Intracranial pilocytic astrocytoma with spinal drop metastasis: A case review, discussion of its current management and related literature

Pilocytic astrocytoma (PA) is a low grade benign tumor, commonly occurs in Cerebellum (42-60%), Optic & hypothalamic region (9-30%), Brain Stem (9%). They rarely spread. It rarely occurs within the ventricle. In this report, we described our experience with cranial pilocytic astrocytoma in a 14-year-old child, who initially treated with near total decompression of tumor. Four and half years later, recurrence of primary tumor with obstructive hydrocephalus occurred for which he underwent ventriculo-peritoneal shunt followed by re-excision. As further treatment was being evaluated for radiotherapy in view of recurrence at the primary site, he got detected to have significant spinal drop metastasis seen on MRI Spine. Finally, he underwent craniospinal irradiation (CSI).

The impact of extent of resection in surgical outcome of pilomyxoid astrocytoma: a case study

The pilomyxoid astrocytoma (PMA) is a rare glioma that has recently been identified as a separate entity and is frequently found in the hypothalamic region. PMA is a subtype of pilocytic astrocytoma (PA), with clinical, histological, and molecular data indicating a close relationship as well as more aggressive biological behaviour in the former. There is still doubt in surgical outcome of PMA that the extent of resection, independent of location or age, is a key factor of recurrence and subsequent therapeutic choices. However, further study is needed to better understand its behaviour and, as a result, establish a consensus on its management. This research features a 2-year-6-month-old female who sought medical attention after complaining of weight loss for four weeks and vomiting for two weeks prior to her visit to the doctor. She had no additional symptoms. Only bilateral pailledema was found during the physical examination. The magnetic resonance imaging (MRI) scans revealed a tumor in the sellar area with heterogeneous enhancement. The patient had ventriculoperitoneal (VP) shunting followed by partial tumor excision twice (Extent of resection 35 percent followed by 16 percent as total 51 percent). The histology and immunohistochemical investigations revealed typical PMA characteristics. Adjuvant treatment, which included chemotherapy and radiosurgery, was initiated for the patient. She has been asymptomatic for two years and has showed no indications of progression of the disease on follow-up scans.

Restricted proliferation during neurogenesis contributes to regionalization of the amphioxus nervous system.

The central nervous system of the cephalochordate amphioxus consists of a dorsal neural tube with an anterior brain. Two decades of gene expression analyses in developing amphioxus embryos have shown that despite the lack of overt segmentation the amphioxus neural tube is highly regionalized at the molecular level. However, little is known about the mechanisms that generate such precise regionalization. Proliferation is a key driver of pattern formation and cell type diversification, but in amphioxus it has never been studied in detail nor in the specific context of neurogenesis. Here, we describe the dynamics of cell division during the formation of the central nervous system in amphioxus embryos and its contributions to the regionalization of the neural axis. We show that after gastrulation, proliferation pauses to become spatially restricted to the anterior and posterior ends of the neural tube at neurula stages. Only at the onset of larval life, proliferation resumes in the central part of the nervous system. By marking specific populations and inhibiting cell division during neurulation, we demonstrate that proliferation in the anterior cerebral vesicle is required to establish the full cell type repertoire of the frontal eye complex and the putative hypothalamic region of the amphioxus brain, while posterior proliferating progenitors, which were found here to derive from the dorsal lip of the blastopore, contribute to elongate the caudal floor plate. Between these proliferative domains, we find trunk nervous system differentiation is independent from cell division, which decreases during neurulation and resumes at the early larval stage. Taken together, our results highlight multiple roles for proliferation in shaping the amphioxus nervous system.

Disorders of sodium balance in patients with hypothalamic-pituitary lesions in traumatic brain injury

Background. Traumatic brain injury (TBI) still remains the leading cause of death in people of working age. In Ukraine, the frequency of TBI varies from 2.3 to 6 cases (average of 4–4.2) per 1,000 population annually depending on the regions. Patients with primary damage to the brain and hypothalamic-pituitary system are at risk of developing cerebral edema due to the water-electrolyte imbalance and, accordingly, osmolar imbalance between cellular and extracellular spaces. Water-electrolyte imbalance as a result of damage to the hypothalamic-pituitary system in traumatic brain injury is not described enough in the literature. The functioning of the central and peripheral links of the endocrine system depending on the location, nature and severity of injury is examined not enough. The question of diagnostic and prognostic values of various indicators of volume status in patients with trauma is also underinvestigated. The purpose of this study was to examine the types of disorders of sodium balance in patients with isolated TBI and hypothalamic-pituitary lesions; to clarify the influence of sodium imbalance type on mortality in patients with TBI and hypothalamic-pituitary lesions. Material and methods. We examined 74 patients (men/women = 60/14) with focal cerebral contusion and lesions of the hypothalamic region. Forty-seven of them were diagnosed with hypovolemia combined with hyponatremia. Hypernatremia with hypervolemia was found in 15 patients. Intracranial pressure monitoring was performed using a multifunction monitor (BSM-3562, Japan, 2018, Nihon Kohden Corporation) with a line for invasive pressure measurement. Continuous non-invasive measurement of organ tissue oxygenation (rSO2) was carried out using Somanetics Invos Oximeter Cerebral/Somatic monitor (Covidien, Mansfield, MA, USA, 2020). Plasma electrolytes were evaluated in all patients. Conclusions. Patients with TBI and hypothalamic-pituitary lesion have different types of water-sodium imbalance, which demand the differentiated approach to their treatment. Given the small number of observations, we do not dare to link the type of sodium imbalance with lethality in patients with brain trauma and hypothalamic-pituitary lesions. We consider this requires further researches.

Inhibitory Effects of Trifluoperazine on Peripheral Proinflammatory Cytokine Expression and Hypothalamic Microglia Activation in Obese Mice Induced by Chronic Feeding With High-Fat-Diet

Microglia and astrocytes are the glial cells of the central nervous system (CNS) to support neurodevelopment and neuronal function. Yet, their activation in association with CNS inflammation is involved in the initiation and progression of neurological disorders. Mild inflammation in the periphery and glial activation called as gliosis in the hypothalamic region, arcuate nucleus (ARC), are generally observed in obese individuals and animal models. Thus, reduction in peripheral and central inflammation is considered as a strategy to lessen the abnormality of obesity-associated metabolic indices. In this study, we reported that acute peripheral challenge by inflammagen lipopolysaccharide (LPS) upregulated the expression of hypothalamic dopamine type 2 receptor (D2R) mRNA, and chronic feeding by high-fat-diet (HFD) significantly caused increased levels of D2R in the ARC. The in vitro and in vivo studies indicated that an FDA-approved antipsychotic drug named trifluoperazine (TFP), a D2R inhibitor was able to suppress LPS-stimulated activation of microglia and effectively inhibited LPS-induced peripheral inflammation, as well as hypothalamic inflammation. Further findings showed daily peripheral administration intraperitoneally (i.p.) by TFP for 4 weeks was able to reduce the levels of plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in accompany with lower levels of plasma glucose and insulin in obese mice receiving HFD for 16 weeks when compared those in obese mice without TFP treatment. In parallel, the activation of microglia and astrocytes in the ARC was also inhibited by peripheral administration by TFP. According to our results, TFP has the ability to suppress HFD-induced ARC gliosis and inflammation in the hypothalamus.

Sleep disturbances in craniopharyngioma: a challenging diagnosis

Craniopharyngiomas are rare solid or mixed solid and cystic tumors that arise from Rathke’s pouch remnants along the pituitary-hypothalamic axis, from the sella turcica to the brain third ventricle. Both the tumor and its treatment can lead to significant neurological and endocrinological complications. Due to the essential role of the hypothalamus in the complex neurophysiologic process of sleep, tumors involving the hypothalamic area may be responsible for disturbances in sleep–wake regulation with alterations in the circadian rhythm, sleep fragmentation, and increased daytime sleepiness. We report two cases of patients with craniopharyngioma, who came to our attention due to the occurrence of episodes characterized by psychomotor slowing and afinalistic limb movements, temporal and spatial disorientation, psychomotor agitation, and oneiric stupor like episodes. A comprehensive clinical data collection and a targeted diagnostic work-up led to a diagnosis of severe sleep disorder characterized by hypersomnia, altered sleep–wake rhythm, and sleep-related breathing disorder. In addition, the polysomnography revealed peculiar alterations in the sleep structure. The diagnostic work-up lead to an accurate differential diagnosis between epileptic seizures and episodes expressions of sleep disturbances. These clinical features can be challenging to diagnose and can lead to misdiagnosis and inappropriate treatment. Diagnosis of sleep disorders is crucial, considering the impact of sleep on general health, cognition, and neuropsychological functioning. These findings support the need to incorporate a comprehensive sleep evaluation in childhood brain tumor involving the suprasellar/hypothalamic region.

The Dopamine D2R Antagonist Trifluoperazine Suppresses High-Fat Diet-Induced Hyperglycemia and Hypothalamic Gliosis in Obese Mice

Microglia, the resident macrophages of the central nervous system (CNS), as well as astrocytes, are CNS glia cells to support neurodevelopment and neuronal function. Yet, their activation-associated with CNS inflammation is involved in the initiation and progression of neurological disorders. Mild inflammation in the periphery and glial activation called gliosis in the hypothalamic region, arcuate nucleus (ARC), are generally observed in the obese individuals and animal models. Thus, reduction in peripheral and central inflammation is considered as a strategy to lessen the abnormality of obesity-associated metabolic indices. In this study, we reported that acute peripheral challenge by inflammagen lipopolysaccharide (LPS) triggered an upregulation of hypothalamic dopamine type 2 receptor (D2R) expression, and chronic feeding by high fat diet (HFD) caused an increased levels of D2R in the ARC. The in vitro and in vivo studies indicated that a D2R antagonist named trifluoperazine (TFP) was able to suppress LPS-stimulated activation of microglia and effectively inhibited LPS-induced peripheral inflammation, as well as hypothalamic inflammation. Further findings showed daily peripheral administration intraperitoneally (i.p.) by TFP for 4 weeks was able to reduce the levels of plasma and hypothalamic tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in obese mice receiving HFD for 16 weeks. Moreover, plasma glucose and insulin were effectively decreased by daily treatment with TFP for 4 weeks. In parallel, microglia and astrocytes in the ARC was also inhibited by peripheral administration by TFP. According to our results, TFP has the ability to suppress HFD-induced hyperglycemia, inflammation and gliosis in hypothalamus.

Lithium Enhances the GABAergic Synaptic Activities on the Hypothalamic Preoptic Area (hPOA) Neurons

Lithium (Li+) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area contains GABAergic and glutamatergic neurons and their receptors, which regulate various hypothalamic functions such as the release of neurohormones, control circadian activities. At the neuronal level, several neurotransmitter systems are modulated by lithium exposure. However, the effect of Li+ on hypothalamic neuron excitability and the precise action mechanism involved in such an effect have not been fully understood yet. Therefore, Li+ action on hypothalamic neurons was investigated using a whole-cell patch-clamp technique. In hypothalamic neurons, Li+ increased the GABAergic synaptic activities via action potential independent presynaptic mechanisms. Next, concentration-dependent replacement of Na+ by Li+ in artificial cerebrospinal fluid increased frequencies of GABAergic miniature inhibitory postsynaptic currents without altering their amplitudes. Li+ perfusion induced inward currents in the majority of hypothalamic neurons independent of amino-acids receptor activation. These results suggests that Li+ treatment can directly affect the hypothalamic region of the brain and regulate the release of various neurohormones involved in synchronizing the neuroendocrine axis.

Novel Neuroimaging Biomarker for Sleep Quality in Insomnia Disorder: A Hypothalamus Resting State Study

Despite striking progress in the understanding of the neurobiology of insomnia disorder (ID), about 40% of ID patients do not reach sustained remission with the primary treatments. It is necessary to reveal novel neuroimaging biomarkers for sleep quality in ID. The hypothalamus has a central role in sleep-wake regulation by communicating with different brain regions. However, the functional implications of hypothalamus circuitry with other brain areas remains largely unknown in ID. It may be speculated that dysfunctional circuitry in the hypothalamus is involved in the pathogenesis of ID. Thus, we investigated the different network organizations of the bilateral hypothalamus during the resting-state between 26 ID patients and 28 healthy controls (HC). Correlation analysis has been carried out to link the neuroimaging findings and Pittsburgh sleep quality index (PSQI) scores. Group comparisons reveal that the resting-state functional connectivity (RSFC) between the left hypothalamic region and a few other brain regions, including the medial prefrontal cortex (mPFC) and pallidum, are significantly higher in ID compared with HC. The right inferior temporal cortex showed reduced RSFC with the left hypothalamus. No significantly different RSFC between ID and HC was detected for the right hypothalamus. Positive correlations with PSQI scores were observed for RSFC strength between the left hypothalamus and bilateral mPFC (left: r = 0.2985, p = 0.0393; right: r = 0.3723, p = 0.0056). Similarly, the RSFC strength between the right hypothalamus and bilateral mPFC (left: r = 0.3980, p = 0.0029; right: r = 0.2972, p = 0.0291) also showed significant positive correlations with PSQI scores. In conclusion, we reveal a novel neuroimaging biomarker for sleep quality, i.e., the RSFC strength of the hypothalamus-mPFC pathway. Consistent with the hyperarousal model of ID, our results shed new insights into the implications of the hyper-connection within hypothalamus circuits in the pathology of the ID.