Long-term neuropsychological and psychosocial outcomes of decompressive hemicraniectomy following malignant middle cerebral artery infarctions

Purpose: This study examines long-term neuropsychological and psychosocial outcomes of survivors of malignant middle cerebral artery infarction treated via decompressive hemicraniectomy. Method: A case series design facilitated a detailed analysis of the outcomes among five participants. Neuropsychological domains assessed included premorbid and current IQ, sustained, selective and divided attention, visual and auditory memory, executive functioning and visuo-spatial ability. Psychosocial domains assessed included self-rated depression, anxiety and quality of life. Participants and their main carer were asked about their retrospective view of surgery. Results: All participants showed neuropsychological impairments in multiple cognitive domains, with preserved ability in others. Effects of laterality of brain function were evident in some domains. Clinically significant depression was evident in two participants. Overall quality of life was within average limits in three of four assessed participants. Four participants retrospectively considered surgery as having been a favourable course of action. Conclusion: While neuropsychological impairments are highly likely post-surgery, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life. Results do not support the suggestion that decompressive hemicraniectomy following malignant middle cerebral artery infarction necessarily leads to unacceptable neuropsychological or psychosocial outcomes.

MRZ-99030 – a novel modulator of Aβ aggregation: II – reversal of Aβ oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice.

β-amyloid1-42 (Aβ1-42) is a major endogenous pathogen underlying the aetiology of Alzheimer's disease (AD). Recent evidence indicates that soluble Aβ oligomers, rather than plaques, are the major cause of synaptic dysfunction and neurodegeneration. Small molecules that suppress Aβ aggregation, reduce oligomer stability or promote off-pathway non-toxic oligomerization represent a promising alternative strategy for neuroprotection in AD. MRZ-99030 was recently identified as a dipeptide that modulates Aβ1-42 aggregation by triggering a non-amyloidogenic aggregation pathway, thereby reducing the amount of intermediate toxic soluble oligomeric Aβ species. The present study evaluated the relevance of these promising results with MRZ-99030 under pathophysiological conditions i.e. against the synaptotoxic effects of Aβ oligomers on hippocampal long term potentiation (LTP) and two different memory tasks. Aβ1-42 interferes with the glutamatergic system and with neuronal Ca2+ signalling and abolishes the induction of LTP. Here we demonstrate that MRZ-99030 (100–500 nM) at a 10:1 stoichiometric excess to Aβ clearly reversed the synaptotoxic effects of Aβ1-42 oligomers on CA1-LTP in murine hippocampal slices. Co-application of MRZ-99030 also prevented the two-fold increase in resting Ca2+ levels in pyramidal neuron dendrites and spines triggered by Aβ1-42 oligomers. In anaesthetized rats, pre-administration of MRZ-99030 (50 mg/kg s.c.) protected against deficits in hippocampal LTP following i.c.v. injection of oligomeric Aβ1-42. Furthermore, similar treatment significantly ameliorated cognitive deficits in an object recognition task and under an alternating lever cyclic ratio schedule after the i.c.v. application of Aβ1-42 and 7PA2 conditioned medium, respectively. Altogether, these results demonstrate the potential therapeutic benefit of MRZ-99030 in AD.

Path-Dependency, Stocks, Switching Points, Flows: Reflections on Long-term Global Change and Local Opportunities

This paper examines the possibilities for peripheral localities to achieve upward mobility in the world-system by “hooking on” to larger processes of world-system accumulation. In particular, is it possible for economies that are dependent on foreign investment to receive a flow of investments that is high enough to overcome the negative impacts of a high stock of foreign investment, thus enabling them to cross a threshold and achieve upward mobility in the world-system? An analysis of therecent experience of the southern Irish “Celtic Tiger” economy during 1990-2000 indicates that such an upward movement is possible on the basis of massive foreign investment inflows. On closer examination, however, the Irish-type model appears to be highly deficient, because a high proportion of growth is illusionary and also on grounds of social desirability and lack of generalizability.