A comparative study of diagnostic and imaging techniques for osteoarthritis of the trapezium

Objectives. The aims of this study were to determine whether micro-CT is a reliable investigation method to evaluate the severity of OA in the trapezium and to develop a novel micro-CT scoring system based on a quantitative assessment of the subchondral bone thickness in order to better assess OA through an objective parameter.Methods. We compared different diagnostic and imaging techniques performed consecutively on each sample: X-ray, visual analysis, micro-CT and histology. OA and healthy trapezia were subjected to semi-quantitative and quantitative analyses to be classified in four degrees of severity in OA (control, OA-2, OA-3 and OA-4). Specifically, samples were analysed using Dell's score for X-ray, Brown's score for visual analysis and Mankin's score for histology. Micro-CT was scored using a novel quantitative scoring system based on subchondral bone thickness measurements. Results obtained with each technique were then compared and correlated.Results. X-ray analysis showed a higher frequency of OA-2 (27%) and OA-3 (32%) compared with OA-4 (5%), whereas visual analysis, micro-CT and histology showed a lower percentage for OA-2 (18%, 18% and 14%) and OA-3 (23%) and increased frequency for OA-4 (45%, 32% and 40%). Only the micro-CT score of subchondral bone thickness correlated significantly with all the other techniques (P < 0.05).Conclusion. This is the first comparison of techniques proposing a novel scoring system based on objective and quantitative micro-CT data that can be applied as a useful diagnostic tool for OA, providing a deeper comprehension of the pathophysiology of OA in trapezium

Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France

OBJECTIVE: To determine the observed and expected incidence rates of paraneoplastic neurologic syndromes (PNSs) and autoimmune encephalitides (AEs) diagnosed in France between 2016 and 2018, we conducted a population-based epidemiologic study. METHODS: Observed incidence rates were stratified by sex, age groups, region of care, year of diagnosis, and disease subgroups. National expected incidence rates were calculated based on rates obtained in the area directly adjacent to the Reference Center using a mixed Poisson model and compared with observed incidence rates. RESULTS: Six hundred thirty-two patients with definite PNS or AE met the inclusion criteria. The observed incidence rate of definite PNS and AE in France was 3.2 per million person-years (CI95%: 2.9-3.4) compared with an expected incidence rate of 7.1 per million person-years (CI95%: 3.9-11.4). The national observed incidence rate for the antibody-positive AE subgroup increased from 1.4 per million person-years (CI95%: 1.2-1.7) in 2016 to 2.1 per million person-years (CI95%: 1.7-2.4) in 2018, thus surpassing the incidence rate of classical PNS (1.2 per million person-years [CI95%: 1.0-1.5]) of 2018. CONCLUSIONS: There was a significant widespread year-to-year increase in the incidence of diagnoses registered with the Reference Center for all subgroups of PNS and AE studied. The national observed incidence rate is likely underestimated due to underdiagnosis and underreporting

Impact of multiple sclerosis risk loci in postinfectious neurological syndromes

Background: The genetic component of multiple sclerosis (MS) is now set to 200 autosomal common variants. However, it is unclear how genetic knowledge be clinically used in the differential diagnosis between MS and other inflammatory conditions like adult-onset postinfectious neurological syndromes (PINS). The aim of this study was to investigate whether PINS and MS have a shared genetic background using an updated polygenic risk scores. / Methods: Eighty-eight PINS patients have been consecutively recruited between 1996 and 2016 at Mondino Foundation of Pavia, diagnosed according to clinical, MRI and CSF findings and followed-up for several years. Patients were typed using Illumina array, and genotypes imputed using the 1000 Genomes Project reference panel. A weighted genetic risk score (wGRS) has been calculated based on autosomal MS risk loci derived from large-scale studies, and an HLA genetic burden (HLAGB) was also calculated on loci associated to MS. / Results: PINS occurred as an episode of myelitis in 44% of patients, encephalomyelitis in 44%, and encephalitis in remaining cases, with an involvement of peripheral nervous system in 41% of patients. Mean age of onset was 50.1 years, and female:male ratio was 1.4. Patients were followed-up for a mean of 7.2 years, and at last visit 55% had a low disability grade (mRS 0–1). Disease was monophasic in 67% of patients, relapsing in 18% and chronic-progressive in 15%. The wGRS of PINS cases was comparable to 370 healthy controls, while significantly lower compared to 907 bout-onset MS (BOMS) cases (wGRS= 20.9 vs 21.2; p<0.0001). The difference was even larger for PINS with peripheral nervous system involvement (wGRS=20.6) vs BOMS. / Conclusion: The distinction between MS and PINS is not easy to make in clinical practice. However, our study shows that the new set of MS risk alleles does not confer increased susceptibility to PINS. These data support the importance to discriminate these cases from MS with pathophysiological and therapeutic implications

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity

Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis

OBJECTIVE: Antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) characterize a limbic encephalitis (LE) strongly associated with HLA-DRB1*07:01, although some patients lack LGI1-Abs in CSF or do not carry this allele. Whether they represent a different subtype of disease or have different prognoses is unclear. METHODS: Retrospective analysis of clinical features, IgG isotypes, and outcome according to LGI1-Ab CSF positivity and DRB1*07:01 in a cohort of anti-LGI1 LE patients. RESULTS: Patients with LGI1-Abs detected in both CSF and serum (105/134, 78%) were compared with those who were CSF negative (29/134, 22%). Both groups had similar clinical features and serum levels, but CSF-positive patients had shorter diagnostic delay, more frequently hyponatremia, inflammatory CSF, and abnormal MRI (p 0.05). HLA and IgG isotypes were not associated with poor outcome (mRS >2 at last follow-up) in univariate analyses; CSF positivity was only identified as a poor outcome predictor in the multivariate analysis including the complete follow-up, whereas age and female sex also remained when just the first year was considered. CONCLUSIONS: LE without CSF LGI1-Abs is clinically indistinguishable and likely reflects just a lesser LGI1-Ab production. HLA association is sex and age biased and presents clinical particularities, suggesting subtle differences in the immune response. Long-term outcome depends mostly on demographic characteristics and the intensity of the intrathecal synthesis

Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci.

Recent genome-wide association studies of glioma have led to the discovery of single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence to investigate the relationship between risk SNPs and glioma subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter mutation and 1p/19q co-deletion. These data allowed definition of five molecular subgroups of glioma: triple-positive (IDH mutated, 1p/19q co-deletion, TERT promoter mutated); TERT-IDH (IDH mutated, TERT promoter mutated, 1p/19q-wild-type); IDH-only (IDH mutated, 1p/19q wild-type, TERT promoter wild-type); triple-negative (IDH wild-type, 1p/19q wild-type, TERT promoter wild-type) and TERT-only (TERT promoter mutated, IDH wild-type, 1p/19q wild-type). Most glioma risk loci showed subtype specificity: (1) the 8q24.21 SNP for triple-positive glioma; (2) 5p15.33, 9p21.3, 17p13.1 and 20q13.33 SNPs for TERT-only glioma; (3) 1q44, 2q33.3, 3p14.1, 11q21, 11q23.3, 14q12, and 15q24.2 SNPs for IDH mutated glioma. To link risk SNPs to target candidate genes we analysed Hi-C and gene expression data, highlighting the potential role of IDH1 at 2q33.3, MYC at 8q24.21 and STMN3 at 20q13.33. Our observations provide further insight into the nature of susceptibility to glioma

Post irradiation lesions of the brachial plexus.

The authors discuss the clinical and therapeutic problems of post irradiation lesions of the brachial plexus resulting from radiotherapy in the treatment of breast cancer. Twelve such cases were referred to our clinic in the 2 year period ending June 1980. The results after 2 years are reported and the literature on the subject is reviewed. Surgical treatment aimed at mobilising the nerve roots (neurolysis) is recommended, but we would stress that the best treatment is prophylactic. With more strict control of the radiotherapeutic technique, particularly with regard to the total dosage administered, it should never happen

Nitrogen, phosphorus and organics removal in two vertical flow experimental wetlands receiving pretreated municipal wastewater.

Pollutants removal in two vertical flow experimental wetlands receiving pre-treated municipal wastewater was investigated. Laboratory investigations using microcosms were also carried out in order to identify key processes regulating pollutants removal. Results obtained from experimental wetlands seem to confirm the ability of a single stage installation, where nitrification and denitrification processes are jointly optimised using a gravel medium, always wet but not saturated with water. Results obtained from microcosm investigations show the prominent role of O-2 supply, of microbial activity and of bio-available C from vegetal metabolism in the nitrogen removal

Diagnosis and therapy of acute disseminated encephalomyelitis and its variants

Acute disseminated encephalomyelitis (ADEM) is traditionally regarded as a monophasic demyelinating disorder of the central nervous system occurring in children after infection or vaccination. ADEM in children has a polysymptomatic presentation that includes encephalopathy, fever and meningeal signs. In adults, encephalopathy is less frequent and the clinical presentation is usually dominated by long tract involvement. Despite the initial clinical severity, the functional outcome is favorable in most cases. ADEM is a subgroup within the broader spectrum of postinfectious neurological syndromes (PINSs), which includes variants characterized by additional peripheral nervous system involvement, and variants characterized by a relapsing or chronic progressive course. The literature on the matter is scarce, mostly consisting of retrospective studies. The aims of this paper are to review the clinical and paraclinical profile of ADEM and its variants, to identify potential predictors of outcome, to summarize current treatment strategies and to outline research perspectives