Deformation of the corona radiata and internal capsule in normal pressure hydrocephalus

Background and purposeThe pathophysiology of the clinical manifestations in normal pressure hydrocephalus (NPH) remains obscure. Ventricular dilatation could generate forces on the paracentral fibers of the corona radiata (CR), hence interfering with their function and producing the classical clinical triad. The analysis of the regional displacement and deformation of the white matter bundles, forming the corona radiata and internal capsule, may clarify the relationship between ventricular dilatation and clinical manifestations in NPH.MethodAn experimental finite element (FE) analysis was used to simulate ventricular dilatation in 3 dimensions (3D) and to calculate the strain and deformation on the surrounding parenchyma. Magnetic resonance diffusion tensor imaging-based white matter tractography was then applied to retrieve the displacement and deformation exerted along various fiber bundles of the corona radiata and internal capsule. Anterior and posterior limb displacements and elongations were compared using a paired samples t-test.ResultsThe internal capsule, hence the corona radiata, of each cerebral hemisphere was segmented into anterior and posterior limbs. Mean displacements and elongations were calculated for each limb. Mean displacement was significantly larger in the anterior limb whereas mean deformation was larger in the posterior limb (P < 0.01).ConclusionThe present simulation demonstrates that ventricular dilatation does not have a homogeneous effect on the periventricular fibre tracts, with a particular load on the corticospinal tract. The affection of this tract remains thereby a potential factor in the generation of the NPH gait disorders.     

An insight into electrical resistivity of white matter and brain tumors

BackgroundThere is a lack of information regarding electrical properties of white matter and brain tumors.ObjectiveTo investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter.MethodsA bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω1m) were compared between different intracranial tissues and brain tumors.ResultsNinety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω1m) than within peritumoral edema (8.5 ± 1.6 Ω1m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω1m, WHO III:6.3 ± 0.9 Ω1m), enhancing (WHO IV:5 ± 1 Ω1m, metastasis:5.4 ± 1.3 Ω1m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω1m, metastasis:4.3 ± 1.3 Ω1m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively.ConclusionsThe technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors.     

A paradigm for awake intraoperative memory mapping during forniceal stimulation

We report the case of a chess player with superior premorbid cognitive function who presented to the Cognitive Disorders clinic at the National Hospital for Neurology and Neurosurgery with a 2-year history of symptoms of possible memory loss. Initially the MRI scan appearance was within normal limits and his cognitive scores inside the normal range; subsequently his cognitive function deteriorated and he fulfilled criteria for Mild Cognitive Impairment (MCI) two years later. Unexpectedly he died of an unrelated illness seven months later and post mortem examination of the brain was carried out, revealing advanced Alzheimer’s disease (CERAD definite and NIA-Regan Institute high likelihood).

This case highlights the difficulties encountered in assessing patients with superior premorbid function in the early stages of Alzheimer’s disease, and reveals the value of serial MRI and neuropsychological assessment in detecting and monitoring early neurodegenerative disease.     

Determinants of the White‐Coat Effect in Normotensives and Never‐Treated Mild Hypertensives

The prognostic significance of the white‐coat effect (WCE) is unclear. Knowledge of the predictors of the WCE may help illuminate the clinical significance of this phenomenon. The purpose of this study was to (i) compare characteristics of subjects demonstrating a WCE, those not demonstrating a WCE, and those demonstrating a reverse WCE and (ii) determine clinical features that may influence the size of the WCE. Forty‐one subjects with normotension or mild hypertension who had never been treated with antihypertensive medications were recruited for the study. All subjects underwent a battery of anthropometrical measurements and clinic blood pressure (BP) measurements. To calculate arterial compliance, impedance cardiography was used to measure resting stroke volume in each subject. All subjects performed a laboratory mental stress protocol to determine the size of the BP reactivity. Ambulatory blood pressure (ABP) profiles were studied in each subject with the use of an oscillometric ABP recorder. White‐coat effect was determined by subtracting the awake period of the ambulatory systolic blood pressure (SBP) from the clinical SBP. Subjects were grouped according to the size of their WCE. Those who showed a WCE of 5 mmHg and above were assigned to the WCE group; those who showed a WCE of between ?5 and 5 mmHg were assigned to the no white coat effect (NWCE) group; those who exhibited a WCE of ?5 mmHg and lower were assigned to the reverse white‐coat effect (RWCE) group. Subjects with a positive WCE had significantly higher body mass index (BMI) than those without a WCE and those with a RWCE. The WCE group had significantly higher clinic SBP and heart rate (HR) than the RWCE group. Arterial compliance was significantly lower in the WCE group as compared to the NWCE group and the RWCE group. The three groups had comparable ABP profiles. In terms of BP variability, the increase in SBP in response to mental stress did not differ among the three study groups nor did the 24‐hour and awake BP variability. For the sample as a whole, clinic HR and clinic‐ambulatory SBP difference were higher and arterial compliance were lower in women than in men. Furthermore, clinic SBP significantly correlated with the systolic WCE (r = 0.40, P = 0.009). When men and women were analyzed separately, the correlation between clinic SBP and the systolic WCE was significant in women (r = 0.63, P = 0.001) but not in men (P = 0.95). Multiple linear regression showed that sex (P = 0.013) and clinical SBP (P = 0.003) were the only two variables that significantly influenced the systolic WCE. These two variables together accounted for 29% of the variation in the systolic WCE. In conclusion sex and clinic BP are two major determinants of the WCE. The results of this study indicate that WCE is not related to higher stress reactivity or higher BP variability.     

White matter hyperintensities mediate the impact of amyloid ß on future freezing of gait in Parkinson's disease

BackgroundFreezing of gait (FOG) is a common symptom in Parkinson's Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β deposition. However, there is a paucity of research on the concurrent impact of white matter damage.ObjectivesTo assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other.MethodsWe used baseline MRI and longitudinal gait data from 423 de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG.ResultsSN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels.ConclusionsAmyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.     

The impact of cerebrovascular aging on vascular cognitive impairment and dementia

As human life expectancy rises, the aged population will increase. Aging is accompanied by changes in tissue structure, often resulting in functional decline. For example, aging within blood vessels contributes to a decrease in blood flow to important organs, potentially leading to organ atrophy and loss of function. In the central nervous system, cerebral vascular aging can lead to loss of the integrity of the blood-brain barrier, eventually resulting in cognitive and sensorimotor decline. One of the major of types of cognitive dysfunction due to chronic cerebral hypoperfusion is vascular cognitive impairment and dementia (VCID). In spite of recent progress in clinical and experimental VCID research, our understanding of vascular contributions to the pathogenesis of VCID is still very limited. In this review, we summarize recent findings on VCID, with a focus on vascular age-related pathologies and their contribution to the development of this condition.