Changes in retinal structures as markers of multiple sclerosis progression

The involvement of the visual pathway in multiple sclerosis (MS) pathology determines the importance of studying the structures of the retina for earlier diagnosis and monitoring the severity of the neurodegeneration. The introduction of the reference method of optical coherence tomography (OCT) allows high resolution in vivo visualization of the retinal structures.Objective: to identify changes in various retinal structures in remitting (RMS) and secondary-progressive (SPMS) MS phenotypes.Patients and methods. The study included 80 patients with RMS (n=48) and SPMS (n=32); the control group included 20 age- and sex-adjusted healthy individuals. Clinical assessment was carried out using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). All patients were examined by an ophthalmologist. To assess changes in the retina, OCT was performed using the RTVue XR Avanti apparatus (Optovue, USA).Results and discussion. We found a significant (p<0.001) decrease in the thickness of the retina of the foveal and parafoveal regions, the thickness of the ganglionic cell complex when comparing the parameters of the retina of the control group and patients with RMS. There was also a significant (p<0.01) decrease in the retinal thickness in the perifoveal region, the thickness of the layer of retinal nerve fibers, the magnitude of focal and global losses. During comparation of the retinal OCT data between patients with RMS and SPMS, we revealed significant differences (p<0.001) in the thickness of the retinal nerve fiber layer, the retinal thickness in the parafoveal and foveal regions, and a significant (p<0.01) decrease in the thickness of the peripheral region, the thickness of the ganglionic cell complex, the volume of focal and global losses. Assessment of the correlations of OCT parameters with the EDSS and MSSS scales in both phenotypes showed a single significant (p<0.05) strong negative correlation (r=-0.70) of the EDSS score and retinal thickness in the foveal region in patients with SPMS.Conclusion. As a domain of criteria for the MS course without signs of disease activity (No Evidence of Disease Activity, NEDA), it is advisable to use retinal OCT with analysis of the retinal thickness in the foveal region, the thickness of the retinal nerve fiber layer, the ganglion cell complex for dynamic monitoring of the inflammatory process activity in patients with RMS and assessment of its progression in patients with SPMS.

Immunohistochemical analysis of the arterial supply and mast cells of the trigeminal ganglion

The aim of this study was to quantify the distribution of microvessels and mast cells in all three parts of the trigeminal ganglion (TG). Statistical analyses were applied to investigate possible micromorphological regional differences in their density. Five serially sectioned human TGs were prepared for CD34 and mast cell tryptase immunostaining. The following quantifications were performed in microscopic fields of three parts of the TG: microvessel density (MVD), mast cell density (MCD) and ganglionic cell count. The density of CD34-positive microvessels was not significantly different in any of the three observed parts of the TG. The distribution of neurons showed no significant statistical difference in three parts of the TG. There was no difference in the density of tryptase-positive mast cells within the TG, but there was an abundant presence of mast cells in the periganglionic dural and subdural tissues, a finding hitherto not reported. We can say that there is a homogenous vascular pattern within the TG which excludes local predominance in pathogenesis of trigeminal neuralgia. Second, and more important, the finding of peri-trigeminal mast cells indicates their important role in migraine pain and confirms their degranulation as the main therapeutic goal for this condition.

Evaluation of Changes in the Ganglionic Cell Inner Plexiform Layer and Macular Retinal Nerve Fibre Layer in Patients Receiving Hydroxychloroquine

Backgrounds: To evaluate changes in the thickness of ganglionic cell-inner plexiform layer and macular retinal nerve fiber layer using ocular coherence tomographyin patients exposed to hydroxychloroquine .Methods: This was a retrospective, cross-sectional study of patients on hydroxychloroquine therapy. Ocular coherence tomography images showing of ganglionic cell-inner plexiform cell layer and macular retinal nerve fiber layer thickness were obtained and compared to those of the control groups. The relationship between the thickness of of ganglionic cell-inner plexiform and macular retinal nerve fibre layer and the duration and cumulative dose of hydroxychloroquine was evaluated.Results: In all, 219 patients were included in this study; the mean age was 43.38 (±17.39) years. The study group comprised 100 (20 male and 80 female) patients, with a mean age of 45.28 (± 12.24) years; the control group had 119 patients (44 males and 75 females), with a mean age of 41.79 (± 20.67) years, with no significant difference in age between the groups (p = 0.123). There was a significant difference in mean of ganglionic cell-inner plexiform thickness between the study and control groups (85.6+/- 8 μm ) vs. (88.6+/-6 μm ) (p = 0.006), with a mean difference of 0.31 (95% confidence interval). The average RNFL thickness was similar in the study and control groups, 28.8±2.5 μm (range: 23 – 38) and 29.2±2.8 μm (range: 22 – 35) respectively, (p = 0.389). There was no significant correlation between of ganglionic cell-inner plexiform and macular retinal nerve fibre layer with daily dose (p = 0.229) or cumulative dose of hydroxychloroquine (p = 0.678). Conclusion : The average thickness of ganglionic cell -inner plexiform cell layer was significantly lower in those taking hydroxychloroquine than in controls. Thinning of this layer could be an early indicator of retinal toxicity before the appearance of clinical retinopathy. However, thickness of the macular retinal nerve fibre laye showed no decrease in hydroxychloroquine users and did not correlate with the duration or cumulative doses of hydroxychloroquine. Therefore, macular retinal nerve fibre layer thickness is not a useful biomarker for the early detection of hydroxychloroquine retinal toxicity.

Ganglion Cells and Topographically Related Nerves in the Vallate Papilla/von Ebner Gland Complex

Ganglion cells and topographically related nerves in the vallate papilla/von Ebner gland complex were investigated in rat tongue by cytochemical, immunocytochemical, and ultrastructural methods to evaluate the possible presence of different neuronal subpopulations. Immunostaining for neurofilaments and protein gene product 9.5 revealed ganglionic cell bodies and nerve fibers. A large part of the neurons were positive at immunostaining for neuronal nitric oxide synthase (NOS), vesicular acetylcholine transporter (VAChT), or vasoactive intestinal peptide (VIP). A small subset of nerve fibers revealed immunoreactivity for cholecystokinin. Axons traveling under the lingual epithelium were evidenced by their content of calcitonin gene-related peptide (CGRP) or substance P (SP). Cell bodies positive for SP or CGRP were not detected. Using methods of co-localization, three different neuronal classes were detected. The main population was composed of AChE/NADPH-diaphorase (NADPHd)-positive cells. Small groups of acetylcholine esterase (AChE)-positive/NADPHd-negative cells were visible. Isolated neurons were AChE-negative/NADPHd-positive. The results of co-localization experiments for VAChT/NOS were consistent with those obtained by cytochemical co-localization of AChE and NADPHd. Experiments of co-localization for peptidergic and nitrergic structures revealed CGRP- and SP-immunoreactive fibers in the vallate papilla/von Ebner gland ganglion. In conclusion, the results demonstrated in the VP/VEG complex peptidergic, cholinergic, and nitrergic neurons. The presence of different neuronal subclasses suggests that a certain degree of functional specialization may exist.

Parvalbumin and calbindin D-28K immunoreactivity in central ganglioglioma and dysplastic gangliocytoma of the cerebellum

✓ Calbindin D-28K and parvalbumin immunocytochemistry were used in the study of central ganglionic cell tumors. Most neurons in the ganglioglioma were immunoreactive to calbindin D-28K, but a few cells were labeled with antibodies against parvalbumin. In contrast, most cells in dysplastic gangliocytoma of the cerebellum were parvalbumin immunoreactive, but fewer reacted with anti-calbindin antibodies. These latter cells had two or three dendrites with claw-shaped terminals and axons with recurrent collateral branches and varicose terminals filled with strings and buttons. These observations suggest that central ganglionic cell tumors, including dysplastic gangliocytoma of the cerebellum, are composed of neurons which, on the basis of their calcium-binding protein content, have particular metabolic and electrophysiological properties.