Autoimmune Neurological Disorders - Does the Age Matter?
1 Autoimmune neurological disorders - does the age matter? Yael Hacohen1,2 and Angela Vincent3 1. Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, 2. Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London. 3. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford. Antibodies binding to central nervous system (CNS) channels, receptors and other synaptic or glial proteins are now recognised as a likely cause of neurological disorders in both adults and children (see Table). Autoimmune encephalopathies are characterized variously by impaired alertness, amnesia, seizures, movement disorders, psychiatric features or autonomic instability, but without focal neurological deficits. The neuronal cell-surface antigens are essential to cellular function or neurotransmission and are generally expressed throughout the nervous system1. Autoimmune forms of demyelinating disorders, by contrast, can present as optic neuritis, transverse myelitis or a range of CNS presentations reflecting the site of the lesions. The glial (myelin or astrocyte) cell-surface antigens are widely expressed throughout the CNS. All these patients frequently respond well to immunotherapies, and in some cases the disorders are monophasic and do not require long-term immunosuppression2. By contrast, the typical paraneoplastic antibodies are generated against tumour antigens that are shared with the nervous system, and are usually associated with T cell-mediated pathogenic mechanisms; the antibodies represent an epiphenomenon of the disease but can be useful biomarkers for the existence of the appropriate tumour. Unfortunately, patients with the intracellular antibodies often progress relentlessly and do not respond to immunotherapies3. The strongest levels of evidence linking identified cell surface antibodies to the pathology of specific disorders are found with AQP4 antibody in neuromyelitis optica spectrum disorder and NMDAR antibody in NMDAR-antibody encephalitis.
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