Is structural connectivity different in child and adolescent relatives of patients with bipolar disorder? A narrative review according to studies with DTI.

INTRODUCTION: Bipolar disorder (BD) has been associated with a decrease in white matter integrity. Diffusion tensor imaging (DTI) studies have enabled these changes to be elucidated with higher quality. Due to BD's high heritability, some studies have been conducted in relatives of BD patients looking at white matter integrity, and have found that structural connectivity may also be affected. This alteration has been proposed as a potential BD biomarker of vulnerability. However, there are few studies in children and adolescents. OBJECTIVE: To conduct a review of the literature on changes in white matter integrity determined by DTI in high-risk children and adolescents. RESULTS: Brain structural connectivity in the paediatric population is described in studies using DTI. Changes in the myelination process from its evolution within normal neurodevelopment to the findings in fractional anisotropy (FA) in BD patients and their high-risk relatives are also described. CONCLUSIONS: Studies show that both BD patients and their at-risk relatives present a decrease in FA in specific brain regions. Studies in children and adolescents with a high risk of BD, indicate a reduced FA in axonal tracts involved in emotional and cognitive functions. Decreased FA can be considered as a vulnerability biomarker for BD.

¿Es diferente la conectividad estructural en niños y adolescentes familiares de pacientes con trastorno bipolar? Una revisión narrativa según estudios con DTI

Introducción: El trastorno afectivo bipolar (TAB) se ha asociado con una disminución de la integridad de la sustancia blanca. Los estudios con imágenes con tensor de difusión (DTI) han permitido elucidar con una mayor calidad estos cambios. Debido a la gran heredabilidad del TAB, se han realizado estudios en familiares de pacientes con TAB acerca de la integridad de la sustancia blanca, y se ha encontrado que la conectividad estructural también puede estar afectada. Dicha alteración se ha propuesto como un potencial biomarcador de vulnerabilidad a este trastorno. Sin embargo, los estudios en niños y adolescentes son pocos. Objetivo: Revisar la literatura sobre los cambios en la integridad de la sustancia blanca determinados mediante DTI en niños y adolescentes con alto riesgo. Resultados: Se describe la conectividad estructural cerebral en la población pediátrica en estudios que utilizaron DTI. Se describen los cambios en el proceso de mielinización desde su evolución dentro del neurodesarrollo normal hasta los hallazgos en la anisotropía fraccional (AF) en pacientes con TAB y los familiares en alto riesgo. Conclusiones: Los estudios demuestran que tanto pacientes con TAB como sus familiares en riesgo presentan disminución de la AF en regiones cerebrales específicas. Los estudios en niños y adolescentes con riesgo familiar de TAB señalan una AF reducida en tractos axonales implicados en funciones emocionales y cognitivas. La disminución de la AF puede considerarse como un biomarcador de vulnerabilidad al TAB.

Introduction: Bipolar disorder (BD) has been associated with a decrease in white matter integrity. Diffusion tensor imaging (DTI) studies have enabled these changes to be elucidated with higher quality. Due to BD's high heritability, some studies have been conducted in relatives of BD patients looking at white matter integrity, and have found that structural connectivity may also be affected. This alteration has been proposed as a potential BD biomarker of vulnerability. However, there are few studies in children and adolescents. Objective: To conduct a review of the literature on changes in white matter integrity determined by DTI in high-risk children and adolescents. Results: Brain structural connectivity in the paediatric population is described in studies using DTI. Changes in the myelination process from its evolution within normal neurodevelopment to the findings in fractional anisotropy (FA) in BD patients and their high-risk relatives are also described. Conclusions: Studies show that both BD patients and their at-risk relatives present a decrease in FA in specific brain regions. Studies in children and adolescents with a high risk of BD, indicate a reduced FA in axonal tracts involved in emotional and cognitive functions. Decreased FA can be considered as a vulnerability biomarker for BD.

Characteristics of white matter structural connectivity in healthy adults with childhood maltreatment.

Background: Childhood maltreatment (CM) is a common psychological stressor associated with multiple mental disorders. While CM is associated with vulnerability to depression and anxiety, little is known about the specific mechanism underlying this relationship.Objective: This study aimed to investigate the white matter (WM) of healthy adults with CM and their relationships with depression and anxiety to provide biological evidence for the development of mental disorders in subjects with childhood trauma.Methods: The CM group included 40 healthy adults with CM. The non-CM group included 40 healthy adults without CM. Diffusion tensor imaging (DTI) data were collected, and tract-based spatial statistics (TBSS) were applied to the whole brain to assess WM differences between the two groups; post-hoc fibre tractography was used to characterise the developmental differences; and mediation analysis was used to assess the relationships among the Child Trauma Questionnaire (CTQ) results, DTI indices, and depression and anxiety scores.Results: Relative to the non-CM group, the CM group revealed significantly lower fractional anisotropy (FA) in the right posterior corona radiata (PCR-R), right anterior corona radiata (ACR-R), left super corona radiata (SCR-L), anterior thalamic radiation (ATR), and right posterior limb of the internal capsule (PLIC-R). Additionally, shorter fibre bundles passed through the PCR-R, ACR-R, and ATR in the CM group compared with the non-CM group. Besides, the length of the ACR-R mediated the relationship between CM and trait anxiety.Conclusions: The alteration of white matter microstructure associated with childhood trauma in healthy adults may reflect biomarkers of childhood trauma. Besides, an alteration of WM microstructure in healthy adults with CM mediates the association between CM and trait anxiety, which may represent the vulnerability to developing mental disorders after childhood trauma experiences.

In this paper, we found specific alterations associated with CM in healthy adults, which may mediate the relationship between childhood trauma and trait anxiety in later life.

Neuroimaging in small vessel disease / Neuroimagen en la enfermedad cerebral de vaso pequeño

The objective of this article is to review the literature on neuroimaging in small vessel disease. A review was carried out through the Pubmed search engine, without a filter of years, using terms such as: cerebral small vessel disease; white matter hyperintensity; brain microbleed; WBC. Small vessel disease is the most common vascular pathology. Its basis is in the affectation of the small cerebral vessels that eventually causes an alteration in the blood–brain barrier. Its clinical implication is highly relevant. Using magnetic resonance imaging, different expressions of the disease have been observed, such as white matter hyperintensities, microbleeds or lacunar infarcts. Other more recent techniques, such as brain blood flow measurements, are helping to increase understanding of the pathophysiology of this disease. (AU)

El objetivo de este artículo es realizar una revisión bibliográfica sobre la neuroimagen en la enfermedad de vaso pequeño. Se ha realizado una revisión a través del buscador PubMed, sin filtro de años, usando términos como: cerebral small vessel disease; white matter hyperintensity; cerebral microbleed; CMB. La enfermedad de vaso pequeño es la patología vascular más común. Su base está en la afectación de los pequeños vasos cerebrales que causa a la larga una alteración en la barrera hematoencefálica. Su implicación clínica, dada la prevalencia que presenta, es muy relevante. Mediante la resonancia magnética, se han podido objetivar diferentes expresiones de la enfermedad tales como las hiperintensidades de sustancia blanca, los microsangrados o los infartos lacunares. Otras técnicas más recientes como las mediciones del flujo cerebral, están ayudando para comprender mejor la fisiopatología de esta enfermedad. (AU)

Neuroimaging in small vessel disease.

The objective of this article is to review the literature on neuroimaging in small vessel disease. A review was carried out through the Pubmed search engine, without a filter of years, using terms such as: cerebral small vessel disease; white matter hyperintensity; brain microbleed; WBC. Small vessel disease is the most common vascular pathology. Its basis is in the affectation of the small cerebral vessels that eventually causes an alteration in the blood-brain barrier. Its clinical implication is highly relevant. Using magnetic resonance imaging, different expressions of the disease have been observed, such as white matter hyperintensities, microbleeds or lacunar infarcts. Other more recent techniques, such as brain blood flow measurements, are helping to increase understanding of the pathophysiology of this disease.

Encefalomielitis aguda diseminada asociada a infección por el SARS-CoV-2 sin afectación respiratoria / Acute disseminated encephalomyelitis associated with SARS-CoV-2 infection without respiratory compromise

Introducción: COVID-19 (coronavirus disease-2019) es la enfermedad secundaria a la infección por el coronavirus de tipo 2 o SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2), que se ha constituido como pandemia desde diciembre de 2019. Si bien la afectación más frecuente y grave es la pulmonar, las complicaciones neurológicas secundarias a la COVID-19 son cada vez más reconocidas. La encefalomielitis aguda diseminada (EMAD) es una enfermedad autoinmune poco frecuente, clásicamente secundaria a una infección viral previa o concomitante. Existen informes de EMAD asociada a la COVID-19, casi todos con afectación respiratoria asociada. Presentamos el caso de una mujer joven diagnosticada con EMAD secundaria a la infección por el SARS-CoV-2 sin afectación respiratoria. Caso clínico: Mujer de 20 años que consultó por cuadro de desorientación y alteración conductual de una semana de evolución. Destaca en la historia la presencia de anosmia y sensación febril dos semanas antes del inicio de los síntomas neurológicos. En el examen físico destacó somnolencia, desorientación, hemianopsia homónima izquierda y síndrome piramidal ipsilateral. Se realizó una resonancia magnética encefálica que mostró múltiples lesiones inflamatorias desmielinizantes bihemisféricas de la sustancia blanca sugerentes de EMAD. La reacción en cadena de la polimerasa del SARS-CoV-2 en aspirado nasofaríngeo resultó positiva. Se descartaron otras causas de lesiones inflamatorias. Recibió esteroides con excelente respuesta. Conclusión: La EMAD es una complicación extremadamente rara en pacientes con COVID-19 que debe considerarse como una causa tratable de encefalopatía y/o déficits neurológicos multifocales en pacientes con infección activa o reciente por SARS-CoV-2 con o sin manifestaciones respiratorias.(AU)

Introduction: COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to grow all over the world since december of 2019. Although the main clinical manifestation is pulmonary disease, neurological manifestations are a prominent and increasingly recognized feature of the disease. The Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune disorder, most commonly triggered by a viral infection. There are a few case reports of ADEM associated with COVID-19, almost all of them associated pulmonary disease. We report the case of a young patient with diagnosis of ADEM with SARS-CoV-2 infection without clinical respiratory symptoms. Case report: A 20-year-old woman with no relevant medical history was brought to the emergency department with a progressive confusional state lasted for 7 days. Family reported the development of smell and taste deficit since two weeks before the onset of neurological symptoms. There were no complaints of pulmonary symptoms. At admission, she was drowsy and disoriented. Left homonymous hemianopsia and an ipsilateral Babinski sign was identified. A brain magnetic resonance image was done showing multiple hyperintense bilateral, asymmetric patchy and poorly marginated lesions with gadolinium enhancement. She was SARS-CoV-2 PCR positive on nasopharyngeal swab. Intravenous high-dose glucocorticoids were administered with marked clinical improvement. Conclusion: ADEM is an extremely uncommon complication of SARS-CoV-2infection. Acute disseminated encephalomyelitis should be considered a potentially treatable cause of encephalopathy or multifocal neurological deficits in COVID-19 patients, even in the absence of respiratory symptoms.(AU)

Triphasic waves and brain atrophy in patients with acute encephalopathy / Ondas trifásicas y atrofia cerebral en pacientes con encefalopatía aguda

Abstract Introduction: Triphasic waves (TW) constitute an electroencephalographic pattern associated with certain kinds of encephalopathy. Brain atrophy may be a predisposing factor linked with TW. Objective: To compare the degree of brain atrophy and white matter disease between patients with acute encephalopathy with and without TW. Methods: A retrospective observational study including adult patients with encephalopathy, with and without TW, hospitalized between 2016 and 2017. The degree of brain atrophy and white matter lesion were defined using the Global Cortical Atrophy and Age Related White Matter Changes (ARWMC) scales, respectively. Scores were compared between groups. Mortality rates were registered. Results: Sixteen patients with TW were identified matched by age and sex with 30 patients without TW. The mean age was 80 years in the TW group. Women represented 87.5%. Multifactorial encephalopathy was the most frequent diagnosis followed by metabolic encephalopathy. Patients with TW had more brain atrophy (10.43 vs 6.9, p= 0.03). Mean ARWMC was 9.43±6.5 and 8.5 ±7.89 in patients with and without TW respectively (p= 0.5). Mortality rate was higher in the TW group (31.25 vs 6.66% p= 0.02). Conclusions: Patients with acute encephalopathy and TW had higher degree of cerebral atrophy. It is possible that this structural alteration predisposes to the appearance of TW. There was no significant difference in white matter lesion degree. The mortality of the TW group was high, so future studies are necessary to determine their prognostic value.

Resumen Introducción: Las ondas trifásicas (OT) constituyen un patrón electroencefalográfico asociado con diversas encefalopatías. La atrofia cerebral podría predisponer a su aparición. Objetivo: Comparar el grado de atrofia cerebral y de lesión de sustancia blanca en pacientes con encefalopatía aguda con y sin OT. Métodos: Estudio observacional retrospectivo, incluyó pacientes adultos con encefalopatía aguda con y sin OT internados entre 2016 y 2019. El grado de atrofia cerebral y de lesión de sustancia blanca se definieron según las escalas Global Cortical Atrophy y Age Related White Matter Changes (ARWMC), respectivamente. Se compararon los puntajes entre grupos. Se registró la mortalidad. Resultados: Se identificaron 16 pacientes con OT y 30 sin OT pareados según edad y sexo. La edad promedio del grupo con OT fue 80 años. El 87.5% fueron mujeres. La encefalopatía multifactorial fue el diagnóstico más frecuente seguido de la encefalopatía metabólica. El grado de atrofia fue mayor en pacientes con OT (10.43 vs 6.9, p= 0.03). El puntaje ARWMC fue 9.43 ±6.5 y 8.5 ±7.89 en pacientes con y sin OT respectivamente (p= 0.5). La mortalidad fue mayor en el grupo con OT (31.25 vs 6.66% p= 0.02). Conclusiones: Pacientes con encefalopatía aguda y OT tuvieron mayor grado de atrofia cerebral. Dicha alteración estructural podría relacionarse con la aparición de OT. No hubo diferencias significativas en el grado de lesión de sustancia blanca. La mortalidad del grupo con OT fue elevada. Son necesarios estudios para determinar su valor pronóstico.

Is Structural Connectivity Different in Child and Adolescent Relatives of Patients with Bipolar Disorder? A Narrative Review According to Studies with DTI. / ¿Es diferente la conectividad estructural en niños y adolescentes familiares de pacientes con trastorno bipolar? Una revisión narrativa según estudios con DTI.

INTRODUCTION: Bipolar disorder (BD) has been associated with a decrease in white matter integrity. Diffusion tensor imaging (DTI) studies have enabled these changes to be elucidated with higher quality. Due to BD's high heritability, some studies have been conducted in relatives of BD patients looking at white matter integrity, and have found that structural connectivity may also be affected. This alteration has been proposed as a potential BD biomarker of vulnerability. However, there are few studies in children and adolescents. OBJECTIVE: To conduct a review of the literature on changes in white matter integrity determined by DTI in high-risk children and adolescents. RESULTS: Brain structural connectivity in the paediatric population is described in studies using DTI. Changes in the myelination process from its evolution within normal neurodevelopment to the findings in fractional anisotropy (FA) in BD patients and their high-risk relatives are also described. CONCLUSIONS: Studies show that both BD patients and their at-risk relatives present a decrease in FA in specific brain regions. Studies in children and adolescents with a high risk of BD, indicate a reduced FA in axonal tracts involved in emotional and cognitive functions. Decreased FA can be considered as a vulnerability biomarker for BD.

Relación médico legal de la enfermedad de sustancia blanca evanescente como un estado anterior y su implicación ante el trauma craneoencefálico: reporte de caso / Medical-legal relationship of evanescent white matter disease as a previous state and its implication in the cranioencephalic trauma: case report

Resumen La enfermedad de sustancia blanca representa una enfermedad poco común en usuarios que se apersonan al Organismo de Investigación Judicial, por este motivo al valorar un caso es necesario investigar los antecedentes de la medicina legal para establecer mecanismos causales con hechos representados en la sociedad. Además, es necesario abordar la enfermedad de sustancia blanca desde su aparición, incidencia, aspectos clínicos, hallazgos ante una posible autopsia, explorar el desarrollo de fisiopatología como indagar acerca de las formas de diagnosticar la enfermedad y valorar las opciones terapéuticas. Estos conocimientos son base para establecer una relación médico legal y analizar si el caso de una niña de 9 años tiene correlación con una historia de trauma en cabeza que no evidencia cambios inflamatorios, aumento de volumen de tejidos blandos o duros, excoriaciones, equimosis, hematomas, cicatrices, gradas o callos óseos y con valoraciones médicas que indican tetraparesia flácida en ausencia de hallazgos patológicos al reporte de tomografía axial computarizada y resonancia magnética de columna cervicodorsal.

Abstract White matter disease represents a rare disease in users who go to the Organismo de Investigación Judicial (Judicial Investigation Agency) for this reason, when evaluating a case, it is necessary to investigate the antecedents of legal medicine to establish causal mechanisms with facts represented in society. In addition, it is necessary to address white matter disease from its appearance, incidence, clinical aspects, findings in a possible autopsy, explore the development of pathophysiology such as inquire about ways to diagnose the disease, and assess therapeutic options. This knowledge is the basis for establishing a legal medical relationship and analyzing whether the case of a 9-year-old girl has a correlation with a history of head trauma that does not show inflammatory changes, increased soft or hard tissue volume, excoriations, bruising, bruising. , scars, bleachers or calluses and with medical evaluations that indicate flaccid tetraparesis in the absence of pathological findings on the report of computed tomography and magnetic resonance imaging of the cervicodorsal spine.

Riesgo de daño cerebral en prematuros menores de 34 semanas expuestos a corioamnionitis histológica, Lima, Perú / Risk of brain damage in premature infants under 34 weeks of gestational age exposed to histological chorioamnionitis Lima, Peru

RESUMEN Objetivos: Evaluar el riesgo de daño cerebral en prematuros menores de 34 semanas expuestos a corioamnionitis histológica (CAH). Materiales y métodos: Se realizó un estudio de cohortes en el Hospital Cayetano Heredia, durante el 2015. Fueron incluidos prematuros menores de 34 semanas que tuvieran examen histopatológico de la placenta. Los tipos de CAH evaluados fueron subcorionitis, corionitis, corioamnionitis, con o sin funisitis. El daño cerebral se evaluó en tres periodos de edad, entre 0 y 7 días, entre 7 y 30 días y a las 40 semanas gestacionales corregidas. Se realizó un seguimiento neurológico y controles con ecografía cerebral. Resultados: Se estudiaron 85 prematuros, 47,1% eran mujeres y la media de la edad gestacional fue de 30,9 semanas. El 42% (36/85) nacieron expuestos a CAH. La ruptura prematura de membrana fue la principal generatriz de sepsis, y la sepsis se relacionó con daño neurológico. La CAH estuvo asociada con hemorragia intraventricular (HIV) durante la primera semana y con lesiones de la sustancia blanca entre los 7 y 30 días de edad (p = 0,035). El tipo corioamnionitis de CAH se asoció al daño neurológico durante la primera semana (RR = 2,11; IC 95%: 1,09-4,11) y entre los 7 y 30 días de vida (RR = 2,72; IC 95%: 1,07-6,88). Conclusiones: La corioamnionitis fue un factor de riesgo para desarrollar lesiones cerebrales en prematuros menores de 34 semanas, para HIV durante los primeros 7 días y lesiones de sustancia blanca entre los 7 y los 30 días de edad. A las 40 semanas de edad corregida, los prematuros extremos con CAH tuvieron lesiones cerebrales más extensas.

ABSTRACT Objectives: To assess the risk of brain damage in premature infants under 34 weeks of gestational age exposed to histological chorioamnionitis (HCA). Materials and methods: A cohort study was conducted at the Hospital Cayetano Heredia, during 2015. Premature infants under 34 weeks of gestational age, who had histopathological examination of the placenta, were included. The types of HCA evaluated were sub-chorionitis, chorionitis, chorioamnionitis, with or without funisitis. Brain damage was evaluated in three age periods, between 0 and 7 days, between 7 and 30 days and at 40 weeks of corrected gestational age. A neurological follow-up and regular controls were performed with brain ultrasound. Results: A total of 85 premature infants were included, 47.1% were women and the mean gestational age was 30.9 weeks. From the total, 42% (36/85) were born exposed to HCA. Premature rupture of membranes was the main cause of sepsis, which was related to neurological damage. HCA was associated with intraventricular hemorrhage (IVH) during the first week and with white matter lesions between 7 and 30 days of age (p = 0.035). The chorioamnionitis type of HCA was associated with neurological damage during the first week (RR = 2.11, 95% CI: 1.09-4.11) and between 7 and 30 days of age (RR = 2.72, 95% CI: 1.07-6.88). Conclusions: Chorioamnionitis was a risk factor for developing brain injuries in premature infants under 34 weeks of gestational age. It was also a risk factor for HIV during the first 7 days and for white matter injuries between 7 and 30 days of age. At 40 weeks of corrected gestational age, extreme premature infants with HCA had more extensive brain damage.

[The cognitive-behavioural impact of hypertension]. / El impacto cognitivo-conductual de la hipertensión.

Arterial hypertension is considered the main modifiable vascular risk factor that causes silent damage to brain vessels. This vascular brain injury could be the common nucleus that justifies the cognitive (cognitive impairment, dementia and Alzheimer's disease) and behavioural symptoms (late-life depression) of target organ damage mediated-hypertension. Incomplete knowledge about the complex pathophysiology that links hypertension with cognitive-behavioural changes is overlooking brain involvement and underestimating cardio and cerebrovascular risk. The confluence of cognitive impairment, depression and arterial hypertension in elderly adults, warns of the need for a comprehensive evaluation to plan treatment, improve prognosis and contribute to reducing the risk of dementia and its incidence.

Volumetría de fascículos cerebrales en población sana / Brain fascicles volumetry in healthy population

Objetivo Desde la aparición de la tractografía, al tratarse de una técnica no invasiva y que usa la ampliamente conocida resonancia magnética (RM), el estudio de la sustancia blanca se ha facilitado. A partir de eso, se han logrado grandes descubrimientos en cuanto a fascículos cerebrales involucrados en funciones cognitivas. Sin embargo, su evaluación sigue siendo subjetiva y depende de la experiencia y entrenamiento del evaluador, razón por la cual se ha limitado su aplicabilidad en la práctica clínica. En ese sentido, es conveniente parametrizar volúmenes cerebrales de sustancia blanca en población sana a través de una herramienta electrónica que se pueda reproducir y así poderlo aplicar en enfermos. Materiales y métodos Se reportan 10 sujetos sanos desde el punto de vista neurológico. Para cada sujeto, se adquirieron imágenes ponderadas por difusión y los resultados se visualizaron mediante FiberNavigator (http://scilus.github.io/fibernavigator). Finalmente, esa misma herramienta fue utilizada para purificar los fascículos objeto de estudio y realizar el conteo de las fibras. Resultados Se obtuvieron valores de volumetría del fascículo longitudinal superior (FLS), fascículo longitudinal inferior (FLI), fascículo frontoccipital inferior (FFI), fascículo uncinado (FU) y fascículo del cíngulo (FC), identificando que no existen diferencias estadísticamente significativas entre el número de fibras que componen los fascículos cerebrales. Discusión Los resultados alcanzados de la anatomía y la direccionalidad de fibras de los fascículos cerebrales de este estudio coinciden con el resto de la evidencia publicada hasta el momento, sin encontrar diferencias en cuanto a su organización y recorrido. Conclusión Aunque esos resultados no sirven como valores de referencia para ser aplicados en pacientes con patología neurológica, brindamos información inexistente hasta el momento, con ese equipo en específico y la reproducción entre los distintos usuarios y el software.

Objective Since the appearance of tractography, as it is a non-invasive technique and uses the widely known magnetic resonance (MR), the study of white matter has been facilitated. After this, great discoveries have been made regarding the brain fascicles involved in cognitive functions. However, its evaluation continues to be subjective and depends on the evaluator's experience and training. That the reason why its applicability has been limited in clinical practice. Because of this, it is convenient to parametrize cerebral volumes of white matter in healthy population through an electronic, reproducible tool that could be applied in patients. Materials and Methods Ten neurologically healthy subjects are reported, for each subject we acquired images weighted by diffusion and the results were visualized by means of FiberNavigator (http://scilus.github.io/fibernavigator). Finally, this same tool was used to purify the fascicles under study and perform the fiber count. Results Volumetric values of the upper longitudinal fasciculus, inferior longitudinal fasciculus, inferior frontoccipital fasciculus, uncinated fasciculus and cingulate fasciculus were obtained, identifying that there are not statistically significant differences in the number of fibers that make up the cerebral fascicles. Discussion The results achieved of the anatomical and fiber directionality of the cerebral fascicles of this study, coincide with the rest of the evidence published up to now, without finding differences regarding its organization and route. Conclusion Although these results do not serve as reference values to be applied in patients with neurological pathology, do we provide nonexistent information so far, with this specific equipment and the reproducibility between the different users and the software.

Association between white matter lesions and the cerebral glucose metabolism in patients with cognitive impairment. / Asociación entre daños en la sustancia blanca y metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva.

AIM: White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment. It has not been sufficiently evident that cognitive impairment in patients with Alzheimer's disease is caused by WMLs as well as ß-amyloid (Aß) pathology. The aim of this study was to evaluate relationship between WMLs and cerebral glucose metabolism in patients with cognitive impairment after adjustment of cerebral Aß burden. MATERIALS AND METHODS: Eighty-three subjects with cognitive performance ranging from normal to dementia, who underwent brain MRI and 18F-florbetaben positron emission tomography (PET) and 18F-fluorodeoxyglucose PET, were included in this cross-sectional study. The Fazekas scale was used to quantify WMLs on brain T2-weighted MRI. The cerebral Aß burden and cerebral glucose metabolism were quantitatively estimated using volume-of-interest analysis. Differences in the regional cerebral glucose metabolism were evaluated between low-WML (Fazekas scale<2) and high-WML (Fazekas scale≥2) groups. Multiple linear regression analysis adjusted for age, sex and cerebral Aß burden was performed to evaluate the relationship between the Fazekas scale score and cerebral glucose metabolism. RESULTS: The regional cerebral glucose metabolism for the bilateral frontal, temporal, and parietal cortices, and limbic lobes in the high-WML group were significantly lower than those in the low-WML group. There were significant negative correlations between the Fazekas scale score and regional cerebral glucose metabolism in the bilateral frontal, bilateral temporal and left parietal cortices, and bilateral limbic lobes. Multiple linear regression analysis revealed that the Fazekas scale score was an independent determinant of the glucose metabolism in the bilateral frontal and temporal cortices and limbic lobes. CONCLUSIONS: WMLs are associated with decreased cerebral glucose metabolism. Our findings suggest that small vessel disease, as well as Aß pathology, may contribute to cognitive impairment in patients with Alzheimer's disease.

Head-up and body positioning might impair dynamic cerebral autoregulation in patients with silent cerebral small vessel disease. Protocol and operational definitions / El posicionamiento elevado de cabeza y cuerpo podrían afectar la autorregulación cerebral dinámica en pacientes con enfermedad silente de pequeño vaso cerebral. Protocolo y definiciones operacionales

ABSTRACT Background: Cerebral autoregulation (CA) is the ability of intracranial vessels to maintain a constant cerebral blood flow (CBF) during changes of cerebral perfusion pressure (CPP) related to fluctuations in blood pressure, postural changes or increased metabolic demands. It has been suggested that individuals with silent cerebral small vessel disease (SVD) may have impaired CA, but information is inconclusive. We describe the protocol of a study aimed to assess the association between white matter hyperintensities (WMH) of presumed vascular origin and poor dynamic CA, and to determine the effects of head-up and body positioning in patients with this condition. Methods: Using a case-control study design, we will assess the relationship between severity of WMH and dynamic CA, measured by continuous transcranial Doppler assessment of CBF velocities in the middle cerebral arteries (MCAs) combined with beat-to-beat blood pressure monitoring. Dynamic CA will be analyzed by calculating the mean flow index as the ratio of median arterial pressure and mean flow velocities of the MCAs. Participants will be categorized as case-patients if the MRI shows moderate-to-severe WMH. For every case-patient, an age- and sex-matched healthy individual with no neuroimaging evidence of SVD will be selected as a control. Comment: This study will assess whether head-up and body positioning impairs dynamic CA in the setting of diffuse subcortical damage related to SVD, providing further evidence on the importance of CPP in maintaining the CBF. If positive, the study will provide evidence favoring the stop of aggressive hypertensive therapy or interventions promoting orthostatic hypotension to reduce the risk of further ischemic brain damage in these cases.

RESUMEN Antecedentes: La autorregulación cerebral (CA) es la capacidad de los vasos cerebrales de mantener un flujo sanguíneo constante durante cambios en la presión de perfusión cerebral (PPC) relacionados con fluctuaciones de la presión arterial, cambios posturales o aumento de las demandas metabólicas. Se ha sugerido que las personas con enfermedad de pequeño vaso cerebral pueden tener CA deteriorada, pero la información no es concluyente. Describimos el protocolo de un estudio cuyo objetivo es evaluar la asociación entre hiperintensidades de substancia blanca y CA dinámica deficiente, para determinar los efectos del posicionamiento de cabeza y cuerpo en estos pacientes. Métodos: Utilizando un diseño de caso-control, evaluaremos la relación entre la severidad de las hiperintensidades de substancia blanca y la CA dinámica, mediante Doppler transcraneal continuo de las velocidades de flujo en las arterias cerebrales medias (ACM) combinadas con monitoreo de la presión arterial. La CA dinámica se analizará calculando el índice de flujo medio y la relación entre la presión arterial media y las velocidades medias de flujo de las ACM. Los participantes se clasificarán como casos si la IRM muestra hiperintensidades de substancia blanca. Para cada caso, se seleccionará a un individuo sin evidencia de enfermedad de pequeño vaso como control. Comentario: Este estudio evaluará si el posicionamiento de la cabeza hacia arriba afecta la CA dinámica en el contexto del daño subcortical difuso relacionado con enfermedad de pequeño vaso, proporcionando evidencia adicional sobre la importancia de la PPC en el mantenimiento del flujo en estos sujetos. El estudio proporcionará evidencia sobre el uso de terapia hipertensiva agresiva o intervenciones que promueven la hipotensión ortostática para reducir el riesgo de daño cerebral isquémico.

[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.

11C-PIB retention patterns in white and grey cerebral matter in idiopathic normal pressure hydrocephalus patients. A visual analysis. / Patrones de retención de 11C-PIB en la sustancia blanca y en la sustancia gris cerebral de pacientes con hidrocefalia a presión normal idiopática. Un análisis visual.

OBJECTIVE: Cortical cerebral amyloid disease, a hallmark of Alzheimer's disease, has also been observed in idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to compare the 11C-PIB PET/CT retention pattern in iNPH patients and healthy subjects. MATERIAL AND METHODS: A comparison was made of the 11C-PIB PET/CT retention pattern in 13 iNPH patients selected for surgical deviation, compared to a normal control population. Images were visually analyzed and scored for gray matter and white matter (WM) from 1 to 4 (slight to very high PIB retention). The scoring was analyzed in both groups separately for infra- and supra-tentorial regions. A comprehensive clinical report was presented in terms of positive, negative, or equivocal. RESULTS: 11C-PIB PET/CT scan were reported as negative in 8, positive in 3, and equivocal in 2. Five of 13 patients showed at least one cortical area with PIB retention with an intensity higher than that observed in the control group. Overall, white matter (WM) PIB retention of iNPH scored lower than in the control group, showing a statistically significant difference in the infratentorial WM (92/104 vs 54/56; p<.05) and a tendency to be lower in the supratentorial regions (70/84 vs 122/156, p=.327), in particular in the upper periventricular region (25/28 vs 40/52; p=.134). CONCLUSIONS: The PIB retention pattern seems to be different in NPH, compared to normal subjects. PIB retention in WM of NPH appears less intense than in healthy subjects, and they show a higher degree of PIB retention in cortical regions. This deserves to be taken it into account.

Asociación entre la mutación homocigota c.318A>T en el exón 2 del gen EIF2B5 y la forma infantil de la leucoencefalopatía con sustancia blanca evanescente / Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy

Resumen: Introducción: La leucoencefalopatía con sustancia blanca evanescente es una de las leucodistrofias más frecuentes. Generalmente inicia en la infancia y presenta un patrón de herencia autosómica recesiva. El 90% de los casos manifiesta mutaciones en uno de los genes que codifican para las cinco subunidades del factor de iniciación eucariótica 2 (EIF2B5). El diagnóstico se realiza por las manifestaciones clínicas, hallazgos en la resonancia magnética cerebral y estudios moleculares confirmatorios. Caso clínico: Paciente masculino de 13 meses con neurodesarrollo previo normal. Antecedente de internamiento por vómito, hipertermia, irritabilidad y rechazo a la vía oral de 15 días de evolución. Ante la exploración presentó perímetro cefálico y pares craneales normales. Se encontró hipotónico, con reflejos incrementados, sin datos meníngeos ni de cráneo hipertensivo. La tomografía de cráneo mostró hipodensidad generalizada de la sustancia blanca. Egresó sin recuperar deambulación. A los 15 días presentó somnolencia y crisis convulsivas focales después de traumatismo craneoencefálico. En la resonancia magnética se observó hipointensidad generalizada de sustancia blanca. Ante la sospecha de leucoencefalopatía con sustancia blanca evanescente, se solicitó la secuenciación del gen EIF2B5, que reportó mutación homocigota c.318A>T en el exón 2. El paciente requirió múltiples hospitalizaciones por hipertermia y descontrol de crisis convulsivas. Posteriormente mostró deterioro cognitivo, motor y pérdida de la agudeza visual. Falleció a los 6 años por neumonía severa. Conclusiones: Este caso contribuye a conocer el espectro de mutaciones que se presenta en pacientes mexicanos y permite ampliar el fenotipo asociado con esta mutación.

Abstract: Background: Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. Case report: We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. Conclusions: This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation.

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.

Síndrome de encefalopatía posterior reversible: reporte de un caso fatal y análisis de factores predictores de mal pronóstico / Posterior reversible encephalopathy syndrome: Report of a fatal case and analysis of predictive factors of a poor prognosis

El síndrome de encefalopatía posterior reversible es una condición que responde a múltiples causas y presenta características clínicas o radiológicas distintivas; los intensivistas y los médicos de urgencias deben conocerlo con el fin de hacer el diagnóstico y ordenar el tratamiento oportuno. Se presenta un caso fatal de síndrome de encefalopatía posterior reversible, en el cual se determinaron los factores de riesgo relacionados con el resultado final. Un hombre de 60 años sin antecedentes médicos ingresó por urgencias con depresión de la conciencia, convulsiones y tensión arterial elevada. Las imágenes de la tomografía revelaron un hematoma cerebeloso posterior, y las de resonancia magnética mostraron zonas isquémicas, edema vasogénico que se extendía desde los tálamos hacia el tallo cerebral, los pedúnculos cerebelosos medios y la sustancia blanca profunda de los hemisferios cerebelosos, así como zonas de transformación hemorrágica. A pesar del tratamiento médico y quirúrgico recibido, el paciente falleció. Se determinaron los factores de riesgo que se han descrito como causa de muerte en este síndrome. Este caso demuestra que dicho síndrome puede ocurrir sin que se hayan detectado factores de riesgo desencadenantes y pone en evidencia la necesidad de su reconocimiento temprano para establecer una intervención adecuada y evitar daños o un desenlace fatal. Además, abre el camino a nuevos estudios sobre la propensión a desarrollarlo y las medidas preventivas que pueden adoptarse.

Posterior reversible encephalopathy syndrome is an illness with multiple causes and distinctive clinicalradiological characteristics that should be known by intensivists and emergency room physicians for a timely diagnosis and treatment. A fatal case of posterior reversible encephalopathy syndrome is presented, and the risk factors related to the outcome are identified. A 60-year-old man without a relevant medical history arrived at the emergency room presenting with depressed consciousness, seizures, and high blood pressure. Tomographic images revealed a posterior cerebellar hematoma. Resonance images showed ischemic zones, vasogenic edema from the thalamus to the brain stem, middle cerebellar peduncles, deep white matter of the cerebral hemispheres, and zones of hemorrhagic transformation. Despite medical-surgical management, the patient died. The risk factors described as the cause of the fatal outcome were identified. This case demonstrates that posterior reversible encephalopathy syndrome can occur without triggering risk factors and highlights the need for early recognition to establish an appropriate intervention to avoid injury or a fatal outcome. Cases of posterior reversible encephalopathy syndrome provide opportunities to investigate the susceptibility for the development of this condition and to establish appropriate preventive measures.

[Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy]. / Asociación entre la mutación homocigota c.318A>T en el exón 2 del gen EIF2B5 y la forma infantil de la leucoencefalopatía con sustancia blanca evanescente.

BACKGROUND: Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. CASE REPORT: We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. CONCLUSIONS: This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation.