Novos métodos de reabilitação cognitiva e motora: desenvolvimento e validação clínica

Doutoramento em Ciências e Tecnologias da SaúdeNervous system disorders are associated with cognitive and motor deficits, and are responsible for the highest disability rates and global burden of disease. Their recovery paths are vulnerable and dependent on the effective combination of plastic brain tissue properties, with complex, lengthy and expensive neurorehabilitation programs. This work explores two lines of research, envisioning sustainable solutions to improve treatment of cognitive and motor deficits. Both projects were developed in parallel and shared a new sensible approach, where low-cost technologies were integrated with common clinical operative procedures. The aim was to achieve more intensive treatments under specialized monitoring, improve clinical decision-making and increase access to healthcare. The first project (articles I – III) concerned the development and evaluation of a web-based cognitive training platform (COGWEB), suitable for intensive use, either at home or at institutions, and across a wide spectrum of ages and diseases that impair cognitive functioning. It was tested for usability in a memory clinic setting and implemented in a collaborative network, comprising 41 centers and 60 professionals. An adherence and intensity study revealed a compliance of 82.8% at six months and an average of six hours/week of continued online cognitive training activities. The second project (articles IV – VI) was designed to create and validate an intelligent rehabilitation device to administer proprioceptive stimuli on the hemiparetic side of stroke patients while performing ambulatory movement characterization (SWORD). Targeted vibratory stimulation was found to be well tolerated and an automatic motor characterization system retrieved results comparable to the first items of the Wolf Motor Function Test. The global system was tested in a randomized placebo controlled trial to assess its impact on a common motor rehabilitation task in a relevant clinical environment (early post-stroke). The number of correct movements on a hand-to-mouth task was increased by an average of 7.2/minute while the probability to perform an error decreased from 1:3 to 1:9. Neurorehabilitation and neuroplasticity are shifting to more neuroscience driven approaches. Simultaneously, their final utility for patients and society is largely dependent on the development of more effective technologies that facilitate the dissemination of knowledge produced during the process. The results attained through this work represent a step forward in that direction. Their impact on the quality of rehabilitation services and public health is discussed according to clinical, technological and organizational perspectives. Such a process of thinking and oriented speculation has led to the debate of subsequent hypotheses, already being explored in novel research paths.As doenças do sistema nervoso estão associadas a défices cognitivos e motores, sendo responsáveis pelas maiores taxas de incapacidade e impacto global. A sua recuperação é difícil e depende em simultâneo da plasticidade cerebral e de programas de neurorreabilitação complexos, longos e dispendiosos. Este trabalho explora duas linhas de investigação, que visam soluções sustentáveis para melhoria do tratamento de défices cognitivos e motores. Ambos os projetos foram desenvolvidos em paralelo, partilhando uma abordagem assisada onde se combinam tecnologias de baixo custo com processos clínicos comuns. O objetivo era obter tratamentos mais intensivos e supervisionados, melhorar o processo de decisão clínica e eliminar barreiras no acesso aos cuidados de saúde. O primeiro projeto (artigos I – III) permitiu o desenvolvimento e avaliação de uma plataforma online para treino cognitivo (COGWEB), adequada para uso intensivo, em casa ou instituições, e num largo espectro de idades e doenças com envolvimento das funções cognitivas. A sua usabilidade foi testada numa consulta de memória, sendo de seguida implementada numa rede colaborativa que envolveu 41 centros e 60 profissionais. A taxa de adesão aos planos de treino cognitivo online foi 82,8% aos 6 meses, verificando-se uma intensidade média de 6 horas/semana. O segundo projeto (artigos IV – VI) originou a construção e validação de um dispositivo de reabilitação inteligente para doentes com acidente vascular cerebral (AVC). Permite estímulos proprioceptivos no lado hemiparético, enquanto caracteriza o movimento tridimensional em ambulatório (SWORD). A estimulação vibratória foi bem tolerada pelos doentes e um sistema automático de caracterização motora revelou resultados comparáveis aos de uma escala utilizada frequentemente na prática clínica. O sistema integrado foi testado num ensaio clínico randomizado e controlado com placebo para avaliação do impacto numa tarefa de reabilitação motora na fase subaguda após AVC. O número de movimentos correctos numa tarefa mão-boca aumentou em média 7,2/minuto, enquanto a probabilidade de ocorrência de erro se reduziu de 1:3 para 1:9. A neurorreabilitação e a neuroplasticidade têm incorporado abordagens de múltiplos domínios das neurociências. Em simultâneo, a sua utilidade para os doentes e sociedade está dependente do desenvolvimento de tecnologias mais eficazes que facilitem também a disseminação do conhecimento entretanto produzido. Os resultados obtidos através do presente trabalho representam um passo adicional nessa direcção. O seu impacto na qualidade dos serviços de reabilitação e saúde pública são discutidos segundo perspectivas clínica, tecnológica e organizacional. Este processo de reflexão foi gerador de novas hipóteses, algumas já em exploração através de linhas de investigação específicas

Anxiety and depression in patients with prostate cancer, at cancer diagnosis and after a one-year follow-up

Prostate cancer (PCa) is the most prevalent among men, and psychological symptoms may affect many patients. This study aims to describe the prevalence of probable anxiety and depression before PCa treatments and after one year and to identify sociodemographic and clinical factors associated with these outcomes. Between February 2018 and March 2020, 292 patients recently diagnosed with PCa were recruited at the Instituto Português de Oncologia—Porto. The Hospital Anxiety and Depression Scale (HADS) was used to define probable anxiety and depression (cutoff = 11). The prevalence of probable anxiety remained stable from baseline to one year (7.8% vs. 8.5%, p = 0.866) while there was an increase in probable depression (3.1% vs. 6.8%, p = 0.012). After one year, probable depression persisted in 55.6% of patients with probable depression at baseline and 47.8% of those with probable anxiety at the first assessment had normal anxiety scores. At baseline, anxiety was more frequent among dwellers in rural areas (adjusted odds ratio—aOR, 95%CI: 2.80, 0.91–8.58) and less frequent in patients with body mass index 25–29.9 kg/m2 (aOR, 95%CI: 0.33, 0.12–0.91) compared to 18.5–24.9 Kg/m2, while those living alone had higher odds of depression (aOR, 95%CI: 6.35, 1.43–28.30). The frequency of anxiety and depression fluctuated during the course of treatment. Monitoring these symptoms would identify the most affected patients, contributing for a better use of mental health services.This study was funded by the European Regional Development Fund through the Operational Program Competitiveness and Internationalization, and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project “NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit, UIDB/04750/2020; ITR, LA/P/0064/2020) financed by national funds from FCT. AC, CL, and SM were funded under the scope of the project “NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). SM also received funding under EPIUnit—Junior Research—Prog Financing (UIDP/04750/2020). An individual PhD grant attributed to NA (SFRH/BD/119390/2016) was funded by FCT and the “Programa Operacional Capital Humano” (POCH/FSE)

Prevalence of cognitive impairment before prostate cancer treatment

Cognitive impairment is common among patients with different types of cancer, even before cancer treatment, but no data were reported among patients with prostate cancer (PCa), who may be at high risk due to advanced age. This study aims to estimate the prevalence of cognitive impairment before PCa treatment. Between February 2018 and April 2021, the NEON-PC cohort recruited 605 patients with PCa proposed for treatment at the Portuguese Institute of Oncology of Porto. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. Participants with a MoCA n = 351 men aged ≥40 years, evaluated in 2013–2015) were used for comparison. The prevalence of PCI was 17.4% in EPIPorto and 14.7% in NEON-PC (age- and education-adjusted odds ratio: 0.82, 95%CI: 0.58,1.18). Neuropsychological assessment was performed in 63 patients with PCa: 54.0% had cognitive impairment. These results suggest that the impact of PCa on cognitive performance could be negligible in the short term, contrary to what other studies have reported regarding other types of cancer.This study was funded by the European Regional Development Fund through the Operational Program Competitiveness and Internationalization, national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project ‘NEON-PC-Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia-Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020) and ITR (LA/P/0064/2020), financed by national funds from FCT. A.C., C.L., and S.M. were funded under the scope of the project ‘NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). S.M. also received funding under EPIunit-Junior Research-Prog Financing (UIDP/04750/2020). An individual PhD grant attributed to N.A. (SFRH/BD/119390/2016) was funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE)

Nationwide access to endovascular treatment for acute ischemic stroke in portugal

Publisher Copyright: Copyright Ordem dos M dicos 2021.Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts. Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture. Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity. Discussion: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions. Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitalspublishersversionpublishe

Spasticity as the First Manifestation of Ischaemic Lesions Involving the Cingulum

Background and Purpose. Spasticity is a positive sign of upper motor neuron syndrome that usually develops weeks after a stroke. The mechanisms that lead to its appearance are not completely understood, namely, the cortical regions whose lesion may induce spasticity. Summary of Cases. We report two patients with an ischaemic stroke entailing the anterior cingulate gyrus (pericallosal artery territory), who presented with acute hemiplegia and spasticity since symptom onset. Spasticity resolved within days after onset. Conclusions. The acute destruction of the anterior cingulate region, interrupting inhibitory projections towards lower motor centres, probably explains the acute onset of spasticity that occurred in these two patients. Further studies addressing the role of this region in acute and chronic disturbances of muscular tone are necessary

Spasticity as the First Manifestation of Ischaemic Lesions Involving the Cingulum

Background and Purpose. Spasticity is a positive sign of upper motor neuron syndrome that usually develops weeks after a stroke. The mechanisms that lead to its appearance are not completely understood, namely, the cortical regions whose lesion may induce spasticity. Summary of Cases. We report two patients with an ischaemic stroke entailing the anterior cingulate gyrus (pericallosal artery territory), who presented with acute hemiplegia and spasticity since symptom onset. Spasticity resolved within days after onset. Conclusions. The acute destruction of the anterior cingulate region, interrupting inhibitory projections towards lower motor centres, probably explains the acute onset of spasticity that occurred in these two patients. Further studies addressing the role of this region in acute and chronic disturbances of muscular tone are necessary

Superficial Siderosis and Anticoagulation Therapy: Different Presentations, Different Outcomes

Superficial siderosis is a potentially manageable neurodegenerative disorder, caused by chronic subarachnoid haemorrhage and iron deposition along the central nervous system surfaces. Association with oral anticoagulant therapy is well known, but its definite role as a causative agent is yet to be clarified. Two Caucasian women, both under long-term oral anticoagulation: a 74 year old woman with slowly progressive hearing loss and mild cerebellar ataxia; a 72 year old woman suffering from behavioural changes, rapidly progressive cognitive decline and latter developing paraparesis. Magnetic resonance imaging showed striking hypointensities along the surfaces of cerebellum, brainstem, frontotemporal cortices, spinal cord, and lumbar arachnoid therefore suggesting superficial siderosis. No specific bleeding source was found in any of the patients. Anticoagulation could not be stopped in the first patient due to a mechanic valve and slowly progressive worsening occurred. In contrast, for the second patient anticoagulation withdrawal was feasible and marked motor and cognitive improvement ensued. Superficial siderosis is associated with unvarying progression, mostly when no direct source of bleeding is identified. Nonetheless, we verified striking motor and cognitive improvement after anticoagulants withdrawal in one of the patients. This may reinforce the need to consider such modifiable factor in future patient management

Trajectories of cognitive performance over five years in a prospective cohort of patients with breast cancer (NEON-BC)

Purpose: To identify trajectories of cognitive performance up to five years since diagnosis and their predictors, in a cohort of patients with breast cancer (BCa). Methods: A total of 464 women with BCa admitted to the Portuguese Institute of Oncology, Porto, during 2012, were evaluated with the Montreal Cognitive Assessment (MoCA) before any treatment, and after one, three and five years. Probable cognitive impairment (PCI) at baseline was defined based on normative age- and education-specific reference values. Mclust was used to define MoCA trajectories. Receiver Operating Characteristic curves were used to assess the predictive accuracy for cognitive trajectories. Results: Two trajectories were identified, one with higher scores and increasing overtime, and the other, including 25.9% of the participants, showing a continuous decline. To further characterize each trajectory, participants were also classified as scoring above or below the median baseline MoCA scores. This resulted in four groups: 1) highest baseline scores, stable overtime (0.0% with PCI); 2) lowest baseline scores (29.5% with PCI); 3) mid-range scores at baseline, increasing overtime (10.5% with PCI); 4) mid-range scores at baseline, decreasing overtime (0.0% with PCI). Adding the change in MoCA during the first year to baseline variables significantly increased the accuracy to predict the downward trajectory (area under the curve [AUC] = 0.732 vs. AUC = 0.841, P < 0.001). Conclusion: Four groups of patients with BCa with different cognitive performance trends were identified. The assessment of cognitive performance before treatments and after one year allows for the identification of patients more likely to have cognitive decline in the long term