Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice.

AIMS: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a life-threatening condition often associated with highly raised serum antibodies to glycine receptors (GlyRs); these bind to the surface of large neurons and interneurons in rodent brain and spinal cord sections and, in vitro, inhibit function and reduce surface expression of the GlyRs. The effects in vivo have not been reported. METHODS: Purified plasma IgG from a GlyR antibody-positive patient with PERM, and a healthy control (HC), was injected daily into the peritoneal cavity of mice for 12 days; lipopolysaccharide (LPS) to open the blood-brain barrier, was injected on days 3 and 8. Based on preliminary data, behavioural tests were only performed 48 h post-LPS on days 5-7 and 10-12. RESULTS: The GlyR IgG injected mice showed impaired ability on the rotarod from days 5 to 10 but this normalized by day 12. There were no other behavioural differences but, at termination (d13), the GlyR IgG-injected mice had IgG deposits on the neurons that express GlyRs in the brainstem and spinal cord. The IgG was not only on the surface but also inside these large GlyR expressing neurons, which continued to express surface GlyR. CONCLUSIONS: Despite the partial clinical phenotype, not uncommon in passive transfer studies, the results suggest that the antibodies had accessed the GlyRs in relevant brain regions, led to antibody-mediated internalization and increased GlyR synthesis, compatible with the temporary loss of function.

Glycine receptor antibody mediated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM): a rare but treatable neurological syndrome.

A 40-year-old man presented with respiratory compromise and was intubated. After tracheostomy, he was found to have ophthalmoplegia, severe limb rigidity, stimulus-sensitive myoclonus and autonomic dysfunction. For 1 week before admission, there had been a prodromal illness with low mood, hallucinations and limb myoclonus. Serum glycine receptor antibodies were strongly positive: we diagnosed progressive encephalomyelitis with rigidity and myoclonus. Despite a relapse, he has done well following immunotherapies. The clinical syndrome of encephalomyelitis with rigidity, described in 1976, often has a severe progressive course. A minority of patients have glutamic acid decarboxylase antibodies. The association with glycine receptor antibody was first reported in 2008, and we briefly review subsequent case reports to illustrate the range of clinical features. The antibody is likely to be disease mediating, although this remains unproven. The spectrum of diagnosable and treatable antibody mediated neurological syndromes is expanding. It is vital to recognise these conditions early to reduce morbidity and mortality.

Prevalence and age of onset of Parkinson's disease in Cardiff: a community based cross sectional study and meta-analysis.

BACKGROUND: Previous prevalence studies of Parkinson's disease (PD) in the UK have spanned a 40 year period and have predominantly been in the North of the country. These have presented rates by current age but have not examined this by age at disease onset. METHODS: A community based prevalence study was undertaken which attempted to identify all clinically diagnosed cases of PD from primary and secondary care for the city of Cardiff, Wales, UK. A meta-analysis of all past studies in the UK, including our own, was also undertaken. RESULTS: Overall, 380 cases of PD were identified from a population of 292 637 residents, giving a crude prevalence rate of 130 per 100 000 (95% CI 117 to 144) and an age standardised rate of 142 per 100 000 (95% CI 128 156), standardised to the 1997 England and Wales population. Our prevalence rates were very similar to the weighted average of previous UK studies although there was evidence of between study heterogeneity (p = 0.0006). 5.4% and 31.2% of prevalent PD patients had their disease onset below the age of 50 or 65 years, respectively. CONCLUSIONS: The data suggest that there are no major geographical variations in the prevalence of PD in the UK and that the age adjusted prevalence rate has remained relatively stable over the past 40 years. Although PD risk is far greater in older subjects, patients with young onset are not that uncommon in the community, and health and social care provision should reflect their needs.

The effect of onset age on the clinical features of Parkinson's disease.

Many clinicians view age at onset as an important determinant of clinical phenotype in Parkinson's disease (PD) and this has been reinforced by the identification of Mendelian genes that account for some cases of younger onset PD. A systematic review of OVID Medline for articles relevant to the relationship between clinical features and age at onset in PD published in English between 1950-2007 was performed. There are very few prospective community based studies which focus on the relationship between age at onset and the features of PD and a variety of case definitions are used in the literature. Most studies of young onset PD are based on specialist clinic referral series. The available evidence suggests that PD patients with a younger age at onset have: (i) a slower disease progression, (ii) an increased rate of dystonia at onset and during treatment, (iii) a lower rate of dementia and (iv) an increased rate of dyskinesias in response to L-DOPA treatment. The majority of the available studies do not report patient genotype data, but it is probably that the clinical heterogeneity of PD will be further refined with detailed clinico-genetic studies.

Effects of ageing on touch.

A decline in the main sensory modalities is well reported to occur with ageing. This article outlines the normal pathways involved in touch sensation and includes a review of available evidence relating to the study of ageing and touch. The authors try to use what is known about the neuroanatomy and neurophysiology of ageing to explain the impact on some broad functional deficits seen in the elderly population. The importance of understanding how the normal ageing process affects touch sensation is emphasised.