Genetics in medicine : official journal of the American College of Medical Genetics, Aug 16, 2017
PurposeCongenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotro... more PurposeCongenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined.MethodsRare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated.ResultsOf the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibi...
We aimed to describe the frequency and characteristics of acute ischemic stroke and transient isc... more We aimed to describe the frequency and characteristics of acute ischemic stroke and transient ischemic attacks presenting predominantly with amnesia (ischemic amnesia) and to identify clinical clues for differentiating them from transient global amnesia (TGA). We retrospectively analyzed and described all patients presenting with diffusion-weighted imaging magnetic resonance imaging-confirmed acute ischemic stroke/transient ischemic attacks with antero- and retrograde amnesia as the main symptom over a 13.5-year period. We also compared their clinical features and stroke mechanisms with 3804 acute ischemic stroke from our ischemic stroke registry. Thirteen ischemic amnesia patients were identified, representing 0.2% of all patients with acute ischemic stroke/ transient ischemic attack. In 69% of ischemic amnesia cases, amnesia was transient with a median duration of 5 hours. Ischemia was not considered in 39% of cases. Fifty-four percent of cases were clinically difficult to disting...
Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently... more Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently shown to be effective. Timely knowledge of the presence, site, and extent of arterial occlusions in the ischemic territory has the potential to influence patient selection for endovascular treatment. We aimed to find predictors of large vessel occlusive strokes, on the basis of available demographic, clinical, radiological, and laboratory data in the emergency setting. Patients enrolled in ASTRAL registry with acute ischemic stroke and computed tomography (CT)-angiography within 12 h of stroke onset were selected and categorized according to occlusion site. Easily accessible variables were used in a multivariate analysis. Of 1645 patients enrolled, a significant proportion (46.2%) had a large vessel occlusion in the ischemic territory. The main clinical predictors of any arterial occlusion were in-hospital stroke [odd ratios (OR) 2.1, 95% confidence interval 1.4-3.1], higher initial National Institute of Health Stroke Scale (OR 1.1, 1.1-1.2), presence of visual field defects (OR 1.9, 1.3-2.6), dysarthria (OR 1.4, 1.0-1.9), or hemineglect (OR 2.0, 1.4-2.8) at admission and atrial fibrillation (OR 1.7, 1.2-2.3). Further, the following radiological predictors were identified: time-to-imaging (OR 0.9, 0.9-1.0), early ischemic changes (OR 2.3, 1.7-3.2), and silent lesions on CT (OR 0.7, 0.5-1.0). The area under curve for this analysis was 0.85. Looking at different occlusion sites, National Institute of Health Stroke Scale and early ischemic changes on CT were independent predictors in all subgroups. Neurological deficits, stroke risk factors, and CT findings accurately identify acute ischemic stroke patients at risk of symptomatic vessel occlusion. Predicting the presence of these occlusions may impact emergency stroke care in regions with limited access to noninvasive vascular imaging.
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2013
ABSTRACT Abstract No. 358 Objectives: For the past decade, MRI and PET with 18F-fluoro-ethyl-tyro... more ABSTRACT Abstract No. 358 Objectives: For the past decade, MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used in the evaluation of patients with gliomas. However, tumor grading remains challenging. The purpose of this study was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET parameters for glioma grading. Methods: Thirty-eight patients (42±15y aged, F:M 0.46) with untreated histologically proven brain gliomas were included. All underwent MRI with spectroscopy and diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumor FET time-activity-curve (slope), early-to-middle SUVmax ratio, Choline/Creatine ratio and apparent diffusion coefficient (ADC) histogram distribution pattern to distinguish between low and high-grade gliomas were assessed. Combination of these parameters and respective odds were also evaluated by multivariate logistic regression analysis. Results: Tumor time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Early-to-middle ratio and MRS had lower accuracy of 58% and 48% respectively. Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 62-67% to 100% (P<0.008). On multivariate logistic regression analysis, tumor time-activity-curve on dynamic FET-PET however remains the best predictor of high-grade glioma (odds 69.8, SE 130, P= 0.023). Conclusions: Combination of dynamic FET-PET results and diffusion MRI reached excellent performance to distinguish between low and high-grade gliomas. The use of FET-PET/MR seems highly relevant in the initial assessment of primary brain tumors.
To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the ... more To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. We acquired high in-plane resolution (1.2×1.2 mm2) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm2, in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting.
Restorative Neurology and Neuroscience, Feb 1, 2007
Cognitive deficits that are present in the acute stage of a focal hemispheric lesion tend to be g... more Cognitive deficits that are present in the acute stage of a focal hemispheric lesion tend to be greater and more general than residual deficits, which persist into the chronic stage. We have investigated the patterns of recovery and the relationship between deficits and damage to specialized networks taking as model auditory cognitive functions. Evidence from human psychophysical, activation and neuropsychological studies suggests that sound recognition and sound localization are processed in anatomically and functionally distinct cortical networks, the auditory "What" and "Where" processing streams, that are each present in both hemispheres. Focal left or right hemispheric lesions centred on these networks were found to be associated, in the chronic stage, with the corresponding deficits in sound recognition and/or sound localization. We report here on recovery patterns in 24 patients who sustained focal hemispheric lesions and were deficient in sound recognition, sound localization and/or sound motion perception at a first evaluation in the acute (n=9), subacute (n=6) or early chronic stages (n=9). All 24 patients had initially a deficit in sound localization and/or sound motion perception. In the acute stage this deficit occurred without damage to the auditory "Where" stream in almost half of the patients, a situation which was never observed in the early chronic stage. Lack of recovery tended to be associated with damage to the specialized stream plus the persistence of deficits beyond the acute stage, and was only loosely related to the size of the lesion and to the extent of damage to a specialized network. Our results suggest that different mechanisms underlie deficits and recovery at different time points.
We report 2 previously healthy children who developed sudden unexpected respiratory arrest and br... more We report 2 previously healthy children who developed sudden unexpected respiratory arrest and brain death, during a presumed Epstein-Barr meningitis in one case and a multisystemic infection of unknown etiology in the other. Diffuse swelling of the cerebellum with upward transtentorial and downward tonsillar herniation, shown by brain CT-scan and MRI obtained after the acute event, was the most probable cause of death. Review of CT images performed before or at the onset of deterioration already showed discrete signs of early upward herniation of the cerebellar vermis that were initially overlooked. At autopsy in the first case, an acute lymphomonocytic meningoencephalitis with predominant involvement of the cerebellum was observed. Few similar cases were found in the literature, indicating that acute cerebellar swelling is either a very rare or an unrecognized, possibly preventable cause of death in acute inflammatory or non-inflammatory encephalopathies in children.
Lemierre's syndrome is an anaerobic sepsis occurring after oropharyngeal infection in hea... more Lemierre's syndrome is an anaerobic sepsis occurring after oropharyngeal infection in healthy teenagers and young adults. We report two cases of adolescent girls suffering from Lemierre's syndrome studied with cervical color Doppler ultrasonography (CDUS), cervicothoracic helical CT, and high-resolution CT (HRCT) scanning. In both patients, HRCT allowed a good depiction of multiple cavitated pulmonary nodules of various sizes suggestive of this entity and was able to detect small or peripheral nodules. CDUS helped to pinpoint the extent of thromboses of the internal jugular vein demonstrated by CT. CDUS and HRCT should be performed as early as possible to confirm and treat this life-threatening condition.
Genetics in medicine : official journal of the American College of Medical Genetics, Aug 16, 2017
PurposeCongenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotro... more PurposeCongenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined.MethodsRare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated.ResultsOf the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibi...
We aimed to describe the frequency and characteristics of acute ischemic stroke and transient isc... more We aimed to describe the frequency and characteristics of acute ischemic stroke and transient ischemic attacks presenting predominantly with amnesia (ischemic amnesia) and to identify clinical clues for differentiating them from transient global amnesia (TGA). We retrospectively analyzed and described all patients presenting with diffusion-weighted imaging magnetic resonance imaging-confirmed acute ischemic stroke/transient ischemic attacks with antero- and retrograde amnesia as the main symptom over a 13.5-year period. We also compared their clinical features and stroke mechanisms with 3804 acute ischemic stroke from our ischemic stroke registry. Thirteen ischemic amnesia patients were identified, representing 0.2% of all patients with acute ischemic stroke/ transient ischemic attack. In 69% of ischemic amnesia cases, amnesia was transient with a median duration of 5 hours. Ischemia was not considered in 39% of cases. Fifty-four percent of cases were clinically difficult to disting...
Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently... more Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently shown to be effective. Timely knowledge of the presence, site, and extent of arterial occlusions in the ischemic territory has the potential to influence patient selection for endovascular treatment. We aimed to find predictors of large vessel occlusive strokes, on the basis of available demographic, clinical, radiological, and laboratory data in the emergency setting. Patients enrolled in ASTRAL registry with acute ischemic stroke and computed tomography (CT)-angiography within 12 h of stroke onset were selected and categorized according to occlusion site. Easily accessible variables were used in a multivariate analysis. Of 1645 patients enrolled, a significant proportion (46.2%) had a large vessel occlusion in the ischemic territory. The main clinical predictors of any arterial occlusion were in-hospital stroke [odd ratios (OR) 2.1, 95% confidence interval 1.4-3.1], higher initial National Institute of Health Stroke Scale (OR 1.1, 1.1-1.2), presence of visual field defects (OR 1.9, 1.3-2.6), dysarthria (OR 1.4, 1.0-1.9), or hemineglect (OR 2.0, 1.4-2.8) at admission and atrial fibrillation (OR 1.7, 1.2-2.3). Further, the following radiological predictors were identified: time-to-imaging (OR 0.9, 0.9-1.0), early ischemic changes (OR 2.3, 1.7-3.2), and silent lesions on CT (OR 0.7, 0.5-1.0). The area under curve for this analysis was 0.85. Looking at different occlusion sites, National Institute of Health Stroke Scale and early ischemic changes on CT were independent predictors in all subgroups. Neurological deficits, stroke risk factors, and CT findings accurately identify acute ischemic stroke patients at risk of symptomatic vessel occlusion. Predicting the presence of these occlusions may impact emergency stroke care in regions with limited access to noninvasive vascular imaging.
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2013
ABSTRACT Abstract No. 358 Objectives: For the past decade, MRI and PET with 18F-fluoro-ethyl-tyro... more ABSTRACT Abstract No. 358 Objectives: For the past decade, MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used in the evaluation of patients with gliomas. However, tumor grading remains challenging. The purpose of this study was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET parameters for glioma grading. Methods: Thirty-eight patients (42±15y aged, F:M 0.46) with untreated histologically proven brain gliomas were included. All underwent MRI with spectroscopy and diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumor FET time-activity-curve (slope), early-to-middle SUVmax ratio, Choline/Creatine ratio and apparent diffusion coefficient (ADC) histogram distribution pattern to distinguish between low and high-grade gliomas were assessed. Combination of these parameters and respective odds were also evaluated by multivariate logistic regression analysis. Results: Tumor time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Early-to-middle ratio and MRS had lower accuracy of 58% and 48% respectively. Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 62-67% to 100% (P<0.008). On multivariate logistic regression analysis, tumor time-activity-curve on dynamic FET-PET however remains the best predictor of high-grade glioma (odds 69.8, SE 130, P= 0.023). Conclusions: Combination of dynamic FET-PET results and diffusion MRI reached excellent performance to distinguish between low and high-grade gliomas. The use of FET-PET/MR seems highly relevant in the initial assessment of primary brain tumors.
To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the ... more To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. We acquired high in-plane resolution (1.2×1.2 mm2) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm2, in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting.
Restorative Neurology and Neuroscience, Feb 1, 2007
Cognitive deficits that are present in the acute stage of a focal hemispheric lesion tend to be g... more Cognitive deficits that are present in the acute stage of a focal hemispheric lesion tend to be greater and more general than residual deficits, which persist into the chronic stage. We have investigated the patterns of recovery and the relationship between deficits and damage to specialized networks taking as model auditory cognitive functions. Evidence from human psychophysical, activation and neuropsychological studies suggests that sound recognition and sound localization are processed in anatomically and functionally distinct cortical networks, the auditory "What" and "Where" processing streams, that are each present in both hemispheres. Focal left or right hemispheric lesions centred on these networks were found to be associated, in the chronic stage, with the corresponding deficits in sound recognition and/or sound localization. We report here on recovery patterns in 24 patients who sustained focal hemispheric lesions and were deficient in sound recognition, sound localization and/or sound motion perception at a first evaluation in the acute (n=9), subacute (n=6) or early chronic stages (n=9). All 24 patients had initially a deficit in sound localization and/or sound motion perception. In the acute stage this deficit occurred without damage to the auditory "Where" stream in almost half of the patients, a situation which was never observed in the early chronic stage. Lack of recovery tended to be associated with damage to the specialized stream plus the persistence of deficits beyond the acute stage, and was only loosely related to the size of the lesion and to the extent of damage to a specialized network. Our results suggest that different mechanisms underlie deficits and recovery at different time points.
We report 2 previously healthy children who developed sudden unexpected respiratory arrest and br... more We report 2 previously healthy children who developed sudden unexpected respiratory arrest and brain death, during a presumed Epstein-Barr meningitis in one case and a multisystemic infection of unknown etiology in the other. Diffuse swelling of the cerebellum with upward transtentorial and downward tonsillar herniation, shown by brain CT-scan and MRI obtained after the acute event, was the most probable cause of death. Review of CT images performed before or at the onset of deterioration already showed discrete signs of early upward herniation of the cerebellar vermis that were initially overlooked. At autopsy in the first case, an acute lymphomonocytic meningoencephalitis with predominant involvement of the cerebellum was observed. Few similar cases were found in the literature, indicating that acute cerebellar swelling is either a very rare or an unrecognized, possibly preventable cause of death in acute inflammatory or non-inflammatory encephalopathies in children.
Lemierre's syndrome is an anaerobic sepsis occurring after oropharyngeal infection in hea... more Lemierre's syndrome is an anaerobic sepsis occurring after oropharyngeal infection in healthy teenagers and young adults. We report two cases of adolescent girls suffering from Lemierre's syndrome studied with cervical color Doppler ultrasonography (CDUS), cervicothoracic helical CT, and high-resolution CT (HRCT) scanning. In both patients, HRCT allowed a good depiction of multiple cavitated pulmonary nodules of various sizes suggestive of this entity and was able to detect small or peripheral nodules. CDUS helped to pinpoint the extent of thromboses of the internal jugular vein demonstrated by CT. CDUS and HRCT should be performed as early as possible to confirm and treat this life-threatening condition.
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