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.

Blood pressure is not associated with haematoma enlargement in acute intracerebral haemorrhage.

BACKGROUND AND PURPOSE: We performed an observational study that compared baseline and subsequent blood pressure (BP) measurements and its association with haematoma enlargement (HE) in patients with intracerebral haemorrhage (ICH). METHODS: We prospectively studied consecutive patients with supratentorial spontaneous ICH within the first 6 h after the onset of symptoms. HE was defined as an increase >or=33% in the volume of haematoma on the CT obtained 24-48 h after the onset of symptoms as compared with the CT at admission. We recorded systolic BP (SBP), diastolic BP (DBP) and mean BP (MBP) at admission and at 6, 12, 18 and 24 h after onset; the maximum SBP, DBP and MBP during the study period; the maximum SBP and DBP within intervals; the mean of all BP readings; administration of antihypertensive agents. RESULTS: We studied 60 patients whose mean age was 72.1 +/- 11.3 years. HE was observed in 27 (45%) patients. No statistically significant differences were observed in any of the analyses that compared BP parameters between the HE and non-HE groups (two-way anova). CONCLUSIONS: In an exploratory analysis, we did not find an association between BP and HE within the first 24 h after an acute ICH.

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.

Leuko-araiosis on magnetic resonance imaging and speed of mental processing.

The clinical significance of white matter abnormalities seen in brain imaging studies, termed leuko-araiosis (LA), still remains uncertain. Leuko-araiosis has been associated with a global decline in cognitive performance, although little is known about the cognitive functions that LA may account for. We present the correlates between LA severity on magnetic resonance imaging and mental deterioration in a selected sample of 41 elderly patients with vascular risk factors. We found that LA was related to performance on tasks measuring the speed of information processing and, in particular, on those that involve complex processes. This impairment can be important in producing reduction in daily living activities as it is in the support to the relationship found with some commonly used behavioral rating scales. Leuko-araiosis is also related to the presence of some primitive reflexes, suggesting that their disinhibition may be due to diffuse corticofugal fibers damage.

Lesions in the left arcuate fasciculus region and depressive symptoms in multiple sclerosis.

Depression is a common mood disturbance in multiple sclerosis (MS) patients. Epidemiologic data suggest a causative relationship between depressive symptoms and cerebral demyelination, although a specific lesion site responsible for depressed mood has not been identified. Given that depression in neurologic disease is closely related to frontal and temporal lobe damage, we focused our study on investigating the extent to which lesions in the white matter connecting both cerebral lobes may account for depressive symptoms in MS. Forty-five patients were assessed using the Beck Depression Inventory and an MRI protocol conceived to quantify lesions separately in the basal, medial, and lateral frontotemporal white matter. The presence of lesions in the left suprainsular white matter, the region that mainly includes the arcuate fasciculus, was specifically associated with depressive symptoms, accounting for a significant 17% of the depression score variance. Although a multifactorial origin is suspected for depression in MS, this finding gives support to the existence of a direct negative effect of demyelination on mood.

Motion of the cerebellar tonsils in Chiari type I malformation studied by cine phase-contrast MRI.

We studied the effects on CSF dynamics at the foramen magnum and the clinical significance of the abnormal tonsillar motion in 14 patients with Chiari type I malformation and 14 control subjects using cine phase-contrast MRI. Dynamic MRI consisted of axial and sagittal cine phase-contrast sequences. CSF and tonsillar motion were qualitatively and quantitatively evaluated, and the subarachnoid space at the foramen magnum measured. In Chiari patients, cine phase-contrast MRI detected the abnormal pulsatile motion of the cerebellar tonsils, which produced a selective obstruction of CSF flow from the cranial cavity to the spine. The amplitude of the tonsillar pulsation and the severity of the arachnoid space reduction were associated with the symptom of cough-strain headache, but not with the presence of syringomyelia. The finding of abnormal valve dynamics of the cerebellar hernia revealed by cine phase-contrast MRI conforms to the pathophysiologic mechanisms suggested in pressure register studies and opens a new possibility in the presurgical assessment of Chiari patients with exertional symptoms.

Neurospectroscopic alterations and globus pallidus hyperintensity as related magnetic resonance markers of reversible hepatic encephalopathy.

In patients with chronic hepatic encephalopathy, proton magnetic resonance spectroscopy can be used to detect specific metabolic abnormalities in the brain; MRI shows a hyperintense globus pallidus on T1-weighted sequences. We investigated the relationship between these two MR findings in a series of 25 patients with the use of quantitative data and a multiple regression analysis model. The cerebral increase in glutamine compounds and the decrease in myoinositol and choline correlated separately with globus pallidus hyperintensity, and each was complementary in accounting for this imaging finding. Such as association suggests that spectroscopic and imaging alterations are two different expressions of the reversible events that occur in the brain of patients with hepatic encephalopathy in that both disappear after liver transplantation. Globus pallidus hyperintensity seems to be a global indicator of the cerebral metabolic disorder, and the spectroscopic pattern denotes the specific metabolic alterations.

Left-ear extinction in patients with MRI periventricular lesions.

A dichotic listening test was administered to 22 elderly vascular patients with periventricular white matter changes on magnetic resonance imaging. We found four patients with a moderate-to-severe extent of these changes who showed a pattern of left-ear extinction. These findings suggest that periventricular lesions in patients with vascular risk factors may be associated with a functional disconnection of the interhemispheric auditory pathways.

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.

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.

Beck Depression Inventory factors related to demyelinating lesions of the left arcuate fasciculus region.

This study was conducted to further establish the significance of the previously reported association between depressive symptoms and demyelinating lesions in the region of the left arcuate fasciculus in multiple sclerosis patients. The Beck Depression Inventory (BDI) was broken down into its main symptom categories on the basis of well-established factor analyses from the literature, and the correlation pattern between the resulting BDI subscores and lesion measurements was analyzed. We found that lesions of the left arcuate fasciculus region were selectively associated with BDI items expressing patients' Affective Symptoms and Somatic Complaints. Specifically, lesion measurements from this brain location accounted for 26% of symptom score variance of the BDI part that includes only these two factors. Performance Difficulties and Cognitive Distortions were not consistently associated with the lesion measurement. Performance Difficulties, however, showed a high correlation with the neurologic deficit detected in the physical examination. These results show that lesions in the left arcuate fasciculus region are associated with the core of the depressive syndrome rather than marginal symptoms and, thus, further suggest that this left suprainsular brain region involves white matter tracts relevant to mood regulation.

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.

[Hospital mortality in subarachnoid hemorrhage. Experience of the "Barcelona Registry of Cerebrovascular Diseases"]. / Mortalidad hospitalaria en la hemorragia subaracnoidea. Experiencia del "Registro Barcelona de Enfermedades Cerebrovasculares".

OBJECTIVES: To determine clinical predictors of in-hospital mortality in patients with non-traumatic subarachnoid hemorrhage. PATIENTS AND METHODS: Data de 184 patients with subarachnoid hemorrhage were obtained from consecutive stroke included in the prospective "Barcelona Stroke Registry". Demographic, anamnestic, clinical, neuroimaging and outcome variables in the subgroup of patients who died were compared with those in the surviving subgroup. The independent predictive value of each variable on the development of death was assessed with a logistic regression analysis. Three predictive models were constructed. A first model was based on demographic and clinical variables (total 10 variables). A second model was based on demographic, clinical and neuroimaging variables (total 17). A third model was based on demographic, clinical, neuroimaging and outcome variables (total 21). RESULTS: In-hospital death was observed in 44 patients (24%). Transient neurological deficit (OR = 13.92; 95% CI: 1.01-191.95), progressive deficit (OR = 4.21; 95% IC: 1.28-13.86), limb weakness (OR = 3.24; 95% IC: 1.49-7.08) and age (OR = 1.05; 95% CI: 1.02-1.09) appeared to be independent prognostic factors of in-hospital mortality in the first predictive model. In addition to these variables, intraventricular hemorrhage (OR = 5.51; 95% CI: 1.94-16.04) was selected in the second predictive model. Transient neurological deficit (OR = 41.2; 95% CI: 1.61-1056.2), neurological complications (OR = 11.04; CI del 95%: 3.85-31.74), carotid aneurysm (OR = 6.61; 95% CI: 1.23-35.43), intraventricular hemorrhage (OR = 5.51; 95% CI: 1.65-18.4), progressive deficit (OR = 5.35; 95% CI: 1.11-25.90) and hemispheric intracerebral hemorrhage (OR = 4.32; 95% CI: 1.35-13.90), appeared to be independent prognostic factors of in-hospital mortality in the third model. CONCLUSIONS: Clinical features easily obtained at the patient's bedside in addition to neuroimaging data easily obtained in routine neuroimaging studies help clinicians to predict in-hospital mortality in patients with subarachnoid hemorrhage. Transient neurological deficit prior to definitive subarachnoid hemorrhage was the main clinical predictor of in-hospital mortality.

[Affective disorders in subcortical ischemic cerebrovascular pathology. Prospective clinical study of 43 patients]. / Trastornos afectivos en la patología vascular cerebral isquémica subcortical. Estudio clínico prospectivo en 43 pacientes.

To evaluate the prevalence and clinical features of affective disorders (AD) associated with subcortical ischemic cerebrovascular disease (mainly localized in the deep areas depending from the anterior, middle and posterior cerebral arteries), a prospective clinical study was carried out in 43 patients with lacunar infarctions (LI). It was found that AD were uncommon in these patients (25%) (1/43). The prevalences of depression in the major lacunar syndromes of the series were the following, from more to less common: pure motor hemiparesis (35%) (7/20); dysarthria-clumsy hand (25%) (1/4); pure sensorial syndrome (16.5%) (2/12), and atypical syndromes (no patient). The capsular topography was associated with AD in 32% (7/22); this association was more uncommon in thalamic (15%) (2/13) or pontine (25%) (1/4) areas. AD had a significant predominance (p = 0.027) in the lesions involving the dominant cerebral hemisphere (63.5%), mainly when these resulted in clinically mild or moderate/severe disability. Past history of AD was also significantly associated with depression (p = 0.0018). Our results show that affective disorders in lacunar infarctions are usually associated with: 1) the type of clinical syndrome; 2) the topography of the lesion; 3) the involved cerebral hemisphere; 4) the associate neurological focality, and 5) the previous occurrence of affective disorders.

[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.

[Study of cerebral activity with functional magnetic resonance]. / Estudio de la actividad cerebral con resonancia magnética funcional.

BACKGROUND: Functional magnetic resonance is a new imaging method which allows the incruent observation of human cerebral activity. The authors describe their method of functional magnetic resonance and the results of cerebral activation. METHODS: A total of 364 functional sequences were performed in 52 volunteers with a magnetic resonance system of 1.5 Tesla. A gradient echo sequence with a long echo time sensitive to the changes in oxygenation of venous blood was used. Different cortical areas were stimulated by visual, motor and language maneuvers and by complex mental operations. RESULTS: Different cerebral areas representative of different levels of cerebral functional complexity were consistently activated and reproduced. Experiments of activation of primary cerebral cortex (visual and motor), premotor regions, specific area of language and areas of cortical association for cognitive operations are described. CONCLUSIONS: Functional magnetic resonance imaging is a sensitive method for the observation of cerebral activity and provides functional images with great spatial and temporal resolution. This may be useful in both clinical and basic investigation.

[Cerebral single-photon emission-computed tomography. A semiquantitative analysis of vascular areas in patients with cerebrovascular pathology]. / Tomografía cerebral por emisión de fotón único. Análisis semicuantitativo de territorios vasculares en pacientes con patología vascular cerebral.

BACKGROUND: Brain SPECT perfusion studies in patients with cerebral stroke may be useful to evaluate distant perfusion abnormalities. METHODS: 99mTc-HMPAO brain SPECT studies were performed in 17 patients with ischemic lesions in the basal ganglia and/or internal capsule demonstrated by NMR. Regions of interest were adjusted in representative transverse slices to the vascular territories of the anterior, middle, posterior and communicating cerebral arteries. RESULTS: Patients with ischemic lesions in the right basal ganglia showed increased cerebral perfusion in the left middle artery territory (0.95 +/- 0.13 versus 0.80 +/- 0.06; p = 0.0365). Patients with ischemic lesions in the left basal ganglia showed increased perfusion in the right anterior artery territory (0.93 +/- 0.09 versus 0.82 +/- 0.09; p = 0.0464), in the left anterior artery territory (0.93 +/- 0.09 versus 0.83 +/- 0.14; p = 0.0464), in the left middle artery territory (0.92 +/- 0.09 versus 0.78 +/- 0.05; p = 0.0079) and in the left posterior artery territory (1.05 +/- 0.14 versus 0.90 +/- 0.09; p = 0.036). Patients with ischemic lesions in the right internal capsule showed increased perfusion in the right posterior artery territory (0.95 +/- 0.11 versus 1.10 +/- 0.18; p = 0.0431). CONCLUSIONS: These results show the presence of delayed luxury perfusion phenomena in regions distant from the ischemic site.

[Systemic lupus erythematosus induced by anticonvulsivant drug (author's transl)]. / Lupus eritematoso sistémico inducido por anticonvulsivante.

A 20-year-old patient with previous history since 9 years of age of epileptic crises, was followed since then by anticonvulsivant therapy. Eight months before her admittance to the hospital ethosuximide was added to the anticonvulsivant treatment with good results. The development of fever, pain in the joints, and pleuropericarditis decided her admittance, being the clinical evaluation analytically and immunologically compatible with a systemic lupus erythematosus. The discontinuance of the anticonvulsivant medication determined at the end of the 3rd week the clinical and analytical recovery of the patient. The immunological study was normal after 3 months. The addition of other anticonvulsivant drugs, without having modified the normal condition of the patient, establishes a cause-effect relationship after the administration of ethosuximide. The infrequency of this observation is commented on, and the present knowledge of the possible mechanisms implicated in the drug-induction of a systemic lupus erythematosus is discussed.

[Transitory ischemic accidents. A retrospective study of 150 cases of ischemic infarction in the region of the median cerebral artery (author's transl)]. / Los accidentes isquémicos transitorios. Estudio retrospectivo de 150 casos de infarto isquémico en el territorio de la arteria cerebral media.

Transitory ischemic accident is an episode that commences abruptly with subjective or objective neurological disturbances, persists for a brief time, and returns to normal within 24 hours of onset with complete recuperation of neurological function. Using this as a basic definition, the authors specify the characteristic symptoms of different types of transitory ischemic accident and review in retrospect 150 cases of ischemic infarction in the region of the median cerebral artery. Thirty-eight percent of the patients suffered transitory ischemic accidents prior to stroke. The symptoms included the following, in order of frequency: motor nerve disorder, sensory nerve disorders, speech disturbances, and visual defects. Most of these patients presented a definite stroke within less than one month's time following the last transitory ischemic accident. The similarity of the symptoms in both conditions was noticeable. The authors study the angiographic images, the pharmacologic and toxic previous histories, and other associated diseases in each patient. They point out, lastly, that transitory ischemic accident should be considered the first manifestation of a cerebrovascular disease and not just as an isolate, reversible episode of little importance.

[Cysticercosis and angiomatosis. Clinicopathological study of one case (author's transl)]. / Cisticercosis y angiomatosis. Estudio clinicopatológico de un caso.

This is a discussion of the clinical condition of a 49-year-old patient who had been presenting intermittent episodes of intracranial hypertension since the age of 9, at which time she suddenly began a serious psychic deterioration which impaired her normal intellectual development. A new episode of intracranial hypertension led to the emergency admittance to the medical center, and was the cause of death. The cerebral post mortem study showed a large ventricular dilatation and the existence of a translucent cysticercus of a lobular shape which was adhered by a fine filament ot the internal wall of the right ventricle, very near to Monro's foramen; the possibility, therefore, was attributed to it of having had the effect of a valve mechanism which might have been causing the crises and the intracranial hypertension. At the same time, it was also observed that there existed an angiomatosis at the level of the temporal lobe, which does not seem to be related to the process, especially because of its small area and the integrity of the blood vessels.