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Cell-to-cell spreading of misfolded α-synuclein (αSYN) is supposed to play a key role in the pathological progression of Parkinson's disease (PD) and other synucleinopathies. Receptor-mediated endocytosis has been shown to contributes to the uptake of αSYN in both neuronal and glial cells. To determine the receptor involved in αSYN endocytosis on the cell surface, we performed unbiased, and comprehensive screening using a membrane protein library of the mouse whole brain combined with affinity chromatography and mass spectrometry. The candidate molecules hit in the initial screening were validated by co-immunoprecipitation using cultured cells; sortilin, a vacuolar protein sorting 10 protein family sorting receptor, exhibited the strongest binding to αSYN fibrils. Notably, the intracellular uptake of fibrillar αSYN was slightly but significantly altered, depending on the expression level of sortilin on the cell surface, and time-lapse image analyses revealed the concomitant internalization and endosomal sorting of αSYN fibrils and sortilin. Domain deletion in the extracellular portion of sortilin revealed that the ten conserved cysteines (10CC) segment of sortilin was involved in the binding and endocytosis of fibrillar αSYN; importantly, pretreatment with a 10CC domain-specific antibody significantly hindered αSYN fibril uptake. The presence of sortilin in the core structure of Lewy bodies and glial cytoplasmic inclusions in the brain of synucleinopathy patients was confirmed via immunohistochemistry, and the expression level of sortilin in mesencephalic dopaminergic neurons may be altered with disease progression. These results provide compelling evidence that sortilin acts as an endocytic receptor for pathogenic form of αSYN, and yields important insight for the development of disease-modifying targets for synucleinopathies.
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Proteínas Adaptadoras del Transporte Vesicular , Enfermedad de Parkinson , Sinucleinopatías , Animales , Ratones , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , alfa-Sinucleína/metabolismo , Proteínas Portadoras , Enfermedad de Parkinson/metabolismoRESUMEN
The etiology of central diabetes insipidus (DI) is classified into (1) idiopathic, (2) familial, and (3) secondary. Of these, familial central diabetes insipidus shows an autosomal dominant inheritance. We herein report a case in which this disease was diagnosed based on a family history of nocturnal enuresis. A 40-year-old man had had symptoms of polydipsia, polyuria and nocturia since childhood and found that his daughter had the same symptoms. Despite reaching nine years old, his daughter's nocturnal enuresis still had not improved, resulting in her consulting a pediatrician. She was suspected of having familial neurohypophyseal diabetes insipidus (FNDI) based on her family history and was referred along with her father for a detailed examination and treatment. A hypertonic saline load test (HSLT) to evaluate the arginine vasopressin (AVP) reaction was performed in both the proband and his daughter. The results showed no increase in AVP levels in response to high plasma osmolality. The water deprivation test (WDT) revealed he was suffering from partial DI. Based on the above findings and considering the possibility of familial central diabetes insipidus, we performed a gene mutation analysis of AVP-neurophysin II (NPII). Both the father and daughter had an exon 2 abnormality in this gene (c232_234delGAG; pGlu78del), and this gene mutation is known to cause NPII protein abnormality, abolishing the function of AVP as a carrier protein. This case was considered to have provided an opportunity to understand the role of an NPII gene abnormality in familial central diabetes insipidus.
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Diabetes Insípida Neurogénica , Diabetes Mellitus , Enuresis Nocturna , Adulto , Arginina Vasopresina , Niño , Diabetes Insípida Neurogénica/diagnóstico , Diabetes Insípida Neurogénica/genética , Femenino , Humanos , Masculino , Mutación , Neurofisinas/genética , Enuresis Nocturna/etiología , Enuresis Nocturna/genética , LinajeRESUMEN
Myelin oligodendrocyte glycoprotein (MOG)-IgG detected by the cell-based assay is associated with demyelinating diseases of the central nervous system, such as optic neuritis, myelitis, and acute disseminated encephalomyelitis, but rarely with peripheral neuropathy. Here, we describe the case of a 32-year-old MOG-IgG+ woman who developed central and peripheral demyelinating lesions. In contrast to previous similar cases, she uniquely presented with repeated subsequent relapses in the peripheral nerve, mimicking chronic inflammatory demyelinating polyneuropathy. Possible pathogenic implications of MOG-IgG in combined central and peripheral nervous system diseases are considered.
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Enfermedades Desmielinizantes , Enfermedades del Sistema Nervioso Periférico , Adulto , Autoanticuerpos , Enfermedades Desmielinizantes/tratamiento farmacológico , Femenino , Humanos , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , EsteroidesRESUMEN
APS001F is a strain of Bifidobacterium longum genetically engineered to express cytosine deaminase that converts 5-fluorocytosine (5-FC) to 5-fluorouracil. In the present study, antitumor effects of APS001F plus 5-FC (APS001F/5-FC) in combination with anti-PD-1 monoclonal antibody were investigated using a CT26 syngeneic mouse model. Both of dosing of APS001F/5-FC before and after anti-PD-1 mAb in the combination dosing exhibited antitumor effects as well as prolonged survival over the nontreated control. The survival rate in the combination therapy significantly increased over the monotherapy with APS001F/5-FC and that with anti-PD-1 mAb. Regulatory T cells among CD4+ T cells in tumor decreased in the combination therapy, while the ratio of CD8+ T cells was maintained in all groups. Taken these results together, APS001F/5-FC not only demonstrates a direct antitumor activity, but also immunomodulatory effects once localized in the hypoxic region of the tumor, which allows anti-PD-1 mAb to exert potentiated antitumor effects.
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Anticuerpos Monoclonales/inmunología , Antineoplásicos/farmacología , Bifidobacterium longum/fisiología , Flucitosina/farmacología , Ingeniería Genética , Receptor de Muerte Celular Programada 1/inmunología , Animales , Bifidobacterium longum/genética , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , RatonesRESUMEN
Early neurosyphilis commonly appears in basilar meninges, and its meningeal inflammation can spread to neighboring cranial nerves, resulting in some cranial nerve palsies. Herein, we report a case of a 51-year-old man who presented with right peripheral facial nerve palsy. His symptoms completely disappeared with prednisolone monotherapy without antibiotics use and were not exacerbated during clinical treatment. However, 2 months after remission of seventh cranial neuropathy, fifth and eighth cranial neuropathies appeared on the right side. Serologic tests for syphilis were revealed to be abnormal. Finally, the patient was diagnosed with early neurosyphilis with multiple cranial palsies. His neurological symptoms were markedly improved by combined penicillin-corticosteroid treatment. Systemic corticosteroids could be effective as adjunctive therapy to ameliorate neurological sequelae in early neurosyphilis.
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Antibacterianos/uso terapéutico , Enfermedades de los Nervios Craneales/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Neurosífilis/tratamiento farmacológico , Treponema pallidum/aislamiento & purificación , Encéfalo/diagnóstico por imagen , Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades de los Nervios Craneales/etiología , Quimioterapia Combinada/métodos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurosífilis/complicaciones , Neurosífilis/diagnóstico , Neurosífilis/microbiología , Penicilina G/uso terapéutico , Prednisolona/uso terapéutico , Trabajadores Sexuales , Factores de Tiempo , Resultado del TratamientoRESUMEN
We demonstrate universal non-adiabatic non-abelian holonomic single quantum gates over a geometric electron spin with phase-modulated polarized light and 93% average fidelity. This allows purely geometric rotation around an arbitrary axis by any angle defined by light polarization and phase using a degenerate three-level Λ-type system in a negatively charged nitrogen-vacancy center in diamond. Since the control light is completely resonant to the ancillary excited state, the demonstrated holonomic gate not only is fast with low power, but also is precise without the dynamical phase being subject to control error and environmental noise. It thus allows pulse shaping for further fidelity.
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Development of paradoxical cerebral embolism requires both unstable venous thrombosis and right-to-left shunt (RLS). Gastrointestinal endoscopy (GE) has the potential to affect intrathoracic and abdominal venous thrombi and to enhance RLS because the procedure alters intrathoracic and abdominal pressure. We describe a patient with Crohn's disease who developed paradoxical cerebral embolism after GE. Both an unstable venous thrombus in the superior vena cava and RLS through patent foramen ovale were thought to be responsible for the stroke. Considering that patients with digestive system diseases undergo GE as a routine examination or therapy, screenings for hypercoagulable state and intrathoracic and abdominal thrombi are important to prevent thromboembolism related to GE.
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Enfermedad de Crohn/diagnóstico por imagen , Embolia Paradójica/etiología , Endoscopía Gastrointestinal , Embolia Intracraneal/etiología , Complicaciones Posoperatorias , Anciano , Encéfalo/diagnóstico por imagen , Enfermedad de Crohn/complicaciones , Embolia Paradójica/diagnóstico por imagen , Embolia Paradójica/tratamiento farmacológico , Humanos , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/tratamiento farmacológico , MasculinoRESUMEN
A 28-year-old healthy man was admitted to our hospital because of right-sided headache, vomiting, and lower back pain after the administration of vardenafil. Computed tomography and magnetic resonance imaging of the brain showed a small, right-sided, subdural hematoma. A lumbar magnetic resonance imaging showed a longitudinally extended subdural hematoma. He had no history of trauma. We speculated that vardenafil might have had an association with the bleeding. Several reports have suggested a relationship between phosphodiesterase-5 inhibitors and intracerebral or subarachnoid hemorrhage. Our case suggested that there may also be risks of bleeding into the subdural space. Although headache and nausea are common side effects of vardenafil, hemorrhagic diseases should also be considered when symptoms are severe or prolonged.
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Hematoma Subdural Agudo/inducido químicamente , Hematoma Intracraneal Subdural/inducido químicamente , Hematoma Subdural Espinal/inducido químicamente , Hemorragias Intracraneales/inducido químicamente , Inhibidores de Fosfodiesterasa 5/efectos adversos , Diclorhidrato de Vardenafil/efectos adversos , Adulto , Tratamiento Conservador , Hematoma Subdural Agudo/diagnóstico por imagen , Hematoma Subdural Agudo/terapia , Hematoma Intracraneal Subdural/diagnóstico por imagen , Hematoma Intracraneal Subdural/terapia , Hematoma Subdural Espinal/diagnóstico por imagen , Hematoma Subdural Espinal/terapia , Humanos , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/terapia , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical library for anti-viral activity against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5'-triphosphate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity. Since the catalytic domain of RdRp is conserved among various types of RNA viruses, this mechanism of action underpins a broader spectrum of anti-viral activities of favipiravir. Favipiravir is effective against a wide range of types and subtypes of influenza viruses, including strains resistant to existing anti-influenza drugs. Of note is that favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of which are known to cause fatal hemorrhagic fever. These unique anti-viral profiles will make favipiravir a potentially promising drug for specifically untreatable RNA viral infections.
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Amidas/farmacología , Antivirales/farmacología , ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Pirazinas/farmacología , Virus/enzimología , Animales , Humanos , Virus/efectos de los fármacosRESUMEN
α-Synuclein (αS) is a key molecule in the pathomechanism of Parkinson's disease. Most studies on αS to date have focused on its function in the neuronal cytosol, but its action in the nucleus has also been postulated. Indeed, several lines of evidence indicate that overexpressed αS leads to epigenomic alterations. To clarify the functional role of αS in the nucleus and its pathological significance, HEK293 cells constitutively expressing αS were used to screen for nuclear proteins that interact with αS by nanoscale liquid chromatography/tandem mass spectrometry. Interactome analysis of the 229 identified nuclear proteins revealed that αS interacts with the BRG1-associated factor (BAF) complex, a family of multi-subunit chromatin remodelers important for neurodevelopment, and protein arginine methyltransferase 5 (PRMT5). Subsequent transcriptomic analysis also suggested a functional link between αS and the BAF complex. Based on these results, we analyzed the effect of αS overexpression on the BAF complex in neuronally differentiated SH-SY5Y cells and found that induction of αS disturbed the BAF maturation process, leading to a global increase in symmetric demethylation of histone H4 on arginine 3 (H4R3me2s) via enhanced BAF-PRMT5 interaction. Chromatin immunoprecipitation sequencing confirmed accumulated H4R3me2s methylation near the transcription start site of the neuronal cell adhesion molecule (NRCAM) gene, which has roles during neuronal differentiation. Transcriptional analyses confirmed the negative regulation of NRCAM by αS and PRMT5, which was reconfirmed by multiple datasets in the Gene Expression Omnibus (GEO) database. Taken together, these findings suggest that the enhanced binding of αS to the BAF complex and PRMT5 may cooperatively affect the neuronal differentiation process.
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Histonas , Proteína-Arginina N-Metiltransferasas , alfa-Sinucleína , Humanos , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Histonas/metabolismo , Histonas/genética , Metilación , Células HEK293 , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , ADN Helicasas/metabolismo , ADN Helicasas/genética , Arginina/metabolismo , Neuronas/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patologíaRESUMEN
Since the identification of vacuolar protein sorting (VPS) 35, as a causative molecule for familial Parkinson's disease (PD), retromer-mediated endosomal machinery has been a rising factor in the pathogenesis of the disease. The retromer complex cooperates with sorting nexin (SNX) dimer and DNAJC13, another causal molecule in PD, to transport cargoes from endosomes to the trans-Golgi network, and is also involved in mitochondrial dynamics and autophagy. Retromer dysfunction may induce neuronal death leading to PD via several biological cascades, including misfolded, insoluble α-synuclein (aS) accumulation and mitochondrial dysfunction; however, the detailed mechanisms remain poorly understood. In this study, we showed that the stagnation of retromer-mediated retrograde transport consistently occurs in different PD-mimetic conditions, i.e., overexpression of PD-linked mutant DNAJC13, excess aS induction, or toxin-induced mitochondrial dysfunction. Mechanistically, DNAJC13 was found to be involved in clathrin-dependent retromer transport as a functional modulator of SNX1 together with heat shock cognate 70 kDa protein (Hsc70), which was controlled by the binding and dissociation of DNAJC13 and SNX1 in an Hsc70 activity-dependent manner. In addition, excess amount of aS decreased the interaction between SNX1 and VPS35, the core component of retromer. Furthermore, R33, a pharmacological retromer chaperone, reduced insoluble aS and mitigated rotenone-induced neuronal apoptosis. These findings suggest that retrograde transport regulated by SNX1-retromer may be profoundly involved in the pathogenesis of PD and is a potential target for disease-modifying therapy for the disease.
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BACKGROUND: DYT-KMT2B, also known as DYT28, is a childhood-onset hereditary dystonia caused by KMT2B mutation. The pathogenesis of DYT-KMT2B involves haploinsufficiency of KMT2B, an enzyme that catalyzes specific histone methylation (H3K4me3). Dysmorphic features in patients with DYT-KMT2B suggest that KMT2B dysfunction may extend beyond the neuronal system. Therefore, valuable diagnostic insights may be obtained from readily available tissue samples. OBJECTIVES: To explore the altered H3K4me3 levels in non-neural tissue of DYT-KMT2B patients. METHODS: A database analysis was performed to determine in which parts of the body and in which cells KMT2B is highly expressed. Twelve clinically and genetically diagnosed patients with DYT-KMT2B and 12 control subjects participated in this study. Oral mucosa-derived purified histone proteins were analyzed using Western blotting with anti-H3K4me3 and anti-H4 antibodies. RESULTS: Higher expression of KMT2B was observed in oral keratinocytes and gingival fibroblasts, constituting the oral mucosa. In oral mucosa analyses, DYT-KMT2B cases exhibited markedly reduced H3K4me3 levels compared with the controls. Using a cutoff window of 0.90-0.98, the H3K4me3/H4 expression ratio was able to distinguish patient groups. CONCLUSIONS: Oral mucosa H3K4me3 analysis is currently not sufficient as a diagnostic tool for DYT-KMT2B, but has the advantage for screening test since it is a non-invasive means.
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Trastornos Distónicos , N-Metiltransferasa de Histona-Lisina , Histonas , Mucosa Bucal , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Trastornos Distónicos/genética , Trastornos Distónicos/metabolismo , Fibroblastos/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Histonas/genética , Queratinocitos/metabolismo , Metilación , Mucosa Bucal/metabolismoRESUMEN
Introduction: DYT-KMT2B is a rare childhood-onset, hereditary movement disorder typically characterized by lower-limb dystonia and subsequently spreads into the craniocervical and laryngeal muscles. Recently, KMT2B-encoding lysine (K)-specific histone methyltransferase 2B was identified as the causative gene for DYT-KMT2B, also known as DYT28. In addition to the fact that many physicians do not have sufficient experience or knowledge of hereditary dystonia, the clinical features of DYT-KMT2B overlap with those of other hereditary dystonia, and limited clinical biomarkers make the diagnosis difficult. Methods: Histone proteins were purified from the oral mucosa of patients with de novo KMT2B mutation causing premature stop codon, and then trimethylated fourth lysine residue of histone H3 (H3K4me3) which was catalyzed by KMT2B was analyzed by immunoblotting with specific antibody. We further analyzed the significance of H3K4me3 in patients with DYT-KMT2B using publicly available datasets. Results: H3K4me3 histone mark was markedly lower in the patient than in the control group. Additionally, a reanalysis of publicly available datasets concerning DNA methylation also demonstrated that KMT2B remained inactive in DYT-KMT2B. Discussion: Although only one case was studied due to the rarity of the disease, the reduction of H3K4me3 in the patient's biological sample supports the dysfunction of KMT2B in DYT-KMT2B. Together with informatics approaches, our results suggest that KMT2B haploinsufficiency contributes to the DYT-KMT2B pathogenic process.
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ASB2 proteins are E3 ubiquitin (Ub) ligases that ubiquitinate filamins. There are two ASB2 splice variants, ASB2α and ASB2ß. ASB2ß has a ubiquitin-binding motif (UIM) at the N-terminal region but ASB2α does not. Here, we provide the first evidence that ASB2ß but not ASB2α is monoubiquitinated and that this monoubiquitination involves the UIM. Myc-tagged ASB2ß and hemagglutinin (HA)-tagged Ub were co-expressed in HEK293 cells using the pCMV expression vector. Immunoprecipitation with an anti-Myc antibody followed by immunoblotting with anti-Myc and anti-HA antibodies showed an additional ASB2ß protein band that had both a Myc and a HA tag. The molecular weight of this protein was larger than that of ASB2ß, and the difference in molecular weight between these two proteins corresponded to the molecular weight of monoubiquitin, strongly implying that monoubiquitinated ASB2ß is produced in cells. ASB2ß with mutations in the UIM motif; either Glu·Asp·Glu27-29Ala·Ala·Ala mutations (ASB2ß M1) or a Ser38Ala mutation, (ASB2ß M2) were not monoubiquitinated, suggesting the importance of the UIM for ASB2ß monoubiquitination. Furthermore, an ASB2ß mutant that lacked a SOCS box (ASB2ß ΔC) and did not show E3 Ub ligase activity was monoubiquitinated to the same extent as the wild-type ASB2ß. In contrast, an ASB2ß mutant that lacked the UIM-containing domain (ASB2ß ΔN) was not monoubiquitinated. These results suggest that ASB2ß but not ASB2α might be monoubiquitinated and that the ASB2ß UIM motif, but not its E3 Ub ligase activity, plays a pivotal role in this monoubiquitination.
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Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Ubiquitina/metabolismo , Ubiquitinación , Células HEK293 , Humanos , Mutación , Estructura Terciaria de Proteína , Proteínas Supresoras de la Señalización de Citocinas/genética , Ubiquitina/genéticaRESUMEN
An alternative splicing variant of E3 ubiquitin ligase ASB2, termed ASB2a, has a distinct N-terminal sequence containing a ubiquitin-interacting motif (UIM) consensus sequence. Examination of the minimal essential region for binding to polyubiquitinated proteins indicated that the UIM consensus sequence (residues 26-41) alone is not enough, and that amino acids 12-41 from the N-terminus of ASB2a is essential for binding. ASB2a(12-41) peptide was chemically synthesized and coupled to Sepharose 4B via disulfide bonds. This ASB2a(12-41) peptide-coupled affinity resin bound both K48- and K63-linked polyubiquitinated proteins in cell lysates and comprehensively captured polyubiquitinated proteins, including polyubiquitinated ß-catenin, I-κB, and EGF receptor, which were eluted with 2-mercaptoethanol under non-denaturing conditions. These results indicate that this UIM affinity purification (designated as ubiquitin-trapping) is a useful method to discover polyubiquitinated proteins and their associated proteins.
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Oligopéptidos/química , Proteínas Supresoras de la Señalización de Citocinas/química , Proteínas Supresoras de la Señalización de Citocinas/aislamiento & purificación , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/aislamiento & purificación , Ubiquitinación , Secuencia de Aminoácidos , Cromatografía de Afinidad/métodos , Células HeLa , Humanos , Datos de Secuencia Molecular , Sefarosa/química , Ubiquitina/metabolismoRESUMEN
BACKGROUND: Hashimoto's encephalopathy with serum anti-NH2-terminal of α-enolase (NAE) antibodies occasionally displays clinical symptoms such as cerebellar ataxia and parkinsonism. We studied the frequency of anti-NAE antibodies in patients with Parkinson-plus syndrome. METHODS: We examined the positive rates of anti-NAE antibodies in 47 patients with multiple system atrophy (MSA), 29 patients with Parkinson's disease (PD), eight patients with corticobasal syndrome (CBS), and 18 patients with progressive supranuclear palsy (PSP) using conventional immunoblot analysis. RESULTS: Positive anti-NAE antibody rates of 31.9%, 10.3%, 50.0%, and 11.1% were reported in the MSA, PD, CBS, and PSP patients, respectively. The duration from onset to a wheelchair-bound state in seropositive MSA patients tended to be shorter than that in seronegative MSA patients. CONCLUSIONS: Anti-NAE antibodies are detected in some patients clinically diagnosed with MSA and CBS. Although its pathophysiological significance remains uncertain, serum anti-NAE antibodies might represent a prognostic marker in the clinical course of MSA.
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Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Parálisis Supranuclear Progresiva , Humanos , Atrofia de Múltiples Sistemas/epidemiología , Enfermedad de Parkinson/epidemiología , Fosfopiruvato Hidratasa , Prevalencia , Parálisis Supranuclear Progresiva/epidemiologíaRESUMEN
Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. Methods: 18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination-Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. Results: 18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP. Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.
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The pathophysiological mechanism of resting tremor in Parkinson's disease remains obscure. Spinal/peripheral mechanisms may modulate oscillatory activity from central origin, thereby changing amplitude and frequency of tremor in Parkinson's disease.
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Central nervous system intravascular lymphoma sometimes includes multiple lesions mimicking cerebral infarction. Herein, we report our experience with a case of intravascular large B-cell lymphoma (IVLBCL) with multiple hemorrhages. A 53-year-old woman was admitted to our hospital with clonic convulsions of the left upper limb. Brain MRI revealed a large number of high-intensity areas on FLAIR and low-intensity areas on susceptibility-weighted imaging (SWI). Chest CT showed bilateral multiple high-density lesions in the lungs. Biopsy of pulmonary lesions revealed no abnormal cells. Levetiracetam was administered to prevent the seizures that were assumed to occur due to the cerebral cortex lesions; however, convulsive seizure recurred with a depressed level of consciousness. On a repeat brain MRI examination, severe, multiple new lesions were shown to have developed bilaterally in the cerebral cortex and white matter, exhibiting spotty low intensities on SWI. Biopsy of a new cerebral lesion was carried out and the lesion was pathologically diagnosed as IVLBCL with hemorrhages. IVLBCL should be noted as one of the differential diagnoses not only in case with multiple infarct lesions, but also in case with multiple hemorrhages.
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Encéfalo/irrigación sanguínea , Encéfalo/patología , Hemorragias Intracraneales/etiología , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias Vasculares/complicaciones , Neoplasias Vasculares/diagnóstico , Biopsia , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Hemorragias Intracraneales/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias Vasculares/patologíaRESUMEN
Dysgeusia is rare in Guillain-Barré syndrome, particularly as the initial symptom. We herein report the case of a 59-year-old woman who presented with only dysgeusia as the initial symptom of Guillain-Barré syndrome, followed by gradually worsening muscle weakness and bilateral sensory disturbances in the extremities. Her dysgeusia was so unpleasant that she could not eat anything, so she received nasogastric tube feeding without dysphasia. We speculate that the dysgeusia in our patient was mainly caused by inflammation of the chorda tympani nerves. Guillain-Barré syndrome should be considered a possible cause of acute dysgeusia.