Treatment of Central Nervous System Complications of Renal Dialysis and Transplantation.

PURPOSE OF REVIEW: Most clinical neurologists will have come across individuals receiving renal replacement therapy who have developed a neurological complication, and neurologists working in, or close to, hospitals with a Renal Unit will be very aware of the range of central nervous system (CNS) complications that may develop in these patients. These can often be difficult to differentiate from disorders relating to renal failure or systemic conditions leading to kidney disease and can in fact arise from the interaction between underlying disease and the side effects of treatment. Patients with renal disease frequently have multiple comorbidities, and it is necessary to take a generally inclusive approach to diagnosis and treatment. RECENT FINDINGS: Unfortunately, there is a lack of specific high-quality evidence for a number of CNS complications of renal replacement therapy. Here, we review the major CNS complications of dialysis and transplantation, discussing evidence for treatments where available and detailing standard management approaches where evidence is scarce. Given the lack of specific evidence for interventions in the treatment of CNS complications of renal replacement therapy, it is often necessary to take an individualised approach based on comorbidities and applying findings from the general population. In these complex patients, we must stress the importance of collaborative working between neurologists and renal physicians when treating this complex patient group.

Inflammatory Activity on Natalizumab Predicts Short-Term but Not Long-Term Disability in Multiple Sclerosis.

BACKGROUND: In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis. OBJECTIVE: To study this association in those receiving natalizumab. METHODS: Data were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability. These were correlated with Expanded Disability Status Scale (EDSS) progression at years 1, 2, 3, and 3-7 after treatment initiation, versus pre-treatment baseline. RESULTS: 46/161 patients had a relapse in the first year and 44/161 had EDSS progression by year 2. Relapses and Modified Rio Score in the first year of treatment predicted EDSS progression at year 1 and 2 after treatment initiation. However, this effect disappeared with longer follow-up. Paradoxically, there was a trend towards inflammatory activity on treatment (first year Modified Rio Score, relapses, and MRI activity) predicting a lower risk of EDSS progression by years 3-7, although this did not reach statistical significance. Those with and without EDSS progression did not differ in baseline age, EDSS, or pre-treatment relapse rate. Relapses in year 0-1 predicted further relapses in years 1-3. CONCLUSIONS: Breakthrough inflammatory activity after natalizumab treatment is predictive of short-term outcome measures of relapses or EDSS progression, but does not predict longer term EDSS progression, in this cohort with high baseline disability.

Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium.

The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.