Pathological Threshold Research Articles

Frequency and distribution of polyQ disease intermediate-length repeat alleles in healthy Italian population

Huntington disease (HD) and spinocerebellar ataxia type 1-2-17 (SCA1-2-17) are adult-onset autosomal dominant diseases, caused by triplet repeat expansions in the HTT, ATXN1, ATXN2, and TBP genes. Alleles with a repeat number just below the pathological threshold are associated with reduced penetrance and meiotic instability and are defined as intermediate alleles (IAs). We aimed to determine the frequencies of IAs in healthy Italian subjects and to compare the proportion of the IAs with the prevalence of the respective diseases. We analyzed the triplet repeat size in HTT, ATXN1, ATXN2, and TBP genes in the DNA samples from 729 consecutive adult healthy Italian subjects. IAs associated with reduced penetrance were found in ATXN2 gene (1 subject, 0.1%) and TBP gene (0.82%). IAs at risk for meiotic instability were found in HTT (5.3%) and ATXN2 genes (2.7%). In ATXN1, we found a low percentage of IAs (0.4%). Alleles lacking the common CAT interruption within the CAG sequence were also rare (0.3%). The high frequencies of IAs in HTT and ATXN2 genes suggest a correlation with the prevalence of the diseases in our population and support the hypothesis that IAs could represent a reservoir of new pathological expansions. On the opposite, ATXN1-IA were very rare in respect to the prevalence of SCA1 in our country, and TBP- IA were more frequent than expected, suggesting that other mechanisms could influence the occurrence of novel pathological expansions.

Neuropathology of the Alzheimer's continuum: an update.

Alzheimer's disease (AD), the most common form of dementia worldwide, is a mixed proteinopathy (amyloid and tau). Originally defined as a clinicopathological entity, it is a heterogenous, multifactorial disorder, currently referred to as the Alzheimer's continuum. Its cardinal pathological features are extracellular β-amyloid (amyloid plaques) and intraneuronal tau aggregates forming neurofibrillary tangles, which are accompanied by vascular amyloid deposits (cerebral amyloid angiopathy), synapse and neuronal loss, as well as neuroinflammation and reactive astrogliosis. In addition to "typical" AD, various subtypes with characteristic regional patterns of tau pathology have been described that show distinct clinical features, biomarker levels, and patterns of key network destructions responsible for cognitive decline. AD is frequently associated with other age-related changes including Lewy and TDP-43 pathologies, hippocampal sclerosis, argyrophilic grain disease, cerebrovascular lesions, and others. These additional pathologies influence the clinical picture of AD, may accelerate disease progression, and can cause a number of challenges in our understanding of the disease including the threshold of each individual pathology to cause dementia and the possibility of underlying common etiologies. This article provides an up-to-date overview of AD neuropathology, its heterogeneity, and additional pathologies in order to explain the difficulties in the diagnosis and the failure of clinical trials in AD patients.

Significance of Quantitative Cerebral Blood Flow Measurement in the Acute Stage after Revascularization Surgery for Adult Moyamoya Disease: Implication for the Pathological Threshold of Local Cerebral Hyperperfusion

Objective: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard surgical procedure for adult patients with moyamoya disease (MMD) and plays a role in preventing ischemic and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is a potential complication of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the exact threshold of the pathological increase in postoperative cerebral blood flow (CBF) is unclear. Thus, we analyzed local CBF in the acute stage after revascularization surgery for adult MMD to predict CHP syndrome under modern perioperative management. Materials and Methods: Fifty-nine consecutive adult MMD patients, aged 17–66 years old (mean 43.1), underwent STA-MCA anastomosis with indirect pial synangiosis for 65 affected hemispheres. All patients were perioperatively managed by strict blood pressure control (systolic pressure of 110–130 mm Hg) to prevent CHP syndrome. Local CBF at the site of anastomosis was quantitatively measured using the autoradiographic method by N-isopropyl-p-[¹²³I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. We defined CHP phenomenon as a local CBF increase over 150% compared to the preoperative value. Then, we investigated the correlation between local hemodynamic change and the development of CHP syndrome. Results: After 65 surgeries, 5 patients developed CHP syndrome, including 2 patients with delayed intracerebral hemorrhage (3.0%), 1 with symptomatic subarachnoid hemorrhage (1.5%), and 2 with focal neurological deterioration without hemorrhage. The CBF increase ratio was significantly higher in patients with CHP syndrome (270.7%) than in patients without CHP syndrome (135.2%, p = 0.003). Based on receiver operating characteristic analysis, the cutoff value for the pathological postoperative CBF increase ratio was 184.5% for CHP syndrome (sensitivity = 83.3%, specificity = 94.2%, area under the curve [AUC] value = 0.825) and 241.3% for hemorrhagic CHP syndrome (sensitivity = 75.0%, specificity = 97.2%, AUC value = 0.742). Conclusion: Quantitative measurement of the local CBF value in the early postoperative period provides essential information to predict CHP syndrome after STA-MCA anastomosis in patients with adult MMD. The pathological threshold of hemorrhagic CHP syndrome was as high as 241.3% by the local CBF increase ratio, but 2 patients (3.0%) developed delayed intracerebral hemorrhage in this series that were managed following the intensive perioperative management protocol. Thus, we recommend routine CBF measurement in the acute stage after direct revascularization surgery for adult MMD and satisfactory blood pressure control to avoid the deleterious effects of CHP.

Prevalence and quantitative analysis of indium-111 pentetreotide (Octreoscan) uptake in the pancreatic head on SPECT/CT imaging: establishing a region of interest-based pathological uptake threshold.

Determine the prevalence of benign indium-111 (In) pentetreotide uptake in the pancreatic head and determine if a semi-quantitative method can be used to differentiate physiologic from pathologic uptake. Institutional Review Board-approved, HIPAA-compliant retrospective review of 197 somatostatin receptor scintigraphy studies performed in 136 patients, from December 2012 to November 2013 at a large academic medical center. The pancreatic head uptake was visually graded and for all positive cases, two-dimensional and three-dimensional ratios of the pancreatic head to normal liver uptake were calculated. Statistical analysis using paired and two-sample t-tests was performed. Nineteen of one hundred twenty-nine (14.7%) patients had benign In pentetreotide uptake in the pancreatic head. Seven of seven (100%) patients with neuroendocrine (NE) tumors had definite visual uptake. Uptake was 2.7× more likely benign than malignant. Using a three-dimensional region of interest (ROI) method, the pancreatic head-to-liver ratio was 0.91±0.38 (0.37-1.63) for benign uptake and 8.2±7.3 (1.79-23.6) for pathologic uptake (P<0.001). A threshold of 1.67 provided 100% accuracy for determining the presence or absence of a pancreatic head NE tumor. Using a two-dimensional ROI method, the uptake ratio was 0.88±0.37 (0.28-1.73) for benign and 7.5±6.2 (1.85-19.6) for pathologic uptake (P<0.001); a ratio threshold of 1.62 provided 97% accuracy. There was no difference between the uptake ratios at 4 and 24 h. In pentetreotide uptake in the pancreatic head is common and more frequently benign than malignant. Using simple ROI ratiometric methods helps to differentiate benign physiologic from malignant NE tumor uptake.

Coronary reserve in Dobutamine stress echocardiography: Feasibility study and determination of a pathological threshold for myocardial ischemia in the LAD territory

The evaluation of the coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) during a Dobutamine stress echocardiography (DSE) is few realized in current practice. A threshold < 2 would be in favor of myocardial ischemia according to some studies. The main purposes of this study are to analyze the feasibility of the CFVR and to search for a pathological threshold in order to make it a complementary tool in the non-invasive detection for myocardial ischemia in the LAD territory. One hundred and ninety-six consecutive patients referred for detection of myocardial ischemia with contrast-enhanced DSE were evaluated in the GHPSJ from July 2017 to July 2018. CFVR was calculated as a ratio of the distal LAD diastolic peak velocity at rest and peak of stress. The result of the echocardiography was rendered only on the analysis of wall motion abnormalities as a standard reference. The feasibility of CFVR is 94.9%. The pathological threshold of CFVR is ≤ 2.1 (sensitivity of 84.2%, specificity of 70%). The CFVR is altered at 1.87 ± 0.52 in the positive DSE in the LAD territory vs. 2.67 ± 0.91 in the normal ones ( P < 0.001). No significant difference was found between the diabetic and non-diabetic populations ( P = 0.194). The coronary reserve is a non-invasive feasible technique in current practice, sensitive, allowing to add a quantitative criterion to the detection of a myocardial ischemia during a DSE even in non-echogenic patients who needed contrast agent. ( Figure 1 , Cut off value of CFVR).

Parent-reported sleep disorders in children with motor disabilities: a comparison with the Sleep Disturbance Scale for Children's new norms

ObjectiveChildren with motor disabilities such as cerebral palsy or neuromuscular diseases present more sleep disorders than their typically developing (TD) peers. However, research on these populations has always been performed using historical normative datasets or controls such as siblings. Therefore, we assessed the sleep quality of children with motor disabilities in comparison with a large, contemporary, general population sample. MethodsDemographic, medical, and the Sleep Disturbance Scale for Children (SDSC) questionnaires were sent to parents of children aged 4–18 years and followed by our tertiary pediatric neurorehabilitation clinic, and to those of school-aged children in regional primary and secondary schools. TD participant data allowed us to set pathological sleep score thresholds (T score ≥70). ResultsWe collected 245 responses for children with motor disabilities and 2891 for those from the general population (37% and 26% response rates, respectively). Cerebral palsy was the most frequent diagnosis (N = 109, 44.5%). Children with motor disabilities had significantly more frequent pathological sleep reported in their total SDSC score (7% vs 1.9%, odds ratio (OR) 3.98, 95% confidence interval (CI) 2.17–7.27, p < 0.001) and in five subscores. Single-parent households and drug-resistant epilepsy showed significant positive associations with pathological sleep among children with motor disabilities. For TD peers, parental unemployment and parental nationality were positively associated with pathological sleep. ConclusionThis population-based study robustly estimated the prevalence of sleep disorders in children with motor disabilities. Sleep disorders were significantly more frequent in children with motor disabilities, but at a lower frequency than previously reported.

Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy.

ObjectiveTo provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design.MethodsMR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests.ResultsSignificant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68–0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63–0.73) and peroneals (|ρ| = 0.59–0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation.DiscussionLower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

Intracranial pressure in patients with papilloedema.

Papilloedema is a clinical manifestation of chronically raised intracranial pressure (ICP), often seen in idiopathic intracranial hypertension (IIH). However, the extent of intracranial hypertension required to produce papilloedema is not known. We compare ICP values in IIH patients who developed papilloedema and those who did not. We aim to identify a pathological ICP threshold predictive of the development of papilloedema in IIH patients. Single-centre cohort of IIH patients (2006-2016) who underwent 24-hour ICP monitoring (ICPM) and ophthalmology assessments, prior to intervention. Papilloedema was graded according to the Frisén scale. An unpaired t-test compared 24-hour ICPM between papilloedema and no-papilloedema groups. Fisher's exact test was used to determine predictive value of ICP. Thirty-six patients with IIH (35F: 1M), mean age 32.5±9.49years (mean±SD) were included. Patients with papilloedema had a mean median 24-hour ICP of 10.4±5.32mmHg (n=25), significantly higher than the group without papilloedema 6.31±3.30mmHg (n=11) (P<.05). The papilloedema group were exposed to higher pressures (10mmHg) for 30minutes or more. Using 24-hour median ICP of 10mmHg as a minimum cut-off predictive value gives a specificity=91%, sensitivity=48%, PPV=92% and NPV=44% of detecting papilloedema. A 24-hour ICP of 10mmHg or more is a good predictor for papilloedema and reflects a pathological threshold. The range varied widely suggesting papilloedema can occur at even lower pressures. These results are consistent with emerging evidence suggest that pathologically "high" 24hours ICP is lower than previously quoted.

Prevalence of IgG Autoantibodies against GD3 Ganglioside in Acute Zika Virus Infection

Zika virus (ZIKV) disease has become a global health emergency with devastating effects on public health. Recent evidences implicate the virus as an emergent neuropathological agent promoting serious pathologies of the human nervous system, that include destructive and malformation consequences such as development of ocular and fetal brain lesions, microcephaly in neonates, and Guillain–Barré syndrome (GBS) in adults. These neurological disorders of both central and peripheral nervous systems are thought to be associated to the neurotropic properties of the virus that has ability to infect neural stem cells as well as peripheral neurons, a hallmark of its pathogenicity. The presence of autoantibodies against gangliosides plays a pivotal role in the etiogenesis of GBS and a variety of neurological disorders. Gangliosides are a class of galactose-containing cerebrosides mainly expressed in nervous system tissues playing a critical role in the physiology of neural cells and neurogenesis. Herein, our findings indicate that patients at acute phase of ZIKV infection without any neurological signs show increased levels of IgG autoantibody against GD3 gangliosides, a class of glycolipid found to be highly expressed in neural stem cell acting in the maintenance of their self-renewal cellular capacity. It is possible that a pathological threshold of these antibodies is only acquired in secondary or subsequent infections. In the light of these evidences, we propose that the target of GD3 by autoimmune responses may possibly has an effect in the neuropathy and neurogenesis disorder seen during ZIKV infection.

Pathological fracture risk assessment in patients with femoral metastases using CT-based finite element methods. A retrospective clinical study.

Physician recommendation for prophylactic surgical fixation of a femur with metastatic bone disease (MBD) is usually based on Mirels' criteria and clinical experience, both of which suffer from poor specificity. This may result in a significant number of these health compromised patients undergoing unnecessary surgery. CT-based finite element analyses (CTFEA) have been shown to accurately predict strength in femurs with metastatic tumors in an ex-vivo study. In order to assess the utility of CTFEA as a clinical tool to determine the need for fixation of patients with MBD of the femur, an ad hoc CTFEA was performed on a retrospective cohort of fifty patients. Patients with CT scans appropriate for CTFEA analysis were analyzed. Group 1 was composed of 5 MBD patients who presented with a pathologic femoral fracture and had a scan of their femurs just prior to fracture. Group 2 was composed of 45 MBD patients who were scheduled for a prophylactic surgery because of an impending femoral fracture. CTFEA models were constructed for both femurs for all patients, loaded with a hip contact force representing stance position loading accounting for the patient's weight and femur anatomy. CTFEA analysis of Group 1 patients revealed that they all had higher tumor associated strains compared to typical non-diseased femur bone strains at the same region (>45%). Based on analysis of the 5 patients in Group 1, the ratio between the absolute maximum principal strain in the vicinity of the tumor and the typical median strain in the region of the tumor of healthy bones (typical strain fold ratio) was found to be the 1.48. This was considered to be the predictive threshold for a pathological femoral fracture. Based on this typical strain fold ratio, twenty patients (44.4%) in Group 2 were at low risk of fracture and twenty-five patients (55.5%) high risk of fracture. Eleven patients in Group 2 choose not to have surgery and none fractured in the 5month follow-up period. CTFEA predicted that seven of these patients were below the pathological fracture threshold and four above, for a specificity of 63% Based on CTFEA, 39% of the patients with femoral MBD who were referred and underwent prophylactic stabilization may not have needed surgery. These results indicate that a prospective randomized clinical trial evaluating CTFEA as a criterion for determining the need for surgical stabilization in patients with MBD of the femur may be warranted.

Clinical spectrum of C9orf72 expansion in a cohort of Huntington's disease phenocopies.

The expansion in the C9orf72 gene has been recently reported as a genetic cause of Huntington's disease (HD) phenocopies. We aim to assess the frequency of the C9orf72 gene expansion in a Portuguese HD phenocopies cohort. Twenty HD phenotype-like patients without diagnosis were identified in our institutional database. C9orf72 gene expansion was detected using repeat-primed PCR. Clinical files were reviewed to characterize the phenotype of expansion-positive cases. One patient (5%) was positive for the C9orf72 expansion. A second patient presented 27 repeats-within the intermediate size interval. Both had familial neuropsychiatric disease characterized by diverse movement disorders, dementia, and psychiatric dysfunction that was distinct in severity and clinical expression. C9orf72 disease is clinically heterogeneous and without evident imaging markers. The definition of the role of intermediate alleles and of the pathological threshold for C9orf72 repeat expansions may have diagnostic implications.

People reporting experiences of mediumship have higher dissociation symptom scores than non-mediums, but below thresholds for pathological dissociation.

Background: Dissociative states exist on a continuum from nonpathological forms, such as highway hypnosis and day-dreaming, to pathological states of derealization and depersonalization. Claims of communication with deceased individuals, known as mediumship, were once regarded as a pathological form of dissociation, but current definitions recognize the continuum and include distress and functional disability as symptoms of pathology. This study examined the relationship between dissociative symptoms and mediumship in a large convenience sample. Methods: Secondary analyses of cross-sectional survey data were conducted. The survey included demographics, the Dissociation Experience Scale Taxon (DES-T, score range 0-100), as well as questions about instances of mediumship experiences. Summary statistics and linear and logistic regressions explored the relationship between dissociative symptoms and mediumship endorsement. Results: 3,023 participants were included and were mostly middle-aged (51 years ± 16; range 17-96), female (70%), Caucasian (85%), college educated (88%), had an annual income over $50,000 (55%), and were raised Christian (71%) but were presently described as Spiritual but not Religious (60%). Mediumship experiences were endorsed by 42% of participants, the experiences usually began in childhood (81%), and 53% had family members who reported similar experiences. The mean DES-T score across all participants was 14.4 ± 17.3, with a mean of 18.2 ± 19.3 for those claiming mediumship experiences and 11.8 ± 15.2 for those who did not (t = -10.3, p < 0.0005). The DES-T threshold score for pathological dissociation is 30. Conclusions: On average, individuals claiming mediumship experiences had higher dissociation scores than non-claimants, but neither group exceeded the DES-T threshold for pathology. Future studies exploring dissociative differences between these groups may benefit from using more comprehensive measures of dissociative symptoms as well as assessments of functional impairment, which would help in discerning between pathological and non-pathological aspects of theseexperiences.

People reporting experiences of mediumship have higher dissociation symptom scores than non-mediums, but below thresholds for pathological dissociation

Background: Dissociative states exist on a continuum from nonpathological forms, such as highway hypnosis and day-dreaming, to pathological states of derealization and depersonalization. Claims of communication with deceased individuals, known as mediumship, were once regarded as a pathological form of dissociation, but current definitions recognize the continuum and include distress and functional disability as symptoms of pathology. This study examined the relationship between dissociative symptoms and mediumship in a large convenience sample. Methods: Secondary analyses of cross-sectional survey data were conducted. The survey included demographics, the Dissociation Experience Scale Taxon (DES-T, score range 0-100), as well as questions about instances of mediumship experiences. Summary statistics and linear and logistic regressions explored the relationship between dissociative symptoms and mediumship endorsement. Results: 3,023 participants were included and were mostly middle-aged (51 years ± 16; range 17-96), female (70%), Caucasian (85%), college educated (88%), had an annual income over $50,000 (55%), and were raised Christian (71%) but were presently described as Spiritual but not Religious (60%). Mediumship experiences were endorsed by 42% of participants, the experiences usually began in childhood (81%), and 53% had family members who reported similar experiences. The mean DES-T score across all participants was 14.4 ± 17.3, with a mean of 18.2 ± 19.3 for those claiming mediumship experiences and 11.8 ± 15.2 for those who did not (t = -10.3, p < 0.0005). The DES-T threshold score for pathological dissociation is 30. Conclusions: On average, individuals claiming mediumship experiences had higher dissociation scores than non-claimants, but neither group exceeded the DES-T threshold for pathology. Future studies exploring dissociative differences between these groups may benefit from using more comprehensive measures of dissociative symptoms as well as assessments of functional impairment, which would help in discerning between pathological and non-pathological aspects of these experiences.

Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths.

Huntington’s disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). The prevailing hypothesis is that the monomeric Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 36–37 residues. Here, we test this hypothesis by combining novel semi-synthesis strategies with state-of-the-art single-molecule Förster resonance energy transfer measurements on biologically relevant, monomeric Httex1 proteins of five different polyQ lengths. Our results, integrated with atomistic simulations, negate the hypothesis of a sharp, polyQ length-dependent change in the structure of monomeric Httex1. Instead, they support a continuous global compaction with increasing polyQ length that derives from increased prominence of the globular polyQ domain. Importantly, we show that monomeric Httex1 adopts tadpole-like architectures for polyQ lengths below and above the pathological threshold. Our results suggest that higher order homotypic and/or heterotypic interactions within distinct sub-populations of neurons, which are inevitable at finite cellular concentrations, are likely to be the main source of sharp polyQ length dependencies of HD.

Cognitive dysfunction associated with aluminum hydroxide-induced macrophagic myofasciitis: A reappraisal of neuropsychological profile

Patients with macrophagic myofasciitis (MMF) present with diffuse arthromyalgias, chronic fatigue, and cognitive disorder. Representative features of MMF-associated cognitive dysfunction include attentional dysfunction, dysexecutive syndrome, visual memory deficit and left ear extinction. Our study aims to reevaluate the neuropsychological profile of MMF. 105 unselected consecutive MMF patients were subjected to a neuropsychological battery of screen short term and long-term memory, executive functions, attentional abilities, instrumental functions and dichotic listening. From these results, patients were classified in four different groups: Subsymptomatic patients (n=41) with performance above pathological threshold (−1.65 SD) in all tests; Fronto-subcortical patients (n=31) who showed pathological results at executive functions and selective attention tests; Papezian patients (n=24) who showed pathological results in storage, recognition and consolidation functions for episodic verbal memory, in addition to fronto-subcortical dysfunction; and Extinction patients (n=9) who had a left ear extinction at dichotic listening test in association to fronto-subcortical and papezian dysfunction. In addition, inter-test analysis showed that patients with apparently normal cognitive functions (Subsymptomatic group) performed significantly worse to attention tests compared to others. In conclusion, our study shows that (i) most patients have specific cognitive deficits; (ii) all patients with cognitive deficit have impairment of executive functions and selective attention; (iii) patients without measurable cognitive deficits display significant weakness in attention; (iv) episodic memory impairment affects verbal, but not visual, memory; (v) none of the patients show an instrumental dysfunction.

Current evidence advocates use of a new pathologic tibial tubercle-posterior cruciate ligament distance threshold in patients with patellar instability.

To determine (1) whether a correlation exists between tibial tubercle-posterior cruciate ligament (TT-PCL) and tibial tubercle-trochlear groove (TT-TG) distances in patellar instability patients; (2) reliability when measuring TT-PCL distance; (3) whether TT-PCL distances measured on MRI are equivalent to those on CT; and (4) whether a correlation exists between TT-PCL distance and number of instability events or recurrence of instability following stabilization surgery. A systematic review was performed using PRISMA guidelines. Clinical studies investigating the relationships of TT-PCL with TT-TG on CT and/or MRI in patellar instability patients were sought. English language studies with Levels of evidence I-IV were eligible for inclusion. Four studies (285 subjects [300 knees] with patellar instability [74.2% female; mean age 26.1±8.2years]; 114 controls [144 knees; 77% female; mean age 23.1years]) were included. Mean TT-PCL of instability and control groups was 21.1±4.1 and 18.8±4.0mm (p<0.0001), respectively. Two studies reported significant positive (strong and moderate) correlations between TT-PCL and TT-TG MRI measurements in instability patients. All four investigations reported excellent interobserver and intraobserver reliability in MRI measurement of TT-PCL distance. No study compared TT-PCL distances on MRI and CT. No study assessed correlation between TT-PCL distance and number of instability events or recurrence of instability after surgery. A moderate-to-strong positive correlation exists between TT-PCL and TT-TG measurements taken from MRIs of patellar instability patients. There is excellent interobserver and intraobserver reliability when taking TT-PCL measurements using MRI. This review advocates use of a new pathologic TT-PCL threshold of 21mm. Level III, systematic review of Level II-III studies.

P.207 - Macrophagic myofasciits-associated cognitive dysfunction: A reappraisal of neuropsychological profile

Patients with long-lasting aluminium hydroxide-induced macrophagic myofasciitis (MMF) present with diffuse arthromyalgias, chronic fatigue, and cognitive disorder. One hundred five unselected consecutive MMF patients were subjected to neuropsychological evaluation and brain MR imaging (MRI). From descriptive analysis, 64/105 (61%) patients had fronto-subcortical cognitive deficits with pathological results at executive functions and selective attention tests (performances below -1.65 SD). Among them, 24 had pathological results in storage and consolidation functions for episodic verbal memory, and 9 left ear extinction at dichotic listening test, in addition du fronto-subcortical impairment. Remaining 41 patients (39%) displayed performances above pathological threshold in all tests. However, inter-test analysis showed that these patients performed significantly worse to executive functions and attention tests compared to others. None of the patients had instrumental dysfunction. Brain MRI analysis did not show specific features associated with cognitive impairment.

RNA gets in phase.

Several neurological disorders are linked to tandem nucleotide repeat expansion in the mutated gene. Jain and Vale (2017. Nature. https://doi.org/10.1038/nature22386) show that, above a pathological threshold repeat number, base pairing interactions drive phase separation of RNA into membrane-less gels, suggesting that RNA can scaffold the assembly of phase-separated compartments that sequester proteins/RNAs causing toxicity.

18F-Florbetaben PET beta-amyloid binding expressed in Centiloids

PurposeThe Centiloid (CL) method enables quantitative values from Aβ-amyloid (Aβ) imaging to be expressed in a universal unit providing pathological, diagnostic and prognostic thresholds in clinical practice and research and allowing integration of multiple tracers and methods. The method was developed for 11C-PiB scans with zero CL set as the average in young normal subjects and 100 CL the average in subjects with mild Alzheimer’s disease (AD). The method allows derivation of equations to convert the uptake value of any tracer into the same standard CL units but first requires head-to-head comparison with 11C-PiB results. We derived the equation to express 18F-florbetaben (FBB) binding in CL units.MethodsPaired PiB and FBB PET scans were obtained in 35 subjects. including ten young normal subjects aged under 45 years (33 ± 8 years). FBB images were acquired from 90 to 110 min after injection. Spatially normalized images were analysed using the standard CL method (SPM8 coregistration of PET data to MRI data and the MNI-152 atlas) and standard CL regions (cortex and whole cerebellum downloaded from http://www.gaain.org).ResultsFBB binding was strongly correlated with PiB binding (R2 = 0.96, SUVRFBB = 0.61 × SUVRPiB + 0.39). The equation to derive CL values from FBB SUVR was CL units = 153.4 × SUVRFBB − 154.9. The CL value in the young normal subjects was −1.08 ± 6.81 for FBB scans compared to −0.32 ± 3.48 for PiB scans, giving a variance ratio of 1.96 (SDFBB CL/SDPiB CL).Conclusions18F-FBB binding is strongly correlated with PiB binding and FBB results can now be expressed in CL units.

Flow and wall shear stress characterization after endovascular aneurysm repair and endovascular aneurysm sealing in an infrarenal aneurysm model

BackgroundEndovascular aneurysm repair (EVAR) with a modular endograft has become the preferred treatment for abdominal aortic aneurysms. A novel concept is endovascular aneurysm sealing (EVAS), consisting of dual endoframes surrounded by polymer-filled endobags. This dual-lumen configuration is different from a bifurcation with a tapered trajectory of the flow lumen into the two limbs and may induce unfavorable flow conditions. These include low and oscillatory wall shear stress (WSS), linked to atherosclerosis, and high shear rates that may result in thrombosis. An in vitro study was performed to assess the impact of EVAR and EVAS on flow patterns and WSS. MethodsFour abdominal aortic aneurysm phantoms were constructed, including three stented models, to study the influence of the flow divider on flow (Endurant [Medtronic, Minneapolis, Minn], AFX [Endologix, Irvine, Calif], and Nellix [Endologix]). Experimental models were tested under physiologic resting conditions, and flow was visualized with laser particle imaging velocimetry, quantified by shear rate, WSS, and oscillatory shear index (OSI) in the suprarenal aorta, renal artery (RA), and common iliac artery. ResultsWSS and OSI were comparable for all models in the suprarenal aorta. The RA flow profile in the EVAR models was comparable to the control, but a region of lower WSS was observed on the caudal wall compared with the control. The EVAS model showed a stronger jet flow with a higher shear rate in some regions compared with the other models. Small regions of low WSS and high OSI were found near the distal end of all stents in the common iliac artery compared with the control. Maximum shear rates in each region of interest were well below the pathologic threshold for acute thrombosis. ConclusionsThe different stent designs do not influence suprarenal flow. Lower WSS is observed in the caudal wall of the RA after EVAR and a higher shear rate after EVAS. All stented models have a small region of low WSS and high OSI near the distal outflow of the stents.