Adult Nervous System Research Articles

Machine learning predicts cuproptosis-related lncRNAs and survival in glioma patients.

Gliomas are the most common tumor in the central nervous system in adults, with glioblastoma (GBM) representing the most malignant form, while low-grade glioma (LGG) is a less severe. The prognosis for glioma remains poor even after various treatments, such as chemotherapy and immunotherapy. Cuproptosis is a newly defined form of programmed cell death, distinct from ferroptosis and apoptosis, primarily caused by the accumulation of the copper within cells. In this study, we compared the difference between the expression of cuproptosis-related genes in GBM and LGG, respectively, and conducted further analysis on the enrichment pathways of the exclusive expressed cuproptosis-related mRNAs in GBM and LGG. We established two prediction models for survival status using xgboost and random forest algorithms and applied the ROSE algorithm to balance the dataset to improve model performance.

Research progress on platelets in glioma.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.

Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed with varying polyQ lengths, non-pathogenic-htt (Q15, NP-htt) and pathogenic-htt (Q138, P-htt), with an N-terminal RFP tag for in vivo visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 hours post hatching and significant aggregates form in the segmental nerve branches at 48 hours post hatching. Organelle trafficking up-and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.

The evolution of plasticity in the neuroscientific literature during the second half of the twentieth century to the present

ABSTRACT In the neurosciences, concepts play an important role in the conception and direction of research. Among the theoretical notions and direction of research, plasticity stands out because of the multiple ways in which scientists use it to describe and interpret how the nervous system changes and adapts to different requirements. The occurrence of different conceptualizations of plasticity in the scientific literature during the second half of the twentieth century and up to the present was investigated using bibliometric methods. Throughout the period analyzed, synaptic plasticity has remained the dominant conceptualization of plasticity. However, scientists have continued to introduce novel plasticity concepts reflecting the scientific advances they have made in understanding the dynamic nature of the nervous system. The conceptual evolution of plasticity documents that the view of the adult nervous system as immutable has been replaced by an understanding of the nervous system as capable of lifelong change and adaptation.

Specification and survival of post-metamorphic branchiomeric neurons in a non-vertebrate chordate.

Tunicates are the sister group to the vertebrates, yet most species have a life cycle split between swimming larva and sedentary adult phases. During metamorphosis, larval neurons are replaced by adult-specific ones. The regulatory mechanisms underlying this replacement remain largely unknown. Using tissue-specific CRISPR/Cas9-mediated mutagenesis in the tunicate Ciona, we show that orthologs of conserved hindbrain and branchiomeric neuron regulatory factors Pax2/5/8 and Phox2 are required to specify the 'neck', a cellular compartment set aside in the larva to give rise to cranial motor neuron-like neurons post-metamorphosis. Using bulk and single-cell RNA-sequencing analyses, we characterize the transcriptome of the neck downstream of Pax2/5/8. We present evidence that neck-derived adult ciliomotor neurons begin to differentiate in the larva and persist through metamorphosis, contrary to the assumption that the adult nervous system is formed after settlement and the death of larval neurons during metamorphosis. Finally, we show that FGF signaling during the larval phase alters the patterning of the neck and its derivatives. Suppression of FGF converts neck cells into larval neurons that fail to survive metamorphosis, whereas prolonged FGF signaling promotes an adult neural stem cell-like fate.

Targeting drug resistance in glioblastoma (Review).

Glioblastoma (GBM) is the most common malignancy of the central nervous system in adults. The current standard of care includes surgery, radiation therapy, temozolomide; and tumor‑treating fields leads to dismal overall survival. There are far limited treatments upon recurrence. Therapies to date are ineffective as a result of several factors, including the presence of the blood‑brain barrier, blood tumor barrier, glioma stem‑like cells and genetic heterogeneity in GBM. In the present review, the potential mechanisms that lead to treatment resistance in GBM and the measures which have been taken so far to attempt to overcome the resistance were discussed. The complex biology of GBM and lack of comprehensive understanding of the development of therapeutic resistance in GBM demands discovery of novel antigens that are targetable and provide effective therapeutic strategies.

Neural Delays in Processing Speech in Background Noise Minimized after Short-Term Auditory Training.

Background noise disrupts the neural processing of sound, resulting in delayed and diminished far-field auditory-evoked responses. In young adults, we previously provided evidence that cognitively based short-term auditory training can ameliorate the impact of background noise on the frequency-following response (FFR), leading to greater neural synchrony to the speech fundamental frequency(F0) in noisy listening conditions. In this same dataset (55 healthy young adults), we now examine whether training-related changes extend to the latency of the FFR, with the prediction of faster neural timing after training. FFRs were measured on two days separated by ~8 weeks. FFRs were elicited by the syllable "da" presented at a signal-to-noise ratio (SNR) of +10 dB SPL relative to a background of multi-talker noise. Half of the participants participated in 20 sessions of computerized training (Listening and Communication Enhancement Program, LACE) between test sessions, while the other half served as Controls. In both groups, half of the participants were non-native speakers of English. In the Control Group, response latencies were unchanged at retest, but for the training group, response latencies were earlier. Findings suggest that auditory training can improve how the adult nervous system responds in noisy listening conditions, as demonstrated by decreased response latencies.

Identification of cellular and noncellular components of mature intact human peripheral nerve.

The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues. We combined fluorescent and chromogenic immunostaining methods, myelin-selective fluorophores, and routine histological stains to identify common cellular and noncellular elements in aldehyde-fixed nerve tissue sections. We employed Schwann cell (SC)-specific markers, such as S100β, NGFR, Sox10, and myelin protein zero (MPZ), together with axonal, extracellular matrix (collagen IV, laminin, fibronectin), and fibroblast markers to assess the SC's relationship to myelin sheaths, axons, other cell types, and the acellular environment. Whereas S100β and Sox10 revealed mature SCs in the absence of other stains, discrimination between myelinating and non-myelinating (Remak) SCs required immunodetection of NGFR along with axonal and/or myelin markers. Surprisingly, our analysis of NGFR+ profiles uncovered the existence of at least 3 different novel populations of NGFR+/S100β- cells, herein referred to as nonglial cells, residing in the stroma and perivascular areas of all nerve compartments. An important proportion of the nerve's cellular content, including circa 30% of endoneurial cells, consisted of heterogenous S100β negative cells that were not associated with axons. Useful markers to identify the localization and diversity of nonglial cell types across different compartments were Thy1, CD34, SMA, and Glut1, a perineurial cell marker. Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS-resident cell types in humans.

Comprehensive Treatment of Myeloepithelioma of the Central Nervous System in Adults: A Case Report and Literature Review

Comprehensive Treatment of Myeloepithelioma of the Central Nervous System in Adults: A Case Report and Literature Review

Divergence in developmental patterns of larval and adult nervous systems in direct-developing holothuria Eupentacta fraudatrix suggests their independent evolution

Divergence in developmental patterns of larval and adult nervous systems in direct-developing holothuria Eupentacta fraudatrix suggests their independent evolution

The role of the ubiquitin ligase UBE4B in neural tumors in adults and children.

e14034 Background: In cancers of the nervous system such as neuroblastoma (NB), the ubiquitin ligase UBE4B directly ubiquitinates growth factor receptors (GFRs), influencing their trafficking and lysosomal degradation. While the diverse functions of UBE4B are acknowledged, we hypothesize that UBE4B expression has distinct associations with outcomes in pediatric versus adult nervous system cancers. We examined the impact of UBE4B expression on glioblastoma (GBM) development, growth, and metastasis by correlating its expression with patient outcomes across age groups. Methods: Glioblastoma samples that were IDH1/2 wild type (n = 2072) underwent DNA (592-gene/whole-exome) and RNA (whole transcriptome) sequencing at Caris Life Sciences. Samples were stratified by UBE4B expression (transcripts per million – TPM) quartiles for all GBM tumors (Q4: H and Q1: L) and by patient age at the time of tissue collection (younger: < 30 years; older: > 60 years). Cell infiltration in the tumor microenvironment was inferred by quanTIseq. Gene expression profiles were analyzed for transcriptomic signature predictive of response to immunotherapy. Overall survival (OS) was derived from insurance claims data, and Kaplan-Meier estimates were calculated. Mann-Whitney U and Chi-square/Fisher-Exact tests were applied were appropriate, with p-values adjusted for multiple comparison. Results: UBE4B expression was similar between younger (n = 57) and older (n = 1115) glioblastoma patients (median: 24.7 vs. 21.6 TPM, p = 0.17). In younger patients, those with high UBE4B expression showed improved OS compared to low expressors (24.9 vs 19.2 months [mos]; HR = 0.41, 95% CI 0.15 – 1.11, p = 0.07). However, UBE4B expression was not associated with OS among older GBM patients (13.5 vs 12.9 mos; HR 1.10 95% CI 0.9 – 1.3, p = 0.33). Within the younger cohorts, higher expression of growth factor receptor genes was observed in high compared to low UBE4B expression ( EGFR: 96.57 vs. 7.07 TPM, p = 0.0092; RET: 0.99 vs. 0.30 TPM, p = 0.018; NTRK2: 236.9 vs. 29.5 TPM, p = 0.084). Concurrent mutation of PDGFRA was also exclusively observed in UBE4B-high tumors (42.9% vs. 0% in UBE4B-L, p = 0.024). Transcriptomic analysis, however, showed that UBE4B-high tumors had lower IFN-g signature scores compared to UBE4B-L (-0.62 vs. -0.41 arbitrary units, p = 0.02). M1 macrophage cell fractions were lower in UBE4B-high compared to UBE4B-low (median: 0.33% vs. 3.38%, p = 0.005), while the fraction of B cells was significantly higher (median: 9.57% vs. 8.14%, p = 0.009). Conclusions: Higher UBE4B expression in younger GBM cases correlated with improved OS suggesting it may have utility as a prognostic biomarker. Increased expression of GFRs in younger patients with high UBE4B expression may provide rationale for new treatment strategies in these patients. Future work may prioritize designing drug targets for UBE4B, offering therapeutic opportunities, especially for younger GBM patients.

Constitutive Neurogenesis and Neuronal Plasticity in the Adult Cerebellum and Brainstem of Rainbow Trout, Oncorhynchus mykiss.

The central nervous system of Pacific salmon retains signs of embryonic structure throughout life and a large number of neuroepithelial neural stem cells (NSCs) in the proliferative areas of the brain, in particular. However, the adult nervous system and neurogenesis studies on rainbow trout, Oncorhynchus mykiss, are limited. Here, we studied the localization of glutamine synthetase (GS), vimentin (Vim), and nestin (Nes), as well as the neurons formed in the postembryonic period, labeled with doublecortin (DC), under conditions of homeostatic growth in adult cerebellum and brainstem of Oncorhynchus mykiss using immunohistochemical methods and Western Immunoblotting. We observed that the distribution of vimentin (Vim), nestin (Nes), and glutamine synthetase (GS), which are found in the aNSPCs of both embryonic types (neuroepithelial cells) and in the adult type (radial glia) in the cerebellum and the brainstem of trout, has certain features. Populations of the adult neural stem/progenitor cells (aNSPCs) expressing GS, Vim, and Nes have different morphologies, localizations, and patterns of cluster formation in the trout cerebellum and brainstem, which indicates the morphological and, obviously, functional heterogeneity of these cells. Immunolabeling of PCNA revealed areas in the cerebellum and brainstem of rainbow trout containing proliferating cells which coincide with areas expressing Vim, Nes, and GS. Double immunolabeling revealed the PCNA/GS PCNA/Vim coexpression patterns in the neuroepithelial-type cells in the PVZ of the brainstem. PCNA/GS coexpression in the RG was detected in the submarginal zone of the brainstem. The results of immunohistochemical study of the DC distribution in the cerebellum and brainstem of trout have showed a high level of expression of this marker in various cell populations. This may indicate: (i) high production of the adult-born neurons in the cerebellum and brainstem of adult trout, (ii) high plasticity of neurons in the cerebellum and brainstem of trout. We assume that the source of new cells in the trout brain, along with PVZ and SMZ, containing proliferating cells, may be local neurogenic niches containing the PCNA-positive and silent (PCNA-negative), but expressing NSC markers, cells. The identification of cells expressing DC, Vim, and Nes in the IX-X cranial nerve nuclei of trout was carried out.

Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development

Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of invivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 vectors across AAV serotypes combined with a transposon system, we substantially amplified labeling efficacy and accelerated invivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% by lentivirus, to achieve analysis of over 30,000 cells in one experiment and enable massively parallel invivo Perturb-seq. Compatible with various phenotypic measurements (single-cell or spatial multi-omics), it presents a flexible approach to interrogate gene function across cell types invivo, translating gene variants to their causal function.

Non-Tumor Cells within the Tumor Microenvironment-The "Eminence Grise" of the Glioblastoma Pathogenesis and Potential Targets for Therapy.

Glioblastoma (GBM) is the most common malignancy of the central nervous system in adults. GBM has high levels of therapy failure and its prognosis is usually dismal. The phenotypic heterogeneity of the tumor cells, dynamic complexity of non-tumor cell populations within the GBM tumor microenvironment (TME), and their bi-directional cross-talk contribute to the challenges of current therapeutic approaches. Herein, we discuss the etiology of GBM, and describe several major types of non-tumor cells within its TME, their impact on GBM pathogenesis, and molecular mechanisms of such an impact. We also discuss their value as potential therapeutic targets or prognostic biomarkers, with reference to the most recent works on this subject. We conclude that unless all "key player" populations of non-tumor cells within the TME are considered, no breakthrough in developing treatment for GBM can be achieved.

Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression.

We describe here the molecular mechanisms by which juvenile experience defines patterns of sexually dimorphic synaptic connectivity in the adult nervous system of the nematode C. elegans. We show that starvation of juvenile males disrupts serotonin-dependent activation of the CREB transcription factor in a nociceptive sensory neuron, PHB. CREB acts through a cascade of transcription factors to control expression of an atypical cadherin protein, FMI-1/Flamingo. During postembryonic development, FMI-1/Flamingo has the capacity to promote and maintain synaptic connectivity of the PHB nociceptive sensory to a command interneuron, AVA, in both sexes, but the serotonin transcriptional regulatory cassette antagonizes FMI-1/Flamingo expression in males, thereby establishing sexually dimorphic connectivity between PHB and AVA. A critical regulatory node in this process is the CREB-target LIN-29, a Zn finger transcription factor which integrates four different layers of information - sexual specificity, past feeding status, time and cell-type specificity. Our findings provide the mechanistic details of how an early juvenile experience defines sexually dimorphic synaptic connectivity.

Abstract 3503: New generation drug development from in-silico identification to preclinical evaluation in glioblastoma

Abstract Glioblastoma(GBM) is the most common malignancy of the central nervous system in adults. Despite medical advancements, stagnant survival rate improvements (&amp;lt;13%) and failure of conventional treatments such as temozolomide, have warranted the need for novel drug discovery methodologies. Considering the enormous potential of drug repurposing, we developed a method to identify a safe, active, and effective treatment for GBM. This method comprises two key stages, drug-target prediction and preclinical functional evaluation. Stage 1 fabricated a novel five phase in-silico pipeline for drug-target prediction against Ephrin-Type-A Receptor 2, chosen through preliminary literature and genomic analysis. Around 1562 FDA approved drugs were screened against the developed criterion and analyzed for bond type, location, repulsion, Gibbs free energy, stability, interactions over time, blood brain barrier permeability, and possible false positives (PAINS). Our results provided five plausible hits: Empagliflozin, Mycophenolate mofetil, Canagliflozin, Rivaroxaban, and Carvedilol. We subsequently evaluated the anti-proliferative effects of these hits using Sulforhodamine-B cytotoxicity assay on glioblastoma cell lines U251 and SF295. Our results demonstrated that Canaglifozin and Empagliflozin reduced the proliferation of GBM cell lines with IC50 value ranging from 30-40 μM. On the other hand, Mycophenolate mofetil (IC50: 5μM) and Carvedilol (IC50:16μM) also exhibited significant cytotoxic effects. Effects of Mycophenolate mofetil and Carvedilol were further evaluated in pancreatic cell line SUIT-2 where results exhibited cytotoxic responses similar to those observed in GBM. Furthermore, Annexin V/FITC analysis showed apoptosis in SUIT-2 cells by Carvedilol. Taken together, our results show the anti-cancer repurposing candidates extracted from our in-silico pipeline show significant cytotoxic effects of compounds identified through in-silico screening. Further studies are currently underway in our laboratory to delineate the anti-cancer mechanism, toxicity and off-target effects of these compounds. Citation Format: Mahesh Arunachalam, Shreyas Gaikwad, Sharavan Ramachandran, Sanjay K. Srivastava. New generation drug development from in-silico identification to preclinical evaluation in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3503.

Non-canonical retinoid signaling in neural development, regeneration and synaptic function.

Canonical retinoid signaling via nuclear receptors and gene regulation is critical for the initiation of developmental processes such as cellular differentiation, patterning and neurite outgrowth, but also mediates nerve regeneration and synaptic functions in adult nervous systems. In addition to canonical transcriptional regulation, retinoids also exert rapid effects, and there are now multiple lines of evidence supporting non-canonical retinoid actions outside of the nucleus, including in dendrites and axons. Together, canonical and non-canonical retinoid signaling provide the precise temporal and spatial control necessary to achieve the fine cellular coordination required for proper nervous system function. Here, we examine and discuss the evidence supporting non-canonical actions of retinoids in neural development and regeneration as well as synaptic function, including a review of the proposed molecular mechanisms involved.

Role of Post-Transcriptional Regulation in Learning and Memory in Mammals.

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is of the most importance in the brain, where all the steps of mRNA maturation, transport to different regions of the cells and actual expression, in response to specific signals, constitute the molecular basis for neuronal plasticity and, as a consequence, for structural stabilization/modification of synapses; notably, these latter events are fundamental for the highest brain functions, such as learning and memory, and are characterized by long-term potentiation (LTP) of specific synapses. Here, we will discuss the molecular bases of these fundamental events by considering both the role of RNA-binding proteins (RBPs) and the effects of non-coding RNAs involved in controlling splicing, editing, stability and translation of mRNAs. Importantly, it has also been found that dysregulation of mRNA metabolism/localization is involved in many pathological conditions, arising either during brain development or in the adult nervous system.

The development of the adult nervous system in the annelid Owenia fusiformis

BackgroundThe evolutionary origins of animal nervous systems remain contentious because we still have a limited understanding of neural development in most major animal clades. Annelids — a species-rich group with centralised nervous systems — have played central roles in hypotheses about the origins of animal nervous systems. However, most studies have focused on adults of deeply nested species in the annelid tree. Recently, Owenia fusiformis has emerged as an informative species to reconstruct ancestral traits in Annelida, given its phylogenetic position within the sister clade to all remaining annelids.MethodsCombining immunohistochemistry of the conserved neuropeptides FVamide-lir, RYamide-lir, RGWamide-lir and MIP-lir with gene expression, we comprehensively characterise neural development from larva to adulthood in Owenia fusiformis.ResultsThe early larval nervous system comprises a neuropeptide-rich apical organ connected through peripheral nerves to a prototroch ring and the chaetal sac. There are seven sensory neurons in the prototroch. A bilobed brain forms below the apical organ and connects to the ventral nerve cord of the developing juvenile. During metamorphosis, the brain compresses, becoming ring-shaped, and the trunk nervous system develops several longitudinal cords and segmented lateral nerves.ConclusionsOur findings reveal the formation and reorganisation of the nervous system during the life cycle of O. fusiformis, an early-branching annelid. Despite its apparent neuroanatomical simplicity, this species has a diverse peptidergic nervous system, exhibiting morphological similarities with other annelids, particularly at the larval stages. Our work supports the importance of neuropeptides in animal nervous systems and highlights how neuropeptides are differentially used throughout development.

Evaluation of Central Nervous System Relapse in Adults with Acute Lymphoblastic Leukemia (ALL) Receiving Hyper-CVAD Treatment in Seyyed Al-Shohada Hospital: Isfahan, 2014-2019.

Background: Recurrence of ALL in the central nervous system, CNS Relapse, is known as a poor prognostic factor. Few studies have been performed on the CNS Relapse in adults with ALL. This study aimed to evaluate the recurrence of acute lymphoblastic leukemia in the central nervous system, CNS relapse, in adults with ALL. Materials and Methods: Seventy newly diagnosed patients with acute lymphoblastic leukemia aged 15 years and older referred to Seyyed Al-Shohada Hospital in Isfahan between 2014 and 2019 were included in this study. All patients treated with the Hyper-CVAD regimen underwent prophylaxis for the central nervous system based on the risk of CNS relapse. All study participants with CNS relapse underwent intrathecal chemotherapy. Results: The median age of patients was 34 years. Four patients (5.7%) had primary central nervous system involvement. Out of 70 patients receiving the Hyper-CVAD regimen, 59 (84.2%) achieved complete remission. Of the 59 patients achieving CR, ten (16.94%) developed CNS relapse. The median duration of CR before CNS relapse was 21 weeks. Out of 10 patients with CNS relapse, seven (70%) achieved complete remission. Of seven patients achieving CR in the central nervous system, one had a second recurrence in the central nervous system, but finally achieved CNS complete remission. The median survival of patients after CNS relapse was four months. The results also showed that out of 10 patients with CNS relapse, four (40%) survived one year. Conclusion: This study shows that the prognosis of CNS relapse in adults with ALL has not improved much. Limited studies have been conducted on the recurrence of the central nervous system in adults with acute lymphoblastic leukemia. Therefore, further studies on CNS relapse after complete remission of ALL are required to clarify more details.