Clinical, Imaging and Neurogenetic Features of Patients with Gliomatosis Cerebri Referred to a Tertiary Neuro-Oncology Centre.

INTRODUCTION: Gliomatosis cerebri describes a rare growth pattern of diffusely infiltrating glioma. The treatment options are limited and clinical outcomes remain poor. To characterise this population of patients, we examined referrals to a specialist brain tumour centre. METHODS: We analysed demographic data, presenting symptoms, imaging, histology and genetics, and survival in individuals referred to a multidisciplinary team meeting over a 10-year period. RESULTS: In total, 29 patients fulfilled the inclusion criteria with a median age of 64 years. The most common presenting symptoms were neuropsychiatric (31%), seizure (24%) or headache (21%). Of 20 patients with molecular data, 15 had IDH wild-type glioblastoma, with an IDH1 mutation most common in the remainder (5/20). The median length of survival from MDT referral to death was 48 weeks (IQR 23 to 70 weeks). Contrast enhancement patterns varied between and within tumours. In eight patients who had DSC perfusion studies, five (63%) had a measurable region of increased tumour perfusion with rCBV values ranging from 2.8 to 5.7. A minority of patients underwent MR spectroscopy with 2/3 (66.6%) false-negative results. CONCLUSIONS: Gliomatosis imaging, histological and genetic findings are heterogeneous. Advanced imaging, including MR perfusion, could identify biopsy targets. Negative MR spectroscopy does not exclude the diagnosis of glioma.

Management of brain tumour related epilepsy (BTRE): a narrative review and therapy recommendations.

Brain Tumour Related Epilepsy (BTRE) has a significant impact on Quality of Life with implications for driving, employment, and social activities. Management of BTRE is complex due to the higher incidence of drug resistance and the potential for interaction between anti-cancer therapy and anti-seizure medications (ASMs). Neurologists, neurosurgeons, oncologists, palliative care physicians and clinical nurse specialists treating these patients would benefit from up-to-date clinical guidelines. We aim to review the current literature and to outline specific recommendations for the optimal treatment of BTRE, encompassing both Primary Brain Tumours (PBT) and Brain Metastases (BM). A comprehensive search of the literature since 1995 on BTRE was carried out in PubMed, MEDLINE and EMCARE. A broad search strategy was used, and the evidence evaluated and graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Seizure frequency varies between 10 and 40% in patients with Brain Metastases (BM) and from 30% (high-grade gliomas) to 90% (low-grade gliomas) in patients with PBT. In patients with BM, risk factors include number of BM and melanoma histology. In patients with PBT, BTRE is more common in patients with lower grade histology, frontal and temporal tumours, presence of an IDH mutation and cortical infiltration. All patients with BTRE should be treated with ASMs. Non-enzyme inducing ASMs are recommended as first line treatment for BTRE, but up to 50% of patients with BTRE due to PBT remain resistant. There is no proven benefit for the use of prophylactic ASMs, although there are no randomised trials testing newer agents. Surgical and oncological treatments i.e. radiotherapy and chemotherapy improve BTRE. Vagus Nerve Stimulation has been used with partial success. The review highlights the relative dearth of high-quality evidence for the management of BTRE and provides a framework for further studies aiming to improve seizure control, quality of life, and indications for ASMs.KEY POINTSOffer levetiracetam or lamotrigine to all patients with primary or metastatic brain tumours who have seizure(s), irrespective of whether these are partial or generalised.ASM withdrawal for patients in remission is not recommended due to high rates of seizure recurrence.ASM prophylaxis is not generally recommended in the management of seizure-naïve patients.Both levetiracetam and lamotrigine are safe in pregnancy and breastfeeding.

Radiation and the nervous system.

Radiation therapy is widely used for benign and malignant brain tumours as it is effective and well tolerated. However, damage to the surrounding healthy nervous system tissue leads to a variety of complications both in the short term and long term, ranging from mild and self-limiting to irreversible and fatal. Radiation neurotoxicity is due to a combination of early inflammation and oligodendroglial damage followed later by brain tissue necrosis, white matter damage, accelerated vascular disease and the development of secondary tumours. This article explains the basic principles of radiation physics, the different modalities used in clinical practice, how radiotherapy is planned and delivered and the scientific basis of radiation damage. The main body of the article focuses on the clinical features of radiation toxicity in the brain, spinal cord, cranial and peripheral nerves with an emphasis on the distinction between early and delayed complications.

Eligibility to drive and neurology: the how and the why.

Driving is an integral part of adult life and losing a driving licence is potentially a major problem. Many neurological conditions may impact on driving, either by increasing the risk of a sudden disabling event or by affecting cognition, vision, reaction speed, motor coordination, peripheral sensation or visuospatial processing. In the UK, the Drivers Medical Group of the Driver and Vehicle Licensing Agency (DVLA) decides whether an individual's medical condition meets the appropriate standards for driving. The licensing decision rests with the DVLA and is not at the clinician's discretion. However, clinicians must inform patients of their legal obligations towards the DVLA and how their neurological symptoms may restrict their driving. We discuss risk assessment, how chronic disabling neurological disease may impact on driving and the general principles of applying medical standards for fitness to drive. We also highlight how legal driving eligibility varies around the world. Finally, we discuss the practical applications relating to a specific case.

Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma.

Epigenetic mechanisms which play an essential role in normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC) are also responsible for some of the changes in the glioblastoma (GBM) genome. Here we develop a strategy to compare the epigenetic and transcriptional make-up of primary GBM cells (GIC) with patient-matched expanded potential stem cell (EPSC)-derived NSC (iNSC). Using a comparative analysis of the transcriptome of syngeneic GIC/iNSC pairs, we identify a glycosaminoglycan (GAG)-mediated mechanism of recruitment of regulatory T cells (Tregs) in GBM. Integrated analysis of the transcriptome and DNA methylome of GBM cells identifies druggable target genes and patient-specific prediction of drug response in primary GIC cultures, which is validated in 3D and in vivo models. Taken together, we provide a proof of principle that this experimental pipeline has the potential to identify patient-specific disease mechanisms and druggable targets in GBM.

Longitudinal structural and perfusion MRI enhanced by machine learning outperforms standalone modalities and radiological expertise in high-grade glioma surveillance.

PURPOSE: Surveillance of patients with high-grade glioma (HGG) and identification of disease progression remain a major challenge in neurooncology. This study aimed to develop a support vector machine (SVM) classifier, employing combined longitudinal structural and perfusion MRI studies, to classify between stable disease, pseudoprogression and progressive disease (3-class problem). METHODS: Study participants were separated into two groups: group I (total cohort: 64 patients) with a single DSC time point and group II (19 patients) with longitudinal DSC time points (2-3). We retrospectively analysed 269 structural MRI and 92 dynamic susceptibility contrast perfusion (DSC) MRI scans. The SVM classifier was trained using all available MRI studies for each group. Classification accuracy was assessed for different feature dataset and time point combinations and compared to radiologists' classifications. RESULTS: SVM classification based on combined perfusion and structural features outperformed radiologists' classification across all groups. For the identification of progressive disease, use of combined features and longitudinal DSC time points improved classification performance (lowest error rate 1.6%). Optimal performance was observed in group II (multiple time points) with SVM sensitivity/specificity/accuracy of 100/91.67/94.7% (first time point analysis) and 85.71/100/94.7% (longitudinal analysis), compared to 60/78/68% and 70/90/84.2% for the respective radiologist classifications. In group I (single time point), the SVM classifier also outperformed radiologists' classifications with sensitivity/specificity/accuracy of 86.49/75.00/81.53% (SVM) compared to 75.7/68.9/73.84% (radiologists). CONCLUSION: Our results indicate that utilisation of a machine learning (SVM) classifier based on analysis of longitudinal perfusion time points and combined structural and perfusion features significantly enhances classification outcome (p value= 0.0001).

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy following anti-CD19 CAR-T therapy: a case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection with few treatment options and poor survival when reversal of the underlying immune dysfunction is not achievable. JC polyomavirus reactivation resulting in PML can rarely complicate chimeric antigen receptor T-cell (CAR-T) therapy. We describe successful treatment of PML with Programmed death-1 (PD-1) blockade using pembrolizumab, 4 months following axicabtagene ciloleucel. Radiological features of immune reconstitution inflammatory syndrome without clinical deterioration were seen. Evidence of anti-viral immune reconstitution by in vitro detection of JC-specific T-cells and sustained neurological recovery in this patient suggest PD-1 blockade may be an effective treatment approach for PML post-CAR-T.

A case study investigating the role of the anterior temporal lobes in general semantics and semantics specific to persons, emotions and social conceptual knowledge.

The role of the anterior temporal lobes (ATLs) in semantic representation remains still much debated. Long thought to support domain-general semantic processing, recent accounts have alternatively suggested that they may be preferentially involved in the processing of person-related semantic knowledge. Several studies have supported such a distinction, but few have either examined both types of semantic processing together, or considered the role of potentially important confounding variables. Here, we address these issues by investigating both domain-general and person-specific semantic processing in a patient with focal ATL damage. The patient presents with dense anterograde and retrograde amnesia. Performance was impaired on tests of general semantic knowledge, but most striking deficits were for person-related semantics, including recognition and identification, knowledge of emotions and social conceptual knowledge. This unique case provides compelling evidence that, in addition to the role in general semantic knowledge, the ATLs are critical for person-related semantics.

Peripheral nerve neurolymphomatosis: Clinical features, treatment, and outcomes.

This series characterises nine patients with neurohistopathologically proven peripheral nerve neurolymphomatosis. A search of the hospital neuropathology database from 2002 to 2019 identified biopsy proven cases. Clinical data, investigation modalities, treatments, and outcomes were collated. Median age at neuropathy onset was 47 y, the neuropathy commonly as the initial lymphoma disease manifestation. Most (8/9) presented with painful asymmetrical sensory disturbance, with additional cranial nerve involvement in three. Neurophysiology typically demonstrated multiple axonal mononeuropathies. Cerebrospinal fluid protein was often raised (6/8). Magnetic resonance imaging suggested peripheral nerve infiltration in 6/9 and positron emission tomography CT in 4/9. Bone marrow biopsy was abnormal in 6/8. Treatment involved systemic or intrathecal chemotherapy and radiotherapy. Median survival was 23 mo. Neurolymphomatosis is a rare but important cause of neuropathy, particularly in those lacking systemic evidence of lymphoma as correct aggressive treatment can prolong survival. Nerve biopsy is essential to classify lymphoma type and rule out alternatives.

Noninvasive diffusion magnetic resonance imaging of brain tumour cell size for the early detection of therapeutic response.

Cancer cells differ in size from those of their host tissue and are known to change in size during the processes of cell death. A noninvasive method for monitoring cell size would be highly advantageous as a potential biomarker of malignancy and early therapeutic response. This need is particularly acute in brain tumours where biopsy is a highly invasive procedure. Here, diffusion MRI data were acquired in a GL261 glioma mouse model before and during treatment with Temozolomide. The biophysical model VERDICT (Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours) was applied to the MRI data to quantify multi-compartmental parameters connected to the underlying tissue microstructure, which could potentially be useful clinical biomarkers. These parameters were compared to ADC and kurtosis diffusion models, and, measures from histology and optical projection tomography. MRI data was also acquired in patients to assess the feasibility of applying VERDICT in a range of different glioma subtypes. In the GL261 gliomas, cellular changes were detected according to the VERDICT model in advance of gross tumour volume changes as well as ADC and kurtosis models. VERDICT parameters in glioblastoma patients were most consistent with the GL261 mouse model, whilst displaying additional regions of localised tissue heterogeneity. The present VERDICT model was less appropriate for modelling more diffuse astrocytomas and oligodendrogliomas, but could be tuned to improve the representation of these tumour types. Biophysical modelling of the diffusion MRI signal permits monitoring of brain tumours without invasive intervention. VERDICT responds to microstructural changes induced by chemotherapy, is feasible within clinical scan times and could provide useful biomarkers of treatment response.

Neurotoxicity-CAR T-cell therapy: what the neurologist needs to know.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most innovative therapies for haematological malignancies to emerge in a generation. Clinical studies have shown that a single dose of CAR T-cells can deliver durable clinical remissions for some patients with B-cell cancers where conventional therapies have failed.A significant complication of CAR therapy is the immune effector cell-associated neurotoxicity syndrome (ICANS). This syndrome presents a continuum from mild tremor to cerebral oedema and in a minority of cases, death. Management of ICANS is mainly supportive, with a focus on seizure prevention and attenuation of the immune system, often using corticosteroids. Parallel investigation to exclude other central nervous system pathologies (infection, disease progression) is critical. In this review, we discuss current paradigms around CAR T-cell therapy, with a focus on appropriate investigation and management of ICANS.

Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment.

Tumour-associated microglia/macrophages (TAM) are the most numerous non-neoplastic populations in the tumour microenvironment in glioblastoma multiforme (GBM), the most common malignant brain tumour in adulthood. The mTOR pathway, an important regulator of cell survival/proliferation, is upregulated in GBM, but little is known about the potential role of this pathway in TAM. Here, we show that GBM-initiating cells induce mTOR signalling in the microglia but not bone marrow-derived macrophages in both in vitro and in vivo GBM mouse models. mTOR-dependent regulation of STAT3 and NF-κB activity promotes an immunosuppressive microglial phenotype. This hinders effector T-cell infiltration, proliferation and immune reactivity, thereby contributing to tumour immune evasion and promoting tumour growth in mouse models. The translational value of our results is demonstrated in whole transcriptome datasets of human GBM and in a novel in vitro model, whereby expanded-potential stem cells (EPSC)-derived microglia-like cells are conditioned by syngeneic patient-derived GBM-initiating cells. These results raise the possibility that microglia could be the primary target of mTOR inhibition, rather than the intrinsic tumour cells in GBM.

Seizure outcomes and survival in adult low-grade glioma over 11 years: living longer and better.

BACKGROUND: There has been a trend toward earlier and more aggressive resection for low-grade gliomas (LGGs). This study set out to compare seizure control and survival of adults with LGG seen in the same neuro-oncology clinic over 11 years and to determine whether a change in surgical philosophy has led to a corresponding improvement in outcomes. METHODS: We conducted a retrospective analysis using case-note review of 153 adults with histologically verified or radiologically suspected LGG, collecting data on patient, tumor, and seizure characteristics between 2006 and 2017. RESULTS: We studied 79 patients in 2006 and 74 patients in 2017. There was no significant difference between the 2 groups in age at presentation, tumor location, or integrated pathological diagnosis. The numbers of complete or partial resections increased from 21.5% in 2006 to 60.8% in 2017 (P < .05). Five- and 10-year overall survival increased from 81.8% and 51.7% in 2006 to 100% and 95.8% in 2017 (P < .001); similarly, 5- and 10-year progression-free survival increased from 47.0% and 30.7% in 2006 to 93.1% and 68.7% in 2017. The proportion of patients with intractable epilepsy declined from 72.2% in 2006 to 43.2% in 2017 (P < .05). The neurosurgical morbidity rate was identical in both groups (11.8% in 2006 vs 11.1% in 2017). CONCLUSION: Management of LGG over the last 11 years has led to substantial improvements in survival and seizure control. This is most likely thanks to a change in surgical philosophy, with early resection now favored over watchful waiting where possible.

The provision of dental implants: current practice among university and hospital specialists in restorative dentistry within the UK and Ireland.

Objectives To establish current implant practice among university and hospital restorative dental specialists in the United Kingdom (UK) and Ireland and their opinions relating to criteria for implant treatment.Materials and methods An online questionnaire was distributed to 150 university and hospital restorative dental specialists in the UK and Ireland.Results The response rate was 27%. Twenty-nine (70%) respondents provided implant treatment, of which 76% and 100% placed and restored implants respectively. In addition, 79% worked with oral surgeons or oral and maxillofacial surgeons as part of the implant team. Hypodontia and malignancy were cited as the main groups that qualified for NHS dental implant treatment. Irradiation, smoking and bisphosphonates were considered the most important medical factors in patient selection for implant placement, while untreated periodontitis, poor oral hygiene and uncontrolled caries were the most important dental factors.Conclusions The majority of responding university and hospital restorative dental specialists within the UK and Ireland provide dental implant treatment and undertake a multidisciplinary approach where necessary. There is variation in the number of patients treated with implants by each respondent annually. The main patient groups that receive priority for NHS dental implant treatment are malignancy and hypodontia. Otherwise, there is general agreement about the factors considered important when selecting patients for implant treatment on the NHS and this aligns to the Royal College of Surgeons guidelines on selecting patients for the provision of dental implants.

Maintaining peri-implant health: an evaluation of understanding among dental hygienists and therapists in Wales.

Objectives To describe the approach taken by dental hygienists and therapists (DH/Ts) in Wales regarding dental implant maintenance. To gather their opinions about the current level of implant education.Materials and methods Online questionnaires were distributed to 257 DH/Ts within Wales.Results The response rate was 35%. Dental implant care was within the remit of service for 92% of respondents. All respondents that provided implant care stated that they performed oral hygiene instruction, while 98% performed supragingival debridement, 85% subgingival debridement, and 64% clinical assessment of peri-implant health. A high proportion of DH/Ts in Wales did not feel entirely confident in carrying out procedures relating to peri-implant maintenance and only 27% felt confident in clinically assessing dental implants. The majority (83%) felt that postgraduate training in peri-implant maintenance should be obligatory. 'No available courses' was the main reason for not attending further postgraduate training in implantology.Conclusions A high proportion of responding DH/Ts practising in Wales do not feel entirely confident in carrying out procedures relating to peri-implant maintenance. Postgraduate training may be useful in addressing this issue and undergraduate training programmes may need to consider increasing trainees' exposure to dental implant maintenance.

Teaching of implant dentistry in dental hygiene and therapy schools in the UK and Ireland.

Objective The aim of this study was to assess the current status of implant teaching within dental hygiene and therapy schools in the UK and Ireland.Methods An online questionnaire relating to current and future possible trends in dental implantology education was developed and distributed to programme directors in each of the 23 dental hygiene and therapy schools in the UK and Ireland.Results All responding schools (response rate of 60%) provided implant training for their students. The teaching is mainly delivered in lecture-based or phantom head room settings. The majority of schools provided direct clinical experience in procedures relating to peri-implant maintenance, although in some schools it was stated that not every student was guaranteed to receive such experience. In 86% of schools, students gained experience in oral hygiene and scaling, while 71% and 64% provided experience of non-surgical management of patients with peri-implant mucositis and peri-implantitis, respectively. The main barrier to developing the implant programme was an insufficient number of suitable cases.Conclusions Although all responding schools provide implant training, the overall findings show that further development and improvement of implant teaching in dental hygiene and therapy schools within the UK and Ireland is required, particularly with respect to direct clinical experience. This will ensure that newly qualified dental hygienists and therapists are sufficiently prepared for managing implant patients in their clinical practice.

Array analysis for T-cell associated cytokines in gingival crevicular fluid: Identifying altered profiles associated with periodontal disease status.

OBJECTIVE: Cytokine networks regulate innate and adaptive immune responses, which in turn are recognised to direct the progression or arrest of periodontal disease. This study aimed to compare the profile of seven cytokines, implicated in regulating T-cell networks, in gingival crevicular fluid (GCF) samples with differing classification of periodontal status. METHODS: GCF samples were collected from patients with strong clinical evidence for chronic periodontitis, aggressive periodontitis, gingivitis or no gingival inflammation. Cytokines IL-6, IFN-É£, IL-4, IL-2, IL-17 A, IL10 and TNFα were measured in each sample using a commercial cytometric bead array assay. Descriptive statistics were used to indicate central tendency, data scatter and analysis of variance for each cytokine concentrations between respective patient groups. Heat maps with dendrograms were produced to visualise hierarchical clustering and trends within the data. RESULTS: Median concentrations for all cytokines analysed were highest for gingivitis samples and lowest for aggressive periodontitis samples. The median concentration of IL-6 in gingivitis samples was observed to be 10.5 fold higher (˜17,300 pg/µl) than IL-6 in aggressive periodontitis samples (˜1600 pg/µl). Median concentrations of IL-10, IL-17 A and TNFα were also 2-2.2 fold higher in gingivitis samples compared to aggressive periodontitis. CONCLUSIONS: Descriptive statistical analysis noted raised concentrations of IL-6, IL-17 A and TNFα associated with gingivitis; pro-inflammatory cytokines usually associated with periodontal tissue destruction, including bone. Our results would suggest that these cytokines can additionally provide protective roles in preventing progression to advanced forms of periodontal disease. Potential for how these cytokines contribute to providing this role is discussed. CLINICAL SIGNIFICANCE: Defining the roles for the many cytokines involved in the pathogenesis of periodontal disease is far from complete. Consequently the results of this study serve to evidence proposals that cytokines can exhibit both pro- and anti-inflammatory effects, which is dependent on the signalling environment within which they exist and the antagonizing or modifying actions of other cytokines. Whilst future research is necessary to explore mechanistic action, our study contributes new knowledge suggesting that IL-6 and IL-17 A can provide roles in stabilising the lesion to limit disease progression, which does not preclude alternative roles in promoting periodontal bone loss in advanced forms of disease progression, which is also documented in the literature.

Modelling MR and clinical features in grade II/III astrocytomas to predict IDH mutation status.

BACKGROUND AND PURPOSE: There is increasing evidence that many IDH wildtype (IDHwt) astrocytomas have a poor prognosis and although MR features have been identified, there remains diagnostic uncertainty in the clinic. We have therefore conducted a comprehensive analysis of conventional MR features of IDHwt astrocytomas and performed a Bayesian logistic regression model to identify critical radiological and basic clinical features that can predict IDH mutation status. MATERIALS AND METHODS: 146 patients comprising 52 IDHwt astrocytomas (19 WHO Grade II diffuse astrocytomas (A II) and 33 WHO Grade III anaplastic astrocytomas (A III)), 68 IDHmut astrocytomas (53 A II and 15 A III) and 26 GBM were studied. Age, sex, presenting symptoms and Overall Survival were recorded. Two neuroradiologists assessed 23 VASARI imaging descriptors of MRI features and the relation between IDH mutation status and MR and basic clinical features was modelled by Bayesian logistic regression, and survival by Kaplan-Meier plots. RESULTS: The features of greatest predictive power for IDH mutation status were, age at presentation (OR = 0.94 +/-0.03), tumour location within the thalamus (OR = 0.15 +/-0.25), involvement of speech receptive areas (OR = 0.21 +/-0.26), deep white matter invasion of the brainstem (OR = 0.10 +/-0.32), and T1/FLAIR signal ratio (OR = 1.63 +/-0.64). A logistic regression model based on these five features demonstrated excellent out-of-sample predictive performance (AUC = 0.92 +/-0.07; balanced accuracy 0.81 +/-0.09). Stepwise addition of further VASARI variables did not improve performance. CONCLUSION: Five demographic and VASARI features enable excellent individual prediction ofIDH mutation status, opening the way to identifying patients with IDHwt astrocytomas for earlier tissue diagnosis and more aggressive management.

Real-time binding kinetic analyses of the interaction of the dietary stain orange II with dentin matrix.

OBJECTIVES: Dietary stains can be adsorbed into the dentin of teeth. Using Orange II as a model dietary stain, this study investigated the strength of its interaction with the mineral and protein components of dentin matrix and how hydrogen peroxide (H2O2) treatment influences this interaction. METHODS: Dentin slices were prepared from human teeth and were either deproteinized (5.6% sodium hypochlorite, 12 days), demineralised (0.5 M EDTA, 3 days) or left as intact control samples. Samples were stained with Orange II for 1-168 h, during which staining intensity was quantified by image analysis. Similarly, uptake of stain by deproteinized / demineralized samples treated with 10 or 30% H2O2 was investigated. Using surface plasmon resonance technology, real-time binding kinetics were determined assessing the interaction of Orange II with the dentin matrix protein constituents, collagen type I, biglycan, decorin, dentin sialoprotein and osteopontin. RESULTS: Deproteinization of dentin matrix reduced the uptake of the Orange II compared to the intact control. Conversely, demineralization of dentin samples increased the uptake of the dye. Treatment of samples for 48 h with H2O2 reduced subsequent uptake of the Orange II. Real-time kinetic analysis indicated moderate strength of binding for Orange II with collagen type I, weak binding with decorin and biglycan and negligible binding with dentine sialoprotein and osteopontin. CONCLUSION: These results indicate a predominant role for collagen type I, which accounts for 90% of the organic protein matrix of teeth, for attracting dietary stains. Binding analyses indicate that the interaction is highly dissociable, and further binding is reduced following H2O2 treatment. CLINICAL SIGNIFICANCE: This study provides new information regarding adsorption of dietary stains into tooth dentin, suggesting that they are attracted and moderately bound to the collagen type I matrix. This study also contributes valuable information for discussion for considering the effect of H2O2 on bleaching teeth and its influence on subsequent uptake of dietary stains following whitening treatments.