Many patients initially diagnosed with ADEM develop clinically definite MS upon long-term follow-up. The authors found no useful diagnostic criteria for the differentiation of a first episode of MS from monophasic ADEM. The term ADEM may still be employed as a description of a clinical syndrome, but should not be used as a distinct entity until reliable diagnostic criteria have been developed.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+7.0+/-4.8 ml, P<0.05 versus pre-exposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline values, whereas a more marked reduction in ADC in the splenium of the corpus callosum (SCC) was observed (P<0.05). While changes in brain volume and T2rt were not selectively different in AMS, ADC values were consistently lower (P<0.05 versus non-AMS) and associated with the severity of neurologic symptoms. Acute mountain sickness was also characterized by an increased brain to intracranial volume ratio (P<0.05 versus non-AMS). These findings indicate that mild extracellular vasogenic edema contributes to the generalized brain swelling observed at high altitude, independent of AMS. In contrast, intracellular cytotoxic edema combined with an anatomic predisposition to a 'tight-fit' brain may prove of pathophysiologic significance, although the increase in brain volume in hypoxia was only about 0.5% of total brain volume.

Voxel-based morphometry (VBM) shows a differentiated pattern in patients with atypical Parkinson syndrome but so far has had little impact in individual cases. It is desirable to translate VBM findings into clinical practice and individual classification. To this end, we examined whether a support vector machine (SVM) can provide useful accuracies for the differential diagnosis. We acquired a volumetric 3D T1-weighted MRI of 21 patients with idiopathic Parkinson syndrome (IPS), 11 multiple systems atrophy (MSA-P) and 10 progressive supranuclear palsy (PSP), and 22 healthy controls. Images were segmented, normalized, and compared at group level with SPM8 in a classical VBM design. Next, a SVM analysis was performed on an individual basis with leave-one-out cross-validation. VBM showed a strong white matter loss in the mesencephalon of patients with PSP, a putaminal grey matter loss in MSA, and a cerebellar grey matter loss in patients with PSP compared with IPS. The SVM allowed for an individual classification in PSP versus IPS with up to 96.8% accuracy with 90% sensitivity and 100% specificity. In MSA versus IPS, an accuracy of 71.9% was achieved; sensitivity, however, was low with 36.4%. Patients with IPS could not be differentiated from controls. In summary, a voxel-based SVM analysis allows for a reliable classification of individual cases in PSP that can be directly clinically useful. For patients with MSA and IPS, further developments like quantitative MRI are needed.

We studied the diagnostic and prognostic value of diffusion- and perfusion-weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow-up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty-one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients.

While there is a vast amount of research on firms’ choice of ownership form when entering a foreign market, little attention has been paid to changes in ownership forms of operation abroad after initial entry. Using transaction cost economics and institutional theory we identify a number of factors that may help to explain the likelihood of foreign firms’ converting their joint venture with a local firm into a wholly owned subsidiary. We formulate a number of hypotheses and test them against data collected through a questionnaire survey of managers representing foreign subsidiaries in the People's Republic of China (PRC) that are run either as international joint ventures (IJVs) or as wholly owned foreign subsidiaries (WFOEs) that have recently been converted from IJVs into a WFOE. The paper contributes to research by showing that transaction-cost-based thinking is useful for explaining not only the initial choice of ownership mode when entering a new market, but also the potential subsequent changes of this ownership mode. By combining transaction cost theory with arguments from institutional theory, the study identifies a number of factors that contribute to explaining post-entry changes of foreign firms’ ownership forms in the PRC, and provides empirical evidence of this phenomenon. Journal of International Business Studies (2009) 40, 388–404. doi:10.1057/jibs.2008.56

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