Dysembryoplastic neuroepithelial tumor (DNT) is a rare low-grade, mixed neuronal and glial tumor, usually associated with pharmacologically intractable, complex partial or generalized seizures which date from childhood. [1] The mean age of onset of seizures for children with DNTs is 8.1 years old. They are the most common primary brain tumor in adults. Three histological forms are recognized 5: Focal cortical dysplasiais commonly seen in association with DNETs, and unless a component can be identified clearly separate from tumor cells, then it does not warrant a concurrent separate diagnosis. The MRI appearance is T2/FLAIR hyperintensity with corresponding T1 hypointensity (Figure 2). Simple: Specific glioneuronal elements are the sole components of simple DNTs. Despite benign behavior, it may have a high MIB-1 labeling index. PMC FOIA 2019 Dec;132:347-355. doi: 10.1016/j.wneu.2019.08.221. Prognosis is excellent, however, due to the difficulty in managing seizures medically, patients usually undergo resection and even in cases of incomplete resection, seizures frequently cease. Reference article, Radiopaedia.org (Accessed on 04 Mar 2023) https://doi.org/10.53347/rID-1251, {"containerId":"expandableQuestionsContainer","displayRelatedArticles":true,"displayNextQuestion":true,"displaySkipQuestion":true,"articleId":1251,"questionManager":null,"mcqUrl":"https://radiopaedia.org/articles/dysembryoplastic-neuroepithelial-tumour/questions/2141?lang=us"}. National Library of Medicine This means they are malignant (cancerous) and fast-growing. The overall appearance of DNETs varies. One patient had a DNET that involved both frontal and temporal areas. Features include a multinodular and multicystic appearance, the presence of both neuronal and glial (oligodendrocytic and astrocytic) components with little if any cytologic atypia, the presence of accompanying cortical dysplasia, and the lack of an arcuate vascular pattern. 21 (6): 1533-56. 2022 Dec 22;13(1):24. doi: 10.3390/brainsci13010024. In conclusion, DNET is a benign tumor, composed of neuroglial cell, most probably confined to the temporal lobe. sharing sensitive information, make sure youre on a federal Background. Additional locations include the occipital and parietal lobes, deep cerebral nuclei (particularly caudate nuclei), cerebellum, and brainstem. Common age Adults between 15-40 years; com Children beneath 15 years; comprise eighty% of childhood prise 20% of childhood leukaemias leukaemias 2. These tumours, with a glial and/or neuronal component, are challenging in terms of diagnosis and therapeutic management. The lobular aspect with presence of septations can sometimes occur (as in our case). Rugg-Gunn FJ, Simister RJ, Squirrell M, Holdright DR, Duncan JS: Cardiac arrhythmias in focal epilepsy: a prospective long-term study. CAS Although epileptogenicity was complex, congruence between electro-clinical and neuroimaging studies was high and allowed good surgical outcomes at 1 year of follow-up. The patients mother stated her daughter had a 5- to 6-week history of strange, increasingly frequent movements. However, we cannot answer medical or research questions or give advice. [4] With DNTs often causing epileptic seizures, surgical removal is a common treatment, providing high rates of success.[4]. [4] The most common symptom of DNTs are complex partial seizures. One minute of hyperventilation activated a tonic-clonic generalized seizure. Acta Neurochir (Wien). hyperactivity or difficulty sitting still restlessness or being fidgety While these problems are usually diagnosed in childhood, symptoms sometimes persist into the adult years in many people. Bookshelf 3. About 70-90% of surgery are successful in removing the tumour. SHE is difficult to diagnose and treat in the early stages due to its diverse clinical manifestations and difficulties in differentiating from non-epileptic events, which seriously affect patients' quality of life and social behavior. Over the last few decades, deciphering the alteration of molecular pathways in brain tumors has led to impressive changes in diagnostic refinement. BRAF; Brain neoplasm; DNET; Diffusion-weighted MRI; Drug-resistant epilepsy; MR spectroscopy; Neuroepithelial tumor. Before Pathology-MRI Correlations in Diffuse Low-Grade Epilepsy Associated Tumors. Cancers (Basel). Cardiac dysrhythmias during the interictal state is another potentially fatal condition because of chronic autonomic dysfunction, effects of antiepileptic medication and a common genetic susceptibility [6, 7]. DNET is a benign mixed neuronal-glial tumor causing drug-resistant epilepsy primarily in children and young adults. At the time the article was last revised Yuranga Weerakkody had Neurology Today. Thirteen patients (57%) had simple partial, 21 (91%) had complex partial, 16 (70%) had secondarily generalized seizures and 5 patients had only simple partial seizures. 10.1055/b-0034-79116 Dysembryoplastic Neuroepithelial TumorsTene A. Cage, Tarik Tihan, and Nalin Gupta Dysembryoplastic neuroepithelial tumors (DNETs) were first described by Daumas-Duport et al1 in 1988. DNET Seizures Epilepsy Surgery Adult-onset Tumors Introduction Dysembryoplastic neuroepithelial tumors (DNETs), which are characterized by a heterogeneous population of neurons, astrocytes and oligodendroglia-like cells, 1 are a common cause of tumor-related chronic epilepsy. (A) First CT scan show a left temporoparietal diffuse hypodense area, quite inhomogeneous without mass effect. In children and adolescents, dysembryoplastic neuroepithelial tumors (DNETs) of the brain present with seizures almost 100 % of the time, potentially creating significant long-term morbidity and disability despite the generally indolent course of the lesion. DNET is a benign mixed neuronal-glial tumor causing drug-resistant epilepsy primarily in children and young adults. The Food and Drug Administration require warning labels on the risk of SUDEP in association with the use of each of the above-mentioned drugs [14]. [4], Typical DNTs can be detected in an EEG scan when there are rapid repetitive spikes against a contrasted background. Koeller KK, Henry JM. Defined as "a usually supratentorial glial-neuronal neoplasm occurring in children and young adults and characterized by a predominantly cortical location and by drug . The seizures are known to cause central apnea by direct propagation of the electrical discharge to the respiratory center. The published National Institute for Clinical Excellence guidelines state that "individuals with epilepsy and their families and/or carers should be given and have access to information on SUDEP". https://my.statdx.com/document/dnet/4d5ae76b-1c26-495f-881b-b66a81d21f8a?searchTerm=dnet. Accessibility There are four main types of surgery that are performed in an effort to remove lung cancer cells: A wedge resection involves removing a wedge-shaped section of lung tissue containing the tumor. government site. Status epilepticus did not occur. Google Scholar. Afshin-Pour B, Soltanian-Zadeh H, Hossein-Zadeh GA et-al. Macroscopically, DNETs are visible on the surface of the brain, sometimes with an exophytic component. Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm typically associated with intractable, partial complex seizures in children and young adults. Lubricating gland the prostate gland, situated just below the Nursing actions bladder, is taken into account homologous to Skenes Explain the process to the consumer medicine merit . Nervous hunger. Would you like email updates of new search results? Histopathology. Cookies policy. Of 1162 articles, 200 relevant studies have been selected. Ten patients had adult-onset epilepsy. 1,2 Diagnostic criteria include partial seizure disorder that begins before age 20, no neurological deficits, and a cortically based tumor. Thom M, Toma A, An S, et al. Article Sci Rep. 2023 Jan 13;13(1):682. doi: 10.1038/s41598-022-26636-7. An association with Noonan syndrome has been proposed 9,10. The majority of cases are found in the temporal lobe where they can coexist with mesial temporal sclerosis, followed by the frontal, parietal and rarely the occipital lobe. DNTs are heterogenous lesions composed of multiple, mature cell types. J Clin Neurophysiol. Over 100 cases have been reported in the literature since the first description by Daumas-Duport in 1988. This site needs JavaScript to work properly. One minute of hyperventilation activated a tonic-clonic generalized seizure, accompanied by specific EEG recording (Figure 2). 1999, 34 (4): 342-356. We did not include other causes of lesional temporal epilepsy such as tumors (e.g., DNET) or vascular malformations (e.g., cavernoma) to first, avoid anatomical biases in the sample, and second . Clin Neuropathol. Nervousness Giulioni M, Rubboli G, Marucci G, Martinoni M, Marliani AF, Riguzzi P, Calbucci F. Clin Neurol Neurosurg. HHS Vulnerability Disclosure, Help Other tumors have symptoms that develop slowly. Heiland DH, Staszewski O, Hirsch M, Masalha W, Franco P, Grauvogel J, Capper D, Schrimpf D, Urbach H, Weyerbrock A. J Neuropathol Exp Neurol. government site. Immunohistochemical and morphometric studies", "Dysembryoplastic neuroepithelial tumors: where are we now? This is called systemic therapy. [4] In this case, a second operation has to be done in order to completely remove the malignant tumour. DNET tumor; Community Forum Archive. 2010, 68 (6): 898-902. Dilated perivascular spaces with adjacent signal changes, View Frank Gaillard's current disclosures, View Yuranga Weerakkody's current disclosures, see full revision history and disclosures, desmoplastic infantile astrocytomas and ganglioglioma, multinodular and vacuolating neuronal tumors (MVNT), oligodendroglioma, IDH-mutant, and 1p/19q-codeleted, high-grade astrocytoma with piloid features, desmoplastic infantile ganglioglioma/astrocytoma, diffuse leptomeningeal glioneuronal tumor, multinodular and vacuolating neuronal tumor, embryonal tumor with multilayered rosettes, pineal parenchymal tumor of intermediate differentiation, desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant, glioma treatment response assessment in clinical trials, World Health Organization (WHO) oncology response criteria, Response Evaluation Criteria in Solid Tumors (RECIST), lissencephaly type I:subcortical band heterotopia spectrum, mild malformations of cortical development, Dysembryoplastic neuroepithelial tumours (DNET)'s, Dysembryoplastic neuroepithelial tumour (DNET), glial nodules and a multinodular architecture. California Privacy Statement, 2 Clinical Features Most patients pres ent with a long-standing history of partial complex seizures that are poorly responsive or resistant to standard antiepileptic therapy. Medications can be given through the bloodstream to reach cancer cells throughout the body. 2021;23(8):1231-51. 2002, 42 (2): 123-136. 2015. Living with a low grade tumour Please watch a recording of our live panel discussion on living with a low grade tumour. Asphyxiation secondary to an obstructive cause has been postulated to play a role in the deaths of patients who were found in a prone position at the time of death [9]. Surgery can resolve the seizures. Cimino, M.D., Ph.D. and Chris Dampier, M.D. Neurology. Journal of Medical Case Reports DNETs are WHO grade 1 lesions, and specific glioneuronal elements should be present on pathology that are characterized as axon columns lined by uniform oligodendroglioma-like cells with intervening floating neurons.3,4 Histology is differentiated by the subtypes, including simple (only glioneuronal elements), complex (associated with cortical dysplasia), and nonspecific (resemble low-grade glioma with no specific glioneuronal elements).3 In this case the pathology was a low-grade glioneuronal neoplasm most consistent with complex dysembryoplastic neuroepithelial tumor. We assessed clinical, electrographic and surgical outcome features in patients with adult- and childhood-onset epilepsy. I'm from Poland. The tumor usually begins in children and individuals who are 20 years old or younger. Retrospective cohort of 23 patients seen at two major epilepsy centers, with localization-related epilepsy associated with histopathologically demonstrated DNETs. The group of tumors, formerly known as PNETs, are Grade IV tumors. Zhang H, Hu Y, Aihemaitiniyazi A, Li T, Zhou J, Guan Y, Qi X, Zhang X, Wang M, Liu C, Luan G. Brain Sci. Renew or update your current subscription to Applied Radiology. DNET occurs in the tissues that cover the brain and spinal cord. first used the term dysembryoplastic neuroepi-thelial tumor to describe low-grade tu-mors found in young patients with in-tractable partial seizures.4 In 1993 the distinct pathological entity known as DNET was given a place in the WHO classification of brain tumors as a grade I We found no difference in outcomes between adult- and childhood-onset cases. Srbu, CA. Two cases of multinodular and vacuolating neuronal tumour. Based on a review of 39 cases, the authors defined a distinct class of slow-growing, supratentorial, glioneuronal tumors in young adults and children. Intratumoral calcifications may be seen in one-third of cases and peritumoral edema is exceedingly rare. 2. A chest X-ray and cardiology examination were normal. A brain tumor occurs when there is a genetic alteration in the normal cells in the brain. Create a new print or digital subscription to Applied Radiology. . Standard electroencephalogram (EEG) showed interictal abnormalities like spikes and polyspikes. Terms and Conditions, Brain Imaging with MRI and CT. Cambridge University Press. DNET was first proposed as a specific entity by Daumas-Duport et al. PubMed [1] This classification by WHO only covers the simple and complex subunits. The typical radiological pattern is a magnetic resonance imaging (MRI) T1-hypointense, T2-, and fluid-attenuated inversion-recovery hyperintense multicystic lesion involving the cerebral cortex with no edema. Radiographics. The alteration causes the cells to undergo a series of changes that result in a growing mass of abnormal cells. 2007, 69 (5): 434-441. PubMed Short-term outcome is influenced by older age at surgery and longer duration of epilepsy. The relationship of DNT to the epileptogenic foci can be determined by extensive interictal and ictal EEG recordings. Patients with refractory epilepsy should be evaluated for any sleep disorders and should have complete cardiology assessments including electrocardiographic evaluation of cardiac rhythm disturbances. Mnesic activity, general cognitive index (GCI), vocabulary and operational effectiveness of thinking had decreased by 35% (mean range) compared to the previous examination at disease onset. Search 15 social services programs to assist you. DNETs are not the same thing as "gliomas" that are frequently mentioned on this board. [4], Dysembryoplastic neuroepithelial tumours are classified as a benign tumour, Grade I of the World Health Organization (WHO) classification of brain tumours. Google Scholar. [citation needed], The most common course of treatment of DNT is surgery. A clinical report and review of the literature. MR spectroscopy allows the determination of certain biochemical properties of the brain in vivo and reflects the biologic characteristics of benign tumor. Childhood brain tumors are less likely to change from low-grade (slow growing, less aggressive) to high-grade (fast growing, more serious). Sleep-related hypermotor epilepsy (SHE) is a group of clinical syndromes with heterogeneous etiologies. Neuronal and mixed neuronal-glial tumors are a group of rare tumors that occur in the brain or spinal cord. The .gov means its official. Patients with DNETs typically present with longstanding treatment-resistant focal seizures (in 90% of cases the first seizure occurred before the age of 20 8) without associated or progressive neurological deficit 5. Arq Neuropsiquiatr. Therefore postoperative radiation and chemotherapy are not needed, and in infancy and childhood they may be deleterious, so the recognition of surgically curable clinicopathological entities is mandatory. They are most commonly located in the temporal lobe (over 50-60% of cases) and . Neuro-Oncology. [citation needed]. ADVERTISEMENT: Supporters see fewer/no ads, Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys. CAS Seizure control outcomes after resection of dysembryoplastic neuroepithelial tumor in 50 patients. J Neurosurg Pediatr. What does it do? Written informed consent for publication from the patients next of kin could not be obtained despite all reasonable attempts. Beijing Da Xue Xue Bao Yi Xue Ban. The most common symptoms are: Changes in the person's mental function; Headaches; Seizures (especially in older adults) They characteristically cause intractable focal seizures (see temporal lobe epilepsy). On CT, DNET can demonstrate wedge-shaped cortical hypoattenuation and mimic ischemia or infection (Figure 1). Differential diagnosis includes oligodendrogliomas, mixed gliomas and gangliogliomas. nato act chief of staff dnet tumor in older adults. Chemotherapy, trastuzumab, and radiotherapy should be provided as routine adjuvant therapy to women with breast cancer . Hi, my 9 years old son has dnet.He is after a surgery, with seizures. Recurrences and malignant transformations may rarely follow, legitimizing MRI surveillance in cases of subtotal tumor resection. Typically seen as a cortical lesion with hardly any surrounding vasogenic edema. [4] In a study done by Bilginer et al., 2009, looking at patients whose tumour was not completely removed, and saw that they were still experiencing seizures, concluding that the incomplete resection as a being a failure. The differential diagnosis also depends on the location of the tumor. DNETs are most often located in the temporal lobe although all parts of the CNS containing grey matter are potential locations. The occipital lobe is an unusual location for a DNET; most are found within the temporal lobe and less often in the frontal lobe. Most commonly found in the temporal lobe, DNTs have been classified as benign tumours. Polymorphous Low-Grade Neuroepithelial Tumor of the Young: A Case Report with Genomic Findings. PubMed This mixed subunit expresses the glial nodules and components of ganglioglioma. eCollection 2017. [2] DNTs are found in the temporal lobe in 84% of reported cases. no financial relationships to ineligible companies to disclose. Over 100 cases have been reported in the literature since the first description by Daumas-Duport in 1988 [1]. [4] A DNT is most commonly diagnosed in children who are experiencing seizures, and when given medication do not respond to them. An updated and comprehensive review on dysembryoplastic neuroepithelial tumor (DNET) focusing on differential diagnosis, atypical presentation, seizure outcome, and risk of malignant transformation. Most meningioma tumors (85-90 percent) are categorized as benign, with the remaining 10-15 percent being atypical meningioma or malignant meningioma (cancerous). When such growths are at the belt line or underneath the bra strap or on the chest where the seat belt in a car rubs across it, they can becomes symptomatic; "they get inflamed, they get irritated . Conclusions: . Acta Neuropathol Commun. Bethesda, MD 20894, Web Policies Her history included a normal birth and normal psychomotor development. Almeida AG, Nunes ML, Palmini AL, Costa JC: Incidence of SUDEP in a cohort of patients with refractory epilepsy: the role of surgery and lesion localization. Thirteen patients (57%) had simple partial, 21 (91%) had complex partial, 16 (70%) had secondarily generalized seizures and 5 patients had only simple partial seizures. Results: Treatment options and prognosis differ significantly between these lesions. DNTs have a benign course, but there are some reports with malignant transformation. Each event lasted for 15-90 seconds and was associated with head slumping, hand clenching, arm stiffening, and unusual repetitive movements, such as turning in circles, repeating short phrases, or grasping at imaginary objects. The prognosis after surgery is favourable. The term DNT was first introduced in 1988 by Daumas-Duport, terming it dysembryoplastic, suggesting a dysembryoplastic origin in early onset seizures, and neuroepithelial to allow the wide range of possible varieties of tumours to be put into the category. A 24- year-old Caucasian woman was admitted to our department with refractory epilepsy. Siegfried A, Cances C, Denuelle M et-al. Finally, axial fused PET/CT images demonstrated hypometabolism within the left frontal lobe lesion. Mosby Inc. (2003) ISBN:032300508X. [3] A headache is another common symptom. Neuronal markers (synaptophysin, neuron- specific enolase) and glial markers (GFAP, S-100) are positive. [1] These are glioneuronal tumours comprising both glial and neuron cells and often have ties to focal cortical dysplasia. The vast majority are centered in cortical grey matter, arise from secondary germinal layers, and are frequently associated with cortical dysplasia(in up to 80% of cases). 2016 Apr;75(4):358-65. doi: 10.1093/jnen/nlw007. By using this website, you agree to our O'Brien DF, Farrell M, Delanty N, Traunecker H, Perrin R, Smyth MD, Park TS; Children's Cancer and Leukaemia Group. A 24- year-old Caucasian woman had a long period of intractable complex partial seizures, sometimes with tonic-clonic generalization and neuropsychological abnormalities. Other authors show that seizure outcome is not always favorable. In 60% of cases, the event was related to sleep, which might indicate involvement of a sleep-related event. Children with a normal neurologic examination and a cortically based lesion with T2 hyperintensity and minimal mass effect should raise the possibility of a DNET. Abstract. Ewing sarcoma. Only one case of malignant transformation has been reported 5. Provided by the Springer Nature SharedIt content-sharing initiative. Unauthorized use of these marks is strictly prohibited. DNTs are now known to be more frequent in children and young adults than was previously believed. In: Linscott, L. DNET. Dysembryoplastic neuroepithelial tumor. 2005 Apr;102(3 Suppl):288-93. doi: 10.3171/ped.2005.102.3.0288. On the other hand, if resections are not performed, and the tumour is not completely removed, then the patient is still at risk of experiencing the seizures. Patira R, Nathan C, Zubkov S, Gutierrez C, Munyon C, Mukherjee A, Jacobson M. Epilepsy Behav Case Rep. 2017 Sep 12;8:92-95. doi: 10.1016/j.ebcr.2017.09.001. Among the molecular abnormalities triggering and/or driving gliomas, alterations in the MAPK pathway reign supreme in the pediatric population, as it is encountered in almost all low-grade pediatric gliomas. [2] Simple DNTs more frequently manifest generalized seizures. They are located the (supra)sellar region and primarily seen in children with a small second peak incidence in older adults. Halfpenny A, Ferris SP, Grafe M, Woltjer R, Selden N, Nazemi K, Perry A, Solomon DA, Gultekin SH, Moore S, Olson S, Lawce H, Lucas L, Corless CL, Wood MD. [2] Diplopia may also be a result of a DNT. When sectioned they demonstrate heterogeneous, often gelatinous, cut surface with nodules of firmer tissue 8. Although the majority of children remain seizure free after surgical excision of DNTs, a considerable number have recurrent seizures. The oligodendrocyte-like cells are typically S100 and OLIG2 positive, and may also express NOGO-A and myelin-oligodendrocyte glycoprotein 8. [2] In children, DNTs are considered to be the second leading cause of epilepsy. Human and animal data suggest that specific genetic factors might play a role in some cases. 2016 Jan;126(1):1-10. doi: 10.1007/s11060-015-1961-4. 2009, 72 (19): 1702-1703. 1. frequent headache The most common symptom caused by low grade gliomas are seizures. There was no association with cortical dysplasia. volume5, Articlenumber:441 (2011) MRI revealed a 32.3 mm (anteroposterior)43.1 mm (transverse)28.3 mm (craniocaudal) multicystic cortico-subcortical parietal lesion, divided by septations, without edema or mass effect, and no enhancement (Figure 1, panels B, C, D). We shopped around for the right neurosurgeons. In this case, the childs strange behavior was secondary to the DNET. Approximately one-third of tumors are malignant and the remainder are benign or borderline malignant [ 1,2 ]. Nashef L, Ryvlin P: Sudden unexpected death in epilepsy (SUDEP): update and reflections. DNETs usually harbor fibroblast growth factor receptor tyrosine kinase domain duplication (FGFR1-TKDD), shared by pilocytic astrocytomas especially when located outside of the cerebellum 11,12. Keywords: Unable to load your collection due to an error, Unable to load your delegates due to an error. http://www.pathologyoutlines.com/topic/cnstumorDNET.html. 10.1046/j.1365-2559.1999.00576.x. Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions. Patients with refractory epilepsy should have complete sleep disorder and cardiology assessments including electrocardiogram evaluation of cardiac rhythm disturbances, which could be performed at the same time as the EEG. Please enable it to take advantage of the complete set of features! Therapies using medication. "WHO Classification of Tumours of the Central Nervous System. [3] These reports suggest that the neurons found within DNTs are much rarer than previously reported. 2020;8(1):21. gliomas, glioneuronal tumors, and neuronal tumors, diffuse astrocytoma, MYB- or MYBL1-altered, polymorphous low-grade neuroepithelial tumor of the young, diffuse low-grade glioma, MAPK pathway-altered, pediatric-type diffuse high-grade gliomas, diffuse hemispheric glioma, H3 G34-mutant, diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (provisional inclusion), supratentorial ependymoma, ZFTA fusion-positive, supratentorial ependymoma, YAP1 fusion-positive, medulloblastoma, SHH-activated and TP53-wildtype, medulloblastoma, SHH-activated and TP53-mutant, cribriform neuroepithelial tumor (provisional inclusion), CNS tumor with BCOR internal tandem duplication, circumscribed meningeal melanocytic neoplasms, with normal to simplified cortical pattern, microcephaly with extensive polymicrogyria, malformations secondary to inborn errors of metabolism, mitochondrial and pyruvate metabolic disorders, cerebellar hypoplasias, not otherwise specified, focal cerebellar cortical dysplasias/heterotopia, lissencephaly with agenesis of corpus callosum and cerebellar dysplasia, associated with diffuse cerebral polymicrogyria. The long history together with the clinical and imaging data led us to the diagnosis of DNP. On CT and MRI, PXAs are characterized by a well-defined peripheral or cortical partially cystic mass most commonly in the temporal lobe. 2017 Dec 1;76(12):1023-1033. doi: 10.1093/jnen/nlx090.

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