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MEDICAL PROGRESS IN THE JOURNAL OF NEUROLOGYProgress in cerebrovascular disease research in the last yearSergio Amaro •Angel ChamorroReceived:23December 2011/Revised:30December 2011/Accepted:2January 2012/Published online:19January 2012ÓSpringer-Verlag 2012Abstract Herein,we review the main papers in cere-brovascular diseases published in the Journal of Neurology over the last year.Keywords Acute ischemic stroke ÁIntracerebralhemorrhage ÁSubarachnoid hemorrhage ÁAtherosclerosisAcute ischemic stroke:factors related to short-and long-term outcomeFever is common in patients with acute stroke.Increased body temperature is deleterious in experimental ischemia and has been associated with a bad outcome in clinical studies,but the temporal profile of this relationship is not clearly established.The study by den Hertog et al.[1]aimed to assess the relationship between functional out-come and death at 3months with body temperature mea-sured within the first 12h after symptom onset,and with the change in body temperature from admission to 24h.Data from 1,332patients admitted within 12h of stroke onset included in the Paracetamol in Stroke (PAIS)trial were analyzed.No relationship was found between admission body temperature and poor outcome or death.In contrast,increased body temperature in the first 24h after stroke onset was associated with both poor outcome and death.These results support further studies investigating the effects of temperature modulation after ischemic stroke.Greiseneger et al.[2]studied a hospital-based multi-center cohort of patients younger than 60years suffering an ischemic stroke (IS)or transient ischemic attack (TIA)to identify predictive clinical determinants of all-cause mortality.Vascular risk factors,stroke severity,etiology of stroke,and factors influencing all-cause mortality were assessed in this population.After excluding patients who died within the first 30days,661patients were followed for a mean of 8.8years.The cumulative mortality rate was 2.4%after 1year,and 7.8%after 5years.Diabetes,heavy drinking,heart failure,and age were found to be signifi-cantly associated with mortality.In contrast,none of the included factors were associated with mortality in patients younger than 50years.Little is known about the interaction of mood disorders and quality of life (QoL)after thrombolytic treatment.Schwab-Malek et al.[3]assessed mood and QoL at 3and 6months after stroke in consecutive patients who received intravenous thrombolysis in stroke centers and telemedicine hospitals within the TEMPiS network.Several scales were used to quantify clinically relevant depressive symptoms and QoL.Depressive symptoms and impaired QoL were observed in a substantial proportion of stroke patients at 3months after intravenous thrombolysis.Stroke severity at admission was not predictive for depressive symptoms but it predicted poor QoL.As depression is related to increased mortality after stroke,prevention therapy or antidepressive treatment may have effects beyond mood stabilization.Biomarkers in ischemic strokeInflammation is an important mechanism in the patho-physiology of ischemic stroke,but an understanding of theS.Amaro ÁA.Chamorro (&)Comprehensive Stroke Center,Hospital Clinic,University ofBarcelona,Institut d’Investigacions Biome`diques August Pi i Sunyer (IDIBAPS),170Villarroel,08036Barcelona,Spain e-mail:achamorro@J Neurol (2012)259:391–394DOI 10.1007/s00415-012-6408-7exact interactions between pro-inflammatory and anti-inflammatory cytokines remains unclear.Ormstad et al.[4] examined serum levels of13cytokines,C-reactive protein (CRP),glucose and hemoglobin in acute ischemic stroke patients,and their relationship to stroke lateralization,type, and infarct volume.A total of45acute stroke patients and 40controls were evaluated.Blood samples were obtained within72h of stroke onset,and volumetric analyses were performed within1–7days.Levels of interleukin(IL)-1ra, IL-6,IL-8,IL-9,IL-10,IL-12,IL-18and GRO-a(CXCL1) (chemokine(C-X-C)ligand1)were significantly higher in the stroke patients than in the controls.Importantly,ele-vated serum levels of IL-9and GRO-a after acute ischemic stroke had not been previously described.Infarct volume was positively correlated with CRP level and patients with radiologically confirmed infarctions had significantly ele-vated serum levels of GRO-a.These results give further support to the existence of an early pro-inflammatory response and also to an early activation of endogenous immunosuppressive mechanisms.The role of immuno-modulatory strategies after acute ischemic stroke deserves further study.Many stroke survivors require a long-term process of recovery and rehabilitation.Post-stroke fatigue(PSF)is common with a frequency ranging from29to68%(com-pared to20%in control groups)and represents a complex interaction of biological,psychosocial,and behavioral factors.Elevated levels of inflammatory markers are associated with poor outcomes in stroke but their rela-tionship with PSF is unknown.Ormstad et al.[5]investi-gated the association of PSF with stroke type,infarct volume,and laterality,and the levels of various cytokines and other blood components in acute ischemic stroke.Data from45ischemic stroke patients were analyzed.PSF was measured by means of the Fatigue Severity Scale(FSS)at 6,12,and18months after stroke onset.Serum levels of C-reactive protein,hemoglobin,glucose,and13cytokines were measured within72h of stroke onset.Serum levels of IL-1b and glucose were positively correlated with the score on the FSS at6months after the stroke whereas levels of IL-ra and IL-9were negatively correlated with FSS score at12months.Neither stroke lateralization nor infarct volume was associated with subsequent fatigue.These results stressed the role of post-stroke proinflammatory response in the appearance of PSF.Further prospective studies are needed to validate the results of this study. Atherosclerotic diseaseAtherosclerosis is a chronic inflammatory disease associ-ated with ischemic stroke.Inflammation is one of the key pathophysiological mechanisms in the development and progression of atherosclerosis but the stimulus that triggers the inflammatory response remains unclear.Associations between atherosclerosis and induced immune responses to the presence of persistent infectious pathogens,such as Helicobacter pylori(HP)have been described.Specifically, citotoxin-associated gene A(CagA)-positive strains of HP have been found to be significantly more prevalent among patients with carotid artery atherosclerosis and ischemic stroke than in healthy subjects.The study by Rozˇankovic´et al.[6]aimed to clarify whether an association exists between(CagA)-positive strains of HP and carotid plaque instability.A total of64patients with advanced carotid artery stenosis[70%(33of them with symptomatic carotid disease)and treated with carotid endarterectomy were included in the study and compared with data from65 subjects without vascular disease.The titer of anti-CagA antibodies was found to be significantly higher in patients with symptomatic carotid artery stenosis compared to those with asymptomatic carotid artery stenosis and the control group.Moreover,evidence of molecular mimicry between CagA antigen and vascular wall antigens within athero-sclerotic carotid arteries was found and this reaction was more pronounced in the subgroup of patients with symp-tomatic carotid artery disease and in those with ultrasound markers of plaque instability(irregular or ulcerated pla-ques).In multivariate models,the value of CagA antibodies was associated with the symptomatic carotid artery disease. Overall,this study gives further support to the hypothesis that HP may play a role in pathogenesis of atherosclerosis promoting an autoimmune mechanism and contributing to plaque destabilization.The presence of atherosclerotic plaques in the proximal aorta is related to vascular risk factors and is also associ-ated with ischemic stroke.Previous studies have also indicated an association between carotid and aortic plaques and between the presence of intracranial artery calcifica-tions(IAC)and significant carotid artery stenosis in ischemic stroke patients.The relation between IAC and plaques on the ascending aorta in ischemic stroke patients was investigated by Buignicourt and colleagues[7].A total of454patients with ischemic stroke were included.IAC were quantified in the seven major cerebral arteries and complex aortic plaques(CAP)were detected by trans-esophageal echocardiography(TEE)and defined as plaques [4mm thick or with mobile components in the proximal aorta.Forty-two patients(9.3%)had CAP.Patients with CAP were older,had more vascular risk factors,and more significant carotid artery atherosclerosis compared to patients without CAP.IAC was present in100%of patients with CAP and had a high sensitivity(100%)and negative predictive value(100%)for the presence of CAP.The results suggested that IAC is strongly associated with the presence and severity of CAP in ischemic stroke patientsand could help in the decision of whether to perform a TEE.Atherosclerotic intracranial arterial stenosis is an important cause of stroke.The risk of recurrent stroke in patients with symptomatic intracranial stenosis ranges from 10to50%for year depending on associated risk factors such as female sex,high-grade stenosis([70%),collateral circulation,and recently symptomatic disease.Medical treatment reduces this risk,although the best medical therapy remains to be elucidated.Recently,the SAMM-PRIS trial showed that aggressive medical management was superior to percutaneous transluminal angioplasty and stenting(PTAS)with the use of the Wingspan stent system. Lanfranconi et al.[8]reported their single-center experi-ence of PTAS in consecutive patients with intracranial stenosis and compared the safety and performance of balloon-mounted stents versus self-expanding stent sys-tems(Wingspan).A total of34patients with39severe ([70%)intracranial stenosis were analyzed.Stroke or death or any major complication at day30,and procedure technical success were used as endpoints.Technical suc-cess was achieved in all patients.The30-day stroke/death rate was17.9%.The complication rate was similar in the non-Wingspan and in Wingspan groups(18.2and17.6%, respectively)and was higher in recently symptomatic patients.These results support the fact that PTAS should not be used asfirst-line treatment in patients with severe symptomatic intracranial stenosis.Subgroups of patients who are most likely to benefit from PATS and the best timing and technique for endovascular treatment are still uncertain and deserve further study.Aneurysmal subarachnoid hemorrhage:from early complications to long-term recoveryAneurysmal subarachnoid hemorrhage(SAH)is a devas-tating condition.The main factors associated with poor outcome are age,severity at hospital admission,and sev-eral radiological features.Intracerebral hematoma(ICH) occurs in up to one-third of patients with SAH and is associated with poor prognosis.Liu et al.[9]studied clinical and aneurysmal risks factors for the occurrence of ICH from aneurysmal rupture in310SAH patients. Aneurysms originating from the MCA were associated with a higher risk of developing ICH than aneurysms at other locations.Other aneurysmal or clinical factors had no or only minor influence on the risk of ICH after rupture.Acute hydrocephalus is a relatively common complica-tion after SAH.Treatment of acute hydrocephalus depends basically on the site of the obstruction.Lumbar puncture or drainage can be used in communicating hydrocephalus,but in the case of obstructive hydrocephalus,the placement of an external ventricular drainage(EVD)would be the only option.Unfortunately,the distinction between these two types of hydrocephalus is often difficult.The study by Knol et al.[10]aimed to investigate whether the absolute or relative size of the fourth ventricle distinguished between these two types of hydrocephalus.A total of117consec-utive SAH patients with acute hydrocephalus were inclu-ded.No differences were found in the size of the fourth or third ventricle,or in the mean ratio between the third and fourth ventricle between patients with intraventricular blood and those with mainly subarachnoid blood.These results imply that these radiological features would not be useful in making the distinction between communicating and obstructive hydrocephalus.One important contributor to quality of life in survivors after a SAH is fatigue.Determinants of fatigue are unclear.A better knowledge of factors underlying post-SAH fatigue would be important to design focused interventions.Passier et al.[11]assessed the occurrence of fatigue1year after SAH and its relation to physical,cognitive,or emotional impairment or the combination of these factors measured 3months after SAH in a cohort of108patients.Fatigue evaluated by means of the FSS was common(71%of patients)and was strongly correlated with physical and cognitive impairment,a passive coping style,and emo-tional problems,even in those patients with good clinical outcome.Focused interventions aimed to improve educa-tion and occupational therapy programs would result in reduced impact of fatigue in thefirst year after a SAH and should be investigated in future studies.Intracerebral hemorrhage:role of acute blood pressure and minimally invasive surgeryThe optimal management of blood pressure(BP)during acute stroke is controversial,both in ischemic stroke and in intracerebral hemorrhage(ICH).The study by Pezzini et al.[12]aimed to investigate whether acute BP has a differ-ential impact on clinical outcome after an IS or an ICH. Consecutive patients withfirst-ever acute stroke admitted to a Stroke Unit within24h of onset were included in the study.A total of264patients(198IS,66ICH)were ana-lyzed.BP values were automatically recorded at15-min intervals within thefirst48h.Acute high BP levels were found to be overall associated with ICH and directly associated with early neurological deterioration.In patients with ICH,high BP levels were associated with worse functional outcome at3months(modified Rankin scale 3to6)but unrelated to3-month mortality.Overall,the results suggested that elevated BP values and increased BP variability had an impact on the short-and mid-term out-come of patients with acute ICH in comparison to thosewith IS,emphasizing the clinical importance of BP moni-toring in the early phase of acute stroke.Trials focused in early intensive BP-lowering treatment of patients with acute ICH are ongoing.The optimal treatment of ICH remains unclear.The Inter-national Study of the Treatment of Intracranial Hemorrhage (STICH)showed no benefit of conventional aggressive sur-gical treatment over conservative medical treatment.How-ever,in experimental studies,clot reduction has been shown able to limit brain edema and secondary neuronal injury.With this background,novel techniques such as minimally invasive stereotactic puncture and thrombolytic therapy(MISPTT)are matters of ongoing research.Zhou et al.[13]reported their results on the short-and long-term benefits of MISPTT in ICH patients.Data from consecutive patients treated by MISPTT (n=64)were compared with a group of patients treated with conventional craniotomy(CC)(n=58).MISPTT was asso-ciated with lower Glasgow Coma Scale scores after treatment and lower incidence of postoperative complications.No sig-nificant differences in rebleeding rates were observed.Long-term outcome was significantly better in the MISPTT group compared to the CC group.Further investigations with ran-domized allocation to therapeutic options,which includes a medical arm,would be necessary to assess the optimal ther-apeutic approach to these patients and to add data regard-ing the proper selection of patients eligible for surgical approaches.Brain hemodynamicImpaired cerebrovascular reserve capacity(CVR)in car-otid occlusion is a major risk factor for previous and future ischemic events.An increase in CVR has been described after statin treatment in patients with small vessel disease but is unclear if this effect is also seen in patients with internal carotid artery occlusions(ICAO).Reinhard et al.[14]investigated the presence of spontaneous improvement of an exhausted CVR in patients with ICAO and the potential influence of statin treatment and other cofactors on this phenomenon.They analyzed data from66patients included in a prospective observational cohort study on cerebral hemodynamics in severe carotid artery stenosis and occlusion.Twenty patients had exhausted CVR at baseline and in11of them(55%)CVR improved above the cut-off at follow-up.Improvement in CVR was associated with good collateral pattern at baseline and statin treat-ment.Statins may upregulate nitric oxide synthase(eNOS) thus modifying vessel tone and potentially enhancing CVR. Further randomized trials are needed to confirm the effect of statins on CVR in patients with severe stenotic carotid disease.Conflicts of interest None.References1.den Hertog HM,van der Worp HB,van Gemert HM,Algra A,Kappelle LJ,van Gijn J,Koudstaal PJ,Dippel DW(2011)An early rise in body temperature is related to unfavorable outcome after stroke:data from the PAIS study.J Neurol258:302–307 2.Greisenegger S,Zehetmayer S,Ferrari J,Lang W,Fizek J,Auff E,Lalouschek W,Serles W(2011)Clinical predictors of death in young and middle-aged patients with ischemic stroke or transient ischemic attack:long-term results of the Vienna Stroke Registry: clinical predictors of ischemic stroke mortality in patients \60years.J Neurol258:1105–11133.Schwab-Malek S,Vatankhah B,Bogdahn U,Horn M,AudebertHJ(2010)Depressive symptoms and quality of life after throm-bolysis in stroke:the TEMPiS study.J Neurol257:1848–1854 4.Ormstad H,Aass HC,Amthor KF,Lund-Sørensen N,Sandvik L(2011)Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients.J Neurol258:670–676 5.Ormstad H,Aass HC,Lund-Sørensen N,Amthor KF,Sandvik L(2011)Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients,and their relationship to stroke lateral-ization,type,and infarct volume.J Neurol258:677–6856.Rozˇankovic´PB,Huzjan AL,Cupic´H,Bencˇic´IJ,Basˇic´S,Demarin V(2011)Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease.J Neurol258:753–761 7.Bugnicourt JM,Chillon JM,Tribouilloy C,Canaple S,Lamy C,Massy ZA,Godefroy O(2010)Relation between intracranial artery calcifications and aortic atherosclerosis in ischemic stroke patients.J Neurol257:1338–1343nfranconi S,Bersano A,Branca V,Ballabio E,Isalberti M,Papa R,Candelise L(2010)Stenting for the treatment of high-grade intracranial stenoses.J Neurol257:1899–19089.Liu X,Rinkel GJ(2011)Aneurysmal and clinical characteristicsas risk factors for intracerebral haematoma from aneurysmal rupture.J Neurol258:862–86510.Knol DS,van Gijn J,Kruitwagen CL,Rinkel GJ(2011)Sizeof third and fourth ventricle in obstructive and communicating acute hydrocephalus after aneurysmal subarachnoid hemorrhage.J Neurol258:44–4911.Passier PE,Post MW,van Zandvoort MJ,Rinkel GJ,LindemanE,Visser-Meily JM(2011)Predicting fatigue1year after aneu-rysmal subarachnoid hemorrhage.J Neurol258:1091–1097 12.Pezzini A,Grassi M,Del Zotto E,Volonghi I,Giossi A,Costa P,Cappellari M,Magoni M,Padovani A(2011)Influence of acute blood pressure on short-and mid-term outcome of ischemic and hemorrhagic stroke.J Neurol258:634–64013.Zhou H,Zhang Y,Liu L,Huang Y,Tang Y,Su J,Hua W,Han X,Xue J,Dong Q(2011)Minimally invasive stereotactic puncture and thrombolysis therapy improves long-term outcome after acute intracerebral hemorrhage.J Neurol258:661–66914.Reinhard M,Guschlbauer B,Olschewski M,Weiller C,Hetzel A(2011)Improvement of exhausted cerebral vasoreactivity in carotid occlusion:benefit of statins?J Neurol258:791–794。