Optical Coherence Tomography in Parkinsonian Syndromes

BACKGROUND/OBJECTIVE: Parkinson's disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases. METHODS: This cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls. RESULTS: The mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%. CONCLUSION: Different parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes

Current options for the treatment of optic neuritis

John H Pula,1 Christopher J MacDonald21Division of Neuro-ophthalmology, University of Illinois College of Medicine at Peoria, Peoria; 2University of Illinois College of Medicine at Urbana-Champaign, Champaign, IL, USAAbstract: Optic neuritis can be defined as typical (associated with multiple sclerosis, improving independent of steroid treatment), or atypical (not associated with multiple sclerosis, steroid-dependent improvement). Causes of atypical optic neuritis include connective tissue diseases (eg, lupus), vasculitis, sarcoidosis, or neuromyelitis optica. In this manuscript, updated treatment options for both typical and atypical optic neuritis are reviewed. Conventional treatments, such as corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin therapy are all discussed with commentary regarding evidence-based outcomes. Less commonly used treatments and novel purported therapies for optic neuritis are also reviewed. Special scenarios in the treatment of optic neuritis – pediatric optic neuritis, acute demyelinating encephalomyelitis, and optic neuritis occurring during pregnancy – are specifically examined.Keywords: optic neuritis, optic neuropathy, treatment, neuroophthalmolog

Ability of a neuro-ophthalmologist to estimate retinal nerve fiber layer thickness

John H Pula,1 Jorge C Kattah,1 Hauping Wang,1 John Marshall,1 Eric R Eggenberger21University of Illinois College of Medicine at Peoria, Illinois Neurologic Institute, Peoria, IL, USA; 2Michigan State University, East Lansing, MI, USABackground: Qualitative description of the optic disc has clinical value, but optical coherence tomography (OCT) has provided the ability to quantify retinal nerve fiber layer (RNFL) thickness.Methods: We asked three neuro-ophthalmologists of at least 20 years’ experience to estimate the average OCT RNFL thickness of 37 eyes based on fundus photos.Results: The overall correlation coefficient for RNFL thickness estimation variance between two physicians and between physician and OCT was 0.53. The likelihood that the RNFL thickness estimation between physicians, or between physician and OCT, was within 10 µm of each other was 47%–62%. All physicians had disparities in RNFL thickness estimation greater than 30 µm.Conclusion: This study provides information on the ability of an experienced neuro- ophthalmologist to estimate the RNFL thickness based on fundus photos.Keywords: optical coherence tomography, OCT, RNFL, retinal nerve fiber, estimatio

Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma : comprehensive immunohistochemical study using a tissue microarray

Background: Epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial-mesenchymal transition is proposed to occur in various developmental processes and cancer progression. 'Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC). Methods: We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n = 117) using immunohistochemistry on tissue microarrays. Results: Univariate and multivariate analyses revealed that, in addition to N classification (P = 0.0420), the expression of E-cadherin (P = 0.0208), N-cadherin (P = 0.0038) and S100A4 (P = 0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P = 0.0143) in patients with EHCC. Conclusions: These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance.Supplementary Information accompanies this paper on British Journal of Cancer website.http://www.nature.com/bjc/journal/v111/n7/suppinfo/bjc2014415s1.htm

Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes

<p>Abstract</p> <p>Background</p> <p>Reduction of retinal nerve fibre layer (RNFL) thickness was shown as part of the neurodegenerative process in a range of different neurodegenerative pathologies including Alzheimer′s disease (AD), idiopathic Parkinson’s disease (PD), spinocerebellar ataxia (SCA) and multiple system atrophy (MSA). To further clarify the specificity of RNFL thinning as a potential marker of neurodegenerative diseases we investigated RNFL thickness in Hereditary Spastic Paraplegia (HSP), an axonal, length-dependent neurodegenerative pathology of the upper motor neurons.</p> <p>Methods</p> <p>Spectral domain optical coherence tomography (OCT) was performed in 28 HSP patients (clinically: pure HSP = 22, complicated HSP = 6; genetic subtypes: SPG4 = 13, SPG5 = 1, SPG7 = 3, genetically unclassified: 11) to quantify peripapillary RNFL thickness. Standardized examination assessed duration of disease, dependency on assistive walking aids and severity of symptoms quantified with Spastic Paraplegia Rating Scale (SPRS).</p> <p>Results</p> <p>HSP patients demonstrated no significant thinning of global RNFL (<it>p</it>_global = 0.61). Subgroup analysis revealed significant reduction in temporal and temporal inferior sectors for patients with complex (p<0.05) but not pure HSP phenotypes. Two of three SPG7-patients showed severe temporal and temporal inferior RNFL loss. Disease duration, age and severity of symptoms were not significantly correlated with global RNFL thickness.</p> <p>Conclusion</p> <p>Clinically pure HSP patients feature no significant reduction in RNFL, whereas complex phenotypes display an abnormal thinning of temporal and temporal inferior RNFL. Our data indicate that RNFL thinning does not occur unspecifically in all neurodegenerative diseases but is in HSP restricted to subtypes with multisystemic degeneration.</p