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Progression independent of relapse activity (PIRA) is prevalent among Caucasian patients with relapsing and remitting multiple sclerosis (RRMS). However, there is limited knowledge regarding the characteristics of PIRA in Asian patients with RRMS. Therefore, we retrospectively analyzed the clinical and radiological progression of 95 Japanese patients with RRMS during a 2-year observation period. PIRA was observed in three patients who were characterized by young age, large T2 lesion volume, and great reduction in brain volume. Despite having highly active disease, fewer patients with PIRA (33.3%) were treated with high-efficacy drugs compared with those without disease activity (60.7%).
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Progressão da Doença , Esclerose Múltipla Recidivante-Remitente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Coortes , População do Leste Asiático , Japão/epidemiologia , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva , Estudos RetrospectivosRESUMO
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of dormant JC polyomavirus (JCPyV). PML was mainly observed in immunocompromised individuals, such as HIV-positive patients, autoimmune disease patients, and cancer patients. Given that the presence of anti-JCPyV antibodies in serum is a risk indicator for PML development, it is essential to monitor anti-JCPyV antibody levels. In the present study, we established reporter-based single-infection neutralization assays for JCPyV and the genetically similar BK polyoma virus (BKPyV). We then confirmed the lack of cross-reactivity between the two viruses using test sera obtained from mice immunized with plasmids encoding the JCPyV or BKPyV capsid. Next, we compared neutralization antibody titers in sera from healthy donors, patients with multiple sclerosis (MS), and HIV-positive patients using an in-house enzyme-linked immunosorbent assay (ELISA) with JCPyV-like particles (virus-like particles; VLPs). A positive correlation was demonstrated between the neutralization titer (75% infectious concentration; IC75) against JCPyV and the antibody titer obtained by VLP-based JCPyV ELISA. This assay system may be applied to detect antibodies against other PyVs by generation of pseudoviruses using the respective capsid expression plasmids, and is expected to contribute to the surveillance of PyV as well as basic research on these viruses.
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Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.
Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Japão/epidemiologia , Vírus JC/genética , Reação em Cadeia da Polimerase , DNA ViralRESUMO
Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease and may sometimes present with symptoms of subacute encephalopathy, including fever, headache, vomiting, and loss of consciousness. We present a case of adult-onset NIID with subacute encephalopathy, which is confirmed by skin and brain biopsied. The magnetic resonance imaging findings show cortical swelling and hyperintensities in the right temporooccipital lobes on T2-weighted images and magnetic resonance angiography demonstrates vasodilatations of the right middle cerebral artery and posterior cerebral artery. Abnormal enhancement is mainly observed in the gyral crowns (crown enhancement). Pathological examinations reveal new infarcts in the deep layers of the cortices. NIID should be considered in the presence of subacute encephalopathy with cortical swelling, contrast enhancement in the temporooccipital lobes, and vasodilation in adult patients. The encephalopathy targeted on the cortices, and the pathological background included infarctions.
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BACKGROUND: 18F-THK5351 PET estimates the concentrations of monoamine oxidase B (MAO-B) that are preferentially located in astrocytes and can be used to visualize and quantify ongoing astrogliosis. To study images of astrogliosis in neurological disorders, it is essential to understand the detailed binding sites of 18F-THK5351 as the MAO-B ligand under normal conditions. In this study, we examined the detailed distribution pattern of 18F-THK5351 in the healthy brain by comparing 18F-THK5351 uptake between subjects taking and not taking the MAO-B inhibitor. METHODS: Ten healthy controls (HCs: 67.4 [SD, 15.1] years) and 4 patients with Parkinson disease taking the MAO-B inhibitor underwent 18F-THK5351 PET. The uptake ratio index (URI) was defined to quantify 18F-THK5351 uptake, using the cerebellum as a reference region. The cerebellar URI was set to zero. RESULTS: For HCs, regions with URI ≥1 were preferentially observed in the following order: the striatum, globus pallidus, thalamus, hypothalamus, amygdala, periaqueductal gray, substantia nigra, medulla, hippocampus, and pons. The peak URI values in the corresponding regions were 2.93, 2.47, 2.12, 2.04, 1.84, 1.68, 1.67, 1.37, 1.20, and 1.11, respectively. For all patients with Parkinson disease taking the MAO-B inhibitor, the URI values in all these regions were significantly decreased (Z score >2) and were reduced from 60.4% to 99.9%, compared with HCs. CONCLUSIONS: This study presented the detailed distribution pattern of 18F-THK5351 in HCs and suggests that 18F-THK5351 uptake largely reflects MAO-B concentrations under normal conditions.
Assuntos
Aminopiridinas , Encéfalo , Doença de Parkinson , Quinolinas , Aminopiridinas/farmacocinética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Gliose/metabolismo , Humanos , Ligantes , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons , Quinolinas/farmacocinéticaRESUMO
BACKGROUND: AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (<4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment. FINDINGS: Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug. INTERPRETATION: AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis. FUNDING: EA Pharma and Kissei Pharmaceutical. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.
Assuntos
Colite Ulcerativa , Nasofaringite , Colite Ulcerativa/tratamento farmacológico , Humanos , Quimioterapia de Indução/métodos , Integrina alfa4/antagonistas & inibidores , Mesalamina/efeitos adversos , Fenilalanina/análogos & derivados , Quinazolinonas , Resultado do TratamentoRESUMO
BACKGROUND: Coffee intake can decrease the risk for Parkinson's disease (PD). Its beneficial effects are allegedly mediated by caffeine through adenosine A2A receptor (A2A R) antagonist action. OBJECTIVE: We aimed to calculate occupancy rates of striatal A2A Rs by caffeine after coffee intake in PD. METHODS: Five patients with PD underwent 11 C-preladenant positron emission tomography scanning at baseline and after intake of coffee containing 129.5 mg (n = 3) or 259 mg (n = 2) of caffeine. Concurrently, serum caffeine levels were measured. RESULTS: The mean serum caffeine level (µg/mL) was 0.374 at baseline and increased to 4.48 and 8.92 by 129.5 and 259 mg of caffeine, respectively. The mean occupancy rates of striatal A2A Rs by 129.5 and 259 mg of caffeine were 54.2% and 65.1%, respectively. CONCLUSIONS: A sufficient A2A R occupancy can be obtained by drinking a cup of coffee, which is equivalent to approximately 100 mg of caffeine. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Adenosina , Cafeína/farmacologia , Café , Humanos , Doença de Parkinson/diagnóstico por imagem , Receptor A2A de AdenosinaRESUMO
BACKGROUND AND PURPOSE: Little evidence exists on the role of type 1 metabotropic glutamate receptor (mGluR1) in the pathophysiology of Alzheimer's disease (AD), although mGluR1 may be involved in the regulation of neuronal excitability and synaptic plasticity. We have recently reported that mGluR1 availability in the early stage of AD is equivalent to that in healthy subjects. This study aimed to address whether mGluR1 availability changes with the progression of AD. METHODS: Eight patients with AD (79.1 ± 4.6 years) underwent a total of two positron emission tomography (PET) examinations using the mGluR1 radioligand during the early-to-middle stages of AD. The mean interval was 2.8 years. Volumes-of-interest were placed on the frontal, parietal, and temporal cortices, hippocampus, anterior and posterior lobes, and vermis in the cerebellum. The binding potential (BPND ) was calculated to estimate mGluR1 availability, applying partial volume correction to the BPND values. RESULTS: No significant difference was observed in BPND values between the first and second PET examinations in the frontal cortex (p = 0.94), parietal cortex (p = 0.67), temporal cortex (p = 0.20), hippocampus (p = 0.17), anterior lobe (p = 0.73), posterior lobe (p = 0.21), and vermis (p = 0.22). CONCLUSION: This study suggests that mGluR1 availability is unchanged in the follow-up period of a few years during the early-to-middle stages of AD.
Assuntos
Doença de Alzheimer , Receptores de Glutamato Metabotrópico , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Humanos , Tomografia por Emissão de Pósitrons , Receptores de Glutamato Metabotrópico/metabolismoRESUMO
Three patients with neurological disorders (cerebral infarction, progressive multifocal leukoencephalopathy, and multiple sclerosis) underwent F-THK5351 and C-L-deprenyl PET on the same day to visualize lesions undergoing astrogliosis by measuring MAO-B activity. BPND map and SUV image with F-THK5351 as well as Ki map, Ki/K1 map and SUV image with C-L-deprenyl were created. F-THK5351 BPND maps and SUV images clearly identified the lesions undergoing astrogliosis. C-L-deprenyl Ki/K1 maps were close to F-THK5351 images, but very noisy. Ki maps and SUV images were likely affected by the effect of blood flow. Hence, F-THK5351 is superior to C-L-deprenyl for visualizing lesions undergoing astrogliosis.
Assuntos
Aminopiridinas/metabolismo , Radioisótopos de Carbono , Gliose/diagnóstico por imagem , Monoaminoxidase/metabolismo , Doenças do Sistema Nervoso/complicações , Tomografia por Emissão de Pósitrons , Quinolinas/metabolismo , Selegilina/metabolismo , Feminino , Gliose/complicações , Gliose/metabolismo , Humanos , Ligantes , MasculinoAssuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Transtornos Parkinsonianos/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Neoplasias do Tronco Encefálico/complicações , Neoplasias do Tronco Encefálico/secundário , Humanos , Masculino , Transtornos Parkinsonianos/etiologia , Transtornos Parkinsonianos/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/secundárioRESUMO
BACKGROUND: 18F-THK5351 was recently shown to bind to monoamine oxidase B (MAO-B) with high affinity. MAO-B is highly concentrated in astrocytes and increases during astrogliosis. Therefore, 18F-THK5351 accumulates in lesions undergoing astrogliosis. Cerebral infarction causes astrogliosis, which may be beneficial for repairing and regenerating injured cells and tissues in the lesions. Therefore, monitoring the degree of astrogliosis and stroke symptoms is essential for understanding the roles of astrogliosis in cerebral infarction. CASE PRESENTATION: A 72-year-old man, complaining of total loss of sensation in the left index finger, was diagnosed with acute cerebral infarction, and underwent 18F-THK5351 positron emission tomography (PET) on two occasions after the stroke. The first PET scan performed on day 27 revealed intense uptake in the infarct lesion located around the right precentral and postcentral gyri. However, the second PET scan on day 391 showed that the uptake had diminished significantly. The sensory deficit in the left index finger had improved by 30 and 70% at the times of the first and second PET scans, respectively. CONCLUSIONS: 18F-THK5351 uptake in the infarct lesion evidently changed between days 27 and 391, along with improved sensory deficit in the left index finger. Astrocytes reportedly play a role in restoring neuronal integrity. Therefore, the temporal course of astrogliosis may have been related to improving stroke symptoms in this patient, suggesting that the degree of astrogliosis in the infarct lesion may aid in assessing the prognosis in stroke patients.
Assuntos
Aminopiridinas/administração & dosagem , Infarto Cerebral/diagnóstico por imagem , Gliose/diagnóstico por imagem , Quinolinas/administração & dosagem , Idoso , Infarto Cerebral/etiologia , Infarto Cerebral/metabolismo , Lobo Frontal/diagnóstico por imagem , Gliose/complicações , Gliose/metabolismo , Humanos , Masculino , Monoaminoxidase/metabolismo , Tomografia por Emissão de Pósitrons , Córtex Somatossensorial/diagnóstico por imagemRESUMO
A 26-year-old woman with relapsing-remitting multiple sclerosis (MS) underwent F-THK5351 PET during a remission period. PET imaging showed that small regions with elevated uptake of F-THK5351 were scattered in the brain and that the foci of F-THK5351 accumulations corresponded anatomically to MS plaques identified by MRI. Because F-THK5351 binds to monoamine oxidase B highly expressed in astrocytes, F-THK5351 accumulates in lesions undergoing astrogliosis. Hence, elevated uptake of F-THK5351 in the present case can represent ongoing astrogliosis in inactive MS lesions (plaques).
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Aminopiridinas , Esclerose Múltipla/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Quinolinas , Compostos Radiofarmacêuticos , Adulto , Feminino , Gliose/diagnóstico por imagem , HumanosRESUMO
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of the JC virus under an immunosuppressed state. This condition carries a high risk of cryptococcal meningitis. We herein report a 65-year-old woman who simultaneously developed PML and cryptococcal meningitis and presented with bilateral sixth nerve palsy. She had been treated with methotrexate and infliximab for rheumatoid arthritis. Her symptoms improved with antifungal drug treatment and discontinuation of immunosuppression therapy. Although concurrent PML and cryptococcal meningitis is rare, it should be considered in immunosuppressed patients.
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Antifúngicos/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Terapia de Imunossupressão/efeitos adversos , Infliximab/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Meningite Criptocócica/tratamento farmacológico , Metotrexato/efeitos adversos , Idoso , Antirreumáticos/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/etiologia , Meningite Criptocócica/etiologia , Metotrexato/uso terapêutico , Resultado do TratamentoRESUMO
Imaging of type 1 metabotropic glutamate receptor (mGluR1) has recently become possible using positron emission tomography (PET). To date, little evidence exists on the role of mGluR1 in the pathophysiology of Alzheimer's disease (AD). We aimed to examine mGluR1 availability in patients with AD. Ten patients with AD (78.9⯱â¯5.9â¯years) and 12 age-matched volunteers (74.6⯱â¯2.6â¯years) underwent PET using an mGluR1 radiotracer. All patients were anti-dementia drug-naive. Volumes-of-interest were placed on the anterior and posterior lobes and vermis in the cerebellum and frontal, parietal, and temporal cortices. The binding potential (BPND) was calculated to estimate mGluR1 availability, and partial volume correction was applied to the BPND values. Mini Mental State Examination (MMSE) scores were also obtained (22.0⯱â¯4.8). No significant difference was observed in BPND between the AD and control groups in the anterior lobe (pâ¯=â¯.30), posterior lobe (pâ¯=â¯.95), vermis (pâ¯=â¯.96), frontal cortex (pâ¯=â¯.61), parietal cortex (pâ¯=â¯.59), or temporal cortex (pâ¯=â¯.27). No significant correlation was observed between BPND and MMSE scores in the anterior lobe (pâ¯=â¯.59), posterior lobe (pâ¯=â¯.35), vermis (pâ¯=â¯.92), frontal cortex (pâ¯=â¯.78), parietal cortex (pâ¯=â¯.83), or temporal cortex (pâ¯=â¯.82). In conclusions, this study suggests that mGluR1 availability is unchanged in the relatively early stage of AD. However, because regional mGluR1 availability may change with the progression of AD, further longitudinal follow-up is necessary.
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Doença de Alzheimer/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores de Glutamato Metabotrópico/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Radioisótopos de Carbono , Feminino , Humanos , MasculinoRESUMO
A 75-year-old man presented with dysarthria and left facial paralysis. Brain diffusion-weighted MRI revealed a high-signal intensity in the right precentral gyrus, and he was hospitalized under the diagnosis of cerebral infarction. His symptoms worsened and brain MRI findings were consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) JC virus (JCV) was undetectable in the DNA polymerase chain reaction (PCR) test four times, but brain biopsy revealed typical PML histopathology. He had no human immunodeficiency virus infection and history of immunosuppressive treatment, but he was found to have CD4+ lymphocytopenia. He was treated with mefloquine and mirtazapine, and died 29 months after symptoms onset. In cases whose repeated DNA PCR results are negative for CSF JCV, brain biopsy may be useful for the diagnosis of PML.
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Encéfalo/patologia , Linfócitos T CD4-Positivos , DNA Viral/líquido cefalorraquidiano , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Linfopenia/complicações , Resultados Negativos , Idoso , Encéfalo/diagnóstico por imagem , Quimioterapia Combinada , Humanos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/patologia , Imageamento por Ressonância Magnética , Masculino , Mefloquina/administração & dosagem , Mirtazapina/administração & dosagem , Reação em Cadeia da Polimerase , Resultado do TratamentoRESUMO
Istradefylline, an adenosine A2A receptor (A2AR) antagonist, is effective as an adjunct to levodopa and can alleviate "off" time and motor symptoms in patients with Parkinson's disease (PD). The present study aimed to calculate occupancy rates of A2ARs by administrating istradefylline 20â¯mg or 40â¯mg, which is the currently approved dose for PD in Japan. Additionally, A2AR availability was compared between patients with PD and healthy controls. Ten patients with PD under levodopa therapy and six age-matched healthy controls were included. The patients underwent a total of two 11C-preladenant positron emission tomography scans before and after the administration of istradefylline 20â¯mg or 40â¯mg (both nâ¯=â¯5). Binding potential (BPND) was calculated to estimate A2AR availability in the ventral striatum, caudate, and putamen. Maximal A2AR occupancy and ED50 were estimated by modeling the dose-occupancy curves. All patients were around the middle stage of PD, and their characteristics were clinically heterogeneous. Maximal A2AR occupancy and ED50 were 93.5% and 28.6â¯mg in the ventral striatum, 69.5% and 10.8â¯mg in the caudate, and 66.8% and 14.8â¯mg in the putamen, respectively. There were no significant differences in BPND values in the ventral striatum (Pâ¯=â¯0.42), caudate (Pâ¯=â¯0.72), and putamen (Pâ¯=â¯0.43) between the PD and control groups. In conclusion, the present study shows that istradefylline binds to A2ARs dose-dependently. A sufficient occupancy of A2ARs could be obtained by administrating the approved dose of istradefylline.
Assuntos
Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Antiparkinsonianos/uso terapêutico , Encéfalo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Purinas/uso terapêutico , Receptor A2A de Adenosina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Mapeamento Encefálico , Radioisótopos de Carbono , Relação Dose-Resposta a Droga , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons , Pirimidinas , Compostos Radiofarmacêuticos , TriazóisRESUMO
A 63-year-old man complaining of prolonged imbalance underwent C-CB184 PET to assess microglial activation 3 years after being diagnosed with cerebellar ataxia associated with HIV infection. C-CB184 images revealed significant cerebellar uptake where MRI signal abnormalities were observed at disease onset, although these abnormalities had mostly disappeared at the time of C-CB184 PET. Microglia are believed to be a long-term reservoir for HIV infection, causing persistent immune activation (ie, chronic inflammation). Hence, in this case, increased C-CB184 binding may reflect persistent microglial activation along with HIV persistence in the cerebellum. However, further pathological investigations are desired to validate C-CB184 PET.
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Radioisótopos de Carbono , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/patologia , Infecções por HIV/complicações , Imidazóis , Microglia/patologia , Tomografia por Emissão de Pósitrons , Piridinas , Ataxia Cerebelar/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Recent studies using the mouse model of Alzheimer's disease (AD) have shown that donepezil administration reduces brain amyloid-ß (Aß) accumulation. This study investigated whether donepezil administration can reduce brain Aß accumulation in human patients with AD. Ten patients with AD underwent two 11C-Pittsburgh Compound B positron emission tomography sessions approximately one year apart to measure brain Aß accumulation before and after donepezil treatment. Volumes-of-interest were placed on Aß-preferred regions, and the standardized uptake value ratio (SUVR) was calculated considering the cerebellum as a reference region. Three and seven patients received 10mg and 5mg of donepezil, respectively. SUVR was significantly higher in the second than in the first session (P=0.026). This study showed that one year of donepezil administration does not reduce brain Aß accumulation in human patients with AD.
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Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Indanos/farmacologia , Piperidinas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/metabolismo , Donepezila , Feminino , Neuroimagem Funcional , Humanos , Masculino , Nootrópicos/farmacologia , Tomografia por Emissão de Pósitrons , Tiazóis/metabolismo , Fatores de TempoRESUMO
The use of positron emission tomography (PET) imaging in progressive multifocal leukoencephalopathy (PML) has rarely been reported. We herein report a set of PET images in a 63-year-old patient with PML. In PML lesions, the uptake of 18F-fluorodeoxyglucose, 11C-methionine, 11C-flumazenil, and [methyl-11C]4'-thiothymidine was decreased, increased, decreased, and unchanged, respectively. These results suggest that glucose metabolism decreased, protein synthesis increased, neuronal integrity decreased, and the DNA synthesis and cellular proliferation of host cells were not activated in PML lesions. These results may reflect very little infiltration by inflammatory cells and active infection with JC virus in this case.