Customized finite element modelling of the human cornea

Aim To construct patient-specific solid models of human cornea from ocular topographer data, to increase the accuracy of the biomechanical and optical estimate of the changes in refractive power and stress caused by photorefractive keratectomy (PRK). Method Corneal elevation maps of five human eyes were taken with a rotating Scheimpflug camera combined with a Placido disk before and after refractive surgery. Patient-specific solid models were created and discretized in finite elements to estimate the corneal strain and stress fields in preoperative and postoperative configurations and derive the refractive parameters of the cornea. Results Patient-specific geometrical models of the cornea allow for the creation of personalized refractive maps at different levels of IOP. Thinned postoperative corneas show a higher stress gradient across the thickness and higher sensitivity of all geometrical and refractive parameters to the fluctuation of the IOP. Conclusion Patient-specific numerical models of the cornea can provide accurate quantitative information on the refractive properties of the cornea under different levels of IOP and describe the change of the stress state of the cornea due to refractive surgery (PRK). Patient-specific models can be used as indicators of feasibility before performing the surgery. Copyright: © 2015 Simonini, Pandolfi

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports

Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment

The landscape of cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis

Although mutations in the superoxide dismutase 1 gene account for only a minority of total amyotrophic lateral sclerosis cases, the discovery of this gene has been crucial for amyotrophic lateral sclerosis research. Since the identification of superoxide dismutase 1 in 1993, the field of amyotrophic lateral sclerosis genetics has considerably widened, improving our understanding of the diverse pathogenic basis of amyotrophic lateral sclerosis. In this review, we focus on cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis patients. Literature has mostly reported that cognition remains intact in superoxide dismutase 1-amyotrophic lateral sclerosis patients, but recent reports highlight frontal lobe function frailty in patients carrying different superoxide dismutase 1-amyotrophic lateral sclerosis mutations. We thoroughly reviewed all the various mutations reported in the literature to contribute to a comprehensive database of superoxide dismutase 1-amyotrophic lateral sclerosis genotype-phenotype correlation. Such a resource could ultimately improve our mechanistic understanding of amyotrophic lateral sclerosis, enabling a more robust assessment of how the amyotrophic lateral sclerosis phenotype responds to different variants across genes, which is important for the therapeutic strategy targeting genetic mutations. Cognition in superoxide dismutase 1-amyotrophic lateral sclerosis deserves further longitudinal research since this peculiar frailty in patients with similar mutations can be conditioned by external factors, including environment and other unidentified agents including modifier genes

CSF heavy neurofilament may discriminate and predict motor neuron diseases with upper motor neuron involvement

Objective: To assess whether phosphorylated neurofilament heavy chain (pNfH) can discriminate different upper motor neuron (UMN) syndromes, namely, ALS, UMN-predominant ALS, primary lateral sclerosis (PLS) and hereditary spastic paraparesis (hSP) and to test the prognostic value of pNfH in UMN diseases. Methods: CSF and serum pNfH were measured in 143 patients presenting with signs of UMN and later diagnosed with classic/bulbar ALS, UMNp-ALS, hSP, and PLS. Between-group comparisons were drawn by ANOVA and receiver operating characteristic (ROC) analysis was performed. The prognostic value of pNfH was tested by the Cox regression model. Results: ALS and UMNp-ALS patients had higher CSF pNfH compared to PLS and hSP (p < 0.001). ROC analysis showed that CSF pNfH could differentiate ALS, UMNp-ALS included, from PLS and hSP (AUC = 0.75 and 0.95, respectively), while serum did not perform as well. In multivariable survival analysis among the totality of UMN patients and classic/bulbar ALS, CSF pNfH independently predicted survival. Among UMNp-ALS patients, only the progression rate (HR4.71, p = 0.01) and presence of multifocal fasciculations (HR 15.69, p = 0.02) were independent prognostic factors. Conclusions: CSF pNfH is significantly higher in classic and UMNp-ALS compared to UMN diseases with a better prognosis such as PLS and hSP. Its prognostic role is confirmed in classic and bulbar ALS, but not among UMNp, where clinical signs remained the only independent prognostic factors

Psoriatic juvenile idiopathic arthritis associated with uveitis : a case report

According to the definition proposed by the International League of Associations for Rheumatology (ILAR), juvenile idiopathic arthritis (JIA) is defined as an arthritis of unknown etiology, starting under 16 years of age and lasting for at least 6 weeks, once other known conditions have been excluded. JIA represents the most common chronic rheumatic disease of childhood and is considered an important cause of short- and long-term acquired disability in children. It is currently estimated that psoriatic JIA represents up to 10% of all JIA subtypes, and chronic uveitis may occur in 10 to 15% of children with psoriatic JIA. In this report we describe a case of psoriatic JIA complicated by uveitis, in a child failing previous treatments with nonsteroidal anti-inflammatory drugs, methotrexate, and etanercept. Finally, adalimumab was prescribed, which led to sustained clinical remission in both arthritis and uveitis

Young Onset Alzheimer’s Disease Associated with C9ORF72 Hexanucleotide Expansion: Further Evidence for a Still Unsolved Association

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are recognized as part of a disease continuum (FTD-ALS spectrum), in which the most common genetic cause is chromosome 9 open reading frame 72 (C9ORF72) gene hexanucleotide repeat expansion. The clinical phenotype of patients carrying this expansion varies widely and includes diseases beyond the FTD-ALS spectrum. Although a few cases of patients with C9ORF72 expansion and a clinical or biomarker-supported diagnosis of Alzheimer’s disease (AD) have been described, they have been considered too sparse to establish a definite association between the C9ORF72 expansion and AD pathology. Here, we describe a C9ORF72 family with pleomorphic phenotypical expressions: a 54-year-old woman showing cognitive impairment and behavioral disturbances with both neuroimaging and cerebrospinal fluid (CSF) biomarkers consistent with AD pathology, her 49-year-old brother with typical FTD-ALS, and their 63-year-old mother with the behavioral variant of FTD and CSF biomarkers suggestive of AD pathology. The young onset of disease in all three family members and their different phenotypes and biomarker profiles make the simple co-occurrence of different diseases an extremely unlikely explanation. Our report adds to previous findings and may contribute to further expanding the spectrum of diseases associated with C9ORF72 expansion