Carlos Cantú

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.

Cerebral Venous and Sinus Thrombosis in Women

Background and Purpose— Little is known about the gender-specific manifestations of cerebral venous and sinus thrombosis, a disease that is much more common in women than men. Methods— We used data of the International Study on Cerebral Vein and Dural sinus Thrombosis (ISCVT), a multicenter prospective observational study, to analyze gender-specific differences in clinical presentation, etiology, and outcome of cerebral venous thrombosis. Results— Four hundred sixty-five of a total of 624 patients were women (75%). Women were significantly younger, had less often a chronic onset of symptoms, and had more often headache at presentation. There were no gender differences in ancillary investigations or treatment. A gender-specific risk factor (oral contraceptives, pregnancy, puerperium, and hormonal replacement therapy) was present in 65% of women. Women had a better prognosis than men (complete recovery 81% versus 71%l P=0.01), which was entirely due to a better outcome in female patients with gender-specific risk factors. Women without gender-specific risk factors are similar to men in clinical presentation, risk factor profile, and outcome. Logistic regression analysis confirmed that the absence of gender-specific risk factors is a strong and independent predictor of poor outcome in women with sinus thrombosis (OR, 3.7; CI, 1.9 to 7.4). Conclusions— Our study identified important differences between women and men in presentation, course, and risk factors of cerebral venous and sinus thrombosis and showed that women with a gender-specific risk factor have a much better prognosis than other patients.

Intracerebral Hemorrhage in Young People Analysis of Risk Factors, Location, Causes, and Prognosis

BACKGROUND AND PURPOSE The frequency of intracerebral hemorrhages (ICHs) in people aged </=40 years has been poorly studied. We investigated the incidence, causes, locations, and prognosis of ICH in young patients. METHODS We evaluated all consecutive patients with neuroimaging evidence or pathological confirmation of symptomatic ICH. We excluded patients with primary subarachnoid or traumatic hemorrhage, past evidence of vascular malformation, or brain tumor. We analyzed the risk factors, number, locations, and causes of ICH, and final outcome measured by the modified Glasgow Outcome Scale. RESULTS We retrospectively evaluated 200 patients (mean age, 27 years; range, 15 to 40 years). The most frequent risk factors were tobacco use (20%), hypocholesterolemia (35%), hypertension, (13%), and alcohol use (10%). The locations of ICH were lobar (55%), basal ganglia/internal capsule (22%), and others (24%). The most common causes of ICH were vascular malformations (49%), including cavernous angioma, and hypertension (11%). Cryptogenic ICH was considered in 15%. Other causes included cerebral venous thrombosis (5%) and sympathomimetic drug use (4%). The majority of patients with ICH that resulted from hypertension were aged >31 years (odds ratio, 3.48), and those with ICH that resulted from arteriovenous malformations were aged <20 years (odds ratio, 2.80). The final outcome was considered favorable in 60%. CONCLUSIONS ICHs in young people are mainly lobar in location and result from vascular malformation. Hypertension causes most cases in which the ICH is located in the basal ganglia. Mortality and morbidity in the acute phase are low and are related to hypertension as the cause of ICH.

Stroke Associated With Sympathomimetics Contained in Over-the-Counter Cough and Cold Drugs

Background and Purpose— Phenylpropanolamine (PPA) and pseudoephedrine are sympathomimetics contained in over-the-counter cold preparations. A case-control study linked PPA use with hemorrhagic stroke in women. Twenty-two patients with stroke associated with use of these drugs are described. Methods— In a consecutive stroke registry since 1988, 22 patients had stroke associated with over-the-counter sympathomimetics. Sympathomimetic dosage and type, time interval until stroke onset, and neuroimaging findings are described. Results— Ten male and 12 female patients were included. Intracerebral hemorrhage occurred in 17 patients, subarachnoid hemorrhage in 4, and ischemic stroke in 1. Stroke was associated with PPA use in 16 patients (dose 75 to 675 mg), with pseudoephedrine in 4 (dose 60 to 300 mg), and with others administered by the nasal route in 2 (oxymetazoline and phenylephrine). Stroke occurred after a single dose in 17 patients and after daily use during several days in 5. The interval between drug exposure and clinical onset varied from 30 minutes to 24 hours. Stroke occurred after recommended doses of PPA (50 to 75 mg) in 32% and pseudoephedrine (60 mg) in 50% of patients. Eight patients had acute hypertension at stroke onset. Cerebral angiography was normal in 8 cases and showed diffuse vasospasm or beading in 10 patients. Conclusions— Stroke related to over-the-counter sympathomimetics was associated with acute hypertension and/or vasospasm or angiitis mechanisms, most related to the use of PPA; however, stroke also occurred with the use of other sympathomimetics, particularly pseudoephedrine. Although stroke complications occurred when doses were used that were higher than recommended doses, apparently there is also a stroke risk when these agents are taken properly.

Hyperhomocysteinemia, Low Folate and Vitamin B12 Concentrations, and Methylene Tetrahydrofolate Reductase Mutation in Cerebral Venous Thrombosis

Background and Purpose— Elevated plasma levels of homocysteine are associated with an increased risk of deep-vein thrombosis. Through a case–control study, we examined the potential association among homocysteine, folate and vitamin B12 levels, and the common C677→T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene in patients with cerebral venous thrombosis (CVT). Methods— Forty-five patients with CVT and 90 control subjects were studied. Plasma levels of homocysteine (fasting and after methionine load), folate, and vitamin B12 were measured. Genotyping of the MTHFR gene was also performed. The estimated risk of CVT associated with hyperhomocysteinemia, low vitamin levels, and MTHFR mutation were expressed as odds ratio (OR) and its 95% CI (crude and after adjusting by other independent variables). Results— The adjusted OR for CVT associated with high (>90th percentile) fasting levels of homocysteine was 4.6 (1.6 to 12.8). The association between low plasma folate values (<10th percentile) and presence of CVT was 3.5 (1.2 to 10.0) after adjustment for confounding factors. There was a higher frequency of MTHFR mutation in patients with CVT (22% versus 10%), but it was not statistically significant (P = 0.098). Patients with MTHFR mutation and low folate levels presented the highest homocysteine levels. Conclusions— High plasma concentrations of homocysteine and low plasma folate levels were associated with an increased risk of CVT in this population in which low socioeconomic conditions and deficient nutritional status may contribute to its relatively high incidence.

Prospective Study of Single and Multiple Lacunar Infarcts Using Magnetic Resonance Imaging: Risk Factors, Recurrence, and Outcome in 175 Consecutive Cases

Background and Purpose— We investigated whether lacunar infarct (LI) patients with >1 lacune have different vascular risk factors, a different prognosis, and poorer functional outcome than those with a single lacune. Methods— The study included 175 first-ever LI patients. The group was divided according to the presence of multiple (n=136) or single (n=39) LI. The association of single or multiple LI with the principal vascular risk factors, leukoaraiosis, outcome, and recurrence was investigated with logistic regression models that included age, sex, and cardiac disease. Results— No significant differences were found between single and multiple LI with respect to age, hypertension, hyperlipidemia, smoking, and heavy alcohol drinking. Diabetes mellitus (odds ratio [OR], 2.43; 95% CI, 1.09 to 5.4), high levels of hematocrit (>0.47) (OR, 1.09; 95% CI, 1.04 to 1.21), and leukoaraiosis (OR, 3.58; 95% CI, 1.77 to 7.51) were significantly related to multiple but not to single LI. Stroke recurrence rate was 7.7% in patients with single LI and 24.3% in the multiple LI group (OR, 3.84; 95% CI, 1.1 to 13.3). During a median follow-up of 12 months (range, 6 to 156 months), 94% of the single LI patients and 77.2% of the multiple LI patients had favorable outcomes (Rankin Scale score 0 to 2) (OR, 5.4; 95% CI, 1.25 to 23.9). Conclusions— Diabetes mellitus, leukoaraiosis, and high levels of hematocrit are important risk factors in patients with >1 LI. The presence of multiple LI may be an important prognostic indicator not only for functional recovery but also for a higher rate of recurrence.

Noninvasive Cerebrovascular Assessment of Takayasu Arteritis

Background and Purpose Despite prominent neurological symptoms reported in Takayasu arteritis (TA), a complete evaluation of the cerebral circulation has not been consistently performed. The purpose of this study is to describe MR angiography (MRA), color Doppler flow imaging, and transcranial Doppler (TCD) findings in the extracranial and intracranial cerebral arteries in TA. Methods MRA, color Doppler flow imaging, and TCD were performed in 21 patients with TA. Intima-media thickness was measured in the common carotid artery. The correlation between noninvasive studies and panaorto-arteriography was examined for supraortic vessels. Cerebral angiography findings were compared with the noninvasive methods in 7 patients. Intracranial hemodynamic changes detected by TCD were compared with extracranial circulation lesions assessed by panaorto-arteriography. Results Noninvasive vascular techniques showed at least 1 abnormality in the extracranial and/or intracranial cerebral arteries in 20 of 21 patients (95%). Both MRA and color Doppler flow imaging showed a substantial correlation in the ability to detect obstructive lesions in supra-aortic vessels compared with panaorto-arteriography. High-resolution ultrasonography displayed common carotid artery wall thickening in 5 vessels that were considered normal by arteriography. In 24% of patients, MRA and TCD showed abnormalities consistent with stenosis of the basal cerebral arteries. In 10 patients with severe extracranial circulation involvement (detected by arteriography), TCD displayed intracranial hemodynamic changes consisting of dampened or blunted waveforms with low pulsatility. Conclusions The comprehensive assessment of cerebral circulation in TA patients by noninvasive methods allowed the detection of a high rate of diverse vascular abnormalities in both extracranial and intracranial circulation.

Frequency of Cerebral Arteritis in Subarachnoid Cysticercosis: An Angiographic Study

BACKGROUND AND PURPOSE Subarachnoid cysticercosis is a well-recognized cause of cerebral infarction. However, few patients with this infection develop cerebral infarction, and the reason for this is not known. The aim of this study was to determine the frequency of cerebral arteritis in these patients. METHODS Using cerebral arteriography, we studied 28 patients with subarachnoid cysticercosis admitted to our hospital from July 1993 to February 1996. All patients underwent MRI to detect the presence of basal arachnoiditis. We analyzed demographic data, time to cysticercosis since the first symptom onset, mode of onset, stroke syndromes, neuroimaging features of cysticercosis and cerebral infarction, and arteriographic findings for each patient. RESULTS Of the 28 patients (mean age, 37 years), 15 patients had angiographic evidence of cerebral arteritis (53%); 12 of the 15 had a stroke syndrome (P=.02). Eight of the 15 patients (53%) with cerebral arteritis had evidence of cerebral infarction on MRI, whereas only one patient without cerebral arteritis had cerebral infarction (P=.05). The most commonly involved vessels were the middle cerebral artery and the posterior cerebral artery. CONCLUSIONS The frequency of cerebral arteritis in subarachnoid cysticercosis is higher than previously reported, and middle-size vessel involvement is a common finding, even in those patients without clinical evidence of cerebral ischemia.

Dissection of Cervical Arteries: Long-Term Follow-Up Study of 130 Consecutive Cases

Background and Purpose: We describe the natural history, functional prognosis and long-term recurrences of patients with dissection of cervical arteries (DCA) in a sequential observational study. Methods: We describe 130 patients with angiographically-proven DCA admitted to the Neurology Institute in Mexico City (Mexico), and analyzed clinical and neuroimaging data, treatment and outcome. Treatment with either anticoagulation or aspirin was decided by the primary physician. Primary outcome measures were recurrence (stroke and death) and clinical outcome at 6 months. Follow-up studies were performed to determine recanalization. Results: Mean age was 35.4 years; 4 patients died (3%) and 126 were followed for 3,906 person/years; 17 patients (13%) had a heralding ischemic cerebral event (6 strokes, 11 TIAS) about 8 days before the diagnosis of DCA. After diagnosis, recurrent ischemic stroke occurred in 6 patients (4.8%) within the 2 first weeks (1.5 persons/1,000 follow-up years). No significant differences were found between aspirin and anticoagulation. Recanalization was more frequent in vertebral dissections. Complete recanalization of vertebral dissections was associated with a favorable prognosis [OR 3.2 (95% CI 1.1–8.8; p = 0.02)]. Conclusions: In Mexico, DCA affects young adults and may present with a heralding stroke or TIA. We found rare, early ischemic recurrences. Vertebral territory dissections had better prognosis than carotid ones, particularly in patients with demonstrated complete recanalization.

Recurrent Primary Cerebral Hemorrhage Frequency, Mechanisms, and Prognosis

BACKGROUND AND PURPOSE The frequency of recurrent primary cerebral hemorrhage (RPCH), mainly in cases related to hypertension, has been considered low. This study investigated the frequency, mechanisms, and prognosis of RPCH. METHODS We evaluated 359 patients with neuroimaging evidence of cerebral hemorrhage and selected 22 with RPCH. RESULTS Five patients (23%) were older than 70 years at the first cerebral hemorrhage. Mean ages at the first and second hemorrhages were 60 and 63 years, respectively. Risk factors included hypertension (86%), diabetes (27%), and tobacco and alcohol use (each 14%). Hypocholesterolemia was demonstrated in 35% of the patients. The most common pattern of recurrent bleeding was ganglionic-ganglionic, mainly related to hypertension. Overall mortality was 32%. Forty-one percent and 27% of patients, respectively, had incapacitating and nonincapacitating sequelae; 2 of the latter had RPCH with a lobar location. Ganglionic-ganglionic hemorrhage was associated with a poor prognosis; otherwise, this pattern was uncommon in patients with nonincapacitating sequelae. Analysis of the control of risk factors, primarily hypertension after the first cerebral hemorrhage, disclosed that 56% of patients did not gain subsequent control. CONCLUSIONS Rebleeding after a first primary intracerebral hemorrhage is not uncommon. The main topographic pattern of bleeding, ganglionic-ganglionic, is likely the result of hypertension; the less common lobar-lobar pattern probably results from amyloid angiopathy.