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Papers by Christine Lebrun-frenay
Proceedings IEEE International Symposium on Biomedical Imaging, 2002
White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal... more White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal elderly in association with vascular risk factors, such as hypertension or stroke. An accurate WML detection provides significant information for disease tracking, therapy evaluation, and normal aging research. In this article, we present an unsupervised WML segmentation method that uses Gaussian mixture model to describe the intensity distribution of the normal brain tissues and detects the WMLs as outliers to the normal brain tissue model based on extreme value theory. The detection of WMLs is performed by comparing the probability distribution function of a one-sided normal distribution and a Gumbel distribution, which is a specific extreme value distribution. The performance of the automatic segmentation is validated on synthetic and clinical MR images with regard to different imaging sequences and lesion loads. Results indicate that the segmentation method has a favorable accuracy competitive with other state-of-the-art WML segmentation methods.
Multiple sclerosis and related disorders, 2015
No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vit... more No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two pa...
Brain : a journal of neurology, 2015
Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infan... more Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant ...
Revue neurologique
The commonly used test to evaluate naming ability in multiple sclerosis (MS) is the Boston Naming... more The commonly used test to evaluate naming ability in multiple sclerosis (MS) is the Boston Naming Test (BNT). In previous studies the BNP has not shown any specific deficit in MS patients. The BNT score is obtained by adding spontaneously correct answers to correct answers obtained after semantic and phonological clues are given. Our hypothesis was that due to a lexical access deficit based on executive dysfunction, MS patients would need more clues than control subjects to normalize their performances,. Fifteen relapsing-remitting (RR) and 17 secondary progressive (SP) MS patients, and 32 controls matched for sex, age, and educational level, took the BNT. The 32 MS patients also took the BCCog (Short French battery used in MS to evaluate cognitive functions) in order to evaluate their executive functions. MS patients needed significantly more clues than matched controls to normalize their performances (P<0.001). This lexical access deficit was more frequent in the SP than in the...
Revue neurologique, 2013
Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishin... more Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishing white matter disease. Large cavitary lesions are not typical for multiple sclerosis (MS). We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), mini mental state (MMS), vanishing white matter disease genetic analysis, and MRI characteristics of the cavitary lesions were analyzed. Twenty patients were analyzed (6 men and 14 women). Mean age at disease onset was 37.6 (range 17-58). Mean disease duration was 10 years (range 2-20). Five patients had initial relapsing-remitting MS and nine patients had primary-progressive MS. Mean EDSS was 5.5 (range 2-8). Mean MMS was 20/30. Vanishing white matter disease genetic analysis was performed and negative in seven patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were st...
Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. ... more Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. The exact contribution of brain MRI remains a subject of debate, but it is generally considered to provide a more specific and more sensitive outcome measure for monitoring purposes and for testing new therapies. The choice of MRI techniques, and measurement reproducibility for multiple sclerosis brain lesions are not defined with precision for routine practice. There are many sources of error when comparing successive images which can be overcome to some extent with repositioning and image processing techniques. We evaluated the impact of image repositioning on treatment decision-making for twelve relapsing remitting patients. Brain MRIs were performed every three months for a one-year period. Two neurologists interpreted the non-repositioned and repositioned images giving their analysis of changes in the lesions visualized on the T2 sequences and their therapeutic decisions. For the first neurologist, analysis of the non-repositioned images yielded six patients whose lesions had worsened while for the repositioned images there were only three. For the second neurologist, four patients had more lesions with the non-repositioned images and only three with repositioning. The subjective interpretations were the same for the two neurologists when they used repositioned images. Comparison by two neurologists of non-repositioned and repositioned MRI, with no other image processing, affected the analysis and in certain cases propositions for treatment.
Revue Neurologique, 2010
Optic neuropathy is a rare adverse reaction to vaccination. A 62-year-old-woman was hospitalized ... more Optic neuropathy is a rare adverse reaction to vaccination. A 62-year-old-woman was hospitalized for bilateral optic neuropathy with loss of vision. The symptoms occurred 15 days after a seasonal influenza vaccination. Her past medical history included a mixed connective tissue disease with no immunosuppressive treatment for several years. Investigations did not reveal any obvious cause and the hypothesis of post-influenza vaccination bilateral optic neuropathy was retained although a complication of the connective tissue disease complication could not be ruled out. The patient was given intravenous methylprednisolone 1g daily. At a cumulative dose of 8 g, oral steroids were given and tapered off. Few similar case reports have been described in literature. The causal link between vaccination and optic neuropathy thus remains to be confirmed. Clinicians should however consider this etiology.
Revue Neurologique, 2010
Health related quality of life (HRQOL) is often affected in multiple sclerosis (MS). Nevertheless... more Health related quality of life (HRQOL) is often affected in multiple sclerosis (MS). Nevertheless, to our knowledge, there is no longitudinal study in the literature about the correlation between MRI parameters and HRQOL in MS patients. We included 28 patients with clinically definite relapsing remitting MS. All patients initiated subcutaneous interferon beta-1a therapy. To assess HRQOL, we used the SEP-59 scale, the French validated translation of MSQOL-54, and the MusiQoL scale. Conventional MRI was performed every year. Lesion load (LL) and brain atrophy were automatically measured using SepINRIA, a free software developed by INRIA in Sophia Antipolis. The mean EDSS score was 1.7 and disease duration was 2.5 years. Our results revealed that HRQOL was significantly correlated to T1 and T2-LL with both SEP-59 and MusiQoL scales. T1-LL was better correlated with physical dimensions and T2-LL was better correlated with mental components. At 1-year follow-up, patients whose MRI showed either an increase of T1 LL or at least one gadolinium enhancing lesion had a worse HRQOL at the end of the study. Initial brain parenchymal fraction (BPF) measure was also correlated with the long-term follow-up HRQOL. EDSS scored at the end of the study had not significantly changed (1.3; P&amp;amp;amp;gt;0.05). Our study revealed pertinent clinicoradiological correlations between HRQOL and MRI parameters in our cohort.
Proceedings IEEE International Symposium on Biomedical Imaging, 2002
White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal... more White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal elderly in association with vascular risk factors, such as hypertension or stroke. An accurate WML detection provides significant information for disease tracking, therapy evaluation, and normal aging research. In this article, we present an unsupervised WML segmentation method that uses Gaussian mixture model to describe the intensity distribution of the normal brain tissues and detects the WMLs as outliers to the normal brain tissue model based on extreme value theory. The detection of WMLs is performed by comparing the probability distribution function of a one-sided normal distribution and a Gumbel distribution, which is a specific extreme value distribution. The performance of the automatic segmentation is validated on synthetic and clinical MR images with regard to different imaging sequences and lesion loads. Results indicate that the segmentation method has a favorable accuracy competitive with other state-of-the-art WML segmentation methods.
Multiple sclerosis and related disorders, 2015
No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vit... more No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two pa...
Brain : a journal of neurology, 2015
Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infan... more Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant ...
Revue neurologique
The commonly used test to evaluate naming ability in multiple sclerosis (MS) is the Boston Naming... more The commonly used test to evaluate naming ability in multiple sclerosis (MS) is the Boston Naming Test (BNT). In previous studies the BNP has not shown any specific deficit in MS patients. The BNT score is obtained by adding spontaneously correct answers to correct answers obtained after semantic and phonological clues are given. Our hypothesis was that due to a lexical access deficit based on executive dysfunction, MS patients would need more clues than control subjects to normalize their performances,. Fifteen relapsing-remitting (RR) and 17 secondary progressive (SP) MS patients, and 32 controls matched for sex, age, and educational level, took the BNT. The 32 MS patients also took the BCCog (Short French battery used in MS to evaluate cognitive functions) in order to evaluate their executive functions. MS patients needed significantly more clues than matched controls to normalize their performances (P<0.001). This lexical access deficit was more frequent in the SP than in the...
Revue neurologique, 2013
Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishin... more Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishing white matter disease. Large cavitary lesions are not typical for multiple sclerosis (MS). We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), mini mental state (MMS), vanishing white matter disease genetic analysis, and MRI characteristics of the cavitary lesions were analyzed. Twenty patients were analyzed (6 men and 14 women). Mean age at disease onset was 37.6 (range 17-58). Mean disease duration was 10 years (range 2-20). Five patients had initial relapsing-remitting MS and nine patients had primary-progressive MS. Mean EDSS was 5.5 (range 2-8). Mean MMS was 20/30. Vanishing white matter disease genetic analysis was performed and negative in seven patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were st...
Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. ... more Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. The exact contribution of brain MRI remains a subject of debate, but it is generally considered to provide a more specific and more sensitive outcome measure for monitoring purposes and for testing new therapies. The choice of MRI techniques, and measurement reproducibility for multiple sclerosis brain lesions are not defined with precision for routine practice. There are many sources of error when comparing successive images which can be overcome to some extent with repositioning and image processing techniques. We evaluated the impact of image repositioning on treatment decision-making for twelve relapsing remitting patients. Brain MRIs were performed every three months for a one-year period. Two neurologists interpreted the non-repositioned and repositioned images giving their analysis of changes in the lesions visualized on the T2 sequences and their therapeutic decisions. For the first neurologist, analysis of the non-repositioned images yielded six patients whose lesions had worsened while for the repositioned images there were only three. For the second neurologist, four patients had more lesions with the non-repositioned images and only three with repositioning. The subjective interpretations were the same for the two neurologists when they used repositioned images. Comparison by two neurologists of non-repositioned and repositioned MRI, with no other image processing, affected the analysis and in certain cases propositions for treatment.
Revue Neurologique, 2010
Optic neuropathy is a rare adverse reaction to vaccination. A 62-year-old-woman was hospitalized ... more Optic neuropathy is a rare adverse reaction to vaccination. A 62-year-old-woman was hospitalized for bilateral optic neuropathy with loss of vision. The symptoms occurred 15 days after a seasonal influenza vaccination. Her past medical history included a mixed connective tissue disease with no immunosuppressive treatment for several years. Investigations did not reveal any obvious cause and the hypothesis of post-influenza vaccination bilateral optic neuropathy was retained although a complication of the connective tissue disease complication could not be ruled out. The patient was given intravenous methylprednisolone 1g daily. At a cumulative dose of 8 g, oral steroids were given and tapered off. Few similar case reports have been described in literature. The causal link between vaccination and optic neuropathy thus remains to be confirmed. Clinicians should however consider this etiology.
Revue Neurologique, 2010
Health related quality of life (HRQOL) is often affected in multiple sclerosis (MS). Nevertheless... more Health related quality of life (HRQOL) is often affected in multiple sclerosis (MS). Nevertheless, to our knowledge, there is no longitudinal study in the literature about the correlation between MRI parameters and HRQOL in MS patients. We included 28 patients with clinically definite relapsing remitting MS. All patients initiated subcutaneous interferon beta-1a therapy. To assess HRQOL, we used the SEP-59 scale, the French validated translation of MSQOL-54, and the MusiQoL scale. Conventional MRI was performed every year. Lesion load (LL) and brain atrophy were automatically measured using SepINRIA, a free software developed by INRIA in Sophia Antipolis. The mean EDSS score was 1.7 and disease duration was 2.5 years. Our results revealed that HRQOL was significantly correlated to T1 and T2-LL with both SEP-59 and MusiQoL scales. T1-LL was better correlated with physical dimensions and T2-LL was better correlated with mental components. At 1-year follow-up, patients whose MRI showed either an increase of T1 LL or at least one gadolinium enhancing lesion had a worse HRQOL at the end of the study. Initial brain parenchymal fraction (BPF) measure was also correlated with the long-term follow-up HRQOL. EDSS scored at the end of the study had not significantly changed (1.3; P&amp;amp;amp;gt;0.05). Our study revealed pertinent clinicoradiological correlations between HRQOL and MRI parameters in our cohort.