Exploring Links between Pineal Gland Calcification and Central Nervous System Disease

The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives.

Most patients with manic depression and diseases have issues with their circadian rhythms and sleep. Melatonin, which is vital for circadian rhythm and sleep, is secreted by pineal gland. This study evaluated and compared the volume of pineal gland in individuals with psychotic symptoms and manic depression. The aim of study is to find out volume of Pineal glands in Schizophrenic Patients. The data included in this literature review were found using several search engines. Using magnetic resonance imaging, the total mean pineal volume compared with the total pineal gland volume of all patients. In this research's literature evaluation, only 26 articles were used for extraction of data related to topic statement. The current study looked role of MRI to assess volume of pineal gland in in Schizophrenic patients. Patients with manic depression had considerably lower mean volume of pineal gland than the other groups. It is concluded that although more research is needed to fully understand the aspects of medications and more mediating agents on the volume of pineal gland. This difference is not present in patients with manic depression. Pineal gland abnormalities in schizophrenia patients may contribute to the disease's etiology.

Mechanisms of sleep disorders in fibromyalgia (FM) patients, such as insomnia, early morning awakenings and poor quality sleep, have not yet been proven and no consistent and effective treatment is yet available. The aim of this study was to investigate the pineal gland volume and the relationship between total fibre count, total fibre volume and total fibre length of the spinoreticular tract involved in regulation of sleep and wakefulness in terms of the mechanism of sleep disturbance. This study included only female cases, 31 with fibromyalgia and 31 controls. Pittsburgh Sleep Quality Index was used to assess sleep quality. Tractography of targeted pathway from brain diffusion MR images was calculated in Diffusion Studio Imaging (DSI) Studio programme and the volume of the pineal gland was calculated in ITK-SNAP programme. The mean volume of the pineal gland was higher in control group (218.84 ± 64.45 mm3) than in fibromyalgia group (174.77 ± 48.65 mm3), which was statistically significant (p = 0.004). However, there was no statistically significant difference between two groups in total spinoreticular tract (TSRT), total volume (TSRTV), TSRT fractional anisotropy, TSRT mean diffusion, TSRT axial diffusion and TSRT radial diffusion of spinoreticular tract, which is involved in the regulation of sleep and wakefulness (p > 0.05). In conclusion, it is thought that the endocrine system may be more related to sleep disturbance in individuals with FM than central nervous system. Therefore, we believe that it may be more appropriate to work on the endocrine system rather than neural system in the treatment of sleep disturbance in patients with FM.

Multiple sclerosis has a complex pathophysiology, and numerous risk factors can contribute to its development, like exposure to sunlight that is associated with serum levels of melatonin. The aim of this study was to determine whether the volume of the pineal gland, assessed by magnetic resonance imaging (MRI), correlated with the presence of multiple sclerosis. This retrospective study included a total of 394 patients. Subjects were divided into two groups: the first group consisted of 188 patients with a definite diagnosis of multiple sclerosis (based on revised McDonald criteria) and the second group consisted of 206 healthy controls. To examine the influence of age on pineal gland volume, we stratified the whole sample into three age groups: first involved patients under 20 years, second patients between 20 and 40 years, and third group included patients over 40 years. The maximum length (L) and height (H) of the pineal gland were measured on the T1-weighted sagittal images, and the width (W) was measured on the T2-weighted coronal or axial images. The volume of the gland was calculated as an approximation to an ellipse, according to the formula V = (L × H × W)/2. Pineal gland volume of female multiple sclerosis (MS) patients (N = 129) was significantly lower than in healthy females (N = 123) (p = 0.013; p < 0.05), unlike in males where there is not such difference. Also, pineal gland volume is not age-dependent, and the observed smaller pineal gland in MS patients can reliably be attributed to the disease itself. Additionally, large pineal gland size, especially over 62.83 mm3 when compared to pineal gland volume below 31.85 mm3 is associated with more than double reduced risk of multiple sclerosis (OR 0.42; p = 0.003). Our results suggest that women with multiple sclerosis have smaller pineal glands that can theoretically be explained by a lack of input stimuli and the resultant decrease in gland volume. Additionally, the risk of multiple sclerosis is reduced in larger pineal gland volumes.

Safety and Efficacy of Blinatumomab in Patients with Central Nervous System (CNS) Disease: A Single Institution Experience

Sixty-four patients with American Burkitt's lymphoma (AMBL) treated at the National Cancer Institute were reviewed to determine the frequency and characteristics of central nervous system (CNS) involvement. Patients with minimal or completely resected tumor never had CNS disease. Of the 45 patients with more extensive disease, 15 had CNS disease: nine presented with CNS disease, six of whom subsequently had recurrent CNS disease, and six developed CNS disease only at relapse. There was a significant association between CNS and bone-marrow disease at presentation. Therapy of CNS disease consisted of short courses of intrathecal chemotherapy with cytosine arabinoside and methotrexate. Cranial irradiation was given only to patients with CNS relapse. There are six long-term survivors (LTS) who have been disease free for four to six years post chemotherapy. Of these six LTS, three presented with CNS disease, two experienced isolated CNS relapse, and one had CNS disease both at presentation and at relapse. Three of the six LTS never received cranial irradiation. It is concluded that CNS involvement in AMBL can be effectively treated, and that long-term remission, which is probably cure, can be achieved.

Objective To investigate the clinical and radiological features of children with first attack of inflammatory central nervous system disorders and seropositivity to myelin-oligodendrocyte glycoprotein (MOG). Methods The clinical course, cerebrospinal fluid (CSF), MRI studies, MOG status and outcomes were retrospectively analyzed in children with first attack of inflammatory central nervous system disorders and seropositivity to MOG who were hospitalized in Children′s Hospital of Fudan University from January 2016 to April 2017. Results Thirteen patients including 8 males and 5 females were included in this study, the ratio of male/female was 1.6∶1, and the median age was six years. Ten patients were diagnosed with acute disseminating encephalomyelitis, and three with clinically isolated syndromes. Seven patients had elevated CSF lymphocyte cells, and five patients had elevated CSF protein. All the patients′ sera were tested for the anti-MOG IgG, which ranged from 1∶10 to 1∶100 with cell-based assay. MRI results showed that multiple anatomical areas were involved. Twelve patients had brain lesions, in which 10 patients had multiple lobes involved and four had tumefactive demyelinating lesions. The affected anatomical areas included white matters in 11 cases, thalamus/basal ganglias in nine, corpus callosums in three, brainstems in 10, spinal cord in five. The MRI features were characterized by hazy, bilateral lesions without clear boundaries. Clinical symptoms were fully restored in all the patients after treated with intravenous globulin and methyl prednisone. The average follow-up time was 8.9 months, and none of the patients had clinical recurrence. Conclusions MOG was associated with many kinds of inflammatory demyelinating diseases of central nervous system in children. Most of them were diagnosed with acute disseminating encephalomyelitis which has an acute or sub acute clinical course. The clinical manifestations of patients showed diversity. Multiple anatomical areas were involved, and treatment with intravenous globulin and methyl prednisone was effective in the acute phase. All of the patients had a favorable outcome. Key words: Demyelinating autoimmune diseases, CNS; Glycoproteins; Autoantibodies; Child

Neurological disorders are a major global challenge, which counts for a substantial slice of disease burden around the globe. In these, the challenging landscape of central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and neuro-AIDS, demands innovative and novel therapeutic approaches. Curcumin, a versatile natural compound with antioxidant and anti-inflammatory properties, shows great potential as a CNS adjuvant therapy. However, its limited bioavailability and suboptimal permeability to the blood-brain barrier (BBB) hamper the therapeutic efficacy of curcumin. This review explores how nanocarrier facilitates curcumin delivery, which has shown therapeutic efficacy for various non-CNS diseases, for example, cancers, and can also revolutionize the treatment outcomes in patients with CNS diseases. Toward this, intranasal administration of curcumin as a non-invasive CNS drug delivery route can also aid its therapeutic outcomes as an adjuvant therapy for CNS diseases. Intranasal delivery of nanocarriers with curcumin improves the bioavailability of curcumin and its BBB permeability, which is instrumental in promoting its therapeutic potential. Furthermore, curcumin's inhibitory effect on efflux transporters will help to enhance the BBB and cellular permeability of various CNS drugs. The therapeutic potential of curcumin as an adjuvant has the potential to yield synergistic effects with CNS drugs and will help to reduce CNS drug doses and improve their safety profile. Taken together, this approach holds a promise for reshaping CNS disease management by maximizing curcumin's and other drugs' therapeutic benefits.

BackgroundNeuropsychiatric systemic lupus erythematosus (NPSLE) comprises of various neurological and psychiatric conditions in patients with SLE. The frequencies, clinical manifestations and prognosis may vary significantly among different disease entities.MethodsClinical records...

Introduction: Metaplastic breast cancer (MpBC) represents a rare subtype, constituting &amp;lt;1% of all breast cancer cases. It is pathologically characterized by epithelial and mesenchymal cellular components exhibiting a basal molecular pattern, hormone receptor and HER2-negativity, and high grade. Clinically, MpBC exhibits an aggressive course with early disease progression and poor survival. Antibody-drug conjugates (ADCs) have been shown to penetrate the central nervous system (CNS); however, little is known about the response of ADCs in MpBC, particularly in patients with CNS disease. Here we aimed to describe features of CNS disease in a subset of patients (pts) who received an ADC for MpBC . Methods: We conducted a multi-institutional retrospective observational study of pts with advanced MpBC treated with ADCs at 4 NCI-designated cancer centers (abstract #A-345). This analysis includes a subset of this cohort with CNS metastases, with the aim of examining the incidence, characteristics, and treatment patterns. Clinical outcomes were evaluated for pts with information available, including CNS median progression-free survival (mPFS; defined from initiation of systemic therapy to time of further documented CNS progression or death) and median real world PFS (rwPFS; defined from time of treatment initiation to documented disease progression or death). Results: We identified 48 pts with MpBC who received an ADC. Among them, we identified 15 (31%) who developed CNS metastases. Of these, the majority (n=11, 73%) had triple-negative breast cancer, and 4 (27%) had HER2-positive breast cancer. The median age was 50 years (32-75 years). The median interval from the initial MpBC diagnosis to CNS metastasis was 13 months (0-54 months). Excluding those with de novo CNS disease, the median interval from time of metastatic diagnosis to development of CNS metastasis [mets] was 3 months (0-22 months). 4 (27%) pts had de-novo metastatic disease, of which 2 (50%) presented with CNS disease. 4 (27%) pts had screening CNS imaging prior to their diagnosis of CNS metastatic disease. At the time of CNS disease diagnosis, 9 (60%) pts had oligometastatic intraparenchymal CNS disease (defined as &amp;lt;5 CNS mets), 5 (33%) had diffuse (&amp;gt;5 CNS mets) CNS disease, and 1 (6%) had leptomeningeal and intraparenchymal disease. Most pts 14(93%) with CNS disease were symptomatic at time of diagnosis. One pt underwent resection, 9 (60%) underwent stereotactic radiosurgery (SRS), 6 (40%) underwent whole brain radiation therapy (WBRT), and 1 pt received intrathecal chemotherapy with methotrexate. The median number of lines in the metastatic setting prior to documented CNS disease was 1 (range 0-3). The majority 13 (87%) underwent a change in systemic therapy at time of CNS disease diagnosis, with 60% changing to an ADC at the time of CNS diagnosis or progression. Among pts with progression of CNS disease warranting change in systemic therapy, the median time from first CNS event to further CNS progression was 6.5 months. Median CNS PFS was 3.5 months (range 1 -74 months) and median rwPFS was 4.4 months. For those patients who used ADCs after diagnosis of metastatic CNS diagnosis (12/15), median rwPFS was 4 months. Conclusions: Within this CNS sub-cohort study, we found that 31% of pts with MpBC developed CNS metastasis. The majority of pts had neurological symptoms at diagnosis, but most pts did not undergo routing screening for CNS disease. Given the high rate of CNS mets within a short timeframe from diagnosis with poor outcomes, CNS screening should be considered. The extremely short median CNS PFS and low median rwPFS of this cohort highlight the guarded prognosis associated with MpBC. Given the small sample size of this cohort, larger studies are warranted to validate these findings. Citation Format: S. Premji, S. Jacob, A. LeVee, S. Marion, S. Fisch, L. Huppert, J. Mortimer, D. Schmolze, A. Nayak, A. DeMichele, P. Shah, R. Leon-Ferre, D. Idossa. Central nervous system disease in patients with metaplastic breast cancer receiving antibody drug conjugates: a multi-institutional study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-09-07.

Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array of fundamental metabolic processes. The human body maintains a relatively low concentration of copper, which is mostly found in the bones, liver, and brain. Despite its low concentration, Cu plays a crucial role as an indispensable element in the progression and pathogenesis of central nervous system (CNS) diseases. Extensive studies have been conducted in recent years on copper homeostasis and copper-induced cell death in CNS disorders, including glioma, Alzheimer’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, and stroke. Cuproptosis, a novel copper-induced cell death pathway distinct from apoptosis, necrosis, pyroptosis, and ferroptosis, has been identified as potentially intricately linked to the pathogenic mechanisms underlying various CNS diseases. Therefore, a systematic review of copper homeostasis and cuproptosis and their relationship with CNS disorders could deepen our understanding of the pathogenesis of these diseases. In addition, it may provide new insights and strategies for the treatment of CNS disorders.

Disease characteristics and outcomes of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) involvement

Tryptophan (TRP) metabolites, which are produced from TRP via three pathways-kynurenine, 5-hydroxytryptamine, and indole-are key signaling molecules of the gut-brain axis and are involved in a variety of central nervous system (CNS) disease processes, such as Alzheimer's disease, depression, and schizophrenia by orchestrating inflammatory responses, redox imbalances, neurotransmitter dynamics, mitochondrial dysfunction, and apoptotic/autophagic pathways. However, TRP metabolites exhibit bidirectional modulatory effects, combining different neuroprotective and neurotoxic substances, depending on their metabolic environment and concentration thresholds, posing significant challenges for therapeutic strategies. Therefore, it is important to modulate TRP metabolite production factors, including the regulation of key enzymes in metabolic pathways, the gut microbiota, hormones, and the disease pathology microenvironment, to promote the production of neuroprotective metabolites and inhibit neurotoxic metabolite production. In this review, we detail the influencing factors affecting TRP metabolite production, the regulatory role of TRP metabolites in CNS disorders, and therapeutic strategies related to TRP metabolites for CNS disorders. Targeting TRP metabolizing enzymes or remodeling the ecology of the gut microbiota could be a new strategy for the treatment of CNS diseases, providing a theoretical basis for future precision intervention in CNS diseases.

Sleep disruption, nightly restlessness, sundowning, and other circadian disturbances are frequently seen in Alzheimer's disease (AD) patients. Changes in the suprachiasmatic nucleus and pineal gland are thought to be the biological basis for these behavioral disturbances. Melatonin is the main endocrine message for circadian rhythmicity from the pineal. To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 +/- 1.1 yr) and in 82 age-matched controls (mean age, 76 +/- 1.4 yr). Ventricular postmortem CSF was collected from clinically and neuropathologically well defined AD patients and from control subjects without primary neurological or psychiatric disease. In old control subjects (>80 yr of age), CSF melatonin levels were half of those in control subjects of 41-80 yr of age [176 +/- 58 (n = 29) and 330 +/- 66 (n = 53) pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF melatonin levels in control subjects. In AD patients the CSF melatonin levels were only one fifth (55 +/- 7 pg/mL) of those in control subjects (273 +/- 47 pg/mL; P = 0.0001). There was no difference in the CSF melatonin levels between the presenile (42 +/- 11 pg/mL; n = 21) and the senile (59 +/- 8 pg/mL; n = 64; P = 0.35) AD patients. The melatonin level in AD patients expressing apolipoprotein E-epsilon3/4 (71 +/- 11 pg/mL) was significantly higher than that in patients expressing apolipoprotein E-epsilon4/4 (32 +/- 8 pg/ml; P = 0.02). In the AD patients no significant correlation was observed between age of onset or duration of AD and CSF melatonin levels. In the present study, a dramatic decrease in the CSF melatonin levels was found in old control subjects and even more so in AD patients. Whether supplementation of melatonin may indeed improve behavioral disturbances in AD patients should be investigated.

The effects of chronic alcohol consumption on the morphology of the pineal gland are being studied in animals. However, there is almost no literature on changes in the pineal gland due to alcohol use disorder in humans. This study hypothesised that chronic alcohol consumption causes degeneration of the pineal gland, resulting in a reduction in volume. This study compared the pineal gland volumes of 15 patients with alcohol use disorder and 17 healthy controls using T1-weighted brain magnetic resonance imaging. The volume of the pineal gland was significantly lower in individuals with alcohol use disorder than in healthy controls. As sex and age may influence absolute pineal volume, these factors were controlled for in a general linear model. Following adjustment, the reduction in pineal gland volume remained statistically significant in patients with alcohol use disorder. In conclusion, this study provides the first data on the neuroanatomical basis of the sleep disturbances commonly observed in patients with alcohol use disorder in clinical practice.