Endoscopic grading of gastric atrophy on risk assessment of gastric neoplasia: A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic examination of gastric atrophy has been developed to determine the extent of atrophy by identifying the atrophic border of gastric mucosa, but its value in predicting the risk of developing gastric neoplasms is not quantified. Thus, this systematic review and meta-analysis aim to assess the incidence risk of gastric neoplasms on the basis of endoscopic grading of gastric atrophy. METHODS: Two authors independently searched the electronic databases (PubMed, Embase, and the Cochrane Library) from inception through December 31, 2019, without language restriction. The effect size on study outcomes is calculated using random-effects model and presented as risk ratio (RR) with 95% confidence interval (CI). Heterogeneity, publication bias, and quality of included studies were also assessed. RESULTS: Fourteen retrospective studies are identified to perform systematic review and meta-analysis, 11 were cohort studies, and three were cross-sectional research. The pooled RR for developing gastric neoplasms is 3.89 (95% CI 2.92-5.17) among general patients with severe endoscopic atrophy. For patients who underwent endoscopic resection for early gastric neoplasms, nearly two times increased risk of synchronous or metachronous neoplasms is pooled (RR = 1.96, 95% CI 1.39-2.75). In terms of the type of endoscopic atrophy, patients with open-type endoscopic atrophy have a higher risk of gastric cancer development (RR 8.02; 95% CI 2.39-26.88) than those with close type. [Correction added on 22 December 2020, after first online publication: '(RR = 7.27; 95% CI 1.64-32.33)' has been corrected to '(RR 8.02; 95% CI 2.39-26.88)'] CONCLUSIONS: Grading endoscopic atrophy according to the Kimura-Takemoto classification can assess the risk of gastric neoplasia development. Patients with severe or open-type endoscopic gastric atrophy at baseline should undergo rigorous surveillance to early detect premalignant lesions and cancer.

Latent atrophy factors related to phenotypical variants of posterior cortical atrophy.

OBJECTIVE: To determine whether atrophy relates to phenotypical variants of posterior cortical atrophy (PCA) recently proposed in clinical criteria (i.e., dorsal, ventral, dominant-parietal, and caudal) we assessed associations between latent atrophy factors and cognition. METHODS: We employed a data-driven Bayesian modeling framework based on latent Dirichlet allocation to identify latent atrophy factors in a multicenter cohort of 119 individuals with PCA (age 64 ± 7 years, 38% male, Mini-Mental State Examination 21 ± 5, 71% ß-amyloid positive, 29% ß-amyloid status unknown). The model uses standardized gray matter density images as input (adjusted for age, sex, intracranial volume, MRI scanner field strength, and whole-brain gray matter volume) and provides voxelwise probabilistic maps for a predetermined number of atrophy factors, allowing every individual to express each factor to a degree without a priori classification. Individual factor expressions were correlated to 4 PCA-specific cognitive domains (object perception, space perception, nonvisual/parietal functions, and primary visual processing) using general linear models. RESULTS: The model revealed 4 distinct yet partially overlapping atrophy factors: right-dorsal, right-ventral, left-ventral, and limbic. We found that object perception and primary visual processing were associated with atrophy that predominantly reflects the right-ventral factor. Furthermore, space perception was associated with atrophy that predominantly represents the right-dorsal and right-ventral factors. However, individual participant profiles revealed that the large majority expressed multiple atrophy factors and had mixed clinical profiles with impairments across multiple domains, rather than displaying a discrete clinical-radiologic phenotype. CONCLUSION: Our results indicate that specific brain behavior networks are vulnerable in PCA, but most individuals display a constellation of affected brain regions and symptoms, indicating that classification into 4 mutually exclusive variants is unlikely to be clinically useful.

The Value of Corpus Callosum Measurement in the Diagnosis of Cerebral Atrophy.

OBJECTIVE: The study aimed to investigate the relationship between the corpus callosum area (CCa) and the degree of cerebral atrophy in patients with cerebral atrophy. METHODS: 119 patients with brain atrophy were grouped according to the degree of brain atrophy. Median sagittal CCa and intracranial area (ICa) were measured, and the ratio of corpus callosum to the intracranial area (CCa-ICa ratio) was calculated. The data were analyzed using ANOVA. RESULTS: CCa significantly reduced in patients with cerebral atrophy, and the degree of cerebral atrophy was found to be positively correlated with the degree of reduction in the CCa. CONCLUSION: The reduction in the CCa and the CCa-ICa ratio in the median sagittal can be used as a reference indicator for the diagnosis and grading of brain atrophy in clinical practice.

Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis.

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa. Today, endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori (H. pylori) infection and evaluate gastric cancer risk. In 2013, the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification, a new grading system for endoscopic gastritis. The Kyoto classification organized endoscopic findings related to H. pylori infection. The Kyoto classification score is the sum of scores for five endoscopic findings (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness with or without regular arrangement of collecting venules) and ranges from 0 to 8. Atrophy, intestinal metaplasia, enlarged folds, and nodularity contribute to gastric cancer risk. Diffuse redness and regular arrangement of collecting venules are related to H. pylori infection status. In subjects without a history of H. pylori eradication, the infection rates in those with Kyoto scores of 0, 1, and ≥ 2 were 1.5%, 45%, and 82%, respectively. A Kyoto classification score of 0 indicates no H. pylori infection. A Kyoto classification score of 2 or more indicates H. pylori infection. Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8, respectively. A Kyoto classification score of 4 or more might indicate gastric cancer risk.

Progression of Parkinson's disease patients' subtypes based on cortical thinning: 4-year follow-up.

BACKGROUND: Three cortical atrophy patterns were previously identified in non-demented Parkinson's disease patients using a data-driven approach based on cortical thickness data: i) parieto-temporal pattern of atrophy with worse cognitive performance (pattern 1), ii) occipital and frontal cortical atrophy with younger disease onset (pattern 2), and iii) non-detectable cortical atrophy (pattern 3). We aimed to investigate the evolution of these three patterns over time. METHODS: Magnetic resonance imaging and neuropsychological assessment were obtained at baseline and follow-up (3.8 ±â€¯0.4 year apart) in a group of 45 Parkinson's disease patients and 22 healthy controls. FreeSurfer was used for cortical thickness analysis and global atrophy measures. RESULTS: Temporo-parietal cortical thinning occurred in pattern 2, 3 and controls groups, and patients showed decline in processing speed (as measured by the Stroop Word-Color test, the Symbol Digits Modalities test and the Trail Making Test Part B) and in semantic fluency (animals). Pattern 3 patients showed more progressive cortical thinning in the left prefrontal cortex than controls and more right occipital thinning than pattern 2 patients over time. Pattern 1 patients had greater compromise in activities of the daily living and suffered higher attrition rate. CONCLUSION: The Parkinson's disease phenotypes identified using cluster analysis of cortical thickness data showed different progression over time. The presence of prefrontal thinning and younger disease onset at baseline was associated to less cortical degeneration, while non-atrophic patients progressed showing a temporo-parietal cortical thinning.

Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales.

BACKGROUND: In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes. We used visual rating scales to investigate whether identifying atrophy in these areas may be helpful in distinguishing symptomatic patients carrying different causal mutations in the microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame (C9ORF72) genes. We also analysed asymptomatic carriers to see whether it was possible to visually identify brain atrophy before the appearance of symptoms. METHODS: Magnetic resonance imaging of 343 subjects (63 symptomatic mutation carriers, 132 presymptomatic mutation carriers and 148 control subjects) from the Genetic Frontotemporal Dementia Initiative study were analysed by two trained raters using a protocol of six visual rating scales that identified atrophy in key regions of the brain (orbitofrontal, anterior cingulate, frontoinsula, anterior and medial temporal lobes and posterior cortical areas). RESULTS: Intra- and interrater agreement were greater than 0.73 for all the scales. Voxel-based morphometric analysis demonstrated a strong correlation between the visual rating scale scores and grey matter atrophy in the same region for each of the scales. Typical patterns of atrophy were identified: symmetric anterior and medial temporal lobe involvement for MAPT, asymmetric frontal and parietal loss for GRN, and a more widespread pattern for C9ORF72. Presymptomatic MAPT carriers showed greater atrophy in the medial temporal region than control subjects, but the visual rating scales could not identify presymptomatic atrophy in GRN or C9ORF72 carriers. CONCLUSIONS: These simple-to-use and reproducible scales may be useful tools in the clinical setting for the discrimination of different mutations of frontotemporal dementia, and they may even help to identify atrophy prior to onset in those with MAPT mutations.

Atrophy patterns in cerebral amyloid angiopathy with and without cortical superficial siderosis.

OBJECTIVE: To investigate differential atrophy patterns based on the presence of cortical superficial siderosis (cSS) and the role of cSS in predicting amyloid positivity in memory clinic patients fulfilling the diagnostic criteria for probable cerebral amyloid angiopathy (CAA). METHODS: We retrospectively collected data from 44 cognitively impaired patients with probable CAA who underwent 3-dimensional, T1-weighted MRIs (cSS+, n = 27; cSS-, n = 17). Amyloid-positive patients with Alzheimer disease (AD) (n = 56) and amyloid-negative cognitively normal participants (n = 34) were recruited as controls. Among the patients with CAA who underwent amyloid-PET scans (75.0%), we investigated whether amyloid-negative cases were unevenly distributed based on cSS presentation. APOE genotypes, Mini-Mental State Examination scores, and cortical atrophy pattern along with hippocampal volume were compared across groups. RESULTS: Ten patients with probable CAA presented amyloid negativity and all of them belonged to the cSS- group (58.8%). Compared to the cSS- group, the cSS+ group presented higher APOE ε4 frequency, worse memory dysfunction, and lower hippocampal volume. Compared with cognitively normal participants, the cSS+ group exhibited atrophy in the precuneus, posterior cingulate, parietotemporal, superior frontal, and medial temporal areas, a pattern similar to AD-specific atrophy. The cSS- group exhibited atrophy in the parietotemporal, superior frontal, and precentral regions. CONCLUSION: Our findings imply that the current version of the Boston criteria may not be sufficient enough to remove non-CAA cases from a cognitively impaired population, especially in the absence of cSS. Patients with probable CAA presenting cSS appear to reflect a CAA phenotype that shares pathologic hallmarks with AD, providing insight into the CAA-to-AD continuum.

Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline.

OBJECTIVE: To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline. METHODS: Amyloid-positive participants with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD [tADMRI]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models. RESULTS: When participants were divided categorically, the HpSpMRI group showed significantly more AD-like hypometabolism on 18F-fluorodeoxyglucose-PET (p < 0.05) and poorer baseline executive function (p < 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSpMRI also showed faster subsequent clinical decline than participants with LPMRI on the Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog13), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tADMRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog13 score (p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy. CONCLUSIONS: AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.

Classification of the level of mandibular atrophy - A computer-assisted study based on 500 CT scans.

OBJECTIVE: For the optimal treatment of patients with highly atrophic mandibles, it is required to assess and quantify the extent of atrophy. The classification schemes that are well established today are known to be limited with respect to objectivity and reproducibility. Thus, the aim of the study was to generate a computer-aided method of classification, investigate its applicability in comparison with the established methods, and apply it to a large set of data. MATERIALS AND METHODS: Mandibular geometries were segmented from 500 Multislice (MSCT) datasets of atrophic and non-atrophic mandibles and automatically processed to gain virtual images of the mandibular cross-sections. Three different human investigators classified these data according to Cawood and Howell's classification scheme. Additionally, a tailored computer algorithm was applied that could work automatically and thus be observer independent. Furthermore, geometrical properties of the mandibles were investigated, statistically analysed, and correlated to the protocolled dental status and to the human and computer-generated classifications. RESULTS: Whilst the atrophy classification scheme showed highly significant correlation to the local dimensions of the alveolar ridge, its reproducibility was limited. It was shown that the human classifiers could not objectively classify the mandibular atrophy according to the established methods, with only 60.9% of decisions being unequivocal. The computer-aided method showed similar results to the human investigators. CONCLUSION: It is feasible to develop computer-aided procedures for the objective and fully reproducible classification of the level of atrophy. With further research, the established classification scheme may be ameliorated with the aid of computational methods.

Classifying anatomical subtypes of subjective memory impairment.

We aimed to categorize subjective memory impairment (SMI) individuals based on their patterns of cortical thickness and to propose simple models that can classify each subtype. We recruited 613 SMI individuals and 613 age- and gender-matched normal controls. Using hierarchical agglomerative cluster analysis, SMI individuals were divided into 3 subtypes: temporal atrophy (12.9%), minimal atrophy (52.4%), and diffuse atrophy (34.6%). Individuals in the temporal atrophy (Alzheimer's disease-like atrophy) subtype were older, had more vascular risk factors, and scored the lowest on neuropsychological tests. Combination of these factors classified the temporal atrophy subtype with 73.2% accuracy. On the other hand, individuals with the minimal atrophy (non-neurodegenerative) subtype were younger, were more likely to be female, and had depression. Combination of these factors discriminated the minimal atrophy subtype with 76.0% accuracy. We suggest that SMI can be largely categorized into 3 anatomical subtypes that have distinct clinical features. Our models may help physicians decide next steps when encountering SMI patients and may also be used in clinical trials.

New Atrophic Acne Scar Classification: Reliability of Assessments Based on Size, Shape, and Number.

BACKGROUND: Post-acne atrophic scarring is a major concern for which standardized outcome measures are needed. Traditionally, this type of scar has been classified based on shape; but survey of practicing dermatologists has shown that atrophic scar morphology has not been well enough defined to allow good agreement in clinical classification. Reliance on clinical assessment is still needed at the current time, since objective tools are not yet available in routine practice.
OBJECTIVES: Evaluate classification for atrophic acne scars by shape, size, and facial location and establish reliability in assessments.
METHODS: We conducted a non-interventional study with dermatologists performing live clinical assessments of atrophic acne scars. To objectively compare identification of lesions, individual lesions were marked on a high-resolution photo of the patient that was displayed on a computer during the clinical evaluation. The Jacob clinical classification system was used to define three primary shapes of scars 1) icepick, 2) boxcar, and 3) rolling. To determine agreement for classification by size, independent technicians assessed the investigators' markings on digital images. Identical localization of scars was denoted if the maximal distance between their centers was ≤ 60 pixels (approximately 3 mm). Raters assessed scars on the same patients twice (morning/afternoon). Aggregate models of rater assessments were created and analyzed for agreement.
RESULTS: Raters counted a mean scar count per subject ranging from 15.75 to 40.25 scars. Approximately 50% of scars were identified by all raters and ~75% of scars were identified by at least 2 of 3 raters (weak agreement, Kappa pairwise agreement 0.30). Agreement between consecutive counts was moderate, with Kappa index ranging from 0.26 to 0.47 (after exclusion of one outlier investigator who had significantly higher counts than all others). Shape classifications of icepick, boxcar, and rolling differed significantly between raters and even for same raters at consecutive sessions (P<.001 and P=0.4, respectively). Analysis showed only 65% of scars were identical in both sessions. We also found that there is a threshold of detection in terms of size, with poor agreement among investigators for very small scars (<2 mm). The repeatability of identification of scars ≥ 2.0 mm was acceptable, and we found that increasing scar size was positively correlated with agreement. Reliability was improved when only scars >2 mm were included. For smaller scars (<2 mm), inter-rater reliability was poor.
CONCLUSIONS: While intuitively it makes sense that describing scar morphology could guide treatment, we have shown that shape-based evaluations are subjective and do not readily yield strong agreement. Until there is a more objective way to evaluate morphology that is readily available to practicing clinicians, we propose that size should be considered a primary characteristic for scar classification systems. We further suggest classification of <2 mm, 2-4 mm, and >4 mm based on how the size would likely affect diagnostic and therapeutic choices. Finally, we recommend that scars <2 mm not be included in a clinical classification but should be evaluated by an objective method that may be refined in the future.

J Drugs Dermatol. 2016;15(6):693-702.

Is a detailed grading of villous atrophy necessary for the diagnosis of enteropathy?

AIMS: The utility of the 7 level Marsh-Oberhuber classification of mucosal damage in patients with coeliac disease has recently been criticised. Analysis of duodenal biopsies with dissecting microscopy is an unsophisticated method that, however, provides useful information in cases of frank villous atrophy. In the last 15 years, we have always analysed duodenal biopsies with dissecting microscopy before sending them to the pathology department for histology. If the results of dissecting microscopy and traditional histology were comparable, we feel that would be strong evidence that grading of the histological lesion would be unnecessary if not pointless in the everyday diagnosis of enteropathies. METHODS: The clinical notes of all 2075 patients undergoing duodenal biopsy between September 1999 and June 2015 were retrospectively analysed. Results of duodenal mucosal evaluation with both dissecting microscopy and traditional histology were collected and statistically compared. RESULTS: The κ statistics showed a substantial agreement of the two methods (κ statistics 0.78). Sensitivity of dissecting microscopy for detection of severe villous atrophy was 85.1% (95% CI 81.2% to 88.5%) and specificity was 95% (95% CI 93.8% to 96%). CONCLUSIONS: Although dissecting microscopy is an unsophisticated method that obviously cannot substitute traditional histology, our results suggest that in everyday clinical practice, the diagnosis of coeliac disease and other flat enteropathies does not require grading of villous atrophy.

Relationship between the degree of endoscopic atrophy of the gastric mucosa and carcinogenic risk.

BACKGROUND: The relationship between Helicobacter pylori infection and gastric cancer has been demonstrated, and the risk of gastric cancer occurrence is known to increase with the progression of atrophic changes associated with chronic gastritis. Endoscopic evaluation of the degree and extent of atrophy of the gastric mucosa is a simple and very important means of identifying a group at high risk for gastric cancer. This study aimed to clarify the carcinogenic risk in relation to the degree of atrophy. METHODS: A total of 27,777 patients (272 with early gastric cancer and 135 with advanced gastric cancer) were included in this study. Endoscopically evaluated atrophy of the gastric mucosa was classified as C-0 to O-3 according to the Kimura and Takemoto classification system. RESULTS: The cancer detection rate in relation to the degree of gastric mucosal atrophy was 0.04% (2/4,183 patients) for C-0, 0% (0/4,506) for C-1, 0.25% (9/3,660) for C-2, 0.71% (21/2,960) for C-3, 1.32% (75/5,684) for O-1, 3.70% (140/3,780) for O-2 and 5.33% (160/3,004) for O-3. As to the proportions of differentiated and undifferentiated cancers, the latter were relatively frequent in the C-0 to C-2 groups, but differentiated cancers became predominant as atrophy progressed. On the other hand, the number of both differentiated and undifferentiated cancers detected increased as gastric mucosal atrophy progressed. In addition, open-type atrophy was found in 29 (96.7%) of 30 patients with synchronous multiple gastric cancers and in all 20 patients with metachronous multiple gastric cancers. CONCLUSION: Endoscopic evaluation of gastric mucosal atrophy can provide a simple and reliable predictive index for both current and future carcinogenic risk.

Magnetic resonance imaging pattern learning in temporal lobe epilepsy: classification and prognostics.

OBJECTIVE: In temporal lobe epilepsy (TLE), although hippocampal atrophy lateralizes the focus, the value of magnetic resonance imaging (MRI) to predict postsurgical outcome is rather modest. Prediction solely based on the hippocampus may be hampered by widespread mesiotemporal structural damage shown by advanced imaging. Increasingly complex and high-dimensional representation of MRI metrics motivates a shift to machine learning to establish objective, data-driven criteria for pathogenic processes and prognosis. METHODS: We applied clustering to 114 consecutive unilateral TLE patients using 1.5T MRI profiles derived from surface morphology of hippocampus, amygdala, and entorhinal cortex. To evaluate the diagnostic validity of the classification, we assessed its yield to predict outcome in 79 surgically treated patients. Reproducibility of outcome prediction was assessed in an independent cohort of 27 patients evaluated on 3.0T MRI. RESULTS: Four similarly sized classes partitioned our cohort; in all, alterations spanned over the 3 mesiotemporal structures. Compared to 46 controls, TLE-I showed marked bilateral atrophy; in TLE-II atrophy was ipsilateral; TLE-III showed mild bilateral atrophy; whereas TLE-IV showed hypertrophy. Classes differed with regard to histopathology and freedom from seizures. Classwise surface-based classifiers accurately predicted outcome in 92 ± 1% of patients, outperforming conventional volumetry. Predictors of relapse were distributed bilaterally across structures. Prediction accuracy was similarly high in the independent cohort (96%), supporting generalizability. INTERPRETATION: We provide a novel description of individual variability across the TLE spectrum. Class membership was associated with distinct patterns of damage and outcome predictors that did not spatially overlap, emphasizing the ability of machine learning to disentangle the differential contribution of morphology to patient phenotypes, ultimately refining the prognosis of epilepsy surgery.

Optometry-based general population survey of pupil ruff atrophy and ocular hypertension.

BACKGROUND: To evaluate and describe the pupil ruff changes and relationship to intraocular pressure, pseudoexfoliation syndrome and glaucoma status in an optometric population in New Zealand. DESIGN: Prospective cross-sectional survey of an optometric population. PARTICIPANTS: Six hundred and twenty subjects over 50 years old routinely attending the participating optometry practices. Exclusion criteria included previous intraocular surgery, ophthalmic laser, uveitis, angle closure and secondary glaucoma. METHODS: Multicentre study involving 11 optometry practices in the Wellington region, New Zealand. The pupillary ruff and associated gonioscopy findings of study participants were graded based on the previously published Pupil Ruff Atrophy grading system. Parameters evaluated include pupillary ruff absence and abnormality, pseudoexfoliation material and trabecular meshwork pigmentation. MAIN OUTCOME MEASURES: Correlations between intereye Pupil Ruff Atrophy grading differences and inter-eye intraocular pressure and cup:disc ratio differences. RESULTS: Six hundred and twenty subjects were included, with a mean age of 62.2 ± 9.1 years and mean intraocular pressure of 14.8 ± 3.4 mmHg. Four hundred and fourteen (66.8%) had bilateral pupil ruff changes and 12 (1.5%) had pseudoexfoliation. Inter-eye intraocular pressure asymmetry was significantly correlated with amount of missing pupillary ruff (r = 0.111; P = 0.022) and trabecular meshwork pigmentation (r = 0.147; P = 0.002). Inter-eye cup:disc ratio asymmetry was not correlated with any of the Pupil Ruff Atrophy grading parameters. CONCLUSIONS: Asymmetry of pupillary ruff absence and trabecular meshwork pigmentation was correlated with intraocular pressure asymmetry (but not with cup:disc ratio asymmetry) in a general optometric population setting in New Zealand.

MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes.

Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy.

Pupil ruff atrophy correlations with intraocular pressure and cup-to-disc ratio in a glaucoma clinic population.

PURPOSE: To evaluate the correlations between pupil ruff changes and associated gonioscopy findings with intraocular pressure (IOP) and cup-to-disc ratio (CDR). DESIGN: Prospective, observational, comparative study. PARTICIPANTS: A total of 103 patients from a glaucoma clinic population. Patients with pseudoexfoliation, previous intraocular surgery, and IOP-lowering medication were excluded. METHODS: Pupillary ruff and associated gonioscopy findings were graded from photographs based on the pupil ruff atrophy (PRA) grading system. Parameters evaluated include pupillary ruff absence and abnormality, pupil edge pigment, and trabecular meshwork pigment. Inter-eye differences were determined and analyzed for correlations with inter-eye differences in IOP and CDR based on Heidelberg Retinal Tomograph II imaging (Heidelberg Engineering, Dossenheim, Germany). MAIN OUTCOME MEASURES: Correlations between inter-eye PRA grading differences and inter-eye IOP and CDR differences. RESULTS: A total of 103 patients were included, with a mean age of 64 years. The average amount of abnormal and missing ruff was 9.5 and 5 clock hours, respectively. Inter-eye IOP asymmetry was significantly associated with asymmetry of amount of abnormal ruff (P = 0.034) and amount of missing ruff (P = 0.022). Inter-eye CDR asymmetry was significantly associated with asymmetry of the amount of missing ruff (P = 0.001) and trabecular meshwork pigmentation (P = 0.006). The eye with the most pupillary ruff loss was 25% more likely to have the greater CDR. CONCLUSIONS: Asymmetric pupillary ruff changes were associated with asymmetry in both IOP and CDR. However, the clinical significance of this finding requires further evaluation.

Novel grading system for pupillary ruff changes and associated features.

BACKGROUND: To evaluate the reproducibility of a new system for grading pupil ruff changes and associated findings. DESIGN: Observational comparative study. PARTICIPANTS: Forty-seven photograph sets including iris, pupil edge and ruff, and inferior anterior chamber drainage angle. METHODS: A novel system for recording pupillary ruff changes was developed, along with reference iris, pupil and gonioscopy images. A prospective masked agreement study was undertaken using two observers who graded the photograph sets using this new system. Parameters included pupillary ruff absence and abnormality, pupil edge pigment, trabecular meshwork pigment, Sampaolesi line pigment, iris root pigment, and pigment 'lumps' and 'piles'. MAIN OUTCOME MEASURES: Intraobserver and interobserver agreement for the parameters of the grading system, assessed with the intraclass correlation coefficient and Bland-Altman plots. RESULTS: Photographs of 47 eyes of 47 glaucoma suspects and glaucoma patients were evaluated. Agreement percentages of ≥95% (average 96%) and ≥60% (average 70%) were obtained for intraobserver and interobserver agreement, respectively. The average interobserver single-measure intraclass correlation coefficient and repeat-measures intraclass correlation coefficient were 0.75 (range 0.54-0.88) and 0.85 (range 0.70-0.94), respectively. There was a non-significant trend towards interobserver systematic bias on one of the nine parameters (iris stroma pigment at the pupil edge). CONCLUSION: This grading system provides a reliable and reproducible system for encoding of clinical signs of pupil ruff atrophy for clinical research.

Hippocampal volume assessment in temporal lobe epilepsy: How good is automated segmentation?

PURPOSE: Quantitative measurement of hippocampal volume using structural magnetic resonance imaging (MRI) is a valuable tool for detection and lateralization of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE). We compare two automated hippocampal volume methodologies and manual hippocampal volumetry to determine which technique is most sensitive for the detection of hippocampal atrophy in mTLE. METHODS: We acquired a three-dimensional (3D) volumetric sequence in 10 patients with left-lateralized mTLE and 10 age-matched controls. Hippocampal volumes were measured manually, and using the software packages Freesurfer and FSL-FIRST. The sensitivities of the techniques were compared by determining the effect size for average volume reduction in patients with mTLE compared to controls. The volumes and spatial overlap of the automated and manual segmentations were also compared. RESULTS: Significant volume reduction in affected hippocampi in mTLE compared to controls was detected by manual hippocampal volume measurement (p < 0.01, effect size 33.2%), Freesurfer (p < 0.01, effect size 20.8%), and FSL-FIRST (p < 0.01, effect size 13.6%) after correction for brain volume. Freesurfer correlated reasonably (r = 0.74, p << 0.01) with this manual segmentation and FSL-FIRST relatively poorly (r = 0.47, p << 0.01). The spatial overlap between manual and automated segmentation was reduced in affected hippocampi, suggesting the accuracy of automated segmentation is reduced in pathologic brains. DISCUSSION: Expert manual hippocampal volumetry is more sensitive than both automated methods for the detection of hippocampal atrophy associated with mTLE. In our study Freesurfer was the most sensitive to hippocampal atrophy in mTLE and could be used if expert manual segmentation is not available.