Dyad and group-based interventions in physical activity, diet, and weight loss: a systematic review of the evidence.

Studies show that interpersonal relations impact behavior change. Yet, a comprehensive review of their efficacy remains unclear. This systematic review examines the efficacy of dyadic and group-based studies that intervened on primary endpoints: diet, PA, and weight loss in adults and their networks. We searched five databases for eligible articles published from 1980 to present. Final inclusion and risk of bias were independently determined and agreed upon by two of the paper's co-authors. Nine dyads and twelve group-based studies were eligible. Of the studies, 36% (4/11) of PA studies, 60% (3/5) of diet studies and 57% (8/14) of studies with weight loss as primary outcomes, reported significant findings. Compared to dyadic interventions, a greater proportion of group-based interventions demonstrated efficacy in PA gain and weight loss as outcomes. Approximately 43% of studies demonstrated low to moderate methodological quality. This systematic review synthesized the evidence of dyadic and group studies that intervened on PA, diet, and weight in adults from the same network. Moderately-high risk of bias and lack of diverse representation restricts inferences around efficacy. High-quality rigorous research is needed to understand the efficacy of dyadic and group-based interventions in addressing these co-occurring endpoints of interest.

To T or not to T: Differences in Testosterone Use and Discontinuation by HIV Serostatus among Men who Have Sex with Men.

OBJECTIVES: The aim of the study was to characterize contemporary patterns and correlates of testosterone therapy (TTh) use and discontinuation by HIV serostatus among men in the Multicenter AIDS Cohort Study (MACS). METHODS: Self-reported testosterone use data were collected semiannually from 2400 (1286 HIV-infected and 1114 HIV-uninfected) men who have sex with men. Multivariable Poisson regression was used to estimate prevalence ratios for TTh use and predictors of TTh discontinuation (2012-2015). RESULTS: Use was higher among HIV-infected compared with HIV-uninfected men in all age strata, with an age-adjusted prevalence of 17% vs. 5%, respectively (adjusted prevalence ratio 3.7; P < 0.001). Correlates of use in the multivariable model were similar by HIV serostatus: white race, the Los Angeles (LA) site, more than one recent sexual partner, non-smoking status, and higher American Heart Association/American College of Cardiology (AHA/ACC) cardiovascular disease (CVD) risk score category (approximately 70% of testosterone users were in the high-risk category). Compared with HIV-uninfected men, HIV-infected men more frequently reported building muscle mass as a motivation for testosterone use. The TTh discontinuation rate was 20.9/100 person-years [95% confidence interval (CI) 17.3, 25.0/100 person-years]. Relative to HIV-uninfected men, HIV-infected men were half as likely to discontinue (adjusted incidence rate ratio 0.4; P < 0.001). Discontinuation was 40% higher in the period after the US Food and Drug Administration (FDA) safety communication for testosterone in 2014, independent of co-factors (P = 0.06). CONCLUSIONS: Given the high prevalence of both TTh use and CVD risk among HIV-infected men, the benefits and risks of TTh should be examined in future studies of aging HIV-infected men and monitored routinely in clinical practice.

A nationwide epidemiological study of myasthenia gravis in Latvia.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder characterized by fatigable muscle weakness due to antibody-mediated impairment of neuromuscular transmission. The aim of this study was to investigate the incidence and prevalence of MG in Latvia, and to characterize this population by well-established clinical parameters such as age at onset, presence of associated antibodies and thymus pathology. METHODS: All prevalent cases on 1 January 2015 and cases of patients newly presenting with MG symptoms from 1 January 2010 to 31 December 2014 were selected from the database of the Neuromuscular Disease Clinic of Pauls Stradins Clinical University Hospital and Children's Clinical University Hospital. Crude rates were calculated based on population data. These were directly age-standardized to the European and World Health Organization world standard populations. The analysis of clinical characteristics was carried out in a cohort of patients who had undergone a complete set of electrophysiological, serological and radiological investigations (n = 153; 68%). RESULTS: During the study period 99 incident and 226 prevalent cases were identified. The total crude MG incidence was 9.7 per million person-years. The prevalence of MG on 1 January 2015 was 113.8 per million. 54.2% of patients tested positive for acetylcholine receptor antibodies, 7.8% for muscle specific kinase antibodies and 1.3% for lipoprotein related protein 4 antibodies. CONCLUSIONS: This is the first study of MG in Latvia and the second population-based study of MG in Eastern Europe. Our epidemiological results are similar to those in some other European and Northern American countries, and show high prevalence and increasing incidence of late-onset MG.

Thermal conductivity versus depth profiling of inhomogeneous materials using the hot disc technique.

Transient measurements of thermal conductivity are performed with hot disc sensors on samples having a thermal conductivity variation adjacent to the sample surface. A modified computational approach is introduced, which provides a method of connecting the time-variable to a corresponding depth-position. This allows highly approximate-yet reproducible-estimations of the thermal conductivity vs. depth. Tests are made on samples incorporating different degrees of sharp structural defects at a certain depth position inside a sample. The proposed methodology opens up new possibilities to perform non-destructive testing; for instance, verifying thermal conductivity homogeneity in a sample, or estimating the thickness of a deviating zone near the sample surface (such as a skin tumor), or testing for presence of other defects.

Nox2 is a mediator of ischemia reperfusion injury.

Delayed graft function (DGF) results from ischemia-reperfusion injury (IRI) and the generation of reactive oxygen species. We hypothesized that NADPH oxidase 2 (Nox2) plays an important role in pathways leading to DGF. We tested this hypothesis in vitro, in an animal model of IRI using wild type and Nox2(-/-) mice, and in patients with DGF. Under hypoxic conditions, primary tubular epithelial cells from Nox2(-/-) mice had reduced expression of MMP2, vimentin, and HSP27. BUN and creatinine levels were significantly increased in both Nox2(-/-) and WT mice at 4 weeks and 6 months after IRI, suggesting the development of acute and chronic kidney injury. At 4 weeks, kidney fibrosis (α-SMA, picrosirius) and oxidative stress (dihydroethidine, HNE) were significantly reduced in Nox2(-/-) mice, confirming the oxidative and pro-fibrotic effects of Nox2. The molecular signature of IRI using genomic analyses demonstrated a significant decline in hypoxia reponse, oxidative stress, fibrosis, and inflammation in Nox2(-/-) mice. Immunohistochemical analyses of pre-implanatation kidney allograft biopsies from patients with subsequent DGF showed significantly greater Nox2 levels and vascular injury compared with patients without DGF. These studies demonstrate that Nox2 is a modulator of IRI and its absence is associated with reduced inflammation, OS, and fibrosis.

HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS).

OBJECTIVES: HIV-infected individuals bear increased cardiovascular risk even in the absence of traditional cardiovascular risk factors. In the general population, coronary artery calcium (CAC) scanning is of value for cardiovascular risk stratification, but whether a CAC score of zero implies a low noncalcified coronary plaque burden in HIV-infected persons is unknown. METHODS: We assessed the prevalence of noncalcified coronary plaque and compared noncalcified coronary plaque burden between HIV-infected and HIV-uninfected participants who had CAC scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary computed tomography (CT) angiography. RESULTS: HIV infection was associated with the presence of noncalcified coronary plaque among these men with CAC scores of zero. In a model adjusted only for age, race, centre, and pre- or post-2001 cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27 (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for cardiovascular risk factors, HIV infection remained associated with the presence of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval 1.07-1.6; P = 0.01). CONCLUSIONS: Among men with CAC scores of zero, HIV infection is associated with an increased prevalence of noncalcified coronary plaque independent of traditional cardiovascular risk factors. This finding suggests that CAC scanning may underestimate plaque burden in HIV-infected men.

Differences in hepatitis C virus prevalence and clearance by mode of acquisition among men who have sex with men.

We examined the characteristics associated with hepatitis C virus (HCV) antibody (anti-HCV) prevalence and HCV clearance between injection drug using (IDU) and non-IDU men who have sex with men (MSM). Stored serum and plasma samples were tested for anti-HCV and HCV RNA to determine the HCV status of 6925 MSM at enrolment into the Multicentre AIDS Cohort Study (MACS). Prevalence and clearance ratios were calculated to determine the characteristics associated with HCV prevalence and clearance. Multivariable analyses were performed using Poisson regression methods with robust variance estimation. Anti-HCV prevalence was significantly higher among IDU than among non-IDU MSM (42.9% vs 4.0%), while clearance was significantly lower among IDU MSM (11.5% vs 34.5% among non-IDU MSM). HIV infection, Black race, and older age were independently associated with higher prevalence in both groups, while smoking, transfusion history, and syphilis were significantly associated with prevalence only among non-IDU MSM. The rs12979860-C/C genotype was the only characteristic independently associated with HCV clearance in both groups, but the effects of both rs12979860-C/C genotype [clearance ratio (CR) = 4.16 IDUs vs 1.71 non-IDUs; P = 0.03] and HBsAg positivity (CR = 5.06 IDUs vs 1.62 non-IDUs; P = 0.03) were significantly larger among IDU MSM. HIV infection was independently associated with lower HCV clearance only among non-IDU MSM (CR = 0.59, 95% CI = 0.40-0.87). IDU MSM have higher anti-HCV prevalence and lower HCV clearance than non-IDU MSM. Differences in the factors associated with HCV clearance suggest that the mechanisms driving the response to HCV may differ according to the mode of acquisition.

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma.

The major histocompatibility complex (MHC) region on chromosome 6p21.3 is suspected to host susceptibility loci for HIV-related Kaposi's sarcoma (HIV-KS). A nested case-control study in the Multicenter AIDS Cohort Study was designed to conduct fine genetic association mapping across central MHC. Individuals co-infected with HIV-1 and human herpes virus-8 who later developed KS were defined as cases (n=354) and were matched 1:1 with co-infected KS-free controls. We report data for new independent MHC class II and III susceptibility loci. In particular, class II HLA-DMB emerged as a strong candidate, with the intronic variant rs6902982 A>G associated with a fourfold increase of risk (odds ratio (OR)=4.09; 95% confidence interval (CI)=1.90-8.80; P=0.0003). A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95% CI=2.54-43.6; P=0.0012). The class III susceptibility variant is moderately associated with HIV-KS and lies within a 120-kb-long haplotype (OR=1.52; 95% CI=1.01-2.28; P=0.047) formed by rs7029 A>G (GPANK1 3' untranslated region), rs1065356 G>A (LY6G6C), rs3749953 A>G (MSH5-SAPCD1 read through) and rs707926 G>A (VARS). Our data suggest that antigen processing by MHC class II molecules is a target pathway in the pathogenesis of HIV-KS.

Characterization of transfusion-elicited acute antibody-mediated rejection in a rat model of kidney transplantation.

Animal models of antibody-mediated rejection (ABMR) may provide important evidence supporting proof of concept. We elicited donor-specific antibodies (DSA) by transfusion of donor blood (Brown Norway RT1(n) ) into a complete mismatch recipient (Lewis RT1(l) ) 3 weeks prior to kidney transplantation. Sensitized recipients had increased anti-donor splenocyte IgG1, IgG2b and IgG2c DSA 1 week after transplantation. Histopathology was consistent with ABMR characterized by diffuse peritubular capillary C4d and moderate microvascular inflammation with peritubular capillaritis + glomerulitis > 2. Immunofluorescence studies of kidney allograft tissue demonstrated a greater CD68/CD3 ratio in sensitized animals, primarily of the M1 (pro-inflammatory) phenotype, consistent with cytokine gene analyses that demonstrated a predominant T helper (TH )1 (interferon-γ, IL-2) profile. Immunoblot analyses confirmed the activation of the M1 macrophage phenotype as interferon regulatory factor 5, inducible nitric oxide synthase and phagocytic NADPH oxidase 2 were significantly up-regulated. Clinical biopsy samples in sensitized patients with acute ABMR confirmed the dominance of M1 macrophage phenotype in humans. Despite the absence of tubulitis, we were unable to exclude the effects of T cell-mediated rejection. These studies suggest that M1 macrophages and TH 1 cytokines play an important role in the pathogenesis of acute mixed rejection in sensitized allograft recipients.

Mechanisms compensating for visual field restriction in adolescents with damage to the retro-geniculate visual system.

BACKGROUND: To describe visual field (VF) outcome in three adolescents with damage to the optic radiation and to focus on mechanisms that may compensate the practical functional limitations of VF defects. DESIGN: Descriptive, prospective multi-case study in a hospital setting. PARTICIPANTS: Three teenagers with cerebral visual dysfunction because of damage to the retro-geniculate visual pathways. METHODS: Best-corrected visual acuity and eye alignment were assessed. Visual field function was tested with Goldmann perimetry, and with Rarebit, Humphrey Visual Field Analyzer and Esterman computerized techniques. Fixation was registered with video oculography during Rarebit examination. Magnetic resonance imaging of the brain illustrated brain damage and its relation to the posterior visual system. RESULTS: One of the three subjects had bilateral asymmetric white matter damage of immaturity, early-onset exotropia, and a relative homonymous VF defect, but normal binocular VF. The second subject also had bilateral asymmetric white matter damage of immaturity and showed an inferior right quadrantanopia, confirmed by the binocular field. Registration of fixation revealed automatic scanning during perimetry. The third subject had an almost total left homonymous hemianopia after resection of a brain tumour in the right temporal lobe. The hemianopia could be compensated for by fast voluntary scanning. CONCLUSION: Congenital and later-acquired homonymous VF defects may, at least in young subjects, be compensated for by scanning. Exotropia may compensate VF defects and, therefore, the VF should be tested before strabismus surgery.

Nox2 is a mediator of chronic CsA nephrotoxicity.

We hypothesized that Nox2, the classical phagocytic NADPH oxidase, plays an important role in calcineurin inhibitor (CNI)-induced renal fibrosis. We tested this hypothesis in vitro, in animal and in human studies. Cyclosporine A (CsA) and tacrolimus (TAC) were associated with greater levels of Nox2 mRNA and epithelial to mesenchymal transition (EMT) in NRK52E cells. CsA increased Nox2, α-SMA and phosphorylated-p38MAPK, Smad3 and NFκB proteins. Nox2 upregulation and EMT were inhibited in TGF-ß1 knockout cells suggesting that TGF-ß1 is required for Nox2 activation. Fisher344 rats treated with high dose CsA showed increased Nox2 in the tubulointerstitium and greater Nox2, α-SMA, phosphorylated Smad3 and nitrotyrosine by immunoblot analyses. Inhibition of Nox2 by coadministration of apocynin or diphenyleneiodonium was associated with reduced fibrogenesis. We validated these findings by treating wild type and Nox2 null (B6.129S-Cybb(Tm1Din)/J) mice with high dose CsA. Western blot analyses confirmed the absence of Nox2 and significantly lower levels of α-SMA and 4-hydroxynonenal (HNE) in CsA-treated knockout mice. These findings were clinically relevant since Nox2 and α-SMA were increased in the tubulointerstitium of kidneys from 15 liver transplant recipients with biopsy-confirmed chronic CsA or TAC nephrotoxicity. In conclusion, specific Nox2 inhibition strategies may improve chronic CNI nephrotoxicity in solid organ transplantation.

Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia.

Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.

Peripheral nerve hyperexcitability: a clinical and immunologic study of 38 patients.

OBJECTIVE: We studied a case series of peripheral nerve hyperexcitability (PNH) aiming to describe clinical characteristics, immunologic and cancer associations, antibodies against neuronal antigens (voltage-gated potassium channel antibodies [VGKC-Abs] and other), and muscle biopsy findings. METHODS: Patients presenting with clinical and electrophysiologic signs of PNH were selected. We studied clinical and electrophysiologic features; a panel of non-neuronal organ-specific antibodies, immunofluorescence on rat nervous tissues, and radioimmunoprecipitation for VGKC-Abs; and muscle biopsies. RESULTS: Thirty-eight patients were included. After the exclusion of 6 cases with axonopathy of known origin, patients were subdivided according to the presence of electrophysiologic findings of motor axonopathy and association with cancer: axonopathic-PNH (group A: 12 patients), isolated nonparaneoplastic PNH (group B: 16 patients), and isolated paraneoplastic PNH (3 with thymoma and myasthenia gravis, 1 with thyroid carcinoma). PNH clinical features were similar in groups A and B. We found an overall high prevalence of clinical autoimmunity (33% of group A and 63% of group B) and systemic non-neuronal autoantibodies (42% of group A and 75% of group B). However, VGKC-Abs were only positive in 2 patients of group B. Ten patients underwent muscle biopsy, which showed inflammatory changes in 2 cases and nonspecific myopathic features in 8. CONCLUSIONS: PNH is a heterogeneous disorder involving the peripheral nerves in patients with a high propensity for developing autoimmunity. Associated muscle diseases are frequent in the form of myositis, myasthenia gravis, or nonspecific myopathic pathologic findings. VGKC-Abs were uncommon in this series.

Prevalence of XMRV nucleic acid and antibody in HIV-1-Infected men and in men at risk for HIV-1 Infection.

Xenotropic MLV-Related Virus (XMRV) was recently reported to be associated with prostate cancer and chronic fatigue syndrome (CFS). Infection was also reported in 3.7% of healthy individuals. These highly reported frequencies of infection prompted concerns about the possibility of a new, widespread retroviral epidemic. The Multicenter AIDS Cohort Study (MACS) provides an opportunity to assess the prevalence of XMRV infection and its association with HIV-1 infection among men who have sex with men. Reliable detection of XMRV infection requires the application of multiple diagnostic methods, including detection of human antibodies to XMRV and detection of XMRV nucleic acid. We, therefore, tested 332 patient plasma and PBMC samples obtained from recent visits in a subset of patients in the MACS cohort for XMRV antibodies using Abbott prototype ARCHITECT chemiluminescent immunoassays (CMIAs) and for XMRV RNA and proviral DNA using a XMRV single-copy qPCR assay (X-SCA). Although 9 of 332 (2.7%) samples showed low positive reactivity against a single antigen in the CMIA, none of these samples or matched controls were positive for plasma XMRV RNA or PBMC XMRV DNA by X-SCA. Thus, we found no evidence of XMRV infection among men in the MACS regardless of HIV-1 serostatus.

Granzyme B: evidence for a role in the origin of myasthenia gravis.

PURPOSE OF RESEARCH: Although the pathogenesis of myasthenia gravis (MG) as an antibody mediated disorder of acetylcholine receptors (AChRs) at neuromuscular junctions is well understood, the origin of the autoimmune response is unclear. The thymus is intimately involved in initiation of the autoimmune response; the antigen, AChR, is present in the thymus, but how the autoimmune response is triggered is not known. Granzyme B (GrB), a proteolytic enzyme present in cytolytic T cells and natural killer (NK) cells, selectively cleaves many potential autoantigens (but few non-autoantigens), generating novel fragments that trigger autoreactive responses. This protease has been strongly implicated in the pathogenesis of several autoimmune diseases including lupus, rheumatoid arthritis, dermatomyositis, and others. In the studies described in this manuscript, we examined the ability of GrB to cleave the AChR subunits, and performed biochemical, immunohistochemical and molecular studies on thymus glands from myasthenic patients and controls to assess GrB expression. MAIN RESULTS: GrB efficiently and specifically cleaves subunits of AChR, especially the epsilon subunit. GrB is present in thymus glands from myasthenia patients, but is absent in control thymuses. CONCLUSIONS: Our results provide evidence supporting a potential role for GrB in the process of initiation of MG, and are consistent with the concept of an immunodominant epsilon epitope.

Detection of human herpesvirus 8 (HHV-8) in normal prostates.

BACKGROUND: Human herpesvirus 8 (HHV-8) DNA has been detected in semen and prostatic tissues in some, but not all reports. We have analyzed prostate tissues from HHV-8 seropositive men for the expression of viral proteins and determined if expression of these proteins are associated with increased inflammation. METHODS: Paraffin sections of non-cancerous prostates from HHV-8 seropositive (n = 16) and seronegative (n = 2) men who died with AIDS were screened for expression of three viral proteins by immunohistochemistry. Levels of inflammation were determined by expression of CD68 and CD20. Cellular proliferation was determined by expression of Ki67. RESULTS: Among the 16 HHV-8 seropositive cases, 68.9% (11/16) (95% C.I. = 0.41-0.89) were positive for HHV-8 protein expression, while the 2 seronegative patients showed no HHV-8 protein expression. There was increased inflammation among HHV-8 positive prostates. CONCLUSIONS: These results demonstrate that HHV-8 is present in normal prostates of HIV-infected men and the expression of viral proteins is associated with increased localized inflammation.

Scenarios for autoimmunization of T and B cells in myasthenia gravis.

We have studied responses in thymoma patients to interferon-alpha and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic epithelial cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently provoke germinal center formation in EOMG. Our unifying hypothesis proposes that AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells aberrantly prime helper T cells, whether generated locally or infiltrating from the circulation. These helper T cells then induce antibody responses against linear epitopes that cross-react with whole AChR and attack myoid cells in the EOMG thymus. The resulting antigen-antibody complexes and the recruitment of professional antigen-presenting cells increase the exposure of thymic cells to the infiltrates and provoke local germinal center formation and determinant spreading. Both these and the consequently enhanced heterogeneity and pathogenicity of the autoantibodies should be minimized by early thymectomy.

Optic disc morphology may reveal timing of insult in children with periventricular leucomalacia and/or periventricular haemorrhage.

AIMS: To evaluate the relation between optic disc morphology and timing of periventricular white matter damage, defined as either periventricular leucomalacia (PVL) or periventricular haemorrhage (PVH), as estimated by neuroradiology. METHODS: 35 children with periventricular white matter damage who had had neuroradiology performed and ocular fundus photographs taken had their photographs analysed by digital image analysis and compared with a control group of 100 healthy full term children. Timing of brain lesion was estimated by analysis of the brain lesion pattern on neuroradiological examinations (magnetic resonance imaging or computed tomography). RESULTS: Four of 35 children had a small optic disc area; these four children had a brain lesion estimated to have occurred before 28 weeks of gestation. Nine of 11 children with a large cup area had a PVL/PVH estimated to have occurred after 28 weeks of gestation. The children with PVL/PVH had a significantly larger cup area (median 0.75 mm(2)) than the control group (median 0.33 mm(2)) (p = 0.001) and a significantly smaller neuroretinal rim area (median 1.58 mm(2)) than the controls (median 2.07 mm(2)) (p = 0.001). CONCLUSION: In a child with PVL/PVH and abnormal optic disc morphology, the possibilities of timing of the lesion should be considered.

Visual and perceptual characteristics, ocular motility and strabismus in children with periventricular leukomalacia.

The immature visual system is vulnerable to adverse events. Periventricular leukomalacia (PVL), an end-stage lesion after hypoxia-ischemia at gestational age 24-34 weeks affecting the visual radiation, has become a principal cause of visual impairment in children. Cerebral visual dysfunction caused by PVL is characterized by delayed visual maturation, subnormal visual acuity, crowding, visual field defects, and visual perceptual-cognitive problems. Magnetic resonance imaging is the method of choice for diagnosing this brain lesion, which is associated with optic disk abnormalities, strabismus, nystagmus, and deficient visually guided eye movements. Children with PVL may present to the ophthalmologist within a clinical spectrum from severe visual impairment in combination with cerebral palsy to only early-onset esotropia, normal intellectual level and no cerebral palsy. Optimal educational and habilitational strategies need to be developed to meet the needs for this group of children.