Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months–4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment.We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.

ObjectiveThere were two main objectives: to describe and compare clinical outcomes and Patient-Reported Outcome Measures (PROMs) collected using standardised procedures across the European Registers of Stroke (EROS) at 3 and 12 months after stroke; and to examine the relationship between patients’ Health-Related Quality of Life (HRQoL) at 3 months after stroke and survival up to 1 year across the 5 populations.DesignAnalysis of data from population-based stroke registers.SettingEuropean populations in Dijon (France); Kaunas (Lithuania); London (UK); Warsaw (Poland) and Sesto Fiorentino (Italy).ParticipantsPatients with ischaemic or intracerebral haemorrhage (ICH) stroke, registered between 2004 and 2006.Outcome measures(1) HRQoL, assessed by the physical component summary (PCS) and mental component summary (MCS) of the Short-Form Health Survey (SF-12), mapped into the EQ-5D to estimate responses on 5 dimensions (mobility, activity, pain, anxiety and depression, and self-care) and utility scores. (2) Mortality within 3 months and within 1 year of stroke.ResultsOf 1848 patients, 325 were lost to follow-up and 500 died within a year of stroke. Significant differences in mortality, HRQoL and utility scores were found, and remained after adjustments. Kaunas had an increased risk of death; OR 2.34, 95% CI (1.32 to 4.14) at 3 months after stroke in Kaunas, compared with London. Sesto Fiorentino had the highest adjusted PCS: 43.54 (SD=0.96), and Dijon had the lowest adjusted MCS: 38.67 (SD=0.67). There are strong associations between levels of the EQ-5D at 3 months and survival within the year. The trend across levels suggests a dose–response relationship.ConclusionsThe study demonstrated significant variations in survival, HRQoL and utilities across populations that could not be explained by stroke severity and sociodemographic factors. Strong associations between HRQoL at 3 months and survival to 1 year after stroke were identified.

BackgroundFabry Disease (FD) is characterized by globotriaosylceramide-3 (Gb3) accumulation in several tissues and a small fibre neuropathy (SFN), however the underlying mechanisms are poorly known. This study aimed to: 1) ascertain the presence of Gb3 deposits in skin samples, by an immunofluorescence method collected from FD patients with classical GLA mutations or late-onset FD variants or GLA polymorphisms; 2) correlate skin GB3 deposits with skin innervation.Methodswe studied 52 genetically-defined FD patients (32 with classical GLA mutations and 20 with late-onset variants or GLA polymorphisms), 15 patients with SFN associated with a specific cause and 22 healthy controls. Subjects underwent skin biopsy to evaluate Gb3 deposits and epi-dermal innervation.ResultsSkin Gb3 deposits were found in all FD patients with classical GLA mutations but never in FD patients with late-onset variants or GLA polymorphisms or in patients with SFN and healthy controls. Abnormal deposits were found inside different skin structures but never inside axons. FD patients with GB3 deposits showed lower skin innervation than FD patients with late-onset variants or polymorphisms.Conclusions1) Skin Gb3 deposits are specific to FD patients with classical GLA mutations; 2) Gb3 deposits were associated with lower skin innervation but they were not found inside axons, suggesting an indirect damage on peripheral small fibre innervation.

Identification of patients with acute ischaemic stroke who could most benefit from arterial recanalization after endovascular treatment remains an unsettled issue. Although several classifications of collateral circulation have been proposed, the clinical role of collaterals is still debated. We evaluated the effect of the collateral circulation in relation to recanalization as a predictor of clinical outcome. Data were prospectively collected from 103 patients consecutively treated for proximal middle cerebral or internal carotid artery occlusion. The collateral circulation was evaluated with a novel semiquantitative-qualitative score, the Careggi collateral score (CCS), in six grades. Both CCS and recanalization grades (TICI) were analysed in relation to clinical outcome. A statistical analysis was performed to evaluate the effect of interaction between recanalization and collateral circulation on clinical outcome. Out of the 103 patients, 37 (36.3%) had poor collaterals, and 65 (63.7%) had good collaterals. Patients with good collaterals had lower basal National Institute of Health Stroke Scale (NIHSS), more distal occlusion, smaller lesions at 24h CT scan and better functional outcome. After multivariate analysis, the interaction between recanalization and collateral grades was significantly stronger as a predictor of good outcome (OR 6.87, 95% CI 2.11–22.31) or death (OR 4.66, 95% CI 1.48–14.73) compared to the effect of the single variables. Collaterals showed an effect of interaction with the recanalization grade in determining a favourable clinical outcome. Assessment of the collateral circulation might help predict clinical results after recanalization in patients undergoing endovascular treatment for acute ischaemic stroke.