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1.
Br J Radiol ; 95(1135): 20211333, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35522773

ABSTRACT

The lacrimal gland is a bilobed serous gland located in the superolateral aspect of the orbit. Lacrimal system pathologies can be broadly divided into pathologies of the lacrimal gland and those of the nasolacrimal drainage apparatus. These include distinct congenital, infectious, inflammatory, and benign, indeterminate, and malignant neoplastic lesions. Trauma and resultant fractures affecting lacrimal drainage apparatus is not part of this review; only non-traumatic diseases will be discussed. CT is the initial modality of choice because of its ability to delineate lacrimal system anatomy and demonstrate most lacrimal drainage system abnormalities and their extent. It also assesses bony architecture and characterizes any osseous changes. MRI is helpful in further characterizing these lesions and better assessing involvement of the surrounding soft tissue structures. In this pictorial review, we will review the anatomy of the lacrimal system, describe CT/MRI findings of the common and uncommon lacrimal system abnormalities and discuss relevance of imaging with regards to patient management.


Subject(s)
Eye Neoplasms , Lacrimal Apparatus Diseases , Lacrimal Apparatus , Diagnosis, Differential , Eye Neoplasms/diagnostic imaging , Humans , Lacrimal Apparatus/diagnostic imaging , Lacrimal Apparatus Diseases/diagnostic imaging , Lacrimal Apparatus Diseases/pathology , Magnetic Resonance Imaging , Tomography, X-Ray Computed
2.
Endocr Connect ; 10(11): 1445-1454, 2021 Nov 08.
Article in English | MEDLINE | ID: mdl-34636742

ABSTRACT

Hypopituitarism tends to occur in large pituitary adenomas. However, similar tumors could present with strikingly different hormonal deficiencies. In this study, we looked at MRI characteristics in non-functioning pituitary adenomas (NFPA), which could predict secondary adrenal insufficiency (SAI) and central hypothyroidism (CHT). We reviewed the files of patients with NFPA attending our clinic. Tumor size, invasiveness, MR-signal intensity, and gadolinium enhancement in preoperative MRI were recorded along with documented presurgical hypopituitarism profile. Logistic regression was used to predict SAI, CHT, or both (SAI/CHT) based on MRI and demographic parameters. Receiver operating characteristic curves were used to determine their diagnostic utility. One hundred twenty-one patients were included in the study. Older age (P = 0.021), male sex (P = 0.043), stalk deviation (P < 0.0001), contrast enhancement (P = 0.029), and optic chiasma compression (P = 0.012) were associated with SAI/CHT. Adenoma vertical height, largest diameter, and estimated volume were also strongly associated with SAI/CHT (P < 0.0001). These associations remained significant in a multivariate analysis. No tumor smaller than 12 mm in vertical height, 17 mm in largest diameter, or 0.9 cm3 in volume was associated with SAI/CHT. At cut-off ≥18 mm for vertical height, ≥23 mm for largest diameter, and ≥3.2 cm3 the sensitivity was around 90-92% for detecting SAI/CHT. Only vertical height was significantly associated with any one or more pituitary hormonal deficit (P = 0.001). In conclusion, adenoma size, independent of the measurement used, remains the best predictor of SAI/CHT in NFPA. Dynamic testing to rule out SAI is probably indicated in adenomas larger than 18 mm vertical height, 23 mm largest diameter and 3.2 cm3 adenoma volume.

3.
Brain Behav ; 11(8): e2261, 2021 08.
Article in English | MEDLINE | ID: mdl-34152089

ABSTRACT

OBJECTIVES: This study aimed to investigate changes in three intrinsic functional connectivity networks (IFCNs; default mode network [DMN], salience network [SN], and task-positive network [TPN]) in individuals who had sustained a mild traumatic brain injury (mTBI). METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 27 mTBI patients with persistent postconcussive symptoms, along with 26 age- and sex-matched controls. These individuals were recruited from a Level-1 trauma center, at least 3 months after a traumatic episode. IFCNs were established based on seed-to-voxel, region-of-interest (ROI) to ROI, and independent component analyses (ICA). Subsequently, we analyzed the relationship between functional connectivity and postconcussive symptoms. RESULTS: Seed-to-voxel analysis of rs-fMRI demonstrated decreased functional connectivity in the right lateral parietal lobe, part of the DMN, and increased functional connectivity in the supramarginal gyrus, part of the SN. Our TPN showed both hypo- and hyperconnectivity dependent on seed location. Within network hypoconnectivity was observed in the visual network also using group comparison. Using an ICA, we identified altered network functional connectivity in regions within four IFCNs (sensorimotor, visual, DMN, and dorsal attentional). A significant negative correlation between dorsal attentional network connectivity and behavioral symptoms score was also found. CONCLUSIONS: Our findings indicate that rs-fMRI may be of use clinically in order to assess disrupted functional connectivity among IFCNs in mTBI patients. Improved mTBI diagnostic and prognostic information could be especially relevant for athletes looking to safely return to play, as well for individuals from the general population with persistent postconcussive symptoms months after injury, who hope to resume activity.


Subject(s)
Brain Concussion , Brain/diagnostic imaging , Brain Concussion/diagnostic imaging , Brain Mapping , Humans , Magnetic Resonance Imaging , Nerve Net , Parietal Lobe
4.
Radiographics ; 41(4): 1230-1242, 2021.
Article in English | MEDLINE | ID: mdl-34048277

ABSTRACT

Image-guided procedures play a critical role in the clinical practice of radiologists. Training radiology residents in these procedures, with early teaching of basic but fundamental skills, is therefore crucial to develop competence before they become autonomous and start their practice. It has been proposed in the literature that low-fidelity phantoms are appropriate to teach novice trainees. The authors propose a series of phantoms to teach the core skills necessary to perform procedures early in resident training. The phantoms described can be used to train skills necessary for performing US-guided biopsy, US-guided vascular puncture, cone-beam CT drainage, and fluoroscopy-guided lumbar puncture, as well as using the parallax effect to determine relative position at fluoroscopy. Phantoms are a valuable training tool, although it is important to consider the teaching audience when choosing or creating a model. For novices, a range of inexpensive low-fidelity gelatin-based phantoms can be used to train core skills in image-guided procedures. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2021.


Subject(s)
Internship and Residency , Radiology, Interventional , Clinical Competence , Education, Medical, Graduate , Humans , Needles , Phantoms, Imaging , Radiology, Interventional/education , Ultrasonography, Interventional
5.
Can Assoc Radiol J ; 72(1): 109-119, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32063026

ABSTRACT

BACKGROUND: The purpose of this study was to build radiogenomics models from texture signatures derived from computed tomography (CT) and 18F-FDG PET-CT (FDG PET-CT) images of non-small cell lung cancer (NSCLC) with and without epidermal growth factor receptor (EGFR) mutations. METHODS: Fifty patients diagnosed with NSCLC between 2011 and 2015 and with known EGFR mutation status were retrospectively identified. Texture features extracted from pretreatment CT and FDG PET-CT images by manual contouring of the primary tumor were used to develop multivariate logistic regression (LR) models to predict EGFR mutations in exon 19 and exon 20. RESULTS: An LR model evaluating FDG PET-texture features was able to differentiate EGFR mutant from wild type with an area under the curve (AUC), sensitivity, specificity, and accuracy of 0.87, 0.76, 0.66, and 0.71, respectively. The model derived from CT texture features had an AUC, sensitivity, specificity, and accuracy of 0.83, 0.84, 0.73, and 0.78, respectively. FDG PET-texture features that could discriminate between mutations in EGFR exon 19 and 21 demonstrated AUC, sensitivity, specificity, and accuracy of 0.86, 0.84, 0.73, and 0.78, respectively. Based on CT texture features, the AUC, sensitivity, specificity, and accuracy were 0.75, 0.81, 0.69, and 0.75, respectively. CONCLUSION: Non-small cell lung cancer texture analysis using FGD-PET and CT images can identify tumors with mutations in EGFR. Imaging signatures could be valuable for pretreatment assessment and prognosis in precision therapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Image Interpretation, Computer-Assisted/methods , Imaging Genomics/methods , Lung Neoplasms/genetics , Machine Learning , Mutation/genetics , Aged , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , ErbB Receptors/genetics , Female , Fluorodeoxyglucose F18 , Humans , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Male , Positron Emission Tomography Computed Tomography/methods , Predictive Value of Tests , Radiopharmaceuticals , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
6.
Neuroimaging Clin N Am ; 30(3): 311-323, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32600633

ABSTRACT

Multiple applications of dual energy computed tomography (DECT) have been described for the evaluation of disorders in the head and neck, especially in oncology. We review the body of evidence suggesting advantages of DECT for the evaluation of the neck compared with conventional single energy computed tomography scans, but the full potential of DECT is still to be realized. There is early evidence suggesting significant advantages of DECT for the extraction of quantitative biomarkers using radiomics and machine learning, representing a new horizon that may enable this technology to reach its full potential.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Radiography, Dual-Energy Scanned Projection/methods , Tomography, X-Ray Computed/methods , Humans
7.
Can Assoc Radiol J ; 70(4): 394-402, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31519372

ABSTRACT

BACKGROUND: The personalization of oncologic treatment using radiomic signatures is mounting in nasopharyngeal carcinoma (NPC). We ascertain the predictive ability of 3D volumetric magnetic resonance imaging (MRI) texture features on NPC disease recurrence. METHODS: A retrospective study of 58 patients with NPC undergoing primary curative-intent treatment was performed. Forty-two image texture features were extracted from pre-treatment MRI in addition to clinical factors. A multivariate logistic regression was used to model the texture features. A receiver operating characteristic curve on 100 bootstrap samples was used to maximize generalizability to out-of-sample data. A Cox proportional model was used to predict disease recurrence in the final model. RESULTS: A total of 58 patients were included in the study. MRI texture features predicted disease recurrence with an area under the curve (AUC), sensitivity, and specificity of 0.79, 0.73, and 0.71, respectively. Loco-regional recurrence was predicted with AUC, sensitivity, and specificity of 0.82, 0.73 and 0.74 respectively while prediction for distant metastasis had an AUC, sensitivity, and specificity of 0.92, 0.79 and 0.84, respectively. Texture features on MRI had a hazard ratio of 4.37 (95% confidence interval 1.72-20.2) for disease recurrence when adjusting for age, sex, smoking, and TNM staging. CONCLUSION: Texture features on MRI are independent predictors of NPC recurrence in patients undergoing curative-intent treatment.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity
8.
Eur Radiol ; 29(11): 6172-6181, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30980127

ABSTRACT

OBJECTIVES: This study was conducted in order to evaluate a novel risk stratification model using dual-energy CT (DECT) texture analysis of head and neck squamous cell carcinoma (HNSCC) with machine learning to (1) predict associated cervical lymphadenopathy and (2) compare the accuracy of spectral versus single-energy (65 keV) texture evaluation for endpoint prediction. METHODS: Eighty-seven patients with HNSCC were evaluated. Texture feature extraction was performed on virtual monochromatic images (VMIs) at 65 keV alone or different sets of multi-energy VMIs ranging from 40 to 140 keV, in addition to iodine material decomposition maps and other clinical information. Random forests (RF) models were constructed for outcome prediction with internal cross-validation in addition to the use of separate randomly selected training (70%) and testing (30%) sets. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for predicting positive versus negative nodal status in the neck. RESULTS: Depending on the model used and subset of patients evaluated, an accuracy, sensitivity, specificity, PPV, and NPV of up to 88, 100, 67, 83, and 100%, respectively, could be achieved using multi-energy texture analysis. Texture evaluation of VMIs at 65 keV alone or in combination with only iodine maps had a much lower accuracy. CONCLUSIONS: Multi-energy DECT texture analysis of HNSCC is superior to texture analysis of 65 keV VMIs and iodine maps alone and can be used to predict cervical nodal metastases with relatively high accuracy, providing information not currently available by expert evaluation of the primary tumor alone. KEY POINTS: • Texture features of HNSCC tumor are predictive of nodal status. • Multi-energy texture analysis is superior to analysis of datasets at a single energy. • Dual-energy CT texture analysis with machine learning can enhance noninvasive diagnostic tumor evaluation.


Subject(s)
Head and Neck Neoplasms/diagnosis , Lymph Nodes/diagnostic imaging , Machine Learning , Multidetector Computed Tomography/methods , Neoplasm Staging/methods , Squamous Cell Carcinoma of Head and Neck/diagnosis , Female , Head and Neck Neoplasms/secondary , Humans , Lymphatic Metastasis , Male , Neck , Squamous Cell Carcinoma of Head and Neck/secondary
9.
Reg Anesth Pain Med ; 43(4): 367-371, 2018 May.
Article in English | MEDLINE | ID: mdl-29346229

ABSTRACT

BACKGROUND AND OBJECTIVES: Accidental breach of the vertebral artery (VA) during the performance of cervical pain blocks can result in significant morbidity. Whereas anatomical variations have been described for the foraminal (V2) segment of the VA, those involving its V3 portion (between the C2 transverse process and dura) have not been investigated and may be of importance for procedures targeting the third occipital nerve or the lateral atlantoaxial joint. METHODS: Five hundred computed tomography angiograms of the neck performed in patients older than 50 years for the management of cerebrovascular accident or cervical trauma (between January 2010 and May 2016) were retrospectively and independently reviewed by 2 neuroradiologists. Courses of the VA in relation to the lateral aspect of the C2/C3 joint and the posterior surface of the C1/C2 joint were examined. For the latter, any medial encroachment of the VA (or one of its branches) was noted. The presence of a VA loop between C1 and C2 and its distance from the upper border of the superior articular process (SAP) of C3 were also recorded. If the VA loop coursed posteriorly, its position in relation to 6 fields found on the lateral aspects of the articular pillars of C2 and C3 was tabulated. RESULTS: At the C1/C2 level, the VA coursed medially over the lateral quarter of the dorsal joint surface in 1% of subjects (0.6% and 0.4% on the left and right sides, respectively; P = 0.998). A VA loop originating between C1 and C2 was found to travel posteroinferiorly over the anterolateral aspect of the inferior articular pillar of C2 in 55.5% of patients on the left and 41.9% on the right side (P < 0.001), as well as over the SAP of C3 in 0.4% of subjects. When present in the quadrant immediately cephalad to the C3 SAP, VA loops coursed within 2.0 ± 1.5 and 3.3 ± 2.5 mm on the left and right sides, respectively, of its superior aspect (P < 0.001). CONCLUSIONS: The VA commonly travels adjacent to areas targeted by third occipital nerve procedures and more rarely over the access point for lateral atlantoaxial joint injections. Modifications to existing techniques may reduce the risk of accidental VA breach.


Subject(s)
Cervical Vertebrae/anatomy & histology , Cervical Vertebrae/diagnostic imaging , Vertebral Artery/anatomy & histology , Vertebral Artery/diagnostic imaging , Atlanto-Axial Joint/anatomy & histology , Atlanto-Axial Joint/blood supply , Atlanto-Axial Joint/diagnostic imaging , Cervical Vertebrae/blood supply , Female , Humans , Male , Middle Aged , Retrospective Studies
10.
US Army Med Dep J ; (3-17): 1-9, 2017.
Article in English | MEDLINE | ID: mdl-29214613

ABSTRACT

PURPOSE: To determine the clinical effect of antibiotic treatment for patients with low back pain and Modic 1 changes. METHODS: This is a retrospective case series of patients treated at the Canadian Forces Health Services Centre in Ottawa and the McGill University Health Centre. Where available, pain, functional, and imaging outcomes in 11 patients treated between 2013 and 2015 were analyzed to determine effect of antibiotic treatment for patients with low back pain and associated Modic 1 changes on magnetic resonance imaging. RESULTS: Conservatively, only 3 of 11 patients met the criteria for improvement for pain and/or function. While a larger proportion improved in the long term, outcomes were not thought to be temporally attributable to antibiotic treatment, as in most cases, ongoing therapy, medications, and/or injections were required. There did not appear to be a correlation between clinical improvement and associated end plate volume involvement for Modic changes. CONCLUSION: Antibiotics for the treatment of low back pain in the context of Modic changes on MRI did not generally provide significant improvement in pain and function for patients in this small cohort. Despite early excitement regarding this treatment, further research is required.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Low Back Pain/diagnostic imaging , Low Back Pain/drug therapy , Magnetic Resonance Imaging , Adult , Canada , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
11.
J Surg Educ ; 74(6): 1135-1141, 2017.
Article in English | MEDLINE | ID: mdl-28688969

ABSTRACT

Simulation allows for learner-centered health professions training by providing a safe environment to practice and make mistakes without jeopardizing patient care. It was with this goal in mind that the McGill Medical Simulation Center was officially opened on September 14, 2006, as a partnership between McGill University, the Faculty of Medicine and its affiliated hospitals. Its mandate is to provide state-of-the-art facilities to support simulation-based medical and allied health education initiatives. Since its inception, the center, recently renamed the Steinberg Center for Simulation and Interactive Learning (SCSIL), has undergone a major expansion and logged more than 130,000 learner visits. Educational activities are offered at all levels of medical and allied health care training, and include standardized patient encounters, partial task trainers, multidisciplinary courses, and high-fidelity trainers, among many others. In addition to its educational mandate, the center also supports an active research program, programs to enhance collaboration with disciplines outside of health care to spur innovation, and community outreach initiatives.


Subject(s)
Education, Medical/organization & administration , Simulation Training/organization & administration , Total Quality Management , Universities/organization & administration , Academic Medical Centers/organization & administration , Curriculum , Female , Humans , Internship and Residency/statistics & numerical data , Male , Program Development , Program Evaluation , Quebec , Students, Medical/statistics & numerical data
12.
Acta Neurochir (Wien) ; 159(8): 1399-1411, 2017 08.
Article in English | MEDLINE | ID: mdl-28555269

ABSTRACT

BACKGROUND: External ventricular drain (EVD) placement is a frequently performed neurosurgical procedure. Inaccuracies in drain positioning and the need for multiple passes using the classic freehand insertion technique is well reported in the literature, especially in the traumatic brain injury (TBI) population. The purpose of this study was to evaluate if electromagnetic neuronavigation guidance for EVD insertion improves placement accuracy and minimizes the number of passes in severe TBI patients. METHODS: Navigation was applied prospectively for all new severe TBI patients who required ventricular catheter placement over a period of 1 year, and compared with a retrospective cohort of severe TBI patients who had EVD inserted freehand in the preceding year. The placement accuracy was evaluated using the Kakarla grading system; the number of passes was also compared. RESULTS: Fifty-four cases were recruited: 35 (64.8%) had their EVD placed using the freehand technique and 19 (35.2%) using navigation guidance. In the navigation group, the placement accuracy was: 94.7% (18/19) grade 1, 5.3% (1/19) grade 2, and none at grade 3. In comparison, freehand placement was associated with misplacement (grades 2 and 3) in 42.9% of the cases (p value = 0.009). The number of passes was significantly lower in the navigation group (mean of 1.16 ± 0.38), compared with the freehand group (mean of 1.63 ± 0.88) (p value = 0.018). CONCLUSIONS: Using the navigation to guide EVD placement was associated with a significantly better accuracy and a lower number of passes in severe TBI patients.


Subject(s)
Brain Injuries, Traumatic/surgery , Drainage/methods , Neuronavigation/methods , Neurosurgical Procedures/methods , Adult , Aged , Drainage/instrumentation , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/instrumentation , Retrospective Studies , Treatment Outcome , Young Adult
13.
Orbit ; 36(1): 19-21, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28146362

ABSTRACT

A 28-year-old Caucasian female presented with a six-month history of epiphora of the right eye. Diagnostic lacrimal syringing revealed obstruction of the right nasolacrimal duct. During external dacryocystorhinostomy (DCR), the lacrimal sac had an unusual papillary appearance. Frozen sections suggested malignant lymphoid cells. Pathologic examination revealed extranodal NK/T-cell lymphoma, nasal type. Imaging revealed a mass lesion centered on the lacrimal sac. The authors describe the youngest Caucasian patient with a primary NK/T-cell lymphoma of the lacrimal sac, as well as the first case presenting with epiphora as the sole presenting symptom, reported in the literature. Extranodal NK/T-cell lymphomas rarely occur in the orbit, and are known to be rapidly growing, aggressive lesions. Despite chemotherapy, the patient succumbed to her disease twelve months after diagnosis. Lacrimal surgeons should maintain a high index of suspicion in all cases of primary nasolacrimal duct obstruction. Pre- or intra-operative clinical suspicion of malignancy in the lacrimal sac necessitates biopsy.


Subject(s)
Eye Neoplasms/diagnosis , Lacrimal Apparatus Diseases/diagnosis , Lymphoma, Extranodal NK-T-Cell/diagnosis , Nasolacrimal Duct/pathology , Adult , Biomarkers, Tumor/metabolism , Dacryocystorhinostomy , Eye Neoplasms/surgery , Female , Humans , Lymphoma, Extranodal NK-T-Cell/genetics , Lymphoma, Extranodal NK-T-Cell/surgery , Nasolacrimal Duct/surgery , Ophthalmologic Surgical Procedures
14.
Oncotarget ; 7(32): 50986-50996, 2016 08 09.
Article in English | MEDLINE | ID: mdl-27248467

ABSTRACT

PURPOSE: This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). METHOD: 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. RESULTS: Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. CONCLUSIONS: DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.


Subject(s)
Brain Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods , Memantine/therapeutic use , Radiation Injuries/diagnostic imaging , Radiation Injuries/prevention & control , Radiation-Protective Agents/therapeutic use , Adult , Aged , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/radiation effects , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Capillary Permeability , Contrast Media , Cranial Irradiation/adverse effects , Female , Humans , Male , Middle Aged , Pilot Projects
15.
J Allergy Clin Immunol ; 137(4): 1178-1188.e7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26521038

ABSTRACT

BACKGROUND: Caspase recruitment domain-containing protein 9 (CARD9) deficiency is an autosomal recessive primary immunodeficiency conferring human susceptibility to invasive fungal disease, including spontaneous central nervous system candidiasis (sCNSc). However, clinical characterization of sCNSc is variable, hindering its recognition. Furthermore, an in-depth understanding of the bases for this susceptibility has remained elusive. OBJECTIVES: We sought to comprehensively characterize sCNSc and to dissect the mechanisms by which a hypomorphic CARD9 mutation causes susceptibility to Candida species. METHODS: We describe the clinical and radiologic findings of sCNSc caused by CARD9 deficiency in a French-Canadian cohort. We performed genetic, cellular, and molecular analyses to further decipher its pathophysiology. RESULTS: In our French-Canadian series (n = 4) sCNSc had onset in adulthood (median, 38 years) and was often misinterpreted radiologically as brain malignancies; 1 patient had additional novel features (eg, endophthalmitis and osteomyelitis). CARD9 deficiency resulted from a hypomorphic p.Y91H mutation and allelic imbalance established in this population through founder effects. We demonstrate a consistent cellular phenotype of impaired GM-CSF responses. The ability of CARD9 to complex with B-cell CLL/lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is intact in our series, arguing against its involvement in susceptibility to fungi. Instead, we show that the p.Y91H mutation impairs the ability of CARD9 to complex with Ras protein-specific guanine nucleotide-releasing factor 1 (RASGRF1), leading to impaired activation of nuclear factor κB and extracellular signal-regulated kinase (ERK) in monocytes and subsequent GM-CSF responses. Successful treatment of a second patient with adjunctive GM-CSF bolsters the clinical relevance of these findings. CONCLUSIONS: Hypomorphic CARD9 deficiency caused by p.Y91H results in adult-onset disease with variable penetrance and expressivity. Our findings establish the CARD9/RASGRF1/ERK/GM-CSF axis as critical to the pathophysiology of sCNSc.


Subject(s)
CARD Signaling Adaptor Proteins/deficiency , CARD Signaling Adaptor Proteins/genetics , Candidiasis, Invasive/immunology , Central Nervous System Fungal Infections/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Immunologic Deficiency Syndromes/genetics , ras-GRF1/immunology , Adult , Biomarkers/metabolism , Candidiasis, Invasive/diagnosis , Candidiasis, Invasive/genetics , Central Nervous System Fungal Infections/diagnosis , Central Nervous System Fungal Infections/genetics , Cohort Studies , Extracellular Signal-Regulated MAP Kinases/immunology , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Genetic Markers , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/microbiology , Male , Point Mutation , Quebec , Real-Time Polymerase Chain Reaction , ras-GRF1/metabolism
16.
Mult Scler J Exp Transl Clin ; 1: 2055217315589775, 2015.
Article in English | MEDLINE | ID: mdl-28607695

ABSTRACT

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly important for the early detection of suboptimal responders to disease-modifying therapy for relapsing-remitting multiple sclerosis. Treatment response criteria are becoming more stringent with the use of composite measures, such as no evidence of disease activity (NEDA), which combines clinical and radiological measures, and NEDA-4, which includes the evaluation of brain atrophy. METHODS: The Canadian MRI Working Group of neurologists and radiologists convened to discuss the use of brain and spinal cord imaging in the assessment of relapsing-remitting multiple sclerosis patients during the treatment course. RESULTS: Nine key recommendations were developed based on published sources and expert opinion. Recommendations addressed image acquisition, use of gadolinium, MRI requisitioning by clinicians, and reporting of lesions and brain atrophy by radiologists. Routine MRI follow-ups are recommended beginning at three to six months after treatment initiation, at six to 12 months after the reference scan, and annually thereafter. The interval between scans may be altered according to clinical circumstances. CONCLUSIONS: The Canadian recommendations update the 2006 Consortium of MS Centers Consensus revised guidelines to assist physicians in their management of MS patients and to aid in treatment decision making.

17.
Can Assoc Radiol J ; 65(2): 148-57, 2014 May.
Article in English | MEDLINE | ID: mdl-24144924

ABSTRACT

OBJECTIVE: This pictorial essay will review the magnetic resonance imaging anatomy of the temporal lobes and describe the major pathologic processes of this complex area. CONCLUSIONS: Magnetic resonance imaging is an essential tool in the investigation of a patient with suspected temporal lobe pathology. Various conditions may affect this anatomic region, and, therefore, classification of imaging findings into specific groups may help provide a more focused differential diagnosis.


Subject(s)
Brain Diseases/diagnosis , Magnetic Resonance Imaging , Temporal Lobe/anatomy & histology , Temporal Lobe/pathology , Contrast Media , Humans , Imaging, Three-Dimensional
18.
Pain Physician ; 15(4): 333-8, 2012.
Article in English | MEDLINE | ID: mdl-22828687

ABSTRACT

BACKGROUND: The personal and societal impact of chronic low back pain is considerable. The intervertebral disc is considered the etiologic source in up to 40% of patients, with considerable previous efforts directed at developing reliable and efficacious treatments. Recent publications, including a double-blind, randomized, placebo-controlled trial, using a one-time treatment of methylene blue, showed statistically significant, clinically relevant improvements in pain and function in the treatment groups. The postulated mechanism of action of methylene blue is denervation of small nociceptive fibers that grow into the annulus fibrosis, which are implicated in discogenic pain. STUDY DESIGN: Retrospective case series. SETTING: Academic pain management center. OBJECTIVES: To examine the outcomes for a cohort of patients treated with methylene blue for discogenic pain, discuss potential differences in selection and administration protocols and briefly review other proposed treatments for discogenic pain (e.g. intradiscal electrothermy therapy, intradiscal steroids, intradiscal biaccuplasty, rami communicans radiofrequency thermocoagulation, and chymopapain). METHODS: This case series examines the pain and functional outcomes in 8 patients treated with a one-time administration of methylene blue for discogenic back pain. Follow-up information was available between 2 months and over one year, depending on the patient. RESULTS: Application of this treatment for these 8 patients for discogenic pain diagnosed by provocation discography showed only one clinical success at our center. Four patients had a time-limited clinical response in pain and/or function between 2 weeks and 5 months. Patient specific data are outlined in detail herein. CONCLUSIONS: Low back pain ascribed to a discogenic source continues to be an elusive clinical entity to treat. We have reserved further treatment of methylene blue for discogenic pain until other controlled trials have been published. LIMITATIONS: A case series.


Subject(s)
Enzyme Inhibitors/administration & dosage , Intervertebral Disc/drug effects , Low Back Pain/drug therapy , Methylene Blue/administration & dosage , Denervation/methods , Humans , Injections, Spinal , Intervertebral Disc/innervation , Retrospective Studies
20.
Int Forum Allergy Rhinol ; 1(6): 488-91, 2011.
Article in English | MEDLINE | ID: mdl-22144059

ABSTRACT

BACKGROUND: It has been recently reported that the site of attachment of Schneiderian papillomas can be predicted with high accuracy on preoperative computed tomography (CT) scans using bony osteitic changes as an indicator. The objective of this study is to evaluate, in a blinded fashion, the reliability of the osteitis sign at predicting the site of attachment of Schneiderian papillomas. METHODS: A retrospective cohort study of patients who underwent endoscopic surgical resection for inverted papilloma (IP) or cylindrical papilloma between September 2002 and September 2009 in a tertiary care rhinology center was carried out. The preoperative sinus CT scans were collected and reviewed by a fellowship-trained and experienced head and neck radiologist who was blinded to the intraoperative findings. The radiologist attempted to identify and grade bony osteitic changes in the sinuses. The radiological findings were then correlated with the actual site of attachment reported by the surgeon in the operative report. RESULTS: A total of 34 patients were evaluated. Six (18%) patients had a single site of osteitis and 28 (82%) were found to have multiple sites of osteitis. The sensitivity and specificity of the radiological prediction based on the degree of osteitis was found to be 74% (46.5-90.3%) and 0% (0-17%), respectively. The predictive value of the radiological localization was 41%. CONCLUSION: Osteitic changes are very common nonspecific findings on CT scans of patients with Schneiderian papillomas. Their presence as well as the degree of osteitis did not allow preoperative localization of tumor attachment.


Subject(s)
Facial Bones/diagnostic imaging , Nasal Mucosa/diagnostic imaging , Nose Neoplasms/diagnostic imaging , Osteitis/diagnostic imaging , Papilloma, Inverted/diagnostic imaging , Papilloma/diagnostic imaging , Paranasal Sinus Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
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