J. Foncin - Academia.edu (original) (raw)
Papers by J. Foncin
Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1980
Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1971
Comptes rendus des séances de la Société de biologie et de ses filiales, 1964
Les Cahiers de médecine, Jan 30, 1970
Annales de médecine interne, 1977
A 10 1/2 years old boy fell brutally ill with a fit followed by confusion, and then by deep coma,... more A 10 1/2 years old boy fell brutally ill with a fit followed by confusion, and then by deep coma, with 40 degrees C fever and morbilliform rash. Consciousnesse came back within ten days, with transient Parkinson-like tremor. Myoclonus persisted for about six months. Complete recovery was followed up for six years. A diagnosis of encephalitis was considered on early EEG evidence (stereotyped repetitive sharp wave bursts) and was confirmed by isolation of ECHO 5 virus from brain specimen, and ultrastructural observation of characteristic cytopathic effect (disappearance of organelles, proliferation of smooth membranes) and of probable viral particules in astrocytes, without any inflammatory process.
Neuroscience Letters, 1992
Journal of Neurology, 2002
Frontotemporal dementia (FTD) displays significant neuropathological and genetic heterogeneity am... more Frontotemporal dementia (FTD) displays significant neuropathological and genetic heterogeneity among and within affected families. An early diagnosis is often difficult because cognitive symptoms are manifest only at a late stage of the disease. We have been studying a large pedigree segregating frontotemporal dementia (FTD) to which belong 34 identified affected persons, 11 of whom were personally examined. The kindred has been genealogically reconstructed; all FTD patients have been linked to the same ancestors who lived in the early 18(th) century (11 generations before the present one). Autosomal dominant transmission was evident. Clinical features were uniform within the kindred and met the Lund-Manchester criteria. Personality changes with absence of insight, lack of empathy and of social awareness manifested up to 5 years before medical advice was sought. Loss of fluency was the earliest neuropsychological sign, in the absence of memory, orientation and praxis deficits, which evolved late, together with hyperorality. Akinesia was observed early, rigidity appeared late, tremor was absent. Two patients showed myoclonus late in their evolution. No ALS signs were observed in this kindred. Mutations of the MAPt gene, coding for the Tau protein, were not detected in affected family members. Linkage studies excluded chromosomes 3 and 9 and gave indeterminate results that were model dependent for chromosome 17.
Journal of Geriatric Psychiatry and Neurology, 1994
We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's dis... more We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of t...
Experimental Neurology, 1998
European Journal of Human Genetics, 2003
Manic depressive illness (MDI) segregates within a founder population originating from S, a mount... more Manic depressive illness (MDI) segregates within a founder population originating from S, a mountain village in Southern Italy. Identity by descent of affected persons cannot be established by direct genealogical methods. A 56 000 persons family reconstruction data base encompasses the whole population of S in the 17th and 18th centuries, and part of the population of S and neighbouring villages in the 19th and 20th centuries. We selected 10 MDI probands who were members of the S population and not evident close relatives of each other. A total of 10 other MDI probands not evidently related to the S population formed a first control group. A second control group was formed with 10 not closely related persons originating within the S population. We determined the founders common ancestors to all the probands of one group but not ancestors to the probands of other groups, and computed the genetic contribution of each founder to each proband. The distance between probands in the S MDI group was calculated with respect to all the founders. In all, 17 founders present in the ascendancy of all individuals of the S MDI group are not present in the ascendancy of the control groups: MDI patients are derived from a subpopulation within S. Two S MDI probands are far from one another in respect of the 'nonspecific' founders, but are very close in respect of the specific founders: a putative MDI trait originated from specific founders of the MDI subpopulation, and hence is identical by descent in the S population.
Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 1997
Arquivos de Neuro-Psiquiatria, 1967
Nossa primeira hipofisectomia para tratamento de carcinoma metastático do seio foi feita em novem... more Nossa primeira hipofisectomia para tratamento de carcinoma metastático do seio foi feita em novembro de 1951 e a secção da haste pituitária (miscotomia) para o mesmo fim foi iniciada em novembro de 1956. Quando se consegue impedir a regeneração vascular hipotálamo-hipofisária os resultados gerais da miscotomia são pouco diferentes daqueles obtidos com a hipofisectomia. Empregamos a miscotomia sempre que, por condições locais ou gerais, a remoção total da hipófise parece constituir grande risco cirúrgico. Temos publicado estudos anatomo-fisiológicos desde 1958 mostrando: (a) as variações da necrose do lobo anterior da hipófise que não são totais nem definitivas (regeneração pituitária) e a importância das artérias trabeculares a este respeito; b) a grande capacidade de regeneração vascular a partir do hipctálamo e dirigindo-se para a parte restante do lobo anterior da hipófise, o que constitui um novo sistema anatomo-funcional portal; c) após isolamento permanente da pituitária ocorr...
Alzheimer Disease & Associated Disorders, 1988
Acta Neuropathologica, 1978
A 24-year-old woman was found comatose after 2 days of cephalalgia and vomiting. An immediate dia... more A 24-year-old woman was found comatose after 2 days of cephalalgia and vomiting. An immediate diagnosis of carbon monoxyde poisoning was disclaimed when blood carbon monoxyde was found to be 1.75 ml/100. A diagnosis of acute intracranial hypertension led to trephination with ventricular punction and brain biopsy on the third day. The patient died on the eleventh day. Ultrastructural study
Revue Neurologique, 2004
Introduction. Les démences fronto-temporales (DFT) forment un groupe hétérogène. Matériel et méth... more Introduction. Les démences fronto-temporales (DFT) forment un groupe hétérogène. Matériel et méthode. Nous avons étudié une famille dont la mère et quatre enfants étaient atteints de DFT d'expression clinique typique, avec début précoce, avant 40 ans, par des troubles de la personnalité, et évolution prolongée, environ 30 ans, avec longue conservation de l'orientation spatiale, sans signe d'atteinte du motoneurone ni signes extrapyramidaux. Résultats. L'étude neuropathologique d'un cas montra une atrophie massive prédominant au niveau des lobes frontaux. Dans les zones atrophiques, il existait une perte neuronale et un aspect spongieux des couches superficielles. Il n'y avait pas d'inclusion argentophile « de Pick », mais des inclusions marquées par l'anti-ubiquitine, mais non par l'anti-Tau, dans le fascia dentata. Dans le cytoplasme de certains neurones, dans les couches profondes du cortex mais surtout dans le tronc cérébral (réticulée magnocellulaire, noyaux du pont, noyaux moteurs, particulièrement noyau masticateur), de grandes inclusions argentophiles ovoïdes ou réniformes, peu denses, marquées seulement par l'anti-ubiquitine étaient observées. L'étude génétique mettait en évidence un Lod score positif non significatif avec des marqueurs flanquant le gène MAP , en l'absence de mutation décelable de ce gène. L'étude biochimique de la protéine Tau ne montrait pas d'anomalie qualitative. Conclusion. L'affection transmise dans la famille que nous avons étudiée paraît distincte aussi bien des DFT associées à une sclérose latérale amyotrophique (SLA) que des « taupathies ».
Neurology, 2010
Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of s... more Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide. Methods: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 Ϯ 4.8 years) by clinical, neuropsychological, and molecular methodologies. Results: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction. Conclusions: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature. Neurology ® 2010;74:798-806 GLOSSARY AD ϭ Alzheimer disease; EOFAD ϭ early-onset familial Alzheimer disease; FAD ϭ familial Alzheimer disease; HE ϭ hematoxylin-eosin. Alzheimer disease (AD) is a common degenerative disorder of unknown etiology, believed to involve a combination of genetic and environmental factors. About 47% of families with early-onset familial AD (EOFAD) have been attributed to PSEN1 mutations (http://molgen-www.ua.ac.be/ADmutations). Since the early 1970s, we have been studying 2 large Calabrian EOFAD kindreds: the N family 1 and the TO family, 2 both instrumental for the cloning of PSEN1 gene. 3 A shared extended haplotype containing the PSEN1 gene and the Met146Leu (ATG/CTG) mutation was shown to be identical by descent, 3 thus confirming a posteriori the common origin of the families. 4 Both Calabrian kindreds encompass branches inde
Neuroscience Letters, 1991
We examined the ultrastructural localization of amyloid beta-protein in 8 Alzheimer neocortical b... more We examined the ultrastructural localization of amyloid beta-protein in 8 Alzheimer neocortical biopsies. Intense immunoreactivity was located extracellularly on amyloid fibrils and amorphous material. Amorphous labelled material was also found in cell processes. No ultrastructural cell marker, such as glial fibrils, glycogen, tubules, paired helical filaments (PFHs) or synaptic vesicles could be seen in these processes that could allow their identification as glial processes, neurites or presynaptic terminals, respectively; occasional membrane stacks were observed. These findings suggest that preamyloid deposits are related to cell processes and, by elimination, that postsynaptic terminals may be involved in abnormal metabolism of the amyloid fibril precursors.
Brain, 1999
In five generations of the French M-E kindred, 11 members are now known to be or have been affect... more In five generations of the French M-E kindred, 11 members are now known to be or have been affected by a form of spongiform encephalopathy previously recorded as Gerstmann-Sträussler-Scheinker disease. Mean age at onset was 28 years (range 21-34 years). In six instances, these patients were hospitalized in psychiatric institutions with various diagnoses, the most frequent being mania or mania-like symptoms. Dementia occurred progressively after a lengthy course. Histological studies showed atrophy of the cerebellar molecular layer, which contained kuru and multicentric plaques labelled with anti-prion protein
Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1980
Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1971
Comptes rendus des séances de la Société de biologie et de ses filiales, 1964
Les Cahiers de médecine, Jan 30, 1970
Annales de médecine interne, 1977
A 10 1/2 years old boy fell brutally ill with a fit followed by confusion, and then by deep coma,... more A 10 1/2 years old boy fell brutally ill with a fit followed by confusion, and then by deep coma, with 40 degrees C fever and morbilliform rash. Consciousnesse came back within ten days, with transient Parkinson-like tremor. Myoclonus persisted for about six months. Complete recovery was followed up for six years. A diagnosis of encephalitis was considered on early EEG evidence (stereotyped repetitive sharp wave bursts) and was confirmed by isolation of ECHO 5 virus from brain specimen, and ultrastructural observation of characteristic cytopathic effect (disappearance of organelles, proliferation of smooth membranes) and of probable viral particules in astrocytes, without any inflammatory process.
Neuroscience Letters, 1992
Journal of Neurology, 2002
Frontotemporal dementia (FTD) displays significant neuropathological and genetic heterogeneity am... more Frontotemporal dementia (FTD) displays significant neuropathological and genetic heterogeneity among and within affected families. An early diagnosis is often difficult because cognitive symptoms are manifest only at a late stage of the disease. We have been studying a large pedigree segregating frontotemporal dementia (FTD) to which belong 34 identified affected persons, 11 of whom were personally examined. The kindred has been genealogically reconstructed; all FTD patients have been linked to the same ancestors who lived in the early 18(th) century (11 generations before the present one). Autosomal dominant transmission was evident. Clinical features were uniform within the kindred and met the Lund-Manchester criteria. Personality changes with absence of insight, lack of empathy and of social awareness manifested up to 5 years before medical advice was sought. Loss of fluency was the earliest neuropsychological sign, in the absence of memory, orientation and praxis deficits, which evolved late, together with hyperorality. Akinesia was observed early, rigidity appeared late, tremor was absent. Two patients showed myoclonus late in their evolution. No ALS signs were observed in this kindred. Mutations of the MAPt gene, coding for the Tau protein, were not detected in affected family members. Linkage studies excluded chromosomes 3 and 9 and gave indeterminate results that were model dependent for chromosome 17.
Journal of Geriatric Psychiatry and Neurology, 1994
We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's dis... more We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of t...
Experimental Neurology, 1998
European Journal of Human Genetics, 2003
Manic depressive illness (MDI) segregates within a founder population originating from S, a mount... more Manic depressive illness (MDI) segregates within a founder population originating from S, a mountain village in Southern Italy. Identity by descent of affected persons cannot be established by direct genealogical methods. A 56 000 persons family reconstruction data base encompasses the whole population of S in the 17th and 18th centuries, and part of the population of S and neighbouring villages in the 19th and 20th centuries. We selected 10 MDI probands who were members of the S population and not evident close relatives of each other. A total of 10 other MDI probands not evidently related to the S population formed a first control group. A second control group was formed with 10 not closely related persons originating within the S population. We determined the founders common ancestors to all the probands of one group but not ancestors to the probands of other groups, and computed the genetic contribution of each founder to each proband. The distance between probands in the S MDI group was calculated with respect to all the founders. In all, 17 founders present in the ascendancy of all individuals of the S MDI group are not present in the ascendancy of the control groups: MDI patients are derived from a subpopulation within S. Two S MDI probands are far from one another in respect of the 'nonspecific' founders, but are very close in respect of the specific founders: a putative MDI trait originated from specific founders of the MDI subpopulation, and hence is identical by descent in the S population.
Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 1997
Arquivos de Neuro-Psiquiatria, 1967
Nossa primeira hipofisectomia para tratamento de carcinoma metastático do seio foi feita em novem... more Nossa primeira hipofisectomia para tratamento de carcinoma metastático do seio foi feita em novembro de 1951 e a secção da haste pituitária (miscotomia) para o mesmo fim foi iniciada em novembro de 1956. Quando se consegue impedir a regeneração vascular hipotálamo-hipofisária os resultados gerais da miscotomia são pouco diferentes daqueles obtidos com a hipofisectomia. Empregamos a miscotomia sempre que, por condições locais ou gerais, a remoção total da hipófise parece constituir grande risco cirúrgico. Temos publicado estudos anatomo-fisiológicos desde 1958 mostrando: (a) as variações da necrose do lobo anterior da hipófise que não são totais nem definitivas (regeneração pituitária) e a importância das artérias trabeculares a este respeito; b) a grande capacidade de regeneração vascular a partir do hipctálamo e dirigindo-se para a parte restante do lobo anterior da hipófise, o que constitui um novo sistema anatomo-funcional portal; c) após isolamento permanente da pituitária ocorr...
Alzheimer Disease & Associated Disorders, 1988
Acta Neuropathologica, 1978
A 24-year-old woman was found comatose after 2 days of cephalalgia and vomiting. An immediate dia... more A 24-year-old woman was found comatose after 2 days of cephalalgia and vomiting. An immediate diagnosis of carbon monoxyde poisoning was disclaimed when blood carbon monoxyde was found to be 1.75 ml/100. A diagnosis of acute intracranial hypertension led to trephination with ventricular punction and brain biopsy on the third day. The patient died on the eleventh day. Ultrastructural study
Revue Neurologique, 2004
Introduction. Les démences fronto-temporales (DFT) forment un groupe hétérogène. Matériel et méth... more Introduction. Les démences fronto-temporales (DFT) forment un groupe hétérogène. Matériel et méthode. Nous avons étudié une famille dont la mère et quatre enfants étaient atteints de DFT d'expression clinique typique, avec début précoce, avant 40 ans, par des troubles de la personnalité, et évolution prolongée, environ 30 ans, avec longue conservation de l'orientation spatiale, sans signe d'atteinte du motoneurone ni signes extrapyramidaux. Résultats. L'étude neuropathologique d'un cas montra une atrophie massive prédominant au niveau des lobes frontaux. Dans les zones atrophiques, il existait une perte neuronale et un aspect spongieux des couches superficielles. Il n'y avait pas d'inclusion argentophile « de Pick », mais des inclusions marquées par l'anti-ubiquitine, mais non par l'anti-Tau, dans le fascia dentata. Dans le cytoplasme de certains neurones, dans les couches profondes du cortex mais surtout dans le tronc cérébral (réticulée magnocellulaire, noyaux du pont, noyaux moteurs, particulièrement noyau masticateur), de grandes inclusions argentophiles ovoïdes ou réniformes, peu denses, marquées seulement par l'anti-ubiquitine étaient observées. L'étude génétique mettait en évidence un Lod score positif non significatif avec des marqueurs flanquant le gène MAP , en l'absence de mutation décelable de ce gène. L'étude biochimique de la protéine Tau ne montrait pas d'anomalie qualitative. Conclusion. L'affection transmise dans la famille que nous avons étudiée paraît distincte aussi bien des DFT associées à une sclérose latérale amyotrophique (SLA) que des « taupathies ».
Neurology, 2010
Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of s... more Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide. Methods: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 Ϯ 4.8 years) by clinical, neuropsychological, and molecular methodologies. Results: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction. Conclusions: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature. Neurology ® 2010;74:798-806 GLOSSARY AD ϭ Alzheimer disease; EOFAD ϭ early-onset familial Alzheimer disease; FAD ϭ familial Alzheimer disease; HE ϭ hematoxylin-eosin. Alzheimer disease (AD) is a common degenerative disorder of unknown etiology, believed to involve a combination of genetic and environmental factors. About 47% of families with early-onset familial AD (EOFAD) have been attributed to PSEN1 mutations (http://molgen-www.ua.ac.be/ADmutations). Since the early 1970s, we have been studying 2 large Calabrian EOFAD kindreds: the N family 1 and the TO family, 2 both instrumental for the cloning of PSEN1 gene. 3 A shared extended haplotype containing the PSEN1 gene and the Met146Leu (ATG/CTG) mutation was shown to be identical by descent, 3 thus confirming a posteriori the common origin of the families. 4 Both Calabrian kindreds encompass branches inde
Neuroscience Letters, 1991
We examined the ultrastructural localization of amyloid beta-protein in 8 Alzheimer neocortical b... more We examined the ultrastructural localization of amyloid beta-protein in 8 Alzheimer neocortical biopsies. Intense immunoreactivity was located extracellularly on amyloid fibrils and amorphous material. Amorphous labelled material was also found in cell processes. No ultrastructural cell marker, such as glial fibrils, glycogen, tubules, paired helical filaments (PFHs) or synaptic vesicles could be seen in these processes that could allow their identification as glial processes, neurites or presynaptic terminals, respectively; occasional membrane stacks were observed. These findings suggest that preamyloid deposits are related to cell processes and, by elimination, that postsynaptic terminals may be involved in abnormal metabolism of the amyloid fibril precursors.
Brain, 1999
In five generations of the French M-E kindred, 11 members are now known to be or have been affect... more In five generations of the French M-E kindred, 11 members are now known to be or have been affected by a form of spongiform encephalopathy previously recorded as Gerstmann-Sträussler-Scheinker disease. Mean age at onset was 28 years (range 21-34 years). In six instances, these patients were hospitalized in psychiatric institutions with various diagnoses, the most frequent being mania or mania-like symptoms. Dementia occurred progressively after a lengthy course. Histological studies showed atrophy of the cerebellar molecular layer, which contained kuru and multicentric plaques labelled with anti-prion protein