Importantly, terminal complement activation has been shown to be chronically present on the surface of platelets in patients with aHUS who appear to be clinically well while receiving chronic PE/PI.Guidelines issued by the European Paediatric Study Group for HUS recommend rapid administration of plasma exchange or plasma infusion (PE/PI), intensively administered daily for 5 days and then with reducing frequency. However, the American Society for Apheresis offers a "weak" recommendation for plasma exchange to treat aHUS, due to the "low" or "very low" quality of evidence supporting its use. Although some patients experienced improvements in red blood cell and platelet counts, plasma therapies generally did not result in full remission. Monoclonal antibody therapy
Eculizumab (Soliris) appears to be useful for atypical hemolytic uremic syndrome (aHUS). In September 2011 the U.S. Food and Drug Administration (FDA) approved it as an orphan drug to treat people with aHUS. This approval was based on two small prospective trials of 17 people and 20 people. In the UK, NICE issued guidance on the use of Eculizumab for treating aHUS, based on five evidence sources, including those used by the FDA No randomised controlled trials were identified. All prospective studies were phase 2, open‑label, non‑randomised, single‑arm studies that included patients with different clinical baseline characteristics. The prospective studies lasted 26 weeks; however, patients were allowed to continue treatment with eculizumab in a long‑term extension study.Ravulizumab-cwvz (Ultomiris) is a second generation monoclonal antibody for aHUS made by Alexion pharmaceuticals, Inc.
More recent studies have validated these findings; the precise incidence found varies with the nature of the episode and the criteria of "hallucination" adopted, but the basic finding is now well-supported. Non-celiac gluten sensitivity
There is tentative evidence of a relationship with non-celiac gluten sensitivity, the so-called "gluten psychosis". Pathophysiology
Dopaminergic and serotonergic hallucinations
It has been reported that in serotonergic hallucinations, the person maintains an awareness that they are hallucinating, unlike dopaminergic hallucinations. Neuroanatomy
Hallucinations are associated with structural and functional abnormalities in primary and secondary sensory cortices. Reduced grey matter in regions of the superior temporal gyrus/middle temporal gyrus, including Brocas area, is associated with auditory hallucinations as a trait, while acute hallucinations are associated with increased activity in the same regions along with the hippocampus, parahippocampus, and the right hemispheric homologue of Brocas area in the inferior frontal gyrus. Grey and white matter abnormalities in visual regions are associated with visual hallucinations in diseases such as Alzheimers disease, further supporting the notion of dysfunction in sensory regions underlying hallucinations. One proposed model of hallucinations posits that over-activity in sensory regions, which is normally attributed to internal sources via feedforward networks to the inferior frontal gyrus, is interpreted as originating externally due to abnormal connectivity or functionality of the feedforward network. This is supported by cognitive studies of those with hallucinations, who have demonstrated abnormal attribution of self generated stimuli.Disruptions in thalamocortical circuitry may underlie the observed top down and bottom up dysfunction.