Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The condition causes a heavy burden both on those affected, as well as their families. Accurate diagnosis is critical ...and remains founded on clinical grounds as no specific diagnostic test is available so far. The clinical picture of PD is typical in many instances; however, features distinguishing it from other disorders should be thoroughly sought. Monogenic forms of PD also have some distinctive characteristics in many cases. This text is a roadmap to accurate diagnosis in PD, as it approaches clinical features, diagnostic methodology, and leading differential diagnoses. Therapeutic issues are also briefly discussed.
Parkinson's disease is the second most common neurodegenerative disorder, and a significant increase in its prevalence in the past three decades has been documented. Environmental and genetic factors ...contribute to the pathophysiology of this disease, and 5% - 10% of cases have a monogenic cause. The diagnosis relies on clinical findings, supported by adequate testing. There is no absolute method to diagnose Parkinson's disease in vivo, except for genetic testing in specific circumstances, whose usefulness is limited to a minority of cases. New diagnostic criteria have been recently proposed with the aim of improving diagnostic accuracy, emphasizing findings that might point to other causes of parkinsonism. The available therapeutic options are clinically useful, as they improve the symptoms as well as the quality of life of patients. After the introduction of levodopa, deep brain stimulation emerged as the second therapy with an important symptomatic impact in the treatment of Parkinson's disease. Non-motor symptoms and motor complications are responsible for a large proportion of disability, so these should be identified and treated. Current scientific research is focused on the identification of disease biomarkers allowing correct and timely diagnosis, and on creating more effective therapies, thus fulfilling current clinical unmet needs. This paper presents an updated review on Parkinson's disease, guiding the readership through current concepts, and allowing their application to daily clinical practice.
•Understanding hospitalization burden in dementia is crucial for choosing effective clinical strategies and define healthcare policies.•Hospital admissions were analyzed in a European Union country ...with universal health coverage using an official government database (2000–2014).•Admission rates increased 4.7 times from 2000 to 2014, median hospital length was 8.0 days, and in-hospital mortality was 16.1%.•Patients were mainly admitted due to infectious diseases, whereas dementia itself is the cause of admission in a minority of cases.•Further research should be encouraged, as dementia greatly impacts on healthcare systems, and it is expected to increase in the following decades.
Dementia is a leading cause of disability worldwide. It is associated with an increased risk of hospitalization, imposing a significant burden on healthcare systems. The evidence on the long-term evolution of this issue and broadly on healthcare systems is currently limited. This study aims to describe the hospitalizations of people who received a diagnosis of dementia admitted to public general hospitals in a western European country with universal health coverage, over more than a decade.
This retrospective observational study analyzed all inpatient episodes from 2000 to 2014 with a primary or secondary diagnosis of dementia using a national hospitalization database from mainland Portuguese public hospitals.
A total of 288 096 hospital admissions were registered. Hospitalization rates increased 4.7 times throughout the study period. Pneumonia and urinary tract infections were the most frequent main diagnoses, while dementia itself was the cause of admission in a minority (6.8%) of cases. Cerebrovascular disease, diabetes without chronic complications, and congestive heart failure were the most prevalent comorbidities; 5.9% of patients with dementia admitted to hospital underwent a surgical procedure, orthopedic surgeries being the most frequent. The median length of hospital stay was 8.0 days, and in-hospital mortality rate was 16.1%.
Dementia patients represent a significant amount of hospital admissions. Most leading causes of hospital admissions are preventable if timely diagnosed and could be effectively managed in the outpatient setting. These findings may be useful for healthcare resource planning and allocation. Further research should drive evidence-based reorganization of health care systems.
In Portugal, heterozygous loss-of-function mutations in the progranulin (
) gene account for approximately half of the genetic mediated forms of frontotemporal dementia (FTD).
mutations reported thus ...far cause FTD through a haploinsufficiency disease mechanism. Herein, we aim to unveil the
mutation spectrum, investigated in 257 FTD patients and 19 family members from the central/north region of Portugal using sequencing methods. Seven different pathogenic variants were identified in 46 subjects including 40 patients (16%) and 6 relatives (32%). bvFTD was the most common clinical presentation among the
mutation patients, who showed a global pattern of moderate-to-severe frontotemporoparietal deficits in the neuropsychological evaluation. Interestingly, two mutations were novel (p.Thr238Profs*18, p.Leu354Profs*16), and five were previously described, although three of them only in the Portuguese population, suggesting a population-specific
mutational spectrum. The subjects harboring a
mutation showed a significant reduction in serum PGRN levels, supporting the pathogenic nature of these variants. This work broadens the mutation spectrum of
and the identification of the underlying
mutations provided an accurate genetic counselling and allowed the enrolment of subjects with
mutations (both asymptomatic and symptomatic) in ongoing clinical trials, which is essential to test new drugs for the disease.
Importance
Accurately diagnosing neurodegenerative dementia is often challenging due to overlapping clinical features. Disease specific biomarkers could enhance diagnostic accuracy. However, CSF ...analysis procedures and advanced imaging modalities are either invasive or high-priced, and routinely unavailable. Easily accessible disease biomarkers would be of utmost value for accurate differential diagnosis of dementia subtypes.
Objective
To assess the diagnostic accuracy of blood-based biomarkers for the differential diagnosis of AD from Frontotemporal Lobar Degeneration (FTLD), or AD from Dementia with Lewy Bodies (DLB).
Methods
Systematic review. Three databases (PubMed, Scopus, and Web of Science) were searched. Studies assessing blood-based biomarkers levels in AD versus FTLD, or AD versus DLB, and its diagnostic accuracy, were selected. When the same biomarker was assessed in three or more studies, a meta-analysis was performed. QUADAS-2 criteria were used for quality assessment.
Results
Twenty studies were included in this analysis. Collectively, 905 AD patients were compared to 1262 FTLD patients, and 209 AD patients were compared to 246 DLB patients. Regarding biomarkers for AD versus FTLD, excellent discriminative accuracy (AUC >0.9) was found for p-tau181, p-tau217, synaptophysin, synaptopodin, GAP43 and calmodulin. Other biomarkers also demonstrated good accuracy (AUC = 0.8-0.9). For AD versus DLB distinction, only miR-21-5p and miR-451a achieved excellent accuracy (AUC >0.9).
Conclusion
Encouraging results were found for several biomarkers, alone or in combination. Prospective longitudinal designs and consensual protocols, comprising larger cohorts and homogeneous testing modalities across centres, are essential to validate the clinical value of blood biomarkers for the precise etiological diagnosis of dementia.
Parkinson's disease (PD) is a common, disabling, neurodegenerative condition, and the disease prevalence is expected to increase worldwide in the next few decades. Symptomatic therapy remains ...unsatisfactory, and greatly needed neuroprotective therapies have not been successfully developed so far. Physical exercise (PE) has been associated with a lower risk of developing a neurodegenerative disease. The literature has been searched, and results have been systematized and interpreted with regard to the effects of PE in PD. Published data show the following: 1) PE has been associated with a lower risk of developing PD; 2) PE has been shown to improve disease symptoms, mobility, balance, gait and quality of life (in this regard, walking training, tai-chi and tango dancing have demonstrated the highest level of evidence of efficacy); and 3) neuroprotective effects from PE could be expected in PD, although this has been suggested in animal studies only. Further research on this topic should be encouraged. Multidisciplinary cooperation between neurologists, sports physicians and researchers is paramount.
Physiotherapy and exercise are associated with motor and non-motor benefits in Parkinson’s disease (PD). Community exercise programs may increase ongoing exercise participation and help people with ...Parkinson’s disease actively participate in their health management. But there is still limited knowledge about these programs regarding their benefits, safety, implications over the long-term, and effective implementation. These questions could hold relevant clinical implications. In this perspective article, we identify the current challenges and reflect upon potential solutions to help community exercise to be implemented as an additional anchor to personalize management models for Parkinson’s disease.
Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated ...individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity.
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