Family Clustering of Viliuisk Encephalomyelitis in Traditional and New Geographic Regions

Transmission occurs through patient contact; human migration from disease-endemic villages leads to disease emergence in new communities

Neuroimaging in chronic Viliuisk encephalomyelitis (VE).

<p>(<b>A,B</b>) Representative magnetic resonance imaging (MRI) of mild (<b>A</b>) and severe (<b>B</b>) chronic VE showing severity-dependent enlargement of the lateral and third ventricles. Shown are transaxial FLAIR, coronar T1w and sagittal T2w images demonstrating ventricular enlargement including the 3^rd ventricle, periventricular hyperintense signal, thinning of the corpus callosum, but normal cortical and infratentorial structures. The extent of these changes correlated to disease severity. (<b>C</b>) Semi-quantitative measurement of ventricular volume in VE patients compared to Yakutian and age- and sex-matched Caucasian controls (see Supporting Information online for technical details). As an estimate of ventricular volumes, the sums of normalized ventricular areas from all slices showing ventricles obtained with a standardized acquisition protocol are displayed (bars and crosses are mean values ± SD). # indicates <i>P<</i>0.0001 when compared to all other groups (ANOVA with post-hoc <i>t</i>-test including Bonferroni correction). (<b>D</b>) Representative pneumoencephalography of subacute VE showing ventricular enlargement (arrows indicate enlarged “bloated” lateral ventricles) and absent air filling of the subarachnoidal spaces of the hemispheric convexities (arrowheads indicate the stops of air filling), suggestive for arachnoideal adhesions.</p

Schematic map of the Republic of Sakha marking the places of origin of studies subjects.

<p>Closed symbols represent chronic VE patients, open symbols indicate controls (refer to text for details), red symbols mark cities/villages.</p

Neuropathology in subacute Viliuisk encephalomyelitis (VE).

<p>(<b>A</b>) Representative brain histology microphotograph for all three available VE brain samples showed massive intraparenchymal and meningeal infiltrations (Giemsa and DAPI staining confirmed, not shown). (<b>B</b>) Anti-ECP immunohistochemistry proved increased appearance of eosinophilic leucocytes. Scale bar, 100 µm.</p

Communicating Hydrocephalus Following Eosinophilic Meningitis Is Pathogenic for Chronic Viliuisk Encephalomyelitis in Northeastern Siberia

<div><p>Background</p><p>Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic.</p><p>Methodology and Principle Findings</p><p>In search for the pathophysiology and causative agent of VE, we performed a cross-sectional study on clinical, serological and neuroimaging data on chronic VE patients during two medical expeditions to three villages within the Viliuiski river basin in the Republic of Sakha in 2000 and to the capital Yakutsk in 2006. The severity of the core clinical picture with predominant sensory ataxia, gait apraxia, lower limb spasticity, cognitive impairment and bladder dysfunction correlated with the degree of MRI findings showing enlargement of inner ventricular spaces as in communicating hydrocephalus. Laboratory studies revealed transient eosinophilia during the preceding acute meningitis-like phase, but no ongoing inflammatory process in the CSF. We found immune reactions against <i>Toxocara canis</i> in the majority of chronic VE patients but rarely in controls (<i>P</i> = 0.025; Fisher's exact test). Histological analysis of subacute to subchronic VE brain samples showed eosinophilic infiltrations with no signs of persistent <i>Toxocara canis</i> infection.</p><p>Conclusions and Significance</p><p>Our data showed that pressure by the communicating hydrocephalus as a mechanical factor is the major pathogenic mechanism in chronic VE, most likely triggered by eosinophilic meningitis. There are no signs for an ongoing inflammatory process in chronic VE. The past eosinophilic reaction in VE might be caused by <i>Toxocara</i> ssp. infection and might therefore represent the first hint for an initial cause leading to the development of chronic VE. Our data provide a framework for future studies and potential therapeutic interventions for this enigmatic epidemic neurological disease potentially spreading in Sakha Republic.</p></div

CSF results in VE patients and controls.

<p>Data are number of patients (%) with pathological results, or mean±SD (range).</p><p>Fisher's exact test for comparison of pathological vs. normal results did not reveal significant differences between both groups for all parameters.</p><p>OCIBs, oligoclonal IgG bands; AI, antibody index.</p

Immunoreactivity against organisms associated with eosinophilic meningitis in patients with VE and controls.

$<p>Relative risks and 95% confidence interval (CI) for comparison of pathological results vs. normal results.</p>Δ<p>Fisher's exact test for comparison of pathological results vs. normal results.</p>a<p>Normal results for all tests are: Not detectable.</p