The clinical-radiological paradox in multiple sclerosis: myth or truth?

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, degenerative, demyelinating disease that ranges from benign to rapidly progressive forms. A striking characteristic of the disease is the clinical-radiological paradox. OBJECTIVES: The present study was conducted to determine whether, in our cohort, the clinical-radiological paradox exists and whether lesion location is related to clinical disability in patients with MS. METHODS: Retrospective data from 95 patients with MS (60 women and 35 men) treated at a single center were examined. One head-and-spine magnetic resonance imaging (MRI) examination from each patient was selected randomly, and two independent observers calculated lesion loads (LLs) on T2/fluid attenuation inversion recovery sequences manually, considering the whole brain and four separate regions (periventricular, juxtacortical, posterior fossa, and spinal cord). The LLs were compared with the degree of disability, measured by the Kurtzke Expanded Disability Status Scale (EDSS), at the time of MRI examination in the whole cohort and in patients with relapsing-remitting (RR), primarily progressive, and secondarily progressive MS. RESULTS: High LLs correlated with high EDSS scores in the whole cohort (r = 0.34; p < 0.01) and in the RRMS group (r = 0.27; p = 0.02). The EDSS score correlated with high regional LLs in the posterior fossa (r = 0.31; p = 0.002) and spinal cord (r = 0.35; p = 0.001). CONCLUSIONS: Our results indicate that the clinical-radiological paradox is a myth and support the logical connection between lesion location and neurological repercussion.

ANTECEDENTES: A esclerose múltipla (EM) é uma doença inflamatória, degenerativa e desmielinizante que varia de formas benignas a rapidamente progressivas. Uma característica marcante da doença é o paradoxo clínico-radiológico. OBJETIVOS: O presente estudo foi realizado para determinar, se na nossa amostragem, o paradoxo clínico-radiológico existe e se a localização das lesões está relacionada à incapacidade clínica em pacientes com EM. MéTODOS: Foram examinados retrospectivamente dados de 95 pacientes com EM (60 mulheres e 35 homens) atendidos em um único centro. Um exame de ressonância magnética de cada paciente foi selecionado aleatoriamente, e dois observadores independentes calcularam as cargas lesionais (CLs) em sequências T2 e FLAIR manualmente, considerando todo o cérebro e quatro regiões separadamente (periventricular, justacortical, fossa posterior e medula espinhal). As CLs foram comparadas com o grau de incapacidade, medido pela Escala de Status expandido de incapacidade (EDSS, na sigla em inglês) de Kurtzke, no momento do exame de ressonância magnética (RM) em toda a coorte e em pacientes com as formas surto remissão (SR), primariamente progressiva (PP), e secundariamente progressiva (SP) da EM. RESULTADOS: Cargas lesionais elevadas foram correlacionadas com altos índices de EDSS considerando toda a coorte (r = 0.34; p < 0.01) e no grupo SR (r = 0.27; p = 0.02). O EDSS foi correlacionado com CLs altas na fossa posterior (r = 0.31; p = 0.002) e na medula (r = 0.35; p = 0.001). CONCLUSõES: Nossos resultados indicam que o paradoxo clínico-radiológico é um mito e apoiam a conexão lógica entre a localização da lesão e a repercussão neurológica.

The clinical-radiological paradox in multiple sclerosis: myth or truth? / O paradoxo clínico radiológico na esclerose múltipla: mito ou verdade?

Abstract Background Multiple sclerosis (MS) is an inflammatory, degenerative, demyelinating disease that ranges from benign to rapidly progressive forms. A striking characteristic of the disease is the clinical-radiological paradox. Objectives The present study was conducted to determine whether, in our cohort, the clinical-radiological paradox exists and whether lesion location is related to clinical disability in patients with MS. Methods Retrospective data from 95 patients with MS (60 women and 35 men) treated at a single center were examined. One head-and-spine magnetic resonance imaging (MRI) examination from each patient was selected randomly, and two independent observers calculated lesion loads (LLs) on T2/fluid attenuation inversion recovery sequences manually, considering the whole brain and four separate regions (periventricular, juxtacortical, posterior fossa, and spinal cord). The LLs were compared with the degree of disability, measured by the Kurtzke Expanded Disability Status Scale (EDSS), at the time of MRI examination in the whole cohort and in patients with relapsing-remitting (RR), primarily progressive, and secondarily progressive MS. Results High LLs correlated with high EDSS scores in the whole cohort (r = 0.34; p< 0.01) and in the RRMS group (r = 0.27; p= 0.02). The EDSS score correlated with high regional LLs in the posterior fossa (r = 0.31; p= 0.002) and spinal cord (r = 0.35; p= 0.001). Conclusions Our results indicate that the clinical-radiological paradox is a myth and support the logical connection between lesion location and neurological repercussion.

Resumo Antecedentes A esclerose múltipla (EM) é uma doença inflamatória, degenerativa e desmielinizante que varia de formas benignas a rapidamente progressivas. Uma característica marcante da doença é o paradoxo clínico-radiológico. Objetivos O presente estudo foi realizado para determinar, se na nossa amostragem, o paradoxo clínico-radiológico existe e se a localização das lesões está relacionada à incapacidade clínica em pacientes com EM. Métodos Foram examinados retrospectivamente dados de 95 pacientes com EM (60 mulheres e 35 homens) atendidos em um único centro. Um exame de ressonância magnética de cada paciente foi selecionado aleatoriamente, e dois observadores independentes calcularam as cargas lesionais (CLs) em sequências T2 e FLAIR manualmente, considerando todo o cérebro e quatro regiões separadamente (periventricular, justacortical, fossa posterior e medula espinhal). As CLs foram comparadas com o grau de incapacidade, medido pela Escala de Status expandido de incapacidade (EDSS, na sigla em inglês) de Kurtzke, no momento do exame de ressonância magnética (RM) em toda a coorte e em pacientes com as formas surto remissão (SR), primariamente progressiva (PP), e secundariamente progressiva (SP) da EM. Resultados Cargas lesionais elevadas foram correlacionadas com altos índices de EDSS considerando toda a coorte (r = 0.34; p< 0.01) e no grupo SR (r = 0.27; p= 0.02). O EDSS foi correlacionado com CLs altas na fossa posterior (r = 0.31; p= 0.002) e na medula (r = 0.35; p= 0.001). Conclusões Nossos resultados indicam que o paradoxo clínico-radiológico é um mito e apoiam a conexão lógica entre a localização da lesão e a repercussão neurológica.

COPD patient education and support - Achieving patient-centredness.

BACKGROUND: The art of medicine is undergoing a dramatic shift in focus, evolving to focus on patient involvement as partners in care, transforming the traditional, prescriptive, reactive practice of healthcare into a proactive discipline. The personal and societal burden of chronic diseases is burgeoning and unsustainable in current systems, novel approaches are required to address this. DISCUSSION: Although considerable progress has been made in the development of diagnostics, therapeutics and care guidelines for patients with chronic obstructive pulmonary disease (COPD), questions remain surrounding the implementation of best practice education and support. Current educational programmes, personal limitations and preferences and patient-clinician communication in modification of coping styles and behaviour are discussed. A novel holistic model, the Kaleidoscope Model of Care is proposed to address the barriers to optimal self-care behaviours. CONCLUSION AND PRACTICE IMPLICATIONS: Holistic approaches are essential for optimal self-management and improved outcomes. Guidance on personalised goals for patients to help meeting their therapy priorities is needed to aid healthcare professionals (HCPs) and funders to minimise healthcare burden and costs. The novel KALMOD approach may optimise patient empowerment, exploring whole-life factors that impact COPD care and improve interactions between patients and HCPs for optimised outcomes.

Synthesis and 2D-QSAR studies of neolignan-based diaryl-tetrahydrofuran and -furan analogues with remarkable activity against Trypanosoma cruzi and assessment of the trypanothione reductase activity.

Two series of diaryl-tetrahydrofuran and -furan were synthesised and screened for anti-trypanosomal activity against trypomastigote and amastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. Based on evidence that modification of a natural product may result in a more effective drug than the natural product itself, and using known neolignan inhibitors veraguensin 1 and grandisin 2 as templates to synthesise simpler analogues, remarkable anti-trypanosomal activity and selectivity were found for 3,5-dimethoxylated diaryl-furan 5c and 2,4-dimethoxylated diaryl-tetrahydrofuran 4e analogues with EC50 0.01 µM and EC50 0.75 µM, respectively, the former being 260-fold more potent than veraguensin 1 and 150-fold better than benznidazole, the current available drugs for Chagas disease treatment. The ability of the most potent anti-trypanosomal compounds to penetrate LLC-MK2 cells infected with T. cruzi amastigotes parasite was tested, which revealed 4e and 5e analogues as the most effective, causing no damage to mammalian cells. In particular, the majority of the derivatives were non-toxic against mice spleen cells. 2D-QSAR studies show the rigid central core and the position of dimethoxy-aryl substituents dramatically affect the anti-trypanosomal activity. The mode of action of the most active anti-trypanosomal derivatives was investigated by exploring the anti-oxidant functions of Trypanothione reductase (TR). As a result, diarylfuran series displayed the strongest inhibition, highlighting compounds 5d-e (IC50 19.2 and 17.7 µM) and 5f-g (IC50 8.9 and 7.4 µM), respectively, with similar or 2-fold higher than the reference inhibitor clomipramine (IC50 15.2 µM).

Differences in change in coping styles between good responders, moderate responders and non-responders to pulmonary rehabilitation.

INTRODUCTION: Pulmonary rehabilitation (PR) improves exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). Data on the effects of PR on coping styles are limited. Aim of the present study was to compare changes in coping styles between patients who had a good, moderate and no improvement in either exercise tolerance or health status after PR. METHODS: Coping styles of 439 COPD patients undergoing PR were assessed by the Utrecht Coping List (UCL) at baseline and after PR. Patients' pulmonary function, six-minute walking distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) and Hospital Anxiety and Depression Scale (HADS-A and HADS-D) were recorded. Good, moderate and non-responders were defined on the basis of minimally clinically important difference (MCID) for SGRQ total score and/or 6MWD. RESULTS: Overall, 54.0% of the patients fulfilled the criteria for good responders, while 22.1% were moderate responders. Change in passive reaction pattern coping style differed significantly between good responders and non-responders following PR (p < 0.001). Moreover, within the groups, changes in coping styles after PR occurred among the good responders, whereas the majority of moderate responders' and non-responders' coping styles were not significantly influenced by PR. CONCLUSION: Good responders decreased their passive reaction pattern coping style in contrast to non-responders after PR. In general, PR did not change the coping among moderate and non-responders. Further research is warranted to determine whether including interventions targeting coping styles may modify coping behaviour of COPD patients, as well as improvement in exercise tolerance or health status after PR.

Attitudes of healthcare professionals providing pulmonary rehabilitation toward partnership in care.

OBJECTIVES: This multicenter study sought to explore attitudes of pulmonary rehabilitation (PR) professionals toward self-management and which patients' competencies are considered important. BACKGROUND: Self-management in patients with chronic obstructive pulmonary disease (COPD) requires a patients' active role. Whether patient-clinician partnership in care is supported by PR professionals remains unknown. METHODS: Attitudes of 75 PR professionals were assessed using an online version of the Clinician Support - Patient Activation Measure (CS-PAM) 13™. RESULTS: Mean CS-PAM 13™ activation score was 66.5 (11.9) points - professionals support patient's participation in the care process. However, competencies related to patient as member of a care team and patient as an independent information seeker were only extremely important for 30.7-38.7% and 9.3-17.3% of the professionals, respectively. CONCLUSION: PR professionals embrace the idea of a patients' active role in the process of COPD self-management. Nonetheless, endorsement of the patient's involvement as an independent information seeker is needed.

Mortality from dementia in a community-dwelling Brazilian population.

BACKGROUND: The influence of dementia on mortality has not yet been reported for a Latin American country. OBJECTIVES: To evaluate the influence of dementia on mortality of a community-dwelling elderly population in Brazil, and to verify the extent to which the diagnosis of dementia is reported on death certificates. METHODS: A cohort of 1,656 individuals, aged 65 and over, was screened for dementia at their domiciles, in 1997. The same population was re-evaluated in 2000, and information on deaths was obtained from relatives and from the municipal obituary service. Kaplan-Meier curves were used for the survival analysis, and the mortality risk ratio (MMR) was calculated using Cox proportional hazards models. RESULTS: We obtained data from 1,393 subjects, corresponding to 84.1% of the target population. The number of deaths was 58 (51.3%) among the patients with dementia and 163 (12.7%) among those without dementia in 1997 (p <0.0001). Dementia and Alzheimer's disease (AD) decreased survival, with hazards ratios of 5.16 [95% Confidence Interval (CI): 3.74-7.12] for dementia and 4.76 (95% CI: 3.16-7.18) for AD. The Cox proportional hazards model identified dementia (MMR=3.92, 95% CI: 2.80-5.48) as the most significant predictor of death, followed by age, history of stroke, complaints of visual impairment and heart failure and by severe arterial hypertension in the baseline evaluation. Dementia and/or AD were mentioned in only 12.5% of the death certificates of individuals with dementia. CONCLUSIONS: Dementia causes a significant decrease in survival, and the diagnosis of dementia is rarely reported on death certificates in Brazil.

Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with Alzheimer's disease and other dementias: preliminary findings.

Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and tau-associated neurofibrillary tangles in the cerebral tissue. The search for antemortem biomarkers is intense including analysis of cerebrospinal fluid (CSF) beta-amyloid and tau proteins concentrations seeking for an accurate and early diagnosis. Levels of hyperphosphorylated tau at threonine 181 were measured in the CSF of 34 patients with AD (19 with senile AD - SAD and eight with presenile AD - PSAD) and seven with other dementias (OD). The levels of CSF phosphotau were significantly higher in the AD patients compared to OD (AUC 0.812), with no association with severity of dementia, age of onset, duration of the disease or scores in the Mini-Mental State Examination. There were no differences of phosphotau levels between SAD and PSAD patients. These findings corroborate some previous studies and indicate that CSF phosphotau may help to differentiate AD from other dementias.

Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with Alzheimer's disease and other dementias: preliminary findings

A doença de Alzheimer (DA) se caracteriza pelo achado anátomo-patológico de acúmulo de placas senis e emaranhados neurofibrilares associados à proteína tau no tecido cerebral. A pesquisa por marcadores biológicos antemortem está focada nas concentrações das proteínas b-amilóide e tau no líquido cefalorraqueano (LCR) objetivando um diagnóstico mais precoce e acurado da doença. Os níveis de proteína tau hiperfosforilada no sítio 181 foram determinados no LCR de 34 pacientes com DA (19 com DA senil - DAS e oito com DA pré-senil -DAPS) e sete pacientes com outras demências (OD). Os níveis de fosfotau foram significativamente mais elevados em pacientes com DA quando comparados com OD (AUC 0,812), sem relação com gravidade da demência, idade de início, duração da doença e escores do Mini-Exame do Estado Mental. Não foram observadas diferenças entre os níveis de fosfotau em pacientes com DAS e DAPS. Estes achados corroboram os dados encontrados em estudos prévios e indicam que o nível de fosfotau no LCR dos pacientes pode colaborar na diferenciação da DA com outras demências.

Prevalence of potentially reversible dementias in a dementia outpatient clinic of a tertiary university-affiliated hospital in Brazil

The importance of investigating the etiology for dementia lies in the possibility of treating potentially reversible dementias. The aims of this retrospective study are to determine the prevalence of potentially reversible dementias among 454 outpatients seen at the Cognitive and Behavioral Neurology Unit, Hospital das Clínicas, São Paulo University School of Medicine - Brazil, between the years of 1991 and 2001, and observe their evolution in follow-up. Among the initial 454 patients, 275 fulfilled the DSM-IV criteria for dementia. Alzheimer's disease was the most frequent diagnosis (164 cases; 59.6 percent). Twenty-two cases (8.0 percent) of potentially reversible dementia were observed, the most frequent diagnoses being neurosyphilis (nine cases) and hydrocephalus (six cases). Full recovery was observed in two patients and partial recovery in 10 patients. Two cases were not treated and eight cases were lost on follow-up. The prevalence found in the present study falls within the range reported in previous studies (0-30 percent)

Prevalence of potentially reversible dementias in a dementia outpatient clinic of a tertiary university-affiliated hospital in Brazil.

The importance of investigating the etiology for dementia lies in the possibility of treating potentially reversible dementias. The aims of this retrospective study are to determine the prevalence of potentially reversible dementias among 454 outpatients seen at the Cognitive and Behavioral Neurology Unit, Hospital das Clínicas, São Paulo University School of Medicine-Brazil, between the years of 1991 and 2001, and observe their evolution in follow-up. Among the initial 454 patients, 275 fulfilled the DSM-IV criteria for dementia. Alzheimer's disease was the most frequent diagnosis (164 cases; 59.6%). Twenty-two cases (8.0%) of potentially reversible dementia were observed, the most frequent diagnoses being neurosyphilis (nine cases) and hydrocephalus (six cases). Full recovery was observed in two patients and partial recovery in 10 patients. Two cases were not treated and eight cases were lost on follow-up. The prevalence found in the present study falls within the range reported in previous studies (0-30%).

Doenca de Machado-Joseph: atualizacao

A doenca de Machado-Joseph (DMJ) e a heredodegeneracao cerebelo-medular autossomica dominante mais comum na pratica clinica. Caracteriza-se por uma ataxia cerebelar associada, em graus variaveis, a sindrome piramidal, extrapiramidal rigido-distonica e neuropatia periferica. Deve-se a presenca de mutacao genetica constituida de repeticoes trinucleotidicas instaveis (Citosina, Adenina, Guanina) no locus 14q 24.3-q32. Neste artigo, reveem-se os principais aspectos clinicos e etiopatogenicos da doenca, apresentando-se tambem dois casos de uma mesma familia do Rio de Janeiro.