Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis – a CMR study

Background

Myocardial edema is a substantial feature of the inflammatory response in human myocarditis. The relation between myocardial edema and myocardial mass in the course of healing myocarditis has not been systematically investigated. We hypothesised that the resolution of myocardial edema as visualised by T2-weighted cardiovascular magnetic resonance (CMR) is associated with a decrease of myocardial mass in steady state free precession (SSFP)-cine imaging.

Methods

21 patients with acute myocarditis underwent CMR shortly after onset of symptoms and 1 year later. For visualization of edema, a T2-weighted breath-hold black-blood triple-inversion fast spin echo technique was applied and the ratio of signal intensity of myocardium/skeletal muscle was assessed. Left ventricular (LV) mass, volumes and function were quantified from biplane cine steady state free precession images.11 healthy volunteers served as a control group for interstudy reproducibility of LV mass.

Results

In patients with myocarditis, a significant decrease in LV mass was observed during follow-up compared to the acute phase (156.7 ± 30.6 g vs. 140.3 ± 28.3 g, p < 0.0001). The reduction of LV mass paralleled the normalization of initially increased myocardial signal intensity on T2-weighted images (2.4 ± 0.4 vs. 1.68 ± 0.3, p < 0.0001).In controls, the interstudy difference of LV mass was lower than in patients (5.1 ± 2.9 g vs. 16.3 ± 14.2 g, p = 0.02) resulting in a lower coefficient of variability (2.1 vs 8.9%, p = 0.04).

Conclusion

Reversible abnormalities in T2-weighted CMR are paralleled by a transient increase in left ventricular mass during the course of myocarditis. Myocardial edema may be a common pathway explaining these findings.     

Pseudoradicular and radicular low-back pain--a disease continuum rather than different entities? Answers from quantitative sensory testing

To assess whether pseudoradicular low-back pain may be associated with subclinical sensory deficits in the distal extremity, we applied the quantitative sensory testing protocol of the German Research Network on Neuropathic Pain (DFNS) in 15 patients with pseudoradicular pain distribution. Sixteen age- and gender-matched healthy control subjects as well as 12 patients with radicular pain syndromes (L4-S1) were studied with the same protocol. Radicular pain was diagnosed using clinical criteria (pain radiation beyond the knee, motor-, sensory-, or reflex deficits, positive Laségue's test). Z-score QST profiles revealed a selective loss of vibration detection, detection of v. Frey hair contact, and cold detection in the affected dermatomes in the radicular pain group. The contralateral dermatome was also affected, but to a lesser degree. In patients with pseudoradicular pain, the sensory profile was similar, but sensory loss was less pronounced than in the radicular pain patients. There was no significant difference between the two patient groups. Vibration detection was the most sensitive parameter with 73% abnormal values in radicular and 47% in pseudoradicular cases. These data verified the sensitivity of QST to detect sensory loss in radicular compression syndromes, and support a neuropathic component in low-back pain with radiculopathy. In contrast to some central pain syndromes this sensory loss involved predominantly large fiber functions. The subclinical sensory loss in pseudoradicular cases suggests that these patients may also have a neuropathic component of their chronic pain. The spatial incongruence of pain and sensory loss in pseudoradicular pain, however, may also indicate that the two are not causally related.     

Combination therapies in multiple sclerosis

The last years have seen enormous progress in our understanding of pathophysiology of multiple sclerosis. In addition, the armamentarium of available immunomodulatory or immunosuppressive therapies has greatly increased, especially for the relapsing remitting form of the disease. Since their therapeutic efficacy is often limited in individual patients, it is conceivable that combination therapies may bring improved clinical efficacy while managing increasing side effects and toxicity. The combination of agents with additive or synergistic modes of action is of particular interest. Combination of the two classes of recognised firstline treatment, a beta-interferon and glatiramer acetate is currently under evaluation in a large Phase III trial. However, there are theoretical reasons for thinking that such a combination may not be particularly beneficial. None of the combination studies performed with beta-interferons to date have shown unequivocal evidence of benefit, including combinations with statins, natalizumab and azathioprine. On the other hand, for glatiramer acetate, the combination with mitoxantrone used as induction therapy may be of interest and preliminary data on combination with minocycline are also promising.     

Tracing of temporo-entorhinal connections in the human brain: cognitively impaired argyrophilic grain disease cases show dendritic alterations but no axonal disconnection of temporo-entorhinal association neurons

Argyrophilic grain disease (AGD), a neurodegenerative disorder, is often associated with mild to moderate Alzheimer’s disease (AD)-related pathology. The development of dementia in AGD is associated with the extent of coexisting AD-related pathology. Therefore, the question arises whether the degenerative changes in the neuronal network of demented AGD-patients represent a distinct pattern or show similar changes of disconnection as considered for AD. We were able to apply DiI-tracing in two human autopsy cases with mild AD-related pathology (controls), in one AD-patient, in one non-demented patient with advanced AD-related pathology, and in three cognitively impaired AGD-patients. DiI-crystals were injected into the entorhinal cortex. Pyramidal neurons of layers III and V of the adjacent temporal neocortex (area 35) were retrogradely marked with the tracer and analyzed. The AD case did not exhibit any retrogradely labeled neurons in the temporal neocortex. In the non-demented case with advanced AD-related pathology, the number of traced neurons was reduced as compared to that in the two controls and in the three AGD cases. In contrast, all three cognitively impaired AGD cases exhibited labeled pyramidal neurons in area 35 in an almost similar number as in the controls. However, alterations in the dendritic tree were observed in the AGD cases. These results show the existence of temporo-entorhinal connections in the adult human brain similar to those reported in animal models. Furthermore, the present study based on seven cases is the first attempt to study changes in the neuronal network in a human tauopathy with targeted axonal tracing techniques. Our findings in three cognitively impaired AGD cases suggest that AGD-related dementia constitutes a distinct disorder with a characteristic pattern of degeneration in the neuronal network.     

Effect of visual impairment on goal-directed aiming movements in children

This study investigated potential differences in motor control between children with a visual impairment (diagnosed albinism; n=11, mean age 8y 4mo [SD 7mo]; seven males, four females,) and children with normal vision (n=11, mean age 8y 4mo [SD 7mo]; six males, five females). Mean near visual acuity in the albinism group was 0.19 (SD 0.07, Snellen: 20/104). Children performed two types of movements (discrete and cyclic) in two orientations (azimuthal and radial, i.e. along the viewing and lateral direction), and with two amplitudes (10 and 20cm). All movements were performed in two subsequent target conditions: with and without visual information on the target location. Overall, children with visual impairment displayed larger endpoint variability. Discrete movements and movements over large distances were less fluent in both groups, but especially in the children with visual impairment. Children with visual impairment seemed to have more difficulties with calibrating the sensory information. Specifically, they made larger errors along the lateral direction, when the target was not visible. Results suggest that children with visual impairment have specific differences in motor control compared with children with normal vision, which are not all directly related to their poorer vision.     

Regional and cellular localization of the CXCl12/SDF-1 chemokine receptor CXCR7 in the developing and adult rat brain

The chemokine stromal cell-derived factor-1 (SDF-1) regulates neuronal development via the chemokine receptor CXCR4. In the adult brain the SDF-1/CXCR4 system was implicated in neurogenesis, neuromodulation, brain inflammation, tumor growth, and HIV encephalopathy. Until the recent identification of RDC1/CXCR7 as the second SDF-1 receptor, CXCR4 was considered to be the only receptor for SDF-1. Here we provide the first map of CXCR7 mRNA expression in the embryonic and adult rat brain. At embryonic stages, CXCR7 and CXCR4 were codistributed in the germinative zone of the ganglionic eminences, caudate putamen, and along the routes of GABAergic precursors migrating toward the cortex. In the cortex, CXCR7 was identified in GABAergic precursors and in some reelin-expressing Cajal-Retzius cells. Unlike CXCR4, CXCR7 was abundant in neurons forming the cortical plate and sparse in the developing dentate gyrus and cerebellar external germinal layer. In the adult brain, CXCR7 was expressed by blood vessels, pyramidal cells in CA3, and mature dentate gyrus granule cells, which is reminiscent of the SDF-1 pattern. CXCR7 and CXCR4 overlapped in the wall of the four ventricles. Further neuronal structures expressing CXCR7 comprised the olfactory bulb, accumbens shell, supraoptic and ventromedial hypothalamic nuclei, medial thalamus, and brain stem motor nuclei. Also, GLAST-expressing astrocytes showed signals for CXCR7. Thus, CXCR4 and CXCR7 may cooperate or act independently in SDF-1-dependent neuronal development. In mature neurons and blood vessels CXCR7 appears to be the preponderant SDF-1-receptor.     

Response inhibition in Huntington's disease-a study using ERPs and sLORETA

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, with neurodegeneration mainly affecting the striatum. We investigated executive functions related to response inhibition in (HD) and healthy controls by means of event-related potentials (ERP) in a simple Go/Nogo-task. In Nogo as opposed to Go trials two fronto-central ERP components are elicited: the Nogo-N2 and Nogo-P3. These components are supposed to depend on (medial) prefrontal regions, especially the anterior cingulate cortex (ACC). The results show that the Nogo-N2 did not differ between the groups, while the Nogo-P3 demonstrated a strong attenuation in the HD-group, which also showed more false alarms in the Nogo-condition. Using sLORETA it is shown that this attenuation was related to the medial frontal cortex, especially the ACC, and superior frontal cortex areas. Moreover, the attenuation was related to the underlying genetic disease load (CAG-index). The decline in inhibition is likely mediated via a dysfunction in the ACC, which is known to be dysfunctional in HD. Moreover, the results may be interpreted that the decline in response inhibition in HD is gene-associated. The differentially affected Nogo-components suggest that they rely on different neuronal circuits, even within the ACC. For HD this suggests that this structure is not entirely dysfunctional.