Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome: prevalence, main characteristics, and outcomes in a Brazilian center / Síndrome inflamatória de reconstituição imune da leucoencefalopatia multifocal progressiva associada à síndrome da imunodeficiência adquirida: prevalência, principais características e desfecho em um hospital brasileiro

Abstract Background Progressive multifocal leukoencephalopathy (PML) - immune reconstitution inflammatory syndrome (IRIS) in people living with HIV/AIDS (PLWHA) has been rarely described in low- and middle-income countries. Objective To describe the prevalence of PML-IRIS among PLWHA with PML and its main features in a tertiary hospital in Brazil. Methods We performed a retrospective cohort study. We included PLWHA with PML-IRIS patients admitted at Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, between 2011 and 2021. We retrieved information on neurological manifestations, neuroimaging findings, treatments, and outcomes. Results We identified 11 (11.8%) PML-IRIS cases among 93 patients with definite PML. Eight (73%) cases were men and had a median (IQR) age of 41 (27-50) years. Seven (63.6%) patients developed unmasking PML-IRIS and 4 (36.4%) had paradoxical PML-IRIS. The median (IQR) time from initiation of combined antiretroviral therapy (cART) to IRIS diagnosis was 49 (30-70) days. Ten (90.9%) patients received corticosteroids. There were 4 (36%) in-hospital deaths and 3 were associated with hospital-acquired pneumonia. Among the 7 (64%) patients who survived, 5 (71.5%) had sequelae at discharge. One year after the PML-IRIS diagnosis, 6 (54.5%) patients were alive. Conclusion The prevalence of PML-IRIS was 11.8%. Most patients had unmasking PML-IRIS. In-hospital mortality and morbidity were high. One-year survival was similar to that described in some high-income countries.

Resumo Antecedentes A síndrome inflamatória de reconstituição imune (SIRI) da leucoencefalopatia multifocal progressiva (LEMP) em pessoas vivendo com HIV/Aids (PVHA) foi raramente descrita em países de baixa e média renda. Objetivo Descrever a prevalência da SIRI-LEMP- em PVHA com LEMP e suas principais características em um hospital no Brasil. Métodos Foi realizado um estudo de coorte retrospectivo. Incluímos PVHA com SIRI-LEMP admitidos no Instituto de Infectologia Emílio Ribas, São Paulo, Brasil, entre 2011 e 2021. Recuperamos informações sobre manifestações neurológicas, neuroimagem, tratamento e desfecho. Resultados Identificamos 11 (11,8%) casos de SIRI-LEMP entre 93 pacientes com LEMP definitiva. Oito (73%) casos eram homens e a mediana de idade (amplitude interquartile - AIQ) foi de 41 (27-50) anos. Sete (63,6%) pacientes desenvolveram SIRI-LEMP "desmascarada" e 4 (36,4%) casos apresentaram SIRI-LEMP "paradoxal". A mediana de tempo (AIQ) desde o início da terapia antirretroviral combinada (cART) até o diagnóstico de SIRI foi de 49 (30-70) dias. Dez (90,9%) pacientes receberam corticoide. Houve 4 (36%) óbitos intra-hospitalares e 3 foram associados à pneumonia hospitalar. Dos 7 (64%) pacientes que sobreviveram, 5 (71,5%) ficaram com sequelas na alta. Um ano após o diagnóstico de SIRI-LEMP, 6 (54,5%) pacientes estavam vivos. Conclusão A prevalência de SIRI-LEMP foi de 11,8%. A maioria dos pacientes apresentava SIRI-LEMP "desmascarada". A mortalidade e morbidade hospitalar foram altas. A sobrevida em 1 ano foi semelhante à descrita em alguns países de alta renda.

Leucoencefalopatía multifocal progresiva: enfermedad grave en el paciente inmunosuprimido. Reporte de caso / Progressive multifocal leukoencephalopathy: severe disease in the immunosuppressed patient. Case report

RESUMEN INTRODUCCIÓN: Los pacientes con compromiso del sistema inmune pueden desarrollar una enfermedad neurológica incapacitante e incluso mortal, como lo es la leucoencefalopatía multifocal progresiva (LMP) producida por el virus de John Cunningham (JC). PRESENTACIÓN DEL CASO: Se presenta el caso de un hombre de 26 años con diagnóstico reciente de infección por virus de la inmunodeficiencia humana (VIH) que presentó síntomas constitucionales, déficit neurológico progresivo por hemiparesia espástica izquierda, disminución de la agudeza visual y cambios comportamentales. En las imágenes de resonancia magnética (IRM) cerebral contrastada se encontró afectación subcortical difusa de la sustancia blanca con compromiso de las fibras en U que, correlacionado con una prueba de reacción en cadena de la polimerasa (PCR) para virus JC en LCR, confirmó el diagnóstico de LMP. DISCUSIÓN: La LMP puede manifestarse por medio de síntomas cognitivos usualmente imperceptibles para el clínico, pero también como déficit sensorio-motor y visual que se puede corroborar en las IRM al identificar las lesiones típicas en la sustancia blanca, o bien por medio de detección del virus por PCR en líquido cefalorraquídeo. El manejo específico de la causa que desencadenó la inmunosupresión sigue siendo el pilar de tratamiento. CONCLUSIÓN: La mínima sospecha diagnóstica en aquellos pacientes con factores de riesgo y manifestaciones clínicas concordantes con la enfermedad debe llevar a que se confirme el diagnóstico y que se inicie prontamente el manejo terapéutico en búsqueda de restablecer la respuesta inmune.

ABSTRACT INTRODUCTION: Patients with immunocompromised or weakened immune system can develop a disabling and even life-threatening neurological disorder such as progressive multifocal leukoencephalopathy (PML) caused by John Cunningham (JC) virus. CASE PRESENTATION: We present the case of a 26-year-old man with a recent diagnosis of human immunodeficiency virus (HIV) infection who presented constitutional symptoms, progressive neurological deficit due to left spastic hemiparesis with decreased visual acuity and behavioral changes. The brain Magnetic Resonance Imaging (MRI) showed diffuse subcortical involvement of the white matter including the U-fibers, which, correlated with a detection of JC virus DNA by polymerase chain reaction (PCR) cerebrospinal fluid, confirmed the diagnosis of PML. DISCUSSION: PML can range from subtle cognitive impairment imperceptible to the clinician to sensory-motor deficits and visual disturbances that can be corroborated in MRI by identifying the typical lesions in the white matter or by detecting the virus by PCR in cerebrospinal fluid. The specific management of the cause that triggered the immunosuppression continues to be the mainstay of treatment. CONCLUSION: At the minimum diagnostic suspicion in patients with risk factors and clinical manifestations consistent with the disease should proceed to confirm the diagnosis and promptly immune reconstitution.

Leucoencefalopatía multifocal progresiva / Progressive multifocal leukoencephalopathy

RESUMEN La leucoencefalopatía multifocal progresiva es una enfermedad desmielinizante secundaria a la infección por el virus de John Cunnigham, con baja incidencia a pesar de su alta seroprevalencia en la población general. Su principal factor de riesgo es la inmunosupresión, incluyendo la infección por el virus de la inmunodeficiencia humana (VIH), cánceres hematológicos, enfermedades inflamatorias crónicas y medicamentos inmunosupresores sistémicos. Después de la infección primaria, el virus queda latente y por mutaciones en su genoma adquiere la capacidad neuroinvasiva e infecta a los oligodendrocitos, a los que lleva a su destrucción, con el consecuente proceso desmielinizante, mientras se enfrenta a la inmunidad celular del huésped. El diagnóstico se basa en manifestaciones clínicas secundarias al compromiso encefálico, clásicamente supratentorial, así como la demostración de la presencia de genoma viral o anticuerpos en suero o líquido cefalorraquídeo y hallazgos imagenológicos e histopatológicos de lesiones en la sustancia blanca cerebral. El tratamiento, en general, consiste en la recuperación de la función inmune alterada, con reparos cuando esta se presenta en el contexto de un estado de reconstitución inmune. En este escrito se revisan los aspectos básico-clínicos más relevantes de esta enfermedad.

SUMMARY The progressive multifocal leukoencephalopathy is a demyelinating disease secondary to infection to John Cunningham Virus, it has a low incidence despite a high seroprevalence in the general population. The principal risk factor for its development is an immunosuppression, including Human Immunodeficiency Virus infection, hematologic neoplasms, chronic inflammatory diseases and systemic immunosuppressive drugs. After the primary infection, the virus stays in a latent state, acquiring a neuroinvasive capacity following a set of mutations in its genome. After infecting oligodendrocytes it takes them to destruction with the consequent demyelinating process whilst its fight to the host's cellular immune system. The diagnosis is based on a set of clinical findings secondary to encephalic compromise, classically supratentorial, in addition to a demonstration of viral genome or antibodies in serum or cerebrospinal fluid and the presence of diagnostic images and histopathologic findings on the cerebral white matter. Its treatment is based on the enhancement of the disturbed immune function, with the exception of immune reconstitution state where other strategies are applied. In this paper we will review the more relevant basic and clinical aspects of this disease.

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis / Perfil sorológico do vírus John Cunningham (JCV) em pacientes com esclerose múltipla

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

RESUMO As opções terapêuticas para esclerose múltipla (EM) modificaram-se ao longo dos últimos anos, trazendo uma nova categoria de drogas com melhor perfil de eficácia. No entanto, estas drogas vieram com um novo perfil de potenciais eventos adversos que exigem que o neurologista os reconheça bem e rapidamente. Uma das complicações mais temidas destes tratamentos para a EM é a leucoencefalopatia multifocal progressiva (LEMP), causada pela reativação do vírus John Cunningham (JCV). Objetivo: Identificar o perfil sorológico de JCV em pacientes com EM. Métodos: Dados sorológicos de JCV foram obtidos através do ensaio por enzimas imuno-adsorvidas (ELISA) fornecido pelo programa STRATIFY-JCV. Resultados: Um total de 1.501 testes sanguíneos foram obtidos de 1.102 pacientes com EM. O grupo teve 633 pacientes (57,1%) soropositivos para anticorpos anti-JCV e 469 pacientes negativos (42,9%). Vinte e três pacientes se tornaram posivitos após resultados iniciais negativos para anticorpos anti-JCV. A taxa de soroconversão foi 18,5% em 22 meses. Conclusão: O perfil sorológico do JCV e a soroconversão nos pacientes brasileiros foi semelhante àquela descrita em outros países.

Study on the relationship between H type hypertension as well as the changes of serum lipid and white matter lesions / 中国基层医药

Objective To investigate the relationship between H type hypertension as well as the changes of serum lipid and white matter lesions(WML).Methods From January 2015 to October 2017,the clinical characteristics of 507 WML patients who admitted to the Affiliated Hospital of Chengde Medical College were analyzed retrospectively. The patients were divided into simple hypertension group(A group,hypertension accompanied by Hcy ＜10μmol/L, 111cases),simple homocysteine group(B group,patients without high blood pressure with homocysteine ＞10μmol/L, 132cases)and H type hypertension group (C group,hypertension accompanied by homocysteine ＞10μmol/L,264cases)according to homocysteine concentration and hypertension.The patients'clinical data,including imaging information such as MRI,diffusion weighted imaging(DWI),and levels of homocysteine (Hcy),serum lipid were collected.The patients were divided into three subgroups based on the severity of WML,including the mild,moderate,severe.The differences of TG,TC,HDL -C,LDL -C,Apo -A1,Apo -B in each group were compared.Results The levels of TC in A,B and C group were (4.14 ±1.16)mmol/L,(4.39 ±1.39)mmol/L,(3.67 ±1.29)mmol/L,respectively.The levels of LDL -C in the three groups were (2.24 ±0.88)mmol/L,(2.38 ±0.91)mmol/L and (1.99 ±0.89)mmol/L,respectively.Compared with A group and B group,the levels of TC and LDL -C in C group were lower(F =15.411,9.271,all P <0.05).In A group,the number of mild WML,moderate and severe WML accounted for 51.4%,32.4% and 16.2%,which in B group accounted for 50.0%,33.3% and 16.7%,which in C group accounted for 32.6%,33.3% and 34.1%.The number of WML patients had statistically significant differences between A group and C group(χ2 =16.407,P <0.05),and B group and C group(χ2 =15.912,P <0.05).In A group,the TC levels in the moderate group [(4.45 ±1.07)mmol/L]and severe group[(5.04 ±0.99)mmol/L] were significantly higher than that in the mild group [(3.68 ±1.03)mmol/L],the difference was statistically significant(F =22.391,P <0.05);the LDL -C level in the severe group[(2.88 ±0.65)mmol/L]was significantly higher than (1.98 ±0.84)mmol/L in the mild group and (2.33 ±0.89)mmol/L in the moderate group(F =14.764,P <0.05).In B group,the TC levels in the moderate group [(4.79 ±1.38)mmol/L]and the severe group [(5.20 ±1.43)mmol/L]were significantly higher than (3.85 ±1.16)mmol/L in the mild group,the difference was statistically significant(F =20.515,P <0.05).Compared with the mild group[(2.13 ±0.83)mmol/L],the LDL –C level was higher in the severe group[(2.81±1.01)mmol/L],the difference was statistically significant(F =9.235, P <0.05).In C group,the levels of TC and LDL -C in the moderate group were (3.94 ±1.22)mmol/L and (2.02 ± 0.74)mmol/L,respectively,which in the severe group were (3.93 ±1.16)mmol/L and (2.30 ±0.85)mmol/L,respectively,which were significantly higher than those in the mild group [(3.12 ±1.34 )mmol/L,(1.62 ±0.88)mmol/L],the differences were statistically significant(F =27.141,27.078,all P <0.05).Spearman correlation analysis showed that there was a positive correlation between hypertension,TC,LDL -C and the severity of WML(H type hypertension:r =0.211,P <0.05;TC:r =0.266,P <0.05;LDL -C:r =0.258,P <0.05).Conclusion H type hypertension and high levels of TC,LDL -C can increase the number and severity of WML.

Effect of repetitive normobaric hypoxic preconditioning on white matter lesions and cognitive impairment in chronic cerebral ischemia rats / 中华老年心脑血管病杂志

Objective To study the effect of repetitive normobaric hypoxic preconditioning (RNHP) on white matter lesions (WMLs) and cognitive impairment in chronic cerebral ischemia rats.Methods Twenty-four healthy adult male SD rats were divided into sham operation group,model group,and RNHP group (8 in each group).The bilateral common carotid arteries in sham operation group were isolated but not ligated in ambient air,those in model group were ligated in ambient air,and those in RNHP group were preconditioned for 2 weeks before ligation.Their cognitive function was assessed in Morris water maze test,their WMLs were caluculated with KlüverBarrera staining.The astroglia,microglia and oligodendrocyte in cerebral white matter were stained with immunolabelling technique using antibodies to glial fibrillary acidic protein,Iba-1 and CNPase.Results The percentage of target quadrant swimming time was significantly higher in RNHP group and sham operation group than in model group (27.26％ ± 2.06％,29.06％ ± 1.72％ vs 20.58％±2.23％,P＜0.05,P＜0.01).The scores of WMLs in corpus callosum,caudate putamen and anterior commissure were significantly lower,the number of astrocytes and microglias was significantly smaller while that of oligodendrocytes was significantly greater in RNHP group and sham operation group than in model group (P＜0.05,P＜0.01).Conclusion RNHP can improve WMLs and cognitive impairment in chronic cerebral ischemia rats.

Progressive cavitating leukoencephalopathy: four cases and literatures review / 中华儿科杂志

Objective@#To analyze the clinical and genetic features of progressive cavitating leukoencephalopathy (PCL).@*Method@#The data of clinical and genetic features of 4 PCL patients diagnosed by Beijing Children′s Hospital between January 2015 and January 2016 were analyzed. The cases with complete clinical data retrieved on literature search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to August 2016) by using search terms of"NDUFV1" ,"NDUFS1" , or"leukoencephalopathy" , were summarized.@*Result@#There were three females and one male, two of which were compatriots. The age of onset ranged from 6 months to 15 months. All four children′s first symptoms were motor development regression, and the developmental milestones were almost normal before the onset. Of the 4 patients, 3 had cognitive impairment, 1 had seizures, 4 had dystonia and pyramidal impairment, 2 had emaciation, and 1 had nystagmus. The lactate concentrations of 4 patients were normal in blood. One patient had lactaciduria in the urinary organic acid analysis. Cranial magnetic resonance imaging (MRI) of all patients showed leukoencephalopathy, involved in the corpus callosum, and three patients accompanied by cystic lesions. Follow up for 2-13 years showed that the physical and language development were improved. Genetic analysis revealed that mutations in NDUFS1 were found in three patients and NDUFV1 mutation was found in one patient. All six mutations (p.Arg377Cys and p. Arg377His in NDUFV1; p. Arg482Glyfs*5, p.Thr368Pro, p.Tyr454X and p. Asp565Gly in NDUFS1) are novel. Five English case reports including 10 PCL patients were collected. Together with this group of 4 cases, a total of 14 cases were involved. All 14 children patients had motor development regression, 11 cases had cognitive impairment and dystonia, 6 cases had pyramidal impairment, 5 cases had irritability, 4 cases had epilepsy and nystagmus, 3 cases had strabismus and swallowing difficulty. Cranial MRI showed patchy leukoencephalopathy with cavities, involved in the corpus callosum. Follow up for 19 months-15 years that the neurology development were improved slowly in all patients.@*Conclusion@#NDUFS1 and NDUFV1 gene mutation screening should be performed firstly in patients with PCL clinical and imaging feature.

Analysis of risk factors of different locational white matter changes in elderly patients with cerebral infarction / 中国医师杂志

Objective To explore risk factors of different locational leukoaraiosis in elderly patients with cerebral infarction.Methods Patients were collected who aged 60 to 85 with cerebral infarctions came to the Fourth Affiliated Hospital of China Medical University and took cerebral magnetic resonance imaging (MRI) [fluid-attenuated inversion recovery (FLAIR), T1, and T2].The patients were divided into periventricular white matter changes (PVWMCs) and deep white matter changes (DWMCs), and scored by Fazekas scale, respectively.We registered past medical history, medical systems and neurological examination, blood lipids, regular blood test, and resting blood pressure measurements in the morning.Univariate analysis was used to choose risk factors which ~fected white matter changes.After that, rank multivariate logistic regression analysis was used to test risk factors of PVWMCs and DWMCs, respectively.Results There were significant age differences in both PVWMCs and DWMCs, the degree of risk was associated with age.Conclusions PVWMCs and DWMCs risk factors vary, and we should take control of risk factors actively for the elderly in order to reduce the harm arising from WMC.

Comparison and application of three visual rating scales for white matter lesions in Alzheimer's disease and mild cognitive impairment / 中华老年医学杂志

Objective To compare the clinical value of three visual rating scales (VRS) for white matter lesions (WML) in Alzheimer's disease (AD) and mild cognitive impairment (MCI).Methods Totally 184 subjects (including 107 AD patients,47 MCI patients and 30 normal controls)were recruited.All subjects underwent comprehensive neuropsychological tests and were examined with a standard protocol of MR imaging.WML burden was rated with the Age-Related White Matter Changes (ARWMC) rating scale,Cholinergic Pathways Hyperintensities Scale (CHIPS) and Fazekas scale.Consistence of the three rating scales were analyzed,and detection results of WML in AD/ MCI/NC group with the three rating scales were compared.The relationship between WML and cognitive function in AD and MCI groups were explored.Results ARWMC rating scale,CHIPS and Fazekas scales were moderately to highly correlated with WML (r=0.61-0.78,all P＜0.01).ARWMC showed that WML were in the left and right frontal lobes in AD and MCI groups and in the right frontal lobe and left temporal lobe in NC group,which had significant differences (F=4.20,4.69,4.69,3.36,respectively,all P＜0.05).WML in the left temporal lobe had a significant difference between MCI group and NC group (F=3.36,P＜0.05).CHIPS showed that WML in the front left side of centrum semiovale in AD and MCI groups had significant difference as compared with that in NC group (F=4.88,P＜0.05),and WML in the rear right side of low external capsule had a significant difference between AD and NC groups (F=3.04,P＜0.05).Fazekas scale showed that there was no difference in WML among AD,MCI and NC groups.ARWMC showed that scores of WML in right temporal lobe were positively correlated with concentration and visual construction,and bilateral basal ganglia were negatively correlated with the concentration.Fazekas scale showed that scores of WML in periventricular were negatively correlated with concentration,MMSE and orientation,scores of WML in deep white matter were negatively correlated with concentration,abstraction and judgment,and the whole scores were negatively correlated with concentration.CHIPS showed that the scores of WML in the rear left side of low external capsule were negatively correlated with short-term memory in MCI group.Conclusions The three rating scales well consistent with each other.ARWMC rating scale and CHIPS can detect the differences in WML between AD,MCI and NC groups.The scores of CHIPS in WML are related with cognition in MCI group,while scores of ARWMC and Fazekas scale in WML are correlated with many aspects in cognitive function in AD group.In general speaking,CHIPS in MCI patients and ARWMC rating scale in AD patients show more advantages in the detection of WML and have better correlation with cognitive function.

MRI findings in children with vanishing white matter disease / 中华放射学杂志

Objective To describe the MRI features of vanishing white matter disease (VWM).Methods Ten patients diagnosed as VWM between 2008-2013 were enrolled,with the mean age of(40 ±23)months.The clinical materials and MR images of them were reviewed retrospectively.The findings of MRI were analyzed by two experienced neuroradiologists in this study,including the location (cerebrum,cerebellum,brainstem,corpus callosum and internal/external capsule),size and signal intensity of the lesions,as well as the presence of cystic degeneration,cerebrum atrophy and the abnormal signal of the basal nuclei.Results MRI of brain typically showed extensive abnormal signal in the cerebral central white matter (10/10) and the focal lesion in subcortical white matter (9/10).The involvement of U-fibers was present in 7 cases.Cystic degeneration of the affected white matter was found in 7 cases.Abnormal signal also appeared in the white matter of posterior limb of the internal capsule (8/10),the external capsule (7/10),the inner rim (the callosal-septal interface) of the corpus callosum (8/10).The lesions of the thalamus and globus pallidus were detected in 2 cases.The white matter of the brainstem and cerebellum were involved in 6 and 7 cases respectively.Conclusion VWM typically shows a diffuse and symmetrical abnormal signal in the cerebral white matter with cystic degeneration on MRI,which is usually diagnostic.

Human immunodeficiency virus-associated mild cognitive function decline: a preliminary study of the combination of diffusion tensor imaging and resting-state functional magnetic resonance imaging / 中华传染病杂志

Objective The purpose of this study was to use diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) alone or in combination to observe the distribution of white matter lesions and cortical malfunctional areas in human immunodeficiency virus (HIV) infected patients with mild cognitive decline and to explore the relationship between the DTI and the rs-fMRI methods.Methods Twenty-six HIV infected patients with mild cognitive impairment and 30 healthy volunteers were selected by Montreal Cognitive Asessment (MoCA) scale evaluation.DTI data and rs-fMRI data were obtained,fractional anisotropy (FA) value images were obtained with voxel based analysis and the resting-state default mode network (DMN),functional connectivity images were obtained with cingulate gyrus as a seed point.Overlay images were obtained with FA,DMN and Ch2 standard images.Results Compared with the control group,the white matter FA values were significantly decreased in the left precuneus(t=4.0499,P＜0.005) and right precuneus (t=5.1553,P＜0.005),right superior frontal gyrus(t=5.1517,5.1484,P＜0.005),right middle frontal gyrus (t=4.1444,P＜0.005),right precentral gyrus (t=3.7395,P＜0.005),right occipital lobe (t=7.2236,P＜0.005),and right inferior parietal lobule (t=4.1450,P＜0.005) in acquired immunodeficiency syndrome (AIDS) patients.In resting-state default mode network,areas significantly related to cingulate gyrus seed point included the left cingulate gyrus (t =32.78,P＜0.005),left precuneus (t =4.51,P＜0.005),left superior frontal gyrus (t =14.33,4.53,P＜0.005),left middle temporal gyrus (t =10.01,5.72,P＜ 0.005),left inferior temporal gyrus (t =5.99,P＜0.005),left parahippocampal gyrus (t =7.63,P＜0.005),right posterior cingulate (t =34.81,P＜0.005),right precuneus (t=32.09,P＜0.005),right superior frontal gyrus(t =14.12,P＜0.005),right middle frontal gyrus (t=17.71,P＜0.005),right superior temporal gyrus (t=14.59,P＜0.005),and right middle temporal gyrus (t=11.83,P＜0.005); while areas not significantly related to the cingulate gyrus seed point included the left precuneus (t =5.39,P＜0.01),left anterior cingulate gyrus (t =3.66,P＜0.01),left cerebellar tonsils (t =7.51,P＜0.01),right superior parietal lobule (t=4.44,P＜0.01),right parahippocampa gyrus (t =3.69,P＜0.01),and right cerebellar tonsil (t=6.15,P＜0.01).Overlayed images showed that the white matter FA value of the left precuneus were decreased and the functional activitis of the corresponding cortex were significantly decreased; while the white matter FA values of the left precuneus,right precuneus,right superior frontal gyrus,right middle frontal gyrus were decreased without affection of the functional activity of the corresponding cortex in AIDS patients.Conclusion White matter nerve fiber disconnection of multiple brain regions and its corresponding cortical function decline with compensatory activity co-participated in the pathogenesis of AIDS mild cognitive decline.

Leukoencephalopathy with cerebral calcification and cysts: a case report and review of literature / 中华内科杂志

Objective To improve the diagnostic ability of leukoencephalopathy with cerebral calcifications and cysts (LCC),a rare central nervous system disease.Methods The clinical manifestations,neuroimages and neuropathological features of a 19-year-old male patient were analyzed.A total of 20 cases from 14 literatures were reviewed.Results The patient was admitted with right limb weakness,cognitive decline,headache and blurred eyesight.Head CT scan showed multiple calcifications,cysts formation and leukoencephalopathy.Brain MRI showed several cysts in bilateral hemisphere,basal ganglia,thalamus and paraventricular areas.A mural nodule was noted inside one of the cyst,which was enhanced on the contrasted MRI.The wall of the cysts was partially enhanced,but not with the fluid inside the cysts.The corresponding CT calcifications foci showed on T1 and T2 with either both hyperintensity or both hypointensity,which was also partial enhanced.Extensive leukoencephalopathy was formed around the cysts and the ventricles.But neither Cho nor NAA changed a lot on MRS.Amplitude diagram of SWI series exhibited multiple round small dark signals all over the affected areas with mixed signals showed in the phase diagram,which indicated both calcifications and microbleedings at the lesions.Neuropathological examinations found no tumor cells in the operated cyst,and showed angiomatous small blood cells were dominant in the cyst wall.Hyaline degenerations,microcalcifications and hemosiderin deposition were observed.No obvious demyelination was discovered,while gliosis,numerous Rosenthal fibers and fibrinoid vascular necrosis were found around the lesions.The clinical,neuroimaging and pathological features of this patient were in accordance with the cases reported in the literatures.Conclusions Neuroimaging is the most important method for the diagnosis of LCC.As small vessel lesions are probably closely related to the pathophysiology of LCC,SWI could be recommended to further reveal the etiology of LCC.

Clinical analysis of 11 patients with reversible posterior leukoencephalopathy syndrome / 中国基层医药

ObjectiveTo explore the clinical characteristics of reversible posterior leukoencephalopathy syndrome ( RPLS ),in order to deepen the awareness of the disease.MethodsThe clinical data of 11 patients with RPLS in our hospital were retrospectively analyzed.ResultsIn the 11 cases with RPLS,there were two cases of pregnancy induced hypertension,preeclampsia(38 weeks pregnant),four eases of chronic renal insufficiency,four cases of malignant hypertension,and one case of lung cancer after chemotherapy.The main clinical presentations were headache,abnormality of visual perception,mental and behavioral abnormalities,ataxia,epileptic seizure and so on.The neuroimaging performances were extensive white matter abnormalities of the rear of the bilateral cerebral hemispheres,such as the parietal-occipital temporal lobe lesions,also involving the brain stem,cerebellum,thalamus and other parts.ConclusionThe clinical characteristics and neuroimaging performances of RPLS has certain characteristics,the majority of lesions were reversible,if the early diagnosis and treatment,the prognosis is usually good.

Cerebral autosomal recessive arteriopathy with subcortical infarets and leukoencephalopathy / 国际脑血管病杂志

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive hereditary cerebral artery disease in the adolescence,and its main clinical manifestations are dementia,stroke,low back pain and alopecia.At present,most cases are from Japan.3-6 exon point mutations in the HTRA1 gene are associated with the onset of CARASIL.Brain histopathological examination showed a small arterial intimal thickening medial smooth muscle cell loss and hyalinization.Brain MRI showed a diffuse white matter abnormal signal and multiple subcortical infarcts.The diagnosis mainly depends on the characteristic clinical symptoms,imaging characteristics and genetic testing.It should be differentiated from cerebral autosomal dominant arteriopathy with sulcortical infarcts and leucoencephalopathy.

Relationship between chronic kidney disease and cerebral small vessel disease in elderly patients / 中华老年医学杂志

ObjectiveTo explore the relationship between chronic kidney disease (CKD) and cerebral small vessel disease (SVD) in elderly patients. MethodsOne hundred and fifty-two elderly male CKD patients for experimental group and 158 elderly male for control group were recruited. Demographic data and vascular risk factors were recorded. White matter lesion (WML) was semi-quantitatively assessed by cerebral magnetic resonance imaging (MRI), and lacunar infarction (LI) was also calculated. Results(1) The prevalenees of hypertentsion and diabetes mellitus were higher in elderly CKD patients than those in control group (30. 9% vs. 19.0%, 23.7%vs. 14.6%;both P～0. 05). (2) The percentages of grade 2 and grade 3 WMLs were higher in elderly CKD patients than those in control group (34.9% vs. 24.1%, 25.7% vs. 16.5%;both P<0.05). Prevalence of LI was higher in elderly CKD patients than that in control group (45.4% vs.25.3% ,X2= 13. 70, P<0. 05). The similar Resultswere also obtained except for control subjects with hypertension and diabetes mellitus. (3) The logistic regression analysis showed that age, hypertension and low glomerular filtration rate (GFR) were closely associated with SVD in elderly CKD patients. ConclusionsHypertention and diabetes mellitus are risk factors for CKD in elderly patients. SVD is associated with CKD, and age, hypertension and low GFR may be risk factors for SVD in elderly CKD patients.

Leukoencephalopathy with cerebral calcifications and cysts: 2 cases report / 中华神经科杂志

Objective To explore the features of leukoencephalopathy with cerebral calcifications and cysts (LCC) in clinic, radiology and pathology in order to improve skills in diagnosis. Methods Two female patients had CT and/or MRI scan, and case 2 had contrast enhancement MRI scan additionally. Both cases had blood biochemistry examinations including calcium, phosphorus and alkaline phosphatase et al. Case 2 had lumbar puncture and cerebrospinal fluid test. The major cystic lesion was surgically removed in both patients and offered a histopathological examination. Results CT scan reveaed diffuse calcifications in the bilateral basal ganglia, white matter of frontal lobe and/or dentate nuclei of cerebellum in both cases, and major cystic lesion in right frontal lobe (case 1) and the left parietal lobe (case 2). The rim of enhancement was observed in cystic lesion on MRI. Histopatbological examination revealed angiomatous rearrangements of the microvessels with fibroid, hyaline degeneration and haemosiderin deposits, brain tissue associated with areas of demyelinization, some Rosenthal fibers, gliosis, calcium deposits and hemorrhage, fibrinoid necrosis occurs in partial vessels associated with thrombogenesis and stenosis as changes in arteriolitis. Blood biochemistry examination showed normal. Cerebrospinal fluid test in case 2 showed increased intracranial pressure(350 mm H_2O,I mm H_2O =0. 0098 kPa). Conclusions The onset of LCC varies and occurs from early infancy to adult. The asymmetrical calcification is characteristic in LCC. Hemorrhage could be involved in the pathogenesis of cystic formation. LCC is characterized by a cerebral obliterative microangiopathy, both demyelinization and the edematous changes could probably result in white matter abnormalities on neuroimaging.

Detecção do DNA do poliomavírus humano JC em amostras de líquido cefalorraquidiano de pacientes com AIDS e lesões não expansivas de substância branca do sistema nervoso central / Detection of human polyomavirus JC in cerebrospinal fluid samples from aids patients with non-expansive focal lesions of CNS white matter

Doenças neurológicas focais em pacientes com aids podem ser causadas por vários patógenos oportunistas. Dentre estas se inclui a encefalite por Toxoplasma gondii, os linfomas primários do sistema nervoso central causados pelo vírus Epstein-Barr, as encefalites virais (CMV, HSV, VZV) e a leucoencefalopatia multifocal progressiva (LEMP), causada pelo vírus JC (VJC). O presente estudo teve por objetivos detectar o DNA do vírus JC em amostras de líquido cefalorraquidiano de pacientes com aids e lesões não expansivas de substância branca do SNC, bem como caracterizar esses pacientes com relação ao número de células TCD4+, sexo, idade e ocorrência de outros diagnósticos etiológicos. A detecção do DNA do VJC foi realizada através da técnica de reação em cadeia por polimerase. O protocolo de PCR empregado, anteriormente descrito, utiliza um par de primers complementar à região precoce do vírus JC (antígeno T), resultando em um fragmento de 173 pb. Todas as amostras positivas foram submetidas a etapa posterior de tipagem com enzima de restrição Bam H1, resultando em dois fragmentos menores (120 e 53 pb), característicos do vírus JC. Com o intuito de estimar a sensibilidade da técnica empregada, um controle positivo quantificável foi padronizado. O fragmento de 173 pb amplificado de uma das amostras de líquor estudadas foi inserido em plasmídio, e o recombinante obtido foi quantificado através de espectrofotometria, titulado e submetido a PCR. Através desta metodologia foi possível estimar que o teste é capaz de detectar a partir de 200 cópias/ µl. A especificidade do teste foi avaliada através da análise de amostras de líquor de pacientes com e sem aids e outros diagnósticos neurológicos, não compatíveis com LEMP. A pesquisa do DNA do vírus JC foi negativa em 119 de 120 amostras testadas, demonstrando uma especificidade de 99,17%. Foram incluídas no estudo 56 amostras de líquor de pacientes com lesão focal não expansiva de substância branca, compatível com LEMP...

Focal neurological diseases in aids patients can be caused by a range of opportunistic pathogens such as Toxoplasma gondii, EBV-associated primary CNS lymphomas, viral encephalitis (CMV, HSV, VZV) and JC virus causing the progressive multifocal leukoencephalopathy (PML). In the present study, we evaluated the detection of JC virus DNA in CSF samples from aids patients with white matter non-expansive lesions of CNS by polymerase chain reaction (PCR) and characterize this finding in relation to the number of TCD4+, age, gender, and other etiological diagnosis. The primers used to amplify the T antigen region of JC virus resulted in a fragment of 173 base pairs. Since JC virus harbor a BAM H1 restriction site in this region, digestion of the PCR product with the enzyme resulted in two fragments of 120 and 53 base pairs, characteristic of JC virus. To estimate the sensitivity of the assay, the 173 bp fragment obtained from one of the samples was inserted into a plasmid and the recombinant quantified by spectrophotometry. The sensitivity of the PCR was 200 copies / µL. The specificity of the assay was evaluated in CSF samples from patients with and without aids and other neurological conditions, not suggestive of PML. The PCR resulted negative in 119 of the 120 CSF samples tested showing a specificity of 99,17%. In 56 CSF samples from patients with neurological symptoms and radiological signs of PML, JC virus was detected in 27 (48.2%) by PCR. In 23 of the remaining 29 patients (79.3%) other neurological conditions were diagnosed: T. gondii encephalitis (9 cases), HIV encephalitis (5 cases), tuberculosis (3 cases) and other diagnosis (8 cases). In six patients no neurological disease diagnosis could be established. In the group of patients characterized as JC virus-DNA positive the mean number of TCD4+ was significantly lower as compared to the JC virus-DNA negative patients. No statistical difference was seen in relation to gender or age distribution...

The cranial MRI appearance of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a family / 中华放射学杂志

ObjectiveTo recognize the cranial MRI appearance in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL). MethodsFive patients with CADASIL from two generations in a family underwent routine MRI and MRA examinations.Three patients with CADASIL were confirmed by the Notch3 genetic testing and the vascular pathological Resultsand one was diagnosed on basis of MR and clinical manifestations. The imaging data from 4 patients with CADASIL were analyzed.ResultsFour cases achieved preliminary diagnosis of CADASIL and one was excluded by MRI.In 4 patients with CADASIL,bilateral symmetrical,confluent white matter lesions in the subcortical and Deriventricular regions were seen frequently in the temporal,frontal and parietal lobes,but the occipital lobes were less involved.These lesions appeared as long T1 and long T2 signal.O'Sul]ivan sign was shown in all cases and subcortical lacunar lesions was seen in 2 cases. In the centrum semiovale,well-defined,round or oval cystic infarcts(black holes)were demonstrated in 3 cases and multiple tiny round enlarged perivascular spaces(pepperpot appearance)in all cases.The corpus callosum was involved in all cases,and it was evidently atrophic in 2 cases.The anterior part of internal capsule and external capsule were were present in the basal ganglia and brainstem. Only one case revealed a small infarct in the right cerebellum. Four Datients shared mild or moderate atrophy of brainstem, cerebellum and cerebrum. No marked abnorillalitv of large vessels was seen in all cerebral MRA. ConclusionsThe cranial MRI appearance in CADASIL shows some characteristics.MRI may give some infotznation in the preliminary diagnosis or exclusion of CADASIL.

Quantitative MR measures in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationships with clinical scales / 中华放射学杂志

Objective To analyze white matter hyperintensities(WMH)and brain volumes quantitatively in patients with Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy(CADASIL)on conventional MRI and correlate them with clinical parameters.Methods Fifteen patients with CADASIL confirmed by pathological investigation underwent conventional MRI examinations.Involvement of centrum semiovale,posterior limbs of the internal capsule,corpus callosum,external capsules and white matter of the temporal poles was determined by an experienced radiologist.Normalized brain volume(NBV)and the percentage of WMH to brain volume were calculated with softwares and they were correlated with NIHSS and MMSE statistically.Results Involvement of white matter in the brains of patients with CADASIL included:semiovale centrum in 13 cases,white matter of the temporal poles in 10 cases,external capsules in 8 cases,posterior limbs of the internal capsule in 5 cases,corpus callosum in 4 cases.The percentage of WMH to brain volume was(5.7±1.4)%,and the NBV was(1602±58)×103mm3.Spearman test showed a significant relationship between age and NBV(r=-0.555,P＜0.05).There was a significant relationship between NBV and NIHSS(r=-0.624.P＜0.05).The percentage of WMH to brain volume correlated significantly with NIHSS and MMSE(r=0.522,P＜0.05;r=-0.679,P＜0.01).Conclusions The white matter hvperintensities and brain volume in patients with CADASIL can be assessed quantitatively,which showed correlation with severity of the clinical scale.The development of WMH may refleet the degree of cognitive impairment in CADASIL.