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Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP-induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP-induced hepatotoxicity was investigated. Twenty-eight Balb-C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin-2 (MFN2), optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC-1α, cGAS, and STING mRNA expression were assessed by real-time PCR. Histopathological changes and immunohistochemistry of INF-ß, p-NF-κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF-ß, p-NF-κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP-injected group, PGC-1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP-generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system-related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP-induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING-dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.
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Acetaminofen , Compostos Benzidrílicos , Doença Hepática Induzida por Substâncias e Drogas , Dinaminas , GTP Fosfo-Hidrolases , Glucosídeos , Proteínas de Membrana , Dinâmica Mitocondrial , Nucleotidiltransferases , Animais , Masculino , Camundongos , Acetaminofen/toxicidade , Acetaminofen/efeitos adversos , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Dinaminas/metabolismo , Dinaminas/genética , Glucosídeos/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , NF-kappa B/metabolismo , Nucleotidiltransferases/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Background: Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage. Methods: Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg). Results: The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK's ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1ß and TNF-α, besides downregulation of NF-κB and IL-1ß expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features. Conclusion: These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.
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Apoptose , Estresse Oxidativo , Triazinas , Animais , Ratos , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triazinas/farmacologia , Masculino , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Relação Dose-Resposta a Droga , Antioxidantes/farmacologia , Ratos Sprague-Dawley , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/prevenção & controle , Ratos Wistar , Relação Estrutura-AtividadeRESUMO
Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.
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Medicina Regenerativa , Células-Tronco , Humanos , Células-Tronco/citologia , Medicina Regenerativa/métodos , Animais , Urina/citologia , Diferenciação Celular , Procedimentos de Cirurgia Plástica/métodos , Regeneração/fisiologia , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Células-Tronco Mesenquimais/citologiaRESUMO
Background The most common teaching method in science is the lecture-based approach. E-learning is one of the advanced teaching methodologies that have gained attention in recent decades. It was hypothesized that the intervention of e-learning improved students' scores and satisfaction in biology classes. The purpose of this study was to determine if e-learning combined with traditional learning methods of lectures would improve unified students' scores and satisfaction in biology classes. Methodology The study design was a quasi-experimental approach. This study was conducted at the College of Science and Health Professions Jeddah, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia. The study subjects comprised first-year female students (pre-professional program) in two different classes. The total number of participants was 150 (75 students in each group). The systematic random sampling technique was used. Randomly, one class (experimental group) received e-learning in addition to traditional lectures, and the other group (control group) received traditional lecture. The "Biology for Health Sciences" course was selected for this purpose. Scientific pre-test and post-tests were performed, and a satisfaction questionnaire was filled in for both groups. Results We found that e-learning and traditional lecture improved students' scores (P<0.01). Learning progress in the e-learning group was significantly more than that in the control group (P<0.05). Lecture has been shown to increase learning gains by 33%, and the integration of e-learning increased learning gains by 62%. Analysis of questionnaire results showed improved student satisfaction with the course in the study group. Conclusion The integration of e-learning approach significantly improved the retention and students' scores and satisfactions. E-learning could be applied more in pre-professional year science courses. According to these advantages, the quality of science education can be improved with this approach.
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Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.
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Apoptose , Colite Ulcerativa , Estresse Oxidativo , Triterpenos Pentacíclicos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Animais , Triterpenos Pentacíclicos/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , Colo/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Ratos WistarRESUMO
Digital dermoscopy is used to identify cancer in skin lesions, and sun exposure is one of the leading causes of melanoma. It is crucial to distinguish between healthy skin and malignant lesions when using computerised lesion detection and classification. Lesion segmentation influences categorization accuracy and precision. This study introduces a novel way of classifying lesions. Hair filters, gel, bubbles, and specular reflection are all options. An improved levelling method is employed in an innovative method for detecting and removing cancerous hairs. The lesion is distinguished from the surrounding skin by the adaptive sigmoidal function; this function considers the severity of localised lesions. An improved technique for identifying a lesion from surrounding tissue is proposed in the article, followed by a classifier and available features that resulted in 94.40% accuracy and 93% success. According to research, the best method for selecting features and classifications can produce more accurate predictions before and during treatment. When the recommended strategy is put to the test using the Melanoma Skin Cancer Dataset, the recommended technique outperforms the alternative.
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Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma. Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4. Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events. Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.
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A medication's approximate release profile should be sustained in order to generate the desired therapeutic effect. The drug's release site, duration, and rate must all be adjusted to the drug's therapeutic aim. However, when designing drug delivery systems, this may be a considerable hurdle. Electrospinning is a promising method of creating a nanofibrous membrane since it enables drugs to be placed in the nanofiber composite and released over time. Nanofiber composites designed through electrospinning for drug release purposes are commonly constructed of simple structures. This nanofiber composite produces matrices with nanoscale fiber structure, large surface area to volume ratio, and a high porosity with small pore size. The nanofiber composite's large surface area to volume ratio can aid with cell binding and multiplication, drug loading, and mass transfer processes. The nanofiber composite acts as a container for drugs that can be customized to a wide range of drug release kinetics. Drugs may be electrospun after being dissolved or dispersed in the polymer solution, or they can be physically or chemically bound to the nanofiber surface. The composition and internal structure of the nanofibers are crucial for medicine release patterns.
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Lung cancer is a dangerous type of cancer in men and the third leading cause of cancer-related death in women, behind breast and colorectal cancers. Thymoquinone (THQ), a main compound in black seed essential oils, has a variety of beneficial effects, including antiproliferative, anti-inflammatory, and antioxidant properties. On the other hand, scorpion venom peptides (SV) induce apoptosis in the cancer cells, making it a promising anticancer agent. THQ, SV, and Phospholipon® 90H (PL) were incorporated in a nano-based delivery platform to assess THQ's cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human alveolar epithelial cells (A549). Several nanovesicles were prepared and optimized using factorial experimental design. The optimized phytosome formulation contained 79.0 mg of PL and 170.0 mg of SV, with vesicle size and zeta potential of 209.9 nm and 21.1 mV, respectively. The IC50 values revealed that A549 cells were significantly more sensitive to the THQ formula than the plain formula and THQ. Cell cycle analysis revealed that THQ formula treatment resulted in significant cell cycle arrest at the S phase, increasing cell population in this phase by 22.1%. Furthermore, the THQ formula greatly increased cell apoptosis (25.17%) when compared to the untreated control (1.76%), plain formula (11.96%), or THQ alone (13.18%). The results also indicated that treatment with THQ formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to plain formula and THQ. In terms of the inflammatory markers, THQ formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and THQ only. Overall, the findings from the study proved that a phytosome formulation of THQ could be a promising therapeutic approach for the treatment of lung adenocarcinoma.
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The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. The objective of the current work was to evaluate the efficacy of the combined complex of Sitagliptin (SIT) with melittin (MEL) against SARS-CoV-2 virus. SIT-MEL nano-conjugates were optimized by a full three-factor bi-level (23) factorial design. In addition, SIT concentration (mM, X1), MEL concentration (mM, X2), and pH (X3) were selected as the critical factors. Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for Fourier-transformed infrared (FTIR) was carried out. The optimized formula showed particle size and zeta potential values of 77.42 nm and 27.67 mV, respectively. When compared with SIT and MEL, the combination of SIT-MEL complex has shown anti-viral potential against isolate of SARS-CoV-2 with IC50 values of 8.439 µM with significant improvement (p < 0.001). In addition, the complex showed IC50 in vitro 3CL-protease inhibition with IC50 7.216 µM. Molecular docking has revealed that formula components have good predicted pocket accommodation of the SARS-CoV-2 3-CL protease. An optimized formulation of SIT-MEL could guarantee both enhanced delivery to the target cells and the enhanced cellular uptake with promising activities against SARS-CoV-2.
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OBJECTIVES: Medical knowledge is constantly changing; this puts pressure on educators to adapt instructional strategies to their students' learning styles (LSs). Therefore, identifying the LSs of medical students could help teachers to develop teaching strategies to achieve better outcomes. The purpose of this study was to determine the LSs of health science university students, and to assess the relationship between LSs and student satisfaction with educational activities. METHODS: This cross-sectional descriptive study was conducted in the Colleges of Medicine and Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) Jeddah. We used Kolb's LS and a modified Student Satisfaction Survey from Mott Community College, Michigan. All participants received self-administered questionnaires; LS and demographic data were used as predictor variables. Students' satisfaction levels were considered the outcome variable. RESULTS: A total of 359 students were recruited (mean age 19.0 ± 1.4 years; 53.5% males). The most popular LS was Accommodator (29.2%), followed by Assimilator (27.9%) and Diverger (25.6%), while the Converger style (17.3%) was the least preferred LS. The satisfaction scores of the students showed that they were generally satisfied with a mean score of 64.4%. Males were found to have higher satisfaction across all variables than females (p = 0.002). CONCLUSIONS: This study could not find a predominant LS or satisfaction difference across LSs among health science students. Thus, the current educational programmes in KSAU-HS meet students' LSs and satisfaction. Educators need to broaden their strategies for instruction, so as to build an effective learning environment.
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OBJECTIVE: To review and analyze the neurological complications from bariatric surgery in Kingdom of Saudi Arabia. METHODS: This cross sectional study was carried out in King Abdulaziz Medical City, Jeddah, Kingdom of Saudi Arabia from January 2009 to December 2015. Important personal and clinical data were collected from the charts of the patients who underwent bariatric surgery. Data on follow up visit and remote complication if present, was also collected. All patients with neurological complications were reviewed in detail. The significant difference was calculated by using T-test and p-value<0.05 was considered significant. RESULTS: A total of 451 patients underwent bariatric surgery, 15 cases had neurological complications (3%). Axonal polyneuropathy was the most frequent neurological complication, but cases of Wernicke syndrome, vitamin B12 deficiency, Guillain-Barre syndrome and copper deficiency were also identified. Fourteen patients (93.3%) had full recovery from the neurological signs and symptoms; one patient died. CONCLUSION: Bariatric surgery is not free of potential neurological complications. Complications may affect both central and peripheral nervous system and death is a possibility. Multidisciplinary care including consultation of different teams is highly recommended.
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Cirurgia Bariátrica , Síndrome de Guillain-Barré/epidemiologia , Obesidade Mórbida/cirurgia , Polineuropatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Deficiência de Vitamina B 12/epidemiologia , Encefalopatia de Wernicke/epidemiologia , Adulto , Cobre/deficiência , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Obesidade/cirurgia , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Encefalopatia de Wernicke/diagnóstico por imagemRESUMO
Lamotrigine (LTG) is a well-tolerated broad-spectrum antiepileptic drug, which is chemically unrelated to other existing antiepileptic medications. The drug has also some mood-stabilizing properties and, according to some studies, modest antidepressant effects. The exact mechanism of action is unknown, but some animal studies suggest the inhibition of neuronal glutamate release. Despite being relatively safe, LTG has been demonstrated to have proconvulsant effect especially in certain types of epilepsies like myoclonic status epilepticus. Myoclonic status epilepticus and its variations including generalized myoclonic status epilepticus, status myoclonus, and prolonged myoclonus describe a variety of clinical states, which have continuous, unremitting seizures lasting longer than 5 minutes. It is not a commonly reported treatment-emergent neurological complication, but the treatment is always a medical emergency. We report a case of a 46-year-old man who developed generalized myoclonus status epilepticus a few hours after suicidal ingestion of LTG. He remained hemodynamically stable throughout hospitalization and started to recover and achieved complete recovery 3 days later. This is the first reported case of this de novo complication induced by LTG toxicity. We proposed a subcortical mechanism for this complication induced by the toxic doses of LTG.
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Anticonvulsivantes/intoxicação , Overdose de Drogas/complicações , Epilepsias Mioclônicas/induzido quimicamente , Espasticidade Muscular/induzido quimicamente , Triazinas/intoxicação , Humanos , Lamotrigina , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Tentativa de SuicídioRESUMO
Cerebral venous thrombosis is a rare serious neurological disorder that may cause vital or morbid consequences if not diagnosed and treated promptly. It is a unique cerebrovascular disorder that predominantly affects adults in their third and fourth decades. The incidence of CVST in adults is estimated to be 4 cases per million of the population, and 7 cases per million in children. In the last 2 decades, the awareness and prognosis of the disease have improved due to development of sophisticated neuroimaging techniques and effective treatment. This comprehensive review of the topic aims to improve knowledge among neurologists and internists who are involved in the management of these patients.
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Encéfalo/patologia , Trombose dos Seios Intracranianos , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Radiografia , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/fisiopatologia , Trombose dos Seios Intracranianos/terapia , Tomógrafos ComputadorizadosRESUMO
Schistosomiasis affects over 200 million people worldwide. Involvement of the CNS is a rare occurrence. We report 2 young males who presented with rapidly progressing paraparesis associated with urinary incontinence. In both cases, MRI of the spine demonstrated a diffusely enhancing mass at the conus medullaris with extensive spinal cord edema. Laboratory investigations revealed mild peripheral eosinophilia and abnormal, but non-specific, CSF analysis. In one patient, the diagnosis was made based on a rising schistosomal titer with a positive rectal biopsy. In the other patient, spinal cord biopsy revealed a granuloma. Both cases were caused by Schistosoma mansoni and patients were treated with praziquantel and steroid therapy. They both made a remarkable neurological recovery. We emphasize that a high index of suspicion should be raised in the differential diagnosis of transverse myelitis in endemic areas.
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Paraplegia/etiologia , Paraplegia/parasitologia , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/complicações , Animais , Humanos , Imageamento por Ressonância Magnética , Masculino , Bulbo/patologia , Paraplegia/diagnóstico , Medula Espinal/parasitologia , Medula Espinal/patologia , Adulto JovemRESUMO
Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.
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Cerebelo/patologia , Córtex Cerebral/patologia , Hemiplegia/complicações , Deficiência Intelectual/complicações , Convulsões/complicações , Adulto , Atrofia/etiologia , Atrofia/patologia , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Cerebral venous sinus thrombosis (CVST) is an uncommon but serious disorder with highly variable clinical presentation. Over the past decade, more cases of CVST have been diagnosed more frequently and at an early stage of the disease process. This is mainly attributed to increased awareness by neurologists and the availability of sensitive non-invasive neuro-imaging techniques. Cerebral venous sinus thrombosis often affects children, adolescents, and young adults with female preponderance. We report a case of Parkinsonism secondary to deep CVST (DCVST), which recovered completely following treatment. Recognition of DCVST as a cause for Parkinsonism is of paramount importance due to its reversibility and favorable outcome when appropriately managed.