Primary angiitis of the central nervous system: emerging variants

BACKGROUND: Primary angiitis of the central nervous system (PACNS), a serious disease, has not featured prominently in the spectrum of multi-organ disease seen in vasculitis clinics. AIM: To evaluate the presentation, natural history and features of PACNS variants and compare to those of systemic vasculitides. DESIGN: Retrospective analysis. METHODS: Patients (n=105) presented during 1988-2003 to a tertiary regional vasculitis clinic receiving unselected disease types. Data were collected from a clinical database, patient and laboratory records. RESULTS: The frequency of PACNS presentation rose over the study period, compared with most of the other vasculitides. When PACNS was divided into small- and middle-sized vessel disease (SVD/MVD), their clinical courses differed substantially. SVD PACNS was responsive to immunosuppressive drugs, but relapsed during prolonged periods in all patients on maintenance immunosuppressives, or after withdrawal of treatment, causing recurrent, severe and irreversible CNS injury. MVD PACNS had isolated episodes at presentation, with a paucity of relapses during prolonged follow-up. DISCUSSION: Similarities between SVD PACNS and microscopic polyarteritis suggest the former may represent a limited form of the latter. MVD PACNS has a distinctly more benign relapse pattern than its multisystem counterpart polyarteritis nodosa. Acute-phase serology was useful in designating inflammatory processes at presentation of patients presenting with encephalopathy caused by SVD only, but were unhelpful in defining relapses in this form of PACNS, the definition of which in all cases rested on clinical assessment and MR scanning. Direct cerebral angiography was not diagnostic in any case of SVD PACNS; positive brain biopsy is diagnostically unequivocal, but the total clinical syndrome with imaging may establish a diagnosis with highest probability. In MVD PACNS, angiography with MR scan proved diagnostic. We suggest an algorithm for a rational, minimally invasive approach to investigation. In PACNS, SVD and MVD are important variants, and decisions about therapy should incorporate these distinctions.     

ROUTINE CLINICAL BIOCHEMISTRY TESTS COLLECTED FROM PATIENTS DYING IN HOSPITAL

SUMMARY A study conducted of the collection of samples from patients dying in hospital and the results of their analysis found that samples are often collected unnecessarily from patients dying in hospital, and are collected more often from women than from men.     

Influence and involvement of support people in adolescent and young adult HIV testing

HIV incidence and mortality are high among adolescents and young adults (AYA) in sub-Saharan Africa, but testing rates are low. Understanding how support people (SP), such as peers, partners, or parents, influence AYA may improve HIV testing uptake. AYA aged 14–24 seeking HIV testing at a referral hospital in Nairobi, Kenya completed a post-test survey assessing the role of SP. Among 1062 AYA, median age was 21. Overall, 12% reported their decision to test was influenced by a parent, 20% by a partner, and 22% by a peer. Young adults (20–24 years old) were more likely than adolescents (14–19 years old) to be influenced to test by partners (23% vs. 12%, p?<?.001), and less likely by parents (6.6% vs. 27%, p?<?.001), healthcare workers (11% vs. 16%, p?<?.05), or counselors (9.4% vs. 19%, p?<?.001). Half of AYA were accompanied for testing (9.9% with parent, 10% partner, 23% peer, 4.3% others, and 2.1% multiple types). Young adults were more likely than adolescents to present alone (58% vs. 32%, p?<?.001) or with a partner (12% vs. 6.7%, p?<?.05), and less likely with a parent (1.6% vs. 31%, p?<?.001). Similar proportions of adolescents and young adults came with a peer or in a group. Correlates of presenting with SP included: younger age (aRR?=?1.55 [95%CI?=?1.30–1.85]), female sex (aRR?=?1.45 [95%CI?=?1.21–1.73]), and school enrollment (aRR?=?1.41 [95%CI?=?1.05–1.88]). SP play an important role in AYAs’ HIV testing and varies with age. Leveraging SP may promote uptake of HIV testing and subsequent linkage care for AYA.     

Mutational screening of ACVR1 gene in Brazilian fibrodysplasia ossificans progressiva patients

Carvalho DR, Navarro MMM, Martins BJAF, Coelho KEFA, Mello WD, Takata RI, Speck‐Martins CE. Mutational screening of ACVR1 gene in Brazilian fibrodysplasia ossificans progressiva patients. Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disorder reported worldwide. A specific heterozygous mutation (c.617G> A; p.R206H) in the activin A type I receptor gene (ACVR1) is regarded as the genetic cause of FOP in all classically affected individuals worldwide. However, a few patients with FOP variants harbor distinct mutations in ACVR1. We screened a group of FOP Brazilian population for mutations in ACVR1. Of 16 patients with a classic FOP phenotype (10 males and 6 females, age range of 3–42 years), all had the classic mutation (p.R206H). One 21‐year‐old woman with a variant FOP phenotype had the previously reported c.983G> A mutation (p.G328E). Our study contributes to the understanding of the predominant FOP phenotype and genotype and suggests that variant FOP phenotypes are associated with specific mutations in ACVR1 gene.     

Analysis of the hexanucleotide repeat in C9ORF72 in Alzheimer's disease

Frontotemporal lobar degeneration (FTLD) is a highly familial neurodegenerative disease. It has recently been shown that the most common genetic cause of FTLD and amyotrophic lateral sclerosis (ALS) is a hexanucleotide repeat expansion in C9ORF72. To investigate whether this expansion was specific to the FTLD/ALS disease spectrum, we genotyped the hexanucleotide repeat region of C9ORF72 in a large cohort of patients with Alzheimer's disease (AD). A normal range of repeats was found in all cases. We conclude that the hexanucleotide repeat expansion is specific to the FTLD/ALS disease spectrum.     

High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia [see comments]

Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine.