This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.

Fingolimod (FTY) is the first oral medication approved for treatment of relapsing–remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long‐term post‐marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side‐effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post‐marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy‐related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.

BackgroundVarious postural deformities appear during progression of Parkinson’s disease (PD), but the underlying pathophysiology of these deformities is not well understood. The angle abnormalities seen in individual patients may not be due to distinct causes, but rather they may have occurred in an interrelated manner to maintain a balanced posture.MethodsWe measured the neck flexion (NF), fore-bent (FB), knee-bent (KB) and lateral-bent (LB) angles in 120 PD patients, and examined their mutual relationships, and correlations with clinical predictors such as sex, age, disease duration, Hoehn and Yahr (H&Y) stage, medication dose (levodopa equivalent dose, LED; total dose of dopamine agonists, DDA). The relationship between the side of the initial symptoms and the direction of LB angle was also investigated.ResultsOur main findings were: (1) Significant relationships between NF and KB, NF and LB, FB and KB, KB and LB were observed. (2) NF angle was larger in males than in females, but FB, KB and LB angles showed no significant difference between the sexes. (3) FB and KB angles became larger with advancing age. (4) NF and FB angles were associated with disease duration. (5) NF, FB, KB and LB angles all increased significantly with increase of H&Y stage. (6) FB angle was significantly associated with LED, but DDA did not show a significant relationship with any of the measured angles. (7) Direction of LB angle was not associated with the side of initial symptoms.ConclusionsPostural abnormalities are interrelated, possibly to maintain a balanced posture.

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Background: It remains unclear whether high-sensitivity CRP (hs-CRP) is predictive of atherosclerosis in the intracranial artery. The aim of this study is to assess the role of hs-CRP in asymptomatic intracranial artery occlusive diseases. Methods: Of the 3,366 apparently healthy subjects who received a brain checkup, 138 with ≧25% intracranial artery stenosis on magnetic resonance angiography, 267 with ≧25% extracranial carotid artery stenosis on B-mode ultrasonography and 435 without intracranial artery or extracranial carotid artery stenosis (age-matched controls) were selected for this study. Results: The mean CRP concentration in the subjects with intracranial artery stenosis was not significantly different from that in the control subjects, and the differences of mean CRP concentrations among the subgroups with 25–49, 50–74 and 75% or greater stenosis in the intracranial artery were not significant. The odds ratios of hs-CRP for extracranial carotid artery stenosis tended to increase with increasing CRP concentrations, but those of hs-CRP for intracranial artery stenosis showed no significant difference. Conclusion: The degree of atherogenic inflammation in asymptomatic intracranial artery stenosis may be less than that in extracranial carotid artery stenosis.

Background: The predictive value of asymptomatic intracranial artery stenosis for future stroke remains uncertain. The aim of this study is to assess the stroke risk of asymptomatic intracranial artery stenosis and to compare it with that of extracranial artery disease. Methods: The study subjects were 2,924 participants (mean age 55 years) without any history of stroke. We examined the relation between intra- or extracranial large-artery disease and subsequent cerebrovascular events (mean follow-up 63 months). Results: The incidence rate of total cerebrovascular events in persons with intracranial artery stenosis was 1.3% per year. In the group without plaque in the extracranial carotid arteries, the annual rate of total cerebrovascular events was only 0.6%, but in the group with plaque, the rate was 3.6%. Kaplan-Meier analysis of total events showed a significant difference between the 2 groups (p = 0.002). Conclusions: The stroke risk in subjects with asymptomatic extracranial artery disease is markedly increased if intracranial artery stenosis is also present.

Objective Renal dysfunction may be related to cerebrovascular disease. The aim of this study was to assess the relationship between mild renal dysfunction and carotid artery atherosclerosis detected by ultrasonography in apparently healthy subjects. Methods A total of 2,106 persons (1,368 men and 738 women, mean age+/-S.D.: 56 +/-10 years) with no history of stroke were enrolled. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR), calculated by using the relationship 194Cr -1.094 ×Age -0.287 ×0.739 (if female), where Cr is serum creatinine concentration. Atherosclerosis on ultrasonography was defined as regional intimal thickening or nodular lesion. Results Atherosclerotic lesions were significantly more frequent in subjects with CKD stage 3 than in CKD stage 1 or 2 (p<0.001). Odds ratios for atherosclerotic lesions were significantly increased to 1.11 (95% confidence interval: 1.09-1.12, p<0.001) for increasing age, 1.66 (1.31-2.10, p<0.001) for male sex, 1.76 (1.43-2.16, p<0.001) for systolic blood pressure !130 mmHg and/or diastolic blood pressure !85 mmHg, 1.61 (1.28-2.01, p<0.001) for LDL-cholesterol !140 mg/dL, and 1.59 (1.23-2.05, p=0.003) for smoking habit versus no risk factor. The odds ratio of CKD stage 3 for !50% carotid artery stenosis was significantly increased to 3.47 (1.09-11.08, p=0.035), although CKD stage 2 and stage 3 were not significant (0.77, 95% CI: 0.59-1.01, p=0.068; 0.99, 95%CI: 0.67-1.46, p=0.981, respectively). Conclusion Renal dysfunction defined in terms of eGFR might be associated with early-stage carotid atherosclerosis, but traditional vascular risk factors, including increasing age or hypertension, appear to play a major role.