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1.
Anaerobe ; 82: 102763, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37499933

RESUMO

OBJECTIVE: Although the genus Prevotella is part of the general human microbiota, species of this anaerobic gram-negative bacterium have been described as causes of persisting nonpuerperal breast abscesses. Collecting punctate samples and testing these samples for anaerobic bacteria is not part of the common diagnostic workflow in atypical breast abscesses. The causative anaerobic micro-organism can remain unclear and patients can be treated with multiple inadequate antibiotics and/or extensive surgical procedures. The aim of this cohort study of Prevotella induced breast abscesses is to gain more insights into the diagnostic procedures and treatment. METHODS: Medical charts of patients with a Prevotella induced breast abscess between 2015 and 2021, were retrospectively reviewed on patient characteristics, diagnostic procedures, treatment and outcome. RESULTS: Twenty-one patients were included. Six subspecies of Prevotella were determined by culturing. High susceptibility was observed for amoxicillin/clavulanic acid (100%, n = 12). Nine patients (43%) were treated with antibiotics, eight patients (38%) with antibiotics and incision and drainage, and four patients (19%) with only incision and drainage. Recurrence was observed in nine patients (43%), of whom five patients were treated with antibiotics and three patients had surgery. The mean duration of antibiotic administration in patients with recurrence was significantly shorter compared to those without recurrence (5.6 days vs. 19.5 days, p = 0.039). CONCLUSION: Specific anaerobic culturing should be common practice in atypical breast abscesses to confirm Prevotella species. The high recurrence rate emphasizes the need of further research for optimal treatment. Prolonged duration of antibiotics could be considered and amoxicillin/clavulanic acid seems to be the first choice.


Assuntos
Empiema Pleural , Mastite , Feminino , Humanos , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Estudos Retrospectivos , Prevotella , Estudos de Coortes , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Empiema Pleural/tratamento farmacológico , Drenagem/métodos , Amoxicilina/farmacologia , Ácido Clavulânico
2.
Eur Radiol ; 27(4): 1352-1360, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27436017

RESUMO

OBJECTIVES: Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. METHODS: Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. RESULTS: PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. CONCLUSIONS: Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. KEY POINTS: • PhFTD shows brain abnormalities that are similar to bvFTD. • PhFTD shows increased functional connectivity in the parietal default mode network. • PhFTD shows microstructural white matter abnormalities in the frontal lobe. • We hypothesise phFTD and bvFTD may belong to the same disease spectrum.


Assuntos
Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/patologia , Imageamento por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Idoso , Imagem de Tensor de Difusão/métodos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos
3.
Breast Dis ; 42(1): 325-330, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37899052

RESUMO

BACKGROUND: Fibroadenomas are the most common benign breast lesions in women. They present as a unilateral mass and can rapidly enlarge in size through hormonal changes. Fibroadenomas could be classified as small or giant, and as simple or complex. They are classified as 'giant' when the size exceeds 5 cm and/or weight 500 gram; and as 'complex' if one of the following characteristics is present: cysts with a size >3 mm, epithelial calcifications, sclerosing adenosis and papillary apocrine metaplasia. Giant fibroadenomas can cause compression of surrounding breast tissue or breast asymmetry, requiring surgical excision in order to preserve a normal breast shape. CASE: A 26-year-old pregnant woman was referred with a palpable mass of her right breast. The mass rapidly increased in size to a diameter of 13 cm during the second trimester of her pregnancy. A tru-cut biopsy confirmed a fibroadenoma. The rapid growth and compression of normal breast tissues indicated a lumpectomy during her pregnancy. The mass was easily excised without any consequences for the pregnancy. Pathological examination showed a complex giant fibroadenoma. CONCLUSION: A unique case of a pregnant woman with rapid progression of a fibroadenoma that met the criteria of a complex and giant fibroadenoma, was presented. This case emphasizes the importance of timely surgical intervention, even during pregnancy, to prevent permanent breast tissue damage.


Assuntos
Neoplasias da Mama , Fibroadenoma , Doença da Mama Fibrocística , Gravidez , Feminino , Humanos , Adulto , Neoplasias da Mama/patologia , Gestantes , Fibroadenoma/diagnóstico , Fibroadenoma/cirurgia , Fibroadenoma/patologia , Mama/patologia , Doença da Mama Fibrocística/diagnóstico , Doença da Mama Fibrocística/cirurgia , Doença da Mama Fibrocística/patologia
4.
Clin Genet ; 79(3): 264-72, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20528887

RESUMO

The creatine transporter defect is an X-linked cause of mental retardation. We investigated the clinical features and pattern of X-inactivation in a Dutch cohort of eight female heterozygotes. We show that symptoms of the creatine transporter defect (mental retardation, learning difficulties, and constipation) can be present in female heterozygotes. We further show that the diagnosis in females is not straightforward: (i) The creatine/creatinine ratio in urine was elevated only in three of eight females. (ii) Although as a group the females had a significantly decreased cerebral creatine concentration, individual females had creatine concentrations overlapping with normal controls. (iii) Skewed X-inactivation was found in the cultured fibroblasts, in favour of either the mutated or the wild-type allele, leading to either deficient or normal results in the creatine uptake studies in fibroblasts. Thus, screening by these tests is unreliable for the diagnosis. In addition, we found no consistent skewing of the X-inactivation in peripheral tissues indicating that there is no selection against the creatine transporter defect. We conclude that testing for creatine transporter defect should be considered in females with (mild) mental retardation. Screening by DNA analysis of the SLC6A8 gene is recommended.


Assuntos
Heterozigoto , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteínas do Tecido Nervoso/genética , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética , Inativação do Cromossomo X/genética , Adulto , Idoso , Células Cultivadas , Creatina/metabolismo , Feminino , Humanos , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Pessoa de Meia-Idade , Mutação , Países Baixos , Testes Neuropsicológicos
5.
J Neurol Neurosurg Psychiatry ; 82(1): 41-4, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20667857

RESUMO

BACKGROUND: Asymptomatic cerebral lesions on MRI such as white matter lesions (WML), lacunes and microbleeds are commonly seen in older people. We examined the role of a series of candidate genes involved in blood pressure regulation and amyloid metabolism. MATERIALS AND METHODS: The study was embedded in a family-based cohort sampled from a Dutch genetically isolated population. We selected individuals between 55 and 75 years of age with hypertension (N=129). Volumes of WML and presence of lacunes and microbleeds were assessed with MRI. We studied three genes involved in blood pressure regulation (angiotensin, angiotensin II type 1 receptor, α-adducin) and two genes involved in the amyloid pathway (apolipoprotein E (APOE) and sortilin-related receptor gene (SORL1)). RESULTS: All participants had WML (median volume, 3.1 ml; interquartile range, 1.5-6.5 ml); lacunar infarcts were present in 15.5% and microbleeds in 23.3%. Homozygosity for the APOE ε4 allele was associated with lacunes (OR, 4.8; 95% CI, 1.2 to 19.3). Individuals carrying two copies of the variant allele of four single nucleotide polymorphism (SNPs) located at the 3'-end of SORL1 (rs1699102, rs3824968, rs2282649, rs1010159) had significantly more often microbleeds (highest OR, 6.87; 95% CI, 1.78 to 26.44). CONCLUSION: The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.


Assuntos
Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/genética , Hipertensão/epidemiologia , Hipertensão/genética , Idoso , Amiloide/genética , Amiloide/metabolismo , Apolipoproteínas E/genética , Pressão Sanguínea/fisiologia , Proteínas de Ligação a Calmodulina/genética , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Estudos de Coortes , Feminino , Genótipo , Humanos , Hipertensão/complicações , Proteínas Relacionadas a Receptor de LDL/genética , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Angiotensina/genética
6.
Eur J Epidemiol ; 25(8): 561-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20585974

RESUMO

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)-levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women.


Assuntos
Transtornos Cognitivos/genética , Função Executiva/fisiologia , Síndrome Metabólica/genética , Adiponectina/sangue , Adiponectina/genética , Adiponectina/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Proteína C-Reativa/genética , Proteína C-Reativa/fisiologia , Transtornos Cognitivos/sangue , Transtornos Cognitivos/etiologia , Estudos de Coortes , Estudos Transversais , Família , Feminino , Humanos , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Modelos Lineares , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Países Baixos , Fatores Sexuais , Adulto Jovem
7.
J Neurol ; 255(6): 910-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18484237

RESUMO

OBJECTIVES: To investigate cognitive functioning shortly after multiple sclerosis (MS) diagnosis and to examine the relationship with disability, depression and anxiety. METHODS: Data were available for 101 recently diagnosed MS patients and 117 healthy controls. Neuropsychological and clinical assessment included Rao's Brief Repeatable Battery, Expanded Disability Status Scale (EDSS), and Hospital Anxiety and Depression scale (HADS). RESULTS: Patients had lower scores than controls on timed tasks (Paced Auditory Serial Addition Test (PASAT3, p-value adjusted for age, sex and education = 0.04; PASAT2, p = 0.001), Word List Generation Test (WLG, p = 0.04)). Scores on Symbol Digit Modalities Test (SDMT; p = 0.001), PASAT3 (p = 0.01) and PASAT2 (p < 0.001) showed significant association with EDSS. Patients with EDSS >or= 3.0 had significantly lower scores on Selective Reminding Test (SRTC, p = 0.04), SDMT (p = 0.002), PASAT3 (p = 0.002), PASAT2 (p < 0.001) and WLG (p = 0.01) than controls from the general population. Patients with clinically borderline scores of depression scored lower on SDMT (49.5 versus 57.1, p = 0.06) and PASAT3 (39.8 versus 47.1, p = 0.03). However, after adjustment for EDSS and time since disease onset, these differences were not statistically significant. CONCLUSION: Within two years after diagnosis, patients with MS had lower scores compared to healthy controls on timed tasks, suggesting cognitive slowing in patients with early MS. Cognitive impairment was associated with symptoms of depression, but this association could be explained by differences in disability.


Assuntos
Transtornos Cognitivos/epidemiologia , Transtorno Depressivo/epidemiologia , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/psicologia , Atividades Cotidianas/psicologia , Adulto , Fatores Etários , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/psicologia , Cognição/fisiologia , Transtornos Cognitivos/diagnóstico , Comorbidade , Transtorno Depressivo/diagnóstico , Avaliação da Deficiência , Pessoas com Deficiência , Feminino , Pesar , Humanos , Incidência , Masculino , Memória/fisiologia , Processos Mentais/fisiologia , Esclerose Múltipla/fisiopatologia , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Desempenho Psicomotor/fisiologia , Fatores Sexuais , Fatores de Tempo
8.
Neurology ; 44(3 Pt 1): 454-61, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8145915

RESUMO

We studied the diagnostic accuracy of single-photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) in 48 patients with probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria and in 60 controls recruited from a population-based study. With logistic regression, we identified decreased temporal regional cerebral blood flow as the best discriminating variable between patients and controls. Receiver-operator characteristic curves showed that the discriminative ability of SPECT improved with increasing dementia severity. With specificity set at 90%, sensitivity figures were 42% in mild, 56% in moderate, and 79% in severe AD. The diagnostic gain as a function of the prior probability of the disease being present was computed for those with mild AD. When the prior probability varied at around 50%, the diagnostic gain for mild AD patients was substantial (a maximum of 34%) for a positive test result but poor for a negative test result. The results suggest that the practical usefulness of SPECT as a diagnostic adjunct in patients suspected of having mild AD is confined to situations in which, on clinical grounds, there is considerable diagnostic doubt.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Compostos de Organotecnécio , Oximas , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único
9.
J Am Geriatr Soc ; 46(8): 962-7, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9706883

RESUMO

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.


Assuntos
Alelos , Doença de Alzheimer/complicações , Apolipoproteínas E/genética , Disfunção Ventricular Esquerda/complicações , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doenças Cardiovasculares/complicações , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
10.
J Neurol ; 248(11): 965-70, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11757960

RESUMO

OBJECTIVE: As metabolic and structural changes in frontotemporal-subcortical pathways have been reported in patients with obsessive-compulsive disorders, we investigated the correlation between complex compulsive behaviour (CCB) and the distribution of atrophy in a group of 90 patients with frontotemporal dementia (FTD). METHODS: CCB was defined as complex, intentional, and time consuming repetitive behaviour, which was distinguished from simple compulsive behaviour (SCB), such as verbal and motor repetitions and utilisation behaviour. Cortical atrophy on CT and/or MRI was semi-quantitatively assessed in frontal, temporal, parietal and occipital regions, and the pattern of atrophy was compared between patients with and without CCB or SCB. Linear measures were used to establish the presence of caudate atrophy (bicaudate ratio) and ventricular enlargement (bifrontal ratio). RESULTS: CCB was reported in 18 (21%) and SCB in 53 (61%) FTD patients. Frontotemporal atrophy was present in 64 patients (74%), and predominant temporal atrophy in 23 (26%). The pattern of atrophy was asymmetric in 25 patients (29%). Logistic regression analysis showed that temporal lobe atrophy (p < 0.005), as well as asymmetry of atrophy (p < 0.05) were independently associated with CCB, after adjusting for age at onset, gender, duration of symptoms at the time of imaging, severity of atrophy, and bicaudate and bifrontal ratio. No relationship was found between the presence of SCB and the distribution of atrophy, although patients with SCB tended to have more caudate atrophy (p < 0.1). CONCLUSION: Temporal lobe atrophy appears to mediate CCB in patients with FTD, especially if asymmetry of atrophy is present. Future studies with quantitative and volumetric measurements of the cortical and subcortical structures may further clarify the aetiology of CCB in FTD.


Assuntos
Comportamento Compulsivo/etiologia , Demência/psicologia , Lobo Frontal/patologia , Lobo Temporal/patologia , Idoso , Atrofia , Comportamento Compulsivo/fisiopatologia , Demência/patologia , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade
11.
Clin Neuropharmacol ; 21(3): 190-5, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9617511

RESUMO

In this article, the authors examine the effect of lisuride on 22 patients with probable Alzheimer's disease (NINCDS/ADRDA criteria) in a randomized double-blind, placebo-controlled, parallel group design. Ten patients received lisuride and 12 patients received placebo. Lisuride was administered in a dose-finding phase of four weeks and an efficacy phase of eight weeks, with a maximum dose of 0.3 mg daily. Outcome measures included global clinical impression, general cognitive function, mood, verbal and visual memory, attention, and psychomotor function. Average decline in Mini-Mental State Examination score after 12 weeks treatment was less often statistically significant in lisuride treated patients than in patients receiving a placebo (p < 0.05). Patients treated with lisuride improved their average total score and short-delay cued recall score on the California Verbal Learning Test, a test of verbal memory, whereas placebo-treated patients showed worse performance compared with baseline. These differences approached statistical significance, with p = 0.06 and p = 0.05, respectively. No other differences between the treatment groups were evident. The authors failed to find a consistent effect of lisuride on symptoms of Alzheimer's disease. However, this study's sample size was relatively small, and larger studies are needed to ascertain the treatment effects of serotonergic antagonists on Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Lisurida/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Escalas de Graduação Psiquiátrica , Psicometria , Segurança , Resultado do Tratamento , Comportamento Verbal/efeitos dos fármacos
12.
Neurology ; 77(4): 384-92, 2011 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-21753175

RESUMO

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous disorder. The aim of this study was to compare clinical features and perfusion patterns on SPECT of patients with familial FTLD-TAR DNA binding protein 43 kDa (TDP) and MAPT mutations. METHODS: Patients were included if they had MAPT or GRN mutations, positive family history with pathologically proven FTLD in the patient or first-degree relative, or were part of FTD-MND families. All patients and 10 age- and gender-matched controls underwent measurement of brain perfusion using (99m)Tc-HMPAO SPECT. We used SPM8 to perform image processing and voxel-based group analyses (p < 0.001). Gender and age were included as nuisance variables in the design matrices. RESULTS: Of the 29 patients with familial FTLD, 19 had familial FTLD-TDP (GRN mutations in 6), and 10 had MAPT mutations. At clinical presentation, familial FTLD-TDP patients were older at onset (p = 0.030) and had more memory deficits (p = 0.011), whereas patients with MAPT had more naming deficits (p < 0.001) and obsessive-compulsive behavior (p = 0.001). The between-groups SPECT analyses revealed significantly less perfusion in the right frontal lobe, precuneus, cuneus, and inferior parietal lobule in familial FTLD-TDP, whereas significantly less perfusion was found in the left temporal and inferior frontal gyri in MAPT. Post hoc analysis of familial FTLD-TDP with unknown genetic defect vs MAPT revealed less perfusion in the right frontal and parietal lobe. CONCLUSION: Familial FTLD-TDP shows relatively more posterior hypoperfusion, including the precuneus and inferior parietal lobule, possibly related to significant memory impairment. Patients with MAPT were characterized by impaired perfusion of the temporal regions and naming deficits.


Assuntos
Encéfalo/irrigação sanguínea , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas tau/fisiologia , Encéfalo/diagnóstico por imagem , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Feminino , Degeneração Lobar Frontotemporal/complicações , Degeneração Lobar Frontotemporal/psicologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Transtornos da Memória/complicações , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/genética , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos/estatística & dados numéricos , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/fisiopatologia , Progranulinas , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Proteínas tau/genética
14.
Neurology ; 70(19 Pt 2): 1827-35, 2008 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-18458217

RESUMO

OBJECTIVE: To evaluate the diagnostic value of CSF biomarkers in patients with known pathology due to frontotemporal lobar degeneration (FTLD). BACKGROUND: It is important to distinguish FTLD from other neurodegenerative diseases like Alzheimer disease (AD), but this may be difficult clinically because of atypical presentations. METHODS: Patients with FTLD (n = 30) and AD (n = 19) were identified at autopsy or on the basis of genetic testing at University of Pennsylvania and Erasmus University Medical Center. CSF was obtained during a diagnostic lumbar puncture and was analyzed using assays for total tau and amyloid-beta 1-42 (A beta(42)). Patients also were assessed with a brief neuropsychological battery. RESULTS: CSF total tau level and the ratio of CSF total tau to A beta(42) (tau/A beta(42)) were significantly lower in FTLD than in AD. Receiver operating characteristic curve analyses confirmed that the CSF tau/A beta(42) ratio is sensitive and specific at discriminating between FTLD and AD, and is more successful at this than CSF total tau alone. Although some neuropsychological measures are significantly different in autopsy-proven FTLD and AD, combining these neuropsychological measures with CSF biomarkers did not improve the ability to distinguish FTLD from AD. CONCLUSIONS: The ratio of CSF tau/A beta(42) is a sensitive and specific biomarker at discriminating frontotemporal lobar degeneration from Alzheimer disease in patients with known pathology.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Encéfalo/metabolismo , Encéfalo/patologia , Demência/líquido cefalorraquidiano , Demência/patologia , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/análise , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Encéfalo/fisiopatologia , Demência/fisiopatologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Emaranhados Neurofibrilares , Testes Neuropsicológicos , Fragmentos de Peptídeos/análise , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Valor Preditivo dos Testes , Prognóstico , Proteínas tau/análise
15.
Neurology ; 71(16): 1220-6, 2008 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-18703462

RESUMO

BACKGROUND: Frontotemporal dementia (FTD) is the second most common type of presenile dementia and can be distinguished into various clinical variants. The identification of MAPT and GRN defects and the discovery of the TDP-43 protein in FTD have led to the classification of pathologic and genetic subtypes. In addition to these genetic subtypes, there exist familial forms of FTD with unknown genetic defects. METHODS: We investigated the frequency, demographic, and clinical data of patients with FTD with a positive family history in our prospective cohort of 364 patients. Genetic analysis of genes associated with FTD was performed on all patients with a positive family history. Immunohistochemical studies were carried out with a panel of antibodies (tau, ubiquitin, TDP-43) in brains collected at autopsy. RESULTS: In the total cohort of 364 patients, 27% had a positive family history suggestive for an autosomal mode of inheritance, including MAPT (11%) and GRN (6%) mutations. We identified a new Gln300X GRN mutation in a patient with a sporadic FTD. The mean age at onset in GRN patients (61.8 +/- 9.9 years) was higher than MAPT patients (52.4 +/- 5.9 years). In the remaining 10% of patients with suggestive autosomal dominant inheritance, the genetic defect has yet to be identified. Neuropathologically, this group can be distinguished into familial FTLD+MND and familial FTLD-U with hippocampal sclerosis. CONCLUSION: Future genetic studies need to identify genetic defects in at least two distinct familial forms of frontotemporal dementia (FTD) with unknown genetic defects: frontotemporal lobe degeneration with ubiquitin-positive inclusions with hippocampal sclerosis and frontotemporal lobe degeneration with motor neuron disease.


Assuntos
Demência/classificação , Demência/genética , Adulto , Idade de Início , Idoso , Demência/fisiopatologia , Complexos Endossomais de Distribuição Requeridos para Transporte , Feminino , Lobo Frontal/patologia , Humanos , Padrões de Herança , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas do Tecido Nervoso/genética , Testes Neuropsicológicos , Linhagem , Progranulinas , Estudos Prospectivos , Lobo Temporal/patologia , Proteínas tau/genética
16.
Neurobiol Aging ; 28(5): 735-41, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-16698126

RESUMO

Impaired cognition in later life may result from Alzheimer's disease-related pathology, but also from vascular pathology. We studied to what extent vascular risk explained heritability of cognition in 780 individuals, related in one extended pedigree in a genetically isolated population, in the ERF study. Heritability was estimated using variance components modelling (SOLAR). Univariate analyses included models with and without vascular disease; bivariate analyses included both cognitive and vascular traits, such as blood pressure, serum glucose or lipids. Heritability for immediate and delayed recall, recognition, semantic fluency, Trail making B and Stroop tests was significant, with estimates from 0.16 to 0.36. Vascular factors did not affect cognitive functions, except immediate recall and the Stroop test. Heritability estimates did not change significantly when adjusted for vascular disease. We found no genetic correlation between cognition and vascular traits. Therefore, in this population vascular disease is mildly associated with cognitive dysfunction, and in those with vascular disease, the underlying genetic risk factors are not likely to account for the genetic variation in cognition at adult age.


Assuntos
Transtornos Cerebrovasculares/genética , Cognição/fisiologia , Variação Genética/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Linhagem , Fenótipo , Fatores de Risco
17.
J Neurol Neurosurg Psychiatry ; 76(2): 263-5, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15654047

RESUMO

BACKGROUND AND OBJECTIVE: Specific screening tests to detect post-stroke dementia are lacking. We recently reported that an adaptation of the Cambridge Cognitive Examination (CAMCOG), the Rotterdam-CAMCOG, had excellent sensitivity and specificity for detecting post-stroke dementia. In this study, we externally validated the diagnostic accuracy of the R-CAMCOG in a new, representative cohort of stroke patients. METHODS: The R-CAMCOG and an extensive neuropsychological examination were administered, independently of each other, in 121 patients aged 55 and over with a stroke in the preceding three to nine months. The gold standard diagnosis of dementia was based on the results of the extensive neuropsychological examination, clinical presentation, and information from a close relative, as well as DSM-IV criteria. RESULTS: Of the 121 patients, 35 had dementia (29%). The diagnostic accuracy at the pre-specified cut-off point of 33/34 was established through receiver operating characteristic (ROC) analyses (sensitivity 66%, specificity 94%). At a cut-off point of 36/37 sensitivity would be 83% and specificity 78%. CONCLUSION: The R-CAMCOG is a useful screening tool for post-stroke dementia in a clinical setting.


Assuntos
Demência/diagnóstico , Demência/etiologia , Entrevista Psiquiátrica Padronizada , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sensibilidade e Especificidade
18.
J Neurol Neurosurg Psychiatry ; 68(6): 726-30, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10811695

RESUMO

OBJECTIVE: To investigate the effect of missing values due to behavioural disturbances on the neuropsychological test profile in frontotemporal dementia (FTD). The neuropsychological examination of patients with FTD poses a methodological problem. In many patients it is impossible to administer a complete test battery, due to behavioural disturbances inherent to the disease. This study describes the test behaviour of patients with FTD, the number of missing values due to disturbed test behaviour, and its influence on neuropsychological test results. METHODS: Thirty one patients with probable FTD were administered a neuropsychological test battery including measures of memory, intelligence, and executive functioning. Moreover, patients were rated on a global deterioration scale and a test behaviour scale, constructed for this study. RESULTS: The more disturbing the test behaviour, the less tests were assessable, leading to many missing values. The most disturbing features were "positive symptoms" of FTD, such as perseveration and stimulus boundedness. The effect of test behaviour was largest for tests measuring executive functions and reasoning capabilities. The replacement of the missing values due to behavioural disturbances by the lowest score also showed the largest effect on tests of executive function and reasoning abilities. CONCLUSION: Data imputation of missing values due to test behaviour disturbances provides a more differentiated picture of cognitive deficits in FTD.


Assuntos
Demência/diagnóstico , Testes Neuropsicológicos , Adulto , Idoso , Demência/fisiopatologia , Demência/psicologia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Psicometria , Lobo Temporal/fisiopatologia
19.
Haemostasis ; 28(3-4): 158-66, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-10420063

RESUMO

Brief dementia screening instruments, or mental status tests are frequently used to screen for cognitive impairment. We discuss the strengths and weaknesses of existing mental status tests in dementia screening in general. Most screening instruments that are used in clinical practice are developed to detect dementia compatible with Alzheimer's disease, and their value in detecting dementia after stroke is less well known. A stroke may cause both cortical and subcortical deficits, and the clinical expression of post-stroke dementia is different from that of Alzheimer's disease. Existing brief mental status tests have limited value in this patient group because they tend to ignore specific problems which may occur in stroke patients. Some expanded screening instruments, like the CAMCOG, are more useful and have additional diagnostic value. With the growing interest in research for vascular factors in dementia over the past years, however, a specific screening instrument for post-stroke dementia would be a valuable contribution.


Assuntos
Demência/diagnóstico , Acidente Vascular Cerebral/complicações , Envelhecimento , Doença de Alzheimer/diagnóstico , Demência/etiologia , Diagnóstico Diferencial , Humanos , Testes de Inteligência
20.
Stroke ; 31(7): 1502-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10884444

RESUMO

BACKGROUND AND PURPOSE: The CAMCOG is a feasible cognitive screening instrument for dementia in patients with a recent stroke. A major disadvantage of the CAMCOG, however, is its lengthy and relatively complex administration for screening purposes. We therefore developed the Rotterdam CAMCOG (R-CAMCOG), based on the original version. Our aim was to reduce the estimated administration time to 15 minutes or less and to retain or perhaps even improve its diagnostic accuracy. METHODS: We analyzed the item scores on the CAMCOG of 300 consecutive stroke patients, after exclusion of patients with a severe aphasia or lowered consciousness level, who were entered in the Rotterdam Stroke Databank. The diagnosis of dementia was made independent of the R-CAMCOG score, on the basis of clinical examination and neuropsychological test results. The R-CAMCOG was constructed in 3 steps. First, items with floor and ceiling effects were removed. Next, subscales with no additional diagnostic value were excluded. Finally, we removed items that did not contribute to the homogeneity of the subscales. The diagnostic accuracy of the R-CAMCOG and the original CAMCOG was determined by means of the area under the receiver operating characteristic (ROC) curve. RESULTS: In the 3 steps, the number of items was reduced from 59 to 25, divided over the subscales orientation, memory (recent, remote, and learning), perception, and abstraction. The subscale orientation did not reach significance in a logistic regression model but was included in the R-CAMCOG because of its high face validity in dementia screening. Internal validation with ROC analysis suggests that the R-CAMCOG and the CAMCOG are equally accurate in screening for poststroke dementia (area under the curve was 0.95 for both tests). CONCLUSIONS: The R-CAMCOG has overcome the disadvantages of the original CAMCOG. It is a promising, short, and easy-to-administer screening instrument for poststroke dementia. It seems to be sufficiently accurate for this purpose, but the test has yet to be validated in a separate, independent study.


Assuntos
Demência Vascular/diagnóstico , Programas de Rastreamento , Escalas de Graduação Psiquiátrica , Acidente Vascular Cerebral/diagnóstico , Idoso , Cognição , Estudos de Coortes , Árvores de Decisões , Demência Vascular/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
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