Neuropathological features of genetically confirmed DYT1 dystonia: investigating disease-specific inclusions

IntroductionEarly onset isolated dystonia (DYT1) is linked to a three base pair deletion (¿GAG) mutation in the TOR1A gene. Clinical manifestation includes intermittent muscle contraction leading to twisting movements or abnormal postures. Neuropathological studies on DYT1 cases are limited, most showing no significant abnormalities. In one study, brainstem intraneuronal inclusions immunoreactive for ubiquitin, torsinA and lamin A/C were described. Using the largest series reported to date comprising 7 DYT1 cases, we aimed to identify consistent neuropathological features in the disease and determine whether we would find the same intraneuronal inclusions as previously reported.ResultThe pathological changes of brainstem inclusions reported in DYT1 dystonia were not replicated in our case series. Other anatomical regions implicated in dystonia showed no disease-specific pathological intracellular inclusions or evidence of more than mild neuronal loss.ConclusionOur findings suggest that the intracellular inclusions described previously in DYT1 dystonia may not be a hallmark feature of the disorder. In isolated dystonia, DYT1 in particular, biochemical changes may be more relevant than the morphological changes

Post-intravitreal anti-VEGF endophthalmitis in the United Kingdom : incidence, features, risk factors, and outcomes

To describe the incidence, features, management, and risk factors of post-intravitreal anti-VEGF endophthalmitis (PIAE) in patients undergoing treatment for exudative age-related macular degeneration in the United Kingdom. Prospective observational case control study. Forty-seven cases of PIAE were identified through the British Ophthalmological Surveillance Unit from January 2009 to March 2010. Data collected at diagnosis and at 6 months follow-up included patient demographics, intravitreal injection details, pre- and post-injection management, visual acuity, clinical features and management of PIAE, causative organisms, and clinical outcomes. Details were compared with 200 control cases from 10 control centres to identify potential risk factors. Estimated PIAE was 0.025%. Culture-positive PIAE incidence was 0.015%. Mean age of presentation was 78 years. Mean number of intravitreal injections before PIAE was 5. Mean days to presentation was 5 (range 1-39). Positive microbiology culture was found in 59.6%. The majority of causative organisms were Gram positive (92.8%). Significant risk factors were failure to administer topical antibiotics immediately after the injection (P=0.001), blepharitis (P=0.006), subconjunctival anaesthesia (P=0.021), patient squeezing during the injection (P=0.021), and failure to administer topical antibiotics before anti-VEGF injection (P=0.05). The incidence of PIAE in the United Kingdom is comparable to other studies at a rate of 0.025%. The most common causative organisms were Gram positive. Measures to minimise the risk of PIAE include treatment of blepharitis before injection, avoidance of subconjunctival anaesthesia, topical antibiotic administration immediately after injection with consideration to administering topical antibiotics before injection