Biomedical subjects

M Verny

Publications and source records attributed to M Verny.

At least 19 recordsLinked to original sources

PubMed2006

[Neurological manifestations of type 1 Gaucher's disease: Is a revision of disease classification needed?].

INTRODUCTION: Gaucher's disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. The resulting accumulation of glucocerebrosides in lysosomes of macrophages leads to hepatosplenomegaly, anemia, thrombocytopenia, and various bone manifestations. Gaucher's disease is classified into 3 types based on the nature of its effects on the central nervous system. Type 1, the most common variant, is classically nonneuronopathic. However, the occurrence of Parkinsonism seems to be more frequent in type I Gaucher's disease than in the general population. Furthermore, heterozygotes for certain glucocerebrosidase gene mutations have a higher risk to develop Parkinson's disease. OBSERVATIONS: We report our experience about 9 patients with Gaucher's disease and their association with neurological manifestations. CONCLUSION: These recent data may discuss Gaucher's classification and the existence of a continuum between neurologic and non-neurologic forms of the disease.

Adult↗

PubMed2005

[Consensus statement on severe dementia].

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary group of experts, including geriatricians, neurologists, epidemiologists, psychiatrists, pharmacologists, and public health specialists developed consensus recommendations about care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians, and specialists, based on the knowledge currently available (2005). The aim of care at all stages is to mitigate the quality-of-life of patient, caregiver, and family insofar as possible, combining care and future planning until the end of life. Management, to take into account problems including nutritional status, behavior disorders, and ability (or inability) to perform activities of daily living, must be global, multidisciplinary, and coordinated and must optimize use of local medical and social resources. The group also stressed the importance of clinical research to improve knowledge of disease course and assess management strategies and recommended specific area for research.

Aged↗

PubMed2005

[Medical comorbidity in Alzheimer's disease: baseline characteristics of the REAL.FR Cohort].

PURPOSE: Alzheimer's disease (AD) evolves over about ten years with cognitive decline that can be considered as linear. Comorbidities are frequent in geriatric population. The major objective of this study is to determine whether comorbidity influences natural history of AD. MATERIALS AND METHODS: This is a prospective, multicentric French study (REAL.FR) of a cohort of ambulatory patients suffering from AD from a mild to a moderately severe stage, with a Mini-Mental State between 10 and 26, and followed with a caregiver. We evaluated the comorbidities and they were quantified using the Charlson index. RESULTS: We analysed 579 AD patients enrolled between April 2000 and June 2002. Majority of patients were women (72%). Average age and MMS average score were respectively 77.4 +/- 7.1 and 20.1 +/- 4.5. Cardiovascular diseases were the most frequent comorbid conditions (34%), before sensorial handicap (23%), and neurological diseases (18%) apart from dementia. Four AD patients groups differed according to the comorbidities figures, from none to more than three (maximum 8). Average Charlson index was 1.5 +/- 0.9. CONCLUSION: The follow-up of the four AD patients groups, differentiated by the comorbidities figures, should allow to precise the influence of comorbidities on the AD evolution. Charlson index could be used to quantify the comorbidities in the cohort's follow-up. However, this index, validated in a cohort of cancer patients, show limits for its use in geriatric population.

Aged↗

PubMed2005

[Behavioral and psychological symptoms in dementia: description and management].

Behavioral and Psychological Symptoms in Dementia (BPSD) are, beside cognitive disorders, major features of Alzheimer's disease and related disorders. Diagnosis is important to enhance our knowledge of the pathophysiology of dementia and of their functional consequences for patients and caregivers. Pharmacological and non-pharmacological management of dementia depends to a large extent on the presence of BPSD. A committee of geriatricians, neurologists and psychiatrists specialized in dementia (THEMA 2) has promoted an epidemiological, diagnostic and therapeutic update in this field. This work was based on the BPSD Consensus Conference Report edited in 2000 by the International Psychogeriatric Association. This report was updated with the most recent literature reports, and was adapted to the French environment. This paper is a synthesis of this meeting, validated and corrected by the entire Thema 2 group.

Aged↗

PubMed2005

[Consensus statement on severe dementia].

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

Aged↗

PubMed2004

[Imaging of dementia with magnetic resonance].

The diagnostic approach of dementia has clearly improved with the progress in medical imaging, notably magnetic resonance imaging. The conventional T1 and T2 sequences or morphological imaging have demonstrated their interest in the positive and differential diagnosis of dementia, together with the more precise description of normal ageing of the brain. The ANAES (French medicines agency) proposes systematic brain imaging, notably by magnetic resonance imaging (MRI) in their practical guidelines for the diagnosis of Alzheimer's disease (http://www.anaes.fr). THE INTEREST OF CERTAIN IMAGING TECHNIQUES: The therapeutic progress in treatment of dementia implies that the different affections be recognised as early as possible. With this in mind, the functional MRI is capable of describing the damage in cases when morphological imaging is not sufficiently specific. Recent studies have reported the interest of diffusion and perfusion imaging, activation MRI and proton spectroscopy. FROM A THERAPEUTIC POINT OF VIEW: The combination of morphological and functional approaches will provide a better definition of the groups at risk in order to target current treatments and those to come.

Aged↗

PubMed2003

[Recent neuropathology of parkinsonian syndromes].

The understanding of the molecular mechanisms underlying Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy has made significant progress in the recent years. Lewy body appears to be principally made of alpha-synuclein, a presynaptic protein. It also contains ubiquitin and some components of the proteasome: this suggests that alteration of protein catabolism may be involved in its formation. In favor of this hypothesis, it should be noted that Parkin, a protein that is mutated in autosomal recessive Parkinson disease, is a ubiquitin ligase. Immunohistochemistry has shown that alpha-synuclein accumulates not only in the cell body of the neurones (Lewy body) but also in their processes (Lewy neurites); it has emphasized the severity of the pathology in the nucleus basalis of Meynert, amygdala, CA2-3 sector of the hippocampus and cerebral cortex. Cortical Lewy bodies are not considered any more the marker of dementia with Lewy bodies: they are, indeed, found in true Parkinson disease cases. In progressive supranuclear palsy, 4 repeats tau accumulates in the cytoplasm of neurones and glia. At electron microscopy, the accumulation is made of straight filaments. It involves not only the neurones (where it is the main constituent of the neurofibrillary tangles) but also the glia. Astrocytic tuft is to day considered the morphological marker of progressive supranuclear palsy. Tau protein accumulates in the cell body of the oligodendrocyte as a "coiled body"; the protein is also integrated in the myelin sheath, when the cytoplasm of the oligodendrocyte wraps around the axon. This explains the numerous "threads" that are visible in cases of progressive supranuclear palsy. Striato-nigral degeneration, sporadic olivo-ponto-cerebellar atrophy and primitive orthostatic hypotension are various clinico-pathologic aspects of the same disorder: multiple system atrophy. It is also characterized by a morphological marker: the accumulation of alpha-synuclein in the cytoplasm of glial cells, particularly oligodendrocytes. The term synucleinopathy has been proposed to describe both idiopathic Parkinson disease and multiple system atrophy. The reason explaining the cellular topography of alpha-synuclein accumulation, neuronal in Parkinson disease, glial in multiple system atrophy is still unknown.

Amygdala↗

PubMed2003

[The elderly and dementia: clinical approach].

When you take care of elderly, you need to evaluate cognitive functions due to the frequency of dementia. However, before this evaluation, you must be aware of difficulties that you will encounter. You have to determine general characteristics of elderly patients and use geriatric reasoning in order to list pathologies that can interfere with cognitive functions. Thereafter, you need to precise frontiers between normal cognitive functions and dementia. When dementia is confirmed, CT scan or MRI appears very useful to exclude a cause of reversible dementia or to precise the nature of dementia. CT scan or MRI are useful during dementia to define the etiology of dementia or acute deterioration during evolution. A close collaboration between radiologist and clinician is mandatory to avoid diagnostic errors.

Age Factors↗

PubMed2002

Clinical features and assessment of severe dementia. A review.

Sound understanding of the dementia syndrome requires adequate acquaintance with its entire spectrum, from the lightest to the most advanced stages. Most studies of dementia deal with light to moderate stages of the condition, while relatively little attention has been paid to its most severe stages. This review presents a clinical description of patients with severe dementia and of the tests currently available to evaluate their cognitive, behavioural, and functional status. Available instruments such as the Hierarchic Dementia Scale or the Severe Impairment Battery now allow quantification of the cognitive and behavioural status of patients with severe dementia. Experience with severe dementia shows that, far from being in a "vegetative state", as is commonly thought, late-stage patients are in fact quite different from one another and in most cases continue to have an interaction with their environment. This ability to better define the characteristics of patients with severe dementia provides the basis for correlations between clinical data and data derived from neuroimaging, neurochemistry, or neuropathology. It also sets the stage for possible therapeutic trials involving these patients.

Alzheimer Disease↗

PubMed2001

Progression of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders.

BACKGROUND: Dysarthria and dysphagia are known to occur in parkinsonian syndromes such as Parkinson disease (PD), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Differences in the evolution of these symptoms have not been studied systematically in postmortem-confirmed cases. OBJECTIVE: To study differences in the evolution of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. PATIENTS AND METHODS: Eighty-three pathologically confirmed cases (PD, n = 17; MSA, n = 15; DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis for a multicenter clinicopathological study organized by the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Cases with enough clinicopathological documentation for the purpose of the study were selected from research and neuropathological files of 7 medical centers in 4 countries (Austria, France, England, and the United States). RESULTS: Median dysarthria latencies were short in PSP and MSA (24 months each), intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months). Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months), and long in PD (130 months). Dysarthria or dysphagia within 1 year of disease onset was a distinguishing feature for atypical parkinsonian disorders (APDs) (specificity, 100%) but failed to further distinguish among the APDs. Survival time after onset of a complaint of dysphagia was similar in PD, MSA, and PSP (15 to 24 months, P =.7) and latency to a complaint of dysphagia was highly correlated with total survival time (rho = 0.88; P<.001) in all disorders. CONCLUSIONS: Latency to onset of dysarthria and dysphagia clearly differentiated PD from the APDs, but did not help distinguish different APDs. Survival after onset of dysphagia was similarly poor among all parkinsonian disorders. Evaluation and adequate treatment of patients with PD who complain of dysphagia might prevent or delay complications such as aspiration pneumonia, which in turn may improve quality of life and increase survival time.

Aged↗

PubMed2000

Disposition in rats of N-pyridinium-propyl-cyclam, N-triethylammonium-propyl-cyclam, and N-[Triethylammonium]-3-propyl-[15]ane-N5, potential cartilage imaging agents.

Quaternary ammonium compounds are known to highly concentrate in articular cartilages after i.v. administration. This property was used to synthesize new potential radiodiagnostic agents for joint imaging. Pharmacokinetic study was performed in rats for three new compounds: N-pyridinium-propyl-cyclam (NPPC), N-triethylammonium-propyl-cyclam (NTPC), and N-[triethylammonium]-3-propyl-[15]ane-N5 (NTP 15-5). After i.v. administration, [(3)H]NPPC and [(3)H]NTPC highly and rapidly concentrated in articular cartilage, this uptake being followed by a single exponential decrease with half-lives of, respectively, 75 and 82 min. Except cartilage, only the kidney was highly labeled. After complexation of (99m)Tc by NPPC, NTPC, and NTP 15-5, only (99m)Tc-NTP 15-5 exhibited a high affinity for cartilage. On the other hand, the pharmacokinetic behavior of (99m)Tc-NTPC and (99m)Tc-NPPC was very different from those of their (3)H-labeled analogs. Concentration in cartilaginous tissues was strongly diminished, and liver and bone were highly labeled. For all labeled species, the major route of excretion was urine, and HPLC analysis showed that [(3)H]NTPC and [(3)H]NPPC were excreted under their unchanged form. On the other hand, no (99m)Tc-NTPC and (99m)Tc-NPPC were found in the urine, the radioactivity being mainly due to free technetium, contrary to (99m)Tc-NTP 15-5, which was excreted in the urine under the complexed form. These data can explain the striking differences observed between the three (99m)Tc-labeled molecules, the lack of concentration of (99m)Tc-NTPC, and (99m)Tc-NPPC in cartilages in comparison with their (3)H-labeled analogs due to an instability in vivo of these technetiated complexes.

Animals↗

PubMed1999

New quaternary ammonium oxicam derivatives targeted toward cartilage: synthesis, pharmacokinetic studies, and antiinflammatory potency.

Analogues of nonsteroidal antiinflammatory drugs (NSAIDs) oxicams, in which the active group was linked to a quaternary ammonium function [(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)2-methylpyridinium iodide or piroxicam-N(+) and [3-(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)propyl]trimethylammonium iodide or propoxicam-N(+)] were synthesized. Compounds were labeled with tritium for piroxicam-N(+) and carbon-14 for propoxicam-N(+). Pharmacokinetic studies conducted on rats showed that these molecules were able to highly concentrate in joint cartilages but their bioavailability by the oral way was low. Only propoxicam-N(+) exhibited a sufficient water solubility to be administered intravenously. This molecule was able to restore proteoglycans biosynthesis in cultured articular chondrocytes treated with Interleukin-1beta with an efficiency identical to that of indomethacin. These results suggest that the functionalization of oxicam derivatives by a quaternary ammonium group greatly increases their affinity toward articular cartilage without eliminating their pharmacological activity. New drugs synthesized according to this scheme could be useful to obtain a significant decrease of the efficient administered dose and consequently an attenuation of adverse effects such as digestive toxicity.

Animals↗

PubMed1999

Progression of falls in postmortem-confirmed parkinsonian disorders.

Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value.

Accidental Falls↗

PubMed1999

Clinical features differentiating patients with postmortem confirmed progressive supranuclear palsy and corticobasal degeneration.

Progressive supranuclear palsy (PSP) and cortocobasal degeneration (CBD) are often clinically confused with each other because they share a rapid disease progression, parkinsonism that responds poorly or transiently to levodopa therapy, and associated signs (e.g., ocular abnormalities, pyramidal signs and cognitive involvement). To improve the accuracy in diagnosing these disorders, this study examined the clinical features of 51 patients pathologically diagnosed with PSP and CBD. Logistic regression analysis identified two sets of predictors (models) for CBD patients, one consisting of asymmetric parkinsonism, cognitive disturbances at onset and instability and falls at first clinic visit, and the other one of asymmetric parkinsonism, cognitive disturbances at symptom onset and speech disturbances. While PSP patients often had severe postural instability at onset, symmetric parkinsonism, vertical supranuclear gaze palsy, speech and frontal lobe-type features, CBD patients presented with lateralized motor (e.g., parkinsonism, dystonia or myoclonus) and cognitive signs (e.g., ideomotor apraxia, aphasia or alien limb). On the other hand, CBD patients presenting with an alternate phenotype characterized by early severe frontal dementia and bilateral parkinsonism were generally misdiagnosed. PSP patients without vertical supranuclear gaze palsy were misdiagnosed. Recognizing the features which differentiate these disorders and the less obvious disease presentations as well as developing an increased index of suspicion will improve the diagnostic accuracy of these disorders.

Aged↗

PubMed1999

Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study.

OBJECTIVE: Although both orthostatic hypotension and urinary incontinence have been reported in a number of parkinsonian syndromes, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of these features have not been studied systematically in pathologically confirmed cases. METHODS: 77 cases with pathologically confirmed parkinsonian syndromes (PD, n=11; MSA, n=15; DLB, n=14; CBD, n=13; PSP, n=24), collected up to 1994, formed the basis for a multicentre clinicopathological study organised by the NINDS to improve the differential diagnosis of parkinsonian disorders. The present study determined the time course-that is, latency to onset and duration from onset to death, of symptomatic orthostatic hypotension, and urinary incontinence in the NINDS series. Furthermore, the diagnostic validity of a predefined latency to onset within 1 year of disease onset of symptomatic orthostatic hypotension or urinary incontinence was analysed. RESULTS: Significant group differences for latency, but not duration, of symptomatic orthostatic hypotension and urinary incontinence were found. Latencies to onset of either feature were short in patients with MSA, intermediate in patients with DLB, CBD, and PSP, and long in those with PD. Symptomatic orthostatic hypotension occurring within the first year after disease onset predicted MSA in 75% of cases; early urinary incontinence was less predictive for MSA (56%). CONCLUSION: Latency to onset, but not duration, of symptomatic orthostatic hypotension or urinary incontinence differentiates PD from other parkinsonian syndromes, particularly MSA.

Age of Onset↗

PubMed1999

[Cortical lesions in progressive supranuclear palsy (Steele-Richardson-Olszewski disease)].

Histopathological changes seen in progressive supranuclear palsy (Steele-Richardson-Olszewski disease) have been thought to be located in subcortical nuclei. However, abundant neurofibrillary tangles have been found recently in several neocortical areas. Their morphology and ultrastructure, regional and laminar distributions, as well as antigenic and biochemical properties make them clearly different from the neurofibrillary tangles observed in Alzheimer's disease and aging. Tau positive fibrillary accumulation in the nevroglia has also been seen in the cortex. The topographical distribution of the lesions is rather stereotyped, but some uncommon distributions (such as pallido-luysonigral) have been identified. Factorial analysis has shown that cortical and subcortical lesions are independent; pedonculopontine nucleus could play a role in the cortical diffusion of the lesions.

Cerebral Cortex↗

PubMed1998

Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study.

BACKGROUND: Whether Parkinson disease (PD) and dementia with Lewy bodies (DLB) represent 2 distinct nosologic entities or are diverse phenotypes of Lewy body disease is subject to debate. OBJECTIVES: To determine the accuracy of the diagnoses of Lewy body disease, PD, and DLB by validating the clinical diagnoses of 6 neurologists with the neuropathologic findings and to identify early predictors of the diagnoses. METHODS: Six raters who were unaware of the neuropathologic diagnoses analyzed 105 clinical vignettes corresponding to 29 cases of Lewy body disease (post hoc analysis of 15 patients with PD and 14 with DLB) and 76 patients without PD or DLB whose cases were confirmed through autopsy findings. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value (PPV) were chosen as validity measures and the K statistic as a reliability measure. RESULTS: Interrater reliability for the diagnoses of Lewy body disease and PD was moderate for the first visit and substantial for the last, whereas agreement for diagnosis of DLB was fair for the first visit and slight for the last. Median sensitivity for diagnosis of Lewy body disease was 56.9% for the first visit and 67.2% for the last; median PPV was 60.0% and 77.4%, respectively. Median sensitivity for the diagnosis of PD was 73.3% for the first visit and 80.0% for the last; median PPV was 45.9% and 64.1%, respectively. Median sensitivity for the diagnosis of DLB was 17.8% for the first visit and 28.6% for the last; median PPV was 75.0% for the first visit and 55.8% for the last. The raters' results were similar to those of the primary neurologists. Several features differentiated PD from DLB, predicted each disorder, and could be used as clinical pointers. CONCLUSIONS: The low PPV with relatively high sensitivity for the diagnosis of PD suggests overdiagnosis. Conversely, the extremely low sensitivity for the diagnosis of DLB suggests underdiagnosis. Although the case mix included in the study may not reflect the frequency of these disorders in practice, limiting the clinical applicability of the validity measures, the raters' results were similar to those of the primary neurologists who were not exposed to such limitations. Overall, our study confirms features suggested to predict these disorders, except for the early presence of postural imbalance, which is not indicative of either disorder.

Adult↗

PubMed1998

Pharmacological therapy in progressive supranuclear palsy.

BACKGROUND: To our knowledge, previous reports on drug treatment in progressive supranuclear palsy have not evaluated autopsy-confirmed cases. OBJECTIVE: To evaluate pharmacological treatment responses from detailed clinical records in patients with autopsy-confirmed progressive supranuclear palsy. SUBJECTS AND METHODS: We reviewed medical records for clinical presentation and pharmacological response in 12 patients with autopsy-confirmed progressive supranuclear palsy diagnosed using the National Institute of Neurological Disorders and Stroke pathologic criteria. For each drug class, exposure, global positive response, and specific positive response (parkinsonism, other movement disorders, or gaze dysfunction) were recorded. RESULTS: Drug classes examined were dopaminergics (all patients), tricyclics (3 patients), methysergide maleate (3 patients), 5-hydroxytryptophan (2 patients), and anticholinergics and selective serotonin inhibitors (1 patient). Positive clinical response was detected in 7 of the patients receiving dopaminergic drugs and in 1 patient each receiving tricyclics, methysergide, and 5-hydroxytryptophan, respectively. None of the patients responded markedly however, and there was no persistent beneficial effect. Use of dopaminergic drugs most frequently improved parkinsonian features, but disabling adverse effects included orthostatic hypotension (6 patients), hallucinations and delusions (3 patients), gastrointestinal complaints (3 patients), and dizziness (1 patient). Only 1 patient developed dyskinesia. CONCLUSION: Use of antiparkinsonian medications and other neurotransmitter replacement therapies was largely ineffective and caused frequent adverse effects in this series of patients with autopsy-confirmed with progressive supranuclear palsy.

5-Hydroxytryptophan↗