circulating melatonin rhythms to approximately a half in intact pigeons, neither pinealectomy nor blinding abolished any of these rhythms. However, when pinealectomy and blinding were combined, the rhythms of locomotor activity and body temperature disappeared in prolonged constant dim light, and melatonin concentration was reduced to the minimum level of detection. In order to examine the role of melatonin in the pigeon's circadian system, it was administered either daily or continuously to PX + EX-pigeons in LLdim. Daily administration of melatonin restored circadian rhythms of locomotor activity which entrained to melatonin injections, but continuous administration did not induce any remarkable change of locomotor activity. These results suggest that melatonin synthesized in the pineal body and the eye contributes to circulating melatonin and its rhythmicity is important for the control of circadian rhythms of locomotor activity and body temperature in the pigeon.

Objective To conduct anatomic study of structures and exposure of the posterior third ventricle by simulating superior and inferior transtentorial approach with endoscope and to provide anatomical basis for treatment involving this area with endoscope. Methods Five formalin-fixed cadaver heads (10 sides) were dissected bilaterally. To observe and measure anatomical structures of the posterior third ventricle by endoscopic infratentorial-supracerebellar (midline or paramedian) approach and occipital-tentorial approach with comparison of exposure using different surgical approaches. Results (1) Measurement of anatomical structures: Average number of bridging veins of the cerebellum was 3.6±0.6. The diameter of the vein of Galen was 5.6±0.6 mm. The distance from Habenular commissure to confluence of sinuses was 74.4±6.7 mm and the distance from anterior commissure to confluence of sinuses was 107.2±7.3 mm. (2) Comparison of different surgical approaches: The exposed area of pineal glands was 19.6±2.8 mm2, which was almost the same to that in operations through infratentorial-supracerebellar (midline or paramedian) approach and occipital-tentorial approach. The average of exposed area in splenium of corpus callosum was 55.2±7.9 mm2, 34.7±7.9 mm2 and 44.9±5.9 mm2 , respectively, and in ipsilateral superior colliculus was 153.8±13.4 mm2, 177.5±24.0 mm2 and 197.6±19.8 mm2 , respectively. Both had statistically significant difference (all P<0.05). Conclusions Endoscopic superior and inferior transtentorial approach seems feasible and safe for removal of tumors in the posterior third ventricle. Selection of surgical approaches should be based on the tumor type, size, location and its relationship to the surrounding structures. Key words: Natural orifice endoscopic surgery; Anatomy; Surgical approach; Posterior third ventricle tumor