Filipa Falcão

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Thrombolytics for Cerebral Sinus Thrombosis

Background and Purpose: The use of thrombolytics is frequently mentioned in patients with cerebral venous or dural sinus thrombosis (CVDST) who deteriorate despite anticoagulant therapy. The aim of this review was to collect all the published information about their use in CVDST and to assess their efficacy and safety. Methods: To find cases of CVDST treated with thrombolytics, we performed a MEDLINE search from 1966 to July 2001, checked all reference lists of studies found and hand searched volumes of 11 journals. Data was extracted by means of a standardised data extraction form. Proportions and 95% confidence intervals (CI) were calculated for outcomes and complications of thrombolytics. Cases were stratified according to variables that may influence the outcome and subgroups were compared by odds ratios and 95% CI. Results: No randomised clinical trial (RCT) was found. Seventy-two studies (169 patients) were included. Urokinase was the thrombolytic most frequently administered (76%). In the majority of cases the thrombolytic was locally infused in the occluded sinus (88%). At discharge, 10 cases (7%; 95% CI 3–12%) were dependent and 9 cases (5%; 95% CI 2–9%) died. Intracranial haemorrhages occurred in 17% of cases. In 5% they were associated with clinical deterioration. Extracranial haemorrhages occurred in 21%, but only 2% required blood transfusion. Conclusions: Thrombolytics appeared to be reasonably safe in CVDST, but its efficacy cannot be assessed from the published data. Considering that CVDST is an uncommon disease, a randomised controlled trial to assess effectiveness and safety of local thrombolytics in cases of CVDST with poor prognosis is difficult but not impossible to undertake, on a multicentre international collaboration trial.

Lumbar Puncture and Dural Sinus Thrombosis – A Causal or Casual Association?

Background: A few cases of cerebral venous thrombosis (CVT) were reported after a lumbar puncture (LP), suggesting a causal association. The purpose of our study was to document that LP might predispose to CVT by decreasing blood flow velocities (BFV) in veins or dural sinus. Methods: We performed a transcranial Doppler ultrasound study to register the mean BFV of the straight sinus (SS) before, during and after LP. Results: Thirteen patients were studied. LP induced a decrease of 47% of mean BFV in the SS. The mean decrease of BFV was significant immediately at the end (p = 0.003), 30 min after (p = 0.015) and more than 6 h after LP (p = 0.008). Conclusions: LP induced a sustained decrease of mean BFV in the SS. The decrease of venous blood flow is a possible mechanism contributing to the occurrence of CVT.

Vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage.

Abstract No data have been published on the role of vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage (PMSAH). In a case-control study we compared the prevalence of vascular risk factors in 40 consecutive patients who suffered a perimesencephalic subarachnoid hemorrhage with that in two controls groups: (a) 120 subjects registered with a general practitioner (GP; matched at a 3 : 1 ratio for age and sex) and (b) 81 proxies of patients of a hospital outpatient clinic. A conditional multivariate logistic regression model was performed taking into account the matched design. Hypertension was more frequent among PMSAH patients than among the two control group subjects for men and women. Among women, smoking was more common in PMSAH than in the GP control group. The conditional multivariate logistic regression model confirmed that hypertension was an independent risk factor for PMSAH (P = 0.036) Hypertension is a preventable risk factor of PMSAH.

Headache in acute stroke. A prospective study in the first 8 days

We aimed to describe and classify headaches associated with acute stroke, by interviewing patients consecutively admitted to a stroke unit using a validated headache questionnaire and the International Classification of Headache Disorders of the International Headache Society (IHS). One hundred and twenty-four patients (61% ischaemic and 39% haemorrhagic stroke) reported headache. Headaches started mostly on the day of stroke, were more often continuous, pressure-type, bilateral and located in the anterior region, were increased by movement and by cough and lasted for a mean of 3.8 days. Tension-type was the most frequent type of headache. Eleven per cent of headaches could not be classified using the criteria of the IHS. Previous primary headache was documented in 71 patients. The presence of nausea/vomiting due to acute stroke can confound headache classification using the IHS criteria. In up to half of the patients, headache seems to be a reactivation of previous primary headache.

N-terminal probrain natriuretic peptide as a biomarker of cardioembolic stroke

Background and purpose N-terminal probrain natriuretic peptide, which is mainly produced by the heart, is increased in acute stroke. We aimed to determine if N-terminal probrain natriuretic peptide could be a biomarker for ischemic stroke with a cardioembolic cause. Methods Consecutive sample of acute stroke patients admitted to a Stroke Unit. Ischemic stroke subtype was classified using the TOAST classification. Blood samples were drawn within 72 h after stroke onset. Serum N-terminal probrain natriuretic peptide concentration was measured using an electrochemiluminescence immunoassay. Mean values of N-terminal probrain natriuretic peptide were compared between patients with hemorrhagic stroke vs. ischemic stroke, cardioembolic stroke vs. noncardioembolic stroke, cardioembolic stroke with atrial fibrillation vs. noncardioembolic stroke using t-test. Receiver operating characteristic curves were used to test the ability of N-terminal probrain natriuretic peptide values to identify cardioembolic stroke and cardioembolic stroke with atrial fibrillation. Results Ninety-two patients were included (66 with ischemic stroke) with a mean age of 58·6 years. Twenty-eight (42·4%) ischemic strokes had a cardioembolic cause. Mean N-terminal probrain natriuretic peptide values for cardioembolic stroke were significantly higher (P < 0·001) (491·6; 95% confidence interval 283·7–852·0 pg/ml) than for noncardioembolic ischemic stroke (124·7; 86·3–180·2 pg/ml). The area under the receiver operating characteristic curve for N-terminal probrain natriuretic peptide in cardioembolic stroke was 0·77. The cut-off point with the highest sensitivity and specificity was set at 265·5 pg/ml (71·4% and 73·7% respectively). The area under the curve of N-terminal probrain natriuretic peptide for cardioembolic stroke related to atrial fibrillation was 0·92, cut-off was set at 265·5 pg/ml (sensitivity 94·4%, specificity 72·9%). Conclusion N-terminal probrain natriuretic peptide is a biomarker with a good accuracy to predict ischemic stroke of cardioembolic cause, namely associated with atrial fibrillation.

Study of cerebral cavernous malformation in Spain and Portugal : High prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene)

ObjectiveWe aimed to study clinical, radiological and molecular genetic features of patients with cerebral cavernous malformations (CCMs) from the Iberian Peninsula.MethodsWe screened Krit1(CCM1), MGC4607(CCM2), and PDCD10(CCM3) by systematic SSCP and direct sequencing of coding exons in 48 nuclear families and 30 sporadic cases of CCM from Spain and Portugal.ResultsScreening of CCM patients detected nine different mutations in 19 families. We found four new mutations in Krit1. Three of them were caused by either a small insertion or deletion, which lead to frameshift and premature termination codons. We also found a missense L308H mutation located in a highly conserved sequence within the ankyrin domain of Krit1. In CCM2, we found a redundant 14 bp deletion in exon 5 of MGC4607 which predicts a truncated protein at residue 230. We did not find mutations in CCM3.ConclusionsFinding that the 14 bp deletion was present in eleven families from the Iberian Peninsula indicates a high prevalence of this mutation. This redundant CCM2 mutation is worth considering in molecular diagnosis and genetic counselling of cerebral cavernous malformations.

Chiropractic manipulation: reasons for concern?

Chiropractics popularity is rising among the general population. Moreover, few studies have been conducted to properly evaluate its safety. We report three cases of serious neurological adverse events in patients treated with chiropractic manipulation. The first case is a 41 years old woman who developed a vertebro-basilar stroke 48 h after cervical manipulation. The second case represents a 68 years old woman who presented a neuropraxic injury of both radial nerves after three sessions of spinal manipulation. The last case is a 34 years old man who developed a cervical epidural haematoma after a chiropractic treatment for neck pain. In all three cases there were criteria to consider a causality relation between the neurological adverse events and the chiropractic manipulation. The described serious adverse events promptly recommend the implementation of a risk alert system.

Dural sinus thrombosis mimicking “capsular warning syndrome”

Sirs: Cerebral vein and dural sinus thrombosis is a difficult clinical diagnosis as its presentation can be misleading. Increased awareness and the diagnostic use of magnetic resonance imaging and magnetic resonance venography have expanded our knowledge of its initial clinical manifestations. Cerebral vein thrombosis presenting as clustering transient ischemic attacks has been reported only twice [1, 2]. We report a 44-year-old man admitted for repeated episodes of left hemiplegia and sensory loss. He was a former smoker and heavy drinker (9 drinks/day) and had a history of myocardial infarction. One week previously he had suffered moderate bifrontal and left orbital headache. He was seen at another hospital, where the results of neurological examination and cranial computed tomography were normal. On the day before admission he had two sudden episodes of left-sided weakness and sensory loss (with no “march” or “shaking”) lasting a few minutes. Similar episodes occurred on the morning of admission and while he was being examined by one of us (J. F.) in the emergency room. Computed tomography disclosed a delta sign. Therefore the patient was started on continuous intravenous heparin, but magnetic resonance imaging could not be performed because of claustrophobia. Echocardiography showed an enlarged left atrium and ventricle with decreased systolic function, akinetic segments, and a nonprotuberant hyperechogenic apical thrombus. Duplex and transcranial Doppler ultrasound results were normal. Monitoring by transcranial Doppler ultrasound for 30 min detected no high intensity transient signals. During the next 5 days he experienced several episodes of left hemiparesis and sensory loss despite activated partial thromboplastin time being within the therapeutic range and the administration of additional aspirin. On the 6th hospital day the patient described episodes starting as an ascending left-sided numbness followed by weakness. Intravenous valproate was started with complete cessation of the episodes. Magnetic resonance imaging and magnetic resonance venography performed after sedation demonstrated bilateral parietal hyperintensities, occlusion of the superior sagittal (Fig. 1), and right lateral sinus and partial thrombosis of the left lateral sinus. The patient had both prothrombin GA 20210 and Ala/Val MT HFR mutations. He was kept on warfarin and valproate with no recurrences during 14 months of follow-up. This patient presented as repeated transient episodes of hemiplegia, a clinical syndrome known as “capsular warning syndrome” [4]. This type of clustering transient ischemic attack is usually due to small vessel disease [3, 5], causing ischemia of the posterior limb of the internal capsule [5] or of the basis pons [6]. To our knowledge, there have been only two previous reports of cerebral vein thrombosis mimicking clustering transient ischemic attack. In the patient with superior sagittal sinus thrombosis reported by Bousser and Russel [1] focal seizures followed the episodes of hemiplegia. The patient described by Chang et al. [2] had episodes of either right or left hemiparesis. Transient hemiparesis and seizures can be related to congestion of the cortical veins [7], elevated venous pressure, and focal areas of cerebral edema. Cerebral vein thrombosis should be considered in the diagnosis of “capsular warning syndrome,” in particular when repeated episodes of hemiplegia are associated with headaches or combined with focal seizures.

Improvement of sleep architecture in the follow up of a patient with bilateral paramedian thalamic stroke

Normal sleep architecture and arousal require an intact thalamus. Thalamic vascular lesions, particularly in the paramedian region may cause arousal disturbances and hypersomnolence. Although hypersomnolence is one of the main characteristics of acute bilateral paramedian thalamic infarcts, there are only scarce reports in literature concerning polysomnographic follow-up of these patients. The few reported cases in literature show that sleep stages do not significantly change from the acute to chronic phase. We present a case report of a patient with a bilateral paramedian thalamic infarct in which a polysomnographic evaluation of sleep was performed four days and five months after stroke. In the acute phase, polysomnography showed an impairment of phase 2 NREM and absence of phase 3 and 4 NREM with absent sleep spindles. After the acute stroke phase, hypersomnolence improved and sleep spindles reappeared as well as phase 3 and 4 of NREM sleep. Our patient clear clinical and polysomnographic improvement makes us suppose that in this case the initial impairment could have been essentially due to a functional transitory impairment of the thalamocortical and corticothalamic connections. This case report is peculiar because it discloses a marked improvement of sleep architecture which to the best of our knowledge has not been clearly described before.