RESUMO
BACKGROUND: Pediatric magnetic resonance imaging (MRI) and computed tompgraphy (CT) require patient immobility and therefore often require sedation or general anesthesia of patients. Consensus on these procedures is lacking in France. OBJECTIVE: Thus, the aim of this study was to describe the current sedation practices for pediatric MRI and CT in France. MATERIAL AND METHODS: From January 2019 to December 2019, an online questionnaire was delivered by electronic mail to a representative radiologist in 60 pediatric radiology centers registered by the French-speaking pediatric and prenatal imaging society. Questions included protocols, drugs used, monitoring and side effects. RESULTS: Representatives of 40 of the 60 (67%) radiology centers responded to the survey. Among them, 31 performed sedation including 17 (55%) centers where radiologists performed sedation without anesthesiologists present during the procedure. The premedication drugs were hydroxyzine (n = 8, 80%) and melatonin (n = 2, 20%), Sedation drugs used for children ages 0 to 6 years old were pentobarbital (n = 9, 60%), midazolam (n = 2, 13%), chloral hydrate (n = 2, 13%), diazepam (n = 1, 6.5%) and chlorpromazine (n = 1, 6.5%). A written sedation protocol was available in 10/17 (59%) centers. In 6/17 (35%) centers, no monitoring was used during the procedures. Blood pressure monitoring and capnography were rarely used (< 10%) and post-sedation monitoring was heterogeneous. No life-threatening adverse effect was reported, but 6 centers reported at least one incident per year. CONCLUSION: For half of the responding radiology centers, radiologists performed sedation alone in agreement with the local anesthesiology team. Sedation procedures and monitoring were heterogenous among centers. Adjustment and harmonization of the practices according to the capacity of each center may be useful.
Assuntos
Hidrato de Cloral , Hipnóticos e Sedativos , Criança , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Hidrato de Cloral/efeitos adversos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Inquéritos e Questionários , Sedação Consciente/efeitos adversos , Espectroscopia de Ressonância MagnéticaRESUMO
Forensic age estimation is a challenging field in forensic sciences because of the increase of migratory flows. Medicolegal age assessment is a key point because it has many implications for authorities. Dental age estimation is an essential part of the global age assessment. The aim of this study was to evaluate and test the accuracy of Cameriere's cutoff values of the third molar maturity index (I3M) in assessing legal adult age of 18 years in a French population. The sample was constituted of 431 orthopantomograms performed between January 2014 and August 2017 on patients aged between 14 and 22 years. The reproducibility and repeatability of the method were high. Age distribution gradually decreases as I3M increases in both sexes. 0.08 seemed to be the best I3M cutoff. For females, the sensitivity and specificity of the test were 74.51% and 88.23%, respectively. The sensitivity and specificity for males were 92.19% and 88.35%, respectively. The accuracies were 80.74% for female, 90.57% for male. Estimated post-test probabilities were 0.879 for female and 0.899 for male. To conclude, the specific cutoff value of I3M Ë 0.08 may be a useful additional tool in discriminating adults and minors in French population.
Assuntos
Determinação da Idade pelos Dentes/métodos , Odontologia Legal , Dente Serotino/diagnóstico por imagem , Dente Serotino/crescimento & desenvolvimento , Adolescente , Feminino , França , Humanos , Masculino , Curva ROC , Radiografia Panorâmica , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: The diagnosis of acute rejection in cardiac transplant recipients requires invasive technique with endomyocardial biopsy (EMB) which has risks and limitations. Cardiovascular magnetic resonance imaging (CMR) with T2 and T1 mapping is a promising technique for characterizing myocardial tissue. The purpose of the study was to evaluate T2, T1 and extracellular volume fraction (ECV) quantification as novel tissue markers to diagnose acute rejection. METHODS: CMR was prospectively performed in 20 heart transplant patients providing 31 comparisons EMB-CMR. CMR was performed close to EMB. Images were acquired on a 1.5 Tesla scanner including T2 mapping (T2 prepared balanced steady state free precession) and T1 mapping (modified Look-Locker inversion recovery sequences: MOLLI) at basal, mid and apical level in short axis view. Global and segmental T2 and T1 values were measured before and 15 min (for T1 mapping) after contrast administration. RESULTS: Acute rejection was diagnosed in seven patients: six cellular rejections (4 grade IR, 2 grade 2R) and one antibody mediated rejection. Patients with acute rejection had significantly higher global T2 values at 3 levels: 58.5 ms [55.0-60.3] vs 51.3 ms [49.5-55.2] (p = 0.007) at basal; 55.7 ms [54.0-59.7] vs 51.8 ms [50.1-53.6] (p = 0.002) at median and 58.2 ms [54.0-63.7] vs 53.6 ms [50.8-57.4] (p = 0.026) at apical level. The area under the curve (AUC) for each level was 0.83, 0.79 and 0.78 respectively. Patients with acute rejection had significantly higher ECV at basal level: 34.2% [32.8-37.4] vs 27.4% [24.6-30.6] (p = 0.006). The AUC for basal level was 0.84. The sensitivity, specificity and diagnosis accuracy for basal T2 (cut off: 57.7 ms) were 71, 96 and 90% respectively; and for basal ECV: (cut off 32%) were 86, 85 and 85% respectively. Combining basal T2 and basal ECV allowed diagnosing all acute rejection and avoiding 63% of EMB. CONCLUSIONS: In heart transplant patients, a combined CMR approach using T2 mapping and ECV quantification provides a high diagnostic accuracy for acute rejection diagnosis and could potentially decrease the number of routine EMB.
Assuntos
Rejeição de Enxerto/diagnóstico por imagem , Transplante de Coração/efeitos adversos , Imageamento por Ressonância Magnética , Miocárdio/patologia , Doença Aguda , Adulto , Biópsia , Estudos de Casos e Controles , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
Ultrasound is currently recommended as the first-line examination for abdominal symptoms in children. However, a pediatric radiologist is not always available on site, especially during on-call duty. This study was aimed at evaluating the reliability of an innovative 3-D virtual abdominal tele-ultrasonography in this context. A prospective study was conducted between December 2020 and May 2021 that recruited 103 children undergoing ultrasound for abdominal pain. Trauma cases were excluded. Four tridimensional acquisitions were performed with a Smart Sensor 3D device (Canon Medical Systems, Otawara, Japan). Each tele-ultrasonography was secondarily blindly reviewed by two radiologists (one senior and one resident) with Fusion software (Canon Medical Systems). Acceptance and quality of the acquisitions were evaluated on a Likert scale. Inter-rater reliability was quantified using Cohen's κ coefficient and intraclass correlation coefficient. The ultrasound examination was normal in 66 cases (64%), abnormal in 36 cases (35%) and inconclusive in 1 case (1%). The acquisitions were obtained without objections from the children, their parents or the operators in more than 95% of cases. The quality of the acquisitions was considered good to excellent in 84% and 70% of cases. The sensitivity of the senior radiologist and the resident was 86% and 84%, respectively; specificity was 95% and 92%, positive predictive value 92% and 86% and negative predictive value 92 and 91% when comparing the conclusions of the standard and the tele-ultrasound examinations. Cohen's κ coefficients of the diagnosis obtained with the standard and the tele-ultrasound examinations were 0.82 and 0.71, respectively. The inter-rater Cohen's κ coefficient was 0.84. The intraclass correlation coefficient between the standard abdominal examination and the 3-D tele-ultrasound reformatted images for the following quantitative variables on pathological cases was 0.99 (confidence interval: 0.98-0.99). Virtual abdominal tele-ultrasonography is a promising method in pediatric emergencies.
Assuntos
Abdome , Exame Físico , Abdome/diagnóstico por imagem , Criança , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Ultrassonografia/métodosRESUMO
Recently, we described three components of a normal pharyngeal swallowing sound. The aim of the present study was to identify variations of these components using synchronized acoustic-radiological data in partially laryngectomized (PL) and totally laryngectomized (TL) patients before and after surgery. In this prospective study, from January 2003 to December 2006 we enrolled 14 patients in a PL group and 9 patients in a TL group. A fluoroscopy camera and a microphone were connected to a computer to obtain acoustic-radiological data (25 images/s). The subjects were asked to perform six deglutitions of 10 ml of barium suspension. The average durations of the sound variables were measured before and after surgery. The duration of the preoperative pharyngeal sound was 602 ms in the PL group and 562 ms in the TL group. It was significantly decreased after the TL (296 ms) and was increased after the PL (740 ms). A typical profile of the swallowing sound for each group was obtained. This study allowed us to describe the main variations of the pharyngeal swallowing sound induced by PL and TL. This noninvasive tool could be useful to assess postoperative swallowing function.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Deglutição/fisiologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Neoplasias Faríngeas/cirurgia , Adulto , Idoso , Auscultação , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Espectrografia do SomRESUMO
Pelvis radiography is a frequent X-ray examination. The objective of our study was to determine the minimum dose to be delivered without reducing the quality. We included 60 children having a pelvis X-ray in four groups that were equally represented by weight ranges. A software simulated, for each radiograph, six additional simulated photonic noise images corresponding to 100, 80, 64, 50, 40 and 32% of the initial dose. The 360 radiographs were blindly scored by two radiologists using a semi-quantitative Likert scale. There was no significant difference in scoring between the reference radiograph and simulated radiographs at 80% of the dose in children between 0 and 15 kg and over 35 kg. Inter-observer reproducibility was moderate to very good. Pelvis X-ray doses might be reduced by 20% in children in our institution. Software that produces simulated X-ray with decreasing dose might be a useful tool for an optimization process.
Assuntos
Pelve , Software , Criança , Humanos , Pelve/diagnóstico por imagem , Doses de Radiação , Radiografia , Reprodutibilidade dos Testes , Raios XRESUMO
PURPOSE: Ultrasonographic quantitative measurements enable characterizing the stiffness and viscosity of liver parenchyma. Normal Shear Wave Elastography (SWE) values have been reported in adults and children. The Attenuation Imaging (ATI) coefficient is a measure of local sound energy loss thought to reflect steatosis in adults. The aim of our study was to provide normal SWE and ATI liver values in healthy children. METHODS: A prospective monocentric study was conducted recruiting 86 children (45 boys and 41 girls) from a single University Hospital between January 2019 and June 2020, having a clinically indicated ultrasound examination, without a known or documented history of liver disease. Examinations were performed using an Aplio i800 (Canon Medical Systems) ultrasound system with an i8CX1 transducer. SWE measurements were obtained using a color map showing an automated measurement area grid overlay. ATI coefficients were generated automatically for each region of interest in the right liver. RESULTS: Overall median age for the pediatric population was 106 months (1-180 months; SD 49 months). Children were normal weighted. Liver SWE was available for all children. The median liver SWE was 4.6 kPa [3.3-6.6]. ATI yielded valid measurements in 77 patients. The median ATI coefficient was 0.65 [0.5-0.81] dB/cm/MHz. No impact of age, sex, weight and Body Mass Index was observed. CONCLUSION: SWE and ATI liver values were provided in healthy children. The normative quantitative data might be useful to characterize liver parenchyma in children better.
Assuntos
Técnicas de Imagem por Elasticidade , Fígado Gorduroso , Hepatopatias , Adulto , Criança , Feminino , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática , Hepatopatias/diagnóstico por imagem , Masculino , UltrassonografiaRESUMO
Camptocormia is defined by a pathological involuntary flexion of the thoracic and lumbar spine that is fully reducible in the supine position. Although originally described as a manifestation of conversion disorder, it is more commonly caused by a wide range of neurological diseases, in particular movement and neuromuscular disorders. We describe here a rare case of late onset camptocormia caused by autosomal dominant calpainopathy due to a heterozygous in-frame deletion in CAPN3 leading to loss of a single lysin amino acid in the catalytic domain of calpain-3. Creatine kinase levels, electromyography, and thigh muscle MRI were normal. Muscle biopsy did not show lobulated fibers and calpain-3 protein expression was not decreased, but in vitro functional assays showed impaired proteolytic function of. Lys254del CAPN3. Autosomal dominant calpainopathy should be considered in the differential diagnosis of late onset camptocormia and unexplained paravertebral myopathies even in presence of normal creatine kinase levels, and in absence of lobulated fibers, of decreased calpain-3 protein expression, and of muscle limb involvement.
Assuntos
Calpaína/genética , Proteínas Musculares/genética , Atrofia Muscular Espinal/genética , Curvaturas da Coluna Vertebral/genética , Idade de Início , Idoso , Eletromiografia , Feminino , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Deleção de SequênciaRESUMO
BACKGROUND: This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance to assess myocardial involvement in Takotsubo syndrome (TTS). We hypothesized that non-contrast mapping techniques can be accurate and sufficient. METHODS: We prospectively analysed 30 patients with TTS and 34 controls. CMR was performed a mean 5 days after the onset of symptoms and after a mean 3 month follow-up. RESULTS: On admission, compared to controls, TTS patients had significantly higher global T2 values (59 ± 8 ms vs 51 ± 4 ms, p < 0.001), native T1 (1053 ± 75 ms vs 960 ± 61 ms, p < 0.001) and extracellular volume (ECV) fraction (29% ± 5 vs 23% ±3, p < 0.001). The sensitivity and specificity for T2 (cut off: 56 ms) were 62% and 97% respectively; for native T1: (cut off 1011 ms) were 72% and 91% respectively; and for ECV (cut off: 27%) were 72% and 97% respectively. Combining T2 and native T1 provided the best sensitivity (91.7%) with a good specificity (88.2%). No patients had late gadolinium enhancement. Segmental analysis showed that T2, native T1 and ECV values were significantly higher in regions with wall motion abnormalities (WMA) compared to normokinetic segments (62 ± 9 ms vs 55 ± 5 ms, p < 0.001; 1060 ± 65 ms vs 1025 ± 56 ms, p = 0.02; and 34% ± 5 vs 29% ± 1, p = 0.02). At follow up, native T1 and ECV values did not normalized. CONCLUSION: In TTS patients, a non-contrast mapping technique provides a high diagnostic accuracy allowing identification of acute and persistent myocardial injury. Segmental analysis showed that myocardial injury is preferably detected in segments with WMA.
Assuntos
Cardiomiopatia de Takotsubo , Estudos de Casos e Controles , Meios de Contraste , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Cardiomiopatia de Takotsubo/diagnóstico por imagemRESUMO
PURPOSE: Rapid prototyping is a technique used for creating computer images in three dimensions more efficiently than classic techniques. Percutaneous nephrolithotomy (PCNL) is a popular method to remove kidney stones; however, broader use by the urologic community has been hampered by the morbidity associated with needle puncture to gain access to the renal calix (bleeding, pneumothorax, hydrothorax, inadvertent colon injury). A training model to improve technique and understanding of renal anatomy could improve complications related to renal puncture; however, no model currently exists for resident training. MATERIALS AND METHODS: We created a training model using the rapid prototyping technique based on abdominal CT images of a patient scheduled to undergo PCNL. This allowed our staff and residents to train on the model before performing the operation. This model allowed anticipation of particular difficulties inherent to the patient's anatomy. RESULTS: After training, the procedure proceeded without complication, and the patient was discharged at postoperative day 1 without problems. CONCLUSIONS: We hypothesize that rapid prototyping could be useful for resident education, allowing the creation of numerous models for research and surgical training. In addition, we anticipate that experienced urologists could find this technique helpful in preparation for difficult PCNL operations.
Assuntos
Simulação por Computador , Cálculos Renais/cirurgia , Nefrostomia Percutânea , Procedimentos Cirúrgicos Urológicos/educação , Interface Usuário-Computador , Idoso , Animais , Humanos , Imageamento Tridimensional , Técnicas In Vitro , Cálculos Renais/diagnóstico por imagem , Masculino , Imagens de Fantasmas , Sus scrofa , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The objective of the study was to assess the prognostic role of skeletal muscle index (SMI) in metastatic renal cell carcinoma (mRCC) patients treated with everolimus, and its effect of on everolimus-induced toxicity. PATIENTS AND METHODS: Consecutive mRCC patients treated with everolimus between February 2007 and November 2014 underwent computed tomography scans at a single center performed by the same radiologist. SMI was assessed before everolimus treatment using the L3 cross-sectional area. Overall survival (OS) was analyzed according to SMI value. Results were adjusted using the International Metastatic Database Consortium (IMDC) prognostic group, body mass index (BMI), and/or number of previous tyrosine kinase inhibitor lines (NPL). RESULTS: One hundred twenty-four mRCC patients (mean age, 60.21 years) were treated with everolimus as second- or third-line (82.3%) or > third-line (17.7%) therapy. Most patients (87.9%) had clear cell carcinoma. IMDC prognostic group was "favorable" (32.3%), "intermediate" (50%), or "poor" (17.7%). Median SMI was 40.75. OS was longer in patients from the highest versus lowest SMI tercile: 21.9 versus 10 months (P = .002). Continuous SMI at baseline was not significantly associated with OS after adjustment for IMDC prognostic group, BMI, or NPL but the highest versus lowest SMI tercile was an independent prognostic factor in multivariate analysis (P = .025). There was no difference in everolimus toxicity between SMI tercile groups. CONCLUSION: SMI was an independent prognostic factor for mRCC patients treated with everolimus. Whether this provides additional prognostic value to IMDC criteria needs to be confirmed in a larger cohort. SMI does not seem to be predictive of everolimus-induced toxicity.
Assuntos
Antineoplásicos/toxicidade , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/toxicidade , Neoplasias Renais/tratamento farmacológico , Músculo Esquelético/diagnóstico por imagem , Idoso , Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/diagnóstico por imagem , Intervalo Livre de Doença , Everolimo/administração & dosagem , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We report a rare case of amebiasis generating 19 large liver abscesses. Such a quantity of abscesses is rare, especially when occurring in a young casual traveler without any immunodeficiency disorders. A possible co-infection was excluded. By contrast, the amebic etiology was confirmed by means of serology and real-time PCR.
Assuntos
Antiprotozoários/uso terapêutico , Disenteria Amebiana/diagnóstico , Entamoeba histolytica/isolamento & purificação , Abscesso Hepático Amebiano/diagnóstico , Adulto , Anticorpos Antiprotozoários/isolamento & purificação , Astenia/parasitologia , Diarreia/parasitologia , Disenteria Amebiana/tratamento farmacológico , Entamoeba histolytica/genética , Entamoeba histolytica/imunologia , Transtornos da Alimentação e da Ingestão de Alimentos/parasitologia , Febre/parasitologia , Humanos , Abscesso Hepático Amebiano/complicações , Abscesso Hepático Amebiano/tratamento farmacológico , Masculino , Metronidazol/uso terapêutico , Oxiquinolina/análogos & derivados , Oxiquinolina/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Tomografia Computadorizada por Raios X , Viagem , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
PURPOSE: The GreenLight laser is one of the main alternative treatments for benign prostatic hyperplasia (BPH). Ultrasonography with contrast (ECUS) is one of the main innovations in radiology that has led to the examination of tissue vascularity. The objective of the study was to measure the impact of photovaporization of the prostate (PVP) on the prostate gland with ECUS. PATIENTS AND METHODS: We conducted a pilot study to assess the impact of PVP on the prostate by using ECUS intraoperatively (ethical committee approval No. 2012-001451-39). Twelve patients undergoing PVP for symptomatic BPH were enrolled in this study after providing their informed consent. ECUS was performed just before and after PVP in the operating room and at 1 month postoperatively. RESULTS: Comparative analysis showed that after PVP, a nonvascularized area with an average thickness of 11.1 mm was observed beyond the operative cavity. The nonvascularized area was thinner at 1 month postoperatively and disappeared at 6 months for the six patients evaluated. This is the first study using contrast-enhanced ultrasonography to measure the impact of PVP on the prostate. Our study has the limitations of a pilot study with a small population and a short follow-up. Based on these results, we would advise beginners to take into account the necrosis thickness and to limit the depth of vaporization. CONCLUSIONS: Through the use of ECUS, our study demonstrated that a large area of necrosis is induced around the surgical cavity from the action of the GreenLight laser. Being aware of this phenomenon will certainly reduce the risk of complications induced by surgery.
Assuntos
Terapia a Laser/instrumentação , Próstata/cirurgia , Prostatectomia/instrumentação , Hiperplasia Prostática/cirurgia , Ultrassonografia de Intervenção/instrumentação , Idoso , Humanos , Terapia a Laser/métodos , Lasers , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Prostatectomia/métodos , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/patologia , Resultado do Tratamento , Ultrassonografia de Intervenção/métodosAssuntos
Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Tomografia Computadorizada por Raios X , Meios de Contraste/administração & dosagem , Tomada de Decisões , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: To compare clinical features of CCM1, CCM2, and CCM3 mutation carriers. METHODS: A detailed clinical and molecular analysis of 163 consecutive cerebral cavernous malformation (CCM) families was performed. RESULTS: A deleterious mutation was detected in 128 probands. Three hundred thirty-three mutation carriers were identified (238 CCM1, 67 CCM2, and 28 CCM3). Ninety-four percent of the probands with an affected relative had a mutation compared with 57% of the probands with multiple lesions but no affected relative (p < 0.001). The number of affected individuals per family was lower in CCM3 families (p < 0.05). The proportion of patients with onset of symptoms before 15 years of age was higher in the CCM3 group (p < 0.0025). Cerebral hemorrhage was the most common initial presentation in CCM3 patients. The average number of T2-weighted imaging lesions was similar in the three groups, in contrast with a significantly lower number of gradient-echo sequence lesions in CCM2 patients (p < 0.05). The number of gradient-echo sequence lesions increased more rapidly with age in CCM1 than in CCM2 patients (p < 0.05). INTERPRETATION: Despite similarities among the three groups, there is a significantly lower number of affected individuals in CCM3 pedigrees, CCM3 mutations may confer a higher risk for cerebral hemorrhage, particularly during childhood, and the increment of gradient-echo sequence lesions with age differs between CCM1 and CCM2 patients.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Mutação Puntual/genética , Adolescente , Adulto , Idoso , Encéfalo/patologia , Proteínas de Transporte/genética , Hemorragia Cerebral/epidemiologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Imagem de Difusão por Ressonância Magnética , Feminino , Genótipo , Hemangioma Cavernoso do Sistema Nervoso Central/epidemiologia , Humanos , Proteína KRIT1 , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Fenótipo , Proteínas Proto-Oncogênicas/genética , Convulsões/epidemiologia , Índice de Gravidade de DoençaRESUMO
Cerebral Cavernous Malformations (CCM/OMIM 604214) are vascular malformations causing seizures and cerebral hemorrhages. They occur as a sporadic and autosomal dominant condition, the latter being characterized by the presence of multiple CCM lesions. Stereotyped truncating mutations of KRIT1, the sole CCM gene identified so far, have been identified in CCM1 linked families but the clinical features associated with KRIT1 mutations have not yet been assessed in a large series of patients. We conducted a detailed clinical, neuroradiological and molecular analysis of 64 consecutively recruited CCM families segregating a KRIT1 mutation. Those families included 202 KRIT1 mutation carriers. Among the 202 KRIT1 mutation carriers, 126 individuals were symptomatic and 76 symptom-free. Mean age at clinical onset was 29.7 years (range, 2-72); initial clinical manifestations were seizures in 55% of the cases and cerebral hemorrhages in 32%. Average number of lesions on T2 weighted MRI was 4.9 (+/-7.2) and on gradient echo sequences 19.8 (+/-33.2). Twenty-six mutation carriers harbored only one lesion on T2-weighted MRI, including 4 mutation carriers, aged from 18 to 55 yr-old, who presented only one CCM lesion both on T2-weighted and on highly sensitive gradient echo MRI sequences. Five symptom free mutation carriers, aged from 27 to 48 yr-old, did not have any detectable lesion both on T2WI and gradient echo MRI sequences. Within KRIT1/CCM1 families, both clinical and radiological penetrance are incomplete and age dependent. Importantly for genetic counseling, nearly half of the KRIT1 mutation carriers aged 50 or more are symptom-free. The presence of only one lesion, even when using gradient echo MRI sequences, can be observed in some patients with an hereditary form of the disease. Incomplete neuroradiological penetrance precludes the use of cerebral MRI to firmly establish a non carrier status, even at an adult age and even when using highly sensitive gradient echo MRI. Altogether these data suggest that the hereditary nature of the disorder may be overlooked in some mutation carriers presenting as sporadic cases with a unique lesion.