Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Endokrynol Pol ; 75(2): 130-139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646982

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Radioisótopos do Iodo , Humanos , Glioblastoma/radioterapia , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Radioisótopos do Iodo/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Recidiva Local de Neoplasia/prevenção & controle , Terapia Combinada
3.
Scand Cardiovasc J ; 56(1): 100-102, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549584

RESUMO

CHA2DS2-VASc score system aids in clinical decision-making in subjects with atrial fibrillation (AF). Little is known on the association between CHA2DS2-VASc scores and brain structure in patients without cardiac arrhythmia. Detailed brain architecture analysis was performed. Assessment of bivariate correlation between the volume of segmented brain structures and Z-scores of CHA2DS2-VASc showed that higher risk scores correlated negatively and significantly with various brain framework. Our study confirms that a cluster of risk factors incorporated in a well-established risk score correlated with brain tissue volume independently of the presence of an arrhythmia.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Encéfalo , Humanos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
4.
J Otolaryngol Head Neck Surg ; 51(1): 10, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246260

RESUMO

BACKGROUND: To compare the clinical features of two time cohorts of patients: "pre-COVID-19" and "COVID-19"-admitted as emergency with intracranial otogenic complications, with special regard to sigmoid sinus thrombosis (CVST). METHODS: Retrospective analysis of patients documentation concerning urgent procedures of intracranial otogenic complications at tertiary-referral otolaryngology department. Analysed database-pre-COVID-19 cohort (January-February 2019/2020): 1434 otological outpatient visits, 509 planned otosurgeries and 17 urgent otological procedures; COVID-19 cohort (March-April 2020/2021): 1150, 566 and 20 respectively. Overall intracranial complications: 5 and 9 respectively. Analysed outcome measures: incidence proportion of otogenic intracranial complications in relation to planned and urgent otosurgical procedures; incidence proportion of intracranial complications in relation to the total number of emergency and planned outpatient consultations and the total number of planned surgical procedures. RESULTS: There were 14 intracranial complications, 5 in the pre-COVID and 9 in the COVID cohort, including 1 and 5 sigmoid sinus thrombosis, respectively. Out of them, 3 and 5 patients reported a prior history of chronic otitis media, respectively. In COVID period, CVST was more prevalent, with 2 cases (22.2%) presenting solitary CVST, and 3 cases (33.3%) CVST and a simultaneous brain abscess or meningitis. CVST was much more frequent in the COVID period (p < 0.01). CONCLUSIONS: Despite the published data which suggest that CVST is a rare event associated with COVID-19 infection, based on our experience, CVST can be expected as a frequent component of intracranial otogenic complications during COVID-19 pandemic time. Trial registration This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the Bioethics Committee at Poznan University of Medical Sciences who determined that our study did not need ethical approval. An official waiver of ethical approval was granted from the Bioethics Committee at Poznan University of Medical Sciences.


Assuntos
COVID-19 , Trombose dos Seios Intracranianos , Adulto , COVID-19/complicações , COVID-19/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologia
5.
Lasers Med Sci ; 37(1): 163-169, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33219871

RESUMO

Incorporeal lithotripsy by using holmium:YAG laser has been recently successfully spread and used in the treatment of urolithiasis. Although this method is not as common in salivary gland surgery, it is also recommended for endoscopic treatment of sialolithiasis. In this study, we decided to analyse effectiveness of holmium:YAG laser method among patients with midsize stones as the treatment in this particular population is still not determined and remains in dispute. Thus, the primary aim of the study is a prospective, complex analysis of incorporeal holmium:YAG laser lithotripsy effectiveness and safety in patients suffering from sialolithiasis. The examined group consisted of 32 consecutive patients, 17 female (53%) and 15 male (47%). The average age was 42 (age range 22-70). In our series, sialoendoscopy with intraductal lithotripsy was performed in patients with wide range of stone's diameter (3 to 10 mm). The calculi were removed with foreign body forceps or retrieval basket, after stone fragmentation with holmium:YAG laser. The power of the laser during surgery was set at 2.5 to 3.5 W. One shot energy equalled 0.5-0.7 J with frequency of 5 Hz. The bivariate Pearson Correlation and a point-biserial correlation were used to analyse the data. Total success rate of holmium:YAG laser lithotripsy in this consecutive group was equal to 90% and efficacy in the group with excluded cases when endoscopic approach difficulties were experienced (stone not visible) reached 93%. The long-term follow-up revealed that in 26 patients (84%), complete recovery was achieved. Two patients developed Wharton's duct stenosis and one Stensen's duct orifice stenosis (9.5%), of whom one required reoperation. Two patients eventually underwent total excision of submandibular gland. Sialoendoscopy combined with incorporeal laser-assisted lithotripsy proved to be effective and safe method for treatment of sialothiasis with midsize stones (4-8 mm) in population of clinic. Even taking into account the prevalence of complications associated with holmium:YAG laser, it is still safer alternative compared to open surgery where there is a significant risk of the bleeding, wound infection or injury of the facial nerve.


Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Litotripsia , Cálculos das Glândulas Salivares , Adulto , Idoso , Feminino , Hólmio , Humanos , Lasers de Estado Sólido/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cálculos das Glândulas Salivares/cirurgia , Glândulas Salivares , Resultado do Tratamento , Adulto Jovem
6.
J Clin Med ; 12(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36614902

RESUMO

Peripheral arteriovenous malformations (PVMs) can be classified into high-flow malformations (HFVMs) and low-flow malformations (LFVMs). Adequate distinguishment is crucial for therapeutic decision and can be done using dynamic contrast-enhanced MRI (DCE-MRI). The main aim of this retrospective study was to determine the diagnostic value of quantitative DCE-MRI ratios for differentiation between HFVM and LFVM, their optimal cut-off points, and predictive values. DCE-MRI time-resolved angiography with stochastic trajectory (TWIST) examinations of 90 patients with PVMs were included [28 HFVM (31%), 62 LFVM (69%)]. The measurements of artery-lesion time, maximum lesion enhancement, slope of the enhancement curve, and maximum percentage increase of signal intensity (SI) were obtained. The optimal cut-offs for HFVMs calculated using the Youden index were: for slope of enhancement curve < 8.7 s (sensitivity of 86%, specificity of 89%), artery-lesion time ≤ 5.6 s (sensitivity of 89%, specificity of 77%), time to maximum enhancement ≤ 30 s (sensitivity of 94%, specificity of 100%), and maximum percentage enhancement of the lesion > 662% (sensitivity of 68%, specificity of 69%). To summarize, DCE-MRI is very valuable for differentiation between HFVM and LFVM, especially if quantitative measurements are done.

7.
Cent European J Urol ; 74(3): 321-326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729220

RESUMO

INTRODUCTION: The study aimed to assess the suitability of multiparametric magnetic resonance prostate imaging (mpMRI) in combination with clinical parameters [prostate-specific antigen (PSA), digital rectal examination (DRE)] in the identification of men at risk of the presence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa, Gleason Score ≥3+4) in the cognitive fusion with systematic prostate biopsy. MATERIAL AND METHODS: We retrospectively evaluated a population of 215 biopsy - naive patients with a clinical suspicion of prostate cancer. The results of mpMRI, DRE, PSA and biopsy were analyzed. MpMRI of the prostate according to the Prostate Imaging Reporting and Data System (PI-RADS) v.2.0 scheme preceded cognitive fusion and systematic transrectal prostate biopsy. Uni- and multivariable logistic regression analysis (MVA) was used to identify the variables determining the risk of detecting PCa overall and csPCa. RESULTS: In MVA, it was established that the combination of variables such as PSA level [odds ratio (OR) 1.195; p = 0.002], PI-RADS ≥3 (OR 7.7; p = 0.002), prostate volume (OR 0.98; p = 0.017) significantly determines the probability of PCa detection in biopsy, while for csPCa it is PSA level (OR 1.14; p = 0.004), DRE (+) (OR 5.75; p <0.001), PI-RADS ≥4 (OR 6.5; p <0.001). Analysis of mpMRI diagnostic value for PI-RADS ≥4 revealed better sensitivity (88.9% vs 82.6%) and better negative predictive value (NPV) (94.5% vs 82.4%) for detection of csPCa than for PCa overall. CONCLUSIONS: MpMRI results combining with DRE and PSA parameters help to identify men at high - or low risk of csPCa detection in the first - time biopsy.

8.
Clin Pract ; 11(4): 763-774, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34698089

RESUMO

INTRODUCTION: Proper planning of laparoscopic radical prostatectomy (RP) in patients with prostate cancer (PCa) is crucial to achieving good oncological results with the possibility of preserving potency and continence. AIM: The aim of this study was to identify the radiological and clinical parameters that can predict the risk of extraprostatic extension (EPE) for a specific site of the prostate. Predictive models and multiparametric magnetic resonance imaging (mpMRI) data from patients qualified for RP were compared. MATERIAL AND METHODS: The study included 61 patients who underwent laparoscopic RP. mpMRI preceded transrectal systematic and cognitive fusion biopsy. Martini, Memorial Sloan-Kettering Cancer Center (MSKCC), and Partin Tables nomograms were used to assess the risk of EPE. The area under the curve (AUC) was calculated for the models and compared. Univariate and multivariate logistic regression analyses were used to determine the combination of variables that best predicted EPE risk based on final histopathology. RESULTS: The combination of mpMRI indicating or suspecting EPE (odds ratio (OR) = 7.49 (2.31-24.27), p < 0.001) and PSA ≥ 20 ng/mL (OR = 12.06 (1.1-132.15), p = 0.04) best predicted the risk of EPE for a specific side of the prostate. For the prediction of ipsilateral EPE risk, the AUC for Martini's nomogram vs. mpMRI was 0.73 (p < 0.001) vs. 0.63 (p = 0.005), respectively (p = 0.131). The assessment of a non-specific site of EPE by MSKCC vs. Partin Tables showed AUC values of 0.71 (p = 0.007) vs. 0.63 (p = 0.074), respectively (p = 0.211). CONCLUSIONS: The combined use of mpMRI, the results of the systematic and targeted biopsy, and prostate-specific antigen baseline can effectively predict ipsilateral EPE (pT3 stage).

10.
Ann Med Surg (Lond) ; 67: 102483, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34168874

RESUMO

INTRODUCTION AND IMPORTANCE: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing gastroenteropathy of unknown etiology, characterized by impaired lymphatic vessels drainage. The pathological changes in PIL result in usually localized or diffuse dilatation of intestinal lacteals, leading to leakage of lymphatic fluid rich of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. PIL may be asymptomatic or mildly symptomatic in moderate forms of the disease. In some patients, though, the outcome may be poor or even life-threatening. This case report demonstrates the severity of protein malnutrition, in some cases, and the extent of GI tract affected, requiring to start PN early and the need for its continuation as home parenteral nutrition (HPN). CASE PRESENTATION: We present a case of 39-year-old male with Factor V Leiden deficiency, who presented initially with symptoms of malnutrition and anasarca. The diagnosis was confirmed by histopathological findings pathognomonic for PIL from biopsies of the stomach, small intestine and colon. CLINICAL DISCUSSION: The patient was started on low fat, high protein parenteral nutrition from the beginning of the treatment and required a long-term HPN for 3 years, because trials of tapering off and discontinuation of PN led to worsening of the biochemical results and recurrence of symptoms. Patient gradually improved and stabilized with persistent nutritional support. CONCLUSIONS: The presented case report shows the magnitude of nutritional support (HPN) needed for severe PIL patients. HPN offers PIL patients with poor outcome and life-threatening complications a chance to improve and lead a normal life.

11.
Pol J Radiol ; 86: e692-e699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35059062

RESUMO

Chest computed tomography (CT) is proven to have high sensitivity in COVID-19 diagnosis. It is available in most emergency wards, and in contrast to polymerase chain reaction (PCR) it can be obtained in several minutes. However, its imaging features change during the course of the disease and overlap with other viral pneumonias, including influenza pneumonia. In this brief analysis we review the recent literature about chest CT features, useful radiological scales, and COVID-19 differentiation with other viral infections.

12.
Eur Radiol ; 31(5): 2994-3001, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33151392

RESUMO

OBJECTIVES: To obtain information from radiology departments throughout Europe regarding the practice of emergency radiology METHODS: A survey which comprised of 24 questions was developed and made available online. The questionnaire was sent to 1097 chairs of radiology departments throughout Europe using the ESR database. All data were collected and analyzed using IBM SPSS Statistics software, version 20 (IBM). RESULTS: A total of 1097 radiologists were asked to participate, 109 responded to our survey. The response rate was 10%. From our survey, 71.6% of the hospitals had more than 500 beds. Ninety-eight percent of hospitals have an active teaching affiliation. In large trauma centers, emergency radiology was considered a dedicated section. Fifty-three percent of institutions have dedicated emergency radiology sections. Less than 30% had all imaging modalities available. Seventy-nine percent of institutions have 24/7 coverage by staff radiologists. Emergency radiologists interpret cross-sectional body imaging, US scans, and basic CT/MRI neuroimaging in more than 50% of responding institutions. Cardiac imaging examinations/procedures are usually performed by cardiologist in 53% of institutions, while non-cardiac vascular procedures are largely performed and interpreted by interventional radiologists. Most people consider the European Diploma in Emergency Radiology an essential tool to advance the education and the dissemination of information within the specialty of emergency radiology. CONCLUSION: Emergency radiologists have an active role in the emergency medical team. Indeed, based upon our survey, they have to interact with emergency physicians and surgeons in the management of critically ill patients. A broad skillset from ultrasonography and basic neuroimaging is required. KEY POINTS: • At most major trauma centers in Europe, emergency imaging is currently performed by all radiologists in specific units who are designated in the emergency department. • Radiologists in the emergency section at present have a broad skillset, which includes cross-sectional body imaging, ultrasonography, and basic neuroimaging of the brain and spine. • A dedicated curriculum that certifies a subspecialty in emergency radiology with a diploma offered by the European Society of Emergency Radiology demonstrates a great interest by the vast majority of the respondents.


Assuntos
Serviço Hospitalar de Emergência , Radiologia , Estudos Transversais , Europa (Continente) , Humanos , Inquéritos e Questionários , Recursos Humanos
14.
Neurol Neurochir Pol ; 54(5): 410-415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085075

RESUMO

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.


Assuntos
Esclerose Múltipla , Neurologia , Atrofia/patologia , Encéfalo/patologia , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Polônia , Sociedades Médicas
15.
Int J Mol Sci ; 21(16)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796691

RESUMO

Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely LHX4, HESX1, and OTX2. Among new CPHD loci, the most interesting seem to be the region covering SIX3 gene, that is abundantly expressed in developing brain, and together with HESX1 contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology.


Assuntos
Variações do Número de Cópias de DNA/genética , Hipopituitarismo/genética , Criança , Feminino , Rearranjo Gênico/genética , Genoma Humano , Humanos , Masculino
16.
Artigo em Inglês | MEDLINE | ID: mdl-32612575

RESUMO

Background: The mutation frequencies of pituitary transcription factors genes in patients with combined pituitary hormone deficiencies (CPHD) vary substantially between populations. However, apart from PROP1 the mutation rate of other genes is low and for almost half of the patients with CPHD the routine sequencing of known genes is unsuccessful in the identification of genetic causes. Methods: A cohort of 66 sporadic and nine familial CPHD cases (80 patients in total) were subjected to initial testing of the genes PROP1, POU1F1, LHX3, LHX4, and HESX1 using a targeted gene panel and MLPA. In patients who tested negative, a whole exome sequencing approach was employed. Results: In nine of the familial cases and 32 of the sporadic patients mutations in the PROP1 gene were found (the common pathogenic variants included c.301_302delAG and c.150delA). Mutations were also found in genes so far not related directly to CPHD. A unique homozygous and clinically relevant variant was identified in the SEMA3A gene, which may contribute to neural development and his phenotypic spectrum including short stature and isolated hypogonadotropic hypogonadism (IHH). Another pathogenic variant p.A1672T was found in the IGSF10 gene reported to be responsible for delayed puberty and neuronal migration during embryogenesis. Several suspected novel but predicted benign variants were also identified for the CHD7, WDR11 and FGF17 genes. Conclusion: Although PROP1 defects account for a majority of CPHD patients, identification of rare, less frequent variants constitutes a big challenge. Multiple genetic factors responsible for CPHD are still awaiting discovery and therefore the usage of efficient genomic tools (i.e., whole exome sequencing) will further broaden our knowledge regarding pituitary development and function.


Assuntos
Hipopituitarismo/genética , Imunoglobulinas/genética , Semaforina-3A/genética , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Mutação , Linhagem , Conformação Proteica , Sequenciamento do Exoma
17.
Pol J Radiol ; 85: e272-e276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612727

RESUMO

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.

18.
Folia Neuropathol ; 58(1): 83-92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32337960

RESUMO

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary, progressive ischemic disease of small vessels of the brain characterized by migraine with aura (MA), recurrent subcortical ischemic episodes, cognitive decline and psychiatric disorders. CADASIL is caused by mutations in the NOTCH3 gene. We identified the NOTCH3 Y189C mutation as a genetic cause of CADASIL in a Polish family and provided its first clinical manifestation. MATERIAL AND METHODS: The study included twelve subjects from one family. The NOTCH3 mutation, APOE and MTHFR polymorphisms were determined by high-resolution melting analyses (HRMA) and Sanger sequencing. Neuroimaging included CT and MRI. Ultrastructural examination of skin-muscle biopsy material of the proband was performed. RESULTS: The NOTCH3 Y189C mutation was present in a 36-year-old woman and her two sisters (aged 40 and 27) from 6 siblings. The MA was found in all of them, and started or became more severe after childbirth. The numerous T2/FLAIR hyperintense lesions were shown in the brain MRI. The deposition of granular osmiophilic material in the wall of small vessels of the proband observed in histopathological analysis confirmed the high degree of CADASIL severity. CONCLUSIONS: Patients with the Y189C mutation of NOTCH3 from the same family display a similar phenotype of CADASIL.


Assuntos
CADASIL/genética , Receptor Notch3/genética , Adulto , Feminino , Humanos , Mutação , Linhagem , Polônia
19.
Pediatr Blood Cancer ; 67(6): e28224, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32196935

RESUMO

AIM: The aim of the study was to assess long-term consequences of central nervous system (CNS) prophylaxis in patients with high-risk ALL (HR-ALL) treated according to ALL IC-BFM 2002 and to compare observed abnormalities in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with those who received only prophylactic CNS irradiation (12 Gy) and with control group. PATIENTS AND METHODS: We studied 29 patients with HR-ALL in CR1 after treatment according to protocol ALL IC-BFM 2002 (14 with allo-HSCT conditioned with fractionated total body irradiation [FTBI] and 15 without HSCT) and 16 children with newly diagnosed ALL (control group). The median time from therapy completion to evaluation was 5 years. To assess brain status, volumetric T1-weighted sequences of magnetic resonance imaging were used. Neuropsychological assessment based on battery neuropsychological tests. RESULTS: Transplanted patients had significantly lower volumes of white and gray matter (P = .048 and P < .001) and also of subcortical structures, including the thalamus (P < .001), the hippocampus (P = .007), the putamen (P = .011), the globus pallidus (P = .001), and the accumbens (P < .001). In addition, these patients had generally lower cognitive performance, especially in vocabulary (P = .011), visuospatial ability (P = .047), executive functions and attention (P = .034; P = .002; P = .048), and processing speed (P = .049 and P = .037). The thalamus volume is correlated with neuropsychological performance in verbal functions (P < .001), executive functions (P < .001 and P = .024), and processing speed (P < .001). CONCLUSIONS: In pediatric patients treated for ALL, FTBI-based preparative regimen preceding allo-HSCT causes reduction of subcortical structure volumes and decline in cognitive performance. The observed long-term structural and functional CNS sequelae are significantly more pronounced in transplanted HR-ALL patients than in those treated with prophylactic CNS- radiotherapy only.


Assuntos
Encéfalo/patologia , Disfunção Cognitiva/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irradiação Corporal Total/efeitos adversos , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Disfunção Cognitiva/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Transplante Homólogo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA