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D Hannequin

Publications and source records attributed to D Hannequin.

At least 19 recordsLinked to original sources
PubMed2006

Valosin-containing protein gene mutations: clinical and neuropathologic features.

BACKGROUND: Hereditary inclusion body myopathy (IBMPFD) with Paget disease of bone (PDB) and frontotemporal dementia (FTD) is a rare multisystem disorder with autosomal dominant inheritance. Recently, missense mutations in the gene encoding valosin-containing protein (VCP) have been found in individuals with IBMPFD. VCP/P97, which exerts a variety of cellular functions, plays a key role in the ubiquitin-proteasome dependent degradation of cytosolic proteins and in the retrotranslocation of misfolded proteins from the endoplasmic reticulum into the cytoplasm. METHODS: The authors describe the clinical features of two kindreds in which VCP R93C and R155C missense mutations segregate and perform a histopathologic examination of brain, muscle, bone, and liver of three subjects harboring the R155C mutation. RESULTS: Frontotemporal dementia was present in 100% of affected subjects in Family F1 and 70% in Family F2, as compared with an average of 30% in previously described IBMPFD families. In contrast, PDB was a more inconstant clinical feature. Biochemical and histopathologic data are consistent with the hypothesis that VCP R155C mutation disrupts normal VCP function, leading to diffuse accumulation of ubiquitinated proteins within the cells. CONCLUSIONS: VCP mutations are present in two families in which FTD is the most prominent symptom. The histopathologic study performed in patients harboring the R155C mutation supports the hypothesis that this mutation disrupts normal VCP function, leading to diffuse accumulation of ubiquitinated proteins within the cells. IBMPFD belongs to a class of genetic diseases associated with an alteration of the ubiquitin-proteasome system.

Adenosine Triphosphatases↗
PubMed2006

[Sporadic cerebral amyloidotic angiopathy].

INTRODUCTION: Sporadic cerebral amyloid angiopathy (CAA) is a microangiopathy identified by neuropathological examination in more than 30 percent of patients over 85 years of age. STATE OF ART: Boston criteria for diagnosis of CAA--related hemorrhage are as follows: "definite CAA", "Probable CAA with supporting pathology", "Probable CAA" and "Possible CAA". Clinical manifestations of CAA are either lobar, cortical, corticosubcortical or cerebellar hemorrhages associated with progressive dementia. Dementia, corresponding either to Alzheimer disease, vascular or mixed dementia, precedes hemorrhages in 25 to 40 percent of cases. Brain MRI can demonstrate microbleeding. PERSPECTIVES: This review compares data regarding CAA prevalence, intracranial hemorrhages, and their risk factors in old patients. Diagnosis and preventive strategies are discussed. It would be useful to identify those affected by CAA among elderly demented patients with atrial fibrillation requiring anticoagulation therapy. CONCLUSIONS: CAA is suspected in the presence of recurrent lobar or cerebellar hemorrhages, and moreover if associated with pre-existing dementia. In elderly demented patients, MRI criteria to detect CAA should be considered in order to prevent hemorrhage risk, particularly after anticoagulation therapy.

Animals↗
PubMed2005

Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes.

BACKGROUND: Myoclonus dystonia syndrome (MDS) is an autosomal dominant movement disorder caused by mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q21. METHODS: We have screened for SGCE mutations in index cases from 76 French patients with myoclonic syndromes, including myoclonus dystonia (M-D), essential myoclonus (E-M), primary myoclonic dystonia, generalised dystonia, dystonia with tremor, and benign hereditary chorea. All coding exons of the SGCE gene were analysed. The DYT1 mutation was also tested. RESULTS: Sixteen index cases had SGCE mutations while one case with primary myoclonic dystonia carried the DYT1 mutation. Thirteen different mutations were found: three nonsense mutations, three missense mutations, three splice site mutations, three deletions, and one insertion. Eleven of the SGCE index cases had M-D and five E-M. No SGCE mutations were detected in patients with other phenotypes. The total number of mutation carriers in the families was 38, six of whom were asymptomatic. Penetrance was complete in paternal transmissions and null in maternal transmissions. MDS patients with SGCE mutation had a significantly earlier onset than the non-carriers. None of the patients had severe psychiatric disorders. CONCLUSION: This large cohort of index patients shows that SGCE mutations are primarily found in patients with M-D and to a lesser extent E-M, but are present in only 30% of these patients combined (M-D and E-M).

Adolescent↗
PubMed2005

Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update.

BACKGROUND: Autosomal dominant early onset Alzheimer's disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified. OBJECTIVE: To further clarify the respective contribution of these genes to ADEOAD. METHODS: 31 novel families were investigated. They were ascertained using stringent criteria (the occurrence of probable or definite cases of Alzheimer's disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer's disease. The entire coding regions of PSEN1 and PSEN2 genes and exons 16 and 17 of APP gene were sequenced from genomic DNA RESULTS: PSEN1 mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and APP mutations were found in five families. In this sample, the mean ages of disease onset in PSEN1 and APP mutation carriers were 41.7 and 51.2 years, respectively. CONCLUSIONS: Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to PSEN1 mutations and 16% to APP mutations, while 18% remained unexplained.

Adult↗
PubMed2005

Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family.

We report a familial disorder occurring in three patients that presented as frontotemporal dementia (FTD). A neuropathological study was performed in a 58-year-old patient, who developed FTD 2 years prior to the onset of motor neuron disease (MND), and died at age 62. Lesions indicative of associated MND were observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies, axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased neuronal density and laminar microvacuolation of layers II and III in the frontal and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the spinal cord and medulla, but were absent from the temporal and frontal cortex. There were also widespread deposits of various neuronal and glial inclusions containing abnormally phosphorylated tau protein, the Western blotting pattern of which was characterized by two major bands of 64 and 69 kDa. There were no abnormalities of the entire coding sequences of microtubule-associated protein tau (MAPT) and copper-zinc superoxide dismutase (SOD(1)) genes. Our results suggest that FTD associated with MND can be caused by a larger spectrum of neuropathological lesions than commonly accepted.

Blotting, Western↗
PubMed2005

[Autosomal dominant limb-girdle muscular dystrophy associated with conduction defects (LGMD1B): a description of 8 new families with the LMNA gene mutations].

INTRODUCTION: Limb girdle muscular dystrophy type 1b (LGMD1B), due to LMNA gene mutations, is a relatively rare form of LGMD characterized by proximal muscle involvement associated with heart involvement comprising atrio-ventricular conduction blocks and dilated cardiomyopathy. Its clinical and genetic diagnosis is crucial for cardiac management and genetic counselling. Seven LMNA mutations have been previously reported to be responsible for LGMD1B. PATIENTS AND METHODS: We describe the neurological and cardiologic features of 14 patients belonging to 8 families in whom we identified 6 different LMNA mutations, 4 of them having never been reported. Results. Eleven patients had an LGMD1B phenotype with scapulohumeral and pelvic-femoral involvement. Thirteen patients had cardiac disease associating conduction defects (12 patients) or arrhythmias (9 patients). Seven patients needed cardiac device (pacemaker or implantable cardiac defibrillator) and two had heart transplantation. CONCLUSION: This study allowed us to specify the clinical characteristics of this entity and to outline the first phenotype/genotype relations resulting from these observations.

Adolescent↗
PubMed2005

[Anti-Ri paraneoplastic syndrome associated with ophtalmoplegia, blepharospasm and palilalia].

INTRODUCTION: Anti-Hu and anti-Yo are the most well-known anti-neuronal antibodies. The anti-Ri antibodies, which are less common, are generally found in subjects with opsoclonus-myoclonus, often associated with breast cancer. CASE REPORT: A 54-year-old woman presented anti-Ri antibodies associated with a paraneoplastic syndrome and unusual symptoms of ophthalmoplegia, blepharospasm, palilalia and ataxia. Adenocarcinoma of the breast was also found. After chemotherapy, radiotherapy, and several immunoglobulin infusions, the patient did not improve ten months after tumor surgery. CONCLUSION: Anti-Ri antibodies associated with paraneoplastic syndrome can be observed in patients who develop a rapidly progressive brainstem tumor. Breast or lung cancer and conduct to search a breast or pulmonary cancer.

Adenocarcinoma↗
PubMed2002

Angiographic cerebral vasospasm and delayed ischemic deficit on anterior part of the circle of Willis. Usefulness of transcranial Doppler.

BACKGROUND AND PURPOSE: After subarachnoid hemorrhage (SAH), cerebral vasospasm (VS) may be revealed by cerebral angiography, during follow-up clinical examination with the occurrence of delayed ischemic deficit (DID). Moreover, transcranial Doppler (TCD) could be useful in determining the level of the velocimetric threshold. The aims of the study were, on a prospectively collected series of 460 patients, to assess angiographic VS incidence, to determine possible risk factors, and to evaluate diagnostic sensitivity and specificity of TCD. PATIENTS AND METHOD: A total of 460 patients consecutively operated on for an aneurysm located on the anterior portion of the circle of Willis (mean age 47.2 +/- 14 years, sex ratio F/M=1.18) were included in the study. Preventive treatment against VS was administered in all patients. On the 10(th) day, we performed the following routine examinations: cerebral angiography, CT scan and TCD. RESULTS: Angiographic VS occurred in 38.5% of the patients, and the single risk factor was delayed admission (p=0.02, Mann-Whitney test). DID occurred in 15.6% and was complicated by cerebral infarct in 4.7%. The risk factors were admission date (p=0.001, Mann-Whitney test) and severity of arterial narrowing (significant tendency). Diagnostic sensitivity of TCD decreased from 83.6% for MCA aneurysms, to 66.6% for ICA aneurysms and 40.6% for AcoA aneurysms. Diagnosis specificity remained between 88.6% and 97.6% for the 3 locations. CONCLUSION: The unique risk factor for angiographic VS and DID was the admission date. TCD demonstrated high specificity but its sensitivity was too low for the aneurysms located far from the middle cerebral artery bifurcation.

Albumins↗
PubMed2001

Use of haplotype information to test involvement of the LRP gene in Alzheimer's disease in the French population.

The low density lipoprotein receptor-related protein gene (LRP) is a good candidate gene for Alzheimer's Disease (AD). Its protein is involved in the physiopathology of AD and has been found in senile plaques; on the other hand, LRP is located in 12q, a region in which genetic linkage to AD was reported. Two common polymorphisms, a tetranucleotide repeat in the 5' untranslated region and a single nucleotide polymorphism at position 766 in exon 3, were found to be associated with AD, but contradictory results were obtained in subsequent association studies. In the absence of clear hypotheses concerning the association of these polymorphisms with AD and their functional role, our objective was to test the association between AD and the two LRP polymorphisms in a large French case-control sample (274 Caucasian AD patients and 290 matched controls) using haplotype analysis. First, the separate study of each polymorphism showed no significant difference in genotype and allele frequencies between AD cases and controls. Second, strong linkage disequilibrium was found between alleles of the two polymorphisms in controls and in cases and the linkage disequilibrium between the 91 bp and C alleles were opposite in cases and in controls. Third, we found that the frequency of the 91-C haplotype was higher in cases than in controls, but the type I error was 0.061, slightly higher than the conventional one of 5%. The haplotype frequencies did not vary significantly as a function of age and APOE epsilon4 status. One interest in this study is the use of the haplotype analysis, which can be used to combine information from several polymorphisms, taking into account their dependence.

Adult↗
PubMed2001

Pediatric cerebral aneurysms.

OBJECT: The exceptional pediatric aneurysm can be distinguished from its adult counterpart by its location and size; however, patient outcomes remain difficult to evaluate based on the published literature. METHODS: Twenty-two children, all consecutively treated in three neurosurgery departments, were included in this study. Each patient's preoperative status was determined according to the Hunt and Hess classification. Routine computerized tomography scanning and angiography were performed in all children on the 10th postoperative day. Each patient's clinical status was evaluated 2 to 10 years postoperatively by applying the Glasgow Outcome Scale (GOS). Twenty-one children presented with a subarachnoid hemorrhage (SAH) and one child harbored an asymptomatic giant aneurysm. Thirteen patients were in good preoperative grade (Hunt and Hess Grades I to III) and eight in poor preoperative grade (Hunt and Hess Grade IV or V). The symptomatic aneurysms were located on the internal carotid artery bifurcation (36.4%); middle cerebral artery (36.4%), half of which were found on the distal portion; anterior communicating artery (18.2%); and within the vertebrobasilar system (9.1%). A giant aneurysm was observed in 14% of patients. Overall outcome was favorable (GOS Score 5) in 14 children (63.6%) and death occurred in five (22.7%). Causes of unfavorable outcome included the initial SAH in four children, a complication in procedure in three children, and edema in one child. CONCLUSIONS: Pediatric aneurysms have a specific distribution unlike that of aneurysms in the adult population. The incidence of giant aneurysms and outcomes were similar to those in the adult population. The major cause of poor outcome was the initial SAH, in particular, the high proportion of rebleeding possibly due to a delay in diagnosis.

Adolescent↗
PubMed2001

[Musical hallucinosis following infarction of the right middle cerebral artery].

A 44-year-old woman demonstrated a musical hallucinosis four months after a massive infarction in the territory of the right middle cerebral artery. This musical hallucinosis consisting of familiar tunes, was continuous and perceived by both ears. Magnetic Resonance Imaging, middle and late auditory evoked potentials suggested that right Heschl's gyrus and associative areas were imparied. Audiometry demonstrated a low right transmission deafness. The hallucinosis was persistent for seven months and stopped just after hemorrhage of the right ear. This case gives the opportunity to review the different mechanisms responsible for musical hallucinosis.

Adult↗
PubMed2001

[Dominant forms of Alzheimer's disease: from genotype to phenotype].

This review is devoted to the relationships between phenotype and genotype of the autosomal dominant forms of Alzheimer's disease caused by mutations of presenilins (PSs) and amyloid precursor protein (APP) genes. A first part examines the clinical characteristics mainly the early age of onset and argues about the diversity of age of onset between different mutations and also between patients bearing the same mutation in large families. The second part reports several arguments demonstrating that the main effect of the PSs and APP mutations is the elevation of Ab42 peptide. The pathological and behavioral effects observed in transgenic APP or PSs animals suggest that intra cellular deposits of Ab42 play a role in the pathophysiological process.

Adult↗
PubMed2001

[Therapeutic efficacy during active phases of multiple sclerosis: gait analysis and comparison with the EDSS score].

Fifteen patients experiencing a flare-up of multiple sclerosis were given 1 g methylprednosolone per day for 5 days. The EDSS score and gait analysis using spatio-temporal variables were recorded for these patients on days 0, 5 and 45. Both methods evidenced significant improvement but the significance was observed between day 0 and day 5 for the EDSS and between day 5 and 45 for gait speed and between day 0 and 45 for step rate. Gait speed was correlated with the pyramidal scale but not with the other functional scales of the EDSS. These results suggest that EDSS and spatio-temporal gait analysis are different tools for the assessment of therapeutic effect. Gait analysis can provide a precise quantitative assessment of the locomotor handicap as a function of the proposed treatment.

Adult↗
PubMed2000

Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation.

The authors report a presenilin 1 (PSEN1) mutation (L113P) in a family with six cases of dementia. The patients had personality changes and behavioral disorders, whereas spatial orientation and praxis were preserved late in the course of the illness. Neuroimaging features were consistent with the diagnosis of frontotemporal dementia. The authors conclude that PSEN1 mutations can be associated with clinical features of frontotemporal dementia.

Adult↗
PubMed2000

[Confusional state and agitation].

Delirium is a neurologic emergency representative of 10% of the hospitalized patients. It is characterized by an acute and fluctuating change of consciousness and cognition. A strict procedure is necessary to treat quickly the responsible cause among the multiple possible ones. An associated agitation need a quick specific treatment. The treatment should prevent the risk factors, notably iatrogenic, especially in the elderly patients or with previous altered cognitive functions.

Confusion↗