Diagnosis of CADASIL disease in normotensive and non-diabetics with lacunar infarct.

BACKGROUND: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is characterized by recurrent cerebral ischemic episodes of the lacunar subtype usually without traditional vascular risk factors. We investigated the frequency of CADASIL among selected patients with cerebral ischemia of the lacunar subtype. METHODS: we studied patients under 65 years old who presented cerebral ischemia of the lacunar subtype without hypertension, diabetes mellitus or other causes that explained the cerebral ischemia. On the skin biopsies, we performed immunostaining analysis on 5µm frozen sections with monoclonal antibody anti-Notch 3 (1E4). We also performed a genetic analysis of the Notch 3 gene (exons 3,4,5,6,11 and 19). RESULTS: of 1.519 patients analyzed, only 57 (3.7%) fulfilled the selection criteria, and 30 of them accepted to participated in the study. We studied 30 patients, mean age was 53 years (range 34 to 65), 50% were men and all patients suffered a lacunar stroke. Immunostaining analysis was positive in two patients (6.6%) and the genetic analysis confirmed a mutation characteristic of CADASIL in exon 4 nt 622C/T (Arg 182 Cys) and 694 T/C (Cys206Arg) respectively. CONCLUSIONS: CADASIL disease was present in 6.6% of patients younger than 65 years with a lacunar stroke and without hypertension or diabetes mellitus. Screening for CADASIL should be considered in these patients.

Proliferation in the human ipsilateral subventricular zone after ischemic stroke.

BACKGROUND: It is uncertain whether neurogenesis occurs in humans after stroke. We studied the morphologic changes that occurred in the subventricular zone (SVZ) in patients who died following an acute ischemic stroke. METHODS: We examined coronal brain slices from patients who died after a first-ever cerebral nonlacunar infarction in the middle cerebral artery territory. We evaluated the morphologic changes in the ipsilateral and contralateral SVZ by light and electron microscopy. Using immunochemistry with Ki-67 and PCNA, we detected cell proliferation. We used Tuj-1 for immature neurons and PSA-NCAM for migrating cells. RESULTS: The study included 7 patients with a mean age of 82 +/- 5 (mean +/- SD) years; 4 were men. They died a mean of 10 +/- 5 days after the ischemic stroke. Brain samples were obtained a mean of 4 +/- 2 hours after death. In comparison with the contralateral SVZ, the following changes were observed in the ipsilateral SVZ: an increase in the width of the gap and ribbon layers, as well as in the cell density of the ribbon layer, an enlargement of the cytoplasmic volume of astrocytes, and an increase of Ki-67-positive cells. In the ipsilateral SVZ, mitoses and cells that stained for either Tuj-1 or PSA-NCAM markers were observed more frequently than in the contralateral SVZ. CONCLUSION: We found unequivocal evidence of active cell proliferation in the ipsilateral subventricular zone following an acute ischemic stroke in our patients.

[Carotid thrombus and cerebral infarction as the initial clinical manifestation of polycythemia vera]. / Trombo carotídeo e infarto cerebral como manifestación clínical inicial de policitemia vera.

Polycythemia vera (PV) can produce cerebral infarction. The mechanisms proposed by most authors are hyperviscosity-related diminished cerebral blood flow and platelet function abnormalities. We present a 36-year-old woman whose initial clinical manifestation of PV consisted of cerebral ischemia due to a carotid thrombus, as well as occlusion of the middle cerebral artery and cortical branches of the anterior cerebral artery demonstrated by angiography. To our knowledge, this is the first published case of cerebral infarction in PV caused by a thrombus of an extracranial artery. Therefore, PV can produce ischemic stroke due to thrombosis not only in small distal arteries or arterioles but also in the carotid artery or main branches. Treatment of intraluminal thrombus in non-arteriosclerotic carotid artery is discussed. Myeloproliferative disorders, including PV, must be suspected in all stroke patients with an elevated platelet count, even in those who have potential causes of reactive thrombocytosis.

New concepts in lacunar stroke etiology: the constellation of small-vessel arterial disease.

OBJECTIVE: To update the less frequent etiologies causing lacunar infarcts (LIs). To highlight recent advances in risk factors, clinical syndromes, topography, complementary tests and long-term prognosis in this subtype of ischemic stroke. PATIENTS AND METHODS: The most important studies are analyzed, from CM Fisher works, selecting those referring to LIs of unusual etiology, and recent advances and controversies in the clinical management of LI are discussed. RESULTS: LIs are found in approximately 11% of patients admitted with stroke. The pure motor hemiparesis (55%) constitutes the most usual lacunar syndrome. However, lacunar syndromes may not be caused by LIs in 10-20% of cases. LIs caused by microembolism and cholesterol embolism from the aortic arch are reviewed. Hematological diseases can also cause LI, such as polycythemia rubra vera, essential thrombocythemia and primary antiphospholipidic antibody syndrome. Other etiologies are carotid plaque embolism, severe stenosis of a perforated arteriole and amyloid angiopathy. Infectious arteritis by neurolues, neurocysticercosis, neuroborreliosis, by AIDS or Helicobacter pylori infection have also been associated with the presence of LIs. Likewise, inflammatory arteritis in systemic lupus erythematosus or granulomatous angiitis, cocaine abuse and panarteritis nodosa have been related to LI, although in the latter LI would be caused by a thrombotic microangiopathy and not by vasculitis. CONCLUSIONS: LI is an ischemic stroke subtype with a characteristic clinical presentation and a short-term favorable prognosis. Although high blood pressure constitutes the main risk factor and the main etiology, LIs may be caused, in less than 5% of cases, by various etiologies, mainly hematological diseases and infectious or inflammatory arteritis. It is essential to make a correct etiological diagnosis for LI as treatment will be different according to its etiology.

Blood pressure variability in Binswanger's disease and isolated lacunar infarction.

UNLABELLED: To determine whether blood pressure (BP) variability is increased in hypertensive patients with Binswanger's disease (BD), we studied two samples of consecutive treated hypertensive patients: (1) 11 with BD (mean age 71.3 +/- 5.2 years); (2) 16 with lacunar infarction (mean age 65.2 +/- 8.3 years) without cognitive impairment. An averaged baseline office BP was obtained for 3 consecutive weeks. Ambulatory BP monitoring was then carried out to obtain the averaged mean systolic (SBP) and diastolic BP, and BP variability was defined as the standard deviation of consecutive BP values. RESULTS: Diurnal SBP variability was significantly increased in the BD group (p = 0.04). However, with the analysis of covariance for age and baseline office BP, the difference was no longer significant (p = 0.17 and p = 0.09, respectively). We conclude that increased BP variability in BD patients is probably due to older age and increased baseline office BP. Increased BP variability may be a risk factor for small-vessel disease, but not for cognitive impairment.

[Non pharmacological treatments in cerebral vascular diseases]. / Tratamientos no farmacológicos en las enfermedades vasculares cerebrales.

Non pharmacological treatments are useful in cerebral vascular diseases. An adequate diet, physical exercise and avoidance of modificable risk factors associated with lifestyle (smoking, obesity and alcohol abuse) are recommended as primary prevention against these diseases. In the early treatment, on initiation of the neurologic focalization, hyperthermia and hyperglycemia should be avoided and adequate nutrition must be achieved. The cephalic position of the patient should be adequate and physiotherapy should be initiated early. Urinary dysfunction, fecal incontinence and cutaneous complications should be prevented and appropriately controlled.

[Cerebral venous thrombosis. Study of 17 cases]. / Trombosis venosa cerebral. Estudio de 17 casos.

BACKGROUND: We undertook this study to determine the clinical, neuroimaging findings, etiologies and final outcome of 17 patients with cerebral venous thrombosis diagnosed in a single center. PATIENTS AND METHODS: In this retrospective study we analyzed the clinical and neuroimaging findings of patients with cerebral venous thrombosis collected at our hospital from 1980 to 1997. The diagnosis of cerebral venous thrombosis was made by angiography and/or magnetic resonance imaging. Final outcome was assessed with the modified Rankin scale and patients were included in two groups. Differences between groups were tested using uni and multivariate analysis. RESULTS: Seventeen patients (10 women) with a mean age of 41.9 years were analyzed. The most frequent clinical pattern was focal cerebral signs (70.5%) followed by symptoms/signs of increased intracranial pressure (12%) and diffuse encephalopathy (12%). The diagnosis of cerebral venous thrombosis was made by conventional angiography in 12 cases (70.5%) and by magnetic resonance imaging in 5 (29.5%). The most frequent site of venous occlusion was superior sagittal sinus (47%) followed by lateral sinus (35%). Etiologies were hematologic disease (29%), neoplasms (23.5%), oral contraceptives (12%), infection (12%) and unknown in 18%. The majority of the patients (59%) had minor neurological sequelae during follow-up. A decreased level of consciousness and neoplasm were associated with a worse functional outcome. CONCLUSIONS: In our series the most frequent clinical pattern was focal cerebral signs and the main etiology was hematologic disease. A relatively good prognosis was observed in those patients. A decreased level of consciousness and presence of neoplasm were the factors associated with a bad prognosis in these cases.

Predictive clinical factors of very early in-hospital mortality in subarachnoid hemorrhage.

This study was conducted to determine clinical predictors of very early in-hospital mortality (within the first 72 h) in patients with non-traumatic subarachnoid hemorrhage. Data of 184 patients with subarachnoid hemorrhage were obtained from consecutive stroke patients included in the prospective Barcelona Stroke Registry. Demographic, anamnestic, clinical, neurological and neuroimaging variables in the subgroup of patients who died within 72 h after the onset of symptoms were compared with those in the subgroup of patients that had survived this initial period. The independent predictive value of each variable on the development of very early death was assessed with a logistic regression analysis. Very early in-hospital death was observed in 18 patients (9.8%). These patients were significantly more likely to have progressive deficit, seizures, altered consciousness, limb weakness, sensory involvement and basal ganglia hematoma than patients without very early death. After multivariate analysis, only progressive deficit (odds ratio (OR) 6.90; 95% confidence interval (95% CI) 2-23.80) and limb weakness (OR 5.46; 95% CI 1.78-16.77) were independent clinical predictors of very early mortality. Progressive neurological deficit and limb weakness at the onset of stroke was independent predictive factors of very early death in patients with non-traumatic subarachnoid hemorrhage. These results further emphasize the need to establish an early etiological diagnosis and to manage these patients aggressively including early surgery in selected cases.

Spontaneous primary intraventricular hemorrhage: clinical data, etiology and outcome.

The clinical features, etiology, and neurological outcome in patients with primary intraventricular hemorrhage (PIVH) have rarely been reported. We retrospectively reviewed the clinical data, complementary examinations, outcome, computed tomography (CT) blood amount, and ventricle size of 13 patients (mean age 60 years, five men). We defined PIVH as hemorrhage detected by CT in the ventricular system only. The major symptoms included headache (n = 13), decreased level of consciousness (n = 9), and nausea/vomiting (n = 7). The cause was unknown in five patients; and was associated with arterial hypertension in five, vascular malformations in two, and tumor in one, although arteriography was performed in only five patients. Outcomes were death in three, asymptomatic in six, mild disability in three, and moderate disability in one. Prognosis was not related to clinical or CT data. Clinical features can suggest the diagnosis of PIVH, but cerebral CT is required for confirmation.

Pentosan polysulfate-induced thrombocytopenia: a case diagnosed with an ELISA test used for heparin-induced thrombocytopenia.

We report a patient who developed severe thrombocytopenia and ischemic stroke following pentosan polysulfate treatment. An ELISA test employed in type-II heparin-induced thrombocytopenia was highly positive. To our knowledge, this is the first case in which this test has been performed in a pentosan polysulfate-induced thrombocytopenia (PIT). Our data suggest that the antibody against pentosan polysulfate-platelet complex also cross-reacts with heparin-platelet factor 4 complex. Due to its greater sensitivity and wider availability, this ELISA test should be used in cases where PIT is suspected.

[Clinico-anatomopathologic analysis of 25 patients with lacunar infarction]. / Análisis clínico-anatomopatológico de 25 pacientes con infartos lacunares.

BACKGROUND: Lacunar infarctions (LI) are associated with an excellent functional prognosis and mortality is exceptional during hospital stay. Therefore, clinico-pathological studies on LI are scarce. METHODS: A retrospective analysis was made of 50 consecutive necropsies of patients with cerebrovascular disease (CVD) from the brain archive of the Pathology Department performed from 1976 and 1985. A macroscopic and microscopic study was carried out of visualized LI which were classified in old or cystic, recent and through perivascular dilation. A clinico-pathologic evaluation was made by analyzing cerebrovascular risk factors, the associated neurological syndromes and mortality causes. RESULTS: Fifty percent of brains with CVD analyzed (25 out of 50) had LI. The total of LI was 107, with a mean of 4.2 +/- 3.4 LI per brain. The main location was at the basal ganglia (54.7%), mainly the putamen (35.8%). The most common lesional diameters ranged from 1 to 4 mm (68.5%). Arterial hypertension was the main cerebrovascular risk factor (84%). Fifty-two percent of brains with LI (n = 13) were asymptomatic (clinically silent LI) Twenty-four percent had a clinical course consistent with a pseudobulbar syndrome (n = 6). Twenty percent had a pure motor hemiparesis (n = 5) and the remaining 4% had a transient ischemic attack associated with the LI topography (n = 1). Mortality causes in LI were non-neurological in nature in 88% (n = 22), whereas in non-lacunar CVD they were neurological in nature in 60% (n = 15) (p < 0,0007). CONCLUSIONS: LI are usually multiple, with a small lesional diameter (from 1 to 4 mm) and clinically silent. Arterial hypertension was associated with 84% of cases and mortality causes are usually non-neurological in nature (88%).

[Latent period before hospital admission in cerebrovascular pathology: determining factors]. / Latencia de ingreso hospitalario en patología vascular cerebral: factores determinantes.

OBJECTIVE: Establish the factors determining the latent period before hospital admission of patients with cerebrovascular disorders. MATERIAL AND METHOD: One hundred patients with cerebrovascular disorders admitted to the Hospital de la Santa Creu i Sant Pau, Barcelona were analyzed. All patients were systematically interviewed, evaluating: age, sex, place of residence, initial condition, type of transport to hospital, vascular risk factors, past history of cerebrovascular disorders, time of onset of symptoms, sleeping-wakefulness state, initial symptom, accompanying symptoms, initial course of illness, complications whilst in hospital, clinical condition and functional ability on leaving hospital, and duration of stay in hospital. All these factors were compared according to the latent period before admission (6 hours or less, or more than 6 hours). RESULTS: Patients with a latent period before admission of 6 hours or less more frequently had: changes in the level of consciousness (p = 0.04), motor disorders (p < 0.01), stable course (p = 0.04), systemic complications (p = 0.02) and were severely affected (p > 0.01). Patients with a latent period of more than 6 hours before admission more frequently: were smokers (p > 0.01), had a clinical course in stages (p < 0.01) and no limitation (p = 0.02). The stay in hospital lasted longer in the first group of patients. No differences were found when comparing: age, sex, place of residence, state at onset, type of transport to the hospital, vascular risk factors apart from smoking, past history of cerebrovascular illness, time of onset of symptoms, state of sleeping-wakefulness, initial symptoms and accompanying symptoms apart from changes in level of consciousness and motor defect. CONCLUSIONS: Factors determining delay in the hospital admission of patients with cerebrovascular disorders are: smoking, the clinical picture (alteration of consciousness, motor disorders) and the initial course of symptoms.

Presurgical identification of the primary sensorimotor cortex by functional magnetic resonance imaging.

The ability of functional magnetic resonance (MR) imaging to detect a selective sensorimotor cortex activation in healthy subjects and the feasibility of motor activation in patients with lesions around the central sulcus were investigated. Twenty-five healthy volunteers performed 100 motor activation trials, using a variety of motor tasks, which were monitored by several image analysis methods. The functional images were obtained using a 1.5-tesla standard MR imaging system magnet with blood oxygenation level-dependent contrast. Four patients were assessed using functional MR imaging and invasive cortical mapping. Rolandic cortex activation was observed in 98% of the trials performed on healthy subjects in which no head motion occurred. Nevertheless, the cortical response was not selective in a task-rest analysis due to concurrent activation of neighboring regions. Across-task comparison analyses were useful in cancelling nonrelevant activity in most cases (86%). In the patient group, the region identified as the sensorimotor cortex by invasive means corresponded accurately to the area that was activated in functional MR imaging. Present data support the feasibility of detecting selective activation of the rolandic cortex, even in the clinical setting, leading the authors to suggest the usefulness of this widely available technique in surgical planning.

Hemorragia cerebral lobar clínica, etiologia, evolução. Revisão de 58 casos / Lobar cerebral hemorrhage. Clinical aspects, etiology and course. Review of 58 cases

Fifty eight patients with spontaneous lobar hemorrhage of a 264 patients series with intracerebral hemorrhage seen during a six years period are reviewed. Twenty nine had arterial hypertension, 9 had other etiologies, and in the remaining 20 cases no apparent etiology was detected. Headache was a prominent symptom and occurred in 56%. Seizures occurred in 12%. Coma was infrequent. Clinical findings on admission depended on the location of the hematoma. Lobar hemorrhage occurred most commonly in the parietal region. Mortality rate was 8.6%. Size of hematoma (larger than 4 cm) on CT and altered consciousness on admission correlated with poor outcome.

Biological significance of iron-related magnetic resonance imaging changes in the brain.

Iron, an essential element for basic cellular metabolism, regularly accumulates in certain brain areas in normal subjects and in patients with certain diseases. Magnetic resonance imaging can depict iron deposition, offering a singular opportunity to correlate the regional iron content with the functional status of the human brain in vivo. We studied the relationship between age and the iron-related signal loss on T2-weighted images in basal ganglia, and observed a strongly significant signal decrease in the globus pallidus at the age of brain development (first two decades of life), but we found no such decrease in later years. Moreover, in healthy adults, subject-to-subject variability was relevant in changes due to iron deposition in magnetic resonance imaging. We found increased signal loss to be associated with poor performance on motor and specific cognitive tasks, suggesting that these image changes can provide functional information with respect to the brain in normal subjects.