Routine blood monitoring in maintenance immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant?

BACKGROUND: Pre-treatment screening for IgA deficiency and close monitoring of full blood count(FBC) and renal function is recommended with intravenous immunoglobulin(IVIg) therapy in neurological diseases. AIMS: To examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia, thrombocytopenia and acute kidney injury(AKI) in a cohort of patients on maintenance Immunoglobulin(Ig) therapy for inflammatory neuropathy. METHODS: A retrospective review of routine blood monitoring in patients from two UK specialist peripheral nerve centres. Accepted definitions for clinically and biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used. RESULTS: 1919 infusion episodes in 90 patients were analysed. Age(mean(S.D)) = 58.09(14.4)years, 63% male, 72% CIDP(28% MMN), 97% IVIg(3% SCIg). Dose = 1.57(0.79)g/kg/month or 97.1(37.3)g/infusion, frequency:3.9(1.4) weeks. Relative IgA deficiency was noted in 2 individuals (prevalence:2.2%, 95%C.I.:0-5.2) who received a combined total of 38 infusions(3800 g IVIg) without adverse event. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to treatment. An asymptomatic drop>10 g/L haemoglobin(Hb) occurred in 3.5%(95%CI:2.7-4.3) of treatment episodes in 38 individuals, mean reduction:17.7(7.4)g/L; lowest Hb:86 g/L. Lower pre-treatment haemoglobin correlated with risk of recurrent Ig-related drop(p:0.007). Two patients with chronic renal failure(stage 1 and 3) received 28(IV) and 104(SC) infusions respectively(6416 g) without impact on estimated glomerular filtration rate(eGFR). CONCLUSIONS: No clinically significant Ig-related episodes of haemolysis or AKI were identified in this representative cohort. This suggests that routine monitoring is not essential in long-term Ig use but should be considered when clinically indicated.

Parkinson's disease: the genetics of a heterogeneous disorder.

Since the first description of Parkinson's disease (PD) in 1817 attempts have been made to resolve the etiology of this common neurodegenerative disorder. In the last century the influence of heredity in PD was controversial. The identification of mutations in six genes responsible for Mendelian forms of PD; alpha-synuclein (SNCA), parkin (PRKN), ubiquitin C-terminal hydrolase L1 (UCH-L1), oncogene DJ-1, PTEN-induced putative kinase 1 (PINK1), and most recently leucine-rich repeat kinase 2 (LRRK2), has confirmed the role of genetics in familial forms of the disease. The exact relationship of these familial disorders and related genes to the more common sporadic form is currently uncertain. The identification of LRRK2 mutations and the association of common variants in SNCA and UCH-L1 in apparently sporadic late-onset disease indicate these genes may be of greater importance than previously believed. The protein products of the six genes are involved in different pathways of neurodegeneration and have opened new avenues of research. This focused research will lead to the development of novel targeted therapies, which may revolutionize the treatment of PD for a substantial proportion of patients.

PINK1 (PARK6) associated Parkinson disease in Ireland.

Mutations in the PINK1 gene have recently been shown to cause autosomal recessive Parkinson disease (PD). The authors assessed the prevalence of PINK1 gene mutations in 290 well-characterized early- and late-onset PD patients from Ireland. In a 51-year-old PD patient with a family history of PD, the authors identified a novel heterozygous mutation (R147H) in exon 2 of the PINK1 gene. Overall, these data indicate that PINK1 mutations are a rare cause of PD in Ireland.