RESUMO
BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.
Assuntos
Diplopia , Transtornos da Motilidade Ocular , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Transtornos da Motilidade Ocular/diagnóstico , Movimentos Oculares , Cerebelo , ParalisiaRESUMO
Oxidative stress has been demonstrated to play a pivotal role in the pathological processes of many neurodegenerative diseases. In the present study, we demonstrated that Chrysanthemum boreale Makino extract (CBME) suppresses oxidative stress-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanism. Our observations revealed that CBME effectively protected neuronal cells against H2O2-induced cell death by preventing caspase-3 activation, Bax upregulation, Bcl-2 downregulation, activation of three mitogen-activated protein kinases (MAPKs), cAMP response element-binding protein (CREB) and NF-κB phosphorylation, and iNOS induction. These results provide evidence that CBME has remarkable neuroprotective properties in SH-SY5Y cells against oxidative damage, suggesting that the complementary or even alternative role of CBME in preventing and treating neurodegenerative diseases is worth further studies.
Assuntos
Chrysanthemum , Neuroblastoma , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Chrysanthemum/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Neuroblastoma/patologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND AND PURPOSE: The recognition of clinical features of transient vestibular symptoms (TVSs) preceding posterior circulation stroke (PCOS) would be informative to discriminate dizziness/vertigo due to vertebrobasilar transient ischemic attack from the acute transient vestibular syndrome. We sought to determine the prevalence and characteristics of TVSs preceding PCOS. METHODS: We performed a prospective multicenter observational study that had recruited 447 patients with PCOS from referral-based 4 university hospitals in Korea. We investigated the timing, pattern, frequency, duration, and accompanying neurological symptoms of TVSs during the 3 months preceding PCOS. RESULTS: The prevalence of TVSs preceding PCOS was 12% (55/447) during the previous 3 months. The TVSs preceding PCOS occurred within 1 week (33%), between 1 week and 1 month (16%), or between 1 and 3 months (51%). The TVSs were mostly dizziness/vertigo with (36%) or without (60%) imbalance, while the remaining 4% had an isolated imbalance. The dizziness/vertigo was spinning in 38% and was aggravated during head position in 45%. The duration of TVSs was mostly a few seconds (55%) or minutes (38%). Approximately 72% of the patients with PCOS had TVSs 1 to 5 times, while 16% had >10 times. Accompanying neurological symptoms, including headache, tinnitus, limb weakness, sensory change, dysarthria, visual field defect, and diplopia, were reported in 11%. CONCLUSIONS: Preceding TVSs can occur in 12% of PCOS during the previous 3 months. Isolated dizziness/vertigo of unknown cause needs to be considered as a vertebrobasilar transient ischemic attack symptom, especially in patients with vascular risk factors. The characteristics of isolated vestibular symptom in vertebrobasilar transient ischemic attacks is highly variable and atypical compared with other transient ischemic symptoms.
Assuntos
Tontura/diagnóstico , Ataque Isquêmico Transitório/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Vertigem/diagnóstico , Sistema Vestibular , Adulto , Idoso , Idoso de 80 Anos ou mais , Tontura/etiologia , Tontura/fisiopatologia , Feminino , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Vertigem/etiologia , Vertigem/fisiopatologia , Sistema Vestibular/fisiopatologia , Adulto JovemRESUMO
Hyperventilation-induced downbeat nystagmus (HV-DBN) has been reported in cerebellar disorders and explained by a loss of the inhibitory cerebellar output via a metabolic effect on cerebellar Ca2+ channels. The aim of this study was to determine the clinical characteristics and underlying pathogenesis of episodic vestibular syndrome (EVS) with HV-DBN. Of 667 patients with EVS, we recruited 22 with HV-DBN and assessed their clinical characteristics, video-oculographic findings, and the results of molecular genetic analyses. The age at symptom onset was 47.5 ± 13.0 years (mean ± SD), and there was a female preponderance (n = 15, 68%). The duration of vertigo/dizziness attacks ranged from minutes to a few days, and 11 patients (50%) fulfilled the diagnostic criteria for vestibular migraine. HV-induced new-onset DBN in 8 patients, while the remaining 14 showed augmentation of spontaneous DBN by HV. The maximum slow-phase velocity of HV-DBN ranged from 2.2 to 11.9°/s, which showed a statistical difference with that of spontaneous DBN (median = 4.95, IQR = 3.68-6.55 vs. median = 1.25, IQR = 0.20-2.15, p < 0.001). HV-DBN was either purely downbeat (n = 11) or accompanied with small horizontal components (n = 11). Other neuro-otologic findings included perverted head-shaking nystagmus (n = 11), central positional nystagmus (n = 7), saccadic pursuit (n = 3), and horizontal gaze-evoked nystagmus (n = 1). Gene expression profiling with a bioinformatics analysis identified 43 upregulated and 49 downregulated differentially expressed genes (DEGs) in patients with EVS and HV-DBN and revealed that the downregulated DEGs were significantly enriched in terms related to the ribosome pathway. Our results suggest that the underlying cerebellar dysfunction would be responsible for paroxysmal attacks of vertigo in patients with EVS and HV-DBN.
Assuntos
Doenças Cerebelares , Nistagmo Patológico , Doenças Vestibulares , Doenças Cerebelares/complicações , Feminino , Humanos , Hiperventilação/complicações , Hiperventilação/genética , Nistagmo Patológico/genética , Vertigem/complicações , Doenças Vestibulares/genéticaRESUMO
Miller Fisher syndrome (MFS) is characterized by a clinical triad of ophthalmoplegia, ataxia, and areflexia, and is closely associated with serum anti-GQ1b antibody. Although the clinical triad is the cardinal diagnostic clue, a variety of other symptoms and signs beyond the triad have been reported. To elucidate the frequency and characteristics of atypical clinical manifestations of MFS, we recruited 38 patients with MFS and evaluated the symptoms or signs beyond the classic triad. Eleven (29%) of 38 patients had atypical clinical manifestations of MFS such as headache (n = 6), delayed facial palsy (n = 3), divergence insufficiency (n = 2), and taste impairment (n = 2). Headache was localized to the periorbital (n = 3), temporal (n = 2), or whole (n = 1) area. Only one of them showed bilateral papilledema and an elevated opening pressure in cerebrospinal fluid analysis. Delayed facial palsy developed after the other signs have reached nadir (n = 1) or started to improve (n = 2), and did not follow a pattern of descending paralysis with other cranial neuropathies. Two patients showed divergence insufficiency without external ophthalmoplegia, and another two had taste impairment over the entire tongue without the other signs of facial and glossopharyngeal nerve involvements. Our study shows that approximately 30% of MFS patients can have atypical clinical manifestations beyond the classic triad. These results reflect the broad clinical spectrum of MFS, and might be associated with the presence of additional antiganglioside antibodies besides anti-GQ1b in patients with MFS.
Assuntos
Paralisia Facial/diagnóstico , Gangliosídeos , Síndrome de Miller Fisher/diagnóstico , Oftalmoplegia/diagnóstico , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Diagnóstico Diferencial , Paralisia Facial/sangue , Paralisia Facial/epidemiologia , Feminino , Gangliosídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/sangue , Síndrome de Miller Fisher/epidemiologia , Oftalmoplegia/sangue , Oftalmoplegia/epidemiologia , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The aim of this study was to determine the prevalence of stroke and efficacy of bedside evaluation in diagnosing stroke in acute transient vestibular syndrome (ATVS). METHODS: We performed a prospective, single-center, observational study that had consecutively recruited 86 patients presenting with ATVS to the emergency department of Pusan National University Yangsan Hospital from January to December 2014. All patients received a constructed evaluation, including HINTS plus (head impulse, nystagmus patterns, test of skew, and finger rubbing) and brain magnetic resonance imagings. Patients without an obvious cause further received perfusion-weighted imaging. Multivariable logistic regression was used to determine clinical parameters to identify stroke in ATVS. RESULTS: The prevalence of stroke was 27% in ATVS. HINTS plus could not be applied to the majority of patients because of the resolution of the vestibular symptoms, and magnetic resonance imagings were falsely negative in 43% of confirmed strokes. Ten patients (12%) showed unilateral cerebellar hypoperfusion on perfusion-weighted imaging without an infarction on diffusion-weighted imaging, and 8 of them had a focal stenosis or hypoplasia of the corresponding vertebral artery. The higher risk of stroke in ATVS was found in association with craniocervical pain (odds ratio, 9.6; 95% confidence interval, 2.0-45.2) and focal neurological symptoms/signs (odds ratio, 15.2; 95% confidence interval, 2.5-93.8). CONCLUSIONS: Bedside examination and routine magnetic resonance imagings have a limitation in diagnosing strokes presenting with ATVS, and perfusion imaging may help to identify strokes in ATVS of unknown cause. Associated craniocervical pain and focal neurological symptoms/signs are the useful clues for strokes in ATVS.
Assuntos
Tontura/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Imageamento por Ressonância Magnética/métodos , Testes Imediatos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tontura/diagnóstico por imagem , Tontura/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , República da Coreia/epidemiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Síndrome , Adulto JovemRESUMO
Episodic ataxia type 6 (EA6) is caused by mutations in SLC1A3 that encodes excitatory amino acid transporter 1 (EAAT1), a glial glutamate transporter. EAAT1 regulates the extent and durations of glutamate-mediated signal by the clearance of glutamate after synaptic release. In addition, EAAT1 also has an anion channel activity that prevents additional glutamate release. We identified a missense mutation in SLC1A3 in a family with EA. The proband exhibited typical EA2-like symptoms such as recurrent ataxia, slurred speech with a duration of several hours, interictal nystagmus and response to acetazolamide, but had late-onset age of sixth decade. Whole-exome sequencing detected a heterozygous c.1177G>A mutation in SLC1A3. This mutation predicted a substitution of isoleucine for a highly conserved valine residue in the seventh transmembrane domain of EAAT1. The mutation was not present in 100 controls, a large panel of in-house genome data and various mutation databases. Most functional prediction scores revealed to be deleterious. Same heterozygous mutation was identified in one clinically affected family member and two asymptomatic members. Our data expand the mutation spectrum of SLC1A3 and the clinical phenotype of EA6.
Assuntos
Ataxia Cerebelar/genética , Transportador 1 de Aminoácido Excitatório/genética , Isoleucina/metabolismo , Mutação , Valina/metabolismo , Acetazolamida/uso terapêutico , Adulto , Idade de Início , Sequência de Aminoácidos , Substituição de Aminoácidos , Anticonvulsivantes/uso terapêutico , Sequência de Bases , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/patologia , Transportador 1 de Aminoácido Excitatório/química , Feminino , Expressão Gênica , Heterozigoto , Humanos , Isoleucina/química , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Linhagem , Fenótipo , Alinhamento de Sequência , Valina/químicaRESUMO
Mycoplasma pneumonia is a major pathogen of primary atypical pneumonia and has been known to cause various kinds of extrapulmonary manifestations involving almost all organs of the human body. Optic neuritis associated with M. pneumoniae infection has rarely been described and mostly, it combined other neurological complications including meningitis, meningoencephalitis, myelitis, and peripheral neuropathy. We report two patients who presented with isolated optic neuritis due to M. pneumoniae infection, and reviewed the literatures on five additional patients. All patients are child or young adults, and optic neuritis was unilateral (n = 3) or bilateral (n = 4). Remarkably, four patients did not have preceding history of respiratory M. pneumonia infection, and ocular pain or headache was accompanied in only three. Although initial visual acuities were severely reduced in most cases, visual outcome was excellent after systemic steroid and/or antibiotics treatment. M. pneumonia infection should be considered in the differential diagnosis of isolated optic neuritis, especially when occurring in a child or young adults, even though there was no preceding pneumonia, accompanying ocular pain, or headache. Various mechanisms including direct local inflammation, vascular occlusion, or indirect immune modulation due to M. pneumonia infection can lead to isolated neurological manifestations without pneumonia.
Assuntos
Cefaleia/microbiologia , Meningoencefalite/microbiologia , Mycoplasma pneumoniae , Neurite Óptica/microbiologia , Pneumonia por Mycoplasma/microbiologia , Criança , Feminino , Cefaleia/etiologia , Humanos , Masculino , Meningoencefalite/complicações , Meningoencefalite/diagnóstico , Neurite Óptica/complicações , Neurite Óptica/diagnóstico , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/diagnóstico , Acuidade Visual/fisiologia , Adulto JovemRESUMO
A 63-year-old man experienced transient vertical oscillopsia lasting several seconds for 2 months. Examination disclosed paroxysmal excyclotorsion of the right eye, spontaneously or triggered by adduction. Eye movements using 3D video-oculography showed intermittent, monocular phasic movements which consisted of excyclotorsion of the right eye mixed with a small amount of supraduction and abduction, and a tonic movement with excyclotorsion and slight elevation. Orbital and brain MRI was unremarkable. Administration of oxcarbazepine markedly decreased the severity and frequency of the episodes. The oculographic characteristics in our patient may indicate that inferior oblique myokymia may be attributed to aberrant, spontaneous discharges in the inferior oblique motor unit.
Assuntos
Técnicas de Diagnóstico Oftalmológico , Movimentos Oculares/fisiologia , Imageamento Tridimensional/métodos , Mioquimia/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Músculos Oculomotores/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mioquimia/fisiopatologia , Transtornos da Motilidade Ocular/fisiopatologia , Músculos Oculomotores/fisiopatologiaAssuntos
Anormalidades Múltiplas/fisiopatologia , Cerebelo/anormalidades , Anormalidades do Olho/fisiopatologia , Doenças Renais Císticas/fisiopatologia , Nistagmo Patológico/fisiopatologia , Retina/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Adolescente , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Anormalidades do Olho/complicações , Anormalidades do Olho/diagnóstico por imagem , Medições dos Movimentos Oculares , Teste do Impulso da Cabeça , Humanos , Doenças Renais Císticas/complicações , Doenças Renais Císticas/diagnóstico por imagem , Masculino , Nistagmo Patológico/etiologia , Retina/diagnóstico por imagem , Retina/fisiopatologia , Potenciais Evocados Miogênicos VestibularesRESUMO
Scrub typhus is an acute febrile infectious disease caused by Orientia tsutsugamushi. The illness is usually characterized by fever, rash, and lymphadenopathy, but severe cases progress to pulmonary and neurological involvement. We report a 69-year-old man who developed ptosis and ophthalmoplegia with a focal nodular lesion in the anterior cavernous sinus detected with magnetic resonance imaging. Found to have scrub typhus, the ptosis and ophthalmoplegia resolved after treatment with doxycycline.
Assuntos
Oftalmoplegia/etiologia , Tifo por Ácaros/complicações , Idoso , Feminino , Humanos , Imageamento por Ressonância MagnéticaRESUMO
To define the cerebellar contribution in modulating the otolithic signals, we investigated the otolithic function in 27 patients with acute unilateral cerebellar infarctions in the territory of the posterior inferior cerebellar artery (PICA, n = 17, 63%), combined PICA and superior cerebellar artery (SCA) (n = 7, 30%), SCA (n = 2, 7%), and anterior inferior cerebellar artery (n = 1, 4%) from 2010 to 2012. The patients had evaluation of the ocular tilt reaction [head tilt, ocular torsion (OT), and skew deviation], tilt of the subjective visual vertical (SVV), cervical vestibular evoked myogenic potentials (VEMPs) in response to air conducted tone bursts, and ocular VEMPs induced by tapping the head at AFz. The evaluation was completed within 2 weeks after symptom onset. Patients often showed OT or SVV tilt (15/27, 55.6%) that was either ipsi- (n = 6) or contraversive (n = 9). Overall, there were no differences in the amplitudes and latencies of cervical and ocular VEMPs between the ipsi- and contralesional sides. However, individual analyses revealed frequent abnormalities of cervical (11/27, 41%) and/or ocular (9/27, 33%) VEMPs. While 11 (73%) of the 15 patients with the OTR/SVV tilt showed abnormalities of cervical (n = 9) and/or ocular (n = 7) VEMP responses, only three (25%) of the 12 patients without the OTR/SVV tilt had abnormal cervical (n = 2) and/or ocular (n = 2) VEMPs (73% vs. 25%, Fisher's exact test, p = 0.021). The concordance rate in the results of cervical and ocular VEMPs was marginally significant (19/27, 70%, p = 0.052, binominal). Unilateral cerebellar lesions may generate otolithic imbalances, as evidenced by the OTR/SVV tilt and asymmetric ocular or cervical VEMP responses, but without directionality according to the lesion side. Patients with the OTR/SVV tilt had abnormal VEMPs more often than those without.
Assuntos
Infarto Encefálico/fisiopatologia , Doenças Cerebelares/fisiopatologia , Membrana dos Otólitos/fisiopatologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/fisiopatologia , Adulto JovemAssuntos
Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/fisiopatologia , Movimentos Sacádicos/fisiologia , Administração Oral , Adulto , Dexametasona/uso terapêutico , Combinação de Medicamentos , Glucocorticoides/uso terapêutico , Humanos , Infusões Intravenosas , Masculino , Transtornos da Motilidade Ocular/tratamento farmacológico , Prednisolona/uso terapêutico , Visão Monocular/fisiologiaRESUMO
OBJECTIVE: This study aimed to correlate the symptoms and signs with the findings of laboratory vestibular function tests in patients with spinocerebellar ataxia (SCA). METHOD: We retrospectively recruited 26 patients with SCA (9 men, median age: 52, age range: 21-67). Assessments included Dizziness Handicap Inventory, EuroQoL Five-Dimension, symptom questionnaires manifesting during walking in daily life, the Scale for the Assessment and Rating of Ataxia (SARA), and vestibular function tests including 3D video-oculography, video head impulse test, subjective visual vertical, and cervical and ocular vestibular evoked myogenic potentials (VEMP). RESULTS: Cross-analyses revealed that the patients with VEMP abnormalities showed higher SARA (p = 0.014) and prevalence of unpredictable falls (p = 0.046). The patients with SCA1 more frequently had unpredictable falls (75%, p = 0.038) and VEMP abnormalities (88%, p = 0.001) compared to SCA2 (29% falls, 17% VEMP abnormalities) and SCA6 (no falls or VEMP abnormalities). CONCLUSION: Abnormal VEMPs are strongly associated with unpredicted falls in patients with SCA, particularly in those with SCA1. Impaired processing of otolithic information may contribute to falls in SCAs, and VEMP may help identifying the patients with a risk for unpredicted falls and preventing fall-related injuries in SCA. Limited number of patients with lower SARA scores warrant further confirmatory studies.
Assuntos
Acidentes por Quedas , Ataxias Espinocerebelares , Potenciais Evocados Miogênicos Vestibulares , Testes de Função Vestibular , Humanos , Masculino , Feminino , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adulto , Pessoa de Meia-Idade , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/complicações , Idoso , Adulto Jovem , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been identified as useful biomarkers for assessing the inflammatory response and for predicting the prognosis of various diseases. This study aimed to determine the clinical significance and effects on prognostic prediction of NLR and PLR in acute unilateral vestibulopathy (AUV). METHODS: We retrospectively recruited 128 patients who were diagnosed with AUV from July 2016 to April 2021, and compared NLR and PLR values between these patients with AUV and age- and sex-matched healthy subjects. We also analyzed the correlations of various clinical parameters with NLR and PLR. RESULTS: NLR and PLR in the AUV group were 3.41±2.80 (mean±standard deviation) and 128.86±67.06, respectively, with only NLR being significantly higher than that in the control group (1.55±0.60, p<0.001). The gain asymmetry of the horizontal vestibulo-ocular reflex (VOR) was slightly larger in patients with high NLR (n=52) than in those with normal NLR (n=76) (41.9%±20.2% vs. 33.6%±17.4%, p=0.048). However, the hospitalization period, preceding infection, canal paresis, and absolute horizontal VOR gain did not differ between patients with high and normal NLR and PLR values. The correlation analyses also revealed that none of the clinical parameters were significantly correlated with NLR or PLR. At 3-month follow-up examinations, NLR and PLR did not differ significantly between patients with and without function recovery of the horizontal VOR. CONCLUSIONS: This study found a high NLR in AUV, suggesting an acute inflammatory status in the vestibular organ. However, the usefulness of NLR and PLR as prognostic markers remains unclear.
RESUMO
The liver is vulnerable to various hepatotoxins, including carbon tetrachloride (CCl4), which induces oxidative stress and apoptosis by producing reactive oxygen species (ROS) and activating the mitogen-activated protein kinase (MAPK) pathway. Cereblon (CRBN), a multifunctional protein implicated in various cellular processes, functions in the pathogenesis of various diseases; however, its function in liver injury remains unknown. We established a CRBN-knockout (KO) HepG2 cell line and examined its effect on CCl4-induced hepatocellular damage. CRBN-KO cells exhibited reduced sensitivity to CCl4-induced cytotoxicity, as evidenced by decreased levels of apoptosis markers, such as cleaved caspase-3, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. CRBN deficiency enhanced antioxidant defense, with increased superoxide dismutase activity and glutathione ratios (GSH/GSSG), as well as reduced pro-inflammatory cytokine expression. Mechanistically, the protective effects of CRBN deficiency appeared to involve the attenuation of the MAPK-mediated pathways, particularly through decreased phosphorylation of JNK and ERK. Overall, these results suggest the crucial role of CRBN in mediating the hepatocellular response to oxidative stress and inflammation triggered by CCl4 exposure, offering potential clinical implications for liver injury in a wide range of liver diseases.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Apoptose , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Estresse Oxidativo , Humanos , Apoptose/efeitos dos fármacos , Células Hep G2 , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Estresse Oxidativo/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/deficiência , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Saccadic oscillations (SOs) mostly occur spontaneously, but can be occasionally triggered by various stimuli. To determine clinical characteristics and underlying mechanisms of triggered SOs, we analyzed the clinical features and quantitative eye-movement recordings of six new patients and 10 patients in the literature who exhibited with triggered SOs. Eleven of the 16 patients (69%) had a lesion involving cerebellum and/or brainstem such as cerebellar degeneration, cerebellitis, or cerebellar infarction. The other causes were vestibular migraine (n = 2), multiple sclerosis (n = 1), Krabbe disease (n = 1), and idiopathic (n = 1). Vestibular stimulation was the most common trigger (n = 11, 69%), followed by removal of visual fixation (n = 4, 25%), hyperventilation (n = 1), light (n = 1), and blink (n = 1). The types of triggered SOs were varied which included ocular flutter (n = 13), opsoclonus (n = 3), vertical SOs (n = 2), and macrosaccadic oscillations (n = 1). Three patients exhibited downbeat nystagmus either before (n = 1) or after (n = 2) the onset of SOs. The frequency of triggered SOs ranged from 4 to 15 Hz, and oscillations with smaller amplitudes had higher frequencies and smaller peak velocities. SOs can be triggered by the modulation of unstable saccadic neural networks through vestibular and visual inputs in lesions of the brainstem and cerebellum.
Assuntos
Transtornos da Motilidade Ocular , Movimentos Sacádicos , Humanos , Movimentos Sacádicos/fisiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/fisiopatologia , Idoso , Adulto JovemRESUMO
OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.