Parkinson's disease in a neurodegenerative disorder that affects as many as 1-2 % of persons aged... more Parkinson's disease in a neurodegenerative disorder that affects as many as 1-2 % of persons aged 60 years and older. Parkinson's disease occurs infrequently under 40 years of age, with major genetic implication. Alpha-synuclein plays significant pathogenic role in Parkinson's disease. Therapeutic advances based on a synucleinrelated mechanism are now developed : immunotherapy against alpha-synuclein for example. The diagnosis of Parkinson's disease remains mostly clinical. DatScan® may be helpful to distinguish parkinsonian syndrome and essential tremor. Current therapy is mainly based on a dopamine replacement strategy using the precursor levodopa (L-Dopa) and dopamine receptor agonists. Parkinson's is also associated with non-motor symptoms like sleep disorders, autonomic symptoms, neuropsychiatric symptoms. Advanced disease is associated with emergence of feature such as freezing, falling and neuropsychological dysfunction. Nonpharmacologic treatments like exercise are fundamental elements of patients' management. Motor complications and dyskinesia are common in advanced Parkinson's disease. Continuous administration of L-Dopa/carbidopa infusion in the jejunum provides more continuous dopaminergic drug delivery and stimulation and reduce motor complications. Further other approach are developped like surgical procedures: ex : high frequency stimulation of subthalamic nucleus, the more rational target for stimulation in Parkinson's disease.
We reviewed 89 breast cancer patients with brain or epidural metastases in order to see whether a... more We reviewed 89 breast cancer patients with brain or epidural metastases in order to see whether a parallelism could be found between disease evolution inside and outside the central nervous system. One-fifth of the patients with brain metastases did not have any other site of relapse before neurological complication. Among the 38 patients who developed brain metastases and had a prior history of relapse outside the brain, 12 had control of constant extracranial sites while disease was progressing at these sites in 26 of them. In the epidural metastases group, all patients but 4 had progressive disease elsewhere when neurological complication appeared.
Introduction: Intraoperative microelectrodes recording with the Ben Gun microdrive system are oft... more Introduction: Intraoperative microelectrodes recording with the Ben Gun microdrive system are often used during DBS surgery. An accurate location of these microelectrodes will directly influence the interest of this recording. We have studied the imprecision of implantation of these microelectrodes. Methods: We have analyzed the stereotactic position of 135 microelectrodes implanted with the Ben Gun microdrive during DBS surgery of 16 patients with advanced Parkinson’s disease. An intracranial CT was obtained and integrated to a stereotactic planification system. We recorded the stereotactic coordinates of the 5 microelectrodes inserted simultaneously in a cross-shape. The coordinates of each microelectrode were compared with coordinates of the other 4 electrodes inserted simultaneously with the Ben Gun and visible on the same iCT image. Thus, this procedure avoids errors from image fusion and from brain shift. We calculate (1) the three-dimensional Euclidian deviation of microelectrodes, (2) the deviation in X- and Y-axes on reconstructed probe’s eye view MR images, and (3) the deviation from the 2-mm theoretical distance between the central electrode and 4 satellite microelectrodes. Results: The median deviation was 0.64 mm in 3-D and 0.58 mm in 2-D probe’s eye view. Satellite electrodes were located from the central electrode theoretically at 2.0 mm and practically within the range 1.9–2.1 mm, 1.5–2.5 mm, 1.0–3.0 mm, and 0.5–3.5 mm for, respectively, 9.3%, 53.7%, 88.0%, and 98.1%, thus highlighting the significant deviation from the theoretical distance. Position imprecisions were similar for the 4 satellite microelectrodes. The imprecision was similar in X-axis and Y-axes and statistically less in Z-axis. For bilateral implantation, the second implantation of the same patient was not associated with a greater risk of deviation of the microelectrodes than for the first side implanted. Conclusion: A significant percentage of microelectrodes for MER can deviate substantially from their theoretical target during DBS procedures. An iCT can be used to estimate the potential deviation of microelectrodes and improve the interpretation of MER during the procedure.
Brain abscesses are classical complications of congenital heart disease (CHD) in children and ado... more Brain abscesses are classical complications of congenital heart disease (CHD) in children and adolescents. This association is rarely observed in adults. We report a 46-year-old man presenting a fronto-parietal abscess associated with an asymptomatic atrial septal defect. Positron emission tomography (PET) study revealed high uptake of L-[methyl-11C]methionine ([11C]methionine) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) around the brain abscess. We suggest (1) to exclude a silent cardiac malformation in the presence of a cerebral abscess of unknown source occurring in adults; (2) to consider the diagnosis of brain abscess in cases of high uptake of [11C]methionine and FDG in relation to a brain lesion.
The diagnosis of idiopathic Parkinson's disease (IPD) remains mostly clinical. Nevertheless, diff... more The diagnosis of idiopathic Parkinson's disease (IPD) remains mostly clinical. Nevertheless, differentiating IPD from essential tremor or other parkinsonian syndromes solely by clinical examination can be challenging in some cases, especially in the early stage of the disease. The introduction of new isotopic functional imaging techniques, and more specifically the labelling of dopamine transporter derivatives, has improved the understanding and early detection of some diseases affecting the basal ganglia. Iodine-123-FP-CIT (DaTSCAN), a (presynaptic) dopamine transporter analogue for nuclear medicine imaging, has recently been introduced for the non-invasive differential diagnosis between IPD and essential tremor or secondary (e.g. drug-related) parkinsonian syndromes. DaTSCAN scintigraphy has also demonstrated some usefulness in the evaluation of other neurodegenerative parkinsonian syndromes such as Lewy-body dementia or multiple system atrophy. For this latter however, the DaTSCAN has to be combined with a second scintigraphy, imaging the post-synaptic dopaminergic receptors, such as the D2-ligand 123I-iodobenzamide. Combining DaTSCAN scintigraphy to a functional study of the brain cortical activity using a brain perfusion scintigraphy or to the evaluation of the cardiac adrenergic system by means of a myocardial MIBG scintigraphy (a norepinephrine storage analogue) can also be helpful to refine the diagnosis. Our experience shows that a good collaboration between the neurologist specialized in movement disorders and the nuclear medicine physician is useful, if not mandatory, to optimize the diagnostic performances of DaTSCAN scintigraphy.
We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) recep... more We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.
Abstract In the presence of carbidopa, L-3, 4-dihydroxy-6-[18 F] fluorophenylalanine ([18 F] fluo... more Abstract In the presence of carbidopa, L-3, 4-dihydroxy-6-[18 F] fluorophenylalanine ([18 F] fluoro-DOPA) is mainly metabolized by catechol-O-methyl transferase. We studied the effects of entacapone, a peripheral catechol-O-methyl transferase inhibitor, on striatal [18 ...
Three patients were examined using PET with L-methyl-11C-methionine (11C-methionine) and 2-18F-fl... more Three patients were examined using PET with L-methyl-11C-methionine (11C-methionine) and 2-18F-fluoro-2-deoxy-D-glucose (FDG) 20 to 32 days after the occurrence of nontumoral brain hematomas. PET revealed high uptake of 11C-methionine in the area surrounding the hematoma in all three patients. In two patients, discrete spots of moderate uptake of FDG were found at the periphery of a hypometabolic area. PET studies were repeated in two patients 76 and 103 days after the bleeding, respectively, and showed a dramatic decrease in 11C-methionine uptake around the hematoma. The spots of FDG uptake disappeared on the repeated late scans. We hypothesize that the subacute gliotic reaction surrounding brain hematomas is responsible for increased uptake of 11C-methionine and for the presence of spots of FDG uptake. PET studies with 11C-methionine and FDG performed 20 to 32 days after the initial symptom are not helpful in the differentiation between neoplastic and non-neoplastic origins of an intracerebral hemorrhage since tracer uptake at the periphery of the lesion may be increased in both.
We used in vitro microdialysis-HPLC to determine L-3,4-dihydroxyphenylalanine (L-DOPA) and its me... more We used in vitro microdialysis-HPLC to determine L-3,4-dihydroxyphenylalanine (L-DOPA) and its metabolites in plasma of patients with advanced Parkinson disease. Blood samples and clinical evaluations were obtained 0, 30, 60, 90, 120, and 150 min after oral administration of carbidopa/L-DOPA (25/100 mg, 12.5/125 mg, and 50/200 mg). In vitro recoveries for L-DOPA and metabolites ranged from 22% to 36%. Linear correlation was found between metabolite concentrations in the dialysate and in the surrounding medium. There was a significant positive correlation between L-DOPA dose and plasma concentration of L-DOPA and homovanillic acid (P < 0.04). Clinical response was maximum 60 min after L-DOPA administration. Threshold L-DOPA plasma concentration averaged 7.74 +/- 3.3 mumol/L. Motor effect is longer with the highest L-DOPA peak concentration (P < 0.01). Microdialysis-HPLC is readily applicable, reproducible, and allows monitoring of plasma L-DOPA and metabolites in parkinsonian patients.
Gliomas are regionally heterogeneous tumors. The local relationship between histologic features a... more Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies. Methods: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples. Results: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C-MET. Conclusion: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures.
We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergo... more We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.
Parkinson's disease in a neurodegenerative disorder that affects as many as 1-2 % of persons aged... more Parkinson's disease in a neurodegenerative disorder that affects as many as 1-2 % of persons aged 60 years and older. Parkinson's disease occurs infrequently under 40 years of age, with major genetic implication. Alpha-synuclein plays significant pathogenic role in Parkinson's disease. Therapeutic advances based on a synucleinrelated mechanism are now developed : immunotherapy against alpha-synuclein for example. The diagnosis of Parkinson's disease remains mostly clinical. DatScan® may be helpful to distinguish parkinsonian syndrome and essential tremor. Current therapy is mainly based on a dopamine replacement strategy using the precursor levodopa (L-Dopa) and dopamine receptor agonists. Parkinson's is also associated with non-motor symptoms like sleep disorders, autonomic symptoms, neuropsychiatric symptoms. Advanced disease is associated with emergence of feature such as freezing, falling and neuropsychological dysfunction. Nonpharmacologic treatments like exercise are fundamental elements of patients' management. Motor complications and dyskinesia are common in advanced Parkinson's disease. Continuous administration of L-Dopa/carbidopa infusion in the jejunum provides more continuous dopaminergic drug delivery and stimulation and reduce motor complications. Further other approach are developped like surgical procedures: ex : high frequency stimulation of subthalamic nucleus, the more rational target for stimulation in Parkinson's disease.
We reviewed 89 breast cancer patients with brain or epidural metastases in order to see whether a... more We reviewed 89 breast cancer patients with brain or epidural metastases in order to see whether a parallelism could be found between disease evolution inside and outside the central nervous system. One-fifth of the patients with brain metastases did not have any other site of relapse before neurological complication. Among the 38 patients who developed brain metastases and had a prior history of relapse outside the brain, 12 had control of constant extracranial sites while disease was progressing at these sites in 26 of them. In the epidural metastases group, all patients but 4 had progressive disease elsewhere when neurological complication appeared.
Introduction: Intraoperative microelectrodes recording with the Ben Gun microdrive system are oft... more Introduction: Intraoperative microelectrodes recording with the Ben Gun microdrive system are often used during DBS surgery. An accurate location of these microelectrodes will directly influence the interest of this recording. We have studied the imprecision of implantation of these microelectrodes. Methods: We have analyzed the stereotactic position of 135 microelectrodes implanted with the Ben Gun microdrive during DBS surgery of 16 patients with advanced Parkinson’s disease. An intracranial CT was obtained and integrated to a stereotactic planification system. We recorded the stereotactic coordinates of the 5 microelectrodes inserted simultaneously in a cross-shape. The coordinates of each microelectrode were compared with coordinates of the other 4 electrodes inserted simultaneously with the Ben Gun and visible on the same iCT image. Thus, this procedure avoids errors from image fusion and from brain shift. We calculate (1) the three-dimensional Euclidian deviation of microelectrodes, (2) the deviation in X- and Y-axes on reconstructed probe’s eye view MR images, and (3) the deviation from the 2-mm theoretical distance between the central electrode and 4 satellite microelectrodes. Results: The median deviation was 0.64 mm in 3-D and 0.58 mm in 2-D probe’s eye view. Satellite electrodes were located from the central electrode theoretically at 2.0 mm and practically within the range 1.9–2.1 mm, 1.5–2.5 mm, 1.0–3.0 mm, and 0.5–3.5 mm for, respectively, 9.3%, 53.7%, 88.0%, and 98.1%, thus highlighting the significant deviation from the theoretical distance. Position imprecisions were similar for the 4 satellite microelectrodes. The imprecision was similar in X-axis and Y-axes and statistically less in Z-axis. For bilateral implantation, the second implantation of the same patient was not associated with a greater risk of deviation of the microelectrodes than for the first side implanted. Conclusion: A significant percentage of microelectrodes for MER can deviate substantially from their theoretical target during DBS procedures. An iCT can be used to estimate the potential deviation of microelectrodes and improve the interpretation of MER during the procedure.
Brain abscesses are classical complications of congenital heart disease (CHD) in children and ado... more Brain abscesses are classical complications of congenital heart disease (CHD) in children and adolescents. This association is rarely observed in adults. We report a 46-year-old man presenting a fronto-parietal abscess associated with an asymptomatic atrial septal defect. Positron emission tomography (PET) study revealed high uptake of L-[methyl-11C]methionine ([11C]methionine) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) around the brain abscess. We suggest (1) to exclude a silent cardiac malformation in the presence of a cerebral abscess of unknown source occurring in adults; (2) to consider the diagnosis of brain abscess in cases of high uptake of [11C]methionine and FDG in relation to a brain lesion.
The diagnosis of idiopathic Parkinson's disease (IPD) remains mostly clinical. Nevertheless, diff... more The diagnosis of idiopathic Parkinson's disease (IPD) remains mostly clinical. Nevertheless, differentiating IPD from essential tremor or other parkinsonian syndromes solely by clinical examination can be challenging in some cases, especially in the early stage of the disease. The introduction of new isotopic functional imaging techniques, and more specifically the labelling of dopamine transporter derivatives, has improved the understanding and early detection of some diseases affecting the basal ganglia. Iodine-123-FP-CIT (DaTSCAN), a (presynaptic) dopamine transporter analogue for nuclear medicine imaging, has recently been introduced for the non-invasive differential diagnosis between IPD and essential tremor or secondary (e.g. drug-related) parkinsonian syndromes. DaTSCAN scintigraphy has also demonstrated some usefulness in the evaluation of other neurodegenerative parkinsonian syndromes such as Lewy-body dementia or multiple system atrophy. For this latter however, the DaTSCAN has to be combined with a second scintigraphy, imaging the post-synaptic dopaminergic receptors, such as the D2-ligand 123I-iodobenzamide. Combining DaTSCAN scintigraphy to a functional study of the brain cortical activity using a brain perfusion scintigraphy or to the evaluation of the cardiac adrenergic system by means of a myocardial MIBG scintigraphy (a norepinephrine storage analogue) can also be helpful to refine the diagnosis. Our experience shows that a good collaboration between the neurologist specialized in movement disorders and the nuclear medicine physician is useful, if not mandatory, to optimize the diagnostic performances of DaTSCAN scintigraphy.
We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) recep... more We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.
Abstract In the presence of carbidopa, L-3, 4-dihydroxy-6-[18 F] fluorophenylalanine ([18 F] fluo... more Abstract In the presence of carbidopa, L-3, 4-dihydroxy-6-[18 F] fluorophenylalanine ([18 F] fluoro-DOPA) is mainly metabolized by catechol-O-methyl transferase. We studied the effects of entacapone, a peripheral catechol-O-methyl transferase inhibitor, on striatal [18 ...
Three patients were examined using PET with L-methyl-11C-methionine (11C-methionine) and 2-18F-fl... more Three patients were examined using PET with L-methyl-11C-methionine (11C-methionine) and 2-18F-fluoro-2-deoxy-D-glucose (FDG) 20 to 32 days after the occurrence of nontumoral brain hematomas. PET revealed high uptake of 11C-methionine in the area surrounding the hematoma in all three patients. In two patients, discrete spots of moderate uptake of FDG were found at the periphery of a hypometabolic area. PET studies were repeated in two patients 76 and 103 days after the bleeding, respectively, and showed a dramatic decrease in 11C-methionine uptake around the hematoma. The spots of FDG uptake disappeared on the repeated late scans. We hypothesize that the subacute gliotic reaction surrounding brain hematomas is responsible for increased uptake of 11C-methionine and for the presence of spots of FDG uptake. PET studies with 11C-methionine and FDG performed 20 to 32 days after the initial symptom are not helpful in the differentiation between neoplastic and non-neoplastic origins of an intracerebral hemorrhage since tracer uptake at the periphery of the lesion may be increased in both.
We used in vitro microdialysis-HPLC to determine L-3,4-dihydroxyphenylalanine (L-DOPA) and its me... more We used in vitro microdialysis-HPLC to determine L-3,4-dihydroxyphenylalanine (L-DOPA) and its metabolites in plasma of patients with advanced Parkinson disease. Blood samples and clinical evaluations were obtained 0, 30, 60, 90, 120, and 150 min after oral administration of carbidopa/L-DOPA (25/100 mg, 12.5/125 mg, and 50/200 mg). In vitro recoveries for L-DOPA and metabolites ranged from 22% to 36%. Linear correlation was found between metabolite concentrations in the dialysate and in the surrounding medium. There was a significant positive correlation between L-DOPA dose and plasma concentration of L-DOPA and homovanillic acid (P < 0.04). Clinical response was maximum 60 min after L-DOPA administration. Threshold L-DOPA plasma concentration averaged 7.74 +/- 3.3 mumol/L. Motor effect is longer with the highest L-DOPA peak concentration (P < 0.01). Microdialysis-HPLC is readily applicable, reproducible, and allows monitoring of plasma L-DOPA and metabolites in parkinsonian patients.
Gliomas are regionally heterogeneous tumors. The local relationship between histologic features a... more Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies. Methods: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples. Results: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C-MET. Conclusion: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures.
We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergo... more We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.
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