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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.

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.

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.

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.

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.

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.

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.

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.

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.

Objective: To evaluate clinical, biological, and pretreatment imaging variables for predictors of tissue plasminogen activator (tPA) related intracerebral haemorrhage (ICH) in stroke patients. Methods: 48 consecutive patients with hemispheric stroke were given intravenous tPA within seven hours of symptom onset, after computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Baseline diffusion weighted (DWI) and perfusion weighted (PWI) imaging volumes, time to peak, mean transit time, regional cerebral blood flow index, and regional cerebral blood volume were evaluated. The distribution of apparent diffusion coefficient (ADC) values was determined within each DWI lesion. Results: The symptomatic ICH rate was 8.3% (four of 48); the rate for any ICH was 43.8% (21 of 48). Univariate analysis showed that age, weight, history of hyperlipidaemia, baseline NIHSS score, glucose level, red blood cell count, and lacunar state on MRI were associated with ICH. However, mean 24 hour systolic blood pressure and a hyperdense artery sign on pretreatment CT were the only independent predictors of ICH. Patients with a hyperdense artery sign had larger pretreatment PWI and DWI lesion volumes and a higher NIHSS score. Analysis of the distribution of ADC values within DWI lesions showed that a greater percentage of pixels had lower ADCs ( −6 mm 2 /s) in patients who experienced ICH than in those who did not. Conclusion: Key clinical and biological variables, pretreatment CT signs, and MRI indices are associated with tPA related intracerebral haemorrhage.

T2*/susceptibility-weighted (T2*SW) MRI enables diagnosis of cerebral venous thrombosis (CVT) by clot visualization as an area of hypointensity.1 This sequence also contributes to the diagnosis of …

Background Unilateral upper limb asterixis related to cortical infarct is an unusual clinical picture. We found this association in two patients. Magnetic resonance imaging (MRI), somatosensory evoked potentials (SEPs), and electromyographic recording were performed. Case Descriptions Two patients developed an acute upper limb ataxia with asterixis. This consisted of frequent arrhythmic loss of extensor muscle tone on instruction to maintain the wrist and fingers extended. Voluntary electromyographic activity in the left extensor digitorum communis muscle showed abrupt periods of interruption ranging from 90 to 260 milliseconds in duration in the first case and from 60 to 220 milliseconds in the second case. SEPs were normal. MRI disclosed a right cortical infarct within the primary motor cortex in both cases. Conclusions These findings indicate that asterixis was not related to a failure in the processing of proprioceptive input controlling the regulation of postural tone of the distal upper limbs because SEPs were normal. The involvement of primary motor cortex might suggest that asterixis results from an impairment of a centrally generated motor-command signal controlling the postural tone of the distal upper limb.

In patients with acute ischemic stroke, early recanalization may save tissue at risk for ischemic infarction, thus resulting in smaller infarcts and better clinical outcome. The hypothesis that clinical and diffusion- and perfusion-weighted imaging (DWI, PWI) parameters may have a predictive value for early recanalization and final infarct size was assessed. Twenty-nine patients were prospectively enrolled and underwent sequential magnetic resonance imaging (1) within 6 hours from hemispheric stroke onset, before thrombolytic therapy; (2) at day 1; and (3) at day 60. Late infarct volume was assessed by T2-weighted imaging. At each time, clinical status was assessed by the National Institutes of Health Stroke Scale (NIHSS). Twenty-eight patients had arterial occlusion at day 0 magnetic resonance angiography (MRA). They were classified into two groups according to day 1 MRA: recanalization (n = 18) versus persistent occlusion (n = 10). Any significant differences between these groups were assessed regarding (1) PWI and DWI abnormality volumes, (2) relative and absolute time-to-peak (TTP) and apparent diffusion coefficient within the lesion on DWI; and (3) day 60 lesion volume on T2-weighted imaging. Univariate and multivariate logistic regression analysis showed that the most powerful predictive factors for recanalization were lower baseline NIHSS score and lower baseline absolute TTP within the lesion on DWI. The best predictors of late infarct size were day 0 lesion volume on DWI and day 1 recanalization. Early PWI and DWI studies and day 1 MRA provide relevant predictive information on stroke outcome.

Background and Purpose— We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA). Methods— Patients with symptoms of acute hemispheric ischemic stroke were recruited. The National Institutes of Health Stroke Scale (NIHSS) score was assessed at baseline and at days 1, 7, and 60, and the modified Rankin scale (mRS) at day 60, by which outcome was classified in terms of independence (mRS score 0, 1, or 2) or severe disability or death (mRS score 3 through 6), was assigned. Multimodal stroke MRI was performed at presentation and repeated at day 1. MRI procedures included magnetic resonance angiography, T2* gradient-echo sequence, echoplanar imaging, and isotropic diffusion- (DWI) and perfusion-weighted (PWI) imaging. Patients were treated with intravenous rtPA after MRI completion. Results— Twenty-nine patients (16 men and 13 women; mean±SD age, 65±14 years) underwent MRI; the mean time from symptom onset to treatment was 255±62 minutes. Twenty-six patients had a vessel occlusion, and 15 patients experienced a partial (Thrombolysis in Myocardial Infarction [TIMI]-2) or total (TIMI-3) recanalization at day 1, whereas 11 patients had a persistent occlusion. Mean NIHSS scores at day 60 were 5.7±5.4 if recanalization had occurred and 14±2 in cases of persistent occlusion. According to the mRS, 13 patients were independent (mRS 0 through 2), whereas severe disability or death (mRS 3 through 6) was observed in 15 patients. A better outcome was observed when recanalization was achieved ( r =−0.68, P =0.0002). PWI volume and time to peak (TTP) within the DWI lesion assessed before therapy were correlated with day-60 NIHSS score (PWI volume: r =0.51, P =0.006, TTP: r =0.35, P =0.07). The day-0 DWI abnormality volume was well correlated with day-60 NIHSS score ( r =0.58, P =0.001). Multiple regression linear analysis showed that 2 factors mainly influenced clinical outcome: (1) recanalization, with a high correlation with NIHSS score at day 60 ( P =0.0001) and (2) day-0 DWI lesion volume, which is closely associated with day-60 NIHSS score ( P =0.03). Conclusions— Baseline DWI volume and recanalization are the main factors influencing clinical outcome after rtPA for ischemic stroke.

Background and Purpose — Intravenous tissue plasminogen activator improves outcome after ischemic stroke when given within 3 hours of symptoms onset in carefully selected patients. However, only a small proportion of acute stroke patients are currently eligible for thrombolysis, mainly because of excessive delay to hospital presentation. We sought to determine the factors associated with early admission in a French stroke unit. Methods — We prospectively studied the admission delay of acute stroke patients in a French stroke unit during a 12-month period ending July 1999. Univariate and multivariate regression analyses were performed to evaluate the factors influencing early stroke unit admission and transport by the Emergency Medical Services (EMS) or Fire Department (FD) ambulances. Results — One hundred sixty-six patients were primarily admitted to the stroke unit, with a median admission time of 4 hours 5 minutes. Twenty-nine percent presented within 3 hours of symptoms onset and 75% within 6 hours. Univariate analysis showed that early stroke unit arrival was significantly associated with the following factors: female sex, stroke severity assessed by the National Institutes of Health Stroke Scale score, lowered consciousness, sudden onset of stroke, not living alone, recognition of symptoms by bystanders, and transport by EMS or FD ambulances. Age, ethnicity, level of education, employment status, nocturnal onset, distance from place of stroke to the stroke unit, stroke lesion location, presence of brain hemorrhage, and awareness about the symptoms and risk factors of stroke had no measurable effect on early admission. A multivariate regression model demonstrated that the most significant factors associated with early stroke unit arrival were transport by EMS or FD ambulances and sudden onset of stroke. Female sex and not living alone were also significantly associated with early admission in the multivariate model. Multivariate analysis of the mode of transport showed that transport by EMS or FD ambulances was significantly more frequent among female patients, when stroke symptoms were recognized by bystanders, and when the general practitioner was not the first medical contact. Conclusions — The present study shows that hospital arrival within the first hours of stroke is feasible in a French stroke unit. As many as 75% of the patients are admitted within the first 6 hours of stroke. This is the first study demonstrating that stroke unit admission in France is fastest in patients brought to the hospital by EMS or FD ambulances. However, only 35% of stroke patients activate the emergency telephone system and are currently transported by EMS or FD ambulances. French stroke patients should be encouraged to seek immediate medical attention by using the emergency telephone system, and stroke management should be reprioritized in the French EMS as a time-dependent medical emergency, with the same level of organization and expertise currently applied to myocardial infarction.

BACKGROUND: Antibodies to glutamic acid decarboxylase (GAD-Ab) are described in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in stiff-man syndrome, and, recently, in a few patients with cerebellar ataxia. OBJECTIVES: To show a link between GAD-Ab and some patients with cerebellar ataxia and to clarify their clinical and immunologic profiles. METHODS: Serum samples were selected from 9000 samples of 4 laboratories. The selection criterion was an immunohistochemical pattern compatible with GAD-Ab that was confirmed by radioimmunoassay. We identified 22 patients with stiff-man syndrome and 14 with cerebellar ataxia and GAD-Ab. RESULTS: Thirteen of the 14 patients with cerebellar ataxia and GAD-Ab were women, and 11 had late-onset IDDM. Patients did not have clinical or radiologic evidence of brainstem involvement. Ten patients had oligoclonal IgG bands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was observed in 5 of the 6 patients studied. The level of GAD-Ab of these patients was similar to those with stiff-man syndrome and significantly higher than those with IDDM or with polyendocrine autoimmunity (P

Background and Purpose —The importance of hemodynamic changes related to a high-grade internal carotid artery (ICA) stenosis remains a matter of controversy. Areas between the vascular territories of major cerebral arteries, namely, the border zones, may be selectively vulnerable to hemodynamic alteration. The aim of this study was to search for any hemodynamic impact of carotid endarterectomy (CEA) on vasodilatory response, in particular, within the border zones, by means of multislice dynamic susceptibility contrast MRI. Methods —Thirteen patients with a high-grade unilateral ICA stenosis (>80%) were examined. Relative regional cerebral blood volume (rrCBV) was determined separately for white matter, gray matter, and anterior and posterior border zones by the acetazolamide test. A vasomotor reactivity index was evaluated from the rrCBV values. Values from the ipsilateral hemisphere were compared with contralateral ones, before and after CEA. Results —Before CEA, rrCBV values in the anterior border zones were significantly ( P Conclusions —High-grade ICA stenosis with efficient primary collateral pathways may have an early limited hemodynamic impact within border-zone areas. The favorable course of these abnormalities after surgery suggests an additional benefit of CEA at this stage.

Background and Purpose —Although new, large, double-blind, randomized studies are needed to establish the efficiency of intravenous thrombolysis, open trials of sufficient size may also provide novel data concerning specific outcomes after thrombolysis. Methods —An open study of intravenous rtPA in 100 patients with internal carotid artery (ICA) territory strokes between 20 and 81 years of age, with a baseline Scandinavian Stroke Scale (SSS) score of Results —At day 90, 45 patients (45%) had a good result, defined as complete regression or slight neurological sequelae (mRS score of 0–1), 18 patients had a moderate outcome (mRS 2–3), and 31 patients had serious neurological sequelae (mRS 4–5). Six patients died, 2 with intracerebral hematoma after immediate heparin. Five of 11 patients (45.5%) treated between 6 and 7 hours had a good result. The overall intracerebral hematoma rate was 7%. Higher values of fibrin degradation products at 2 hours were observed in the subgroup with intracerebral hematomas. Significant predictors of poor outcome on multivariate logistic regression analysis were baseline SSS score of P =0.04), indistinction between white and gray matter on CT scan (OR, 6.59; 95% CI, 2.19 to 19.79; P =0.0008), and proximal internal carotid thrombosis (OR, 3.29; 95% CI, 0.99 to 10.95; P =0.05). Conclusions —Our study confirms the safety of intravenous rtPA at a dose of 0.8 mg/kg and suggests efficacy for this drug even within 7 hours. Outcome and hematoma rates were at least as favorable as for trials of therapy with a 3-hour time window. Subgroups with a poor prognosis include low baseline neurological score, baseline CT changes, and proximal ICA thrombosis. However, approximately 30% of patients with each of these characteristics show a good outcome, so their inclusion in future routine rtPA protocols is still justified.

Activated protein C resistance (APC-R) due to factor V Leiden mutation is the most common thrombophilia associated with cerebral venous thrombosis. It is present in 10% to 20% of patients but usually in association with other constitutional or acquired prothrombotic conditions.1 We present a case of postpartum cerebral venous thrombosis in a patient with protein C deficiency and APC-R due to heterozygous factor V Leiden mutation. In addition to puerperium, the role of intravenous steroids is questioned in this case. A 33 year old woman was admitted because of severe subacute headaches, nausea, and drowsiness. She was not taking oral contraceptives. Her medical history disclosed recent delivery of a second child 3 weeks before and an asthma attack 5 days before entry, treated with intravenous methylprednisolone (120 mg daily). Family history disclosed that the patient’s mother had had postpartum lower limb deep vein thrombosis. On admission, clinical examination disclosed papilloedema. There was no fever and no ear, nose, or throat infection. Brain CT showed a right temporal hypodensity, a delta sign, and small ventricles. Brain MRI (with MRA) demonstrated recent superior sagittal sinus, and right and left lateral sinus thrombosis. High dose intravenous heparin was immediately initiated. Heparin treatment was switched to warfarin after 10 days. At 3 months, neurological examination was normal. Follow up MRA showed complete recanalisation of the superior sagittal sinus and the right lateral sinus, and partial recanalisation of the left …

echo sequence by TR = 600–800 ms, TE = 30–50 ms and flip angle = 10–20°. Diffusion-weighted imaging ( fig. 1 ) showed a left premotor cortex linear infarction involving the precentral sulcus and sparing Broca’s area according to MRI mapping [5] . Two days later, her speech was hypophonic, slow and effortful with pauses between or inside morphemes. She had a monotonous tone with abnormal prosody. Although some phonemes were distorted, she had no phonemic or semantic paraphasias. The grammatical organization of sentences was normal. She did not express any mood disorders such as indifference or catastrophic reactions. She gradually improved; 2 months later, a mild impairment of speech persisted. Our case was consistent with recent descriptions of aphemia characterized by a disturbance in articulation without any other language dysfunction [2] . Indeed, we observed neither linguistic impairment nor any sign of apraxia of speech supported by phonemic errors spontaneously recognized and corrected by the patient [3, 6] . Although initial mutism in aphemia has been reported previously [2, 7] , anatomical correlations between stroke and mutism are scarce. The pathophysiological basis of our observation is quite similar to those of the isolated aphemia which may involve a disruption of the connections between Broca’s area and the region of control of the pharyngolaryngeal and tongue muscles. More specifically, functional imDear Sir, Aphemia was first defined by Broca [1] in 1861 as a defect in the faculty of articulated language. Moreover, the anatomic bases of clinical findings are unclear; some authors reported lesions involving Broca’s area [1, 2] , whereas functional imaging or some clinicoanatomic studies showed damage within the lateral premotor cortex [3, 4] . We report 1 case of aphemia associated with an initial mutism linked to a lateral premotor cortex infarction. A 70-year-old right-handed woman with a medical history of hypertension showed a sudden loss of speech. She was admitted to our stroke unit 6 h later. She was alert and fully oriented. She was unable to produce any sound. Comprehension of spoken language was normal. Her reading comprehension and her writing capacities were normal. Although she was still mute, we did not find any sign suggesting an opercular dysfunction: she was able to make kisses, blow air and stick out her tongue. She did not show any sign of buccofacial apraxia. There was no sign of hemiparesis. Monitored blood pressure was 150/80 mm Hg. Cardiovascular examination, ECT, chest X-ray and routine biological screening were normal. MRI was performed on a Philips 1.5tesla MRI unit 7 h after the symptom onset. The protocol of imaging involved T 1 , T 2 , T 2 * gradient echo, diffusion-weighted imaging, fluid-attenuated inversion recovery and magnetic resonance angiography which were obtained using the following parameters: T 2 * -weighted gradient Received: January 11, 2006 Accepted: March 24, 2006 Published online: June 14, 2006

Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.

Background There is increasing evidence that serotonergic neurotransmission may be damaged in poststroke pathological crying. A correlation between the clinical severity of pathological crying and the size of stroke-induced serotonergic pathway lesions is commonly accepted. We present a case of severe pathological crying after a limited left anterior choroidal artery territory infarction. Case Description A right-handed 55-year-old man who was a heavy smoker was admitted to the hospital after a right hemiplegia of sudden onset. Clinical examination revealed a right global hemiplegia including the face and a right hemihypoesthesia. Cerebral CT scan and MRI showed an infarct in the retrolenticular part of the posterior limb of the left internal capsule extending upward into the posterior paraventricular corona radiata region. Transesophageal echocardiography revealed an atrial septal aneurysm of 15-mm excursion without associated patent foramen ovale. From the first day of admission, the patient exhibited very frequent and intense fits of pathological crying. Their persistence led to initiation of treatment with the selective serotonin reuptake inhibitor paroxetine on day 30. Complete and immediate resolution of pathological crying occurred 24 hours after onset of therapy. Follow-up examination at day 90 confirmed the absence of relapse of pathological crying. Conclusions We conclude that poststroke pathological crying in our patient may have been due to unilateral disruption of the capsular ascending projections of the serotonergic brain stem raphe nuclei. A small left-sided capsular lesion may have led to severe pathological crying. This disabling condition may be reversible with selective serotonin reuptake inhibitor therapy.

Background and Purpose Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized studies are needed, open trials could generate hypotheses concerning (1) the clinical correlations of outcome, (2) the significance of CT scan data during the first week, and (3) the use of adjunctive therapies. Methods We performed an open trial of intravenous rTPA on patients referred to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized during 1994 with completed stroke in the internal carotid artery territory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusion time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTPA was infused for 90 minutes. Intravenous heparin was given either immediately at efficient dosage or after 24 hours. Mannitol was used in patients with severe presentation. The Scandinavian Stroke Scale evaluation was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24±6 hours) and 7. Results Forty-three consecutive patients met the criteria of the protocol. The mean age at inclusion was 65±10.4 years, and the mean interval to treatment was 232±79 minutes. At day 90, 25 patients (58.1%) exhibited a complete regression of symptoms, and 3 had moderate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas. Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated with major neurological improvement at day 1. Intravenous immediate heparin versus delayed heparin after 24 hours improved the ischemic outcome but not the overall outcome. Reinfarction syndromes after major neurological improvement, likely to be rethrombosis syndromes, were observed in 3 patients (6.9%). For the day 1 CT scan, poor outcome was associated with the presence of structured and homogeneous hypodensities likely to represent classic infarcts, as confirmed by day 7 CT scan. Conversely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases and is likely to represent reperfusion images and/or incomplete ischemic damage. Conclusions The results obtained in this open, small study suggest safety and effectiveness of rTPA thrombolysis at the dose of 0.8 mg/kg within 7 hours in acute strokes of the carotid territory, including highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during the first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylobar and heterogeneous, which is likely to correspond to reperfusion images.

Thromboembolic stroke is likely to occur in patients with a restricted cerebral blood flow reserve. Our aims were to determine (1) whether symptomatic patients had any significant hemodynamic restriction ipsilateral to carotid occlusive disease compared with patients whose carotid stenosis is asymptomatic and (2) whether patients with carotid occlusive disease have impaired cerebral perfusion reserve compared with control subjects. We compared cerebral blood flow and collateral capacity using the 133Xe inhalation method and acetazolamide test in symptomatic (n = 10) and asymptomatic (n = 10) patients who had a high-grade internal carotid artery stenosis (range, 70% to 99%). Results were compared with those from 10 healthy control subjects. Mean baseline cerebral blood flow was 40.29 +/- 1.38 mL/100 g per minute on the symptomatic side in symptomatic patients versus 45.20 +/- 2.53 mL/100 g per minute on the lesion side in asymptomatic patients (control subjects, 46.91 +/- 2.11 mL/100 g per minute in the right hemisphere versus 46.17 +/- 1.93 mL/100 g per minute in the left). There was no statistical difference between patients in symptomatic and asymptomatic groups versus control subjects (P > .10). Mean cerebral blood flow increase after acetazolamide was in the same range in symptomatic (52.89 +/- 2.54 mL/100 g per minute) and asymptomatic (56.22 +/- 3.35 mL/100 g per minute) patients (P > .10), and no difference was observed regarding control subjects (54.25 +/- 2.94 mL/100 g per minute; P > .10). Three asymptomatic and two symptomatic patients and three control subjects had no significant cerebral blood flow increase after acetazolamide. An additional hemodynamic factor in thromboembolic ischemia related to severe unilateral carotid stenosis might be an unusual finding in patients without apparent hemodynamic induction of symptoms. The lack of significant variation in postacetazolamide cerebral blood flow in some patients and control subjects implies that this procedure may be inconsistent in assessing the cerebral perfusion reserve in the individual case.

P34 Background : Several factors are suspected in the occurrence of hemorrhages after rtPA thrombolysis in cerebral infarcts, but little is known about coagulation in these patients. Methods and results : One hundred consecutive patients had rtPA at the dose of 0.8 mg/kg infused for 90 minutes.We studied the values of fibrinogen, FDP, aPTT, INR and thrombocyte count before thrombolysis and at 2 and 24 hours. Results: Cerebral bleeding at 24 hours included 16 hemorrhagic infarcts (HI) and 7 parenchymal hematomas (PH). 1. Cerebral bleeding in general. Univariate analysis comparing patientswith HI+PH vs patients without bleeding detected 2 significant factors : severity at entry (p=0.03) and and increased values of FDP at 2 hours (p=0.05). Each early CT symptom and pooled early CT symptoms did not appear as factors of bleeding. Multivariate analysis showed that values of FDP>150mg/L multiplicate the odds of bleeding by 6.9, being then a more powerful factor than severity at entry. 2. Factors of seriousness of bleeding. FDP values>150 mg/L multiplicate the odds of parenchymal hematoma by 17. Comparison of patients with PH and HI only showed one potential factor, the lack of hypercholesterolemia (p=0.06). Interestingly, age, delay, severity at entry, early CT signs of ischemia were not factors of parenchymal invasion. Heparin in the fist 24 hours was a potential factor, but not reaching statistical significance. In a logistic regression model, the lack of hypercholesterolemia multiplicates the risk of PH by 10. Conclusion : The ”making“ of a parenchymal hematoma involves at least 2 phases : (1) an early ”acquired coagulopathy“ characterized by increased FDP values at 2 hours (ie a particularly intense thrombolysis); and (2) an increased vulnerability of the arteriolar wall, possibly related to the lipid content of the vessels. The observation of the ”coagulopathy“ should contraindicate any antithrombotic drug during the first 24 hours and imply a surveyance of haemostasis and cerebral bleeding with T2* gradient-Echo MRI during the following days.

A linkage analysis with chromosome 9 markers was performed in 33 families with Friedreich ataxia (FA). Linkage with D9S15, previously established by S. Chamberlain et al. (1988, Nature London 334:248-249) was confirmed in our sample (z(theta) = 6.82 at theta = 0.02) while INFB (interferon-beta gene) shows looser linkage. An additional marker, D9S5, was also shown to be closely linked to FA (z(theta) = 5.77 at theta = 0.00).

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2∗-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week ( r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).