Hemifacial spasms triggered by compression of tortuous anterior inferior cerebellar artery loop on the facial nerve in the internal auditory canal: A case report.

RATIONALE: Hemifacial spasm (HFS) is triggered by neurovascular compression mostly at the root entry/exit zone of the facial nerve. HFS with the responsible blood vessel located in the internal auditory canal (IAC) is a very rare occurrence. In our case, the HFS was triggered by compression of the anterior inferior cerebellar artery (AICA) loop on the facial nerve in the IAC. PATIENT CONCERNS: A 27-year-old female presented with a 5-year history of right-sided facial twitching with no obvious course. The frequency and severity of the attacks increases when the patient was anxious or agitated which severely affected her quality of life. DIAGNOSIS: Preoperative 3D-TOF magnetic resonance imaging (MRI) evaluation of cranial nerves showed that the right AICA loop had a tortuous course within the IAC and compressed the facial nerve. INTERVENTION: Microvascular decompression (MVD) surgery was carried out to separate the tortuous AICA loop and facial nerve in the IAC using a Teflon pad. OUTCOMES: The abnormal muscle response disappeared intraoperatively and 2-years follow-up revealed no recurrence of her symptomatology. She is current well and go about her daily activities with no neurological deficits. LESSON: The attachment of the facial nerve to the tortuous AICA loop coupled with the pulsatile impulse of tortuous AICA loop may have resulted in the entrapment and compression of the CN VII in the IAC.

Raney clip left behind the titanium mesh after cranial surgery: Case report.

RATIONALE: Raney clips are commonly used in neurosurgical procedures to hold the scalp in place and stop bleeding during surgery. The removal of Raney clips is often the last process during cranial surgery prior to the closure of skin incision. Thus, a Raney clip found underneath the titanium mesh resulting in fever is a very rare occurrence. PATIENT CONCERNS: An 18-year-old male patient underwent cranial surgery due to intracranial abscess in the frontal lobe and subsequently underwent frontal skull repair using titanium mesh during which a Raney clip was unintentional left underneath the titanium mesh resulting in fever. DIAGNOSIS: A thin-slice computed tomography (CT) scan was used to identify the Raney clip. INTERVENTION: A third surgery was performed to remove the Raney clip. OUTCOMES: The patient fever total resolved after the third surgery with no further neurological deficits and 2-years follow-up revealed the patient is well and go about his daily activities. LESSONS: It is crucial to ensure that all foreign objects are removed after the surgery by counting all instruments used at and after each step during the operation, including all Raney clips. This will help prevent complications and ensure the safety as well as the well-being of the patient.

The Pattern of Anemia in Pediatric Solid Tumors Prior to and after Chemotherapy- A Retrospective Cohort Study.

BACKGROUND: Solid pediatric tumors refer to cancers that affect children and adoles-cents, and they present unique challenges due to their distinct biological characteristics and their vulnerability to young patients. This study aims to shed light on addressing anemia and the causes of anemia in patients with solid pediatric tumors. MATERIALS AND METHODS: This retrospective cohort comprised 200 healthy children as controls and 235 patients with solid tumors. The study was conducted at first Affiliated Hospital of Zhengzhou University between January 2020 and June 2023. We evaluated different parameters of blood components in controls and patients with solid tumors such as medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and patients with only these tumors 3 weeks after the first cycle of chemotherapy. Further, we evaluated the relationship between serum ferritin and the weight of patients and assessed the relationship be-tween anemia and metastasis to the bone marrow in patients with neuroblastoma and hepatoblas-toma. RESULTS: We observed various combinations of derangements in blood parameters such as hemo-globin, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscu-lar hemoglobin concentration, hematocrit, red cell distribution width, white blood cells, and plate-let in medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and 3 weeks after first cycle of chemotherapy. We found a significant correlation between serum ferritin levels and weight in neuroblastoma patients who are ≤ 2 years (p = 0.022). Involvement of tumor cells in bone marrow correlates with decreased Hb levels in both neuroblastoma (CI = 93.21-106.68, p = 0.001) and hepatoblastoma (CI = 113.36-121.00, p = 0.001). CONCLUSION: Anemia may manifest as an early symptom in neuroblastoma, hepatoblastoma, and nephroblastoma. Also, anemia may be worse in patients with neuroblastoma and hepatoblastoma after chemotherapy and might warrant anemia therapy.

Advances in synthetic lethality modalities for glioblastoma multiforme.

Glioblastoma multiforme (GBM) is characterized by a high mortality rate, high resistance to cytotoxic chemotherapy, and radiotherapy due to its highly aggressive nature. The pathophysiology of GBM is characterized by multifarious genetic abrasions that deactivate tumor suppressor genes, induce transforming genes, and over-secretion of pro-survival genes, resulting in oncogene sustainability. Synthetic lethality is a destructive process in which the episode of a single genetic consequence is tolerable for cell survival, while co-episodes of multiple genetic consequences lead to cell death. This targeted drug approach, centered on the genetic concept of synthetic lethality, is often selective for DNA repair-deficient GBM cells with restricted toxicity to normal tissues. DNA repair pathways are key modalities in the generation, treatment, and drug resistance of cancers, as DNA damage plays a dual role as a creator of oncogenic mutations and a facilitator of cytotoxic genomic instability. Although several research advances have been made in synthetic lethality modalities for GBM therapy, no review article has summarized these therapeutic modalities. Thus, this review focuses on the innovative advances in synthetic lethality modalities for GBM therapy.

Elucidating the pivotal molecular mechanisms, therapeutic and neuroprotective effects of lithium in traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) refers to damage to brain tissue by mechanical or blunt force via trauma. TBI is often associated with impaired cognitive abilities, like difficulties in memory, learning, attention, and other higher brain functions, that typically remain for years after the injury. Lithium is an elementary light metal that is only utilized in salt form due to its high intrinsic reactivity. This current review discusses the molecular mechanisms and therapeutic and neuroprotective effects of lithium in TBI. METHOD: The "Boolean logic" was used to search for articles on the subject matter in PubMed and PubMed Central, as well as Google Scholar. RESULTS: Lithium's therapeutic action is extremely complex, involving multiple effects on gene secretion, neurotransmitter or receptor-mediated signaling, signal transduction processes, circadian modulation, as well as ion transport. Lithium is able to normalize multiple short- as well as long-term modifications in neuronal circuits that ultimately result in disparity in cortical excitation and inhibition activated by TBI. Also, lithium levels are more distinct in the hippocampus, thalamus, neo-cortex, olfactory bulb, amygdala as well as the gray matter of the cerebellum following treatment of TBI. CONCLUSION: Lithium attenuates neuroinflammation and neuronal toxicity as well as protects the brain from edema, hippocampal neurodegeneration, loss of hemispheric tissues, and enhanced memory as well as spatial learning after TBI.

The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is a rare primitive neuroectodermal tumors originating from the cerebellum. MB is the most common malignant primary brain tumor of childhood. MB originates from neural precursor cells in distinctive regions of the rhombic lip, and their maturation occurs in the cerebellum or the brain stem during embryonal development. Also, apoptosis is a programmed cell death associated with numerous physiological as well as pathological regulations. RECENT FINDINGS: Irradiation (IR)-induce apoptosis triggers cell death, with or without intervening mitosis within a few hours of IR and these share different morphologic alteration such as, loss of normal nuclear structure as well as degradation of DNA. Moreover, MB is strikingly sensitive to DNA-damaging therapies and the role of apoptosis a key treatment modality. Furthermore, in MB, the apoptotic pathways are made up of several triggers, modulators, as well as effectors. Notably, IR-induced apoptotic mechanisms in MB therapy are very complex and they either induce radiosensitivity or inhibit radioresistance leading to potential effective treatment strategies for MB. CONCLUSION: This review explicitly explores the pivotal roles of IR-induced apoptosis in the pathogenesis and therapy of MB.

Aflatoxin B1 induces infertility, fetal deformities, and potential therapies.

Aflatoxin B1 (AFB1) is a subsidiary poisonous metabolite, archetypally spawned by Aspergillus flavus and A. parasiticus, which are often isolated in warm or tropical countries across the world. AFB1 is capable of disrupting the functioning of several reproductive endocrine glands by interrupting the enzymes and their substrates that are liable for the synthesis of various hormones in both males and females. In men, AFB1 is capable of hindering testicular development, testicular degeneration, and reduces reproductive capabilities. In women, a direct antagonistic interaction of AFB1 with steroid hormone receptors influencing gonadal hormone production of estrogen and progesterone was responsible for AFB1-associated infertility. AFB1 is potentially teratogenic and is responsible for the development of malformation in humans and animals. Soft-tissue anomalies such as internal hydrocephalus, microphthalmia, cardiac defects, augmented liver lobes, reproductive changes, immune modifications, behavioral changes and predisposition of animals and humans to neoplasm development are AFB1-associated anomalies. Substances such as esculin, selenium, gynandra extract, vitamins C and E, oltipraz, and CDDO-Im are potential therapies for AFB1. Thus, this review elucidates the pivotal pathogenic roles of AFB1 in infertility, fetal deformities, and potential therapies because AFB1 toxicity is a key problem globally.

Posterior Inferior Cerebellar Artery Aneurysm Shaped Like a "Calabash Gourd" and Mimicking a Tumor.

Posterior inferior cerebellar artery aneurysms are likely to be fusiform, yet they hardly enlarge to mimic a tumor in the posterior fossa on radiology. They constitute about 3%-4% of all cerebral aneurysms. A 65-year-old woman presented with tremor in her right upper limb for 1 year and intermittent dizziness for 8 months. Interestingly, magnetic resonance imaging revealed 2 unanimously enhanced masses like mother and daughter located in the right cerebellum hemisphere. The lesion was resected via surgery, and histopathology established the diagnosis of an aneurysm. Her tremor and dizziness subsided 3 months after the surgery, and at her 2-year follow-up she was well with no further neurologic deficits.

Lhermitte-Duclos disease with excessive calcification in a septuagenarian: A case report.

RATIONALE: Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma (DCG), is a rare tumor originating from the cerebellar cortex. LDD is a benign neuroglial tumor with uncertain prognosis. Over 200 cases have been reported in the literature mostly in the form of case reports. Thus, we present a spectacular case of LDD with excessive calcification in a female septuagenarian. PATIENT CONCERNS: A 72-year-old female presented with progressive dizziness for 8 months and suffered a head and sacrococcygeal region injury 20 days prior to her admission in our neurosurgery department. DIAGNOSIS: Computed tomography scan showed a right nonspecific cerebellar mass with striated calcification. Magnetic resonance imaging revealed a right "tiger-striped" alteration of the cerebellar cortex. H&E staining revealed a low grade glial neural tumor which was consistent with the diagnosis of LDD or DCG. INTERVENTION: The lesion was total resected. OUTCOMES: The patient recovered well and the cerebellar dysfunctional symptoms subsided 3 months after the operation and 2 years follow-up revealed no recurrence of the lesion and no neurological deficits. LESION: We postulate that the calcification of LDD is age-related and the pathogenesis of disease often observed in young adulthood.

Localized Congenital Cutis Verticis Gyrate with Skull Erosion.

Localized congenital cutis verticis gyrate (CVG) is rare and potentially risks skull involvement. A 23-year-old woman presented with a congenital scalp mass in the occipital region. Local thickening of her left occipital scalp with ridges and furrows was observed on examination. Head computed tomography scan showed a lytic area underneath the same area of the occipital calvarium. The mass was surgically removed due to the skull erosion and cosmetic reasons. Pathologic evaluation established CVG. Surgical excision is best for localized congenital CVG with skull erosion due to cosmetic reasons. Surgical excision was rewarding to the patient it allowed her to style her hair.

Giant Brain Arteriovenous Malformation Managed by Staged Embolizations and Surgical Resection with Satisfactory Outcome.

Spetzler-Martin grade V (>6 cm) arteriovenous malformations (AVMs) are traditionally considered inoperable. A 35-year-old man presented with repeated seizures for 7 years, and computed tomography arteriography and magnetic resonance imaging revealed left deep hemispheric AVM. A combination of embolization and surgical resection successfully achieved a cure of the patient. Well-equipped neurosurgery facilities can best manage selective Spetzler-Martin grade V AVMs with no neurologic deficits contrary to their traditionally inoperable concept. Successful surgery offers the patient a better quality of life.

Genetic pathways in cerebral palsy: a review of the implications for precision diagnosis and understanding disease mechanisms.

ABSTRACT: Cerebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture. Patients with cerebral palsy are often only capable of limited activity, resulting from non-progressive disturbances in the fetal or neonatal brain. These disturbances severely impact the child's daily life and impose a substantial economic burden on the family. Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes, the understanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity. This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development. It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development, which can be further influenced by environmental factors. Despite continuous research endeavors, the underlying factors contributing to cerebral palsy remain are still elusive. However, significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development. Moreover, these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping, including thrombosis, angiogenesis, mitochondrial and oxidative phosphorylation function, neuronal migration, and cellular autophagy. Furthermore, exploring targeted genotypes holds potential for precision treatment. In conclusion, advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy. These breakthroughs have the potential to pave the way for new treatments and therapies, consequently shaping the future of cerebral palsy research and its clinical management. The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies. By elucidating the underlying cellular mechanisms, we can develop targeted interventions to optimize outcomes. A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

Rapid disappearance of acute subdural hematoma due to abrogated hyper-fibrinolytic activity by tranexamic acid: Case report.

RATIONALE: Acute subdural hematoma (ASDH) occurs after tearing of bridging veins within the dura resulting in the accumulation of blood between the arachnoid and dura layers within 72 hours after traumatic head injury. Also, antigen fibrin D-dimer (DD) is the principal enzymatic degradation product of cross-linked fibrin by plasmin. We observed that early tranexamic acid (TXA) treatment resolved hyper-fibrinolysis and rapid disappearance ASDH. PATIENTS CONCERNS: A 48-year-old female presented with unconsciousness for 2 hours after head trauma. Her Glasgow Coma Scale score was >8 points. DIAGNOSIS: Computed tomography scan established ASDH with midline shift and brainstem compression and surgery was scheduled. Also, laboratory results indicated high DD spike of 34,820 µg/L and a reduction in plasma fibrinogen 1 hour after the injury. INTERVENTION: She was treated with intravenous TXA immediately after admission. OUTCOMES: Her DD spike decreased remarkably in 48 hours with associated rapid disappearance of ASDH thereby averting surgical intervention. She recovered fully with no long-term complications. LESSONS: Historically, hyper-fibrinolysis is associated with poor outcome in head trauma. However, early initiation of TXA which is noninvasive treatment modality for ASDH could avert surgery and reduce cost, anesthesia, and other complications associated with surgery.

Genome-wide Association Studies of REST Gene Associated Neurological Diseases/traits with Related Single Nucleotide Polymorphisms.

BACKGROUND: Genome-wide association studies (GWAS) have been used to explore the connections between genotypes and phenotypes by comparing the genotype frequencies of genetic changes in individuals with similar origins but distinct traits. OBJECTIVES: The aim is to employ the GWAS catalog to identify and investigate the various correlations between genotypes and phenotypes of the REST gene. METHODS: In this study, we utilized a large dataset of GWAS comprising 62,218,976 individuals in 112 studies and 122 associations with 122 traits (www.ebi.ac.uk/gwas/genes/REST) from European, Asian, Hispanic, African ancestry up to 28 February 2023. Protein-association network evaluation and gene ontology enrichment study was utilized to evaluate the biological function of the discovered gene modules. RESULTS: We identified several associations for both neurodevelopmental and neurodegenerative disorders linked to REST, as well as its mapped gene modules and their functional relationship networks. CONCLUSION: This work offers fresh insights into identifying risk loci of neurological disorders caused by REST.

Screening inflammatory protein biomarkers on premature infants with necrotizing enterocolitis.

OBJECTIVE: This study aimed to explore potential inflammatory biomarkers for early prediction of necrotizing enterocolitis (NEC) in premature infants. METHODS: Plasma samples were collected from premature infants with NEC (n = 30), sepsis (n = 29), and controls without infection (n = 29). The 92 inflammatory-related proteins were assessed via high-throughput OLINK proteomics platform. RESULTS: There were 11 inflammatory proteins that significate differences (p < 0.05) among NEC, sepsis and control preterm infants, which include IL-8, TRAIL, IL-24, MMP-10, CCL20, CXCL1, OPG, TSLP, MCP-4, TNFSF14 and LIF. A combination of these 11 proteins could serve as differential diagnosis between NEC and control infants (AUC = 0.972), or between NEC and sepsis infants (AUC = 0.881). Furthermore, the combination of IL-8, OPG, MCP-4, IL-24, LIF and CCL20 could distinguish Stage II and III of NEC (AUC = 0.977). Further analysis showed the combination of IL-8, IL-24 and CCL20 have the best prediction value for NEC and control (AUC = 0.947), NEC and sepsis (AUC = 0.838) and different severity of NEC (AUC = 0.842). CONCLUSION: Inflammatory proteins were different expressed in premature infants with NEC compared with controls or sepsis. Combining these proteins provide a higher diagnostic potential for preterm NEC infants.

Elucidating the Focal Immunomodulatory Clues Influencing Mesenchymal Stem Cells in the Milieu of Intervertebral Disc Degeneration.

The intervertebral discs (IVDs) are a relatively mobile joint that interconnects vertebrae of the spine. Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain, which is most often related to patient morbidity as well as high medical costs. Patients with chronic IVDD often need surgery that may sometimes lead to biomechanical complications as well as augmented degeneration of the adjacent segments. Moreover, treatment modalities like rigid intervertebral fusion, dynamic instrumentation, as well as other surgical interventions are still controversial. Mesenchymal stem cells (MSCs) have exhibited to have immunomodulatory functions and the ability to differentiate into cartilage, making these cells possibly an epitome for IVD regeneration. Transplanted MSCs were able to repair IVDD back to the normal disc milieu via the activation of the generation of extracellular matrix (ECM) proteins such as aggrecan, proteoglycans and collagen types I and II. IVD milieu clues like, periostin, cluster of differentiation, tumor necrosis factor alpha, interleukins, chemokines, transforming growth factor beta, reactive oxygen species, toll-like receptors, tyrosine protein kinase receptor and disialoganglioside, exosomes are capable of influencing the MSCs during treatment of IVDD. ECM microenvironment clues above have potentials as biomarkers as well as accurate molecular targets for therapeutic intervention in IVDD.

The impact of residual hematoma after evacuation on the outcomes of patients with ruptured intracranial aneurysms with intracerebral hematoma: A longitudinal single-center observational study.

Intracerebral hematoma (ICH) as a result of ruptured of intracranial aneurysms often arises in patients with subarachnoid hemorrhage. Few studies focused on risk factors for ICH and not the impact of residual hematoma after evacuation on the outcomes of the patients. Therefore, 2 questions need to be answered: does residual hematoma after evacuation have impact on the outcome of patients who present with ICH as a result of ruptured intracranial aneurysms? Is radical pursuit of the hematoma necessary? The study was a single-center longitudinal observational type. Data of 2044 consecutive patients with subarachnoid hemorrhage from January 2009 to December 2019 were reviewed. ICHs were established and the locations of aneurysms as well as hematoma volumes were measured by computed tomographic scan before aneurysm occlusion. Only patients who received aneurysm clipping were included. Patients were stratified into hematoma evacuation without residuals versus residual hematoma after evaluation groups, and outcome was assessed according to the modified Rankin Scale (mRS) at 6 months. Out of the 1365 patients who received clipping, 476 patients presented in poor grade, whereas 889 patients' good grade. Our mRS scores revealed that patients who attained hematoma evacuation without residuals in the good-grade category attained better functional outcome than those with residual hematoma after evacuation. Contrarily, our mRS scores did not establish any significant difference in outcome between the poor-grade patients with hematoma evacuation without residuals and patients with residual hematoma after evacuation. Furthermore, our logistic regression model showed that advance age, poor Hunt-Hess grade, and vascular injury due to surgery were contributing factors for poor outcome of patients with ICH. Our data suggested that aggressive hematoma evacuation may not benefit the poor-grade patients. Majority of poor outcomes were due to surgical complications which were vascular related as a result of excessive pursuit of ICH.

Hematoma cavity separation and neomembrane thickness are potential triggers of recurrence of chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is the anomalous and encapsulated accumulation of fluid of complex origin consisting of old blood, mostly or totally liquified and cerebrospinal fluid (CSF) in the subdural space usually after a head injury in the elderly. Almost all the research on surgical techniques and endoscopic assisted evacuation of CSDH focused on the just the evacuation and not abnormal anatomical structures that causes recurrences. OBJECTIVES: We investigated abnormal anatomical structures that triggers recurrence of CSDH during craniotomy as well as burr-hole craniostomy with endoscopic assistance. MATERIALS AND METHODS: We retrospectively analyzed all patients with CSDH who underwent craniostomy and burr-hole craniotomy with endoscopic assisted evacuation of hematoma between April 2017 and November 2020 at our institution. Clinical data obtained was categorized into patient-related, radiology as well as surgery and endoscopic evaluations. RESULTS: A total of 143 patients (109 men and 34 women) aged 43-94 years (mean age, 68.35 years) with CSDH were included in this study. We observed a recurrence rate of 4.9% (7/143). Recurrences occurred between 2 and 6 months after the operation in patients with recurrences. Our data revealed that, age, hypertension, history of injury, diabetes, antiplatelet or anticoagulant use were not associated with hematoma recurrence. Nevertheless, all the patients with recurrence of hematoma were males. Interestingly, our univariate and multivariate analyses found neomembrane thickness and hematoma cavity separation as independent risk factors (OR,45.822; 95% CI,2.666-787.711; p = 0.008) for the recurrence of CSDH (p < 0.05). Also, we observed thickened membranes connecting/separating the dura and the thickened arachnoid/pia matters in all the 7 patients with hematoma recurrence. CONCLUSIONS: The treatment of patients with CSDH ought to include the identification and resection of abnormal thickened membranes connecting/separating the dura and the thickened arachnoid/pia matters to avoid recurrence. Comparatively, endoscopy showed hematoma cavity separation or neomembrane thickness just as seen during craniotomy.

Localized Giant Cell Tumor of the Tendon Sheath of the Upper Cervical Spine: A Case Report.

Introduction: Giant cell tumor of the tendon sheath (GCTTS) is commonly seen in the appendicular skeleton, and rarely arises from the axial skeleton. We describe a rare case of GCTTS in an adolescent in the upper cervical spine. Case Presentation: A previously healthy 16-year-old boy presented with a 6-month history of numbness of right upper extremity, and had experienced a neck pain 4 months ago. Spinal MRI demonstrated a small syrinx at C2 level and a well-circumscribed extradural mass with contrast enhancement extending from the posterior arch of C1 to C2. The extradural mass was totally resected, and the syrinx underwent clinical and imaging surveillance. Discussion: GCTTS should be considered in the differential diagnosis of the axial skeletal lesion although very rare. Gross-total resection is advocated in GCTTS of the upper cervical spine, and subtotal resection with meticulous lesion monitoring should be performed in unresectable cases.

Edifying the Focal Factors Influencing Mesenchymal Stem Cells by the Microenvironment of Intervertebral Disc Degeneration in Low Back Pain.

Intervertebral disc degeneration (IVDD) is one of the main triggers of low back pain, which is most often associated with patient morbidity and high medical costs. IVDD triggers a wide range of pathologies and clinical syndromes like paresthesia, weakness of extremities, and intermittent/chronic back pain. Mesenchymal stem cells (MSCs) have demonstrated to possess immunomodulatory functions as well as the capability of differentiating into chondrocytes under appropriate microenvironment conditions, which makes them potentially epitome for intervertebral disc (IVD) regeneration. The IVD microenvironment is composed by niche of cells, and their chemical and physical milieus have been exhibited to have robust influence on MSC behavior as well as differentiation. Nevertheless, the contribution of MSCs to the IVD milieu conditions in healthy as well as degeneration situations is still a matter of debate. It is still not clear which factors, if any, are essential for effective and efficient MSC survival, proliferation, and differentiation. IVD microenvironment clues such as nucleopulpocytes, potential of hydrogen (pH), osmotic changes, glucose, hypoxia, apoptosis, pyroptosis, and hydrogels are capable of influencing the MSCs aimed for the treatment of IVDD. Therefore, clinical usage of MSCs ought to take into consideration these microenvironment clues during treatment. Alteration in these factors could function as prognostic indicators during the treatment of patients with IVDD using MSCs. Thus, standardized valves for these microenvironment clues are warranted.