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This study aimed to demonstrate that severe neurological motor deficits in the context of late tick-borne disease with mixed microorganism involvement are eligible for long-term combined antibiotic/antiparasitic treatments. The inclusion criteria were: 1. neurological limb paralysis with a disability score >4 according to the EDSS Kurtzke disability scale; 2. serological tests pointing to an involvement of the main tick-borne microorganisms Borrelia burgdorferi s.l., Babesia, Anaplasma, and Bartonella; 3. a general disease for more than 6 months with fatigue, pain and subjective cognitive deficit. The patients were administered long-term treatments with repeated cycles (at least three) of 35-day IV ceftriaxone and repeated oral regimens of azithromycin–doxycycline and azithromycin–doxycycline–rifampicin. For Babesia, repeated courses of atovaquone–azithromycin were administered. Ten patients had intractable or severe motor deficits before treatment in the context of Borrelia (two cases) Borrelia–Babesia (four cases), Borrelia–Babesia–Anaplasma (two cases), Borrelia–Babesia–Anaplasma–Bartonella (one case) and Babesia–Anaplasma (one case). For several months, five had been in wheelchairs, and four had been walking with sticks. Seven patients out of 10 (70%) showed complete remission after a mean active treatment duration of 20.1 + 6.6 months, with a mean number of 4 ceftriaxone cycles. Three patients showed an initial remission but suffered secondary antibiotic/antiparasitic-resistant motor recurrences. Among the nine patients with Borrelia serologic positivity, treatments obtained complete remission in seven cases (77%). The findings of this ten-case series suggest the usefulness of long-term antibiotic/antiparasitic treatments in patients with severe late tick-borne neurological deficits with highly significant elements of tick-borne involvement.

Little is known, in man, in the post-thrombolytic molecular dynamics of haemostasis, particularly the effect of rt-PA on antifibrinolytic components such as alpha2 anti-plasmin and Factor XIII.The purpose of this study was to systematically determine changes in coagulation and fibrinolytic parameters after thrombolysis with rt-PA during 24h. We also aimed to correlate these parameters with different acute ischemic stroke subtypes and global outcome.Eighty consecutive patients with cerebral infarcts treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers measured at baseline (h0), 2 (h2) and 24h (h24) after initiation of thrombolysis. Correlations between the variations of these components were statistically studied, using the Spearman rank test or the Pearson test. These haemostatic parameters were also compared with cardioembolic and non cardioembolic patients, as well as between poor and favourable outcome patients.Between h0 and h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII was observed, while an increase in FDP and D-Dimers took place. These values returned to the initial levels at h24. At 2h, the decrease in fibrinogen was significantly correlated with that of plasminogen (0.48, p=0.01), alpha2-antiplasmin (0.48, p=0.004), and factor XIII (0.44, p=0.01); the decrease in plasminogen was significantly correlated with those of antifibrinolytic components, factor XIII (0.47, p=0.02) and alpha2-antiplasmin (r=0.77, p0.001). These variations were independent of NIHSS. Cardioembolic infarcts showed a statistically significant greater h0-h2 decrease in plasminogen (p=0.04) and an h0-h2 increase in FDP (p=0.02). Poor outcome was linked to low plasminogen values at 2 and 24h.Supposed to be fibrin-specific, rt-PA induces a decrease in circulating fibrinogen, significantly linked to a decrease in plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII and alpha2-antiplasmin is also observed. At 2h, a significant decrease in plasminogen and a significant increase in fibrin(ogen) degradation products (FDP) are observed in cardioembolic infarcts, and appear as early independent predictors of this aetiology. A low plasminogen value at 2h is potentially predictive of poor prognosis at 3months.

Background Some observational and experimental studies have suggested a short-term relationship between air pollutants and ischaemic stroke; however, the results conflict. Aims The objective of this study was to investigate the association between particulate matter less than 2·5 and 10 microns in aerodynamic diameter, nitrogen dioxide, sulphur dioxide and ozone, and short-term risk of ischaemic stroke in Lyon, France. Methods The AVC69 study was a multicenter cohort study in which all consecutive adult patients admitted to one of the emergency or neurological departments of the Rhone area for suspicion of stroke were included during a seven-month period. Only patients with ischaemic stroke living within the study area, composed of Lyon and 18 neighbouring communities with homogenous air pollutants exposure, formed the basis of our study. We adopted a time-stratified case-crossover design to analyse the short-term effect (up to two-days) of air pollutants on ischaemic stroke incidence. Models were adjusted for temperature, variation of atmospheric pressure, minimal relative humidity, influenza epidemics, pollen count, and holidays. Stratified analyses by gender and class age were performed. Different lag times were analysed. Results 376 patients were included. Mean age was 76·6 years (±13·7). 53·7% were women. No association was observed between air pollutants and short-term risk of ischaemic stroke after adjustment for main confounding factors. Results remained unchanged whatever the gender or age. Conclusions These results suggest a lack of association between air pollutant exposure and short-term risk of ischaemic stroke in a French urban area.

Resume Introduction Le traitement des gliomes de bas grade reste controverse. Cependant, certaines tumeurs symptomatiques, de large volume et non accessibles a la chirurgie, necessitent une prise en charge rapide en raison de l’atteinte neurologique, de l’epilepsie pharmaco-resistante ou de la deterioration de la qualite de vie. Methodologie. Nous rapportons le suivi a long terme (71 mois) de sept patients souffrant d’une tumeur oligodendrogliale de bas grade, symptomatique, traitee par procarbazine, CCNU et vincristine (PCV). Resultats. L’âge moyen au moment du diagnostic etait de 47 ans. La chimiotherapie a ete instauree devant une progression clinique ou radiologique, en moyenne 62 mois apres les premiers symptomes cliniques. Tous les patients ont repondu initialement au traitement avec une amelioration neurologique et radiologique. La chimiotherapie a ete bien toleree cliniquement avec principalement une toxicite hematologique. Pendant le suivi de 71 mois, la mediane de survie sans progression a ete de 57 mois (de 38 a 86 mois). Ainsi, aucune progression n’a ete observee chez deux patients, tandis que les cinq autres patients ont presente une progression, en moyenne 56 mois ( 12) apres l’introduction de la chimiotherapie, avec une reponse favorable a un traitement de seconde ligne chez quatre d’entre eux. Conclusion. La chimiotherapie PCV apparait comme une alternative interessante pour le traitement de gliome de bas grade progressivement symptomatique, meme en cas de large volume tumoral. Ce traitement, avec une toxicite moderee, ameliore la qualite de vie et peut procurer une stabilisation tumorale prolongee.

Resume Introduction La decouverte d’un gliome au cours d’une grossesse est une circonstance rare qui pose un double probleme a la fois neuro-oncologique et obstetrical. Quatre observations sont rapportees a partir desquelles nous discutons la prise en charge de cette pathologie. Observations La premiere patiente fut hospitalisee a 29 semaines d’amenorrhee (SA) pour une crise convulsive et une hemiparesie droite revelant un oligodendrogliome anaplasique fronto-insulaire gauche. L’etat neurologique fut stabilise sous traitement par corticoides jusqu’a l’accouchement par cesarienne a 36 SA et un traitement complementaire par chimiotherapie fut ensuite debute. La deuxieme patiente presenta a 26 SA un syndrome d’hypertension intracrânienne (HIC), une hemiparesie droite et une aphasie revelant un volumineux glioblastome fronto-parietal gauche. Une exerese partielle fut realisee a 28 SA. L’etat neurologique resta stable sous traitement par corticoides jusqu’a l’accouchement par cesarienne a 33 SA. Un traitement complementaire par radiotherapie et chimiotherapie fut ensuite debute. La troisieme patiente fut hospitalisee a 12 SA pour un syndrome d’HIC revelant un glioblastome frontal gauche. Une exerese sub-totale fut realisee a 13 SA. Du fait d’une reprise evolutive precoce, 2 semaines apres la chirurgie, il fut decide en accord avec la patiente de proceder a l’interruption therapeutique de la grossesse. La patiente fut ensuite traitee par radiotherapie et chimiotherapie. La quatrieme patiente fut traitee par radiotherapie et chimiotherapie pour une recidive locale d’un gliome thalamo-pedonculaire gauche de haut grade. A posteriori, elle avait recu ce traitement alors qu’elle etait enceinte de 4 mois. La patiente accoucha a terme d’un enfant en bonne sante. Aux dernieres nouvelles, l’enfant âge de 5 ans n’a pas presente de problemes de sante particuliers et la patiente est en remission complete. Conclusion Bien qu’elle semble plus complexe, la prise en charge des gliomes au cours de la grossesse ne devrait pas etre tres differente de la prise en charge habituelle. Les femmes enceintes, du fait de leur jeune âge, peuvent avoir une survie prolongee. Leur grossesse ne doit pas les empecher de beneficier du traitement optimal de leur gliome. Le traitement va dependre du desir de la patiente, du terme, de la presentation clinico-radiologique et de l’histologie. De maniere generale, au cours de la grossesse, le traitement chirurgical des gliomes de haut grade ne doit pas etre differe car avec les progres de la neurochirurgie et de l’anesthesie le risque pour le fœtus est devenu tres faible. Ensuite, si le delai entre la chirurgie et l’accouchement est trop long, il est possible de debuter un traitement complementaire par de la radiotherapie cerebrale. A partir du deuxieme trimestre de grossesse, ce traitement peut etre realise sans risques importants pour l’enfant.

Background and Purpose— Brain hemorrhage after ischemic stroke is a serious complication of treatment; however, its pathology is poorly understood. A classification based on brain imaging may help to better understand and avoid causal factors. Methods— Review of the results of controlled randomized trials and the available literature. Results— Hemorrhagic infarctions have no impact on clinical outcome and are probably not associated with the thrombolytic itself and the type of reperfusion strategy. They are associated with the extent of ischemic damage and most probably to an ischemic vasculopathy. Parenchymal hematomas are often clinically relevant. Their incidence is affected by the thrombolytic itself, the type, and probably the time point of reperfusion strategy. The loss of hemostatic control seems important in their pathogenesis. Extraischemic hematomas (remote from the infarct), unique or multiple, suggest pre-existing brain pathology, especially cerebral amyloid angiopathy. Conclusions— The radiological description of 3 different types of brain hemorrhage is useful to better understand the specific pathology and the impact on clinical outcome. It may help to avoid clinically relevant brain hemorrhages.

Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid to gamma-aminobutyric acid (GABA). Autoantibodies directed against GAD (antiGAD-Ab) have been described in patients with insulin-dependent diabetes mellitus, stiff-man syndrome, and in a few patients with progressive cerebellar ataxia. The presence of these autoantibodies suggests an autoimmune pathophysiological mechanism for the neurological manifestations in these disorders. However, the exact role of antiGAD-Ab and GABAergic neurotransmission in the pathogenesis of the neurological manifestations, particularly in progressive cerebellar ataxia, is not fully understood. The cases of two patients with subacute cerebellar ataxia associated with antiGAD-Ab presenting with abnormal eye movements are reported. One patient presented a periodic alternating nystagmus (PAN), whereas the other presented a downbeat nystagmus (DBN) and slow vertical saccades. The potential role of antiGAD-Ab and the resultant GABAergic neurotransmission deficit in oculomotor manifestations is discussed.

Resume Introduction Les encephalopathies post-anoxiques surviennent parfois de maniere retardee, la semiologie etant alors celle d’une leucoencephalopathie rapidement progressive dont le diagnostic etiologique s’avere difficile lorsque l’anamnese est incomplete. Observation Nous rapportons l’observation d’une patiente presentant un tableau d’encephalopathie progressive a l’issue d’une tentative de suicide medicamenteuse associee a une detresse cardio-respiratoire. L’IRM montrait une atteinte diffuse de la substance blanche dont la nature anoxique fut documentee par la biopsie cerebrale stereotaxique. Conclusion L’encephalopathie post-anoxique d’apparition retardee est une affection rare de physiopathologie complexe dont le diagnostic etiologique reste difficile.

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome (p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion (p=0.009), and in patients with larger pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was associated with a lower final infarct size (p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.

Background— Little is known about the coagulation factors as predictors of cerebral bleeding in rt-PA thrombolysis. The aim of this study was to determine what early coagulation parameters could predict early hemorrhagic lesions. Methods— Consecutive patients were included in the Lyon rt-PA protocol. Early hematomas (within 24 hours), diagnosed on an anatomoradiological basis (symptomatic and not symptomatic) were considered for the study. Fibrinogen and fibrin(ogen) degradation products (FDP) were assessed at entry and at 2 and 24 hours after the beginning of thrombolysis. Results— Of 157 patients, 11 had early parenchymal hematomas (7%), 31 had early hemorrhagic infarcts (19.7%), and 115 had no bleeding (73.2%). In logistic regression, FDP at 2 hours was the single predictor of parenchymal hematomas (OR: 2.5; CI: 1.09 to 5.8), whereas an increase of FDP >200 mg/L multiplied the odds of parenchymal hematoma by 4.95 (IC: 1.09 to 22.4). Early parenchymal hematomas were indicative of a poor prognosis at 3 months ( P =0.001). Conclusions— Early parenchymal hematomas appear as both “malignant” and exclusively related to an explosive increase of FDP at 2 hours, ie, an early fibrinogen degradation coagulopathy (EFDC). All patients scheduled to rt-PA thrombolysis should have an assay of FDP 2 hours after the beginning of thrombolysis: patients with an established EFDC (FDP >200 mg/L) should be monitored specifically, with no antithrombotic drug during the first 72 hours. Patients with FDP >100 mg should share the same monitoring.

Resume Le delai d’admission des patients victimes d’accident vasculaire cerebral (AVC) demeure excessif. La reconnaissance precoce des symptomes peut raccourcir ce delai. L’etude prospective que nous rapportons visait a evaluer le niveau d’information concernant l’AVC des patients hospitalises dans une unite neurovasculaire francaise. Du 2 juillet 1998 au 2 juillet 1999, un questionnaire standardise visant a evaluer ce niveau d’information fut soumis a 166 patients consecutifs venant de presenter un AVC. Seuls 91 patients furent capables de repondre au questionnaire dans les 48 premieres heures. Parmi ceux-ci, seuls 19 patients (21 p. 100) avaient pense qu’ils etaient victimes d’une attaque cerebrale avant d’arriver a l’hopital, 38 patients (42 p. 100) ne pouvaient citer aucun symptome evocateur d’AVC et 33 patients (36 p. 100) ne pouvaient citer aucun facteur de risque d’AVC. Les facteurs de risque d’AVC les plus frequemment cites furent : le tabagisme cite par 31 patients (34 p. 100) et l’hypercholesterolemie citee par 19 patients (21 p. 100). Aucun patient n’a cite les antecedents personnels d’accident ischemique cerebral transitoire ou constitue. Les symptomes evocateurs d’AVC les plus souvent cites furent : la paralysie d’un hemicorps ou d’un membre citee par 40 patients (44 p. 100) et les troubles du langage cites par 15 patients (16 p. 100). En analyse multivariee, le sexe feminin et le fait de « connaitre quelqu’un ayant ete victime d’une attaque cerebrale » sont des facteurs independants influencant la capacite a citer un(des) symptome(s) evocateur(s) d’AVC. Des efforts d’information quant a la reconnaissance des symptomes et a la reaction appropriee doivent etre deployes dans l’espoir de reduire le delai d’admission. Une meilleure information du public concernant les facteurs de risque apparait egalement souhaitable afin d’ameliorer la qualite de la prevention des maladies vasculaires.

This article represents the update of ‘European Stroke Initiative Recommendations for Stroke Management’, first published in this Journal in 2000. The recommendations are endorsed by the 3 European societies which are represented in the European Stroke Initiative: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.

Purpose. Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas.

Friedreich's ataxia is the most common inherited ataxia. Ninety-six percent of patients are homozygous for GAA trinucleotide repeat expansions in the first intron of the frataxin gene. The remaining cases are compound heterozygotes for a GAA expansion and a frataxin point mutation. We report here the identification of 10 novel frataxin point mutations, and the detection of a previously described mutation (G130V) in two additional families. Most truncating mutations were in exon 1. All missense mutations were in the last three exons coding for the mature frataxin protein. The clinical features of 25 patients with identified frataxin point mutations were compared with those of 196 patients homozygous for the GAA expansion. A similar phenotype resulted from truncating mutations and from missense mutations in the carboxy-terminal half of mature frataxin, suggesting that they cause a comparable loss of function. In contrast, the only two missense mutations located in the amino-terminal half of mature frataxin (D122Y and G130V) cause an atypical and milder clinical presentation (early-onset spastic gait with slow disease progression, absence of dysarthria, retained or brisk tendon reflexes, and mild or no cerebellar ataxia), suggesting that they only partially affect frataxin function. The incidence of optic disk pallor was higher in compound heterozygotes than in expansion homozygotes, which might correlate with a very low residual level of normal frataxin produced from the expanded allele.

A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.

pravastatin 20 mg daily. Post-myocardialinfarction echocardiography had demonstrated anteroseptoapical hypokinesia with low left ventricular ejection fraction (50%). On admission, right hemiparesis and aphasia had cleared. The patient had no history of recent infection (no fever, no flu, no respiratory tract symptoms) and reported no prior transient neurological deficit, headache or cervical pain. No Horner’s syndrome was observed. The patient had no skin, joint, eye or skeletal abnormalities suggesting a hereditary connective tissue disorder. No family history of arterial dissection or valvular heart disease was noted. Multimodal MRI performed on June 27 showed no recent ischemic lesion on diffusion-weighted imaging. T 2 -weighted sequences showed bilateral middle cerebral artery/anterior cerebral artery borderzone hyperintensities. Magnetic resonance angiography showed occlusion of the right ICA beginning 1 cm after the bifurcation and narrow stenosis of the left ICA in the subpetrous segment consistent with the diagnosis of bilateral spontaneous ICA dissection ( fig. 2 ). Collateral supply was efficient through the right posterior communicating artery. No intramural hematoma was observed. No angiographic changes of fibromuscular dysplasia were found. Neck Dear Sir, Multiple dissections of the carotid and coronary arteries are exceptional [1] . We report the case of a young woman without known hereditary connective tissue disorder who presented with spontaneous dissection of the left anterior descending coronary artery, followed by spontaneous dissection of both internal carotid arteries (ICA) 3 weeks later. We discuss the pathogenesis of these multiple dissections.

Summary Background Thrombolysis for acute ischaemic stroke has been investigated in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0·9 mg/kg bodyweight) within 6 h of stroke onset. Methods This non-angiographic, randomised, double-blind, trial enrolled 800 patients in Europe, Australia, and New Zealand. Computed tomography was used to exclude patients with signs of major infarction. Alteplase (n=409) and placebo (n=391) were randomly assigned with stratification for time since symptom onset (0–3 h or 3–6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0–1) and unfavourable (score 2–6) outcome. Analyses were by intention to treat. Findings 165 (40·3%) alteplase-group patients and 143 (36·6%) placebo-group patients had favourable mRS outcomes (absolute difference 3·7%, p=0·277). In a post-hoc analysis of mRS scores dichotomised for death or dependency, 222 (54·3%) alteplase-group and 180 (46·0%) placebo-group patients had favourable outcomes (score 0–2; absolute difference 8·3%, p=0·024). Treatment differences were similar whether patients were treated within 3 h or 3–6 h. 85 (10·6%) patients died, with no difference between treatment groups at day 90·14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8·8%) alteplase-group patients and 13 (3·4%) placebo-group patients. Interpretation The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0·9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.

We report a case of spontaneous intracerebral hemorrhage occurring in a young woman and revealing Addison’s disease. This autoimmune primary adrenocortical insufficiency was associated with premature ovarian failure. Exhaustive research for nonhypertensive causes of intracerebral hemorrhage was negative. Initial coagulation studies disclosed severe hypofibrinogenemia and prolonged prothrombin time related to vitamin K-dependent coagulation factor deficit. Clotting abnormalities cleared at 4 months under treatment with hydrocortisone. Glucocorticoids are potent regulators of fibrinogen biosynthesis, increasing fibrinogen secretion. We conclude that primary adrenocortical insufficiency induced this hemorrhagic diathesis leading to spontaneous intracerebral hemorrhage. This latter has never been reported in Addison’s disease. Primary adrenocortical insufficiency should be considered as a rare potential cause of nonhypertensive intracerebral hemorrhage.

Objectives: (1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0–3 vs. 3–6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS). Design and Analysis: Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints. Main Outcome Measures: Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial. Results: In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS. Conclusion: Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.

Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology. Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS). The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied. The weight of each symptomatologic compartment has been carefully designed. The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress.

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure through the investigation of the vasomotor reactivity (VMR). The latter is currently assessed with ACZ using several methods. Dynamic susceptibility contrast-enhanced gradient echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We described the course of VMR in a patient with high-grade internal carotid artery stenosis before and after surgery using DSC-MRI.

International audience; Friedreich's ataxia (FRDA) is an autosomal recessive, degenerative disease that involves the central and peripheral nervous systems and the heart. A gene, X25, was identified in the critical region for the FRDA locus on chromosome 9q13. This gene encodes a 210-amino acid protein, frataxin, that has homologs in distant species such as Caenorhabditis elegans and yeast. A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron.

Background and Purpose Hemodynamic parameters such as regional cerebral blood volume (rCBV), mean transit time (MTT), and regional cerebral blood flow (rCBF) can be assessed by dynamic susceptibility contrast MRI. The aim of the present study was to apply this method in patients who had symptomatic unilateral internal carotid artery occlusion. Methods Relative hemodynamic parameters (rCBV, MTT, and rCBF) were evaluated on the occluded side and thus compared with contralateral hemispheric values. We also attempted to detect any relationship between collateral flow and the hemodynamic parameters. Results Although rCBV was clearly increased in five patients over the whole hemisphere, we did not observe a statistically significant difference regarding the whole sample between sides (mean rCBV, 14.1±4.58 on the occluded side versus 11.8±2.99 on the contralateral side; P >.10). MTT was clearly increased on the occluded side (mean MTT, 4.29±0.83 on the lesion side versus 3.14±0.81 on the contralateral side; P P Conclusions A significant hemodynamic compromise in patients who had unilateral symptomatic carotid occlusion was observed according to CBF and MTT values. This approach might be promising in the understanding of cerebral hemodynamics in patients with vascular disorders.

An increased incidence of ischemic stroke has been reported in patients with Crohn's disease. Cerebral infarcts are usually considered as a complication of the hypercoagulable state associated with this inflammatory bowel disease (IBD). The association between Crohn's disease, hyperhomocysteinemia and large-artery stroke of the young has rarely been reported. A 39-year-old woman, with prior medical history of Crohn's disease and hypertension, presented with an ischemic stroke of the left internal carotid artery (ICA) territory. Etiological workup disclosed bilateral high-grade ICA stenosis and atheroma of the subclavian and vertebral arteries. Exhaustive search for prothrombotic factors showed inflammation, with an increased level of fibrinogen and factor IX, and a marked hyperhomocysteinemia. Both vitamin B1 and vitamin B6 plasmatic levels were decreased. Heterozygous C677T methylene-tetrahydrofolate reductase gene mutation was present. This observation highlights the combined proatherogenic effect of vitamin B deficiency-induced hyperhomocysteinemia and inflammation leading to large-artery stroke of the young in the setting of Crohn's disease. Our case report stresses the importance of vitamin deficiency screening in patients with IBD in terms of stroke prevention.

Resume Les cephalees, associees aux autres symptomes de l’hypertension intracrânienne, constituent le mode de revelation le plus frequent des thrombophlebites cerebrales. Leur installation est le plus souvent subaigue et non soudaine comme dans les cephalees de l’hemorragie meningee. Nous rapportons un cas de thrombophlebite cerebrale du sinus longitudinal superieur et du sinus lateral droit revelee de facon exceptionnelle par une hemorragie sous-arachnoidienne. La regression complete des symptomes fut observee apres traitement precoce par heparine intraveineuse. L’hemorragie sous-arachnoidienne n’etait plus visible sur le scanner X de controle realise 48 heures apres le debut du traitement anticoagulant. A 2 mois, la patiente est indemne de tout deficit neurologique.

We describe a case of a 70-Year-old man who presented subacute pseudo-dementia due to a dural fistula. Neurological assessment and the reversibility of the symptoms after embolization support the originality of this observation.

Background and Purpose The effects of hyperbaric oxygen (HBO) therapy on humans are uncertain. Our study aims first to outline the practical aspects and the safety of HBO treatment and then to evaluate the effect of HBO on long-term disability. Methods Patients who experienced middle cerebral artery occlusion and were seen within 24 hours of onset were randomized to receive either active (HBO) or sham (air) treatment. The HBO patients were exposed daily to 40 minutes at 1.5 atmospheres absolute for a total of 10 dives. We used the Orgogozo scale to establish a pretreatment functional level. Changes in the Orgogozo scale score at 6 months and 1 year after therapy were used to assess the therapeutic efficacy of HBO. In addition, we used the Rankin scale and our own 10-point scale to assess long term-disability at 6 months and 1 year. Two sample t tests and 95% confidence intervals were used to compare the mean differences between the two treatment groups. Student’s two-tailed test was used to compare the differences between pretherapeutic and posttherapeutic scores at 6 months and 1 year in the two treatment groups. Results Over the 3 years of study enrollment, 34 patients were randomized, 17 to hyperbaric treatment with air and 17 to hyperbaric treatment with 100% oxygen. There was no significant difference at inclusion between groups regarding age, time from stroke onset to randomization, and Orgogozo scale scores. Neurological deterioration occurred during the first week in 4 patients in the sham group, 3 of whom died; this worsening was clearly related to the ischemic damage. Treatment was also discontinued for 3 patients in the HBO group who experienced myocardial infarction, a worsening related to the ischemic process, and claustrophobia. Therefore, 27 patients (13 in the sham group and 14 in the HBO group) completed a full course of therapy. The mean score of the HBO group was significantly better on the Orgogozo scale at 1 year ( P P P P Conclusions Although the small number of patients in each group precludes any conclusion regarding the potential deleterious effect of HBO, we did not observe the major side effects usually related to HBO. Accordingly, it can be assumed that hyperbaric oxygen might be safe. We hypothesize that HBO might improve outcome after stroke, as we detected an outcome trend favoring HBO therapy. A large randomized trial might be required to address the efficacy of this therapy.

Up to 4% of strokes in young people are attributed to hematologic disorders. Deficiencies of natural anticoagulant proteins have recently been associated with ischemic strokes. The aim of this study w

Article abstract The authors describe the outcomes in 11 patients who had acute ischemic stroke related to internal carotid artery (ICA) dissection and were treated with IV tissue plasminogen activator (tPA). One symptomatic intracerebral hemorrhage occurred 36 hours after tPA was given. The mean day 90 modified Rankin Scale (m-RS) score was 2.4 (±1.6). No death was observed at 3 months. Four patients of 11 (36.4%) made an excellent recovery (day 90 m-RS score: 0 to 1). This study demonstrates the feasibility of IV thrombolysis with tPA (0.8 mg/kg) in ischemic stroke related to ICA dissection within the first 7 hours.

Mutism defined as a complete loss of speech may be related to psychiatric or neurologic disorders. The ischemic stroke origins of mutism are often difficult to assess at the acute stage. Accordingly, the search for the underlying mechanism as the localization of the damages may be difficult by conventional radiological techniques. Diffusion-weighted (DWI) MRI may accurately identify patients with acute ischemic stroke and distinguish them from those who mimic acute stroke better than clinical and conventional neuroradiological methods. This report aims to demonstrate the utility of DWI-MRI in the diagnosis of acute mutism.

Internal carotid artery (ICA) dissection with tandem internal carotid and middle cerebral artery occlusion may carry a poor prognosis even if intravenous recombinant-tissular plasminogen activator is administered. A better outcome may be expected with the combination of intravenous thrombolysis and endovascular methods (stenting and thromboaspiration). This procedure was performed in 3 patients who had concurrent ICA dissection and intracerebral occlusion. Endovascular treatment was feasible and safe. All our patients had a good clinical outcome. This potential effective approach may need further validation.

Background There are a few reports of moyamoya disease (MMD) in the European Caucasian adult population. We present the clinical manifestations, the neuroradiological aspects, the treatment, and the outcome after surgical revascularization of four French patients with MMD. Patients and methods We identified four adults (age >18years; three women and one man) with MMD who underwent digital subtraction catheter angiography at our institution from 1997 through 2006. The median age at symptom onset was 35years (range, 22 to 41years). The initial clinical presentation was intracerebral hemorrhage in three patients and ischemic stroke in one patient. Results Three patients underwent bilateral surgical revascularization and one patient underwent unilateral surgical revascularization. All patients underwent the same surgical revascularization procedure (encephalo-duro-arterio-myo-synangiosis). The mean (+/−SD) period of follow-up after diagnosis of MMD was 6years and 9months (+/−3years and 5months). No patient experienced any recurrent hemorrhagic or ischemic stroke. No perioperative stroke occurred. No patient was severely disabled or unable to walk. Three patients out of four were employed. Conclusion Our data suggest safety and a potential benefit of surgical revascularization (indirect bypass surgery) in European adult patients with symptomatic MMD. Further long-term prospective multicenter studies are needed. The establishment of a registry would be useful in order to accumulate data in large numbers of European patients with this uncommon disease.

Melatonin's neuroprotective action has been demonstrated in experimental models of brain ischaemia. The relationship between stroke and melatonin levels has been based on scarce and small sample size studies. In addition, the changes have not been correlated with the age of patients. We compared levels of nocturnal urinary melatonin and its metabolite, 6-sulfatoxymelatonin (aMT6S) in a large series of acute ischaemic stroke patients and healthy volunteers. Consecutive ischaemic stroke patients with a first episode of anterior circulation stroke were recruited. Urine samples were collected in 127 patients on day 1 poststroke and in a control population including 216 healthy volunteers, from 20:00 to 08:00 hr. Melatonin and aMT6S were measured by radioimmunoassay. Differences in melatonin and aMT6S levels between ischaemic stroke patients and healthy volunteers were assessed by gender and age categories, using the Student's t-test. Melatonin excretion was decreased in stroke patients compared with healthy volunteers (74.1 +/- 13.9 versus 211.9 +/- 31.0 ng/hr; P = 0.0004), whereas aMT6S level was not significantly reduced (6371 +/- 1028 versus 4469 +/- 508 ng/hr; P = 0.10). Conversely, the stratification by age showed a significant reduction of both melatonin and aMT6S levels among ischaemic stroke patients over 70 yr (P = 0.001 and P = 0.03 respectively). The impact of melatonin at the acute stage of stroke on clinical severity and lesion size needs further assessment, as melatonin may have potential neuroprotective effects.

BACKGROUND AND PURPOSE: The benefit of recanalization in basilar artery occlusion (BAO) has been established. The baseline extent of brain stem damage may also influence the outcome. We investigated whether a baseline diffusion-weighted imaging (DWI) score may provide additional prognostic value in BAO. MATERIALS AND METHODS: We analyzed baseline clinical and DWI parameters in consecutive patients treated with endovascular procedures for acute BAO. Brain stem DWI lesions were assessed by using a semiquantitative score based on arterial territory segmentation. Outcome at 3 months was dichotomized according to the modified Rankin Scale (mRS) as favorable (mRS, 0–2) or unfavorable (mRS, 3–6). Spearman rank correlation tests assessed the correlation between DWI and clinical variables. Univariate and multivariate logistic regression analyses were used to identify clinical and MR imaging predictors of outcome. RESULTS: Twenty-nine patients were included. The brain stem DWI score (median, 3; range, 0–14) was correlated with the baseline National Institutes of Health Stroke Scale (NIHSS) score and the presence and length of coma (r = 0.67, 0.49, and 0.53, respectively; P < .01). Recanalization was achieved in 76%. A higher baseline NIHSS score (P = .02) and brain stem DWI score (P = .03), a lower Glasgow Coma Scale score (P = .04), and the presence of coma (P = .05) were associated with poor outcome in univariate analysis. Multivariate analysis showed that the brain stem DWI score was the only independent baseline predictor for clinical outcome (P = .026). CONCLUSIONS: Baseline brain stem DWI lesion score is an independent marker of outcome in BAO.

Among the patients showing evidence of cerebral metastases without previously known cancer history, lung cancer has been found 37 times as the primary tumor in our institution. There were 34 men and three women and all but two were heavy smokers. Only one presented at diagnosis with thoracic symptoms but the chest radiograph was abnormal in 34. The histologic type of the primary tumor was obtained in 32 cases as a result of thoracic investigations and in five cases from metastatic tumor tissue. The primary tumor appeared to be non-small cell lung carcinoma in 26 cases and small cell lung carcinoma in 11 cases. These results show that patients treated with surgery (20 cases) have a better survival (median 10 months versus 4.5) than the others, and among surgically treated patients only those treated with bifocal resection (eight patients) are long-term survivors. Also, in four of six patients, objective regression of the neurologic symptoms was seen after radiation therapy alone. Central nervous system relapse was seen in 12 patients, but in none of the patients treated with postoperative radiation therapy. Conventional chemotherapy (11 patients) induced objective responses only in the small cell type and proved to be too toxic when used simultaneously with radiation therapy in inoperable patients.

Tuberothalamic artery infarction (TTAI) results mainly in a myriad of neuropsychological symptoms such as memory impairment, euphoria, apathy, verbal perseverations, constructional apraxia and lack of spontaneity. Language disturbances, acalculia, buccofacial and limb apraxia occur prominently after left TTAI while visual spatial processing deficits and hemispatial neglect occur prominently after the right one. Some cases of TTAI causing Horner’s syndrome in addition of these wide-ranging neurobehavioral symptoms have been reported. Here, we report a case of TTAI with an ipsilateral ptosis as main clinical manifestation. This finding suggests that a Horner’s syndrome can be the main feature of TTAI when neuropsychological manifestations are inconspicuous.

Recurrent cerebral venous thrombosis (CVT), as a manifestation of paraneoplastic angiitis and revealing of nodular lymphocyte predominant Hodgkin's disease (NLPHD), is an extremely rare condition. We herein report a 55-year-old man who developed recurrent CVT despite efficacious anticoagulant therapy and subsequent stenting of the superior longitudinal sinus. Progressive neurological deterioration ensued and a body scan revealed axillary lymph nodes. Pathological analysis led to a diagnosis of NLPHD. Conventional angiography showed CVT and multiple arterial narrowings. A paraneoplastic primary cerebral angiitis with prominent venous structure involvement was suspected. Immunotherapy using rituximab and steroids provided a dramatic recovery. This case of CVT due to paraneoplastic cerebral angiitis is a rare condition and represents a new, very rare manifestation of nodular lymphocyte predominant Hodgkin's disease.

The PROACT II trial showed that intra-arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%.To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions.294 patients with stroke treated with intra-arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors.sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH.With regard to the whole spectrum of cerebral vessel occlusions, an incidence of5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.

Background and Purpose— The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume. Methods— We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests. Results— The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test ( P =0.39) or Spearman test ( P =0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement. Conclusions— USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.

Background and Purpose— Sinus venosus defect is a rare cardiac abnormality, provoking an interatrial shunting outside the interatrial septum. Echographic diagnosis is difficult and may require examination by a specialized cardiologist. Summary of Case— We report the case of a young woman who presented with repeated episodes of hemiparesis. Conclusions— Surgical correction of sinus venosus defect led to disappearance of neurological symptoms.