OBJECTIVE: To identify a presurgical metabolic pattern using (18)FDG-PET which could predict post... more OBJECTIVE: To identify a presurgical metabolic pattern using (18)FDG-PET which could predict postoperative apathy after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson Disease (PD). BACKGROUND: STN-DBS in PD has been associated with postoperative apathy. There is an ongoing debate whether STN-DBS or drug modifications are causal in the development of postoperative apathy. DESIGN/METHODS: Nineteen PD patients scheduled for STN DBS surgery, not clinically apathetic (Lille Apathy Rating Scale [LARS]<-16) nor depressed (Montgomery and Asberg Depression Rating Scale [MADRS] <21) underwent a (18) FDG-PET scan before STN-DBS and were assessed with LARS and MADRS before and one year after surgery. Whole-brain voxel-based (18)FDG-PET intergroup comparison was evaluated between patients with and without postoperative apathy, using SPM8 (p < 0.005, uncorrected). RESULTS: Five patients became apathetic after surgery (LARS蠅-16). Positive correlation were observed between the postoperative LARS and presurgical cerebral metabolism in posterior fossa (p=0.030), temporal area (p=0.038) and cingulum (p=0.057). CONCLUSIONS: These preliminary results confirm that frontal, temporal and posterior area are implicated in apathy (Robert et al, 2012) but suggest a metabolic predisposition to post STN-DBS apathy. This may indicate that STN-DBS and perioperative drug modifications are not the exclusive causes of postoperative apathy. Disclosure: Dr. Gesquiere-Dando has nothing to disclose. Dr. Guedj has nothing to disclose. Dr. Witjas has received personal compensation for activities with GlaxoSmithKline Inc., Medtronic Inc., Boehringer Ingelheim Pharmaceuticals Inc., and UCB Pharma. Dr. Fluchere has nothing to disclose. Dr. Delfini has nothing to disclose. Dr. Mundler has nothing to disclose. Dr. Azulay has received personal compensation for activities with GlaxoSmithKlyne Inc., Boehringer Ingelheim Pharmaceuticals, Inc., UCB Pharma, Novartis, Teva Neuroscience, and Lundbeck Research USA, Inc. Dr. Eusebio has nothing to disclose.
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkins... more Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future.
TDP‐43 (TAR‐DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), a... more TDP‐43 (TAR‐DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontotemporal lobar degeneration (FTLD) and FTLD associated with MND (FTLD‐MND). Mutations in TARDBP gene, coding for TDP‐43, were found in patients with pure MND. We now describe TARDBP mutations in two patients with FTLD‐MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP‐43 may also have a direct pathogenic role in FTLD disorders. Ann Neurol 2009;65:470–474
International audienceThe aim of this study was to investigate the functional brain substrate ă o... more International audienceThe aim of this study was to investigate the functional brain substrate ă of quality of life (QoL) in patients with schizophrenia. Participants ă comprised 130 right-handed patients with schizophrenia who underwent ă whole-brain single photon emission computed tomography (SPECT) with ă Tc-99m-labeled ethylcysteinate dimer (Tc-99m-ECD) for exploring ă correlations of regional cerebral blood flow (rCBF) with the eight ă dimensions score of the Schizophrenia Quality of Life questionnaire ă (S-QoL 18). A significant positive correlation was found between the ă global index of the S-QoL 18 and rCBF in the right superior temporal ă sulcus and between psychological well-being dimension and rCBF in ă Brodmann area (BA)6, BA8, BA9, and BA10 and between self-esteem ă dimension and rCBF in striatum and between family relationship dimension ă and rCBF in BA1, BA2, BA3, BA4, BA8, BA22, BA40, BA42 and BA44 and ă between relationship with friends dimension and rCBF in BA44 and between ă physical well-being dimension and rCBF in parahippocampal gyrus, and ă finally between autonomy dimension and rCBF in cuneus and precuneus. A ă significant negative correlation was found between resilience dimension ă and rCBF in precuneus and between sentimental life dimension and rCBF in ă BA10. Our findings provide neural correlates of QoL. Brain regions ă involved in cognitions, emotional information processing and social ă cognition underlie the different QoL dimensions. (C) 2016 Published by ă Elsevier Ireland Ltd
Sirs: A subset of familial frontotemporal dementia with Parkinsonism is caused by mutations in th... more Sirs: A subset of familial frontotemporal dementia with Parkinsonism is caused by mutations in the tau gene on chromosome 17 (FTDP17) [3].Among those mutations, P301S mutation has been reported in only four families [1, 2, 4, 6], and in a recent issue of this journal, three cases of FTDP-17 from a Jewish-Algerian family have already been reported by Lossos et al. [2]. We propose to complete the phenotype description for this family by providing the description of two members whom we have evaluated during four years. The dominant phenotype in previously reported members in this family was FTDP, with a more aggressive course and later age of onset than usually observed in P301S mutations.We describe a variant clinical presentation in the same family, with two members exhibiting a different phenotype with different treatment sensitivity and prognosis.
Journal of Neurology, Neurosurgery, and Psychiatry, Apr 23, 2021
ObjectiveWe aim to search for predictors of survival among clinical and brain 18F-FDG positron em... more ObjectiveWe aim to search for predictors of survival among clinical and brain 18F-FDG positron emission tomography (PET) metabolic features in our cohort of patients with multiple system atrophy (MSA).MethodsWe included patients with a ‘probable’ MSA diagnosis for whom a clinical evaluation and a brain PET were performed early in the course of the disease (median 3 years, IQR 2–5). A retrospective analysis was conducted using standardised data collection. Brain PET metabolism was characterised using the Automated Anatomical Labelling Atlas. A Cox model was applied to look for factors influencing survival. Kaplan-Meier method estimated the survival rate. We proposed to develop a predictive ‘risk score’, categorised into low-risk and high-risk groups, using significant variables entered in multivariate Cox regression analysis.ResultsEighty-five patients were included. The overall median survival was 8 years (CI 6.64 to 9.36). Poor prognostic factors were orthostatic hypotension (HR=6.04 (CI 1.58 to 23.12), p=0.009), stridor (HR=3.41 (CI 1.31 to 8.87), p=0.012) and glucose PET hypometabolism in the left insula (HR=0.78 (CI 0.66 to 0.92), p=0.004). Good prognostic factors were time to diagnosis (HR=0.68 (CI 0.54 to 0.86), p=0.001) and use of selective serotonin reuptake inhibitor (SSRI) (HR=0.17 (CI 0.06 to 0.46), p&lt;0.001). The risk score revealed a 5-year gap separating the median survival of the two groups obtained (5 years vs 10 years; HR=5.82 (CI 2.94 to 11.49), p&lt;0.001).ConclusionThe clinical prognosis factors we have described support published studies. Here, we also suggest that brain PET is of interest for prognosis assessment and in particular in the search for left insula hypometabolism. Moreover, SSRIs are a potential drug candidate to slow the progression of the disease.
OBJECTIVE: To identify a presurgical metabolic pattern using (18)FDG-PET which could predict post... more OBJECTIVE: To identify a presurgical metabolic pattern using (18)FDG-PET which could predict postoperative apathy after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson Disease (PD). BACKGROUND: STN-DBS in PD has been associated with postoperative apathy. There is an ongoing debate whether STN-DBS or drug modifications are causal in the development of postoperative apathy. DESIGN/METHODS: Nineteen PD patients scheduled for STN DBS surgery, not clinically apathetic (Lille Apathy Rating Scale [LARS]<-16) nor depressed (Montgomery and Asberg Depression Rating Scale [MADRS] <21) underwent a (18) FDG-PET scan before STN-DBS and were assessed with LARS and MADRS before and one year after surgery. Whole-brain voxel-based (18)FDG-PET intergroup comparison was evaluated between patients with and without postoperative apathy, using SPM8 (p < 0.005, uncorrected). RESULTS: Five patients became apathetic after surgery (LARS蠅-16). Positive correlation were observed between the postoperative LARS and presurgical cerebral metabolism in posterior fossa (p=0.030), temporal area (p=0.038) and cingulum (p=0.057). CONCLUSIONS: These preliminary results confirm that frontal, temporal and posterior area are implicated in apathy (Robert et al, 2012) but suggest a metabolic predisposition to post STN-DBS apathy. This may indicate that STN-DBS and perioperative drug modifications are not the exclusive causes of postoperative apathy. Disclosure: Dr. Gesquiere-Dando has nothing to disclose. Dr. Guedj has nothing to disclose. Dr. Witjas has received personal compensation for activities with GlaxoSmithKline Inc., Medtronic Inc., Boehringer Ingelheim Pharmaceuticals Inc., and UCB Pharma. Dr. Fluchere has nothing to disclose. Dr. Delfini has nothing to disclose. Dr. Mundler has nothing to disclose. Dr. Azulay has received personal compensation for activities with GlaxoSmithKlyne Inc., Boehringer Ingelheim Pharmaceuticals, Inc., UCB Pharma, Novartis, Teva Neuroscience, and Lundbeck Research USA, Inc. Dr. Eusebio has nothing to disclose.
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkins... more Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future.
TDP‐43 (TAR‐DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), a... more TDP‐43 (TAR‐DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontotemporal lobar degeneration (FTLD) and FTLD associated with MND (FTLD‐MND). Mutations in TARDBP gene, coding for TDP‐43, were found in patients with pure MND. We now describe TARDBP mutations in two patients with FTLD‐MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP‐43 may also have a direct pathogenic role in FTLD disorders. Ann Neurol 2009;65:470–474
International audienceThe aim of this study was to investigate the functional brain substrate ă o... more International audienceThe aim of this study was to investigate the functional brain substrate ă of quality of life (QoL) in patients with schizophrenia. Participants ă comprised 130 right-handed patients with schizophrenia who underwent ă whole-brain single photon emission computed tomography (SPECT) with ă Tc-99m-labeled ethylcysteinate dimer (Tc-99m-ECD) for exploring ă correlations of regional cerebral blood flow (rCBF) with the eight ă dimensions score of the Schizophrenia Quality of Life questionnaire ă (S-QoL 18). A significant positive correlation was found between the ă global index of the S-QoL 18 and rCBF in the right superior temporal ă sulcus and between psychological well-being dimension and rCBF in ă Brodmann area (BA)6, BA8, BA9, and BA10 and between self-esteem ă dimension and rCBF in striatum and between family relationship dimension ă and rCBF in BA1, BA2, BA3, BA4, BA8, BA22, BA40, BA42 and BA44 and ă between relationship with friends dimension and rCBF in BA44 and between ă physical well-being dimension and rCBF in parahippocampal gyrus, and ă finally between autonomy dimension and rCBF in cuneus and precuneus. A ă significant negative correlation was found between resilience dimension ă and rCBF in precuneus and between sentimental life dimension and rCBF in ă BA10. Our findings provide neural correlates of QoL. Brain regions ă involved in cognitions, emotional information processing and social ă cognition underlie the different QoL dimensions. (C) 2016 Published by ă Elsevier Ireland Ltd
Sirs: A subset of familial frontotemporal dementia with Parkinsonism is caused by mutations in th... more Sirs: A subset of familial frontotemporal dementia with Parkinsonism is caused by mutations in the tau gene on chromosome 17 (FTDP17) [3].Among those mutations, P301S mutation has been reported in only four families [1, 2, 4, 6], and in a recent issue of this journal, three cases of FTDP-17 from a Jewish-Algerian family have already been reported by Lossos et al. [2]. We propose to complete the phenotype description for this family by providing the description of two members whom we have evaluated during four years. The dominant phenotype in previously reported members in this family was FTDP, with a more aggressive course and later age of onset than usually observed in P301S mutations.We describe a variant clinical presentation in the same family, with two members exhibiting a different phenotype with different treatment sensitivity and prognosis.
Journal of Neurology, Neurosurgery, and Psychiatry, Apr 23, 2021
ObjectiveWe aim to search for predictors of survival among clinical and brain 18F-FDG positron em... more ObjectiveWe aim to search for predictors of survival among clinical and brain 18F-FDG positron emission tomography (PET) metabolic features in our cohort of patients with multiple system atrophy (MSA).MethodsWe included patients with a ‘probable’ MSA diagnosis for whom a clinical evaluation and a brain PET were performed early in the course of the disease (median 3 years, IQR 2–5). A retrospective analysis was conducted using standardised data collection. Brain PET metabolism was characterised using the Automated Anatomical Labelling Atlas. A Cox model was applied to look for factors influencing survival. Kaplan-Meier method estimated the survival rate. We proposed to develop a predictive ‘risk score’, categorised into low-risk and high-risk groups, using significant variables entered in multivariate Cox regression analysis.ResultsEighty-five patients were included. The overall median survival was 8 years (CI 6.64 to 9.36). Poor prognostic factors were orthostatic hypotension (HR=6.04 (CI 1.58 to 23.12), p=0.009), stridor (HR=3.41 (CI 1.31 to 8.87), p=0.012) and glucose PET hypometabolism in the left insula (HR=0.78 (CI 0.66 to 0.92), p=0.004). Good prognostic factors were time to diagnosis (HR=0.68 (CI 0.54 to 0.86), p=0.001) and use of selective serotonin reuptake inhibitor (SSRI) (HR=0.17 (CI 0.06 to 0.46), p&lt;0.001). The risk score revealed a 5-year gap separating the median survival of the two groups obtained (5 years vs 10 years; HR=5.82 (CI 2.94 to 11.49), p&lt;0.001).ConclusionThe clinical prognosis factors we have described support published studies. Here, we also suggest that brain PET is of interest for prognosis assessment and in particular in the search for left insula hypometabolism. Moreover, SSRIs are a potential drug candidate to slow the progression of the disease.
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Papers by Eric Guedj