Síndrome de Aicardi-Goutieres: Diagnóstico genético en una lactante

El Síndrome de Aicardi-Goutieres (SAG) se caracteriza por una encefalopatía genética, progresiva, de inicio temprano, que se asocia a un proceso inflamatorio. Además del SNC, puede afectar a la piel, con erupciones tipo sabañones, y presentar microcefalia, talla baja, disfunción hepática, disfunción tiroidea, reactantes de fase aguda elevados, anticuerpos autoinmunes positivos y asociaciones para enfermedades sistémicas autoinmunes como él LES. El SAG presenta locus heterogénicos, con mutaciones identificadas en los genes que codifican el exonucleasa TREX1 3´â†’5´ y las tres subunidades del complejo de endonucleasa RNASEH2. Se presenta el caso de una paciente de 2 años de edad, con retraso del desarrollo psicomotor, sin otras manifestaciones sistémicas, diagnosticada como SAG, con variante c.529G(A (p.Ala177Thr) con efecto patogénico en homocigosis en el gen RNASEH2B.

Aicardi-Goutieres Syndrome (AGS) is characterized by an early-onset, progressive, genetic encephalopathy associated with an inflammatory process. In addition to the CNS, it can affect the skin, with chilblain-like eruptions, and present with microcephaly, short stature, liver dysfunction, thyroid dysfunction, elevated acute phase reactants, positive autoimmune antibodies, and associations for autoimmune systemic diseases such as SLE. SAG presents heterogeneous loci, with mutations identified in the genes encoding the TREX1 3'→5' exonuclease and the three subunits of the RNASEH2 endonuclease complex. We present the case of a female 2-year-old patient, with delayed psychomotor development, without other systemic manifestations, diagnosed as SAG, with variant c.529G>A (p.Ala177Thr) with a pathogenic effect in homozygosis in the RNASEH2B gene.

Clinical and genetic characteristics of adrenomyeloneuropathy / 中华神经科杂志

Objective:To summarize and analyze the clinical and genetic characteristics of Chinese patients with adrenomyeloneuropathy (AMN).Methods:Clinical data were collected and analyzed retrospectively on AMN patients who were diagnosed by genetic testing in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from May 2008 to August 2022. Clinical characteristics of AMN patients with different types of gene mutations were compared. Loe score was used to evaluate the severity of white matter demyelinating, and the serum levels of very long-chain fatty acids (VLCFA) in patients with or without white matter demyelinating were compared. The motor function of the AMN patients was assessed using the Expanded Disability Status Scale (EDSS), and the association between EDSS scores and the course of disease was analyzed.Results:A total of 23 male patients with onset age of (29.52±9.91) years were included in this study. The first symptom of all patients was abnormal lower extremities, of which 17 patients showed stiffness and weakness in their lower limbs (73.9%, 17/23), and 6 patients showed numbness and pain in both lower limbs (26.1%, 6/23). The occurrence of symptoms was not related to the type of gene mutation. White matter demyelination occurred in 33.3% (7/21) of patients over a disease duration of (7.67±4.46) years. There was no statistically significant difference in serum VLCFA level between the white-matter demyelination group and the non-demyelination group. The EDSS score was positively correlated with the disease duration ( r=0.57, P=0.006). Sixteen ABCD1 gene mutations were found in this study, among which c.5_19delinsTCTCCAGG (p.P2Lfs *12) was reported for the first time. Four probands belonging to different families carried the c.1415_1416del (p.Q472Rfs *83) variant. Conclusions:Lower limb movement disorders and sensory dysfunction are the prominent clinical manifestations in AMN patients, with deterioration of motor function associated with the course of disease. AMN may be converted to cerebral type and VLCFA concentration is not associated with the phenotypic changes. The c.1415_1416del (p.Q472Rfs *83) mutation is a hot spot mutation of the disease.

Genetic investigation of dementias in clinical practice / Investigação genética das demências na prática clínica

Abstract Background: The field of neurodegenerative dementia genetics has advanced significantly over the past two decades, but there are still more to be discovered (such as the gene mutation in some familial forms of dementia). Objective: to provide a brief review of the most recent discoveries regarding monogenic dementia, and covering the most frequent genetic diseases that can cause dementia (neurodegenerative or not). Methods: a review of the literature will be carried out. Results: neurodegenerative dementias, vascular dementias and leukoencephalopathies caused by single pathogenic variants are presented. Conclusion: The spectrum of clinical presentations for most of the genes discussed is wide, and hence genetic testing in clinic should try to cover as many genes as possible.

RESUMO Antecedentes: O campo da genética das demências neurodegenerativas avançou significativamente nas últimas duas décadas, mas ainda há mais a ser descoberto (como a mutação genética em algumas formas familiares de demência). Objetivo: fornecer uma breve revisão das descobertas mais recentes sobre demência monogênica, e abrangendo as doenças genéticas mais frequentes que podem causar demência (neurodegenerativa ou não). Métodos: será realizada uma revisão da literatura. Resultados: são apresentadas demências neurodegenerativas, demências vasculares e leucoencefalopatias causadas por variantes patogênicas únicas. Conclusão: O espectro de apresentações clínicas para a maioria dos genes discutidos é amplo e, portanto, os testes genéticos na clínica devem tentar cobrir o maior número possível de genes.

Advance in clinical research of subcortical U fiber / 中华神经科杂志

Subcortical U fibers, also known as arcuate fiber, are kind of short connective fibers connecting adjacent brain gyrus. They located in the outermost layer of white matter, adjacent to the cortex. With the development of imaging, more and more attention has been paid to the differential diagnosis of subcortical U fibers in different white matter lesions. In this article, subcortical U fibers are reviewed from the aspects of definition, anatomy and physiology.

Correlation between acute ischemic stroke with leukoaraiosis and intracranial and extracranial artery stenosis / 中国基层医药

Objective:To correlate acute ischemic stroke with leukoaraiosis with intracranial and extracranial artery stenosis.Methods:A total of 300 patients with acute ischemic stroke admitted to Shaoxing Second Hospital from January to December 2017 were included in this study. All patients underwent magnetic resonance (MRI) examination. According to the examination results, these patients were divided into control (acute ischemic stroke, n = 100) and acute ischemic stroke with leukoaraiosis, n = 200). Carotid artery plaque size and blood sugar level were recorded in each group. Intracranial and extracranial large artery stenosis rates were compared between the two groups. Severity of leukoaraiosis was correlated with intracranial and extracranial artery stenosis. Results:The percentage of patients developing hypertension in the observation group was significantly higher than that in the control group [66.0% (132/200) vs. 44.0% (44/100), χ2 = 13.31, P < 0.01]. The incidence of coronary heart disease in the observation group was significantly higher than that in the control group [49.0% (98/200) vs. 31.0% (31/100), χ2 = 8.81, P < 0.01]. The incidence of carotid artery plaque in the observation group was significantly higher than that in the control group [49.5% (99/200) vs. 34.0% (34/100), χ2 = 6.49, P = 0.01]. The incidence of carotid artery stenosis in the observation group was significantly higher than that in the control group [23.5% (47/200) vs. 12.0% (12/100), χ2 = 5.58, P = 0.01]. There was no significant difference in the incidence of anterior cerebral artery stenosis between observation and control groups [5.5% (11/200) vs. 4.0% (4/100), χ2 = 0.32, P = 0.57]. The size of carotid artery plaque in the observation group was significantly larger than that in the control group [(1.86 ± 0.42) cm vs. (1.39 ± 0.27) cm, t = 10.18, P < 0.01]. The incidence of intracranial and extracranial artery stenosis in the observation group was significantly higher than that in the control group [41.0% (82/200) vs. 24.0% (24/100), χ2 = 8.43, P < 0.01]. The severity of leukoaraiosis was positively correlated with the degree of intracranial and extracranial artery stenosis ( r = 0.79, P < 0.01). Conclusion:Patients with acute ischemic stroke with leukoaraiosis have a high intracranial and extracranial artery stenosis and the severity of leukoaraiosis is positively correlated with intracranial and extracranial artery stenosis.

Changes in cognitive and behavioral function in patients with cerebral small vessel disease and their correlation with serum homocysteine and cystatin C levels / 中国基层医药

Objective:To investigate the changes in cognitive and behavioral function in patients with cerebral small vessel disease and their correlation with serum homocysteine (Hcy) and cystatin C (CysC) levels.Methods:Ninety-four patients with cerebral small vascular disease who received treatment in Zhejiang Xin'an International Hospital from March 2019 to March 2021 were included in the observation group. An additional 80 healthy controls who concurrently received physical examination were included in the control group. The Mini-Mental State Scale (MMSE) and the Montreal Assessment Scale (MoCA) were used to evaluate cognitive function. The activity of daily living (ADL) was used to evaluate behavioral function. Enzyme-linked immunosorbent assay was used to measure serum Hcy and CysC levels. MMSE score, MoCA score, ADL score, serum Hcy and CysC levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of serum Hcy and CysC levels in the diagnosis of cerebral small vessel disease. Pearson correlation analysis was performed to analyze the correlation between serum Hcy and CysC levels and cognitive behavioral function.Results:MMSE score, MoCA score, and ADL score in the observation group were (21.21 ± 2.87) points, (20.18 ± 3.25) points, and (34.32 ± 5.45) points, which were significantly lower than (28.23 ± 1.02) points, (28.45 ± 0.89) points and (76.35 ± 8.29) points in the control group ( t = 20.78, 22.05, 40.03, all P < 0.05). Serum Hcy and CysC in the observation group were (16.28 ± 2.97) μmol/L and (1.21 ± 0.23) mg/L, which were significantly higher than (8.35 ± 1.76) μmol/L and (0.56 ± 0.12) mg/L in the control group ( t = 20.95, 22.77, both P < 0.05). ROC curve analysis showed that the sensitivity and specificity of serum Hcy in diagnosing cerebral small vessel disease were 85.29% and 53.85%, respectively; the sensitivity and specificity of serum CysC in diagnosing cerebral small vessel disease were 81.54% and 41.38%, respectively. Pearson correlation analysis revealed that serum Hcy level was linearly negatively correlated with MMSE score, MoCA score, and ADL score ( r = -0.79, -0.68, -0.71, all P < 0.05); serum CysC level was linearly negatively correlated with MMSE score, MoCA score, and ADL score ( r = -0.67, -0.75, -0.78, P < 0.05). Conclusion:The cognitive and behavioral function of patients with cerebral small vessel disease are decreased, and serum Hcy and CysC levels are increased. Serum Hcy and CysC levels are closely related to the cognitive and behavioral function of patients with cerebral small vessel disease.

Leucoencefalopatia tóxica por inhalación de heroína "Chasing the Dragon": serie de casos / Toxic Leukoencephalopathy by inhaling heroin "Chasing the Dragon": case series

RESUMEN INTRODUCCIÓN: La leucoencefalopatia tóxica es una afección que compromete la sustancia blanca por exposición a sustancias tóxicas. La heroina es una de las implicadas en el desarrollo de la leucoencefalopatia con diferencias exclusivas que suceden con la inhalación según las diversas técnicas en comparación al uso intravenoso, bien sea de la heroína o de otras sustancias psicoactivas. En esta serie describimos cinco casos, de sexo masculino, que desarrollaron leucoencefalopatia espongiforme por heroína (LEH) posterior a la inhalación de vapores, en un hospital del sistema de salud público en la ciudad de Armenia, Colombia. OBJETIVO: El objetivo de este estudio es describir las características demográficas, clínicas, hallazgos de laboratorio e imágenes diagnósticas, así como la mortalidad asociada a LEH en la muestra estudiada. MÉTODOS: Recolección de datos de historias clinicas y búsqueda de imágenes registradas en el Hospital San Juan de Dios de Armenia durante el periodo 2017-2018. RESULTADOS: Se obtienen cinco casos clínicos de pacientes usuarios de vapores inhalados de heroina, quienes ingresan con signos neurológicos de predominio motores y extrapiramidales, con el signo radiológico clásico de "Chasing the Dragon" en estudios de TC cerebral simple en todos los casos. De los cinco casos se presenta un deceso, determinando una mortalidad de 20% comparado con un 25% de mortalidad reportado en la literatura. CONCLUSIONES: La LEH suele estar subdiagnosticada dado que suele confundirse con un trastorno neuropsiquiatríco o de la conducta asociada al consumo de sustancias psicoactivas (SPA), el diagnóstico se realizó con los hallazgos típicos en las imágenes de TC cerebral simple. Se debe tener en cuenta las estadísticas sobre consumo de heroína a la hora de realizar el abordaje de un paciente con historial de consumo de SPA y los signos neurológicos para relacionarlos con esta etiologia y dar un manejo integral a estos pacientes.

ABSTRACT IlNTRODUCTION: Toxic leukoencephalopathy is a condition that compromises the encephalic white matter due to exposure to toxic substances. Heroin is one of those involved in the development of leukoencephalopathy and there are certain differences that occur with its inhalation with the different techniques compared to intravenous use, either heroin or other psychoactive substances. In this serie, we describe five cases of male sex who developed heroin spongiform leukoencephalopathy (HSLE) after inhalation of vapors, in a Hospital of the public health system in the city of Armenia, Colombia. OBJECTIVES: The objective of this study is to describe the demographic and clinical characteristics, laboratory findings and diagnostic images, as well as the mortality associated with HSLE in the sample studied. METHODS: Collection of data from medical records and search of images registered at the San Juan de Dios Hospital in Armenia during the period 2017-2018. RESULTS: Five clinical cases were obtained of patients who were users of inhaled heroin vapors and were admitted to the hospital with predominantly motor and extrapyramidal neurological signs, with simple brain CT studies showing the classic radiological sign of "Chasing the Dragon" in all five cases. One death was presented, with a mortality of 20% compared to the 25% mortality that has been reported in the scientific literature. CONCLUSIONS: HSLE is usually underdiagnosed since it is often confused with a neuropsychiatric or behavioral disorder associated with the consumption of psychoactive substances (PAS). The diagnosis was made with the typical findings in simple brain CT images. Statistics on heroin use must be considered when approaching a patient with a history of PAS use and neurological signs, to relate them to this etiology and provide comprehensive management to these patients.

Nasu-Hakola disease due to a homozygous triggering receptor expressed on myeloid cell 2 gene mutation / 中华神经科杂志

Nasu-Hakola disease is an extremely rare genetic disorder with cognitive dysfunction and fractures as the main clinical manifestations. The clinical characteristics, laboratory, imaging, and genetic data of a Nasu-Hakola case from a consanguineous Chinese family were analyzed. The patient was a 40-year-old female complaining about progressive forgetting and behavior change of three years and urinary incontinence of eight months. Neurological examination of the patient showed tetra-pyramidal signs. Neuropsychological testing revealed severe cognitive and behavioral impairment. Head magnetic resonance imaging showed generalized brain atrophy predominantly involving the frontal lobe, caudate nucleus, and anterior corpus callosum, and head computer tomography showed bilateral basal ganglia calcification. The patient had no history of bone pain or fracture and a skeletal survey showed no abnormalities. Whole exome sequencing identified a novel homozygous triggering receptor expressed on myeloid cells 2 gene mutation (c.523delA) in the patient and confirmed the heterozygous status of her parents and sisters. The patient showed no signs of improvement during the last six months after discharge. Although the patient′s clinical presentations mimicked the behavioral variant of frontotemporal dementia, reduced 42-amino acid form of amyloid-β protein level in the cerebrospinal fluid suggested amyloid deposition in the brain, which might be related to astrocytic dysfunction.

The phenotypic and genetic spectrum of colony-stimulating factor 1 receptor gene-related leukoencephalopathy in China / 中华神经科杂志

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Research progress on retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations / 中华神经科杂志

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare hereditary cerebrovascular disease. The clinical presentations are characterized by early-onset visual impairment, liver and kidney dysfunction and neurological symptoms. Imaging examinations are often misdiagnosed as neoplasms or tumefactive multiple sclerosis for invasive examination. Early and correct identification is essential for optimizing treatment strategies and comprehensive management. This review is to improve the understanding of RVCL-S, which may help to reach more accurate diagnosis and better treatment, and improve further research.

"Chasing the Dragon": A Fatal Case Report of Toxic Leucoencéphalopathie Due to Inhaled Heroin

Leukoencephalopathy is a myelin disorder caused by multiple agents, including substance abuse. A 28-year-old man arrived at the emergency department having suffered from asthenia, dizziness, disorientation and ataxia for two months. He had a two-year history of heroin inhalation. He arrived in a normal physical condition. Brain magnetic resonance showed bilateral diffuse hypointense lesions in the white matter. At day 3 after admission, he presented neurological deterioration, stupor, haemodynamic instability, respiratory failure, and died. Toxic leukoencephalopathy symptoms start with inattention, memory and personality changes, and may eventually cause dementia and death. Heroin inhalation is a common practice and can lead to leukoencephalopathy. Leukoencephalopathy associated with heroin inhalation is a rare entity that mainly affects young adults and has a high social impact. Its aetiology is unclear, it has no effective treatment and there is a high mortality rate. Heroin consumption is on the rise in Colombia, so TL should be considered by medical staff.

La leucoencefalopatía es una patología de la mielina producida por múltiples agentes, incluidas las sustancias de abuso. Un varón de 28 años llegó urgencias por 2 meses de astenia, mareo, desorientación y ataxia. Tenía antecedentes de consumo inhalado de heroína por 2 años. Presentaba condiciones físicas regulares. La resonancia magnética cerebral mostró lesiones hipointensas difusas bilaterales en la sustancia blanca. Al tercer día presentó empeoramiento de su estado neurológico, estupor, inestabilidad hemodinámica, insuficiencia respiratoria y muerte. Los síntomas de leucoencefalopatía tóxica (LT) comienzan con falta de atención, cambios en la memoria y la personalidad, y finalmente demencia y muerte. El consumo de heroína inhalada es una práctica frecuente con riesgo de que produzca LT. La leucoencefalopatía asociada con el uso de heroína inhalada es una entidad rara que afecta principalmente a adultos jóvenes y tiene un alto impacto social. Su etiología no está clara, no tiene un tratamiento efectivo y tiene altas tasas de mortalidad. El consumo de heroína está aumentando en Colombia, por lo que el personal médico debe tener en cuenta la LT.

Diagnóstico clínico imagenológico y evolutivo de leucodistrofia, megaloencefalia y quistes subtemporales en la lactancia / Clinical-epidemiological and evolutive diagnosis of leukodystrophy, megalencephaly and subtemporal cysts during breastfeeding

Introducción: Las leucodistrofias primarias son un grupo de trastornos hereditarios que afectan la sustancia blanca cerebral de forma predominante. El término leucodistrofias primarias unifica las enfermedades que afectan las células gliales con compromiso de la mielina y el axón de base genética. Es un grupo de entidades, más de 30 en la actualidad, en expansión gracias a los avances en resonancia magnética y en genética. Objetivo: Contribuir al conocimiento de esta rara enfermedad con énfasis en la utilidad de su conocimiento clínico y en los estudios de imágenes evolutivos para el diagnóstico. Presentación del caso: Paciente con macrocranea detectada por la familia a los tres meses de nacida, al inicio refirieron que la circunferencia cefálica creció rápidamente y a partir del segundo semestre de vida el crecimiento se hizo más lento. La valoración clínica al año de edad comprobó una discreta dificultad para el control cefálico, intentaba dar pasos con apoyo, lenguaje de 3 a 4 palabras y ninguna otra afectación del neurodesarrollo. Al examen físico, una circunferencia cefálica de 55 cm (por encima de dos desviaciones estándar para la edad cronológica y sexo). Conclusiones: La evolución clínica favorable conjuntamente con el patrón de la resonancia magnética cerebral, que inicialmente mostró afectación de la sustancia blanca compatible con leucodistrofia inespecífica y en estudios evolutivos detecta presencia de quistes subtemporales, permitieron el diagnóstico de esta rara enfermedad infantil. La paciente recibió tratamiento sintomático para la espasticidad, apoyo pedagógico y control de sus crisis epilépticas(AU)

Introduction: Primary leukodistrophies are a group of hereditary disorders that affect in a predominant way the white substance of the brain. The term ´´primary leukodistrophies´´ unifies the diseases that affect the glial cells compromising myelin and the genetic based axon. They are a group of entities, more tan 30 nowadays, which are expanding due to the advances in magnetic resonance and genetics. Objective: To contribute to the understanding of this rare disease with emphasis in the usefulness of its clinical knowledge and in the evolutive studies of images for diagnosis. Case presentation: Female patient with macrocranea detected by the family at 3 months old. At the beginning, the family referred that the cephalic circumference grew quickly and from the second semester of life growing process was slower. The clinical assessment at first year of life proved a discreet difficulty for cephalic control; the patient tried to do support footsteps, and had a language of 3 to 4 words without any other affectation in the neurodevelopment. In the physical examination, she presented a cephalic circumference of 55 cm (higher than the two stantard deviations for the cronological age and sex). Conclusiones: The clinical evolution was favorable jointly with the pattern of brain magnetic resonance that initially showed affectation in the white substance compatible with inespecific leukodistrophy and in the evolutive studies it was detected the presence of subtemporal cysts which allowed to diagnose this rare children disease. The patient received symptomatic treatment for spasticity, pedagogical support and control of the epileptic crisis(AU)

Correlations of plasma homocysteine with cerebral white matter lesion severity and cognitive impairment in elderly patients with hypertension / 中华老年医学杂志

Objective To investigate the correlations of plasma homocysteine(Hcy)levels with cerebral white matter lesion(WML)severity and cognitive impairment in elderly hypertension patients.Methods A retrospective case-control study was conducted.Ninty-eight elderly patients with hypertension were enrolled.Based on the presence or absence of hyperhomocysteinemia(hypertension with plasma Hcy levels ≥10μmol/L was defined as H-type hypertension),patients were divided into two groups:a control group(n =48) and an H-type hypertension group(n =50).The degree of WML was rated by the Fazekas scale using magnetic resonance imaging(MRI)analysis.Neuropsychological examinations including mini-mental state examination(MMSE)and Montreal cognitive assessment (MoCA)were taken to assess cognitive function.The degree of WML and cognitive impairment were compared between the two groups.Correlations of plasma Hcy levels with the degree of WML and cognitive impairment were analyzed.Results Compared with the control group,scores of the Fazekas scale(3.2 ± 1.0 vs.2.5 ± 1.0,P ＜0.05) and deep white matter hyperintensity on MRI(1.7 ± 0.8 vs.1.3±0.7,P＜0.05)increased,and scores of MMSE(24.9±3.3 vs.27.7±1.8,P＜0.05)and MoCA(18.6±3.9 vs.25.0±3.0,P＜0.05)decreased in the H-type hypertension group.Plasma Hcy levels were positively correlated with the degree of WML (r =0.430,P ＜ 0.01) and negatively correlated with cognitive function(r=-0.406 in MMSE and-0.663 in MoCA,P＜0.01).Multivariate logistic regression showed that Hcy,fasting blood-glucose,deep WML,low-density lipoprotein cholesterolin,age and systolic pressure were influencing factors for cognitive impairment (P ＜ 0.01).Conclusions WML and cognitive function are worse in elderly H-type hypertension patients than in hypertension patients with normal Hcy levels.WML and cognitive impairment are aggravated with increased plasma Hcy levels.The plasma Hcy level may be an effective clinical indicator of cognitive function in elderly people with hypertension.

Research progress on effects of vascular risk factors for white matter lesion ／ / 心血管康复医学杂志

White matter lesion (WML) can lead to decreased cognitive ability ,postural balance disorder and abnor‐mal emotion etc .,which affects quality of life and is closely related to treatment of stroke .In recent years ,roles of vessel‐related risk factors and atherosclerosis in WML received considerable attention .The present article made a re‐view on it ,aiming at providing thinking for prevention and treatment of WML .

Influencing factors of cognitive dysfunction in patients with ischemic white matter lesions and clinical intervention strategy for it／ / 心血管康复医学杂志

To explore influencing factors of cognitive dysfunction in patients with ischemic white matter lesions (IWML) and clinical intervention strategy for it .Methods :A total of 98 IWML patients were divided into no cognitive dysfunction group (n＝52) and cognitive dysfunction group (n＝46) according to presence of cognitive dysfunction and no .Age ,gender ,years of education ,levels of total cholesterol (TC) ,low density lipoprotein cho‐lesterol (LDL‐C) ,IWML class and lesion type were compared between two groups .Results : Compared with no cog‐nitive dysfunction group ,there were significant rise in age [ (64. 12 ± 4. 71) years vs.(70. 06 ± 4.82) years] ,serum LDL‐C level [ (2.54 ± 0.67 ) mmol／L vs.(2.89 ± 0. 85 ) mmol／L ] , percentages of hypertension (26.92% vs. 63. 04%) ,diabetes mellitus (23.08% vs.54.35%) and IWML class 3 (3.85% vs.31.43%) ,and significant reduc‐tion in percentage of IWML class 1 (59.62% vs.19. 57%) and years of education [ (9. 97 ± 2.82) years vs .(8. 12 ± 2.36) years] in cognitive dysfunction group , P＜0.05 or ＜0.01 ;multi‐factor Logistic regression analysis indicated that age and IWML class were independent risk factors for cognitive dysfunction (OR＝1.142 , 4.752 ; P＝0.007 , 0.012) ,while years of education was its independent protective factor in IWML patients (OR ＝ 0.514 ; P＝0.020 ).Conclusion : Cognitive dysfunction is closely related with age ,years of education and IWML class in IWML patients .Physicians should take targeted measures in time to prevent occurrence of cognitive dysfunction according to patient’ s comprehensive condition .

Correlation Between Vanishing White Matter Disease and Novel Heterozygous EIF2B3 Variants Using Next-Generation Sequencing: A Case Report

Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantile-onset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decisionmaking, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.

Síndrome epiléptico ligado al cromosoma X por mutación de la protocaderina 19 (OMIM 300088) asociado con leucoencefalopatía y tractopatía posterior reversible / X-linked epileptic syndrome by protocadherin 19 mutation associated with leukoencephalopathy and posterior reversible tractopathy

La epilepsia con retardo mental ligado al cromosoma X por mutación del gen PCDH19, es una condición que solo se presenta en las mujeres. El cuadro clínico suele verse complicado con retardo global del desarrollo y epilepsia. En la edad adulta puede manifestarse con discapacidad intelectual y hasta 20 % de las mujeres afectadas no presentan convulsiones ni retardo intelectual. Se presenta el caso de una niña con epilepsia, retardo del desarrollo y conversión autista, asociados con leucoencefalopatía y tractopatía posterior reversible por mutación del PCDH19 (c.142G>T/ p.Glu48X).

Epilepsy and mental retardation produced by mutations in gene PCDH19 (protocadherin 19) is an X-linked syndrome restricted to females. It starts with global and speech developmental delay and epilepsy; intellectual disability may continue in adults. At least in 20% of cases, there are no seizures or intellectual retardation. We report the case of a girl with epilepsy, developmental delay, and autistic conversion associated with posterior reversible leukoencephalopathy and tractopathy produced by PCDH19 mutation (c.142G>T/ p.Glu48X).

Supraversión de la mirada en intoxicación mortal por bupropión / Sustained upgaze in a patient who ingested high doses of bupropion: report of one case

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

Clinical features and diagnosis of childhood leukoencephalopathy with cerebral calcifications and cysts in four cases / 中华儿科杂志

Objective@#To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC).@*Methods@#The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination.@*Results@#Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time.@*Conclusions@#The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.

Animal models of white matter lesions / 国际脑血管病杂志

White matter lesion is a major subtype of cerebral small vessel disease. Its pathophysiology and mechanism remain unclear. Because the risk factors often coexist in clinical research, it is difficult to judge the relationship between certain risk factors and white matter injury. Moreover, due to the differences in animal and human brain tissue structure, there is currently a lack of reproducible animal models of white matter lesions. Therefore, establishing a practical animal model and further exploring the pathogenesis and risk factors of white matter lesions from the basic research level is crucial for the preclinical study of the treatment of white matter damage. This article reviews the characteristics, optimization measures, and application prospects of the white matter lesion models.