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2.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34643483

RESUMO

Subacute sclerosing panencephalitis (SSPE) is a rare fatal neurodegenerative disease caused by a measles virus (MV) variant, SSPE virus, that accumulates mutations during long-term persistent infection of the central nervous system (CNS). Clusters of mutations identified around the matrix (M) protein in many SSPE viruses suppress productive infectious particle release and accelerate cell-cell fusion, which are features of SSPE viruses. It was reported, however, that these defects of M protein function might not be correlated directly with promotion of neurovirulence, although they might enable establishment of persistent infection. Neuropathogenicity is closely related to the character of the viral fusion (F) protein, and amino acid substitution(s) in the F protein of some SSPE viruses confers F protein hyperfusogenicity, facilitating viral propagation in the CNS through cell-cell fusion and leading to neurovirulence. The F protein of an SSPE virus Kobe-1 strain, however, displayed only moderately enhanced fusion activity and required additional mutations in the M protein for neuropathogenicity in mice. We demonstrated here the mechanism for the M protein of the Kobe-1 strain supporting the fusion activity of the F protein and cooperatively inducing neurovirulence, even though each protein, independently, has no effect on virulence. The occurrence of SSPE has been estimated recently as one in several thousand in children who acquired measles under the age of 5 years, markedly higher than reported previously. The probability of a specific mutation (or mutations) occurring in the F protein conferring hyperfusogenicity and neuropathogenicity might not be sufficient to explain the high frequency of SSPE. The induction of neurovirulence by M protein synergistically with moderately fusogenic F protein could account for the high frequency of SSPE.


Assuntos
Encéfalo/virologia , Vírus SSPE/patogenicidade , Panencefalite Esclerosante Subaguda/virologia , Proteínas Virais de Fusão/metabolismo , Proteínas da Matriz Viral/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Genes Virais , Células Gigantes/virologia , Humanos , Fusão de Membrana , Camundongos , Mutação , Neurônios/virologia , Vírus SSPE/genética , Proteínas Virais de Fusão/genética , Proteínas da Matriz Viral/genética
3.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576123

RESUMO

Nasu-Hakola Disease (NHD) is a recessively inherited systemic leukodystrophy disorder characterized by a combination of frontotemporal presenile dementia and lytic bone lesions. NHD is known to be genetically related to a structural defect of TREM2 and DAP12, two genes that encode for different subunits of the membrane receptor signaling complex expressed by microglia and osteoclast cells. Because of its rarity, molecular or proteomic studies on this disorder are absent or scarce, only case reports based on neuropsychological and genetic tests being reported. In light of this, the aim of this paper is to provide evidence on the potential of a label-free proteomic platform based on the Multidimensional Protein Identification Technology (MudPIT), combined with in-house software and on-line bioinformatics tools, to characterize the protein expression trends and the most involved pathways in NHD. The application of this approach on the Lymphoblastoid cells from a family composed of individuals affected by NHD, healthy carriers and control subjects allowed for the identification of about 3000 distinct proteins within the three analyzed groups, among which proteins anomalous to each category were identified. Of note, several differentially expressed proteins were associated with neurodegenerative processes. Moreover, the protein networks highlighted some molecular pathways that may be involved in the onset or progression of this rare frontotemporal disorder. Therefore, this fully automated MudPIT platform which allowed, for the first time, the generation of the whole protein profile of Lymphoblastoid cells from Nasu-Hakola subjects, could be a valid approach for the investigation of similar neurodegenerative diseases.


Assuntos
Lipodistrofia/metabolismo , Lipodistrofia/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patologia , Proteômica , Panencefalite Esclerosante Subaguda/metabolismo , Panencefalite Esclerosante Subaguda/patologia , Análise por Conglomerados , Análise Discriminante , Humanos , Glicoproteínas de Membrana/metabolismo , Mapas de Interação de Proteínas , Receptores Imunológicos/metabolismo , Biologia de Sistemas
4.
BMJ Case Rep ; 14(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518172

RESUMO

A 13-year-old girl with perinatally acquired HIV infection was admitted to us with acute onset, right-sided hemiparesis of 30 days duration and right-sided myoclonic jerks of 2 days duration affecting the face, upper and lower limbs. On examination, she exhibited increased tone and a pyramidal pattern of weakness in her right upper and lower limbs, along with spontaneous multifocal myoclonic jerks in the affected area. IgG levels in the serum and cerebrospinal fluid for measles were significantly elevated. Brain MRI depicted T2-weighted-hyperintensities in the subcortical white matter. The electroencephalogram demonstrated evidence of lateralised long interval periodic discharges. This patient had no past behavioural problems or poor academic performance. This case underlines the fact that, though subacute sclerosing panencephalitis (SSPE) is a chronic disease, a rare fulminant form of SSPE might develop acutely and atypically, with an increased proclivity for HIV-infected patients.


Assuntos
Infecções por HIV , Panencefalite Esclerosante Subaguda , Adolescente , Eletroencefalografia , Feminino , Infecções por HIV/complicações , Humanos , Neuroimagem , Paresia/etiologia , Panencefalite Esclerosante Subaguda/complicações , Panencefalite Esclerosante Subaguda/diagnóstico
5.
Eur J Paediatr Neurol ; 34: 43-49, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34388650

RESUMO

BACKGROUND: Subacute Sclerosing Panencephalitis (SSPE) is a fatal progressive neurological disorder following measles infection. METHODS: Cases were collated from Paediatric Neurology centres in the UK over 24 months from 2017 to 2019 and represent all cases referred to the National Viral Reference Department (VRD). Diagnosis was established with detection of a raised measles index, demonstrating intrathecal measles antibody production. FINDINGS: Six children presented with SSPE over two years, with median age five years (range 2-7 years) and median latency period three years (range 2-6 years). The majority were exposed to measles during infancy. Atypical features were common, including visual impairment, focal and generalised tonic-clonic seizures, headache, vomiting and movement disorders. EEG demonstrated typical features in five cases, though not always at presentation. Initial MRI was normal in four cases, with two showing focal and widespread white matter changes. Antiviral and immunomodulatory treatment led to minimal or no improvement. All progressed to cognitive regression, seizures and neurological decline within six months. INTERPRETATION: These cases demonstrate the highest incidence of SSPE in the UK since 2000, all progressing to acute fulminant disease, following younger age of onset, short latency period and atypical presentations. Recent global surges in measles cases raise the importance of clinician awareness of SSPE as a potential diagnosis in children with neurological regression. Herd immunity remains the key protective mechanism for infants and groups that cannot be vaccinated. Health care providers, educators and governments must ensure resources continue to target effective education and access to immunisation programmes, the only means to combat this devastating and fatal condition.


Assuntos
Sarampo , Panencefalite Esclerosante Subaguda , Criança , Pré-Escolar , Humanos , Lactente , Imageamento por Ressonância Magnética , Sarampo/complicações , Sarampo/diagnóstico , Sarampo/epidemiologia , Panencefalite Esclerosante Subaguda/diagnóstico , Panencefalite Esclerosante Subaguda/epidemiologia , Reino Unido/epidemiologia , Vacinação
6.
Rev Neurol (Paris) ; 177(9): 1059-1068, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34187690

RESUMO

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare, non-treatable and fatal neurological complication of measles, still present due to the return of the epidemic linked to the loosening of vaccination policies. Its mechanism remains unexplained. OBJECTIVE: The main objective was to investigate explanatory variables relating to the risk of developing SSPE and its pathophysiology. METHODS: Literature analysis was focused on different varieties of SSPE: perinatal forms, short-incubation forms similar to acute measles inclusion body encephalitis (MIBE), rapidly evolving forms, forms occurring in the immunosuppressed, adult forms, and family forms. In addition, several studies on the parameters of innate immunity and interferon responses of patients were analyzed. RESULTS: Two main data were highlighted: a relationship between the so-called fulminant forms and the prescription of corticosteroids was established. In familial SSPE, two groups were individualized according to the duration of the latency period, prompting an analysis of patient exomes. CONCLUSION: Treatment with corticosteroids should be banned. Knowledge of the genes involved and epigenetics should be useful for understanding the pathophysiology of SSPE and other late-onset neurological infections with RNA viruses.


Assuntos
Doenças Transmissíveis , Epidemias , Sarampo , Panencefalite Esclerosante Subaguda , Adulto , Feminino , Humanos , Sarampo/complicações , Sarampo/epidemiologia , Gravidez , Panencefalite Esclerosante Subaguda/diagnóstico , Panencefalite Esclerosante Subaguda/epidemiologia , Vacinação
7.
Eur J Neurol ; 28(8): 2603-2613, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33969597

RESUMO

BACKGROUND AND PURPOSE: Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. METHOD: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. RESULTS: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. CONCLUSION: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.


Assuntos
Demência Frontotemporal , Lipodistrofia , Glicoproteínas de Membrana/genética , Osteocondrodisplasias , Receptores Imunológicos/genética , Panencefalite Esclerosante Subaguda , Adulto , Encéfalo/diagnóstico por imagem , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/genética , Humanos , Imageamento por Ressonância Magnética , Neuroimagem
8.
J Virol ; 95(14): e0052821, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-33910952

RESUMO

Measles virus (MeV), an enveloped RNA virus in the family Paramyxoviridae, is still an important cause of childhood morbidity and mortality worldwide. MeV usually causes acute febrile illness with skin rash, but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). The disease is fatal, and no effective therapy is currently available. Although transsynaptic cell-to-cell transmission is thought to account for MeV propagation in the brain, neurons do not express the known receptors for MeV. Recent studies have shown that hyperfusogenic changes in the MeV fusion (F) protein play a key role in MeV propagation in the brain. However, how such mutant viruses spread in neurons remains unexplained. Here, we show that cell adhesion molecule 1 (CADM1; also known as IGSF4A, Necl-2, and SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, SynCAM2) are host factors that enable MeV to cause membrane fusion in cells lacking the known receptors and to spread between neurons. During enveloped virus entry, a cellular receptor generally interacts in trans with the attachment protein on the envelope. However, CADM1 and CADM2 interact in cis with the MeV attachment protein on the same cell membrane, causing the fusion protein triggering and membrane fusion. Knockdown of CADM1 and CADM2 inhibits syncytium formation and virus transmission between neurons that are both mediated by hyperfusogenic F proteins. Thus, our results unravel the molecular mechanism (receptor-mimicking cis-acting fusion triggering) by which MeV spreads transsynaptically between neurons, thereby causing SSPE. IMPORTANCE Measles virus (MeV), an enveloped RNA virus, is the causative agent of measles, which is still an important cause of childhood morbidity and mortality worldwide. Persistent MeV infection in the brain causes a fatal progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. However, how MeV spreads in neurons, which are mainly affected in SSPE, remains largely unknown. In this study, we demonstrate that cell adhesion molecule 1 (CADM1) and CADM2 are host factors enabling MeV spread between neurons. During enveloped virus entry, a cellular receptor generally interacts in trans with the attachment protein on the viral membrane (envelope). Remarkably, CADM1 and CADM2 interact in cis with the MeV attachment protein on the same membrane, triggering the fusion protein and causing membrane fusion, as viral receptors usually do in trans. Careful screening may lead to more examples of such "receptor-mimicking cis-acting fusion triggering" in other viruses.


Assuntos
Molécula 1 de Adesão Celular/fisiologia , Moléculas de Adesão Celular/fisiologia , Vírus do Sarampo/patogenicidade , Panencefalite Esclerosante Subaguda/virologia , Internalização do Vírus , Animais , Linhagem Celular , Chlorocebus aethiops , Células Gigantes/virologia , Humanos , Camundongos , Células Vero , Proteínas do Envelope Viral/metabolismo , Proteínas Virais de Fusão/metabolismo
9.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542002

RESUMO

Subacute sclerosing panencephalitis (SSPE) is a progressive lethal neurological inflammatory disease due to persistent, wild measles virus infection in the central nervous system that is seen most frequently in children and young adolescents. Atypical presentations are seen in up to 10% of cases. Most frequently and severely affected region in the brain is the parieto-occipital region of the brain. Less commonly involved organs are the cerebellum, basal ganglia and corpus callosum. Brainstem involvement is rare and usually occurs when other areas of brain are involved along with it. Here, we describe an unusual male patient of 15 years age, having SSPE with MRI of brain showing extensive involvement of brainstem with no significant involvement of other cortical structures of the brain. It is very rarely described in SSPE, but one should be vigilant about such involvement of brainstem and cerebellum, and SSPE should not be missed when brainstem hyperintensities are seen in MRI brain with or without other region of the brain to avoid misdiagnosis.


Assuntos
Tronco Encefálico/fisiopatologia , Panencefalite Esclerosante Subaguda/diagnóstico , Adolescente , Tronco Encefálico/virologia , Eletroencefalografia , Paralisia Facial/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Sarampo/virologia , Mioclonia/etiologia
10.
Brain Behav ; 11(4): e02051, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543580

RESUMO

BACKGROUND: The clinical features and outcomes of subacute sclerosing panencephalitis (SSPE) in younger children are different from those of adults, leading easily to misdiagnosis during the early stage. So far, there are limited data related to SSPE in preschool children. METHODS: In order to summarize the clinical data and evolution of SSPE in preschool children and to expand the phenotypes of SSPE, the medical charts of preschool patients diagnosed with SSPE were retrospectively reviewed and analyzed; the clinical outcomes of the enrolled cases were evaluated and followed up. RESULTS: Overall, we included three cases in the study. Their onset age was 5 years and 2 months, 4 years and 3 months, and 4 years and 2 months, respectively. All patients presented drop attacks or jerks as the onset symptom, and one patient had concurrent gait disturbance. Atypical periodic complexes on electroencephalography (EEG) were recorded in all patients. The brain magnetic resonance imaging (MRI) findings of two cases showed demyelinating lesions predominantly on the white matter. The neurological conditions of all cases deteriorated rapidly. Two children died at 21 months and 6 months after onset, respectively. The other case progressively developed vegetative status and akinetic mutism within 4 months. CONCLUSIONS: In younger children, the characteristic features of SSPE may be seizures and gait instability as onset manifestations, atypical periodic complexes on EEG, and rapid worsening of neurological conditions.


Assuntos
Panencefalite Esclerosante Subaguda , Pré-Escolar , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Convulsões , Panencefalite Esclerosante Subaguda/diagnóstico , Panencefalite Esclerosante Subaguda/diagnóstico por imagem
11.
PLoS One ; 16(1): e0245077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33411786

RESUMO

In subacute sclerosing panencephalitis (SSPE) the persistence of measles virus (MeV) may be related to the altered immune response. In this study, cytokine responses of lymphocytes and monocytes were evaluated in SSPE compared to controls with non-inflammatory (NICON) and inflammatory (ICON) diseases. Patients with SSPE (n = 120), 78 patients with ICON and 63 patients with NICON were included in this study. Phenotypes of peripheral blood mononuclear cells (PBMC) have been analyzed by flow cytometry. CD3 and CD28, and S. aureus Cowan strain I (SAC) stimulated and unstimulated cells were cultured and IL-2, IL-10, IFN-γ, IL-12p40, IL-12p70 and IL-23 were detected in supernatants by ELISA. MeV peptides were used for MeV-specific stimulation and IFN-γ secretion of PBMC was measured by ELISPOT. Spontaneous and stimulated secretions of IL-10 were lower in SSPE compared to both control groups. T cell stimulation induced lower IFN-γ production than ICON group, but higher IL-2 than NICON group in SSPE. Stimulated PBMC produced lower IL-12p70 in SSPE and had decreased CD46 on the cell surface, suggesting the interaction with the virus. IFN-γ responses against MeV peptides were not prominent and similar to NICON patients. The immune response did not reveal an inflammatory activity to eliminate the virus in SSPE patients. Even IL-10 production was diminished implicating that the response is self-limited in controlling the disease.


Assuntos
Antígenos CD/imunologia , Citocinas/imunologia , Vírus do Sarampo/imunologia , Panencefalite Esclerosante Subaguda/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Panencefalite Esclerosante Subaguda/patologia
12.
Molecules ; 26(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467470

RESUMO

Subacute sclerosing panencephalitis (SSPE) is a late-onset, intractable, and fatal viral disease caused by persistent infection of the central nervous system by a mutant strain of the measles virus. Ribavirin intracerebroventricular therapy has already been administered to several SSPE patients in Japan based on fundamental and clinical research findings from our group, with positive therapeutic effects reported in some patients. However, the efficacy of this treatment approach has not been unequivocally established. Hence, development of more effective therapeutic methods using new antiviral agents is urgently needed. This review describes the current status of SSPE treatment and research, highlighting promising approaches to the development of more effective therapeutic methods.


Assuntos
Antivirais/uso terapêutico , Panencefalite Esclerosante Subaguda/tratamento farmacológico , Animais , Antivirais/farmacologia , Desenvolvimento de Medicamentos , Humanos
13.
Mov Disord ; 36(2): 497-503, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32986918

RESUMO

BACKGROUND: Repetitive behaviors refer to a broad class of responses ranging from stereotypic body movements to impulsive/compulsive behaviors. They may be associated with neurological disorders. METHODS: This is a case series of six subacute sclerosing panencephalitis (SSPE) patients who presented with a wide spectrum of repetitive motor behaviors and vocalizations. RESULTS: Repetitive motor behaviors involved the upper limbs in all patients and lower limbs in 3 patients. The repetitive movements in the upper limbs were clapping, finger-clicking, hand rubbing, flailing, and dystonic posturing. In the lower limbs, the repetitive movements were rubbing with the heel, pelvic thrusting with flexion extension of the leg, and foot tapping. The spectrum of vocalizations included palilalia, whistling, grunting with spitting, and pathological crying. Repetitive behaviors were the presenting features in 2 patients. CONCLUSIONS: This case series expands the spectrum of repetitive behaviors seen in neurological disorders associated with brain infections. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Transtornos dos Movimentos , Panencefalite Esclerosante Subaguda , Encéfalo , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Panencefalite Esclerosante Subaguda/complicações
14.
Jpn J Infect Dis ; 74(2): 154-156, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32863356

RESUMO

Subacute sclerosing panencephalitis (SSPE) is a late-onset, intractable, and fatal viral disease caused by persistent infection of the central nervous system with a measles virus mutant (SSPE virus). In Japan, interferon-α and ribavirin are administered intracerebroventricularly to patients with SSPE. However, as the therapeutic effect is insufficient, more effective drugs are needed. Favipiravir, which is clinically used as an anti-influenza drug, demonstrates anti-viral effects against RNA viruses. In this study, the antiviral effect of favipiravir against measles virus (Edmonston strain) and SSPE virus (Yamagata-1 strain) was examined in vitro. The 50% effective concentration (EC50) of favipiravir (inhibiting viral plaque formation by 50%) against Edmonston and Yamagata-1 strains were 108.7 ± 2.0 µM (17.1 ± 0.3 µg/mL) and 38.6 ± 6.0 µM (6.1 ± 0.9 µg/mL), respectively, which were similar to those of ribavirin. The antiviral activity of favipiravir against the SSPE virus was demonstrated for the first time in this study.


Assuntos
Amidas/farmacologia , Antivirais/farmacologia , Sarampo/tratamento farmacológico , Pirazinas/farmacologia , Panencefalite Esclerosante Subaguda/tratamento farmacológico , Animais , Chlorocebus aethiops , Humanos , Interferon-alfa/farmacologia , Japão , Sarampo/patologia , Vírus do Sarampo/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ribavirina/farmacologia , Vírus SSPE/efeitos dos fármacos , Panencefalite Esclerosante Subaguda/patologia , Células Vero
15.
J Alzheimers Dis ; 79(1): 25-30, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33216037

RESUMO

Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer's disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer's disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.


Assuntos
Encéfalo/patologia , Lipodistrofia/patologia , Emaranhados Neurofibrilares/patologia , Osteocondrodisplasias/patologia , Placa Amiloide/patologia , Panencefalite Esclerosante Subaguda/patologia , Doença de Alzheimer/patologia , Encéfalo/diagnóstico por imagem , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/patologia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Lipodistrofia/diagnóstico por imagem , Lipodistrofia/genética , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Neocórtex/diagnóstico por imagem , Neocórtex/patologia , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Receptores Imunológicos/genética , Panencefalite Esclerosante Subaguda/diagnóstico por imagem , Panencefalite Esclerosante Subaguda/genética , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
16.
Emerg Infect Dis ; 26(9): 2231-2234, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32818389

RESUMO

We report a fatal case of measles inclusion-body encephalitis occurring in a woman from Romania with AIDS. After an extensive but unsuccessful diagnostic evaluation, a pan-pathogen shotgun metagenomic approach revealed a measles virus infection. We identified no mutations previously associated with neurovirulence.


Assuntos
Síndrome de Imunodeficiência Adquirida , Sarampo , Panencefalite Esclerosante Subaguda , Adulto , Encéfalo/diagnóstico por imagem , Feminino , França , Humanos , Sarampo/diagnóstico , Vírus do Sarampo/genética , Romênia
17.
Pediatr Neurol ; 110: 59-63, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32718528

RESUMO

BACKGROUND: Aprepitant is a neurokinin-1 receptor antagonist approved for the treatment of chemotherapy-induced nausea. We aimed to investigate the safety and efficacy of aprepitant in patients with subacute sclerosing panencephalitis. METHODS: A randomized, double-blind, placebo-controlled study was conducted in patients with subacute sclerosing panencephalitis assigned to receive two courses of aprepitant 250 mg/day orally or placebo for 15 days with an interval of two months between courses. Primary end points were safety and tolerability, and secondary end point was clinical improvement or stabilization assessed by subacute sclerosing panencephalitis scoring system. Electroencephalography (EEG), brain magnetic resonance imaging, and cerebrospinal fluid measles-specific immunoglobulin G index were evaluated before and after treatment. RESULTS: Sixty-two patients with subacute sclerosing panencephalitis were allocated to aprepitant (n = 31, median age 18 years) or placebo (n = 31, median age 22 years) group. Fifteen patients left the study within the first six months and 12 patients left between six and 12 months. Aprepitant was well tolerated and treatment-associated adverse events were similar to those described in the treatment of nausea. Clinical status at six and 12 months' follow-up did not differ between aprepitant and placebo groups. Post-treatment EEG scores at 12 months were better in the aprepitant group (P = 0.015). Cerebral atrophy on magnetic resonance imaging increased in both groups, whereas measles-specific immunoglobulin G index decreased in the placebo group. CONCLUSIONS: In this first clinical trial of aprepitant treatment in patients with subacute sclerosing panencephalitis, the drug was safe and well tolerated. No clinical effect was observed. A modest improvement in EEG findings might justify trials for longer periods because EEG changes can precede clinical findings in subacute sclerosing panencephalitis.


Assuntos
Aprepitanto/farmacologia , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Panencefalite Esclerosante Subaguda/tratamento farmacológico , Adolescente , Adulto , Aprepitanto/administração & dosagem , Aprepitanto/efeitos adversos , Atrofia/patologia , Método Duplo-Cego , Eletroencefalografia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/efeitos adversos , Panencefalite Esclerosante Subaguda/patologia , Panencefalite Esclerosante Subaguda/fisiopatologia , Adulto Jovem
18.
Trop Doct ; 50(4): 354-358, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32664798

RESUMO

Adult onset subacute sclerosing panencephalitis (SSPE) after the third decade of life is rare and the manifestations can mimic disorders such as dysmyelinating and metabolic disorders. This case report presents a patient with acute binocular visual impairment in his fifth decade as the first manifestation of SSPE. This is preventable with immunisation against measles. A prior history of measles infection may not be forthcoming in adult onset SSPE. This should be kept in mind as a differential diagnosis when a patient from endemic area presents with acute visual loss even in the absence of classic features. Periodic generalised discharges on the EEG without myoclonus may be seen in this condition rarely as in this case.


Assuntos
Panencefalite Esclerosante Subaguda/complicações , Panencefalite Esclerosante Subaguda/diagnóstico , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Doença Aguda , Adulto , Diagnóstico Diferencial , Eletroencefalografia , Humanos , Masculino , Sarampo/complicações , Panencefalite Esclerosante Subaguda/fisiopatologia , Transtornos da Visão/fisiopatologia
20.
Pediatr Int ; 62(8): 920-925, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32239783

RESUMO

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disorder caused by the measles virus (MV) and is identified by positive MV-specific antibody titers, detected mainly by hemagglutination inhibition (HI) tests in the cerebrospinal fluid (CSF). However, an alternative method, the enzyme immunoassay (EIA), has increasingly become a preferred method for detecting MV antibodies. To establish the index for SSPE diagnosis using EIA, we investigated the correlation between HI and EIA titers of MV antibodies in SSPE patients. METHODS: Data on MV antibody titers and measurement methods at the time of diagnosis in 89 Japanese SSPE cases diagnosed between 1979 and 2006 were obtained by a survey. We also assessed the serum and CSF MV antibody titers in three patients with SSPE and serum MV antibody titers in 38 healthy adults using immunoglobulin G (IgG)-EIA and HI. RESULTS: In all cases diagnosed as SSPE, IgG-EIA titers in the CSF were ≥0.49 IU/mL. There was a positive correlation between serum antibody values in the controls measured by IgG-EIA and HI. In patients with SSPE, both serum and CSF antibody values, measured by IgG-EIA, and HI, were positively correlated, and a positive correlation was found between the serum and CSF MV antibody titers as measured by IgG-EIA. The serum/CSF MV antibody titer ratios determined by IgG-EIA were <20 in most SSPE patients. CONCLUSIONS: Immunoglobulin G-EIA may be a suitable alternative method for SSPE diagnosis; however, its potential utility and the cut-off point of ≥0.49 IU/mL should be tested with additional patient cohorts.


Assuntos
Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Técnicas Imunoenzimáticas/métodos , Vírus do Sarampo/imunologia , Panencefalite Esclerosante Subaguda/diagnóstico , Adulto , Testes de Inibição da Hemaglutinação/métodos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Japão , Panencefalite Esclerosante Subaguda/sangue , Panencefalite Esclerosante Subaguda/líquido cefalorraquidiano , Panencefalite Esclerosante Subaguda/imunologia , Inquéritos e Questionários
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