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.     

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.

Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.

Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.

Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.     

Acute systemic and lung inflammation in C57Bl/6J mice after intratracheal aspiration of particulate matter from small-scale biomass combustion appliances based on old and modern technologies

Inflammation is regarded as an important mechanism behind mortality and morbidity experienced by cardiorespiratory patients exposed to urban air particulate matter (PM). Small-scale biomass combustion is an important source of particulate air pollution. In this study, we investigated association between inflammatory responses and chemical composition of PM₁ emissions from seven different small-scale wood combustion appliances representing old and modern technologies. Healthy C57Bl/6J mice were exposed by intratracheal aspiration to single dose (10?mg/kg) of particulate samples. At 4 and 18?h after the exposure, bronchoalveolar lavage fluid (BALF) as well as serum was collected for subsequent analyses of inflammatory indicators (interleukin (IL)-6, IL-1β, IL-12, and IL-10; tumor necrosis factor-α (TNF-α); keratinocyte-derived chemoattractant (KC), and interferon-γ (IFN-γ)) in multiplexing assay. When the responses to the PM₁ samples were compared on an equal mass basis, the PM from modern technology appliances increased IL-6, KC, and IL-1β levels significantly in BALF at 4 and 18?h after the exposure. In contrast, these responses were seen only at 4?h time point in serum. Increased cytokine concentrations correlated with metal-rich ash related compounds which were more predominant in the modern technology furnaces emissions. These particles induced both local and systemic inflammation. Instead, polycyclic hydrocarbon (PAH) rich PM₁ samples from old technology (OT) evoked only minor inflammatory responses. In conclusion, the combustion technology largely affects the toxicological and chemical characteristics of the emissions. The large mass emissions of old combustion technology should be considered, when evaluating the overall harmfulness between the appliances. However, even the small emissions from modern technologies may pose significant toxic risks.     

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.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.     

Alexithymia in neurodegenerative disease

We investigated alexithymia, a deficit in the ability to identify and describe one's emotions, in a sample that included patients with neurodegenerative disease and healthy controls. In addition, we investigated the relationship that alexithymia has with behavioral disturbance and with regional gray matter volumes. Alexithymia was examined with the Toronto Alexithymia Scale-20, behavioral disturbance was assessed with the Neuropsychiatric Inventory, and regional gray matter volumes were obtained from structural magnetic resonance images. Group analyses revealed higher levels of alexithymia in patients than controls. Alexithymia scores were positively correlated with behavioral disturbance (apathy and informant distress, in particular) and negatively correlated with the gray matter volume of the right pregenual anterior cingulate cortex, a region of the brain that is thought to play an important role in self and emotion processing.