Statistical evaluation of measured biomechanical properties of human brain aneurysm samples.

Background and purpose:

Human brain aneurysms may often prove fatal if not re­cognized in time and treated accordingly. The understanding of development and rupture of aneurysms can significantly be improved by the application of numerical modelling, which in turn, requires the knowledge of mechanical properties of vessel wall. This study aims to identify assumed differences with respect to age, sex, spatial orientation, and rupture by utilizing detailed statistical analysis of uniaxial tensile measurements of human brain aneurysm samples, performed by the authors in a previous project.

At surgery of 42 patients, aneu­rysm fundi were cut distally to the clip. In each case, depending on size, varying number of stripes (altogether 88) were prepared and uniaxial stress-strain measurements were performed. Quantities related to the capacity, energy absorption or stiffness were determined and statistically analysed.

The number of specimens in the aneurysm sample was sufficient to establish statistical differences with respect to sex and rupture (p<0.05). No significant differences were detected in orientation, though higher values of stresses and deformations were ob­tained in the circumferential direction com­pared to the meridional direction. 

Significant differences bet­ween sexes with respect to ultimate deformations were demonstrated according to expectation, and the hypothesis on equality of energy capacity could be supported. Similarity of curves with respect to specimen orientation was also observed and ruptured aneurysm sacs tended to be smaller in size. It seems that differences and trends described in this paper are realistic and need to be applied in numerical modelling.

Energetically stable curve fitting to hyperelastic models based on uniaxial and biaxial tensile tests.

Hyperelastic constitutive laws in biomechanics are used to model soft tissues, and material model parameters are often determined by performing curve fitting on data from uniaxial or biaxial tensile tests. The strain energy function of the applied constitutive law must to be energetically stable; however, this condition is not inherently provided by most currently available models. This study provides a procedure to determine stable strain energy functions in a biaxial strain space based on either uniaxial or biaxial tensile tests. Instead of conservative, strain-independent conditions, a stability region is defined in the strain space based on the sample's tensile tests, thus allowing optimisation within a wider parameter space, resulting in better approximations. An extension of the Levenberg-Marquardt algorithm incorporating user-defined stability constraints is proposed, and the constrained optimisation algorithm is applied to isotropic and anisotropic models. The uniqueness of solutions of the Fung model is also discussed. The material model parameters of stable solutions for soft tissue measurements from various literature sources are determined to demonstrate the proposed procedure. Applying appropriate constraints in the optimisation algorithm resulted in stable and physically permissible constrained solutions for the strain energy function, in contrast to the results of most unconstrained optimisation cases.

Experimental, Analytical, and Numerical Assessments for the Controversial Elastic Stiffness Enhancement of CFRP-Strengthened Timber Beams.

The strengthening of timber beams with carbon-fibre-reinforced polymers (CFRP) has been widely used in the last decades to enhance the behaviour of historical or new timber structures, usually for bending. While considerable improvement in capacity and ductility is typically achieved, the increase in stiffness was, in many cases, well short of analytical expectations, which tend to overestimate stiffness. This study addresses the problem by investigating the underlying mechanical behaviour using experimental, analytical, and numerical tools on a sample of Norway spruce (Picea abies) beams reinforced with carbon-fibre fabric. In the experimental program, each beam is tested for bending with and without CFRP reinforcement in order to determine specimen-specific stiffness increase on an individual basis. The reinforcement yielded an increase of 27% in capacity, 53% in ultimate displacement, and 133% in compliance, verifying its efficiency. Axial compression tests on an independent sample are also performed to verify modulus of elasticity in compression. Numerical computations based on a beam model and a three-dimensional finite element model are performed with the introduction of separate moduli of elasticity for tension and compression in timber. Inverse computation using the experimental load-deflection curves yielded the moduli and the compression yield stress of timber to provide the best match between tests and simulations. The mean difference of only 6% in stiffness between FEM and the tests is obtained. The dominance of normal stresses in the longitudinal direction is found, in correspondence with the experimentally observed tensile failure of timber (apart from a few defected specimens). Compression yield stresses are within 7% (beam model) and 2% (FEM) error compared with the control axial tests. The differences between FE simulations and tests in ultimate load and compliance are within 1%. This study concludes that the application of CFRP in the composite beams enables the determination of timber material properties opposed to pure timber beams without reinforcement, and the adoption of separate moduli of elasticity for tension and compression leads to adequate modelling of reinforced timber beams.

Strengthening Timber Structural Members with CFRP and GFRP: A State-of-the-Art Review.

The application of fibre-reinforced polymers (FRP) for strengthening timber structures has proven its efficiency in enhancing load-bearing capacity and, in some cases, the stiffness of structural elements, thus providing cost-effective and competitive alternatives both in new design and retrofitting existing historical buildings. Over the last few decades, several reinforcing materials and techniques evolved, and considerable progress was made in numerical modelling, especially using the finite element method. As this field of research has become extensive and diversified, as well as numerous contradicting results have emerged, a thorough review is necessary. This manuscript covers the topics of historical preliminaries, reinforcing with carbon and glass fibre composites, bond characteristics, main reinforcing techniques, modelling of knots, and the effects of the fibre waviness on the composite behaviour. A detailed overview is given on the experimental and numerical investigation of mechanics of strengthened beams. A one-of-a-kind table is presented that compares the stiffness improvement observed in several studies with analytical estimates. Attention is drawn to a number of challenges that have arisen, e.g., the moderate stiffness enhancement, composite-to-wood interface, modelling of knots, and strengthening of defected timber members. This paper can be used as a starting point for future research and engineering projects.

Novel curve fitting method based on constrained optimization for the modelling of human brain aneurysms using Mooney-Rivlin hyperelastic materials in the entire range of deformations til rupture.

PURPOSE: Brain aneurysms often prove fatal if ruptured, therefore, understanding their mechanical behaviour in the coupled system of vessels and blood flow can significantly help preventive surgical treatment. The purpose of this work was to analyse measurement data and to determine material parameters for the hyperelastic Mooney-Rivlin model for model building and numerical simulations of aneurysms. METHODS: A total of 88 human brain aneurysm specimens of 41 patients obtained from surgery were processed in this work based on the tests performed by the authors in a previous project. A novel algorithm was proposed and applied in this work to fit stress-stretch ratio curves for multiple measurement data using constrained optimization with hard conditions to comply with known mechanical behaviour. RESULTS: The method produced parameters of stretch ratio-stress curves for a number of groups of the specimens representing the average as well as the extreme stresses, separately for male and female subsamples. Stretch range both in compression and in tension up to rupture was covered and material stability for the entire range was also verified. CONCLUSIONS: The fitted curves with recommended range of validity are directly applicable to numerical finite element or coupled simulations of aneurysms supporting preventive medical treatment or decision making.

New Insights of Phospholipase A2 Associated Neurodegeneration Phenotype Based on the Long-Term Follow-Up of a Large Hungarian Family.

INTRODUCTION: Phospholipase A2-associated Neurodegeneration (PLAN) is a group of neurodegenerative diseases associated with the alterations of PLA2G6. Some phenotype-genotype association are well known but there is no clear explanation why some cases can be classified into distinct subgroups, while others follow a continuous clinical spectrum. METHODS: Long-term neurological, and psychiatric follow-up, neuropathological, radiological, and genetic examinations, were performed in three affected girls and their family. RESULTS: Two 24-years old twins and their 22-years old sister harbored the p.P622S, and p.R600W mutation in PLA2G6. The age of onset and the most prominent presenting symptoms (gaze palsy, ataxia, dystonia, psychomotor regression indicated atypical neuroaxonal dystrophy (ANAD), however, optic atrophy, severe tetraparesis would fit into infantile neuroaxonal dystrophy (INAD). All siblings had hyperintensity in the globi pallidi and substantiae nigrae which is reported in ANAD, whereas it is considered a later neuroradiological marker in INAD. The slow progression, rigidity, bradykinesis, and the prominent psychiatric symptoms indicate PLA2G6-related dystonia-parkinsonism. Abnormal mitochondria, lipid accumulation and axonal spheroids were observed in the muscle and nerve tissue. Brain deposition appeared 6 years following the initial cerebellar atrophy. Mild MRI alterations were detected in the asymptomatic carrier parents. CONCLUSION: The colorful clinical symptoms, the slightly discordant phenotype, and the neuroimaging data in the family supports the view that despite the distinct definition of age-related phenotypes in PLAN, these are not strict disease categories, but rather a continuous phenotypic spectrum. The mild MRI alterations of the parents and the family history suggest that even heterozygous pathogenic variants might be associated with clinical symptoms, although systematic study is needed to prove this.

Novel dominant MPAN family with a complex genetic architecture as a basis for phenotypic variability.

OBJECTIVE: Our aim was to study a Hungarian family with autosomal dominantly inherited neurodegeneration with brain iron accumulation (NBIA) with markedly different intrafamilial expressivity. METHODS: Targeted sequencing and multiplex ligation-dependent probe amplification (MLPA) of known NBIA-associated genes were performed in many affected and unaffected members of the family. In addition, a trio whole-genome sequencing was performed to find a potential explanation of phenotypic variability. Neuropathologic analysis was performed in a single affected family member. RESULTS: The clinical phenotype was characterized by 3 different syndromes-1 with rapidly progressive dystonia-parkinsonism with cognitive deterioration, 1 with mild parkinsonism associated with dementia, and 1 with predominantly psychiatric symptoms along with movement disorder. A heterozygous stop-gain variation in the C19Orf12 gene segregated with the phenotype. Targeted sequencing of all known NBIA genes, and MLPA of PLA2G6 and PANK2 genes, as well as whole-genome sequencing in a trio from the family, revealed a unique constellation of oligogenic burden in 3 NBIA-associated genes (C19Orf12 p.Trp112Ter, CP p.Val105PhefsTer5, and PLA2G6 dup(ex14)). Neuropathologic analysis of a single case (39-year-old man) showed a complex pattern of alpha-synucleinopathy and tauopathy, both involving subcortical and cortical areas and the hippocampus. CONCLUSIONS: Our study expands the number of cases reported with autosomal dominant mitochondrial membrane protein-associated neurodegeneration and emphasizes the complexity of the genetic architecture, which might contribute to intrafamilial phenotypic variability.

Complete recovery from psychosis upon miglustat treatment in a juvenile Niemann-Pick C patient.

Niemann-Pick disease type C is a rare lipid trafficking disorder characterized by the accumulation of cholesterol and glycosphingolipids in the brain and viscera. Perinatal, early infantile, late infantile, juvenile and adult forms are distinguished based on the age of manifestation. In the juvenile form, patients in their early years are usually, but not always, symptom free, but present with neurodegeneration later in their lives. These include clumsiness, ataxia, seizures, motor and intellectual decline. Psychiatric manifestations may occur at any stage of the disease. These manifestations include schizophrenia, presenile dementia, depression or psychosis. In 2009, miglustat was approved for the therapy of the disease. We present a case of a patient with juvenile Niemann-Pick C disease whose psychosis was reversed completely by miglustat treatment. Based on our clinical experience we suggest considering Niemann-Pick C in cases of therapy-resistant psychosis and encourage the introduction of miglustat in Niemann-Pick C patients even in the most advanced cases, with respect to psychiatric illness.

[Stiff-person syndrome--two Hungarian cases and review of the literature]. / Stiff-person szindróma--Két magyar eset bemutatása a szakirodalom áttekintésével.

The stiff-man syndrome is a rare neurological disorder characterized by progressive stiffness of the axial muscles and co-contraction of agonist and antagonist muscles sometimes accompanied by involuntary sudden muscle spasms. The disease is thought to be caused by immunological changes leading to a GABA transmission disturbance, but the precise pathogenesis is not clear. Two Hungarian cases are presented in this article accompanied by a review of the literature. The aim of the paper is to call the attention on this presumably underdiagnosed disease. The diagnostic laboratory tests of the disease are available in Hungary.

Transcranial Doppler study of the cerebral hemodynamic changes during breath-holding and hyperventilation tests.

BACKGROUND AND PURPOSE: The aim of the present study was to assess the time course of hyperventilation (HV) and breath-holding (BH) tests in healthy volunteers. SUBJECTS AND METHODS: Young healthy volunteers (n = 29) underwent continuous registration of the middle cerebral artery mean blood flow velocity (MCAV) during and after 30 seconds of BH and 60 seconds of HV. Absolute values as well as percentage changes of the MCAV are reported. In 13 subjects, determination of capillary blood gas parameters (pH, pCO2, pO2, and O2 saturation) was performed before tests, after BH and after HV. RESULTS: MCAV during 30 seconds of breath-holding starts to increase after 10 seconds and reaches its highest level at 30 seconds. After breathing normally, MCAV normalizes within 30 seconds. Hyper-ventilation results in a decrease in MCAV, which reaches a plateau at 20 to 30 seconds after starting to hyperventilate, and blood flow velocity did not change significantly any further until the end of the procedure. The normalization of the MCAV is incomplete at 30 seconds after finishing hyperventilation. None of the capillary blood gases changed significantly after breath-holding, whereas capillary pH, pO2, and oxygen saturation increased and pCO2 decreased after hyperventilation. No relationship was found between capillary blood gas parameters and MCAV values. CONCLUSIONS: The authors concluded that breath-holding and hyperventilation tests seem to be a practical alternative to acetazolamide and the CO2 inhalation method in the assessment of cerebral hemodynamics.

Computed tomographic and transcranial Doppler sonographic findings in acute and subacute phases of middle cerebral artery strokes.

PURPOSE: The aim of this study was to compare the sensitivities of visual and densitometric analyses of CT scans and transcranial Doppler sonograms (TCD) in detecting early changes in acute stroke. METHODS: CT and TCD were each performed twice in 12 patients; first in the acute phase (within 28 hours of stroke onset), then in the subacute phase (mean +/- standard deviation, 6 +/- 3 days after onset) of a stroke. Hypodensity on the CT scans was evaluated visually, and the optical density of both the stroke region and the corresponding region on the unaffected side was measured. Measurement of flow parameters in the middle cerebral artery was carried out with TCD before or shortly (within 4 hours) after CT scanning. RESULTS: In the acute phase, blood flow velocities were significantly lower on the affected side than they were on the unaffected side (means, 42 +/- 13 and 55 +/- 25 cm/second, respectively; p = 0.012). Marked asymmetry in flow velocity was found in 3 of the 4 patients who had normal CT scans in the acute phase. The asymmetry in flow velocity disappeared by the sixth day after the stroke. The resistance index did not correlate with the final infarct size. CONCLUSIONS: In some patients, the use of TCD in acute stroke may show alterations that reflect tissue damage that is undetectable on CT. Therefore, CT and TCD should be considered complementary diagnostic tools in the acute phase of stroke.