Kaposi's sarcoma (KS), a vascular tumour that contains characteristic spindle cells forming slit-like spaces, may have an infectious aetiology. Recently, sequences of a new human herpesvirus, KSHV/HHV-8, have been identified in both HIV-associated and classical KS. We sought to identify the target cell of this virus in KS tumour tissue. Using PCR in situ hybridization (PCR-ISH) we show that KSHV/HHV-8 is present in the flat endothelial cells lining vascular spaces of KS lesions as well as in typical KS spindle cells. These findings show that KSHV/HHV-8 is present in the cell types thought to represent neoplastic cells in these lesions.

Research involving children raises complex and well-documented ethical questions and challenges that extend far beyond the reach of formal review and governance systems, where these exist. However, researchers collectively have a wealth of knowledge and experience in applying universal ethical principles in diverse social, cultural and methodological settings, which offers much potential for understanding how ethical concerns are responded to in situ. Through extensive consultation and research, the Ethical Research Involving Children (ERIC) project, discussed in this article, has drawn on this collective knowledge in generating evidence-based resources that highlight best practice while grounding ethical decision-making in lived experience.

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Objective:To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). Methods:The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively.Results: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. Conclusions:Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed. Neurology ® 2012;78:1601-1607 GLOSSARY Ab ϭ antibodies; AChR-Ab ϭ acetylcholine receptor antibody; AChR-MG ϭ acetylcholine receptor antibody-mediated myasthenia gravis; AQP4-Ab ϭ aquaporin-4 antibody; AQP4-NMOSD ϭ aquaporin-4 antibody-mediated neuromyelitis optica spectrum disorder; IgG ϭ immunoglobulin G; IS ϭ immunosuppressive; LETM ϭ longitudinally extensive transverse myelitis; MG ϭ myasthenia gravis; NMO ϭ neuromyelitis optica; NMOSD ϭ neuromyelitis optica spectrum disorder; OCB ϭ oligoclonal bands; ON ϭ optic neuritis; SLE ϭ systemic lupus erythematosus; VGKC ϭ voltage-gated potassium channel.Neuromyelitis optica (NMO) is a recurrent inflammatory and demyelinating CNS disorder that affects predominantly the optic nerve and spinal cord.

Sensory motor neuropathy is associated with various inherited disorders including Charcot-Marie-Tooth disease, X-linked adrenoleukodystrophy/adrenomyeloneuropathy and Refsum disease. In the latter two, the neuropathy is thought to result from the accumulation of specific fatty acids. We describe here three patients with elevated plasma concentrations of pristanic acid (a branched-chain fatty acid) and C27-bile-acid intermediates. Two of the patients suffered from adult-onset sensory motor neuropathy. One patient also had pigmentary retinopathy, suggesting Refsum disease, whereas the other patient had upper motor neuron signs in the legs, suggesting adrenomyeloneuropathy. The third patient was a child without neuropathy. In all three patients we discovered a deficiency of alpha-methylacyl-CoA racemase (AMACR). This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers, which are the only stereoisomers that can be degraded via peroxisomal beta-oxidation. Sequence analysis of AMACR cDNA from the patients identified two different mutations that are likely to cause disease, based on analysis in Escherichia coli. Our findings have implications for the diagnosis of adult-onset neuropathies of unknown aetiology.