OBJECTIVE: The purpose of the study was to present results from a national Dutch cohort of patients with Leber\'s Hereditary Optic Neuropathy (LHON) treated with idebenone.
METHODS: The multicentre, open-label, retrospective evaluation of the long-term outcome of idebenone treatment of Dutch LHON patients on visual function and on thickness of the retinal ganglion cell layer. Patients included in the analysis had a confirmed mutation in their mitochondrial DNA encoding either of the seven subunits of complex I, had a reported loss of vision in at least one eye and had a follow-up of more than 6 months after their treatment was started. Control visits involved routine clinical examinations of visual function and retinal structure at (1) the start of treatment, (2) nadir (time of lowest visual acuity), (3) the time of recovery (if any), (4) the time of termination of treatment and (5) more than 6 months after termination of the treatment.
RESULTS: Data from 72 patients were analysed. Treatment duration was 23.8 ± 14.4 (mean ± SD) months. A positive response, that is either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS), occurred in 53% and 11% of the patients, respectively. The magnitude of CRR was 0.41 ± 1.54 logMAR. CRR of visual acuity is associated with recovery of colour discrimination. The thickness of both the ganglion cell complex (GCC) and the retinal nerve fibre layer (RNFL) is irreversibly reduced.
CONCLUSIONS: Our results confirm that idebenone may help to restore or maintain visual function. Whether this effect will persist is still unknown. Thinning of retinal neural tissue appears to be permanent.

Cutaneous ganglioneuromas (CGNs) are exceptional. We aim to describe the anatomico-clinical profile of primary CGN and report 4 cases. Patients were 2 men and 2 women aged 53 to 76 years, who had flesh-colored nodules on the back, associated with adjacent keratotic changes, that is, epidermal nevus (1 case) or seborrheic keratosis (3 cases). Histopathology showed ganglion cells within a proliferation of Schwann cells. The epidermis was acanthotic, associated with sebaceous induction in 2 cases, with follicular hyperplasia as in fibroepithelial tumors (1 case) or with tricholemmoma (2 cases). Cytokeratin-20 immunostaining showed Merkel cells in the epidermis. A higher density of Merkel cells was observed in BerEP4+ follicular structures. Along with 16 published cases, our study indicates that a nodule associated with seborrheic keratosis on the back may represent a CGN, a complex mesenchymal and epidermal/follicular lesion of neuroectodermal lineage, associating neuronal proliferation and Merkel cell hyperplasia with follicular induction.

OBJECTIVE: To describe and discuss the normal anatomy and function of enteric neurons in the esophagus of aged individuals.
METHODS: We examined ganglion cells in esophagus specimens obtained from 15 elderly cadavers without any macroscopic pathology in the mediastinum and abdomen. Neuronal nitric oxide synthase and vasoactive intestinal polypeptide were used as parasympathetic nerve markers, and tyrosine hydroxylase as a sympathetic nerve marker.
RESULTS: The thoracic and abdominal esophagus contained a well-developed myenteric nerve plexus (S100 protein-positive area) in the intermuscular layer: 0.02-0.03 mm2 per 1-mm length of the circular esophageal wall. The cervical esophagus usually contained no ganglion cells. The number of parasympathetic ganglion cells was maximal in the upper or middle thoracic esophagus (mean 18-23 cells per section), whereas sympathetic cells were considerably less numerous at any sites (mean 1-3 cells).
CONCLUSIONS: In comparison with previous data from elderly cadavers, the esophagus carried much fewer ganglion cells than the intestine and colon; sympathetic cells were particular less numerous. Esophageal smooth muscle exhibits a unique mode of peristalsis characterized by a rebound contraction with a long latency after stimulation. This type of peristalsis appears to be regulated by inhibitory, nNOS-positive nerves with a sparse distribution, which seems to account for the long-span peristalsis unique to the esophagus. The extreme sparsity of ganglion cells in the cervical esophagus suggests that enteric neuron-integrated peristalsis, like that in the intestine and colon, is unlikely. Surgical treatment of the esophagus is likely to change or impair these unique features.

Responses of direction-selective and orientation-selective motion detectors were recorded extracellularly from the axon terminals of ganglion cells in the superficial layers of the tectum opticum of immobilized goldfish, Carassius gibelio (Bloch, 1782). Color stripes or edges moving on some color background (presented on the CRT monitor with known emission spectra of its phosphors) served as stimuli. It was shown that stimuli of any color can be more or less matched with the background by varying their intensities what is indicative of color blindness of the motion detectors. Sets of stimuli which matched the background proved to represent planes in the three-dimensional color space of the goldfish. A relative contribution of different types of cones to the spectral sensitivity was estimated according to orientation of the plane of color matches. The spectral sensitivity of any motion detector was shown to be determined mainly by long-wave cones with a weak negative (opponent) contributions of middle-wave and/or short-wave ones. This resulted in reduced sensitivity in the blue-green end of the spectrum, what may be considered as an adaptation to the aquatic environment where, because of the substantial light scattering of a blue-green light, acute vision is possible only in a red region of the spectrum.

OBJECTIVE: To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.
METHODS: For this study twenty-four New Zealand adult rabbits were divided into four groups (n=6 for each group). 50µg/0.1mL (group 1), 100µg/0.1mL (group 2), 150µg/0.1mL (group 3) and 200µg/0.1mL (group 4), rifampicin were injected into the vitreous of the right eyes of animals, their left eyes were used as control (group 5). After the 28(th) day of application, animals were anesthetised with xylazine (8mg/kg, IM) and then their eyes were enucleated immediately. Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation.
RESULTS: Depending on the high dose of rifampicin, some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level. Using quantitative examination, which was done at the light microscopic level, it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group.
CONCLUSIONS: Based on these findings, low-dose rifampicin (50µg/0.1mL) may be useful for treatment of the ocular diseases.