Cerebral small vessel disease, systemic vascular characteristics and potential therapeutic targets.

INTRODUCTION: Cerebral small vessel disease (SVD) is prevalent in the elderly population and is associated with increased risk of dementia, stroke and disability. Currently there are no clear targets or strategies for the treatment of cerebral SVD. We set out to identify modifiable vascular treatment targets. PATIENTS AND METHODS: 112 participants with and without a history of CVD underwent macrovascular, microvascular and endothelial function tests and an MRI head scan. RESULTS: Increased carotid intima media thickness and carotid-femoral pulse wave velocity were associated with cerebral WMH (ß=1·1 p=0·001 and ß=1·66, p<0·0001 respectively). Adjusted cerebral resistance index (p=0·03) and brachial flow mediated dilation time to peak (p=0·001) were associated with the severity of cerebral WMH independent of age and sex. Post occlusive reactive hyperaemia time as a measure of microvascular reactivity was associated with WMH after adjustment for age and sex (p=0·03). Ankle Brachial Pressure Index and urinary albumin excretion rate predicted the severity of cerebral WMH (p=0·02 and 0·01 respectively). Age and hypertension were the most important risk factors for WMH severity (p< 0·0001). DISCUSSION: In addition to hypertension, microalbuminuria, arterial stiffness, vascular reactivity and cerebrovascular resistance could be potential treatment targets to halt the development or progression of cerebral SVD.

White matter hyperintensities: initial assessments / Hiperintensidades da substância branca: avaliações iniciais

The white matter hyperintensities (WMH, leucoaraiosis) represent the most common kind of ischemic vascular lesion of the white matter due to small vessel diseases, and occurs frequently in the elderly. Consequent to the neuroimaging identification arouse the need for their assessment. The group of Fazekas proposed a systematized semi-quantitative visual scale to score such lesions where two parameters were considered, extent and localization. The original scale was further modified, to a simplified version. Although other more complex scales have appeared, researchers remarked that the relatively simple Fazekas scale, in comparison to the complex ones and to volumetric measures, appeared to be sufficient when analyzing relationships between clinical parameters and WMH load in a clinical setting.

As hiperintensidades da substância branca (HSB, leucoaraiose) representam o tipo de lesão isquêmica mais comum da substância branca decorrente de doenças de pequenos vasos e ocorre frequentemente em idosos. Consequente à identificação por neuroimagem surgiu a necessidade de sua avaliação. O grupo de Fazekas propos uma escala visual semiquantitativa sistematizada para pontuar tais lesões, onde foram considerados dois parâmetros, extensão e localização. A escala original foi modificada para constituir uma versão mais simplificada. Embora outras escalas mais complexas tenham aparecido, pesquisadores comentaram que a relativamente simples escala de Fazekas, em comparação às mais complexas e a método volumétrico, mostrou-se suficiente quando é analisada a relação entre parâmetros clínicos e a carga de HSB em um cenário clínico.

Microalbuminuria as a potential biomarker for Parkinson's disease severity: A hypothesis.

Parkinson's disease (PD) is the second most common neurodegenerative condition characterized by motor and non-motor symptoms causing a great burden in patients' quality of life. PD has been associated with various metabolic factors such as diabetes, hypertension, and more recently chronic kidney disease where proteinuria has been associated with an increased risk. The presence of small amounts of albumin in urine, microalbuminuria, is a common biomarker for endothelial damage and a predictive factor for not only cardiovascular but also neurological dysfunction. Multiple studies have assessed potential biomarkers for PD progression with great heterogeneity, we hypothesize the use of microalbuminuria as a potential marker that correlates with PD severity and might represent a feasible and simple method of evaluating PD patients in clinical practice. Evidence supporting the present hypothesis comes from oxidative stress, insulin resistance, and endothelial dysfunction. Oxidative stress is a key element in PD pathogenesis; studies have shown lower antioxidant capacity as PD progresses. On the other side, insulin signaling plays an important role in neuronal growth and survival, with its resistance being associated with PD. Microalbuminuria has been associated with both processes; increased levels of oxidative stress markers and decreased insulin sensitivity, hence its screening in PD might reflect these common pathological mechanisms. Moreover, the low vitamin D levels observed in PD patients, which are correlated with endothelial dysfunction and disease severity, might contribute to microalbuminuria induction. More evidence on this vascular approach comes from white matter lesions (WML), observed in brain imaging, which have been significantly associated with motor and non-motor function in PD patients and are independently associated with microalbuminuria. In this manner, an oxidant and insulin resistant environment, along with low vitamin D levels in PD patients, which are associated with microalbuminuria, might contribute altogether to WML. As the latter are correlated with motor and non-motor function, microalbuminuria might thus give insight on PD status. Prospective cohort studies with an adequate sample size, follow-up, and a thorough battery of clinical tests for PD are needed to confirm this hypothesis.

Arteriopatía cerebral autosómica dominante con infartos subcorticales yleucoencefalopatía / Autosomal dominant cerebral arteriopathy with subcortical infarctions and leukoencephalopathy

Objetivo: Describir la obtención del diagnóstico de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía, así como el tratamiento dado y la evolución de un paciente.Caso clínico: Paciente femenina de 44 años, con antecedentes de migraña, con aura típica desde los 25 años. Tenía antecedentes familiares de migraña, infartos cerebrales, muerte y discapacidad de origen neurológico en adultos jóvenes. Acudió con un cuadro clínico de encefalopatía aguda, que comenzó con cefalea migrañosa acompañada de vómitos, fotofobia, escotomas y, posteriormente, fiebre yalucinaciones. La imagen de resonancia magnética de cráneo mostró infartos lacunares e hiperintensidades en T2 en la sustancia blanca del polo temporal izquierdo. El electroencefalogramamostró actividad de base lenta. Se diagnosticó una arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía a través de la clínica, signos característicos en la neuroimagen, y la biopsia de piel. Se le indicó tratamiento con aspirina y acetazolamida. La paciente ha tenido una evolución favorable.Conclusiones: El análisis de las características clínicas, los hallazgos de neuroimagen y el examen pormicroscopia electrónica de la biopsia de piel permitieron el diagnóstico en la paciente de una arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía. Se le indicó tratamiento farmacológico con el que la paciente ha tenido una evolución favorable(AU)

ABSTRACTIntroduction: CADASIL (Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an autosomal dominant neurovascular disorder that causes ischemic subcortical stroke, migraine with aura, depression, apathy, and dementia. It have a variable prevalence(at least 2-10.7 per 100,000 adults) and is the most common cause of inherited stroke and vascular dementia in adults.Clinical case: Female patient aged 44 with a history of migraine with aura since age 25. Also, family history of migraine, stroke, death and disability in youngsters. She arrives with clinical picture of acute encephalopathy that begins with a migraine headache accompanied by vomiting, photophobia, scotoma and later fever and hallucinations. Brain MRI shows abnormalities such as several lacunar infarcts and T2 hyperintensities involving the white matter of the left anterior temporal pole. The EEG shows slow background. Diagnosis was confirmed with detection of eosinophilic inclusions in smooth muscle cell of dermic capillary of skin biopsy (osmophilic in transmission electronic microscopy).Conclusions: The patient showed is the first confirmed case in Cuba with CADASIL. Unfortunately, because of similarities in clinical presentation and neuroimaging, this disorder is often misdiagnosed as multiple sclerosis and treated with immunomodulatory medications that confer risk without benefit(AU)

[Small vessel cerebrovascular disease]. / Enfermedad cerebrovascular de pequeño vaso.

Small vessel vascular disease is a spectrum of different conditions that includes lacunar infarction, alteration of deep white matter, or microbleeds. Hypertension is the main risk factor, although the atherothrombotic lesion may be present, particularly in large-sized lacunar infarctions along with other vascular risk factors. MRI findings are characteristic and the lesions authentic biomarkers that allow differentiating the value of risk factors and defining their prognostic value.

Lesiones en la sustancia blanca en el paciente anciano: Utilización de la terminología adecuada / White matter lesions in an elderly patient: Using the proper terminology

En Neurorradiología los cambios de la sustancia blanca periventricular o subcortical en pacientes ancianos son descritos generalmente con leucoaraiosis, fenómenos hipóxico-isquémicos crónicos, leucoencefalopatía microangiopática o simplemente con alteraciones en la densidad o intensidad según el método elegido. Sin embargo, ¿es correcto el empleo de estas denominaciones?, ¿funcionan como sinónimos?, ¿tienen un mismo mecanismo de producción? Las lesiones que afectan a la sustancia blanca se aprecian hipodensas en tomografía computada, hiperintensas en las secuencias ponderadas en T2 o FLAIR e hipointensas en la resonancia magnética en ponderación T1. Describimos las distintas entidades que pueden afectar selectivamente la sustancia blanca en el paciente anciano y sus probables mecanismos de acción, para establecer una correcta denominación y realizar los diagnósticos diferenciales.

In Neuroradiology the changes in the deep or sub-cortical white matter in elderly people are generally described as leukoaraiosis, chronic hypoxic-ischaemic processes, microangiopathic leucoencephalopathy, or they are simply mentioned as density or intensity changes according to the selected imaging method. However, are these terms correct?, Are they synonyms?, Do they have the same aetiology? The lesions that affect white matter are hypodense in computed tomography, hyperintense in T2-weighted or FLAIR, or hypointense in T1 images in magnetic resonance. A description is presented on the different conditions that can selectively affect the white matter in the elderly patient and their probable mechanisms of action in order to establish a correct nomenclature, as well as make differential diagnoses.

Impact of leukoaraiosis on parenchymal hemorrhage in elderly patients treated with thrombolysis.

INTRODUCTION: Severity of vascular damage of white matter may predict hemorrhagic transformation (HT). We assess the relationship between leukoaraiosis (LA) severity and the type of hemorrhagic transformation in elderly patients treated with thrombolysis. METHODS: We retrospectively analyzed the clinical data and pretreatment magnetic resonance imaging (MRI) of 180 consecutive ischemic stroke patients aged over 75 years. LA severity was graded according to the Fazekas scale, and acute diffusion-weighted-imaging (DWI) lesion volumes were semi-automatically outlined. Predictors of hemorrhagic infarction (HI) and parenchymal hemorrhage (PH) were identified using logistic regression analysis and exact multinomial logistic analysis. RESULTS: HT occurred in 31 patients (17 %). Baseline National Institute of Health Stroke Score (NIHSS; p = 0.008), severe LA (p = 0.02), and diffusion lesion volume (p = 0.02) were predictors of HT in univariable logistic regression. Adjusted to lesion volume and baseline NIHSS score, exact multinomial logistic analysis showed that severe LA was the only independent predictor of parenchymal hemorrhage (p = 0.03). CONCLUSION: In elderly patients, LA severity better predicts parenchymal hemorrhage than infarct size.

ACE Gene in Egyptian Ischemic Stroke Patients.

BACKGROUND: Angiotensin-1-converting enzyme (ACE) is a crucial player in vascular homeostasis and in the pathogenesis of atherosclerosis and hypertension. The present study was conducted to determine whether there is an association between the ACE insertion/deletion (I/D) polymorphism and ischemic stroke in Egyptian population. Also, we analyzed the ACE gene I/D polymorphism as a risk factor for small-vessel (SV) versus large-vessel (LV) disease. METHODS: Sixty patients with ischemic stroke were included: 30 with SV disease and 30 with LV disease. In addition, a control group of 30 apparent healthy subjects were studied. Clinical assessment, computed tomography, magnetic resonance imaging brain, and genetic study using the polymerase chain reaction of ACE gene were done for all subjects. RESULTS: We found that the distribution of ACE gene polymorphism frequency was significantly different between the 3 groups. The DD genotype was far more common in stroke patients compared to controls. It was also significantly more common in each of the patient groups compared to controls but rather similar in the 2 patient groups with SV and LV diseases. CONCLUSION: We found that the ACE gene deletion/deletion genotype is common in Egyptian patients with non-cardioembolic ischemic stroke but does not appear to be specific neither to SV nor to LV disease.

The impact of leucoaraiosis on neurological function recovery in elderly patients with acute cerebral infarction: Clinical study involving 279 Chinese patients.

OBJECTIVE: To explore the link between leucoaraiosis and recovery of neurological function in elderly patients with acute cerebral infarction. METHODS: The study included elderly patients, hospitalized with acute cerebral infarction. Magnetic resonance imaging examinations were performed before or within 5 days after admission; T1-weighted, T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequence data were collected. Using the Fazekas scale, leucoaraiosis (white matter hyperintensity [WMH]) was graded as 0 (absent), 1 (mild), 2 (moderate) or 3 (severe) for all participants. RESULTS: The study included 279 patients. WMH grades of 0, 1, 2 and 3 were seen in 27 (9.67%), 90 (32.26%), 104 (37.28%) and 58 cases (20.79%) respectively. Improvement on the National Institutes of Health Stroke Scale for neurological impairment was negatively associated with WMH grade. Patients with severe leucoaraiosis at hospital admission had worse neurological functional recovery and a higher rate of self-care incapability compared with those with mild or no leucoaraiosis. CONCLUSIONS: The results suggest that severe leucoaraiosis in elderly patients with acute cerebral infarction is associated with poor prognosis and poor recovery of neurological function.

Leucoaraiosis. Aspectos fisiopatológicos y diagnóstico por imagen / Leukoaraiosis. Physiopathologic aspects and Ddiagnostic imaging

Introducción: El concepto de Leucoaraiosis, entidad relacionada con la enfermedad de pequeños vasos, hipertensión arterial y envejecimiento poblacional, surge a raíz de la introducción de nuevas modalidades de diagnóstico por imagen como la Tomografía Computarizada y la imagen por Resonancia Magnética. Objetivos: Describir los aspectos fisiopatológicos más importantes de la Leucoaraiosis y la importancia de las técnicas de imagen como la imagen por Resonancia Magnética en su diagnóstico. Material y Métodos: Se realizó una búsqueda bibliográfica automatizada en bases de datos MEDLINE (motor de búsqueda PubMed) a través de las palabras clave: Leucoaraiosis, enfermedad cerebral de pequeños vasos e imagen por Resonancia Magnética, basándonos en la selección y análisis crítico de publicaciones preferentemente emitidas en los últimos 5 años. Desarrollo: La Leucoaraiosis está caracterizada por cambios de la sustancia blanca. Múltiples han sido las hipótesis que sustentan la fisiopatología de la Leucoaraiosis: causa isquémica (la más defendida), disfunción endotelial, ruptura de la barrera hematoencefálica o combinación de ellas. No obstante, los cambios fisiopatológicos asociados a la Leucoaraiosis permanecen inciertos. Por otro lado, técnicas de imagen como la Resonancia Magnética logran profundizar en los diferentes hallazgos que caracterizan a la condición. Conclusiones: El envejecimiento poblacional asociado a la alta prevalencia de Leucoaraiosis unido a la mayor disponibilidad de técnicas de imagen neurodiagnóstica condiciona un mejor entendimiento de sus aspectos fisiopatológicos, los cuales aún son controvertidos.

Introduction: Leukoaraiosis is related to the small cerebral vessel disease and mainly associated with the aging of population and the high prevalence of hypertension. Computed tomography and magnetic resonance imaging pave the way to its apparition. Objectives: To describe the most importance physiopathologic aspects of leukoaraiosis and the relevance of imaging techniques as magnetic resonance imaging to diagnose it. Material and Methods: It was made a review through automatized data base MEDLINE (PubMed as search engine) using leukoaraiosis, cerebral small vessel disease and magnetic resonance imaging as descriptors. The review was based on the selection and critical analysis of publications, most appearing in the last five years. Development: Leukoaraiosis is characterized by changes in the periventricular white matter. The associated physiopathologic changes remain doubtful and not completely explained being the hypothesis centred in the chronic ischemia, bloodbrain barrier breakdown and endothelial damage or in their combination. On the other hand, new neuroradiologic techniques as magnetic resonance imaging appear to allow to deeply analyze the different imaging findings that support the diagnosis of the leukoaraiosis. Conclusions: Aging associated to high prevalence of leukoaraiosis as well as the availability of improved brain imaging techniques permit a better understanding of its physiopathologic aspects which are even controversial.

Leucoaraiosis. Aspectos fisiopatológicos y diagnóstico por imagen / Leukoaraiosis. Physiopathologic aspects and diagnostic imaging

Introducción: el concepto de Leucoaraiosis, entidad relacionada con la enfermedad de pequeños vasos, hipertensión arterial y envejecimiento poblacional, surge a raíz de la introducción de nuevas modalidades de diagnóstico por imagen como la Tomografía Computarizada y la imagen por Resonancia Magnética. Objetivos: describir los aspectos fisiopatológicos más importantes de la Leucoaraiosis y la importancia de las técnicas de imagen como la imagen por Resonancia Magnética en su diagnóstico. Material y Métodos: se realizó una búsqueda bibliográfica automatizada en bases de datos MEDLINE (motor de búsqueda PubMed) a través de las palabras clave: Leucoaraiosis, enfermedad cerebral de pequeños vasos e imagen por Resonancia Magnética, basándonos en la selección y análisis crítico de publicaciones preferentemente emitidas en los últimos 5 años. Desarrollo: la Leucoaraiosis está caracterizada por cambios de la sustancia blanca. Múltiples han sido las hipótesis que sustentan la fisiopatología de la Leucoaraiosis: causa isquémica (la más defendida), disfunción endotelial, ruptura de la barrera hematoencefálica o combinación de ellas. No obstante, los cambios fisiopatológicos asociados a la Leucoaraiosis permanecen inciertos. Por otro lado, técnicas de imagen como la Resonancia Magnética logran profundizar en los diferentes hallazgos que caracterizan a la condición. Conclusiones: el envejecimiento poblacional asociado a la alta prevalencia de Leucoaraiosis unido a la mayor disponibilidad de técnicas de imagen neurodiagnóstica condiciona un mejor entendimiento de sus aspectos fisiopatológicos, los cuales aún son controvertidos(AU)

Introduction: Leukoaraiosis is related to the small cerebral vessel disease and mainly associated with the aging of population and the high prevalence of hypertension. Computed tomography and magnetic resonance imaging pave the way to its apparition. Objectives: To describe the most importance physiopathologic aspects of leukoaraiosis and the relevance of imaging techniques as magnetic resonance imaging to diagnose it. Material and Methods: It was made a review through automatized data base MEDLINE (PubMed as search engine) using leukoaraiosis, cerebral small vessel disease and magnetic resonance imaging as descriptors. The review was based on the selection and critical analysis of publications, most appearing in the last five years. Development: Leukoaraiosis is characterized by changes in the periventricular white matter. The associated physiopathologic changes remain doubtful and not completely explained being the hypothesis centred in the chronic ischemia, bloodbrain barrier breakdown and endothelial damage or in their combination. On the other hand, new neuroradiologic techniques as magnetic resonance imaging appear to allow to deeply analyze the different imaging findings that support the diagnosis of the leukoaraiosis. Conclusions: Aging associated to high prevalence of leukoaraiosis as well as the availability of improved brain imaging techniques permit a better understanding of its physiopathologic aspects which are even controversial(AU)

Hipotensión nocturna y enfermedad cerebrovascular silente / Nocturnal hypotension and silent cerebrovascular disease

La introducción de técnicas para el monitoreo ambulatorio de la presión arterial ha permitido obtener información acerca de las variaciones diurnas de la presión arterial. El patrón de dipper acentuado que equivale a hipotensión nocturna pudiera tener una relación causal específica con enfermedad cerebrovascular silente y lesión de la sustancia blanca mediada por hipoperfusión cerebral. Se presentó un caso con lesiones de la sustancia blanca cerebral sin factores de riesgo vascular convencionales, en el que el monitoreo ambulatorio de la presión arterial demostró una hipertensión ligera con un patrón de dipper acentuado, una condición fisiopatológica susceptible de ser modificada. En el futuro, esta técnica, al parecer, tendrá un uso más extendido en la enfermedad cerebrovascular, especialmente en los ictus lacunares y hemodinámicos, así como en las lesiones vasculares crónicas de la sustancia blanca cerebral.

The introduction of the techniques for the ambulatory monitoring of arterial pressure has allowed to obtain information about the day variations of arterial pressure. The pattern of accentuated Dipper may have a specific causal relation to silent cerebrovascular disease and lesion of the white matter mediated by brain hypoperfusion. A case with lesions of the cerebral white matter without conventional vascular risk factors, was presented. The ambulatory monitoring of the arterial pressure showed a mild hypertension with an accentuated Dipper pattern, a physiopathological condition susceptible to be modified. In the future, it seems that this technique will have a wider use in the cerebrovascular disease, specially in the lacunar and hemodynamic ictus, as well as in the chronic vascular lesions of the cerebral white matter.